Biomedical subjects

Eilon Vaadia

Publications and source records attributed to Eilon Vaadia.

18 recordsLinked to original sources

PubMed2006

Midbrain dopamine neurons encode decisions for future action.

Current models of the basal ganglia and dopamine neurons emphasize their role in reinforcement learning. However, the role of dopamine neurons in decision making is still unclear. We recorded from dopamine neurons in monkeys engaged in two types of trial: reference trials in an instructed-choice task and decision trials in a two-armed bandit decision task. We show that the activity of dopamine neurons in the decision setting is modulated according to the value of the upcoming action. Moreover, analysis of the probability matching strategy in the decision trials revealed that the dopamine population activity and not the reward during reference trials determines choice behavior. Because dopamine neurons do not have spatial or motor properties, we conclude that immediate decisions are likely to be generated elsewhere and conveyed to the dopamine neurons, which play a role in shaping long-term decision policy through dynamic modulation of the efficacy of basal ganglia synapses.

Animals↗

PubMed2005

Comparing information about arm movement direction in single channels of local and epicortical field potentials from monkey and human motor cortex.

Cortical field potentials have been used for decades in neurophysiological studies to probe spatio-temporal activity patterns of local populations of neurons. Recently, however, interest in these signals was spurred as they were proposed as potential control signals for neuronal motor prostheses, i.e., for devices fit to record and decode brain activity to restore motor functions in paralyzed patients. Little is known, however, about the functional significance of these cortical field potentials. Here we compared information about arm movement direction in two types of movement related cortical field potentials, obtained during a four direction center-out arm reaching paradigm: local field potentials (LFPs) recorded with intracortical micro-electrodes from monkey motor cortex, and epicortical field potentials (EFPs) recorded with macro-electrode arrays subdurally implanted on the surface of the human cerebral cortex. While monkey LFPs showed a typical sequence of positive and negative potential peaks, an initial negative peak was the most salient feature of human EFPs. Individual contralateral LFPs from the monkey motor cortex carried approximately twice as much decoded information (DI) about arm movement direction (median 0.27 bit) as did individual EFPs from the contralateral hand/arm area of primary motor cortex in humans (median 0.12 bit). This relation was similar to the relation between median peak signal-to-noise ratios for directional modulation of movement related potentials (MRPs) of both types of signals. We discuss possible reasons for the observed differences, amongst them epi- vs. intracortical recording and the different electrode dimensions used to measure EFPs and LFPs.

Action Potentials↗

PubMed2005

Emerging patterns of neuronal responses in supplementary and primary motor areas during sensorimotor adaptation.

Acquisition and retention of sensorimotor skills have been extensively investigated psychophysically, but little is known about the underlying neuronal mechanisms. Here we examine the evolution of neural activity associated with adaptation to new kinematic tasks in two cortical areas: the caudal supplementary motor area (SMA proper), and the primary motor cortex (MI). We investigate the hypothesis that adaptation starts at premotor areas, i.e., higher in the hierarchy of computation, until a stable representation is formed in primary areas. In accordance with previous studies, we found that adaptation can be characterized by two phases: an early phase that is accompanied by fast and substantial reduction of errors, followed by a late phase with slower and more moderate improvements in behavior. We used unsupervised clustering to separate the activity of the single cells into groups of cells with similar response patterns, under the assumption that each such subpopulation forms a functional unit. We specifically observed the number of clusters in each cortical area during early and late phases of the adaptation and found that the number of clusters is higher in the SMA during early phases of adaptation. In contrast, a higher number of clusters was observed in MI only during late phases. Our results suggest a new approach to analyze responses of large populations of neurons and use it to show a hierarchy of dynamic reorganization of functional groups during adaptation.

Adaptation, Physiological↗

PubMed2005

Specificity of sensorimotor learning and the neural code: neuronal representations in the primary motor cortex.

