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M A Nicolelis

Publications and source records attributed to M A Nicolelis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Independent component analyses for quantifying neuronal ensemble interactions.

The goal of this study was to compare how multivariate statistical methods for dimension reduction account for correlations between simultaneously recorded neurons. Here, we describe applications of principal component analysis (PCA) and independent component analysis (ICA) (Cardoso J-F, Souloumiac A. IEE-Proc F 1993;140:362-70; Hyvarinen A, Oja E. Neural Comput 1997;9:1483-92; Lee TW, Girolami M, Sejnowski TJ. Neural Comp 1999;11:417-41) to neuronal ensemble data. Simulated ensembles of neurons were used to compare how well the methods above could account for correlated neuronal firing. The simulations showed that 'population vectors' defined by PCA were broadly distributed over the neuronal ensembles; thus, PCA was unable to identify independent groupings of neurons that shared common sources of input. By contrast, the ICA methods were all able to identify groupings of neurons that emerged due to correlated firing. This result suggests that correlated neuronal firing is reflected in higher-order correlations between neurons and not simply in the neurons' covariance. To assess the significance of these methods for real neuronal ensembles, we analyzed data from populations of neurons recorded in the motor cortex of rats trained to perform a reaction-time task. Scores for PCA and ICA were reconstructed on a bin-by-bin basis for single trials. These data were then used to train an artificial neural network to discriminate between single trials with either short or long reaction-times. Classifications based on scores from the ICA-based methods were significantly better than those based on PCA. For example, scores for components defined with an ICA-based method, extended ICA (Lee et al., 1999), classified more trials correctly (80.58+/-1.25%) than PCA (73.14+/-0.84%) for an ensemble of 26 neurons recorded in the motor cortex (ANOVA: P < 0.005). This result suggests that behaviorally relevant information is represented in correlated neuronal firing and can be best detected when higher-order correlations between neurons are taken into account.

Action Potentials↗
PubMed1999

Behavioral modulation of tactile responses in the rat somatosensory system.

We investigated the influence of four different behavioral states on tactile responses recorded simultaneously via arrays of microwires chronically implanted in the vibrissal representations of the rat ventral posterior medial nucleus (VPM) of the thalamus and the primary somatosensory cortex (SI). Brief (100 microsecond) electrical stimuli delivered via a cuff electrode to the infraorbital nerve yielded robust sensory responses in VPM and SI during states of quiet immobility. However, significant reductions in tactile response magnitude and latency were observed in VPM and SI during large-amplitude, exploratory movements of the whiskers (at approximately 4-6 Hz). During small-amplitude, 7-12 Hz whisker-twitching movements, a significant reduction in SI response magnitude and an increase in VPM and SI response latencies were observed as well. When pairs of stimuli with interstimulus intervals <100 msec were delivered during quiet immobility, the response to the second stimulus in the pair was reduced and occurred at a longer latency compared with the response to the first stimulus. In contrast, during large-amplitude whisker movements and general motor activity, paired stimuli yielded similar sensory responses at interstimulus intervals >25 msec. These response patterns were correlated with the amount and duration of postexcitatory firing suppression observed in VPM and SI during each of these behaviors. On the basis of these results, we propose that sensory responses are dynamically modulated during active tactile exploration to optimize detection of different types of stimuli. During quiet immobility, the somatosensory system seems to be optimally tuned to detect the presence of single stimuli. In contrast, during whisker movements and other exploratory behaviors, the system is primed to detect the occurrence of rapid sequences of tactile stimuli, which are likely to be generated by multiple whisker contacts with objects during exploratory activity.

Animals↗
PubMed1999

Immediate thalamic sensory plasticity depends on corticothalamic feedback.

