Biology subjects

Shadmehr, R.

Publications and source records attributed to Shadmehr, R..

27 records · Page 2Linked to original sources

bioRxiv2020

Population coding in the cerebellum and its implications for learning from error

The cerebellum resembles a feedforward, three-layer network of neurons in which the "hidden layer" consists of Purkinje cells (P-cells), and the output layer consists of deep cerebellar nucleus (DCN) neurons. However, unlike an artificial network, P-cells are grouped into small populations that converge onto single DCN neurons. Why are the P-cells organized in this way, and what is the membership criterion of each population? To consider these questions, in this review I apply elementary mathematics from machine learning and assume that the output of each DCN neuron is a prediction that is compared to the actual observation, resulting in an error signal that originates in the inferior olive. This signal is sent to P-cells via climbing fibers that produce complex spikes. The same error signal from the olive must also guide learning in the DCN neurons, yet the olivary projections to the DCN are weak, particularly in adulthood. However, P-cells that form a population exhibit a special property: they can synchronize their complex spikes, which in turn suppresses activity of the DCN neuron that produced the erroneous output. Viewed in the framework of machine learning, it appears that the olive organizes the P-cells into populations so that through complex spike synchrony each population can act as a surrogate teacher for the DCN neuron it projects to. This error-dependent grouping of P-cells into populations gives rise to a number of remarkable features of behavior, including multiple timescales of learning, protection from erasure, and spontaneous recovery of memory.

neuroscience↗

bioRxiv2020

Spontaneous recovery and the multiple timescales of human motor memory

In numerous paradigms, from fear conditioning to motor adaptation, memory exhibits a remarkable property: acquisition of a novel behavior followed by its extinction results in spontaneous recovery of the original behavior. A current model suggests that spontaneous recovery occurs because learning is supported by two different adaptive processes: one fast (high error sensitivity, low retention), and the other slow (low error sensitivity, high retention). Here, we searched for signatures of these hypothesized processes in the commands that guided single movements. We examined human saccadic eye movements and observed that following experience of a visual error, there was an adaptive change in the motor commands of the subsequent saccade, partially correcting for the error. However, the error correcting commands were expressed only during the deceleration period. If the errors persisted, the acceleration period commands also changed. Adaptation of acceleration period commands exhibited poor sensitivity to error, but the learning was resistant to forgetting. In contrast, the deceleration period commands adapted with high sensitivity to error, and the learning suffered from poor retention. Thus, within a single saccade, a fast-like process influenced the deceleration period commands, whereas a slow-like process influenced the acceleration period commands. Following extinction training, with passage of time motor memory exhibited spontaneous recovery, as evidenced by return of saccade endpoints toward their initial adapted state. The temporal dynamics of spontaneous recovery suggested that a single saccade is controlled by two different adaptive controllers, one active during acceleration, and the other during deceleration. Significance statementA feature of memory in many paradigms is the phenomenon of spontaneous recovery: learning followed by extinction inevitably leads to reversion toward the originally learned behavior. A theoretical model posits that spontaneous recovery is a feature of memory systems that learn with two independent learning processes, one fast, and the other slow. However, there have been no direct measures of these putative processes. Here, we found potential signatures of the two independent adaptive processes during control of a single saccade. The results suggest that distinct adaptive controllers contribute to the acceleration and deceleration phases of a saccade, and that each controller is supported by a fast and a slow learning process.

neuroscience↗

bioRxiv2019

Asymptotic limits of sensorimotor adaptation

After extended practice, motor adaptation reaches a limit in which learning appears to stop, despite the fact that residual errors persist. What prevents the brain from eliminating the residual errors? Here we found that the adaptation limit was causally dependent on the second order statistics of the perturbation; when variance was high, learning was impaired and large residual errors persisted. However, when learning relied solely on explicit strategy, both the adaptation limit and its dependence on perturbation variability disappeared. In contrast, when learning depended entirely, or in part on implicit learning, residual errors developed. Residual errors in implicit performance were caused by variance-dependent modifications to error sensitivity, not forgetting. These observations are consisted with a model of learning in which the implicit system becomes more sensitive to error when errors are consistent, but forgets this memory of errors over time. Thus, residual errors in motor adaptation are a signature of the implicit learning system, caused by an error sensitivity that depends on the history of past errors.