Human studies show that the learning of a new sensorimotor mapping that requires adaptation to directional errors is local and generalizes poorly to untrained directions. We trained monkeys to learn new visuomotor rotations for only one target in space and recorded neuronal activity in the primary motor cortex before, during and after learning. Similar to humans, the monkeys showed poor transfer of learning to other directions, as observed by behavioral aftereffects for untrained directions. To test for internal representations underlying these changes, we compared two features of neuronal activity before and after learning: changes in firing rates and changes in information content. Specific elevations of firing rate were only observed in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation; namely cells only showed plasticity if their preferred direction was near the training one. We applied measures from information theory to probe for learning-related changes in the neuronal code. Single cells conveyed more information about the direction of movement and this specific improvement in encoding was correlated with an increase in the slope of the neurons' tuning curve. Further, the improved information after learning enabled a more accurate reconstruction of movement direction from neuronal populations. Our findings suggest a neural mechanism for the confined generalization of a newly acquired internal model by showing a tight relationship between the locality of learning and the properties of neurons. They also provide direct evidence for improvement in the neural code as a result of learning.

Action Potentials↗

PubMed2005

Encoding of movement direction in different frequency ranges of motor cortical local field potentials.

Recent studies showed that the low-frequency component of local field potentials (LFPs) in monkey motor cortex carries information about parameters of voluntary arm movements. Here, we studied how different signal components of the LFP in the time and frequency domains are modulated during center-out arm movements. Analysis of LFPs in the time domain showed that the amplitude of a slow complex waveform beginning shortly before the onset of arm movement is modulated with the direction of the movement. Examining LFPs in the frequency domain, we found that direction-dependent modulations occur in three frequency ranges, which typically increased their amplitudes before and during movement execution: < or =4, 6-13, and 63-200 Hz. Cosine-like tuning was prominent in all signal components analyzed. In contrast, activity in a frequency band approximately 30 Hz was not modulated with the direction of movement and typically decreased its amplitude during the task. This suggests that high-frequency oscillations have to be divided into at least two functionally different regimes: one approximately 30 Hz and one >60 Hz. Furthermore, using multiple LFPs, we could show that LFP amplitude spectra can be used to decode movement direction, with the best performance achieved by the combination of different frequency ranges. These results suggest that using the different frequency components in the LFP is useful in improving inference of movement parameters from local field potentials.

Action Potentials↗

PubMed2005

Segregation between acquisition and long-term memory in sensorimotor learning.

It is widely accepted that learning first involves generating new memories and then consolidating them into long-term memory. Thus learning is generally viewed as a single continuous process with two sequential stages; acquisition and consolidation. Here, we tested an alternative hypothesis proposing that acquisition and consolidation take place, at least partly, in parallel. Human subjects learned two visuomotor tasks. One task required moving a cursor under visuomotor rotation and the other required arbitrary association of colour to direction of movement. Subjects learned the two tasks in sequence, and were tested for acquisition of the second immediately after learning the first, and for retention of the first on the following day. The results show that learning one task led to proactive interference to acquisition of the second. However, this interference was not accompanied by retroactive interference to consolidation of the first task, indicating that acquisition and consolidation can be uncoupled.

Adult↗

PubMed2005

Spikernels: predicting arm movements by embedding population spike rate patterns in inner-product spaces.

Inner-product operators, often referred to as kernels in statistical learning, define a mapping from some input space into a feature space. The focus of this letter is the construction of biologically motivated kernels for cortical activities. The kernels we derive, termed Spikernels, map spike count sequences into an abstract vector space in which we can perform various prediction tasks. We discuss in detail the derivation of Spikernels and describe an efficient algorithm for computing their value on any two sequences of neural population spike counts. We demonstrate the merits of our modeling approach by comparing the Spikernel to various standard kernels in the task of predicting hand movement velocities from cortical recordings. All of the kernels that we tested in our experiments outperform the standard scalar product used in linear regression, with the Spikernel consistently achieving the best performance.

Action Potentials↗

PubMed2004

Independent coding of movement direction and reward prediction by single pallidal neurons.

