Tirin Moore

All Publications

• Neural mechanisms underlying robust target selection in response to microstimulation of the oculomotor system. The Journal of neuroscience : the official journal of the Society for Neuroscience Rakhshan, M., Schafer, R. J., Moore, T., Soltani, A. 2024

  Abstract

  Despite its prevalence in studying the causal roles of different brain circuits in cognitive processes, electrical microstimulation often results in inconsistent behavioral effects. These inconsistencies are assumed to be due to multiple mechanisms, including habituation, compensation by other brain circuits, and contralateral suppression. Considering the presence of reinforcement in most experimental paradigms, we hypothesized that interactions between reward feedback and microstimulation could contribute to inconsistencies in behavioral effects of microstimulation. To test this, we analyzed data from electrical microstimulation of the frontal eye field of male macaques during a value-based decision-making task and constructed network models to capture choice behavior. We found evidence for microstimulation-dependent adaptation in saccadic choice, such that in stimulated trials, monkeys' choices were biased toward the target in the response field of the microstimulated site (Tin ). In contrast, monkeys showed a bias away from Tin in non-stimulated trials following microstimulation. Critically, this bias slowly decreased as a function of the time since the last stimulation. Moreover, microstimulation-dependent adaptation was influenced by reward outcomes in preceding trials. Despite these local effects, we found no evidence for the global effects of microstimulation on learning and sensitivity to the reward schedule. By simulating choice behavior across various network models, we found a model in which microstimulation and reward-value signals interact competitively through reward-dependent plasticity can best account for our observations. Our findings indicate a reward-dependent compensatory mechanism that enhances robustness to perturbations within the oculomotor system and could explain the inconsistent outcomes observed in previous microstimulation studies.Significance Statement Electrical microstimulation has been used to study the causal contributions of certain brain areas or circuits to cognition and behavior. Nonetheless, the overall impact of microstimulation on behavior remains inconclusive, hinting at neural mechanisms that interact with experimental perturbation of neural activity. We hypothesized that this interaction could be driven by the reward feedback animals receive while performing tasks, either with or without external perturbations. Using computational modeling and data from microstimulation during a reward-dependent decision-making task, we found microstimulation and reward-value signals competitively interact within the oculomotor system. This interaction enhances the system's robustness to both internal and external perturbations. Our results have important implications for employing microstimulation in basic and clinical research.

  View details for DOI 10.1523/JNEUROSCI.2356-23.2024

  View details for PubMedID 39516041

• Intermittent rate coding and cue-specific ensembles support working memory. Nature Panichello, M. F., Jonikaitis, D., Oh, Y. J., Zhu, S., Trepka, E. B., Moore, T. 2024

  Abstract

  Persistent, memorandum-specific neuronal spiking activity has long been hypothesized to underlie working memory1,2. However, emerging evidence suggests a potential role for 'activity-silent' synaptic mechanisms3-5. This issue remains controversial because evidence for either view has largely relied eitheron datasets that fail to capture single-trial population dynamics or onindirect measures of neuronal spiking. We addressed this controversyby examining the dynamics of mnemonic information on single trials obtained from large, local populations of lateral prefrontal neurons recorded simultaneously in monkeys performing a working memory task. Here we show that mnemonic information does not persist in the spiking activity of neuronal populations during memory delays, but instead alternates between coordinated 'On' and 'Off' states. At the level of single neurons, Off states are drivenby both a loss of selectivity for memoranda and a return of firing rates to spontaneous levels. Further exploiting the large-scale recordings used here, we show that mnemonic information is available in the patterns of functional connections among neuronal ensembles during Off states. Our results suggest that intermittent periods of memorandum-specific spiking coexist with synaptic mechanisms to support working memory.

  View details for DOI 10.1038/s41586-024-08139-9

  View details for PubMedID 39506106

• Comparison of orientation encoding across layers within single columns of primate V1 revealed by high-density recordings. Frontiers in neural circuits Zhu, S., Xia, R., Chen, X., Moore, T. 2024; 18: 1399571

  Abstract

  Primary visual cortex (V1) has been the focus of extensive neurophysiological investigations, with its laminar organization serving as a crucial model for understanding the functional logic of neocortical microcircuits. Utilizing newly developed high-density, Neuropixels probes, we measured visual responses from large populations of simultaneously recorded neurons distributed across layers of macaque V1. Within single recordings, myriad differences in the functional properties of neuronal subpopulations could be observed. Notably, while standard measurements of orientation selectivity showed only minor differences between laminar compartments, decoding stimulus orientation from layer 4C responses outperformed both superficial and deep layers within the same cortical column. The superior orientation discrimination within layer 4C was associated with greater response reliability of individual neurons rather than lower correlated activity within neuronal populations. Our results underscore the efficacy of high-density electrophysiology in revealing the functional organization and network properties of neocortical microcircuits within single experiments.

  View details for DOI 10.3389/fncir.2024.1399571

  View details for PubMedID 39377033

  View details for PubMedCentralID PMC11456443

• Common and distinct neural mechanisms of attention. Trends in cognitive sciences Xia, R., Chen, X., Engel, T. A., Moore, T. 2024

  Abstract

  Despite a constant deluge of sensory stimulation, only a fraction of it is used to guide behavior. This selective processing is generally referred to as attention, and much research has focused on the neural mechanisms controlling it. Recently, research has broadened to include more ways by which different species selectively process sensory information, whether due to the sensory input itself or to different behavioral and brain states. This work has produced a complex and disjointed body of evidence across different species and forms of attention. However, it has also provided opportunities to better understand the breadth of attentional mechanisms. Here, we summarize the evidence that suggests that different forms of selective processing are supported by mechanisms both common and distinct.

  View details for DOI 10.1016/j.tics.2024.01.005

  View details for PubMedID 38388258

• Dissociable components of attention exhibit distinct neuronal signatures in primate visual cortex. Science advances Chandrasekaran, A. N., Vermani, A., Gupta, P., Steinmetz, N., Moore, T., Sridharan, D. 2024; 10 (5): eadi0645

  Abstract

  Attention can be deployed in multiple forms and facilitates behavior by influencing perceptual sensitivity and choice bias. Attention is also associated with a myriad of changes in sensory neural activity. Yet, the relationship between the behavioral components of attention and the accompanying changes in neural activity remains largely unresolved. We examined this relationship by quantifying sensitivity and bias in monkeys performing a task that dissociated eye movement responses from the focus of covert attention. Unexpectedly, bias, not sensitivity, increased at the focus of covert attention, whereas sensitivity increased at the location of planned eye movements. Furthermore, neuronal activity within visual area V4 varied robustly with bias, but not sensitivity, at the focus of covert attention. In contrast, correlated variability between neuronal pairs was lowest at the location of planned eye movements, and varied with sensitivity, but not bias. Thus, dissociable behavioral components of attention exhibit distinct neuronal signatures within the visual cortex.

  View details for DOI 10.1126/sciadv.adi0645

  View details for PubMedID 38306428

• Dissociating the Contributions of Frontal Eye Field Activity to Spatial Working Memory and Motor Preparation. The Journal of neuroscience : the official journal of the Society for Neuroscience Jonikaitis, D., Noudoost, B., Moore, T. 2023

  Abstract

  Neurons within dorsolateral prefrontal cortex of primates are characterized by robust persistent spiking activity exhibited during the delay period of working memory tasks. This includes the frontal eye field (FEF) where nearly half of the neurons are active when spatial locations are held in working memory. Past evidence has established the FEF's contribution to the planning and triggering of saccadic eye movements as well as to the control of visual spatial attention. However, it remains unclear if persistent delay activity reflects a similar dual role in movement planning and visuospatial working memory. We trained male monkeys to alternate between different forms of a spatial working memory task which could dissociate remembered stimulus locations from planned eye movements. We tested the effects of inactivation of FEF sites on behavioral performance in the different tasks. Consistent with previous studies, FEF inactivation impaired the execution of memory-guided saccades, and impaired performance when remembered locations matched the planned eye movement. In contrast, memory performance was largely unaffected when the remembered location was dissociated from the correct eye movement response. Overall, the inactivation effects demonstrated clear deficits in eye movements, regardless of task type, but little or no evidence of a deficit in spatial working memory. Thus, our results indicate that persistent delay activity in the FEF contributes primarily to the preparation of eye movements and not to spatial working memory.Significance StatementMany Frontal Eye Field (FEF) neurons exhibit spatially tuned persistent spiking activity during the delay period of working memory tasks. However, the role of the FEF in spatial working memory remains unresolved. We tested the effects of inactivation of FEF sites on behavioral performance in different forms of a spatial working memory task, one of which dissociated the remembered stimulus locations from planned eye movements. We found that FEF inactivation produced clear deficits in eye movements, regardless of task type, but no deficit in spatial working memory when dissociated from those movements.

  View details for DOI 10.1523/JNEUROSCI.1071-23.2023

  View details for PubMedID 37871965

• Dissociating the Contributions of Frontal Eye Field Activity to Spatial Working Memory and Motor Preparation. bioRxiv : the preprint server for biology Jonikaitis, D., Noudoost, B., Moore, T. 2023

  Abstract

  Neurons within dorsolateral prefrontal cortex of primates are characterized by robust persistent spiking activity exhibited during the delay period of working memory tasks. This includes the frontal eye field (FEF) where nearly half of the neurons are active when spatial locations are held in working memory. Past evidence has established the FEF's contribution to the planning and triggering of saccadic eye movements as well as to the control of visual spatial attention. However, it remains unclear if persistent delay activity reflects a similar dual role in movement planning and visuospatial working memory. We trained monkeys to alternate between different forms of a spatial working memory task which could dissociate remembered stimulus locations from planned eye movements. We tested the effects of inactivation of FEF sites on behavioral performance in the different tasks. Consistent with previous studies, FEF inactivation impaired the execution of memory-guided saccades, and impaired performance when remembered locations matched the planned eye movement. In contrast, memory performance was largely unaffected when the remembered location was dissociated from the correct eye movement response. Overall, the inactivation effects demonstrated clear deficits on eye movements, regardless of task type, but little or no evidence of a deficit in spatial working memory. Thus, our results indicate that persistent delay activity in the FEF contributes primarily to the preparation of eye movements and not to spatial working memory.

  View details for DOI 10.1101/2023.06.12.544653

  View details for PubMedID 37398433

  View details for PubMedCentralID PMC10312624

• Pupil size predicts the onset of exploration in brain and behavior. bioRxiv : the preprint server for biology Shourkeshti, A., Marrocco, G., Jurewicz, K., Moore, T., Ebitz, R. B. 2023

  Abstract

  In uncertain environments, intelligent decision-makers exploit actions that have been rewarding in the past, but also explore actions that could be even better. Several neuromodulatory systems are implicated in exploration, based, in part, on work linking exploration to pupil size-a peripheral correlate of neuromodulatory tone and index of arousal. However, pupil size could instead track variables that make exploration more likely, like volatility or reward, without directly predicting either exploration or its neural bases. Here, we simultaneously measured pupil size, exploration, and neural population activity in the prefrontal cortex while two rhesus macaques explored and exploited in a dynamic environment. We found that pupil size under constant luminance specifically predicted the onset of exploration, beyond what could be explained by reward history. Pupil size also predicted disorganized patterns of prefrontal neural activity at both the single neuron and population levels, even within periods of exploitation. Ultimately, our results support a model in which pupil-linked mechanisms promote the onset of exploration via driving the prefrontal cortex through a critical tipping point where prefrontal control dynamics become disorganized and exploratory decisions are possible.

  View details for DOI 10.1101/2023.05.24.541981

  View details for PubMedID 37292773

  View details for PubMedCentralID PMC10245915

• Intrinsic timescales in the visual cortex change with selective attention and reflect spatial connectivity. Nature communications Zeraati, R., Shi, Y. L., Steinmetz, N. A., Gieselmann, M. A., Thiele, A., Moore, T., Levina, A., Engel, T. A. 2023; 14 (1): 1858

  Abstract

  Intrinsic timescales characterize dynamics of endogenous fluctuations in neural activity. Variation of intrinsic timescales across the neocortex reflects functional specialization of cortical areas, but less is known about how intrinsic timescales change during cognitive tasks. We measured intrinsic timescales of local spiking activity within columns of area V4 in male monkeys performing spatial attention tasks. The ongoing spiking activity unfolded across at least two distinct timescales, fast and slow. The slow timescale increased when monkeys attended to the receptive fields location and correlated with reaction times. By evaluating predictions of several network models, we found that spatiotemporal correlations in V4 activity were best explained by the model in which multiple timescales arise from recurrent interactions shaped by spatially arranged connectivity, and attentional modulation of timescales results from an increase in the efficacy of recurrent interactions. Our results suggest that multiple timescales may arise from the spatial connectivity in the visual cortex and flexibly change with the cognitive state due to dynamic effective interactions between neurons.

  View details for DOI 10.1038/s41467-023-37613-7

  View details for PubMedID 37012299

  View details for PubMedCentralID PMC10070246

• Functional interactions among neurons within single columns of macaque V1. eLife Trepka, E. B., Zhu, S., Xia, R., Chen, X., Moore, T. 2022; 11

  Abstract

  Recent developments in high-density neurophysiological tools now make it possible to record from hundreds of single neurons within local, highly interconnected neural networks. Among the many advantages of such recordings is that they dramatically increase the quantity of identifiable, functional interactions between neurons thereby providing an unprecedented view of local circuits. Using high-density, Neuropixels recordings from single neocortical columns of primary visual cortex in nonhuman primates, we identified 1000s of functionally interacting neuronal pairs using established crosscorrelation approaches. Our results reveal clear and systematic variations in the synchrony and strength of functional interactions within single cortical columns. Despite neurons residing within the same column, both measures of interactions depended heavily on the vertical distance separating neuronal pairs, as well as on the similarity of stimulus tuning. In addition, we leveraged the statistical power afforded by the large numbers of functionally interacting pairs to categorize interactions between neurons based on their crosscorrelation functions. These analyses identified distinct, putative classes of functional interactions within the full population. These classes of functional interactions were corroborated by their unique distributions across defined laminar compartments and were consistent with known properties of V1 cortical circuitry, such as the lead-lag relationship between simple and complex cells. Our results provide a clear proof-of-principle for the use of high-density neurophysiological recordings to assess circuit-level interactions within local neuronal networks.