neuroscience↗

bioRxiv2019

Saccade vigor as an implicit measure of subjective economic value

Decisions are made based on the subjective value that the brain assigns to options. However, subjective value is a mathematical construct that cannot be measured directly, but rather inferred from choices. Recent results have demonstrated that reaction time and velocity of movements are modulated by reward, raising the possibility that there is a link between how the brain evaluates an option, and how it controls movements toward that option. Here, we asked people to choose among risky options represented by abstract stimuli, some associated with gain, others with loss. From their choices in decision trials we estimated the subjective value that they assigned to each stimulus. In probe trials, they were presented with a single stimulus at center and made a saccade to a peripheral location. We found that the reaction time and peak velocity of that saccade varied roughly linearly from loss to gain with the subjective value of the stimulus. Naturally, participants differed in how much they valued a given stimulus. Remarkably, those who valued a stimulus more, as evidenced by their choices in decision trials, tended to move with greater vigor in response to that stimulus in probe trials. Thus, saccade vigor partly reflected the subjective value that the brain assigned the stimulus. However, the influence of subjective value on vigor was only a modest predictor of preference: vigor in probe trials allowed us to predict choice in decision trials with roughly 60% accuracy. New and NoteworthyWe found that saccade vigor tends to vary monotonically with subjective value: smallest for stimuli that predict a loss, and highest for stimuli that predict a gain. Notably, between-subject differences in valuation could be gleaned from the between-subject differences in their patterns of vigor. However, the influence of subjective value on vigor was modest, allowing partial ability to infer subjective value for the purpose of predicting choice in decision trials.

neuroscience↗

bioRxiv2019

Behavioral training of marmosets and electrophysiological recording from the cerebellum

The common marmoset (Callithrix Jacchus) is a promising new model for study of neurophysiological basis of behavior in primates. Like other primates, it relies on saccadic eye movements to monitor and explore its environment. Previous reports have demonstrated some success in training marmosets to produce goal-directed actions in the laboratory. However, the number of trials per session has been relatively small, thus limiting the utility of marmosets as a model for behavioral and neurophysiological studies. Here, we report the results of a series of new behavioral training and neurophysiological protocols aimed at increasing the number of trials per session while recording from the cerebellum. To improve the training efficacy, we designed a precisely calibrated food regulation regime that motivated the subjects to perform saccade tasks, resulting in about a thousand reward-driven trials on a daily basis. We then developed a multi-channel recording system that used imaging to target a desired region of the cerebellum, allowing for simultaneous isolation of multiple Purkinje cells in the vermis. In this report, we describe (1) the design and surgical implantation of a CT guided, subject specific head-post, (2) the design of a CT and MRI guided alignment tool for trajectory guidance of electrodes mounted on an absolute encoder microdrive, (3) development of a protocol for behavioral training of subjects, and (4) simultaneous recordings from pairs of Purkinje cells during a saccade task.\n\nNew and NoteworthyMarmosets present the opportunity to investigate genetically based neurological disease in primates; in particular, diseases that affect social behaviors, vocal communication, and eye movements. All of these behaviors depend on the integrity of the cerebellum. Here, we present training methods that better motivate the subjects, allowing for improved performance, and also present electrophysiological techniques that precisely target the subjects cerebellum, allowing for simultaneous isolation of multiple Purkinje cells.\n\nIn our parks, are there any trees more elegant and luxurious than the Purkinje cell from the cerebellum? Santiago Ramon y Cajal

neuroscience↗

bioRxiv2019

The origins of anterograde interference in visuomotor adaptation

Anterograde interference refers to the negative impact of prior learning on the propensity for future learning. Previous work has shown that subsequent adaptation to two perturbations of opposing sign, A and B, impairs performance in B. Here, we aimed to unveil the mechanism at the basis of anterograde interference by tracking its impact as a function of time through a 24h period. We found that the memory of A biased performance in B for all time intervals. Conversely, learning from error was hindered up to 1h following acquisition of A, with release from interference occurring at 6h. These findings suggest that poor performance induced by prior learning is driven by two distinct mechanisms: a long-lasting bias that acts as a prior and hinders the initial level of performance, and a short-lasting learning impairment that originates from a reduction in error-sensitivity. Our work provides insight into the timeline of memory stabilization in visuomotor adaptation.

