Corey Keller, Postdoctoral Faculty Sponsor
Neurophysiologic predictors of individual risk for post-operative delirium after elective surgery.
Journal of the American Geriatrics Society
BACKGROUND: Post-surgical delirium is associated with increased morbidity, lasting cognitive decline, and loss of functional independence. Within a conceptual framework that delirium is triggered by stressors when vulnerabilities exist in cerebral connectivity and plasticity, we previously suggested that neurophysiologic measures might identify individuals at risk for post-surgical delirium. Here we demonstrate the feasibility of the approach and provide preliminary experimental evidence of the predictive value of such neurophysiologic measures for the risk of delirium in older persons undergoing elective surgery.METHODS: Electroencephalography (EEG) and transcranial magnetic stimulation (TMS) were collected from 23 patients prior to elective surgery. Resting-state EEG spectral power ratio (SPR) served as a measure of integrity of neural circuits. TMS-EEG metrics of plasticity (TMS-plasticity) were used as indicators of brain capacity to respond to stressors. Presence or absence of delirium was assessed using the confusion assessment method (CAM). We included individuals with no baseline clinically relevant cognitive impairment (MoCA scores ≥21) in order to focus on subclinical neurophysiological measures.RESULTS: In patients with no baseline cognitive impairment (N=20, age=72±6), 3 developed post-surgical delirium (MoCA=24±2.6) and 17 did not (controls; MoCA=25±2.4). Patients who developed delirium had pre-surgical resting-state EEG power ratios outside the 95% confidence interval of controls, and 2/3 had TMS-plasticity measures outside the 95% CI of controls.CONCLUSIONS: Consistent with our proposed conceptual framework, this pilot study suggests that non-invasive and scalable neurophysiologic measures can identify individuals at risk of post-operative delirium. Specifically, abnormalities in resting-state EEG spectral power or TMS-plasticity may indicate sub-clinical risk for post-surgery delirium. Extension and confirmation of these findings in a larger sample is needed to assess the clinical utility of the proposed neurophysiologic markers, and to identify specific connectivity and plasticity targets for therapeutic interventions that might minimize the risk of delirium.
View details for DOI 10.1111/jgs.18072
View details for PubMedID 36226896
Experimental suppression of transcranial magnetic stimulation-electroencephalography sensory potentials.
Human brain mapping
The sensory experience of transcranial magnetic stimulation (TMS) evokes cortical responses measured in electroencephalography (EEG) that confound interpretation of TMS-evoked potentials (TEPs). Methods for sensory masking have been proposed to minimize sensory contributions to the TEP, but the most effective combination for suprathreshold TMS to dorsolateral prefrontal cortex (dlPFC) is unknown. We applied sensory suppression techniques and quantified electrophysiology and perception from suprathreshold dlPFC TMS to identify the best combination to minimize the sensory TEP. In 21 healthy adults, we applied single pulse TMS at 120% resting motor threshold (rMT) to the left dlPFC and compared EEG vertex N100-P200 and perception. Conditions included three protocols: No masking (no auditory masking, no foam, and jittered interstimulus interval [ISI]), Standard masking (auditory noise, foam, and jittered ISI), and our ATTENUATE protocol (auditory noise, foam, over-the-ear protection, and unjittered ISI). ATTENUATE reduced vertex N100-P200 by 56%, "click" loudness perception by 50%, and scalp sensation by 36%. We show that sensory prediction, induced with predictable ISI, has a suppressive effect on vertex N100-P200, and that combining standard suppression protocols with sensory prediction provides the best N100-P200 suppression. ATTENUATE was more effective than Standard masking, which only reduced vertex N100-P200 by 22%, loudness by 27%, and scalp sensation by 24%. We introduce a sensory suppression protocol superior to Standard masking and demonstrate that using an unjittered ISI can contribute to minimizing sensory confounds. ATTENUATE provides superior sensory suppression to increase TEP signal-to-noise and contributes to a growing understanding of TMS-EEG sensory neuroscience.
View details for DOI 10.1002/hbm.25990
View details for PubMedID 35770956
A systematic review and meta-analysis of the efficacy of intermittent theta burst stimulation (iTBS) on cognitive enhancement.