Multiple neuron ensemble recordings were obtained simultaneously from both the primary somatosensory (SI) cortex and the ventroposterior medial thalamus (VPM) before and during the combined administration of reversible inactivation of the SI cortex and a reversible subcutaneous block of peripheral trigeminal nerve fibers. This procedure was performed to quantify the contribution of descending corticofugal projections on (i) the normal organization of thalamic somatosensory receptive fields and (ii) the thalamic somatosensory plastic reorganization that immediately follows a peripheral deafferentation. Reversible inactivation of SI cortex resulted in immediate changes in receptive field properties throughout the VPM. Cortical inactivation also significantly reduced but did not completely eliminate the occurrence of VPM receptive field reorganization resulting from the reversible peripheral deafferentation. This result suggests that the thalamic plasticity that is seen immediately after a peripheral deafferentation is dependent upon both descending corticofugal projections and ascending trigeminothalamic projections.

Animals↗
PubMed1999

Real-time control of a robot arm using simultaneously recorded neurons in the motor cortex.

To determine whether simultaneously recorded motor cortex neurons can be used for real-time device control, rats were trained to position a robot arm to obtain water by pressing a lever. Mathematical transformations, including neural networks, converted multineuron signals into 'neuronal population functions' that accurately predicted lever trajectory. Next, these functions were electronically converted into real-time signals for robot arm control. After switching to this 'neurorobotic' mode, 4 of 6 animals (those with > 25 task-related neurons) routinely used these brain-derived signals to position the robot arm and obtain water. With continued training in neurorobotic mode, the animals' lever movement diminished or stopped. These results suggest a possible means for movement restoration in paralysis patients.

Animals↗
PubMed1999

Spatiotemporal properties of layer V neurons of the rat primary somatosensory cortex.

Animals in their natural environments actively process spatiotemporally complex sensory signals in order to guide adaptive behavior. It therefore seems likely that the properties of both single neurons and neural ensembles should reflect the dynamic nature of such interactions. During exploratory behaviors, rats move their whiskers to actively discriminate between different tactile features. We investigated whether this dynamic sensory processing was reflected in the spatial and temporal properties of neurons in layer V of the 'whisker area' in the rat primary somatosensory cortex. We found that the majority of layer V neurons had large (8.5+/-4.9 whiskers) spatiotemporal receptive fields (i.e. individual cells responded best to different whiskers as a function of post-stimulus time), and that the excitatory responses of surround whiskers formed a spatial gradient of excitation that seemed to reflect the greater use of the ventral and caudal whiskers during natural behaviors. Analyses of ensembles of layer V neurons revealed that single-whisker stimuli activated a portion of layer V that extends well beyond a single cortical column (average of 5.6 barrel cortical columns). Based on these results, we conclude that the rat primary somatosensory cortex does not appear to operate as a static decoder of tactile information. On the contrary, our data suggest that tactile processing in rats is likely to involve the on-going interactions between populations of broadly tuned neurons in the thalamocortical pathway.

Animals↗
PubMed1999

Simultaneous reorganization in thalamocortical ensembles evolves over several hours after perioral capsaicin injections.

Reorganization of the somatosensory system was quantified by simultaneously recording from single-unit neural ensembles in the whisker regions of the ventral posterior medial (VPM) nucleus of the thalamus and the primary somatosensory (SI) cortex in anesthetized rats before, during, and after injecting capsaicin under the skin of the lip. Capsaicin, a compound that excites and then inactivates a subset of peripheral C and Adelta fibers, triggered increases in spontaneous firing of thalamocortical neurons (10-15 min after injection), as well as rapid reorganization of the whisker representations in both the VPM and SI. During the first hour after capsaicin injection, 57% of the 139 recorded neurons either gained or lost at least one whisker response in their receptive fields (RFs). Capsaicin-related changes continued to emerge for >/=6 h after the injection: Fifty percent of the single-neuron RFs changed between 1-2 and 5-6 h after capsaicin injection. Most (79%) of these late changes represented neural responses that had remained unchanged in the first postcapsaicin mapping; just under 20% of these late changes appeared in neurons that had previously shown no plasticity of response. The majority of the changes (55% immediately after injection, 66% 6 h later) involved "unmasking" of new tactile responses. RF change rates were comparable in SI and VPM (57-49%). Population analysis indicated that the reorganization was associated with a lessening of the "spatial coupling" between cortical neurons-a significant reduction in firing covariance that could be related to distances between neurons. This general loss of spatial coupling, in conjunction with increases in spontaneous firing, may create a situation that is favorable for the induction of synaptic plasticity. Our results indicate that the selective inactivation of a peripheral nociceptor subpopulation can induce rapid and long-evolving (>/=6 h) shifts in the balance of inhibition and excitation in the somatosensory system. The time course of these processes suggest that thalamic and cortical plasticity is not a linear reflection of spinal and brainstem changes that occur following the application of capsaicin.

