I am currently pursuing a PhD in Neuroscience with Krishna Shenoy in the Neural Prosthetics Systems lab. I am interested the neural basis of movement and motor feedback control. Towards this end, I am engaged in collaborative research employing multielectrode array recordings, optogenetic and electrical stimulation, haptic feedback devices, and high dimensional modeling of population dynamics.
Honors & Awards
Graduate Research Fellowship, National Science Foundation (2009-2012)
Stanford Graduate Fellowship, Stanford University (2009-2014)
NSF IGERT Research Fellowship, Stanford Center for Mind, Brain, and Computation (2012-present)
Doctor of Philosophy, Stanford University, NEURS-PHD (2017)
Bachelor of Elec Engineering, Princeton University, Electrical Engineering (2009)
Causal Role of Motor Preparation during Error-Driven Learning.
Current theories suggest that an error-driven learning process updates trial-by-trial to facilitate motor adaptation. How this process interacts with motor cortical preparatory activity-which current models suggest plays a critical role in movement initiation-remains unknown. Here, we evaluated the role of motor preparation during visuomotor adaptation. We found that preparation time was inversely correlated to variance of errors on current trials and mean error on subsequent trials. We also found causal evidence that intracortical microstimulation during motor preparation was sufficient to disrupt learning. Surprisingly, stimulation did not affect current trials, but instead disrupted the update computation of a learning process, thereby affecting subsequent trials. This is consistent with a Bayesian estimation framework where the motor system reduces its learning rate by virtue of lowering error sensitivity when faced with uncertainty. This interaction between motor preparation and the error-driven learning system may facilitate new probes into mechanisms underlying trial-by-trial adaptation.
View details for DOI 10.1016/j.neuron.2020.01.019
View details for PubMedID 32053768
An Open Resource for Non-human Primate Optogenetics.
Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.
View details for DOI 10.1016/j.neuron.2020.09.027
View details for PubMedID 33080229
- Publisher Correction: Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys. Scientific reports 2019; 9 (1): 18775
Accurate Estimation of Neural Population Dynamics without Spike Sorting.
A central goal of systems neuroscience is to relate an organism's neural activity to behavior. Neural population analyses often reduce the data dimensionality to focus on relevant activity patterns. A major hurdle to data analysis is spike sorting, and this problem is growing as the number of recorded neurons increases. Here, we investigate whether spike sorting is necessary to estimate neural population dynamics. The theory of random projections suggests that we can accurately estimate the geometry of low-dimensional manifolds from a small number of linear projections of the data. We recorded data using Neuropixels probes in motor cortex of nonhuman primates and reanalyzed data from three previous studies and found that neural dynamics and scientific conclusions are quite similar using multiunit threshold crossings rather than sorted neurons. This finding unlocks existing data for new analyses and informs the design and use of new electrode arrays for laboratory and clinical use.
View details for DOI 10.1016/j.neuron.2019.05.003
View details for PubMedID 31171448
Inferring single-trial neural population dynamics using sequential auto-encoders
2018; 15 (10): 805-+
Neuroscience is experiencing a revolution in which simultaneous recording of thousands of neurons is revealing population dynamics that are not apparent from single-neuron responses. This structure is typically extracted from data averaged across many trials, but deeper understanding requires studying phenomena detected in single trials, which is challenging due to incomplete sampling of the neural population, trial-to-trial variability, and fluctuations in action potential timing. We introduce latent factor analysis via dynamical systems, a deep learning method to infer latent dynamics from single-trial neural spiking data. When applied to a variety of macaque and human motor cortical datasets, latent factor analysis via dynamical systems accurately predicts observed behavioral variables, extracts precise firing rate estimates of neural dynamics on single trials, infers perturbations to those dynamics that correlate with behavioral choices, and combines data from non-overlapping recording sessions spanning months to improve inference of underlying dynamics.
View details for PubMedID 30224673
Development of an optogenetic toolkit for neural circuit dissection in squirrel monkeys
2018; 8: 6775
Optogenetic tools have opened a rich experimental landscape for understanding neural function and disease. Here, we present the first validation of eight optogenetic constructs driven by recombinant adeno-associated virus (AAV) vectors and a WGA-Cre based dual injection strategy for projection targeting in a widely-used New World primate model, the common squirrel monkey Saimiri sciureus. We observed opsin expression around the local injection site and in axonal projections to downstream regions, as well as transduction to thalamic neurons, resembling expression patterns observed in macaques. Optical stimulation drove strong, reliable excitatory responses in local neural populations for two depolarizing opsins in anesthetized monkeys. Finally, we observed continued, healthy opsin expression for at least one year. These data suggest that optogenetic tools can be readily applied in squirrel monkeys, an important first step in enabling precise, targeted manipulation of neural circuits in these highly trainable, cognitively sophisticated animals. In conjunction with similar approaches in macaques and marmosets, optogenetic manipulation of neural circuits in squirrel monkeys will provide functional, comparative insights into neural circuits which subserve dextrous motor control as well as other adaptive behaviors across the primate lineage. Additionally, development of these tools in squirrel monkeys, a well-established model system for several human neurological diseases, can aid in identifying novel treatment strategies.