Neuroscience and biobehavioral reviews
Intermittent theta-burst stimulation (iTBS) has been used to focally regulate excitability of neural cortex over the past decade - however there is little consensus on the generalizability of effects reported in individual studies. Many studies use small sample sizes (N < 30), and there is a considerable amount of methodological heterogeneity in application of the stimulation itself. This systematic meta-analysis aims to consolidate the extant literature and determine if up-regulatory theta-burst stimulation reliably enhances cognition through measurable behavior. Results show that iTBS - when compared to suitable control conditions - may enhance cognition when outlier studies are removed, but also that there is a significant amount of heterogeneity across studies. Significant contributors to between-study heterogeneity include location of stimulation and method of navigation to the stimulation site. Surprisingly, the type of cognitive domain investigated was not a significant contributor of heterogeneity. The findings of this meta-analysis demonstrate that standardization of iTBS is urgent and necessary to determine if neuroenhancement of particular cognitive faculties are reliable and robust, and measurable through observable behavior.
View details for DOI 10.1016/j.neubiorev.2022.104587
View details for PubMedID 35202646
Time Perception for Musical Rhythms: Sensorimotor Perspectives on Entrainment, Simulation, and Prediction.
Frontiers in integrative neuroscience
2022; 16: 916220
Neural mechanisms supporting time perception in continuously changing sensory environments may be relevant to a broader understanding of how the human brain utilizes time in cognition and action. In this review, we describe current theories of sensorimotor engagement in the support of subsecond timing. We focus on musical timing due to the extensive literature surrounding movement with and perception of musical rhythms. First, we define commonly used but ambiguous concepts including neural entrainment, simulation, and prediction in the context of musical timing. Next, we summarize the literature on sensorimotor timing during perception and performance and describe current theories of sensorimotor engagement in the support of subsecond timing. We review the evidence supporting that sensorimotor engagement is critical in accurate time perception. Finally, potential clinical implications for a sensorimotor perspective of timing are highlighted.
View details for DOI 10.3389/fnint.2022.916220
View details for PubMedID 35865808
A structured ICA-based process for removing auditory evoked potentials.
2022; 12 (1): 1391
Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs), recorded using electroencephalography (EEG), reflect a combination of TMS-induced cortical activity and multi-sensory responses to TMS. The auditory evoked potential (AEP) is a high-amplitude sensory potential-evoked by the "click" sound produced by every TMS pulse-that can dominate the TEP and obscure observation of other neural components. The AEP is peripherally evoked and therefore should not be stimulation site specific. We address the problem of disentangling the peripherally evoked AEP of the TEP from components evoked by cortical stimulation and ask whether removal of AEP enables more accurate isolation of TEP. We hypothesized that isolation of the AEP using Independent Components Analysis (ICA) would reveal features that are stimulation site specific and unique individual features. In order to improve the effectiveness of ICA for removal of AEP from the TEP, and thus more clearly separate the transcranial-evoked and non-specific TMS-modulated potentials, we merged sham and active TMS datasets representing multiple stimulation conditions, removed the resulting AEP component, and evaluated performance across different sham protocols and clinical populations using reduction in Global and Local Mean Field Power (GMFP/LMFP) and cosine similarity analysis. We show that removing AEPs significantly reduced GMFP and LMFP in the post-stimulation TEP (14 to 400 ms), driven by time windows consistent with the N100 and P200 temporal characteristics of AEPs. Cosine similarity analysis supports that removing AEPs reduces TEP similarity between subjects and reduces TEP similarity between stimulation conditions. Similarity is reduced most in a mid-latency window consistent with the N100 time-course, but nevertheless remains high in this time window. Residual TEP in this window has a time-course and topography unique from AEPs, which follow-up exploratory analyses suggest could be a modulation in the alpha band that is not stimulation site specific but is unique to individual subject. We show, using two datasets and two implementations of sham, evidence in cortical topography, TEP time-course, GMFP/LMFP and cosine similarity analyses that this procedure is effective and conservative in removing the AEP from TEP, and may thus better isolate TMS-evoked activity. We show TEP remaining in early, mid and late latencies. The early response is site and subject specific. Later response may be consistent with TMS-modulated alpha activity that is not site specific but is unique to the individual. TEP remaining after removal of AEP is unique and can provide insight into TMS-evoked potentials and other modulated oscillatory dynamics.