  View details for DOI 10.7554/eLife.79322

  View details for PubMedID 36321687

• Cortical state dynamics and selective attention define the spatial pattern of correlated variability in neocortex. Nature communications Shi, Y., Steinmetz, N. A., Moore, T., Boahen, K., Engel, T. A. 1800; 13 (1): 44

  Abstract

  Correlated activity fluctuations in the neocortex influence sensory responses and behavior. Neural correlations reflect anatomical connectivity but also change dynamically with cognitive states such as attention. Yet, the network mechanisms defining the population structure of correlations remain unknown. We measured correlations within columns in the visual cortex. We show that the magnitude of correlations, their attentional modulation, and dependence on lateral distance are explained by columnar On-Off dynamics, which are synchronous activity fluctuations reflecting cortical state. We developed a network model in which the On-Off dynamics propagate across nearby columns generating spatial correlations with the extent controlled by attentional inputs. This mechanism, unlike previous proposals, predicts spatially non-uniform changes in correlations during attention. We confirm this prediction in our columnar recordings by showing that in superficial layers the largest changes in correlations occur at intermediate lateral distances. Our results reveal how spatially structured patterns of correlated variability emerge through interactions of cortical state dynamics, anatomical connectivity, and attention.

  View details for DOI 10.1038/s41467-021-27724-4

  View details for PubMedID 35013259

• Working memory gates visual input to primate prefrontal neurons. eLife Noudoost, B., Clark, K. L., Moore, T. 2021; 10

  Abstract

  Visually guided behavior relies on the integration of sensory input and information held in working memory (WM). Yet it remains unclear how this is accomplished at the level of neural circuits. We studied the direct visual cortical inputs to neurons within a visuomotor area of prefrontal cortex in behaving monkeys. We show that the efficacy of visual input to prefrontal cortex is gated by information held in WM. Surprisingly, visual input to prefrontal neurons was found to target those with both visual and motor properties, rather than preferentially targeting other visual neurons. Furthermore, activity evoked from visual cortex was larger in magnitude, more synchronous, and more rapid, when monkeys remembered locations that matched the location of visual input. These results indicate that WM directly influences the circuitry that transforms visual input into visually guided behavior.

  View details for DOI 10.7554/eLife.64814

  View details for PubMedID 34133270

• Frontotemporal coordination predicts working memory performance and its local neural signatures. Nature communications Rezayat, E., Dehaqani, M. A., Clark, K., Bahmani, Z., Moore, T., Noudoost, B. 2021; 12 (1): 1103

  Abstract

  Neurons in some sensory areas reflect the content of working memory (WM) in their spiking activity. However, this spiking activity is seldom related to behavioral performance. We studied the responses of inferotemporal (IT) neurons, which exhibit object-selective activity, along with Frontal Eye Field (FEF) neurons, which exhibit spatially selective activity, during the delay period of an object WM task. Unlike the spiking activity and local field potentials (LFPs) within these areas, which were poor predictors of behavioral performance, the phase-locking of IT spikes and LFPs with the beta band of FEF LFPs robustly predicted successful WM maintenance. In addition, IT neurons exhibited greater object-selective persistent activity when their spikes were locked to the phase of FEF LFPs. These results reveal that the coordination between prefrontal and temporal cortex predicts the successful maintenance of visual information during WM.

  View details for DOI 10.1038/s41467-021-21151-1

  View details for PubMedID 33597516

• Top-down coordination of local cortical state during selective attention. Neuron van Kempen, J., Gieselmann, M. A., Boyd, M., Steinmetz, N. A., Moore, T., Engel, T. A., Thiele, A. 2020

  Abstract

  Spontaneous fluctuations in cortical excitability influence sensory processing and behavior. These fluctuations, long thought to reflect global changes in cortical state, were recently found to be modulated locally within a retinotopic map during spatially selective attention. We report that periods of vigorous (On) and faint (Off) spiking activity, the signature of cortical state fluctuations, are coordinated across brain areas with retinotopic precision. Top-down attention enhanced interareal local state coordination, traversing along the reverse cortical hierarchy. The extent of local state coordination between areas was predictive of behavioral performance. Our results show that cortical state dynamics are shared across brain regions, modulated by cognitive demands and relevant for behavior.

  View details for DOI 10.1016/j.neuron.2020.12.013

  View details for PubMedID 33406410

• Separable Influences of Reward on Visual Processing and Choice. Journal of cognitive neuroscience Soltani, A., Rakhshan, M., Schafer, R. J., Burrows, B. E., Moore, T. 2020: 1–16

  Abstract

  Primate vision is characterized by constant, sequential processing and selection of visual targets to fixate. Although expected reward is known to influence both processing and selection of visual targets, similarities and differences between these effects remain unclear mainly because they have been measured in separate tasks. Using a novel paradigm, we simultaneously measured the effects of reward outcomes and expected reward on target selection and sensitivity to visual motion in monkeys. Monkeys freely chose between two visual targets and received a juice reward with varying probability for eye movements made to either of them. Targets were stationary apertures of drifting gratings, causing the end points of eye movements to these targets to be systematically biased in the direction of motion. We used this motion-induced bias as a measure of sensitivity to visual motion on each trial. We then performed different analyses to explore effects of objective and subjective reward values on choice and sensitivity to visual motion to find similarities and differences between reward effects on these two processes. Specifically, we used different reinforcement learning models to fit choice behavior and estimate subjective reward values based on the integration of reward outcomes over multiple trials. Moreover, to compare the effects of subjective reward value on choice and sensitivity to motion directly, we considered correlations between each of these variables and integrated reward outcomes on a wide range of timescales. We found that, in addition to choice, sensitivity to visual motion was also influenced by subjective reward value, although the motion was irrelevant for receiving reward. Unlike choice, however, sensitivity to visual motion was not affected by objective measures of reward value. Moreover, choice was determined by the difference in subjective reward values of the two options, whereas sensitivity to motion was influenced by the sum of values. Finally, models that best predicted visual processing and choice used sets of estimated reward values based on different types of reward integration and timescales. Together, our results demonstrate separable influences of reward on visual processing and choice and point to the presence of multiple brain circuits for the integration of reward outcomes.

  View details for DOI 10.1162/jocn_a_01647

  View details for PubMedID 33166195

• Primate Frontal Eye Field Neurons Selectively Signal the Reward Value of Prior Actions. Progress in neurobiology Chen, X., Zirnsak, M., Vega, G. M., Moore, T. 2020: 101881

  Abstract

  The consequences of individual actions are typically unknown until well after they are executed. This fact necessitates a mechanism that bridges delays between specific actions and reward outcomes. We looked for the presence of such a mechanism in the post-movement activity of neurons in the frontal eye field (FEF), a visuomotor area in prefrontal cortex. Monkeys performed an oculomotor gamble task in which they made eye movements to different locations associated with dynamically varying reward outcomes. Behavioral data showed that monkeys tracked reward history and made choices according to their own risk preferences. Consistent with previous studies, we observed that the activity of FEF neurons is correlated with the expected reward value of different eye movements before a target appears. Moreover, we observed that the activity of FEF neurons continued to signal the direction of eye movements, the expected reward value, and their interaction well after the movements were completed and when targets were no longer within the neuronal response field. In addition, this post-movement information was also observed in local field potentials, particularly in low-frequency bands. These results show that neural signals of prior actions and expected reward value persist across delays between those actions and their experienced outcomes. These memory traces may serve a role in reward-based learning in which subjects need to learn actions predicting delayed reward.

  View details for DOI 10.1016/j.pneurobio.2020.101881

  View details for PubMedID 32628973

• Remote, brain region-specific control of choice behavior with ultrasonic waves. Science advances Kubanek, J. n., Brown, J. n., Ye, P. n., Pauly, K. B., Moore, T. n., Newsome, W. n. 2020; 6 (21): eaaz4193

  Abstract

  The ability to modulate neural activity in specific brain circuits remotely and systematically could revolutionize studies of brain function and treatments of brain disorders. Sound waves of high frequencies (ultrasound) have shown promise in this respect, combining the ability to modulate neuronal activity with sharp spatial focus. Here, we show that the approach can have potent effects on choice behavior. Brief, low-intensity ultrasound pulses delivered noninvasively into specific brain regions of macaque monkeys influenced their decisions regarding which target to choose. The effects were substantial, leading to around a 2:1 bias in choices compared to the default balanced proportion. The effect presence and polarity was controlled by the specific target region. These results represent a critical step towards the ability to influence choice behavior noninvasively, enabling systematic investigations and treatments of brain circuits underlying disorders of choice.

  View details for DOI 10.1126/sciadv.aaz4193

  View details for PubMedID 32671207

  View details for PubMedCentralID PMC7314556

• Dopamine Receptor Expression Among Local and Visual Cortex-Projecting Frontal Eye Field Neurons CEREBRAL CORTEX Mueller, A., Krock, R. M., Shepard, S., Moore, T. 2020; 30 (1): 148–64

  View details for DOI 10.1093/cercor/bhz078

  View details for Web of Science ID 000515101400012

• Parietal Cortex Regulates Visual Salience and Salience-Driven Behavior. Neuron Chen, X. n., Zirnsak, M. n., Vega, G. M., Govil, E. n., Lomber, S. G., Moore, T. n. 2020

  Abstract

  Unique stimuli stand out. Despite an abundance of competing sensory stimuli, the detection of the most salient ones occurs without effort, and that detection contributes to the guidance of adaptive behavior. Neurons sensitive to the salience of visual stimuli are widespread throughout the primate visual system and are thought to shape the selection of visual targets. However, a neural source of salience remains elusive. In an attempt to identify a source of visual salience, we reversibly inactivated parietal cortex and simultaneously recorded salience signals in prefrontal cortex. Inactivation of parietal cortex not only caused pronounced and selective reductions of salience signals in prefrontal cortex but also diminished the influence of salience on visually guided behavior. These observations demonstrate a causal role of parietal cortex in regulating salience signals within the brain and in controlling salience-driven behavior.

  View details for DOI 10.1016/j.neuron.2020.01.016

  View details for PubMedID 32048996

• Differences in Noradrenaline Receptor Expression Across Different Neuronal Subtypes in Macaque Frontal Eye Field. Frontiers in neuroanatomy Lee, M., Mueller, A., Moore, T. 2020; 14: 574130

  Abstract

  Cognitive functions such as attention and working memory are modulated by noradrenaline receptors in the prefrontal cortex (PFC). The frontal eye field (FEF) has been shown to play an important role in visual spatial attention. However, little is known about the underlying circuitry. The aim of this study was to characterize the expression of noradrenaline receptors on different pyramidal neuron and inhibitory interneuron subtypes in macaque FEF. Using immunofluorescence, we found broad expression of noradrenaline receptors across all layers of the FEF. Differences in the expression of different noradrenaline receptors were observed across different inhibitory interneuron subtypes. No significant differences were observed in the expression of noradrenaline receptors across different pyramidal neuron subtypes. However, we found that putative long-range projecting pyramidal neurons expressed all noradrenaline receptor subtypes at a much higher proportion than any of the other neuronal subtypes. Nearly all long-range projecting pyramidal neurons expressed all types of noradrenaline receptor, suggesting that there is no receptor-specific machinery acting on these long-range projecting pyramidal neurons. This pattern of expression among long-range projecting pyramidal neurons suggests a mechanism by which noradrenergic modulation of FEF activity influences attention and working memory.

  View details for DOI 10.3389/fnana.2020.574130

  View details for PubMedID 33328901

• The interdependence of attention, working memory and gaze control: behavior and neural circuitry CURRENT OPINION IN PSYCHOLOGY Jonikaitis, D., Moore, T. 2019; 29: 126–34

  View details for DOI 10.1016/j.copsyc.2019.01.012

  View details for Web of Science ID 000501996000021

• Prefrontal Contributions to Attention and Working Memory. Current topics in behavioral neurosciences Bahmani, Z., Clark, K., Merrikhi, Y., Mueller, A., Pettine, W., Isabel Vanegas, M., Moore, T., Noudoost, B. 2019

  Abstract

  The processes of attention and working memory are conspicuously interlinked, suggesting that they may involve overlapping neural mechanisms. Working memory (WM) is the ability to maintain information in the absence of sensory input. Attention is the process by which a specific target is selected for further processing, and neural resources directed toward that target. The content of WM can be used to direct attention, and attention can in turn determine which information is encoded into WM. Here we discuss the similarities between attention and WM and the role prefrontal cortex (PFC) plays in each. First, at the theoretical level, we describe how attention and WM can both rely on models based on attractor states. Then we review the evidence for an overlap between the areas involved in both functions, especially the frontal eye field (FEF) portion of the prefrontal cortex. We also discuss similarities between the neural changes in visual areas observed during attention and WM. At the cellular level, we review the literature on the role of prefrontal DA in both attention and WM at the behavioral and neural levels. Finally, we summarize the anatomical evidence for an overlap between prefrontal mechanisms involved in attention and WM. Altogether, a summary of pharmacological, electrophysiological, behavioral, and anatomical evidence for a contribution of the FEF part of prefrontal cortex to attention and WM is provided.

  View details for PubMedID 30739308

• The interdependence of attention, working memory and gaze control: behavior and neural circuitry. Current opinion in psychology Jonikaitis, D., Moore, T. 2019; 29: 126–34

  Abstract

  Visual attention, visual working memory, and gaze control are basic functions that all select a subset of visual input to guide immediate or subsequent behavior. In this review, we focus on the relationship between these three functions and describe evidence, both at the behavioral and neural circuit levels that they are heavily interdependent. We start with the demonstration that gaze control - or saccade preparation in particular - leads to spatial attention. Next, we show that spatial attention and working memory interact at the behavioral level and rely on a common set of neural mechanisms. Next, we discuss the evidence that gaze control mechanisms are involved in spatial working memory. Lastly, we highlight the links between gaze control and non-spatial memory.

  View details for PubMedID 30825836

• Both a Gauge and a Filter: Cognitive Modulations of Pupil Size FRONTIERS IN NEUROLOGY Ebitz, R., Moore, T. 2019; 9

  View details for DOI 10.3389/fneur.2018.01190

  View details for Web of Science ID 000456266600001

• Laminar segregation of sensory coding and behavioral readout in macaque V4. Proceedings of the National Academy of Sciences of the United States of America Pettine, W. W., Steinmetz, N. A., Moore, T. n. 2019

  Abstract

  Neurons in sensory areas of the neocortex are known to represent information both about sensory stimuli and behavioral state, but how these 2 disparate signals are integrated across cortical layers is poorly understood. To study this issue, we measured the coding of visual stimulus orientation and of behavioral state by neurons within superficial and deep layers of area V4 in monkeys while they covertly attended or prepared eye movements to visual stimuli. We show that whereas single neurons and neuronal populations in the superficial layers conveyed more information about the orientation of visual stimuli than neurons in deep layers, the opposite was true of information about the behavioral relevance of those stimuli. In particular, deep layer neurons encoded greater information about the direction of planned eye movements than superficial neurons. These results suggest a division of labor between cortical layers in the coding of visual input and visually guided behavior.