Associating action with its reward value is a basic ability needed by adaptive organisms and requires the convergence of limbic, motor, and associative information. To chart the basal ganglia (BG) involvement in this association, we recorded the activity of 61 well isolated neurons in the external segment of the globus pallidus (GPe) of two monkeys performing a probabilistic visuomotor task. Our results indicate that most (96%) neurons responded to multiple phases of the task. The activity of many (34%) pallidal neurons was modulated solely by direction of movement, and the activity of only a few (3%) pallidal neurons was modulated exclusively by reward prediction. However, the activity of a large number (41%) of single pallidal neurons was comodulated by both expected trial outcome and direction of arm movement. The information carried by the neuronal activity of single pallidal neurons dynamically changed as the trial progressed. The activity was predominantly modulated by both outcome prediction and future movement direction at the beginning of trials and became modulated mainly by movement-direction toward the end of trials. GPe neurons can either increase or decrease their discharge rate in response to predicted future reward. The effects of movement-direction and reward probability on neural activity are linearly summed and thus reflect two independent modulations of pallidal activity. We propose that GPe neurons are uniquely suited for independent processing of a multitude of parameters. This is enabled by the funnel-structure characteristic of the BG architecture, as well as by the anatomical and physiological properties of GPe neurons.

Action Potentials↗

PubMed2004

Acquisition and generalization of visuomotor transformations by nonhuman primates.

The kinematics of straight reaching movements can be specified vectorially by the direction of the movement and its extent. To explore the representation in the brain of these two properties, psychophysical studies have examined learning of visuomotor transformations of either rotation or gain and their generalization. However, the neuronal substrates of such complex learning are only beginning to be addressed. As an initial step in ensuring the validity of such investigations, it must be shown that monkeys indeed learn and generalize visuomotor transformations in the same manner as humans. Here, we analyze trajectories and velocities of movements as monkeys adapt to either rotational or gain transformations. We used rotations with different signs and magnitudes, and gains with different signs, and analyzed transfer of learning to untrained movements. The results show that monkeys can adapt to both types of transformation with a time course that resembles human learning. Analysis of the aftereffects reveals that rotation is learned locally and generalizes poorly to untrained directions, whereas gain is learned more globally and can be transferred to other amplitudes. The results lend additional support to the hypothesis that reaching movements are learned locally but can be easily rescaled to other magnitudes by scaling the peak velocity. The findings also indicate that reaching movements in monkeys are planned and executed very similarly to those in humans. This validates the underlying presumption that neuronal recordings in primates can help elucidate the mechanisms of motor learning in particular and motor planning in general.

Animals↗

PubMed2004

Complex locking rather than complete cessation of neuronal activity in the globus pallidus of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primate in response to pallidal microstimulation.

High-frequency stimulation of the globus pallidus (GP) has emerged as a successful tool for treating Parkinson's disease and other motor disorders. However, the mechanism governing its therapeutic effect is still under debate. To shed light on the basic mechanism of deep brain stimulation (DBS), we performed microstimulation in the GP of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkey while recording with other microelectrodes in the same nucleus. We used robust methods to reduce the stimulus artifact, and 600-3000 repetitions of a single stimulus and of high-frequency short trains (10-40 stimuli), enabling high temporal resolution analysis of neural responses. Low-frequency stimulation yielded a typical three-stage response: short-term (2-3 msec duration) activity, followed by mid-term (15-25 msec) inhibition, and occasionally longer-term (30-40 msec) excitation. Trains of high-frequency stimuli elicited complex locking of the response to the stimuli in most neurons. The locking displayed a stereotypic temporal structure consisting of three short-duration (1-2 msec) phases: an initial (mean latency = 2.9 msec) excitation followed by an inhibition (4.6 msec) and a second excitation (6.3 msec). The change in the mean firing rate was mixed; the majority of the neurons displayed partial inhibition during the stimulus train. Slow inhibitory and excitatory multiphase changes in the firing rate were observed after the stimulus trains. The activity of neurons recorded simultaneously displayed rate correlations but no spike-to-spike correlations. Our results suggest that the effect of DBS on the GP is not complete inhibition but rather a complex reshaping of the temporal structure of the neuronal activity within that nucleus.

Animals↗

PubMed2004

Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons.