View details for PubMedID 29712920
ERAASR: an algorithm for removing electrical stimulation artifacts from multielectrode array recordings
JOURNAL OF NEURAL ENGINEERING
2018; 15 (2): 026020
Electrical stimulation is a widely used and effective tool in systems neuroscience, neural prosthetics, and clinical neurostimulation. However, electrical artifacts evoked by stimulation prevent the detection of spiking activity on nearby recording electrodes, which obscures the neural population response evoked by stimulation. We sought to develop a method to clean artifact-corrupted electrode signals recorded on multielectrode arrays in order to recover the underlying neural spiking activity.We created an algorithm, which performs estimation and removal of array artifacts via sequential principal components regression (ERAASR). This approach leverages the similar structure of artifact transients, but not spiking activity, across simultaneously recorded channels on the array, across pulses within a train, and across trials. The ERAASR algorithm requires no special hardware, imposes no requirements on the shape of the artifact or the multielectrode array geometry, and comprises sequential application of straightforward linear methods with intuitive parameters. The approach should be readily applicable to most datasets where stimulation does not saturate the recording amplifier.The effectiveness of the algorithm is demonstrated in macaque dorsal premotor cortex using acute linear multielectrode array recordings and single electrode stimulation. Large electrical artifacts appeared on all channels during stimulation. After application of ERAASR, the cleaned signals were quiescent on channels with no spontaneous spiking activity, whereas spontaneously active channels exhibited evoked spikes which closely resembled spontaneously occurring spiking waveforms.We hope that enabling simultaneous electrical stimulation and multielectrode array recording will help elucidate the causal links between neural activity and cognition and facilitate naturalistic sensory protheses.
View details for PubMedID 29265009
View details for PubMedCentralID PMC5833982
- The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces EXPERIMENTAL NEUROLOGY 2017; 287: 437-451
The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces.
A central goal of neuroscience is to understand how populations of neurons coordinate and cooperate in order to give rise to perception, cognition, and action. Nonhuman primates (NHPs) are an attractive model with which to understand these mechanisms in humans, primarily due to the strong homology of their brains and the cognitively sophisticated behaviors they can be trained to perform. Using electrode recordings, the activity of one to a few hundred individual neurons may be measured electrically, which has enabled many scientific findings and the development of brain-machine interfaces. Despite these successes, electrophysiology samples sparsely from neural populations and provides little information about the genetic identity and spatial micro-organization of recorded neurons. These limitations have spurred the development of all-optical methods for neural circuit interrogation. Fluorescent calcium signals serve as a reporter of neuronal responses, and when combined with post-mortem optical clearing techniques such as CLARITY, provide dense recordings of neuronal populations, spatially organized and annotated with genetic and anatomical information. Here, we advocate that this methodology, which has been of tremendous utility in smaller animal models, can and should be developed for use with NHPs. We review here several of the key opportunities and challenges for calcium-based optical imaging in NHPs. We focus on motor neuroscience and brain-machine interface design as representative domains of opportunity within the larger field of NHP neuroscience.
View details for DOI 10.1016/j.expneurol.2016.08.003
View details for PubMedID 27511294
View details for PubMedCentralID PMC5154795
The Importance of Planning in Motor Learning.
2016; 92 (4): 669–71
The addition of differentiating follow-through motions can facilitate simultaneous learning of multiple motor skills that would otherwise interfere with each other. In this issue of Neuron, Sheahan and colleagues (2016) demonstrate that it is the preparation, not execution, of different follow-through movements that separates motor memories and reduces interference.
View details for PubMedID 27883896
A coaxial optrode as multifunction write-read probe for optogenetic studies in non-human primates.
Journal of neuroscience methods
2013; 219 (1): 142-154
Advances in optogenetics have led to first reports of expression of light-gated ion-channels in non-human primates (NHPs). However, a major obstacle preventing effective application of optogenetics in NHPs and translation to optogenetic therapeutics is the absence of compatible multifunction optoelectronic probes for (1) precision light delivery, (2) low-interference electrophysiology, (3) protein fluorescence detection, and (4) repeated insertion with minimal brain trauma.Here we describe a novel brain probe device, a "coaxial optrode", designed to minimize brain tissue damage while microfabricated to perform simultaneous electrophysiology, light delivery and fluorescence measurements in the NHP brain. The device consists of a tapered, gold-coated optical fiber inserted in a polyamide tube. A portion of the gold coating is exposed at the fiber tip to allow electrophysiological recordings in addition to light delivery/collection at the tip.Coaxial optrode performance was demonstrated by experiments in rodents and NHPs, and characterized by computational models. The device mapped opsin expression in the brain and achieved precisely targeted optical stimulation and electrophysiology with minimal cortical damage.Overall, combined electrical, optical and mechanical features of the coaxial optrode allowed a performance for NHP studies which was not possible with previously existing devices.Coaxial optrode is currently being used in two NHP laboratories as a major tool to study brain function by inducing light modulated neural activity and behavior. By virtue of its design, the coaxial optrode can be extended for use as a chronic implant and multisite neural stimulation/recording.
View details for DOI 10.1016/j.jneumeth.2013.06.011
View details for PubMedID 23867081
View details for PubMedCentralID PMC3789534
Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins.
2012; 9 (2): 159-172
Diverse optogenetic tools have allowed versatile control over neural activity. Many depolarizing and hyperpolarizing tools have now been developed in multiple laboratories and tested across different preparations, presenting opportunities but also making it difficult to draw direct comparisons. This challenge has been compounded by the dependence of performance on parameters such as vector, promoter, expression time, illumination, cell type and many other variables. As a result, it has become increasingly complicated for end users to select the optimal reagents for their experimental needs. For a rapidly growing field, critical figures of merit should be formalized both to establish a framework for further development and so that end users can readily understand how these standardized parameters translate into performance. Here we systematically compared microbial opsins under matched experimental conditions to extract essential principles and identify key parameters for the conduct, design and interpretation of experiments involving optogenetic techniques.
View details for DOI 10.1038/nmeth.1808
View details for PubMedID 22179551
- Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins NATURE METHODS 2012; 9 (2): 159-172
Neocortical excitation/inhibition balance in information processing and social dysfunction
2011; 477 (7363): 171-178
Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
View details for DOI 10.1038/nature10360
View details for Web of Science ID 000294603900027
View details for PubMedID 21796121