  View details for DOI 10.1073/pnas.1819398116

  View details for PubMedID 31249141

• Prefrontal Contributions to Attention and Working Memory PROCESSES OF VISUOSPATIAL ATTENTION AND WORKING MEMORY Bahmani, Z., Clark, K., Merrikhi, Y., Mueller, A., Pettine, W., Vanegas, M., Moore, T., Noudoost, B., Hodgson, T. 2019; 41: 129-153

  View details for DOI 10.1007/7854_2018_74

  View details for Web of Science ID 000834791800008

• Robust Online Spike Recovery for High-Density Electrode Recordings using Convolutional Compressed Sensing Weingartner, S., Chen, X., Akcakaya, M., Moore, T., IEEE IEEE. 2019: 1015–20

  View details for Web of Science ID 000469933200247

• Visions for the Future of Neuroscience NEURON Moore, T., Chestek, C., Polley, D., Chen, A., Hippenmeyer, S., Anikeeva, P. 2018; 98 (3): 464–65

  Abstract

  Neuroscience is a broad discipline that embraces technology at multiple scales to understand the brain and to develop potential therapies. Scientists share their perspectives on the evolution of neuroscience research and what excites them about the future prospects for the field.

  View details for DOI 10.1016/j.neuron.2018.03.037

  View details for Web of Science ID 000432473700005

  View details for PubMedID 29723499

• Dissonant Representations of Visual Space in Prefrontal Cortex during Eye Movements CELL REPORTS Chen, X., Zirnsak, M., Moore, T. 2018; 22 (8): 2039–52

  Abstract

  We used local field potentials (LFPs) and spikes to investigate representations of visual space in prefrontal cortex and the dynamics of those representations during eye movements. Spatial information contained in LFPs of the frontal eye field (FEF) was differentially distributed across frequencies, with a majority of that information being carried in alpha and high-gamma bands and minimal signal in the low-gamma band. During fixation, spatial information from alpha and high-gamma bands and spiking activity was robust across cortical layers. Receptive fields (RFs) derived from alpha and high-gamma bands were retinocentrically organized, and they were spatially correlated both with each other and with spiking RFs. However, alpha and high-gamma RFs probed before eye movements were dissociated. Whereas high-gamma and spiking RFs immediately converged toward the movement goal, alpha RFs remained largely unchanged during the initial probe response, but they converged later. These observations reveal possible mechanisms of dynamic spatial representations that underlie visual perception during eye movements.

  View details for PubMedID 29466732

• Differential Expression of Dopamine D5 Receptors across Neuronal Subtypes in Macaque Frontal Eye Field FRONTIERS IN NEURAL CIRCUITS Mueller, A., Shepard, S. B., Moore, T. 2018; 12: 12

  Abstract

  Dopamine signaling in the prefrontal cortex (PFC) is important for cognitive functions, yet very little is known about the expression of the D5 class of dopamine receptors (D5Rs) in this region. To address this, we co-stained for D5Rs, pyramidal neurons (neurogranin+), putative long-range projection pyramidal neurons (SMI-32+), and several classes of inhibitory interneuron (parvalbumin+, calbindin+, calretinin+, somatostatin+) within the frontal eye field (FEF): an area within the PFC involved in the control of visual spatial attention. We then quantified the co-expression of D5Rs with markers of different cell types across different layers of the FEF. We show that: (1) D5Rs are more prevalent on pyramidal neurons than on inhibitory interneurons. (2) D5Rs are disproportionately expressed on putative long-range projecting pyramidal neurons. The disproportionately high expression of D5Rs on long-range projecting pyramidals, compared to interneurons, was particularly pronounced in layers II-III. Together these results indicate that the engagement of D5R-dependent mechanisms in the FEF varies depending on cell type and cortical layer, and suggests that non-locally projecting neurons contribute disproportionately to functions involving the D5R subtype.

  View details for PubMedID 29483863

• Both a Gauge and a Filter: Cognitive Modulations of Pupil Size. Frontiers in neurology Ebitz, R. B., Moore, T. 2018; 9: 1190

  Abstract

  Over 50 years of research have established that cognitive processes influence pupil size. This has led to the widespread use of pupil size as a peripheral measure of cortical processing in psychology and neuroscience. However, the function of cortical control over the pupil remains poorly understood. Why does visual attention change the pupil light reflex? Why do mental effort and surprise cause pupil dilation? Here, we consider these functional questions as we review and synthesize two literatures on cognitive effects on the pupil: how cognition affects pupil light response and how cognition affects pupil size under constant luminance. We propose that cognition may have co-opted control of the pupil in order to filter incoming visual information to optimize it for particular goals. This could complement other cortical mechanisms through which cognition shapes visual perception.

  View details for DOI 10.3389/fneur.2018.01190

  View details for PubMedID 30723454

  View details for PubMedCentralID PMC6350273

• Exploration Disrupts Choice-Predictive Signals and Alters Dynamics in Prefrontal Cortex NEURON Ebitz, R., Albarran, E., Moore, T. 2018; 97 (2): 450-+

  Abstract

  In uncertain environments, decision-makers must balance two goals: they must "exploit" rewarding options but also "explore" in order to discover rewarding alternatives. Exploring and exploiting necessarily change how the brain responds to identical stimuli, but little is known about how these states, and transitions between them, change how the brain transforms sensory information into action. To address this question, we recorded neural activity in a prefrontal sensorimotor area while monkeys naturally switched between exploring and exploiting rewarding options. We found that exploration profoundly reduced spatially selective, choice-predictive activity in single neurons and delayed choice-predictive population dynamics. At the same time, reward learning was increased in brain and behavior. These results indicate that exploration is related to sudden disruptions in prefrontal sensorimotor control and rapid, reward-dependent reorganization of control dynamics. This may facilitate discovery through trial and error.

  View details for PubMedID 29290550

  View details for PubMedCentralID PMC5774994

• Subclusters of Autistic Traits: Links With Looking at the Eyes, and Face Identity Recognition Ability Palermo, R., Davis, J., Zirnsak, M., Moore, T., O'Kearney, R., Apthorp, D., McKone, E. SAGE PUBLICATIONS LTD. 2017: 19-20

  View details for Web of Science ID 000513010300035

• Linking ADHD to the Neural Circuitry of Attention TRENDS IN COGNITIVE SCIENCES Mueller, A., Hong, D. S., Shepard, S., Moore, T. 2017; 21 (6): 474-488

  Abstract

  Attention deficit hyperactivity disorder (ADHD) is a complex condition with a heterogeneous presentation. Current diagnosis is primarily based on subjective experience and observer reports of behavioral symptoms - an approach that has significant limitations. Many studies show that individuals with ADHD exhibit poorer performance on cognitive tasks than neurotypical controls, and at least seven main functional domains appear to be implicated in ADHD. We discuss the underlying neural mechanisms of cognitive functions associated with ADHD, with emphasis on the neural basis of selective attention, demonstrating the feasibility of basic research approaches for further understanding cognitive behavioral processes as they relate to human psychopathology. The study of circuit-level mechanisms underlying executive functions in nonhuman primates holds promise for advancing our understanding, and ultimately the treatment, of ADHD.

  View details for DOI 10.1016/j.tics.2017.03.009

  View details for PubMedID 28483638

• Selective Modulation of the Pupil Light Reflex by Microstimulation of Prefrontal Cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience Ebitz, R. B., Moore, T. 2017; 37 (19): 5008-5018

  Abstract

  The prefrontal cortex (PFC) is thought to flexibly regulate sensorimotor responses, perhaps through modulating activity in other circuits. However, the scope of that control remains unknown: it remains unclear whether the PFC can modulate basic reflexes. One canonical example of a central reflex is the pupil light reflex (PLR): the automatic constriction of the pupil in response to luminance increments. Unlike pupil size, which depends on the interaction of multiple physiological and neuromodulatory influences, the PLR reflects the action of a simple brainstem circuit. However, emerging behavioral evidence suggests that the PLR may be modulated by cognitive processes. Although the neural basis of these modulations remains unknown, one possible source is the PFC, particularly the frontal eye field (FEF), an area of the PFC implicated in the control of attention. We show that microstimulation of the rhesus macaque FEF alters the magnitude of the PLR in a spatially specific manner. FEF microstimulation enhanced the PLR to probes presented within the stimulated visual field, but suppressed the PLR to probes at nonoverlapping locations. The spatial specificity of this effect parallels the effect of FEF stimulation on attention and suggests that FEF is capable of modulating visuomotor transformations performed at a lower level than was previously known. These results provide evidence of the selective regulation of a basic brainstem reflex by the PFC.SIGNIFICANCE STATEMENT The pupil light reflex (PLR) is our brain's first and most fundamental mechanism for light adaptation. Although it is often described in textbooks as being an immutable reflex, converging evidence suggests that the magnitude of the PLR is modulated by cognitive factors. The neural bases of these modulations are unknown. Here, we report that microstimulation in the prefrontal cortex (PFC) modulates the gain of the PLR, changing how a simple reflex circuit responds to physically identical stimuli. These results suggest that control structures such as the PFC can add complexity and flexibility to even a basic brainstem circuit.

  View details for DOI 10.1523/JNEUROSCI.2433-16.2017

  View details for PubMedID 28432136

• Spatial working memory alters the efficacy of input to visual cortex NATURE COMMUNICATIONS Merrikhi, Y., Clark, K., Albarran, E., Parsa, M., Zirnsak, M., Moore, T., Noudoost, B. 2017; 8

  Abstract

  Prefrontal cortex modulates sensory signals in extrastriate visual cortex, in part via its direct projections from the frontal eye field (FEF), an area involved in selective attention. We find that working memory-related activity is a dominant signal within FEF input to visual cortex. Although this signal alone does not evoke spiking responses in areas V4 and MT during memory, the gain of visual responses in these areas increases, and neuronal receptive fields expand and shift towards the remembered location, improving the stimulus representation by neuronal populations. These results provide a basis for enhancing the representation of working memory targets and implicate persistent FEF activity as a basis for the interdependence of working memory and selective attention.

  View details for DOI 10.1038/ncomms15041

  View details for Web of Science ID 000400155500001

  View details for PubMedID 28447609

• Social and attention-to-detail subclusters of autistic traits differentially predict looking at eyes and face identity recognition ability BRITISH JOURNAL OF PSYCHOLOGY Davis, J., McKone, E., Zirnsak, M., Moore, T., O'Kearney, R., Apthorp, D., Palermo, R. 2017; 108 (1): 191-219

  Abstract

  This study distinguished between different subclusters of autistic traits in the general population and examined the relationships between these subclusters, looking at the eyes of faces, and the ability to recognize facial identity. Using the Autism Spectrum Quotient (AQ) measure in a university-recruited sample, we separate the social aspects of autistic traits (i.e., those related to communication and social interaction; AQ-Social) from the non-social aspects, particularly attention-to-detail (AQ-Attention). We provide the first evidence that these social and non-social aspects are associated differentially with looking at eyes: While AQ-Social showed the commonly assumed tendency towards reduced looking at eyes, AQ-Attention was associated with increased looking at eyes. We also report that higher attention-to-detail (AQ-Attention) was then indirectly related to improved face recognition, mediated by increased number of fixations to the eyes during face learning. Higher levels of socially relevant autistic traits (AQ-Social) trended in the opposite direction towards being related to poorer face recognition (significantly so in females on the Cambridge Face Memory Test). There was no evidence of any mediated relationship between AQ-Social and face recognition via reduced looking at the eyes. These different effects of AQ-Attention and AQ-Social suggest face-processing studies in Autism Spectrum Disorder might similarly benefit from considering symptom subclusters. Additionally, concerning mechanisms of face recognition, our results support the view that more looking at eyes predicts better face memory.

  View details for DOI 10.1111/bjop.12188

  View details for Web of Science ID 000397119800014

  View details for PubMedID 26988108

• Does the Superior Colliculus Control Perceptual Sensitivity or Choice Bias during Attention? Evidence from a Multialternative Decision Framework. journal of neuroscience Sridharan, D., Steinmetz, N. A., Moore, T., Knudsen, E. I. 2017; 37 (3): 480-511

  Abstract

  Distinct networks in the forebrain and the midbrain coordinate to control spatial attention. The critical involvement of the superior colliculus (SC)-the central structure in the midbrain network-in visuospatial attention has been shown by four seminal, published studies in monkeys (Macaca mulatta) performing multialternative tasks. However, due to the lack of a mechanistic framework for interpreting behavioral data in such tasks, the nature of the SC's contribution to attention remains unclear. Here we present and validate a novel decision framework for analyzing behavioral data in multialternative attention tasks. We apply this framework to re-examine the behavioral evidence from these published studies. Our model is a multidimensional extension to signal detection theory that distinguishes between two major classes of attentional mechanisms: those that alter the quality of sensory information or "sensitivity," and those that alter the selective gating of sensory information or "choice bias." Model-based simulations and model-based analyses of data from these published studies revealed a converging pattern of results that indicated that choice-bias changes, rather than sensitivity changes, were the primary outcome of SC manipulation. Our results suggest that the SC contributes to attentional performance predominantly by generating a spatial choice bias for stimuli at a selected location, and that this bias operates downstream of forebrain mechanisms that enhance sensitivity. The findings lead to a testable mechanistic framework of how the midbrain and forebrain networks interact to control spatial attention.Attention involves the selection of the most relevant information for differential sensory processing and decision making. While the mechanisms by which attention alters sensory encoding (sensitivity control) are well studied, the mechanisms by which attention alters decisional weighting of sensory evidence (choice-bias control) are poorly understood. Here, we introduce a model of multialternative decision making that distinguishes bias from sensitivity effects in attention tasks. With our model, we simulate experimental data from four seminal studies that microstimulated or inactivated a key attention-related midbrain structure, the superior colliculus (SC). We demonstrate that the experimental effects of SC manipulation are entirely consistent with the SC controlling attention by changing choice bias, thereby shedding new light on how the brain mediates attention.

  View details for DOI 10.1523/JNEUROSCI.4505-14.2017

  View details for PubMedID 28100734

  View details for PubMedCentralID PMC5242403

• Neural Mechanisms of Selective Visual Attention. Annual review of psychology Moore, T., Zirnsak, M. 2017; 68: 47-72

  Abstract

  Selective visual attention describes the tendency of visual processing to be confined largely to stimuli that are relevant to behavior. It is among the most fundamental of cognitive functions, particularly in humans and other primates for whom vision is the dominant sense. We review recent progress in identifying the neural mechanisms of selective visual attention. We discuss evidence from studies of different varieties of selective attention and examine how these varieties alter the processing of stimuli by neurons within the visual system, current knowledge of their causal basis, and methods for assessing attentional dysfunctions. In addition, we identify some key questions that remain in identifying the neural mechanisms that give rise to the selective processing of visual information.