Midbrain dopamine and striatal tonically active neurons (TANs, presumed acetylcholine interneurons) signal behavioral significance of environmental events. Since striatal dopamine and acetylcholine affect plasticity of cortico-striatal transmission and are both crucial to learning, they may serve as teachers in the basal ganglia circuits. We recorded from both neuronal populations in monkeys performing a probabilistic instrumental conditioning task. Both neuronal types respond robustly to reward-related events. Although different events yielded responses with different latencies, the responses of the two populations coincided, indicating integration at the target level. Yet, while the dopamine neurons' response reflects mismatch between expectation and outcome in the positive domain, the TANs are invariant to reward predictability. Finally, TAN pairs are synchronized, compared to a minority of dopamine neuron pairs. We conclude that the striatal cholinergic and dopaminergic systems carry distinct messages by different means, which can be integrated differently to shape the basal ganglia responses to reward-related events.

Acetylcholine↗

PubMed2004

Spike synchronization in the cortex/basal-ganglia networks of Parkinsonian primates reflects global dynamics of the local field potentials.

Cortical local field potentials (LFPs) reflect synaptic potentials and accordingly correlate with neuronal discharge. Because LFPs are coherent across substantial cortical areas, we hypothesized that cortical spike correlations could be predicted from them. Because LFPs recorded in the basal ganglia (BG) are also correlated with neuronal discharge and are clinically accessible in Parkinson's disease patients, we were interested in testing this hypothesis in the BG, as well. We recorded LFPs and unit discharge from multiple electrodes, which were placed in primary motor cortex or in the basal ganglia (striatum and pallidum) of two monkeys before and after rendering them parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We used the method of partial spectra to construct LFP predictors of the spike cross-correlation functions (CCFs). The predicted CCF is an estimate of the correlation between two neurons under the assumption that their association is explained solely by the association of each with the LFP recorded on a third electrode. In the normal condition, the predictors account for cortical rate covariations but not for the association among the tonically active neurons of the striatum. In the parkinsonian condition, with the appearance of 10 Hz oscillations throughout the cortex-basal ganglia networks, the LFP predictors account remarkably better for the CCFs in both the cortex and the basal ganglia. We propose that, in the parkinsonian condition, the cortex-basal ganglia networks are more tightly related to global modes of brain dynamics that are echoed in the LFP.

Action Potentials↗

PubMed2004

Learning-induced improvement in encoding and decoding of specific movement directions by neurons in the primary motor cortex.

Many recent studies describe learning-related changes in sensory and motor areas, but few have directly probed for improvement in neuronal coding after learning. We used information theory to analyze single-cell activity from the primary motor cortex of monkeys, before and after learning a local rotational visuomotor task. We show that after learning, neurons in the primary motor cortex conveyed more information about the direction of movement and did so with relation to their directional sensitivity. Similar to recent findings in sensory systems, this specific improvement in encoding is correlated with an increase in the slope of the neurons' tuning curve. We further demonstrate that the improved information after learning enables a more accurate reconstruction of movement direction from neuronal populations. Our results suggest that similar mechanisms govern learning in sensory and motor areas and provide further evidence for a tight relationship between the locality of learning and the properties of neurons; namely, cells only show plasticity if their preferred direction is near the training one. The results also suggest that simple learning tasks can enhance the performance of brain-machine interfaces.

Animals↗

PubMed2004

Viewing and doing: similar cortical mechanisms for perceptual and motor learning.

Historically, different groups of researchers have investigated the mechanisms of perceptual learning and motor learning. For sensory cortex, neurophysiological and psychophysical findings have linked changes in perception with altered neuronal tuning properties. However, less information has been forthcoming from motor cortex. This review compares recent findings on perceptual and motor learning, and suggests that similar mechanisms govern both. These mechanisms involve changes in both the center of neuronal tuning functions and their width or slope. The former reflects the values of the sensory or motor parameters that a neuron encodes, and the latter adjusts the encoding sensitivity. These similarities suggest that specific unifying principles for neural coding and computation exist across sensory and motor domains.

Animals↗

PubMed2003

Cortical representation of bimanual movements.