Analysis of Variance↗
PubMed1998

Simultaneous encoding of tactile information by three primate cortical areas.

We used simultaneous multi-site neural ensemble recordings to investigate the representation of tactile information in three areas of the primate somatosensory cortex (areas 3b, SII and 2). Small neural ensembles (30-40 neurons) of broadly tuned somatosensory neurons were able to identify correctly the location of a single tactile stimulus on a single trial, almost simultaneously. Furthermore, each of these cortical areas could use different combinations of encoding strategies, such as mean firing rate (areas 3b and 2) or temporal patterns of ensemble firing (area SII), to represent the location of a tactile stimulus. Based on these results, we propose that ensembles of broadly tuned neurons, located in three distinct areas of the primate somatosensory cortex, obtain information about the location of a tactile stimulus almost concurrently.

Action Potentials↗
PubMed1997

Immediate and simultaneous sensory reorganization at cortical and subcortical levels of the somatosensory system.

The occurrence of cortical plasticity during adulthood has been demonstrated using many experimental paradigms. Whether this phenomenon is generated exclusively by changes in intrinsic cortical circuitry, or whether it involves concomitant cortical and subcortical reorganization, remains controversial. Here, we addressed this issue by simultaneously recording the extracellular activity of up to 135 neurons in the primary somatosensory cortex, ventral posterior medial nucleus of the thalamus, and trigeminal brainstem complex of adult rats, before and after a reversible sensory deactivation was produced by subcutaneous injections of lidocaine. Following the onset of the deactivation, immediate and simultaneous sensory reorganization was observed at all levels of the somatosensory system. No statistical difference was observed when the overall spatial extent of the cortical (9.1 +/- 1.2 whiskers, mean +/- SE) and the thalamic (6.1 +/- 1.6 whiskers) reorganization was compared. Likewise, no significant difference was found in the percentage of cortical (71.1 +/- 5.2%) and thalamic (66. 4 +/- 10.7%) neurons exhibiting unmasked sensory responses. Although unmasked cortical responses occurred at significantly higher latencies (19.6 +/- 0.3 ms, mean +/- SE) than thalamic responses (13. 1 +/- 0.6 ms), variations in neuronal latency induced by the sensory deafferentation occurred as often in the thalamus as in the cortex. These data clearly demonstrate that peripheral sensory deafferentation triggers a system-wide reorganization, and strongly suggest that the spatiotemporal attributes of cortical plasticity are paralleled by subcortical reorganization.

Animals↗
PubMed1997

Topographic and laminar organizations of the incertocortical pathway in rats.

The topographic and laminar organizations of the projection system from the zona incerta to the neocortex were studied by using both retrograde and anterograde methods in the rat. Injections of retrograde fluorescent tracers into different cortical areas revealed that the incertocortical projection neurons have a rough topographic organization with respect to their cortical targets. Furthermore, the incertocortical projecting neurons were found mainly in the dorsal and rostral subdivisions of the zona incerta, and none were found in the ventral subdivision. In cases which included three different fluorescent tracers injected into the frontal, the parietal and the occipital cortices, retrogradely single-labelled cells were found intermingled within the dorsal zona incerta. Very few double-labelled cells were noted, and triple-labelled cells were absent. Injections of anterograde tracers into the dorsal zona incerta demonstrate that labelled fibres traverse the striatum and terminate most densely in the outer half of layer I of the neocortex. The density of incertocortical terminals was greatest in the somatosensory cortex, while the innervation of visual cortical areas was sparse. Very fine and sparse bouton-like swellings of labelled incertocortical fibres were found running parallel along the pial surface. Since it has recently been shown that the incertocortical projections derive from GABAergic neurons, the present results suggest that the diffuse and roughly topographic projection from the zona incerta to the cerebral cortex may play an inhibitory role in widespread areas of cerebral cortex. This inhibitory action may preferentially target the distal dendrites of cortical neurons, since the majority of incertocortical terminals were found in the outer part of layer I of the neocortex.