  View details for DOI 10.1146/annurev-psych-122414-033400

  View details for PubMedID 28051934

• Two Types of Receptive Field Dynamics in Area V4 at the Time of Eye Movements? Frontiers in systems neuroscience Hartmann, T. S., Zirnsak, M., Marquis, M., Hamker, F. H., Moore, T. 2017; 11: 13-?

  Abstract

  How we perceive the world as stable despite the frequent disruptions of the retinal image caused by eye movements is one of the fundamental questions in sensory neuroscience. Seemingly convergent evidence points towards a mechanism which dynamically updates representations of visual space in anticipation of a movement (Wurtz, 2008). In particular, receptive fields (RFs) of neurons, predominantly within oculomotor and attention related brain structures (Duhamel et al., 1992; Walker et al., 1995; Umeno and Goldberg, 1997), are thought to "remap" to their future, post-movement location prior to an impending eye movement. New studies (Neupane et al., 2016a,b) report observations on RF dynamics at the time of eye movements of neurons in area V4. These dynamics are interpreted as being largely dominated by a remapping of RFs. Critically, these observations appear at odds with a previous study reporting a different type of RF dynamics within the same brain structure (Tolias et al., 2001), consisting of a shrinkage and shift of RFs towards the movement target. Importantly, RFs have been measured with different techniques in those studies. Here, we measured V4 RFs comparable to Neupane et al. (2016a,b) and observe a shrinkage and shift of RFs towards the movement target when analyzing the immediate stimulus response (Zirnsak et al., 2014). When analyzing the late stimulus response (Neupane et al., 2016a,b), we observe RF shifts resembling remapping. We discuss possible causes for these shifts and point out important issues which future studies on RF dynamics need to address.

  View details for DOI 10.3389/fnsys.2017.00013

  View details for PubMedID 28377700

• Neural Mechanisms of Selective Visual Attention ANNUAL REVIEW OF PSYCHOLOGY, VOL 68 Moore, T., Zirnsak, M., Fiske, S. T. 2017; 68: 47-72

  View details for DOI 10.1146/annurev-psych-122414-033400

  View details for Web of Science ID 000396040000004

• Selective modulation of cortical state during spatial attention SCIENCE Engel, T. A., Steinmetz, N. A., Gieselmann, M. A., Thiele, A., Moore, T., Boahen, K. 2016; 354 (6316): 1140-1144

  Abstract

  Neocortical activity is permeated with endogenously generated fluctuations, but how these dynamics affect goal-directed behavior remains a mystery. We found that ensemble neural activity in primate visual cortex spontaneously fluctuated between phases of vigorous (On) and faint (Off) spiking synchronously across cortical layers. These On-Off dynamics, reflecting global changes in cortical state, were also modulated at a local scale during selective attention. Moreover, the momentary phase of local ensemble activity predicted behavioral performance. Our results show that cortical state is controlled locally within a cortical map according to cognitive demands and reveal the impact of these local changes in cortical state on goal-directed behavior.

  View details for DOI 10.1126/science.aag1420

  View details for Web of Science ID 000388916400040

  View details for PubMedID 27934763

• Visual sensitivity of frontal eye field neurons during the preparation of saccadic eye movements JOURNAL OF NEUROPHYSIOLOGY Krock, R. M., Moore, T. 2016; 116 (6): 2882-2891

  Abstract

  Primate vision is continuously disrupted by saccadic eye movements, and yet this disruption goes unperceived. One mechanism thought to reduce perception of this self-generated movement is saccadic suppression, a global loss of visual sensitivity just before, during, and after saccadic eye movements. The frontal eye field (FEF) is a candidate source of neural correlates of saccadic suppression previously observed in visual cortex, because it contributes to the generation of visually guided saccades and modulates visual cortical responses. However, whether the FEF exhibits a perisaccadic reduction in visual sensitivity that could be transmitted to visual cortex is unknown. To determine whether the FEF exhibits a signature of saccadic suppression, we recorded the visual responses of FEF neurons to brief, full-field visual probe stimuli presented during fixation and before onset of saccades directed away from the receptive field in rhesus macaques (Macaca mulatta) We measured visual sensitivity during both epochs and found that it declines before saccade onset. Visual sensitivity was significantly reduced in visual but not visuomotor neurons. This reduced sensitivity was also present in visual neurons with no movement-related modulation during visually guided saccades and thus occurred independently from movement-related activity. Across the population of visual neurons, sensitivity began declining ∼80 ms before saccade onset. We also observed a similar presaccadic reduction in sensitivity to isoluminant, chromatic stimuli. Our results demonstrate that the signaling of visual information by FEF neurons is reduced during saccade preparation, and thus these neurons exhibit a signature of saccadic suppression.

  View details for DOI 10.1152/jn.01140.2015

  View details for Web of Science ID 000394019600005

  View details for PubMedID 27683894

  View details for PubMedCentralID PMC5174155

• The What and Where of Visual Attention. Neuron Moore, T., Zirnsak, M. 2015; 88 (4): 626-8

  Abstract

  The selective processing of sensory input during attention is known to take many forms, and different forms of attention likely reflect varying underlying neural mechanisms. Bichot and colleagues (2015) identify neurons that appear specialized for the control of feature-based visual attention.

  View details for DOI 10.1016/j.neuron.2015.11.005

  View details for PubMedID 26590339

• Copula Regression Analysis of Simultaneously Recorded Frontal Eye Field and Inferotemporal Spiking Activity during Object-Based Working Memory JOURNAL OF NEUROSCIENCE Hu, M., Clark, K. L., Gong, X., Noudoost, B., Li, M., Moore, T., Liang, H. 2015; 35 (23): 8745-8757

  Abstract

  Inferotemporal (IT) neurons are known to exhibit persistent, stimulus-selective activity during the delay period of object-based working memory tasks. Frontal eye field (FEF) neurons show robust, spatially selective delay period activity during memory-guided saccade tasks. We present a copula regression paradigm to examine neural interaction of these two types of signals between areas IT and FEF of the monkey during a working memory task. This paradigm is based on copula models that can account for both marginal distribution over spiking activity of individual neurons within each area and joint distribution over ensemble activity of neurons between areas. Considering the popular GLMs as marginal models, we developed a general and flexible likelihood framework that uses the copula to integrate separate GLMs into a joint regression analysis. Such joint analysis essentially leads to a multivariate analog of the marginal GLM theory and hence efficient model estimation. In addition, we show that Granger causality between spike trains can be readily assessed via the likelihood ratio statistic. The performance of this method is validated by extensive simulations, and compared favorably to the widely used GLMs. When applied to spiking activity of simultaneously recorded FEF and IT neurons during working memory task, we observed significant Granger causality influence from FEF to IT, but not in the opposite direction, suggesting the role of the FEF in the selection and retention of visual information during working memory. The copula model has the potential to provide unique neurophysiological insights about network properties of the brain.

  View details for DOI 10.1523/JNEUROSCI.5041-14.2015

  View details for Web of Science ID 000358249000008

  View details for PubMedCentralID PMC4461683

• Copula regression analysis of simultaneously recorded frontal eye field and inferotemporal spiking activity during object-based working memory. The Journal of neuroscience : the official journal of the Society for Neuroscience Hu, M., Clark, K. L., Gong, X., Noudoost, B., Li, M., Moore, T., Liang, H. 2015; 35 (23): 8745-57

  Abstract

  Inferotemporal (IT) neurons are known to exhibit persistent, stimulus-selective activity during the delay period of object-based working memory tasks. Frontal eye field (FEF) neurons show robust, spatially selective delay period activity during memory-guided saccade tasks. We present a copula regression paradigm to examine neural interaction of these two types of signals between areas IT and FEF of the monkey during a working memory task. This paradigm is based on copula models that can account for both marginal distribution over spiking activity of individual neurons within each area and joint distribution over ensemble activity of neurons between areas. Considering the popular GLMs as marginal models, we developed a general and flexible likelihood framework that uses the copula to integrate separate GLMs into a joint regression analysis. Such joint analysis essentially leads to a multivariate analog of the marginal GLM theory and hence efficient model estimation. In addition, we show that Granger causality between spike trains can be readily assessed via the likelihood ratio statistic. The performance of this method is validated by extensive simulations, and compared favorably to the widely used GLMs. When applied to spiking activity of simultaneously recorded FEF and IT neurons during working memory task, we observed significant Granger causality influence from FEF to IT, but not in the opposite direction, suggesting the role of the FEF in the selection and retention of visual information during working memory. The copula model has the potential to provide unique neurophysiological insights about network properties of the brain.

  View details for DOI 10.1523/JNEUROSCI.5041-14.2015

  View details for PubMedID 26063909

  View details for PubMedCentralID PMC4461683

• Diverse coupling of neurons to populations in sensory cortex NATURE Okun, M., Steinmetz, N. A., Cossell, L., Iacaruso, M. F., Ko, H., Bartho, P., Moore, T., Hofer, S. B., Mrsic-Flogel, T. D., Carandini, M., Harris, K. D. 2015; 521 (7553): 511-U189

  Abstract

  A large population of neurons can, in principle, produce an astronomical number of distinct firing patterns. In cortex, however, these patterns lie in a space of lower dimension, as if individual neurons were "obedient members of a huge orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus) and monkey (Macaca mulatta) to investigate the relationship between individual neurons and the population, and to establish the underlying circuit mechanisms. We show that neighbouring neurons can differ in their coupling to the overall firing of the population, ranging from strongly coupled 'choristers' to weakly coupled 'soloists'. Population coupling is largely independent of sensory preferences, and it is a fixed cellular attribute, invariant to stimulus conditions. Neurons with high population coupling are more strongly affected by non-sensory behavioural variables such as motor intention. Population coupling reflects a causal relationship, predicting the response of a neuron to optogenetically driven increases in local activity. Moreover, population coupling indicates synaptic connectivity; the population coupling of a neuron, measured in vivo, predicted subsequent in vitro estimates of the number of synapses received from its neighbours. Finally, population coupling provides a compact summary of population activity; knowledge of the population couplings of n neurons predicts a substantial portion of their n(2) pairwise correlations. Population coupling therefore represents a novel, simple measure that characterizes the relationship of each neuron to a larger population, explaining seemingly complex network firing patterns in terms of basic circuit variables.

  View details for DOI 10.1038/nature14273

  View details for Web of Science ID 000355286600041

  View details for PubMedID 25849776

  View details for PubMedCentralID PMC4449271

• Combined contributions of feedforward and feedback inputs to bottom-up attention FRONTIERS IN PSYCHOLOGY Khorsand, P., Moore, T., Soltani, A. 2015; 6

  Abstract

  In order to deal with a large amount of information carried by visual inputs entering the brain at any given point in time, the brain swiftly uses the same inputs to enhance processing in one part of visual field at the expense of the others. These processes, collectively called bottom-up attentional selection, are assumed to solely rely on feedforward processing of the external inputs, as it is implied by the nomenclature. Nevertheless, evidence from recent experimental and modeling studies points to the role of feedback in bottom-up attention. Here, we review behavioral and neural evidence that feedback inputs are important for the formation of signals that could guide attentional selection based on exogenous inputs. Moreover, we review results from a modeling study elucidating mechanisms underlying the emergence of these signals in successive layers of neural populations and how they depend on feedback from higher visual areas. We use these results to interpret and discuss more recent findings that can further unravel feedforward and feedback neural mechanisms underlying bottom-up attention. We argue that while it is descriptively useful to separate feedforward and feedback processes underlying bottom-up attention, these processes cannot be mechanistically separated into two successive stages as they occur at almost the same time and affect neural activity within the same brain areas using similar neural mechanisms. Therefore, understanding the interaction and integration of feedforward and feedback inputs is crucial for better understanding of bottom-up attention.

  View details for DOI 10.3389/fpsyg.2015.00155

  View details for Web of Science ID 000350277200001

  View details for PubMedID 25784883

  View details for PubMedCentralID PMC4345765

• Saccades and shifting receptive fields: anticipating consequences or selecting targets? TRENDS IN COGNITIVE SCIENCES Zirnsak, M., Moore, T. 2014; 18 (12): 621-628

  Abstract

  Saccadic eye movements cause frequent and substantial displacements of the retinal image, but those displacements go unnoticed. It has been widely assumed that this perceived stability emerges from the shifting of visual receptive fields from their current, presaccadic locations to their future, postsaccadic locations in anticipation of the retinal consequences of saccades. Although evidence consistent with this anticipatory remapping has accumulated over the years, more recent work suggests an alternative view. In this opinion article, we examine the evidence of presaccadic receptive field shifts and their relationship to the perceptual changes that accompany saccades. We argue that both reflect the selection of targets for saccades rather than the anticipation of a displaced retinal image.

  View details for DOI 10.1016/j.tics.2014.10.002

  View details for Web of Science ID 000347131000004

  View details for PubMedID 25455690

  View details for PubMedCentralID PMC4279245

• Eye movement preparation modulates neuronal responses in area v4 when dissociated from attentional demands. Neuron Steinmetz, N. A., Moore, T. 2014; 83 (2): 496-506

  Abstract

  We examined whether the preparation of saccadic eye movements, when behaviorally dissociated from covert attention, modulates activity within visual cortex. We measured single-neuron and local field potential (LFP) responses to visual stimuli in area V4 while monkeys covertly attended a stimulus at one location and prepared saccades to a potential target at another. In spite of the irrelevance of visual information at the saccade target, visual activity at that location was modulated at least as much as, and often more than, activity at the covertly attended location. Modulations of activity at the attended and saccade target locations were qualitatively similar and included increased response magnitude, stimulus selectivity, and spiking reliability, as well as increased gamma and decreased low-frequency power of LFPs. These results demonstrate that saccade preparation is sufficient to modulate visual cortical representations and suggest that the interrelationship of oculomotor and attention-related mechanisms extends to posterior visual cortex.

  View details for DOI 10.1016/j.neuron.2014.06.014

  View details for PubMedID 25033188

  View details for PubMedCentralID PMC4130345

• Persistent Spatial Information in the FEF during Object-based Short-term Memory Does Not Contribute to Task Performance JOURNAL OF COGNITIVE NEUROSCIENCE Clark, K. L., Noudoost, B., Moore, T. 2014; 26 (6): 1292-1299

  Abstract

  We previously reported the existence of a persistent spatial signal in the FEF during object-based STM. This persistent activity reflected the location at which the sample appeared, irrespective of the location of upcoming targets. We hypothesized that such a spatial signal could be used to maintain or enhance object-selective memory activity elsewhere in cortex, analogous to the role of a spatial signal during attention. Here, we inactivated a portion of the FEF with GABAa agonist muscimol to test whether the observed activity contributes to object memory performance. We found that, although RTs were slowed for saccades into the inactivated portion of retinotopic space, performance for samples appearing in that region was unimpaired. This contrasts with the devastating effects of the same FEF inactivation on purely spatial working memory, as assessed with the memory-guided saccade task. Thus, in a task in which a significant fraction of FEF neurons displayed persistent, sample location-based activity, disrupting this activity had no impact on task performance.