It is well established that the discharge of neurons in primate motor cortex is tuned to the movement direction of the contralateral arm. Interestingly, it has been found that these neurons exhibit a directional tuning to the ipsilateral arm as well and that the preferred directions to both arms tend to be similar. A recent study showed that motor cortex cells are also directionally selective to bimanual movements, but the relationship between the bimanual and unimanual representations remains unclear. To address this issue, we analyzed the responses of motor cortical neurons recorded from two macaque monkeys during unimanual and bimanual reaching movements. We decomposed the bimanual movement representation into contralateral and ipsilateral directionally tuned components. Our major finding is that the movement of the contralateral arm modifies the tuning of the cells to the ipsilateral arm such that: (1) the offset and modulation depth of the tuning are suppressed; and (2) the preferred directions are randomly shifted. Both these effects eliminate the correlation between the contralateral and ipsilateral representations during bimanual movements. We suggest that the modification of the ipsilateral arm representation is caused by the recruitment of local inhibition that conveys callosal inputs during bimanual movements. This hypothesis is supported by the analysis of a model of two motor cortical networks, coupled with sparse random interhemispheric projections that reproduce the main features observed in the data. Finally, we show that the modification of the ipsilateral arm representation reduces the interference between the movements of both arms.

Animals↗

PubMed2003

Inference of hand movements from local field potentials in monkey motor cortex.

The spiking of neuronal populations in motor cortex provides accurate information about movement parameters. Here we show that hand movement target and velocity can be inferred from multiple local field potentials (LFPs) in single trials approximately as efficiently as from multiple single-unit activity (SUA) recorded from the same electrodes. Our results indicate that LFPs can be used as an additional signal for decoding brain activity, particularly for new neuroprosthetic applications.

Action Potentials↗

PubMed2003

Preparatory activity in motor cortex reflects learning of local visuomotor skills.

In humans, learning to produce correct visually guided movements to adapt to new sensorimotor conditions requires the formation of an internal model that represents the new transformation between visual input and the required motor command. When the new environment requires adaptation to directional errors, learning generalizes poorly to untrained locations and directions, indicating that such learning is local. Here we replicated these behavioral findings in rhesus monkeys using a visuomotor rotation task and simultaneously recorded neuronal activity. Specific changes in activity were observed only in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation. These changes adhered to the dynamics of behavior during learning and persisted between learning and relearning of the same rotation. These findings suggest a neural mechanism for the locality of newly acquired sensorimotor tasks and provide electrophysiological evidence for their retention in working memory.

Animals↗

PubMed2002

Enhanced synchrony among primary motor cortex neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease.

Primary motor cortex (MI) neurons discharge vigorously during voluntary movement. A cardinal symptom of Parkinson's disease (PD) is poverty of movement (akinesia). Current models of PD thus hypothesize that increased inhibitory pallidal output reduces firing rates in frontal cortex, including MI, resulting in akinesia and muscle rigidity. We recorded the simultaneous spontaneous discharge of several neurons in the arm-related area of MI of two monkeys and in the globus pallidus (GP) of one of the two. Accelerometers were fastened to the forelimbs to detect movement, and surface electromyograms were recorded from the contralateral arm of one monkey. The recordings were conducted before and after systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rendering the animals severely akinetic and rigid with little or no tremor. The mean spontaneous MI rates during periods of immobility (four to five spikes/sec) did not change after MPTP; however, in this parkinsonian state, MI neurons discharged in long bursts (sometimes >2 sec long). These bursts were synchronized across many cells but failed to elicit detectable movement, indicating that even robust synchronous MI discharge need not result in movement. These synchronized population bursts were absent from the GP and were on a larger timescale than oscillatory synchrony found in the GP of tremulous MPTP primates, suggesting that MI parkinsonian synchrony arises independently of basal ganglia dynamics. After MPTP, MI neurons responded more vigorously and with less specificity to passive limb movement. Abnormal MI firing patterns and synchronization, rather than reduced firing rates, may underlie PD akinesia and persistent muscle rigidity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