neuroscience↗

bioRxiv2019

Holding the arm still through subcortical mathematical integration of cortical commands

A period of holding still follows every movement. It has been assumed that for the arm, moving and holding are functionally independent: movement is via an adaptive, feedback-dependent controller that generates commands to transport the arm, while holding is via setting of reflexes that produce a postural field at movement endpoint. This assumption predicts that commands that move the arm should not affect the postural field at movement termination. Surprisingly, we found that as the reach commands changed, so did the ensuing postural field. The postural commands depended on mathematical integration of the reach commands. Following damage to the corticospinal tract, despite severe reach impairments, the holding system faithfully integrated the imperfect reach commands on a trial-by-trial basis. Together, these findings suggest that holding the arm still is accomplished via a separate, likely subcortical structure that acts as a mathematical integrator of the commands generated by the cortical reach controller.

neuroscience↗

bioRxiv2019

Reward prediction error modulates saccade vigor

Movements toward rewarding stimuli exhibit greater vigor, i.e., increased velocity and reduced reaction-times. This invigoration may be due to release of dopamine before movement onset. Dopamine release is strongly modulated by reward prediction error (RPE). Here, we generated an RPE event in the milliseconds before movement onset and tested whether there was a causal relationship between RPE and vigor. Human subjects made saccades toward an image. During the execution of their primary saccade, we probabilistically changed the position and content of the image. This led to a secondary saccade following completion of the primary saccade. We focused on properties of this secondary saccade. On some trials, the content of the secondary image was more valuable than the first image, resulting in a +RPE event that preceded the secondary saccade. On other trials, this content was less valuable, resulting in a -RPE event. We found that reaction-time and velocity of the secondary saccade were affected in an orderly fashion by the magnitude and direction of the preceding RPE event: the most vigorous saccades followed the largest +RPE, whereas the least vigorous saccades followed the largest -RPE. Presence of the secondary saccade indicated that the primary saccade had experienced a movement error, inducing trial-to-trial adaptation: the subsequent primary saccade was changed in the direction of the movement error in the previous trial. However, motor learning from error was not affected by the RPE event. Therefore, reward prediction error, and not reward per se, modulated vigor of saccades. Author summaryDoes dopamine release before onset of a movement modulate vigor of the ensuing movement? To test this hypothesis, we relied on the fact that RPE is a strong modulator of dopamine. Our innovation was a task in which an RPE event occurred precisely before onset of a movement. We probabilistically produced a combination of large or small, negative or positive RPE events before onset of a saccade, and observed that the vigor of the saccade that followed carried a robust signature of the preceding RPE event: high vigor saccades followed +RPE events, while low vigor saccades followed -RPE events. This suggests that control of vigor is partly through release of dopamine in the moments before onset of the movement.

neuroscience↗

bioRxiv2018

Impact of Human Behavioral Papers at Journal of Neuroscience

A recent policy change at Journal of Neuroscience (JN) has significantly increased editorial \"desk rejections\", reducing the number of papers that are considered for publication. Survey results from 130 scientists suggested that the new policy may have had a particularly large impact on studies that focused on human behavioral techniques. To quantify the effects of the new policy, we gathered data on all papers ever published in JN (~35,000), as well as all papers that had cited the JN papers (~2.7 million papers). We found that the recent change in editorial policy had disproportionately affected rejection rates of human behavioral papers: since 2015, the number of human behavioral papers as a proportion of all papers published in JN has seen a 30% decline. While there has been a long-term declining trend in the journals impact factor, we found that this declining impact factor was shared by both human behavioral papers as well as other papers in the journal. This suggested that whatever may have been the source of the declining impact factor at JN, this source was affecting the various areas of research equally. That is, it was unlikely that papers in any one field were responsible for the declining impact factor number at JN. Indeed, when impact was measured over the long-term, we found that the average human behavioral paper at JN consistently outperformed other papers, generating a significantly higher number of citations per year at 5 and 10 years post publication.

scientific communication and education↗