  View details for DOI 10.1162/jocn_a_00599

  View details for Web of Science ID 000335506100009

  View details for PubMedID 24673408

• Global selection of saccadic target features by neurons in area v4. journal of neuroscience Burrows, B. E., Zirnsak, M., Akhlaghpour, H., Wang, M., Moore, T. 2014; 34 (19): 6700-6706

  Abstract

  Psychophysical and neurophysiological studies indicate that during the preparation of saccades, visual processing at the target location is facilitated automatically by the deployment of attention. It has been assumed that the neural mechanisms involved in presaccadic shifts of attention are purely spatial in nature. Saccade preparation modulates the visual responses of neurons within extrastriate area V4, where the responses to targets are enhanced and responses to nontargets are suppressed. We tested whether this effect also engages a nonspatial form of modulation. We measured the responses of area V4 neurons to oriented gratings in two monkeys (Macaca mulatta) making delayed saccades to targets distant from the neuronal receptive field (RF). We varied the orientation of both the RF stimulus and the saccadic target. We found that, in addition to the spatial modulation, saccade preparation involves a feature-dependent modulation of V4 neuronal responses. Specifically, we found that the suppression of area V4 responses to nontarget stimuli during the preparation of saccades depends on the features of the saccadic target. Presaccadic suppression was absent when the features of the saccadic target matched the features preferred by individual V4 neurons. This feature-dependent modulation occurred in the absence of any feature-attention task. We show that our observations are consistent with a computational framework in which feature-based effects automatically emerge from saccade-related feedback signals that are spatial in nature.

  View details for DOI 10.1523/JNEUROSCI.0867-13.2014

  View details for PubMedID 24806696

  View details for PubMedCentralID PMC4012320

• Visual space is compressed in prefrontal cortex before eye movements. Nature Zirnsak, M., Steinmetz, N. A., Noudoost, B., Xu, K. Z., Moore, T. 2014; 507 (7493): 504-507

  Abstract

  We experience the visual world through a series of saccadic eye movements, each one shifting our gaze to bring objects of interest to the fovea for further processing. Although such movements lead to frequent and substantial displacements of the retinal image, these displacements go unnoticed. It is widely assumed that a primary mechanism underlying this apparent stability is an anticipatory shifting of visual receptive fields (RFs) from their presaccadic to their postsaccadic locations before movement onset. Evidence of this predictive 'remapping' of RFs has been particularly apparent within brain structures involved in gaze control. However, critically absent among that evidence are detailed measurements of visual RFs before movement onset. Here we show that during saccade preparation, rather than remap, RFs of neurons in a prefrontal gaze control area massively converge towards the saccadic target. We mapped the visual RFs of prefrontal neurons during stable fixation and immediately before the onset of eye movements, using multi-electrode recordings in monkeys. Following movements from an initial fixation point to a target, RFs remained stationary in retinocentric space. However, in the period immediately before movement onset, RFs shifted by as much as 18 degrees of visual angle, and converged towards the target location. This convergence resulted in a threefold increase in the proportion of RFs responding to stimuli near the target region. In addition, like in human observers, the population of prefrontal neurons grossly mislocalized presaccadic stimuli as being closer to the target. Our results show that RF shifts do not predict the retinal displacements due to saccades, but instead reflect the overriding perception of target space during eye movements.

  View details for DOI 10.1038/nature13149

  View details for PubMedID 24670771

• A distinct contribution of the frontal eye field to the visual representation of saccadic targets. journal of neuroscience Noudoost, B., Clark, K. L., Moore, T. 2014; 34 (10): 3687-3698

  Abstract

  The responses of neurons within posterior visual cortex are enhanced when response field (RF) stimuli are targeted with saccadic eye movements. Although the motor-related activity within oculomotor structures seems a likely source of the enhancement, the origin of the modulation is unknown. We tested the role of the frontal eye field (FEF) in driving presaccadic modulation in area V4 by inactivating FEF neurons at retinotopically corresponding sites within the macaque monkey (Macaca mulatta) brain. As previously observed, FEF inactivation produced profound, and spatially specific, deficits in memory-guided saccades, and increased the latency, scatter, and duration of visually guided saccades. Despite the clear behavioral deficits, we found that rather than being eliminated or reduced by FEF inactivation, presaccadic enhancement of V4 activity was increased. FEF inactivation nonetheless diminished the stimulus discriminability of V4 visual responses both during fixation and in the presaccadic period. Thus, without input from the FEF, V4 neurons signaled more about the direction of saccades and less about the features of the saccadic target. In addition, FEF inactivation significantly increased the suppressive effects of non-RF stimuli on V4 activity. These results reveal multiple sources of presaccadic modulation in V4 and suggest that the FEF contributes uniquely to the presaccadic specification of visual target features.

  View details for DOI 10.1523/JNEUROSCI.3824-13.2014

  View details for PubMedID 24599467

  View details for PubMedCentralID PMC3942584

• Latency of chromatic information in area V4. Journal of physiology, Paris Chang, M., Xian, S., Rubin, J., Moore, T. 2014; 108 (1): 11-17

  Abstract

  In the primate visual system, information about color is known to be carried in separate divisions of the retino-geniculo-cortical pathway. From the retina, responses of photoreceptors to short (S), medium (M), and long (L) wavelengths of light are processed in two different opponent pathways. Signals in the S-opponent pathway, or blue/yellow channel, have been found to lag behind signals in the L/M-opponent pathway, or red/green channel in primary visual area V1, and psychophysical studies have suggested similar perceptual delays. However, more recent psychophysical studies have found that perceptual differences are negligible with the proper controls, suggesting that information between the two channels is integrated at some stage of processing beyond V1. To study the timing of color signals further downstream in visual cortex, we examined the responses of neurons in area V4 to colored stimuli varying along the two cardinal axes of the equiluminant opponent color space. We used information theory to measure the mutual information between the stimuli presented and the neural responses in short time windows in order to estimate the latency of color information in area V4. We found that on average, despite the latency difference in V1, information about S-opponent signals arrives in V4 at the same time as information about L/M-opponent signals. This work indicates a convergence of signal timing among chromatic channels within extrastriate cortex.

  View details for DOI 10.1016/j.jphysparis.2013.05.006

  View details for PubMedID 23811158

• Distinguishing bias from sensitivity effects in multialternative detection tasks. Journal of vision Sridharan, D., Steinmetz, N. A., Moore, T., Knudsen, E. I. 2014; 14 (9)

  Abstract

  Studies investigating the neural bases of cognitive phenomena increasingly employ multialternative detection tasks that seek to measure the ability to detect a target stimulus or changes in some target feature (e.g., orientation or direction of motion) that could occur at one of many locations. In such tasks, it is essential to distinguish the behavioral and neural correlates of enhanced perceptual sensitivity from those of increased bias for a particular location or choice (choice bias). However, making such a distinction is not possible with established approaches. We present a new signal detection model that decouples the behavioral effects of choice bias from those of perceptual sensitivity in multialternative (change) detection tasks. By formulating the perceptual decision in a multidimensional decision space, our model quantifies the respective contributions of bias and sensitivity to multialternative behavioral choices. With a combination of analytical and numerical approaches, we demonstrate an optimal, one-to-one mapping between model parameters and choice probabilities even for tasks involving arbitrarily large numbers of alternatives. We validated the model with published data from two ternary choice experiments: a target-detection experiment and a length-discrimination experiment. The results of this validation provided novel insights into perceptual processes (sensory noise and competitive interactions) that can accurately and parsimoniously account for observers' behavior in each task. The model will find important application in identifying and interpreting the effects of behavioral manipulations (e.g., cueing attention) or neural perturbations (e.g., stimulation or inactivation) in a variety of multialternative tasks of perception, attention, and decision-making.

  View details for DOI 10.1167/14.9.16

  View details for PubMedID 25146574

  View details for PubMedCentralID PMC4141865

• The Influence of Gaze Control on Visual Perception: Eye Movements and Visual Stability. Cold Spring Harbor symposia on quantitative biology Krock, R. M., Moore, T. 2014; 79: 123-130

  Abstract

  Primates make several saccadic eye movements each second, and yet the retinal motion these movements generate goes unnoticed. Saccadic suppression is a profound loss of visual sensitivity occurring around the time of eye movements, and it is thought to contribute to visual stability by blunting the perception of self-generated motion. Neurophysiological studies have produced evidence that neurons throughout the visual system, including both the dorsal and ventral streams of extrastriate visual cortex, show a reduction in visual responses or sensitivity around the time of saccades. However, the source of this suppression remains unknown. We review evidence that oculomotor regions such as the superior colliculus and frontal eye field may play a role, as well as anatomical data that place constraints on possible mechanisms of suppression.

  View details for DOI 10.1101/sqb.2014.79.024836

  View details for PubMedID 25752313

• Distinguishing bias from sensitivity effects in multialternative detection tasks. Journal of vision Sridharan, D., Steinmetz, N. A., Moore, T., Knudsen, E. I. 2014; 14 (9)

  Abstract

  Studies investigating the neural bases of cognitive phenomena increasingly employ multialternative detection tasks that seek to measure the ability to detect a target stimulus or changes in some target feature (e.g., orientation or direction of motion) that could occur at one of many locations. In such tasks, it is essential to distinguish the behavioral and neural correlates of enhanced perceptual sensitivity from those of increased bias for a particular location or choice (choice bias). However, making such a distinction is not possible with established approaches. We present a new signal detection model that decouples the behavioral effects of choice bias from those of perceptual sensitivity in multialternative (change) detection tasks. By formulating the perceptual decision in a multidimensional decision space, our model quantifies the respective contributions of bias and sensitivity to multialternative behavioral choices. With a combination of analytical and numerical approaches, we demonstrate an optimal, one-to-one mapping between model parameters and choice probabilities even for tasks involving arbitrarily large numbers of alternatives. We validated the model with published data from two ternary choice experiments: a target-detection experiment and a length-discrimination experiment. The results of this validation provided novel insights into perceptual processes (sensory noise and competitive interactions) that can accurately and parsimoniously account for observers' behavior in each task. The model will find important application in identifying and interpreting the effects of behavioral manipulations (e.g., cueing attention) or neural perturbations (e.g., stimulation or inactivation) in a variety of multialternative tasks of perception, attention, and decision-making.

  View details for DOI 10.1167/14.9.16

  View details for PubMedID 25146574

  View details for PubMedCentralID PMC4141865

• Prefrontal contributions to visual selective attention. Annual review of neuroscience Squire, R. F., Noudoost, B., Schafer, R. J., Moore, T. 2013; 36: 451-466

  Abstract

  The faculty of attention endows us with the capacity to process important sensory information selectively while disregarding information that is potentially distracting. Much of our understanding of the neural circuitry underlying this fundamental cognitive function comes from neurophysiological studies within the visual modality. Past evidence suggests that a principal function of the prefrontal cortex (PFC) is selective attention and that this function involves the modulation of sensory signals within posterior cortices. In this review, we discuss recent progress in identifying the specific prefrontal circuits controlling visual attention and its neural correlates within the primate visual system. In addition, we examine the persisting challenge of precisely defining how behavior should be affected when attentional function is lost.

  View details for DOI 10.1146/annurev-neuro-062111-150439

  View details for PubMedID 23841841

• Dissociable dopaminergic control of saccadic target selection and its implications for reward modulation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Soltani, A., Noudoost, B., Moore, T. 2013; 110 (9): 3579-3584

  Abstract

  To investigate mechanisms by which reward modulates target selection, we studied the behavioral effects of perturbing dopaminergic activity within the frontal eye field (FEF) of monkeys performing a saccadic choice task and simulated the effects using a plausible cortical network. We found that manipulation of FEF activity either by blocking D1 receptors (D1Rs) or by stimulating D2 receptors (D2Rs) increased the tendency to choose targets in the response field of the affected site. However, the D1R manipulation decreased the tendency to repeat choices on subsequent trials, whereas the D2R manipulation increased that tendency. Moreover, the amount of shift in target selection resulting from the two manipulations correlated in opposite ways with the baseline stochasticity of choice behavior. Our network simulation results suggest that D1Rs influence target selection mainly through their effects on the strength of inputs to the FEF and on recurrent connectivity, whereas D2Rs influence the excitability of FEF output neurons. Altogether, these results reveal dissociable dopaminergic mechanisms influencing target selection and suggest how reward can influence adaptive choice behavior via prefrontal dopamine.

  View details for DOI 10.1073/pnas.1221236110

  View details for Web of Science ID 000315841900075

  View details for PubMedID 23401524

  View details for PubMedCentralID PMC3587234

• Parietal and prefrontal neurons driven to distraction. Nature neuroscience Noudoost, B., Moore, T. 2013; 16 (1): 8-9

  View details for DOI 10.1038/nn.3291

  View details for PubMedID 23257928

• Persistent Spatial Information in the Frontal Eye Field during Object-Based Short-Term Memory JOURNAL OF NEUROSCIENCE Clark, K. L., Noudoost, B., Moore, T. 2012; 32 (32): 10907-10914

  Abstract

  Spatial attention is known to gate entry into visual short-term memory, and some evidence suggests that spatial signals may also play a role in binding features or protecting object representations during memory maintenance. To examine the persistence of spatial signals during object short-term memory, the activity of neurons in the frontal eye field (FEF) of macaque monkeys was recorded during an object-based delayed match-to-sample task. In this task, monkeys were trained to remember an object image over a brief delay, regardless of the locations of the sample or target presentation. FEF neurons exhibited visual, delay, and target period activity, including selectivity for sample location and target location. Delay period activity represented the sample location throughout the delay, despite the irrelevance of spatial information for successful task completion. Furthermore, neurons continued to encode sample position in a variant of the task in which the matching stimulus never appeared in their response field, confirming that FEF maintains sample location independent of subsequent behavioral relevance. FEF neurons also exhibited target-position-dependent anticipatory activity immediately before target onset, suggesting that monkeys predicted target position within blocks. These results show that FEF neurons maintain spatial information during short-term memory, even when that information is irrelevant for task performance.