View details for DOI 10.1038/s41598-022-05397-3
View details for PubMedID 35082350
View details for PubMedCentralID PMC8791940
Cortical Mu Rhythms During Action and Passive Music Listening.
Journal of neurophysiology
Brain systems supporting body movement are active during music listening in the absence of overt movement. This covert motor activity is not well understood, but some theories propose a role in auditory timing prediction facilitated by motor simulation. One question is how music-related covert motor activity relates to motor activity during overt movement. We address this question using scalp electroencephalogram by measuring mu rhythms-- cortical field phenomena associated with the somatomotor system that appear over sensorimotor cortex. Lateralized mu enhancement over hand sensorimotor cortex during/just before foot movement in foot vs. hand movement paradigms is thought to reflect hand movement inhibition during current/prospective movement of another effector. Behavior of mu during music listening with movement suppressed has yet to be determined. We recorded 32-channel EEG (N=17) during silence without movement, overt movement (foot/hand), and music listening without movement. Using an Independent Component Analysis-based source equivalent dipole clustering technique, we identified three mu-related clusters, localized to left primary motor and right and midline premotor cortices. Right foot tapping was accompanied by mu enhancement in the left lateral source cluster, replicating previous work. Music listening was accompanied by similar mu enhancement in the left, as well as midline, clusters. We are the first to report, and also to source-resolve, music-related mu modulation in the absence of overt movements. Covert music-related motor activity has been shown to play a role in beat perception (1). Our current results show enhancement in somatotopically organized mu, supporting overt motor inhibition during beat perception.
View details for DOI 10.1152/jn.00346.2021
View details for PubMedID 34936516
Modality-specific frequency band activity during neural entrainment to auditory and visual rhythms
EUROPEAN JOURNAL OF NEUROSCIENCE
2021; 54 (2): 4649-4669
Rhythm perception depends on the ability to predict the onset of rhythmic events. Previous studies indicate beta band modulation is involved in predicting the onset of auditory rhythmic events (Fujioka et al., 2009, 2012; Snyder & Large, 2005). We sought to determine if similar processes are recruited for prediction of visual rhythms by investigating whether beta band activity plays a role in a modality-dependent manner for rhythm perception. We looked at electroencephalography time-frequency neural correlates of prediction using an omission paradigm with auditory and visual rhythms. By using omissions, we can separate out predictive timing activity from stimulus-driven activity. We hypothesized that there would be modality-independent markers of rhythm prediction in induced beta band oscillatory activity, and our results support this hypothesis. We find induced and evoked predictive timing in both auditory and visual modalities. Additionally, we performed an exploratory-independent components-based spatial clustering analysis, and describe all resulting clusters. This analysis reveals that there may be overlapping networks of predictive beta activity based on common activation in the parietal and right frontal regions, auditory-specific predictive beta in bilateral sensorimotor regions, and visually specific predictive beta in midline central, and bilateral temporal/parietal regions. This analysis also shows evoked predictive beta activity in the left sensorimotor region specific to auditory rhythms and implicates modality-dependent networks for auditory and visual rhythm perception.