  View details for DOI 10.1523/JNEUROSCI.1450-12.2012

  View details for Web of Science ID 000307640000012

  View details for PubMedID 22875925

  View details for PubMedCentralID PMC3491065

• Lumping and Splitting the Neural Circuitry of Visual Attention NEURON Steinmetz, N. A., Moore, T. 2012; 73 (3): 410-412

  Abstract

  Shifts of gaze and of covert attention rely on tightly linked yet divergent neural mechanisms. In this issue of Neuron, Gregoriou et al. (2012) provide interesting evidence that different functional classes of neurons within the frontal eye field contribute uniquely to these two functions.

  View details for DOI 10.1016/j.neuron.2012.01.011

  View details for Web of Science ID 000300140600003

  View details for PubMedID 22325195

• Dissociation of Response Variability from Firing Rate Effects in Frontal Eye Field Neurons during Visual Stimulation, Working Memory, and Attention JOURNAL OF NEUROSCIENCE Chang, M. H., Armstrong, K. M., Moore, T. 2012; 32 (6): 2204-2216

  Abstract

  Recent studies suggest that trial-to-trial variability of neuronal spiking responses may provide important information about behavioral state. Observed changes in variability during sensory stimulation, attention, motor preparation, and visual discrimination suggest that variability may reflect the engagement of neurons in a behavioral task. We examined changes in spiking variability of frontal eye field (FEF) neurons in a change detection task requiring monkeys to remember a visually cued location and direct attention to that location while ignoring distracters elsewhere. In this task, the firing rates (FRs) of FEF neurons not only continuously reflect the location of the remembered cue and select targets, but also predict detection performance on a trial-by-trial basis. Changes in FEF response variability, as measured by the Fano factor (FF), showed clear dissociations from changes in FR. The FF declined in response to visual stimulation at all tested locations, even in the opposite hemifield, indicating much broader spatial tuning of the FF compared with the FR. Furthermore, despite robust spatial modulation of the FR throughout all epochs of the task, spatial tuning of the FF did not persist throughout the delay period, nor did it show attentional modulation. These results indicate that changes in variability, at least in the FEF, are most effectively driven by visual stimulation, while behavioral engagement is not sufficient. Instead, changes in variability may reflect shifts in the balance between feedforward and recurrent sources of excitatory drive.

  View details for DOI 10.1523/JNEUROSCI.2967-11.2012

  View details for Web of Science ID 000300207900030

  View details for PubMedID 22323732

  View details for PubMedCentralID PMC3439504

• The role of neuromodulators in selective attention TRENDS IN COGNITIVE SCIENCES Noudoost, B., Moore, T. 2011; 15 (12): 585-591

  Abstract

  Several classes of neurotransmitters exert modulatory effects on a broad and diverse population of neurons throughout the brain. Some of these neuromodulators, especially acetylcholine and dopamine, have long been implicated in the neural control of selective attention. We review recent evidence and evolving ideas about the importance of these neuromodulatory systems in attention, particularly visual selective attention. We conclude that, although our understanding of their role in the neural circuitry of selective attention remains rudimentary, recent research has begun to suggest unique contributions of neuromodulators to different forms of attention, such as bottom-up and top-down attention.

  View details for DOI 10.1016/j.tics.2011.10.006

  View details for Web of Science ID 000298127900005

  View details for PubMedID 22074811

  View details for PubMedCentralID PMC3351278

• Selective Attention from Voluntary Control of Neurons in Prefrontal Cortex SCIENCE Schafer, R. J., Moore, T. 2011; 332 (6037): 1568-1571

  Abstract

  Animals can learn to voluntarily control neuronal activity within various brain areas through operant conditioning, but the relevance of that control to cognitive functions is unknown. We found that rhesus monkeys can control the activity of neurons within the frontal eye field (FEF), an oculomotor area of the prefrontal cortex. However, operantly driven FEF activity was primarily associated with selective visual attention, and not oculomotor preparation. Attentional effects were untrained and were observed both behaviorally and neurophysiologically. Furthermore, selective attention correlated with voluntary, but not spontaneous, fluctuations in FEF activity. Our results reveal a specific association of voluntarily driven neuronal activity with "top-down" attention and suggest a basis for the use of neurofeedback training to treat disorders of attention.

  View details for DOI 10.1126/science.1199892

  View details for Web of Science ID 000291990000048

  View details for PubMedID 21617042

  View details for PubMedCentralID PMC3371378

• Control of visual cortical signals by prefrontal dopamine NATURE Noudoost, B., Moore, T. 2011; 474 (7351): 372-375

  Abstract

  The prefrontal cortex is thought to modulate sensory signals in posterior cortices during top-down attention, but little is known about the underlying neural circuitry. Experimental and clinical evidence indicate that prefrontal dopamine has an important role in cognitive functions, acting predominantly through D1 receptors. Here we show that dopamine D1 receptors mediate prefrontal control of signals in the visual cortex of macaques (Macaca mulatta). We pharmacologically altered D1-receptor-mediated activity in the frontal eye field of the prefrontal cortex and measured the effect on the responses of neurons in area V4 of the visual cortex. This manipulation was sufficient to enhance the magnitude, the orientation selectivity and the reliability of V4 visual responses to an extent comparable with the known effects of top-down attention. The enhancement of V4 signals was restricted to neurons with response fields overlapping the part of visual space affected by the D1 receptor manipulation. Altering either D1- or D2-receptor-mediated frontal eye field activity increased saccadic target selection but the D2 receptor manipulation did not enhance V4 signals. Our results identify a role for D1 receptors in mediating the control of visual cortical signals by the prefrontal cortex and suggest how processing in sensory areas could be altered in mental disorders involving prefrontal dopamine.

  View details for DOI 10.1038/nature09995

  View details for Web of Science ID 000291647100044

  View details for PubMedID 21572439

  View details for PubMedCentralID PMC3117113

• A reliable microinjectrode system for use in behaving monkeys (vol 194, pg 218, 2011) JOURNAL OF NEUROSCIENCE METHODS Noudoost, B., Moore, T. 2011; 198 (2): 364

  View details for DOI 10.1016/j.jneumeth.2011.04.003

  View details for Web of Science ID 000292435900027

• Probing neural circuitry and function with electrical microstimulation PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Clark, K. L., Armstrong, K. M., Moore, T. 2011; 278 (1709): 1121-1130

  Abstract

  Since the discovery of the nervous system's electrical excitability more than 200 years ago, neuroscientists have used electrical stimulation to manipulate brain activity in order to study its function. Microstimulation has been a valuable technique for probing neural circuitry and identifying networks of neurons that underlie perception, movement and cognition. In this review, we focus on the use of stimulation in behaving primates, an experimental system that permits causal inferences to be made about the effect of stimulation-induced activity on the resulting behaviour or neural signals elsewhere in the brain.

  View details for DOI 10.1098/rspb.2010.2211

  View details for Web of Science ID 000288241300001

  View details for PubMedID 21247952

  View details for PubMedCentralID PMC3049083

• A reliable microinjectrode system for use in behaving monkeys JOURNAL OF NEUROSCIENCE METHODS Noudoost, B., Moore, T. 2011; 194 (2): 218-223

  Abstract

  We describe a modified system for the precise delivery of small volumes of drugs to brain sites of behaving monkeys during simultaneous single-neuron electrophysiology. The system combines a conventional microelectrode for recording single neurons and a small gauge microsyringe in a durable design. It incorporates newly available microfluidic components to achieve high-precision fluidic control. The system is inexpensive, reusable and easy to fabricate; it minimizes neural tissue damage and achieves reliable single-neuron recordings at the injection site.

  View details for DOI 10.1016/j.jneumeth.2010.10.009

  View details for Web of Science ID 000289923100003

  View details for PubMedID 20951736

  View details for PubMedCentralID PMC3161729

• Top-down control of visual attention CURRENT OPINION IN NEUROBIOLOGY Noudoost, B., Chang, M. H., Steinmetz, N. A., Moore, T. 2010; 20 (2): 183-190

  Abstract

  Top-down visual attention improves perception of selected stimuli and that improvement is reflected in the neural activity at many stages throughout the visual system. Recent studies of top-down attention have elaborated on the signatures of its effects within visual cortex and have begun identifying its causal basis. Evidence from these studies suggests that the correlates of spatial attention exhibited by neurons within the visual system originate from a distributed network of structures involved in the programming of saccadic eye movements. We summarize this evidence and discuss its relationship to the neural mechanisms of spatial working memory.

  View details for DOI 10.1016/j.conb.2010.02.003

  View details for Web of Science ID 000278258900008

  View details for PubMedID 20303256

  View details for PubMedCentralID PMC2901796

• Stimulus onset quenches neural variability: a widespread cortical phenomenon NATURE NEUROSCIENCE Churchland, M. M., Yu, B. M., Cunningham, J. P., Sugrue, L. P., Cohen, M. R., Corrado, G. S., Newsome, W. T., Clark, A. M., Hosseini, P., Scott, B. B., Bradley, D. C., Smith, M. A., Kohn, A., Movshon, J. A., Armstrong, K. M., Moore, T., Chang, S. W., Snyder, L. H., Lisberger, S. G., Priebe, N. J., Finn, I. M., Ferster, D., Ryu, S. I., Santhanam, G., Sahani, M., Shenoy, K. V. 2010; 13 (3): 369-U25

  Abstract

  Neural responses are typically characterized by computing the mean firing rate, but response variability can exist across trials. Many studies have examined the effect of a stimulus on the mean response, but few have examined the effect on response variability. We measured neural variability in 13 extracellularly recorded datasets and one intracellularly recorded dataset from seven areas spanning the four cortical lobes in monkeys and cats. In every case, stimulus onset caused a decline in neural variability. This occurred even when the stimulus produced little change in mean firing rate. The variability decline was observed in membrane potential recordings, in the spiking of individual neurons and in correlated spiking variability measured with implanted 96-electrode arrays. The variability decline was observed for all stimuli tested, regardless of whether the animal was awake, behaving or anaesthetized. This widespread variability decline suggests a rather general property of cortex, that its state is stabilized by an input.

  View details for DOI 10.1038/nn.2501

  View details for Web of Science ID 000274860100020

  View details for PubMedID 20173745

  View details for PubMedCentralID PMC2828350

• Changes in the Response Rate and Response Variability of Area V4 Neurons During the Preparation of Saccadic Eye Movements JOURNAL OF NEUROPHYSIOLOGY Steinmetz, N. A., Moore, T. 2010; 103 (3): 1171-1178

  Abstract

  The visually driven responses of macaque area V4 neurons are modulated during the preparation of saccadic eye movements, but the relationship between presaccadic modulation in area V4 and saccade preparation is poorly understood. Recent neurophysiological studies suggest that the variability across trials of spiking responses provides a more reliable signature of motor preparation than mean firing rate across trials. We compared the dynamics of the response rate and the variability in the rate across trials for area V4 neurons during the preparation of visually guided saccades. As in previous reports, we found that the mean firing rate of V4 neurons was enhanced when saccades were prepared to stimuli within a neuron's receptive field (RF) in comparison with saccades to a non-RF location. Further, we found robust decreases in response variability prior to saccades and found that these decreases predicted saccadic reaction times for saccades both to RF and non-RF stimuli. Importantly, response variability predicted reaction time whether or not there were any accompanying changes in mean firing rate. In addition to predicting saccade direction, the mean firing rate could also predict reaction time, but only for saccades directed to the RF stimuli. These results demonstrate that response variability of area V4 neurons, like mean response rate, provides a signature of saccade preparation. However, the two signatures reflect complementary aspects of that preparation.

  View details for DOI 10.1152/jn.00689.2009

  View details for Web of Science ID 000275656200003

  View details for PubMedID 20018834

• Selection and Maintenance of Spatial Information by Frontal Eye Field Neurons JOURNAL OF NEUROSCIENCE Armstrong, K. M., Chang, M. H., Moore, T. 2009; 29 (50): 15621-15629

  Abstract

  Voluntary attention is often allocated according to internally maintained goals. Recent evidence indicates that the frontal eye field (FEF) participates in the deployment of spatial attention, even in the absence of saccadic eye movements. In addition, many FEF neurons maintain persistent representations of impending saccades. However, the role of persistent activity in the general maintenance of spatial information, and its relationship to spatial attention, has not been explored. We recorded the responses of single FEF neurons in monkeys trained to remember cued locations in order to detect changes in targets embedded among distracters in a task that did not involve saccades. We found that FEF neurons persistently encoded the cued location throughout the trial during the delay period, when no visual stimuli were present, and during visual discrimination. Furthermore, FEF activity reliably predicted whether monkeys would detect the target change. Population analyses revealed that FEF neurons with persistent activity were more effective at selecting the target from among distracters than neurons lacking persistent activity. These results demonstrate that FEF neurons maintain spatial information in the absence of saccade preparation and suggest that this maintenance contributes to the selection of relevant visual stimuli.

  View details for DOI 10.1523/JNEUROSCI.4465-09.2009

  View details for Web of Science ID 000272837000002

  View details for PubMedID 20016076

  View details for PubMedCentralID PMC3351279

• Influence and Limitations of Popout in the Selection of Salient Visual Stimuli by Area V4 Neurons JOURNAL OF NEUROSCIENCE Burrows, B. E., Moore, T. 2009; 29 (48): 15169-15177

  Abstract

  The neural mechanism of bottom-up attention and its relationship to top-down attention are poorly understood. Visual stimuli that differ from others in their component features are salient and tend to draw attention in a bottom-up manner. "Popout" stimuli differ uniformly from surrounding items and are more easily detected than stimuli composed of a conjunction of surrounding features. We compared the responses of single area V4 neurons to popout and conjunction stimuli appearing within the classical receptive field (CRF) and found that their responses are modulated by popout. This selectivity was more robust when larger numbers of surrounding items and multiple features were included in the display, and it was absent when only a few items were presented immediately outside the CRF. In addition, the popout modulation of V4 activity was eliminated when top-down attention was directed to locations outside of the CRFs during saccade preparation, indicating that the salience of popout stimuli is not sufficient to drive selection by V4 neurons. These results demonstrate that neurons in feature-selective cortex are influenced by bottom-up attention, but that this influence is limited by top-down attention.

  View details for DOI 10.1523/JNEUROSCI.3710-09.2009

  View details for Web of Science ID 000272361700017

  View details for PubMedID 19955369

  View details for PubMedCentralID PMC2824599

• Dynamic sensitivity of area V4 neurons during saccade preparation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Han, X., Xian, S. X., Moore, T. 2009; 106 (31): 13046-13051

  Abstract

  During the preparation of saccadic eye movements, visual attention is confined to the target of intended fixation and there is a corresponding diminution of visual sensitivity at nontarget locations. Neurons within the macaque visual cortex exhibit correlates of these perceptual changes, such as in area V4, where neuronal responses are enhanced during the preparation of saccades to stimuli within the receptive field (RF), and responses are suppressed during the preparation of saccades to other locations. Both the perceptual and neurophysiological effects suggest that the sensitivity of visual cortical neurons to input is dynamic during saccade preparation. We probed the contrast sensitivity of area V4 neurons to nontarget stimuli at varying times during the preparation of saccades to locations outside of the neuron's receptive field. We found that the contrast sensitivity of many neurons is profoundly altered within 50 ms of saccade onset. The luminance or color contrast sensitivity of individual V4 neurons could increase, decrease, or remain unchanged before saccade onset. For luminance contrast sensitivity, decreases in sensitivity were more frequent and larger in magnitude, resulting in an overall decrement in sensitivity across the population. For color contrast, the effects were smaller and more heterogeneous, resulting in little or no overall change in sensitivity across the population. Our results demonstrate the dynamic influence that saccade preparation has on the sensitivity of visual cortical neurons and suggest a basis for the changes in perception known to occur during saccade preparation.

  View details for DOI 10.1073/pnas.0902412106

  View details for Web of Science ID 000268667600086

  View details for PubMedID 19622736

  View details for PubMedCentralID PMC2722339

• Presaccadic discrimination of receptive field stimuli by area V4 neurons Buenos Aires Workshop on Visual Attention Moore, T., Chang, M. H. PERGAMON-ELSEVIER SCIENCE LTD. 2009: 1227–32

  Abstract

  Previous studies have shown that the visual responses of neurons in extrastriate area V4 are enhanced prior to saccadic eye movements that target receptive field (RF) stimuli. We used receiver-operator characteristic (ROC) analysis to quantify how well V4 neurons could discriminate stable RF stimuli targeted by visually-guided saccades or ignored during saccades elsewhere. We found that discrimination was transiently enhanced prior to saccades to RF stimuli whereas it was reduced prior to saccades elsewhere. Similar to what is observed during covert attention and after frontal eye field microstimulation, the changes in stimulus discrimination were due in part to changes in response magnitude. In addition, we found evidence of an increased reliability of responses when saccades were made to the RF stimulus. These results highlight the similarity of mechanisms driving covert spatial attention and the preparation of visually-guided saccades.

  View details for DOI 10.1016/j.visres.2008.03.018

  View details for Web of Science ID 000267168800018

  View details for PubMedID 18501949

  View details for PubMedCentralID PMC2724369

• Attention governs action in the primate frontal eye field NEURON Schafer, R. J., Moore, T. 2007; 56 (3): 541-551

  Abstract

  While the motor and attentional roles of the frontal eye field (FEF) are well documented, the relationship between them is unknown. We exploited the known influence of visual motion on the apparent positions of targets, and measured how this illusion affects saccadic eye movements during FEF microstimulation. Without microstimulation, saccades to a moving grating are biased in the direction of motion, consistent with the apparent position illusion. Here we show that microstimulation of spatially aligned FEF representations increases the influence of this illusion on saccades. Rather than simply impose a fixed-vector signal, subthreshold stimulation directed saccades away from the FEF movement field, and instead more strongly in the direction of visual motion. These results demonstrate that the attentional effects of FEF stimulation govern visually guided saccades, and suggest that the two roles of the FEF work together to select both the features of a target and the appropriate movement to foveate it.

  View details for DOI 10.1016/j.neuron.2007.09.029

  View details for Web of Science ID 000250774600012

  View details for PubMedID 17988636

  View details for PubMedCentralID PMC2129094

• Electrical signals propagate unbiased in cortex NEURON Gilja, V., Moore, T. 2007; 55 (5): 684-686

  Abstract

  The greater spatial coherence of local field potentials (LFPs) compared with that of spiking activity has been attributed to frequency-dependent propagation of signals through the cortical medium. However, in this issue of Neuron, Logothetis and colleagues show that signal propagation within cortex is largely unbiased across different frequencies, thus suggesting a more functional and interpretable basis of LFP coherence.

  View details for DOI 10.1016/j.neuron.2007.08.012

  View details for Web of Science ID 000249857000004

  View details for PubMedID 17785175

• Temporal patterning of saccadic eye movement signals JOURNAL OF NEUROSCIENCE Kimmel, D. L., Moore, T. 2007; 27 (29): 7619-7630

  Abstract

  Electrical microstimulation is used widely in experimental neurophysiology to examine causal links between specific brain areas and their behavioral functions and is used clinically to treat neurological and psychiatric disorders in patients. Typically, microstimulation is applied to local brain regions as a train of equally spaced current pulses. We were interested in the sensitivity of a neural circuit to a train of variably spaced pulses, as is observed in physiological spike trains. We compared the effect of fixed, decelerating, accelerating, and randomly varying microstimulation patterns on the likelihood and metrics of eye movements evoked from the frontal eye field of monkeys, while holding the mean interpulse interval constant. Our results demonstrate that the pattern of microstimulation pulses strongly influences the probability of evoking a saccade, as well as the metrics of the saccades themselves. Specifically, the pattern most closely resembling physiological spike trains (accelerating pattern) was most effective at evoking a saccade, three times more so than the least effective decelerating pattern. A saccade-triggered average of effective random trains confirmed the positive relationship between accelerating rate and efficacy. These results have important implications for the use of electrical microstimulation in both experimental and clinical settings and suggest a means to study the role of temporal pattern in the encoding of behavioral and cognitive functions.

  View details for DOI 10.1523/JNEUROSCI.0386-07.2007

  View details for Web of Science ID 000248177900001

  View details for PubMedID 17634356

• Rapid enhancement of visual cortical response discriminability by microstimulation of the frontal eye field PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Armstrong, K. M., Moore, T. 2007; 104 (22): 9499-9504

  Abstract

  Visual attention provides a means of selecting among the barrage of information reaching the retina and of enhancing the perceptual discriminability of relevant stimuli. Neurophysiological studies in monkeys and functional imaging studies in humans have demonstrated neural correlates of these perceptual improvements in visual cortex during attention. Importantly, voluntary attention improves the discriminability of visual cortical responses to relevant stimuli. Recent work aimed at identifying sources of attentional modulation has implicated the frontal eye field (FEF) in driving spatial attention. Subthreshold microstimulation of the FEF enhances the responses of area V4 neurons to spatially corresponding stimuli. However, it is not known whether these enhancements include improved visual-response discriminability, a hallmark of voluntary attention. We used receiver-operator characteristic analysis to quantify how well V4 responses discriminated visual stimuli and examined how discriminability was affected by FEF microstimulation. Discriminability of responses to stable visual stimuli decayed over time but was transiently restored after microstimulation of the FEF. As observed during voluntary attention, the enhancement resulted only from changes in the magnitude of V4 responses and not in the relationship between response magnitude and variance. Enhanced response discriminability was apparent immediately after microstimulation and was reliable within 40 ms of microstimulation onset, indicating a direct influence of FEF stimulation on visual representations. These results contribute to the mounting evidence that saccade-related signals are a source of spatial attentive selection.

  View details for DOI 10.1073/pnas.0701104104

  View details for Web of Science ID 000246935700074

  View details for PubMedID 17517599

  View details for PubMedCentralID PMC1890523

• Changes in visual receptive fields with microstimulation of frontal cortex NEURON Armstrong, K. M., Fitzgerald, J. K., Moore, T. 2006; 50 (5): 791-798

  Abstract

  The influence of attention on visual cortical neurons has been described in terms of its effect on the structure of receptive fields (RFs), where multiple stimuli compete to drive neural responses and ultimately behavior. We stimulated the frontal eye field (FEF) of passively fixating monkeys and produced changes in V4 responses similar to known effects of voluntary attention. Subthreshold FEF stimulation enhanced visual responses at particular locations within the RF and altered the interaction between pairs of RF stimuli to favor those aligned with the activated FEF site. Thus, we could influence which stimulus drove the responses of individual V4 neurons. These results suggest that spatial signals involved in saccade preparation are used to covertly select among multiple stimuli appearing within the RFs of visual cortical neurons.

  View details for DOI 10.1016/j.neuron.2006.05.010

  View details for Web of Science ID 000238165000013

  View details for PubMedID 16731516

• The neurobiology of visual attention: finding sources CURRENT OPINION IN NEUROBIOLOGY Moore, T. 2006; 16 (2): 159-165

  Abstract

  The profusion of progress during the past twenty years in identifying neural correlates of selective attention within the visual system has left open the question of how visual representations are biased to favor target stimuli. Studies aimed at specifying the mechanisms that can be causally implicated in the control of visual selective attention have only recently begun in earnest. Employing both the psychophysical and the neuroanatomical data, recent neurophysiological experiments in monkeys and neuroimaging studies in humans are converging on the neural circuits that provide the source of at least some forms of attentional control signals.

  View details for DOI 10.1016/j.conb.2006.03.009

  View details for Web of Science ID 000237234700006

  View details for PubMedID 16563729

• Visual and oculomotor selection: links, causes and implications for spatial attention TRENDS IN COGNITIVE SCIENCES Awh, E., Armstrong, K. M., Moore, T. 2006; 10 (3): 124-130

  Abstract

  Natural scenes contain far more information than can be processed simultaneously. Thus, our visually guided behavior depends crucially on the capacity to attend to relevant stimuli. Past studies have provided compelling evidence of functional overlap of the neural mechanisms that control spatial attention and saccadic eye movements. Recent neurophysiological work demonstrates that the neural circuits involved in the preparation of saccades also play a causal role in directing covert spatial attention. At the same time, other studies have identified separable neural populations that contribute uniquely to visual and oculomotor selection. Taken together, all of the recent work suggests how visual and oculomotor signals are integrated to simultaneously select the visual attributes of targets and the saccades needed to fixate them.

  View details for DOI 10.1016/j.tics.2006.01.001

  View details for Web of Science ID 000236533800010

  View details for PubMedID 16469523

• Representations of faces and body parts in macaque temporal cortex: A functional MRI study PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Pinsk, M. A., DeSimone, K., Moore, T., Gross, C. G., Kastner, S. 2005; 102 (19): 6996-7001

  Abstract

  Human neuroimaging studies suggest that areas in temporal cortex respond preferentially to certain biologically relevant stimulus categories such as faces and bodies. Single-cell studies in monkeys have reported cells in inferior temporal cortex that respond selectively to faces, hands, and bodies but provide little evidence of large clusters of category-specific cells that would form "areas." We probed the category selectivity of macaque temporal cortex for representations of monkey faces and monkey body parts relative to man-made objects using functional MRI in animals trained to fixate. Two face-selective areas were activated bilaterally in the posterior and anterior superior temporal sulcus exhibiting different degrees of category selectivity. The posterior face area was more extensively activated in the right hemisphere than in the left hemisphere. Immediately adjacent to the face areas, regions were activated bilaterally responding preferentially to body parts. Our findings suggest a category-selective organization for faces and body parts in macaque temporal cortex.

  View details for DOI 10.1073/pnas.0502605102

  View details for Web of Science ID 000229048500064

  View details for PubMedID 15860578

  View details for PubMedCentralID PMC1100800

• Methods for functional magnetic resonance imaging in normal and lesioned behaving monkeys JOURNAL OF NEUROSCIENCE METHODS Pinsk, M. A., Moore, T., Richter, M. C., Gross, C. G., Kastner, S. 2005; 143 (2): 179-195

  Abstract

  Methods for performing functional magnetic resonance imaging (fMRI) studies in behaving and lesioned monkeys using a human MR scanner are reported. Materials for head implant surgery were selected based on tests for magnetic susceptibility. A primate chair with a rigid head fixation system and a mock scanner environment for training were developed. To perform controlled visual studies, monkeys were trained to maintain fixation for several minutes using a novel training technique that utilized continuous juice rewards. A surface coil was used to acquire anatomical and functional images in four monkeys, one with a partial lesion of striate cortex. High-resolution anatomical images were used after non-uniform intensity correction to create cortical surface reconstructions of both lesioned and normal hemispheres. Our methods were confirmed in two visual experiments, in which functional activations were obtained during both free viewing and fixation conditions. In one experiment, face-selective activity was found in the fundus and banks of the superior temporal sulcus and the middle temporal gyrus in monkeys viewing pictures of faces and objects while maintaining fixation. In a second experiment, regions in occipital, parietal, and frontal cortex were activated in lesioned and normal animals viewing a cartoon movie. Importantly, in the animal with the striate lesion, fMRI signals were obtained in the immediate vicinity of the lesion. Our results extend those previously reported by providing a detailed account of the technique and by demonstrating the feasibility of fMRI in monkeys with lesions.

  View details for DOI 10.1016/j.jneumeth.2004.10.003

  View details for Web of Science ID 000228708900011

  View details for PubMedID 15814151

• A map of complex movements in motor cortex of primates 1st Behavioural Brain Sciences Symposium Graziano, M. S., Taylor, C. S., Cooke, D. F., Moore, T. PSYCHOLOGY PRESS. 2005: 211–232

  View details for Web of Science ID 000289230900010

• Homeland defense begins in precentral cortex. Focus on "Sensorimotor integration in the precentral gyrus: Polysensory neurons and defensive movements" JOURNAL OF NEUROPHYSIOLOGY Moore, T. 2004; 91 (4): 1456-1456

  View details for DOI 10.1152/jn.01085.2003

  View details for Web of Science ID 000220086100002

  View details for PubMedID 15010494

• Distribution of hand location in monkeys during spontaneous behavior EXPERIMENTAL BRAIN RESEARCH Graziano, M. S., Cooke, D. F., Taylor, C. S., Moore, T. 2004; 155 (1): 30-36

  Abstract

  Recently it was shown that electrical stimulation of the precentral gyrus of monkeys can evoke complex, coordinated movements. In the forelimb representation, stimulation of each site caused the arm to move to a specific final posture, and thus the hand to move to a location in space. Among these stimulation-evoked hand locations, certain regions of the hand's workspace were more represented than others. We hypothesized that a similar non-uniform distribution of hand location should be present during a monkey's spontaneous behavior. The present study examined the distribution of hand location of monkeys in their home cages. This distribution was similar to that found by stimulation of the precentral gyrus. That is, arm postures that were over-represented in spontaneous behavior were also over-represented in the movements evoked by cortical stimulation.

  View details for DOI 10.1007/s00221-003-1701-4

  View details for Web of Science ID 000189201900005

  View details for PubMedID 15064882

• Visually guided behavior after V1 lesions in young and adult monkeys and its relation to blindsight in humans. Progress in brain research Gross, C. G., Moore, T., Rodman, H. R. 2004; 144: 279-294

  Abstract

  After lesions of striate cortex in primates, there is still the capacity to detect and localize visual stimuli. In this chapter we review three aspects of our study of this phenomenon in macaques. First, we found that macaques that received their striate lesions as infants had considerably greater ability to detect and localize stimuli than those that received similar lesions as adults. Second, we suggest that the visual functions that survive striate lesions in macaques made in adulthood resemble those in human 'blindsight'. Third, we report that monkeys with striate lesions made in infancy are able to discriminate direction of visual motion.