View details for DOI 10.1111/ejn.15314
View details for Web of Science ID 000662752900001
View details for PubMedID 34008232
Time course of cognitive training in Parkinson disease
2020; 46 (3): 311-320
People with Parkinson disease (PD) have difficulty initiating internally generated movements. We have shown that computer-based cognitive training can improve movement initiation. However, little is known about the optimal duration of training.To determine the optimal training duration for computer-based neurorehabilitation of internally represented movement initiation in people with PD.Nineteen PD and twenty-one age-matched control participants, ages 50-85 years, were included in analysis of pre- and post-training evaluation and 30 training sessions. Computer training consisted of cued and un-cued movement trials. The presentation of a cue (a combination of numbers on either the right, left or both sides of the screen) indicated that participants should respond by typing the numbers. Successful cued trials were followed by un-cued trials consisting of a green filled circle. Participants re-enter the cued sequence, thus producing an internally represented (IR) movement. The training was adaptive. Outcome measures were reaction time and error rate, and cumulative sum (CUSUM) analysis was used to identify peak training improvement.Participants with PD were divided into impaired (IPD) and unimpaired (UPD) groups, based on mean control group pre-training performance. All three groups showed improved RT and error rates for IR trials; however, the IPD group demonstrated significantly greater improvement in reaction time. Training was most effective in participants with greater disease severity and duration. Peak day of training improvement for the IPD group was 8 days.Optimal training duration was relatively short and the IPD group demonstrated the most gain, indicating that cognitive training should be tailored to individual needs.
View details for DOI 10.3233/NRE-192940
View details for Web of Science ID 000541030200005
View details for PubMedID 32250326
The Role of Posterior Parietal Cortex in Beat-based Timing Perception: A Continuous Theta Burst Stimulation Study
JOURNAL OF COGNITIVE NEUROSCIENCE
2018; 30 (5): 634-643
There is growing interest in how the brain's motor systems contribute to the perception of musical rhythms. The Action Simulation for Auditory Prediction hypothesis proposes that the dorsal auditory stream is involved in bidirectional interchange between auditory perception and beat-based prediction in motor planning structures via parietal cortex [Patel, A. D., & Iversen, J. R. The evolutionary neuroscience of musical beat perception: The Action Simulation for Auditory Prediction (ASAP) hypothesis. Frontiers in Systems Neuroscience, 8, 57, 2014]. We used a TMS protocol, continuous theta burst stimulation (cTBS), that is known to down-regulate cortical activity for up to 60 min following stimulation to test for causal contributions to beat-based timing perception. cTBS target areas included the left posterior parietal cortex (lPPC), which is part of the dorsal auditory stream, and the left SMA (lSMA). We hypothesized that down-regulating lPPC would interfere with accurate beat-based perception by disrupting the dorsal auditory stream. We hypothesized that we would induce no interference to absolute timing ability. We predicted that down-regulating lSMA, which is not part of the dorsal auditory stream but has been implicated in internally timed movements, would also interfere with accurate beat-based timing perception. We show ( n = 25) that cTBS down-regulation of lPPC does interfere with beat-based timing ability, but only the ability to detect shifts in beat phase, not changes in tempo. Down-regulation of lSMA, in contrast, did not interfere with beat-based timing. As expected, absolute interval timing ability was not impacted by the down-regulation of lPPC or lSMA. These results support that the dorsal auditory stream plays an essential role in accurate phase perception in beat-based timing. We find no evidence of an essential role of parietal cortex or SMA in interval timing.
View details for DOI 10.1162/jocn_a_01237
View details for Web of Science ID 000428776900002
View details for PubMedID 29346017
Motor simulation theories of musical beat perception
2016; 22 (6): 558-565
There is growing interest in whether the motor system plays an essential role in rhythm perception. The motor system is active during the perception of rhythms, but is such motor activity merely a sign of unexecuted motor planning, or does it play a causal role in shaping the perception of rhythm? We present evidence for a causal role of motor planning and simulation, and review theories of internal simulation for beat-based timing prediction. Brain stimulation studies have the potential to conclusively test if the motor system plays a causal role in beat perception and ground theories to their neural underpinnings.
View details for DOI 10.1080/13554794.2016.1242756
View details for Web of Science ID 000392626500011
View details for PubMedID 27726485
A pilot study to evaluate multi-dimensional effects of dance for people with Parkinson's disease
CONTEMPORARY CLINICAL TRIALS
2016; 51: 50-55
Parkinson's disease (PD) is a progressive neurodegenerative disease associated with deficits in motor, cognitive, and emotion/quality of life (QOL) domains, yet most pharmacologic and behavioral interventions focus only on motor function. Our goal was to perform a pilot study of Dance for Parkinson's-a community-based program that is growing in popularity-in order to compare effect sizes across multiple outcomes and to inform selection of primary and secondary outcomes for a larger trial. Study participants were people with PD who self-enrolled in either Dance for Parkinson's classes (intervention group, N=8) or PD support groups (control group, N=7). Assessments of motor function (Timed-Up-and-Go, Gait Speed, Standing Balance Test), cognitive function (Test of Everyday Attention, Verbal Fluency, Alternate Uses, Digit Span Forward and Backward), and emotion/QOL (Geriatric Depression Scale, Falls Efficacy Scale-International, Parkinson's Disease Questionnaire-39 (total score and Activities of Daily Living subscale)) were performed in both groups at baseline and follow-up. Standardized effect sizes were calculated within each group and between groups for all 12 measures. Effect sizes were positive (suggesting improvement) for all 12 measures within the intervention group and 7 of 12 measures within the control group. The largest between-group differences were observed for the Test of Everyday Attention (a measure of cognitive switching), gait speed and falls efficacy. Our findings suggest that dance has potential to improve multiple outcomes in people with PD. Future trials should consider co-primary outcomes given potential benefits in motor, cognitive and emotion/QOL domains.
View details for DOI 10.1016/j.cct.2016.10.001
View details for Web of Science ID 000389166100007
View details for PubMedID 27765693
View details for PubMedCentralID PMC5108673
Auditory white noise reduces age-related fluctuations in balance
2016; 630: 216-221
Fall prevention technologies have the potential to improve the lives of older adults. Because of the multisensory nature of human balance control, sensory therapies, including some involving tactile and auditory noise, are being explored that might reduce increased balance variability due to typical age-related sensory declines. Auditory white noise has previously been shown to reduce postural sway variability in healthy young adults. In the present experiment, we examined this treatment in young adults and typically aging older adults. We measured postural sway of healthy young adults and adults over the age of 65 years during silence and auditory white noise, with and without vision. Our results show reduced postural sway variability in young and older adults with auditory noise, even in the absence of vision. We show that vision and noise can reduce sway variability for both feedback-based and exploratory balance processes. In addition, we show changes with auditory noise in nonlinear patterns of sway in older adults that reflect what is more typical of young adults, and these changes did not interfere with the typical random walk behavior of sway. Our results suggest that auditory noise might be valuable for therapeutic and rehabilitative purposes in older adults with typical age-related balance variability.
View details for DOI 10.1016/j.neulet.2016.07.060
View details for Web of Science ID 000383008600035
View details for PubMedID 27495013
Influence of Musical Groove on Postural Sway
JOURNAL OF EXPERIMENTAL PSYCHOLOGY-HUMAN PERCEPTION AND PERFORMANCE
2016; 42 (3): 308-319
Timescales of postural fluctuation reflect underlying neuromuscular processes in balance control that are influenced by sensory information and the performance of concurrent cognitive and motor tasks. An open question is how postural fluctuations entrain to complex environmental rhythms, such as in music, which also vary on multiple timescales. Musical groove describes the property of music that encourages auditory-motor synchronization and is used to study voluntary motor entrainment to rhythmic sounds. The influence of groove on balance control mechanisms remains unexplored. We recorded fluctuations in center of pressure (CoP) of standing participants (N = 40) listening to low and high groove music and during quiet stance. We found an effect of musical groove on radial sway variability, with the least amount of variability in the high groove condition. In addition, we observed that groove influenced postural sway entrainment at various temporal scales. For example, with increasing levels of groove, we observed more entrainment to shorter, local timescale rhythmic musical occurrences. In contrast, we observed more entrainment to longer, global timescale features of the music, such as periodicity, with decreasing levels of groove. Finally, musical experience influenced the amount of postural variability and entrainment at local and global timescales. We conclude that groove in music and musical experience can influence the neural mechanisms that govern balance control, and discuss implications of our findings in terms of multiscale sensorimotor coupling. (PsycINFO Database Record
View details for DOI 10.1037/xhp0000198
View details for Web of Science ID 000372552100002
View details for PubMedID 26727019
Auditory white noise reduces postural fluctuations even in the absence of vision
EXPERIMENTAL BRAIN RESEARCH
2015; 233 (8): 2357-2363
The contributions of somatosensory, vestibular, and visual feedback to balance control are well documented, but the influence of auditory information, especially acoustic noise, on balance is less clear. Because somatosensory noise has been shown to reduce postural sway, we hypothesized that noise from the auditory modality might have a similar effect. Given that the nervous system uses noise to optimize signal transfer, adding mechanical or auditory noise should lead to increased feedback about sensory frames of reference used in balance control. In the present experiment, postural sway was analyzed in healthy young adults where they were presented with continuous white noise, in the presence and absence of visual information. Our results show reduced postural sway variability (as indexed by the body's center of pressure) in the presence of auditory noise, even when visual information was not present. Nonlinear time series analysis revealed that auditory noise has an additive effect, independent of vision, on postural stability. Further analysis revealed that auditory noise reduced postural sway variability in both low- and high-frequency regimes (> or <0.3 Hz) of sway, suggesting that both spontaneous and feedback-driven aspects of postural fluctuations were influenced by acoustic noise. Our results support the idea that auditory white noise reduces postural sway, suggesting that auditory noise might be used for therapeutic and rehabilitation purposes in older individuals and those with balance disorders.