  View details for PubMedID 14650855

• Microstimulation of the frontal eye field and its effects on covert spatial attention JOURNAL OF NEUROPHYSIOLOGY Moore, T., Fallah, M. 2004; 91 (1): 152-162

  Abstract

  Many studies have established that the strength of visual perception and the strength of visual representations within visual cortex vary according to the focus of covert spatial attention. While it is clear that attention can modulate visual signals, the source of this modulation remains unknown. We have examined the possibility that saccade related mechanisms provide a source of spatial attention by studying the effects of electrical microstimulation of the frontal eye fields (FEF) on spatial attention. Monkeys performed a task in which they had to detect luminance changes of a peripheral target while ignoring a flashing distracter. The target luminance change could be preceded by stimulation of the FEF at current levels below that which evoked saccadic eye movements. We found that when the target change was preceded by stimulation of FEF, the monkey could detect smaller changes in target luminance. The increased sensitivity to the target change only occurred when the target was placed in the part of the visual field represented by neurons at the stimulation site. The magnitude of improvement depended on the temporal asynchrony of the stimulation onset and the target event. No significant effect of stimulation was observed when long intervals (>300 ms) between stimulation and the target event were used, and the magnitude of the increased sensitivity decreased systematically with increasing asynchrony. At the shortest asynchrony, FEF stimulation temporally overlapped the target event and the magnitude of the improvement was comparable to that of removing the distracter from the task. These results demonstrate that transient, but potent improvements in the deployment of covert spatial attention can be obtained by microstimulation of FEF sites from which saccadic eye movements are also evoked.

  View details for DOI 10.1152/jn.00741.2002

  View details for Web of Science ID 000187964500013

  View details for PubMedID 13679398

• Visuomotor origins of covert spatial attention NEURON Moore, T., Armstrong, K. M., Fallah, M. 2003; 40 (4): 671-683

  Abstract

  Covert spatial attention produces biases in perceptual performance and neural processing of behaviorally relevant stimuli in the absence of overt orienting movements. The neural mechanism that gives rise to these effects is poorly understood. This paper surveys past evidence of a relationship between oculomotor control and visual spatial attention and more recent evidence of a causal link between the control of saccadic eye movements by frontal cortex and covert visual selection. Both suggest that the mechanism of covert spatial attention emerges as a consequence of the reciprocal interactions between neural circuits primarily involved in specifying the visual properties of potential targets and those involved in specifying the movements needed to fixate them.

  View details for Web of Science ID 000186651200004

  View details for PubMedID 14622573

• Complex movements evoked by microstimulation of the ventral intraparietal area PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Cooke, D. F., Taylor, C. S., Moore, T., Graziano, M. S. 2003; 100 (10): 6163-6168

  Abstract

  Most neurons in the ventral intraparietal area (VIP) of the macaque brain respond to both visual and tactile stimuli. The tactile receptive field is usually on the face, and the visual receptive field usually corresponds spatially to the tactile receptive field. In this study, electrical microstimulation of VIP, but not of surrounding tissue, caused a constellation of movements including eye closure, facial grimacing, head withdrawal, elevation of the shoulder, and movements of the hand to the space beside the head or shoulder. A similar set of movements was evoked by an air puff to the monkey's cheek. One interpretation is that VIP contributes to defensive movements triggered by stimuli on or near the head.

  View details for Web of Science ID 000182939400106

  View details for PubMedID 12719522

• Selective gating of visual signals by microstimulation of frontal cortex NATURE Moore, T., Armstrong, K. M. 2003; 421 (6921): 370-373

  Abstract

  Several decades of psychophysical and neurophysiological studies have established that visual signals are enhanced at the locus of attention. What remains a mystery is the mechanism that initiates biases in the strength of visual representations. Recent evidence argues that, during spatial attention, these biases reflect nascent saccadic eye movement commands. We examined the functional interaction of saccade preparation and visual coding by electrically stimulating sites within the frontal eye fields (FEF) and measuring its effect on the activity of neurons in extrastriate visual cortex. Here we show that visual responses in area V4 could be enhanced after brief stimulation of retinotopically corresponding sites within the FEF using currents below that needed to evoke saccades. The magnitude of the enhancement depended on the effectiveness of receptive field stimuli as well as on the presence of competing stimuli outside the receptive field. Stimulation of non-corresponding FEF representations could suppress V4 responses. The results suggest that the gain of visual signals is modified according to the strength of spatially corresponding eye movement commands.

  View details for DOI 10.1038/nature01341

  View details for Web of Science ID 000180533000042

  View details for PubMedID 12540901

• Visually guided behavior after V1 lesions in young and adult monkeys and its relation to blindsight in humans Conference on the Roots of Visual Awareness Gross, C. G., Moore, T., Rodman, H. R. ELSEVIER SCIENCE BV. 2003: 279–294

  View details for DOI 10.1016/S0079-6123(03)14401-9

  View details for Web of Science ID 000187421400019

• The cortical control of movement revisited NEURON Graziano, M. S., Taylor, C. S., Moore, T., Cooke, D. F. 2002; 36 (3): 349-362

  Abstract

  Recently, we found that electrical stimulation of motor cortex caused monkeys to make coordinated, complex movements. These evoked movements were arranged across the cortex in a map of spatial locations to which the hand moved. We suggest that some of the subdivisions previously described within primary motor and premotor cortex may represent different types of actions that monkeys tend to make in different regions of space. According to this view, primary and premotor cortex may fit together into a larger map of manual space.

  View details for Web of Science ID 000178877700006

  View details for PubMedID 12408840

• Probing cortical function with electrical stimulation NATURE NEUROSCIENCE Graziano, M. S., Taylor, C. S., Moore, T. 2002; 5 (10): 921-921

  View details for DOI 10.1038/nn1002-921

  View details for Web of Science ID 000178242200004

  View details for PubMedID 12352975

• Complex movements evoked by microstimulation of precentral cortex NEURON Graziano, M. S., Taylor, C. S., Moore, T. 2002; 34 (5): 841-851

  Abstract

  Electrical microstimulation was used to study primary motor and premotor cortex in monkeys. Each stimulation train was 500 ms in duration, approximating the time scale of normal reaching and grasping movements and the time scale of the neuronal activity that normally accompanies movement. This stimulation on a behaviorally relevant time scale evoked coordinated, complex postures that involved many joints. For example, stimulation of one site caused the mouth to open and also caused the hand to shape into a grip posture and move to the mouth. Stimulation of this site always drove the joints toward this final posture, regardless of the direction of movement required to reach the posture. Stimulation of other cortical sites evoked different postures. Postures that involved the arm were arranged across cortex to form a map of hand positions around the body. This stimulation-evoked map encompassed both primary motor and the adjacent premotor cortex. We suggest that these regions fit together into a single map of the workspace around the body.

  View details for Web of Science ID 000175951800017

  View details for PubMedID 12062029

• Eye movements modulate visual receptive fields of V4 neurons NEURON Tolias, A. S., Moore, T., Smirnakis, S. M., Tehovnik, E. J., Siapas, A. G., Schiller, P. H. 2001; 29 (3): 757-767

  Abstract

  The receptive field, defined as the spatiotemporal selectivity of neurons to sensory stimuli, is central to our understanding of the neuronal mechanisms of perception. However, despite the fact that eye movements are critical during normal vision, the influence of eye movements on the structure of receptive fields has never been characterized. Here, we map the receptive fields of macaque area V4 neurons during saccadic eye movements and find that receptive fields are remarkably dynamic. Specifically, before the initiation of a saccadic eye movement, receptive fields shrink and shift towards the saccade target. These spatiotemporal dynamics may enhance information processing of relevant stimuli during the scanning of a visual scene, thereby assisting the selection of saccade targets and accelerating the analysis of the visual scene during free viewing.

  View details for Web of Science ID 000167868900024

  View details for PubMedID 11301034

• Control of eye movements and spatial attention PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Moore, T., Fallah, M. 2001; 98 (3): 1273-1276

  Abstract

  Several lines of evidence suggest that planning eye movements and directing visuospatial attention share overlapping brain mechanisms. This study tested whether spatial attention can be enhanced by altering oculomotor signals within the brain. Monkeys performed a spatial attention task while neurons within the frontal eye field, an oculomotor area within prefrontal cortex, were electrically stimulated below the level at which eye movements are evoked. We found that we could improve the monkey's performance with microstimulation when, but only when, the object to be attended was positioned in the space represented by the cortical stimulation site.

  View details for Web of Science ID 000166807300091

  View details for PubMedID 11158629

• Direction of motion discrimination after early lesions of striate cortex (V1) of the macaque monkey PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Moore, T., Rodman, H. R., Gross, C. G. 2001; 98 (1): 325-330

  Abstract

  Previous studies have established that humans and monkeys with damage to striate cortex are able to detect and localize bright targets within the resultant scotoma. Electrophysiological evidence in monkeys suggests that residual vision also might include sensitivity to direction of visual motion. We tested whether macaque monkeys with longstanding lesions of striate cortex (V1), sustained in infancy, could discriminate visual stimuli on the basis of direction of motion. Three monkeys with unilateral striate cortex lesions sustained in infancy were tested 2-5 years postlesion on a direction of motion discrimination task. Each monkey was trained to make saccadic eye movements to a field of moving dots or to withhold such eye movements, depending on the direction of motion in a coherent random dot display. With smaller motion displays, monkeys were unable to detect or discriminate motion within the scotoma, although they could discriminate moving from static stimuli. Yet, each monkey was able to discriminate direction of motion when the motion stimulus was larger, but still confined to the scotoma. The results demonstrate that the recovery after infant damage to striate cortex includes some sensitivity to direction of visual motion.

  View details for Web of Science ID 000166222600061

  View details for PubMedID 11134530

• Shape representations and visual guidance sf saccadic eye movements SCIENCE Moore, T. 1999; 285 (5435): 1914-1917

  Abstract

  One hallmark of primate vision is that the direction of gaze is constantly shifting to position objects of interest appropriately on the fovea, where visual acuity is greatest. This process must involve the close cooperation of oculomotor and visual recognition mechanisms because visual details must be translated into specific motor commands. This paper describes the correspondence between the presaccadic activity of V4 neurons and the degree of visual guidance of saccadic eye movements to objects of different form. The results suggest that neurons that participate in coding visual stimuli are also involved in guiding the eyes to prominent features of objects.

  View details for Web of Science ID 000082638300051

  View details for PubMedID 10489371

• Visual representations during saccadic eye movements PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Moore, T., Tolias, A. S., Schiller, P. H. 1998; 95 (15): 8981-8984

  Abstract

  In normal vision, shifts of attention are usually followed by saccadic eye movements. Neurons in extrastriate area V4 are modulated by focal attention when eye movements are withheld, but they also respond in advance of visually guided saccadic eye movements. We have examined the visual selectivity of saccade-related responses of area V4 neurons in monkeys making delayed eye movements to receptive field stimuli of varying orientation. This task did not require the monkey to attend to orientation per se but merely to foveate the receptive field stimulus. We present evidence that the presaccadic enhancement exhibited by V4 neurons, quite separate from the response at stimulus onset, is a resurgent visual representation that seems as selective as the response is when the stimulus first appears. The presaccadic enhancement appears to provide a strengthening of a decaying featural representation immediately before an eye movement is directed to visual targets. We suggest that this reactivation provides a mechanism by which a clear perception of the saccade goal can be maintained during the execution of the saccade, perhaps for the purpose of establishing continuity across eye movements.

  View details for Web of Science ID 000075143900101

  View details for PubMedID 9671790

• Man, monkey, and blindsight NEUROSCIENTIST Moore, T., Rodman, H. R., Gross, C. G. 1998; 4 (4): 227-230

  View details for Web of Science ID 000074948100010

• Man, Monkey and Blindsight. The Neuroscientist Moore, T., Rodman, H.R., Gross, C.G. 1998; 4: 227-230
• Greater residual vision in monkeys after striate cortex damage in infancy JOURNAL OF NEUROPHYSIOLOGY Moore, T., Rodman, H. R., REPP, A. B., Gross, C. G., Mezrich, R. S. 1996; 76 (6): 3928-3933

  Abstract

  1. Monkeys with large unilateral surgical ablations of striate cortex, sustained either in adulthood or at 5-6 wk of age, were trained on an oculomotor detection and localization task and tested with visual stimuli in the hemifields ipsilateral and contralateral to the lesion 2-5 yr after surgery. 2. Monkeys with lesions sustained in adulthood were largely unable to detect stimuli in the hemifield contralateral to the lesion, with only one monkey showing recovery toward the end of testing. Monkeys with lesions of striate cortex made in infancy, however, each showed residual detection capacity at the beginning of testing and improved to near normal by the end of testing. 3. Each of the monkeys showing a residual ability to detect within the contralateral hemifield was also able to localize visual targets with eye movements. 4. These findings demonstrate that the vision surviving striate cortex damage in primates is more robust after early damage as has been shown to be the case for primary somatosensory, motor, and association cortex.

  View details for Web of Science ID A1996WA80300032

  View details for PubMedID 8985890

• LOCALIZATION OF VISUAL-STIMULI AFTER STRIATE CORTEX DAMAGE IN MONKEYS - PARALLELS WITH HUMAN BLINDSIGHT PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Moore, T., Rodman, H. R., REPP, A. B., Gross, C. G. 1995; 92 (18): 8215-8218

  Abstract

  Blindsight is a phenomenon in which human patients with damage to striate cortex deny any visual sensation in the resultant visual field defect but can nonetheless detect and localize stimuli when persuaded to guess. Although monkeys with striate lesions have also been shown to exhibit some residual vision, it is not yet clear to what extent the residual capacities in monkeys parallel the phenomenon of human blindsight. To clarify this issue, we trained two monkeys with unilateral lesions of striate cortex to make saccadic eye movements to visual targets in both hemifields under two conditions. In the condition analogous to clinical perimetry, they failed to initiate saccades to targets presented in the contralateral hemifield and thus appeared "blind." Only in the condition where the fixation point was turned off simultaneously with the onset of the target--signaling the animal to respond at the appropriate time--were monkeys able to localize targets contralateral to the striate lesion. These results indicate that the conditions under which residual vision is demonstrable are similar for monkeys with striate cortex damage and humans with blindsight.

  View details for Web of Science ID A1995RR84400027

  View details for PubMedID 7667270