View details for DOI 10.1007/s00221-015-4304-y
View details for Web of Science ID 000358322500011
View details for PubMedID 25953650
Using nonlinear methods to quantify changes in infant limb movements and vocalizations
FRONTIERS IN PSYCHOLOGY
2014; 5: 771
The pairing of dynamical systems theory and complexity science brings novel concepts and methods to the study of infant motor development. Accordingly, this longitudinal case study presents a new approach to characterizing the dynamics of infant limb and vocalization behaviors. A single infant's vocalizations and limb movements were recorded from 51-days to 305-days of age. On each recording day, accelerometers were placed on all four of the infant's limbs and an audio recorder was worn on the child's chest. Using nonlinear time series analysis methods, such as recurrence quantification analysis and Allan factor, we quantified changes in the stability and multiscale properties of the infant's behaviors across age as well as how these dynamics relate across modalities and effectors. We observed that particular changes in these dynamics preceded or coincided with the onset of various developmental milestones. For example, the largest changes in vocalization dynamics preceded the onset of canonical babbling. The results show that nonlinear analyses can help to understand the functional co-development of different aspects of infant behavior.
View details for DOI 10.3389/fpsyg.2014.00771
View details for Web of Science ID 000341366500001
View details for PubMedID 25161629
View details for PubMedCentralID PMC4130108
Physical and neural entrainment to rhythm: human sensorimotor coordination across tasks and effector systems
FRONTIERS IN HUMAN NEUROSCIENCE
2014; 8: 576
The human sensorimotor system can be readily entrained to environmental rhythms, through multiple sensory modalities. In this review, we provide an overview of theories of timekeeping that make this neuroentrainment possible. First, we present recent evidence that contests the assumptions made in classic timekeeper models. The role of state estimation, sensory feedback and movement parameters on the organization of sensorimotor timing are discussed in the context of recent experiments that examined simultaneous timing and force control. This discussion is extended to the study of coordinated multi-effector movements and how they may be entrained.
View details for DOI 10.3389/fnhum.2014.00576
View details for Web of Science ID 000340608600001
View details for PubMedID 25136306
View details for PubMedCentralID PMC4118030
Perceived and performance-based executive dysfunction in Parkinson's disease
JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY
2014; 36 (4): 342-355
Executive dysfunction is common in early stage Parkinson's disease (PD). We evaluated the relationship between self- and informant-report measurement of real-world executive functions as well as performance-based neuropsychological measures in mildly cognitively impaired individuals with PD and healthy controls. The PD group reported more difficulty with initiation of complex tasks compared to caregiver ratings, and processing speed was a strong predictor of self-reported executive dysfunction for the PD group, followed by depression. Processing speed and semantic verbal fluency predicted informant-reported executive dysfunction in PD. These findings highlight the contribution of speeded processing for performance of everyday executive tasks in PD.
View details for DOI 10.1080/13803395.2014.892059
View details for Web of Science ID 000335847300002
View details for PubMedID 24611823