Anatomy, Artistic↗
PubMed1997

Reconstructing the engram: simultaneous, multisite, many single neuron recordings.

Little is known about the physiological principles that govern large-scale neuronal interactions in the mammalian brain. Here, we describe an electrophysiological paradigm capable of simultaneously recording the extracellular activity of large populations of single neurons, distributed across multiple cortical and subcortical structures in behaving and anesthetized animals. Up to 100 neurons were simultaneously recorded after 48 microwires were implanted in the brain stem, thalamus, and somatosensory cortex of rats. Overall, 86% of the implanted microwires yielded single neurons, and an average of 2.3 neurons were discriminated per microwire. Our population recordings remained stable for weeks, demonstrating that this method can be employed to investigate the dynamic and distributed neuronal ensemble interactions that underlie processes such as sensory perception, motor control, and sensorimotor learning in freely behaving animals.

Animals↗
PubMed1997

Nonlinear processing of tactile information in the thalamocortical loop.

Rats explore tangible objects in a manner such that, at any given moment in time, multiple facial whiskers simultaneously contact the surface of the object. Although both thalamic and cortical neurons responsible for processing such tactile information have large, multiwhisker receptive fields, it remains unclear what kinds of computations can be carried out by these neuronal populations when behaviorally relevant multiwhisker stimuli are used. By simultaneously recording the activity of up to 78 cortical and thalamic neurons per animal, we observed that the magnitude of sensory responses and the spatial spread of ensemble activity increased in a nonlinear fashion according to the extent and spatial orientation of the multiwhisker stimuli. Supralinear responses were seen more frequently with vertically than with horizontally oriented stimuli. These data suggest that thalamocortical interactions in the rat somatosensory system can generate complex spatial transformations of multiwhisker stimuli that go beyond the classic inhibitory interactions previously observed.

Animals↗
PubMed1997

Neonatal whisker removal reduces the discrimination of tactile stimuli by thalamic ensembles in adult rats.

Simultaneous recordings of up to 48 single neurons per animal were used to characterize the long-term functional effects of sensory plastic modifications in the ventral posterior medial nucleus (VPM) of the thalamus following unilateral removal of facial whiskers in newborn rats. One year after this neonatal whisker deprivation, neurons in the contralateral VPM responded to cutaneous stimulation of the face at much longer minimal latencies (15.2 +/- 8.2 ms, mean +/- SD) than did normal cells (8.8 +/- 5.3 ms) in the same subregion of the VPM. In 69% of these neurons, the initial sensory responses to stimulus offset were followed for up to 700 ms by reverberant trains of bursting discharge, alternating in 100-ms cycles with inhibition. Receptive fields in the deafferented VPM were also atypical in that they extended over the entire face, shoulder, forepaw, hindpaw, and even ipsilateral whiskers. Discriminant analysis (DA) was then used to statistically evaluate how this abnormal receptive field organization might affect the ability of thalamocortical neuronal populations to "discriminate" somatosensory stimulus location. To standardize this analysis, three stimulus targets ("groups") were chosen in all animals such that they triangulated the central region of the "receptive field" of the recorded multineuronal ensemble. In the normal animals these stimulus targets were whiskers or perioral hairs; in the deprived animals the targets typically included hairy skin of the body as well as face. The measured variables consisted of each neuron's spiking response to each stimulus differentiated into three poststimulus response epochs (0-15, 15-30, and 30-45 ms). DA quantified the statistical contribution of each of these variables to its overall discrimination between the three stimulus sites. In the normal animals, the stimulus locations were correctly classified in 88.2 +/- 3.7% of trials on the basis of the spatiotemporal patterns of ensemble activity derived from up to 18 single neurons. In the deprived animals, the stimulus locations were much less consistently discriminated (reduced to 73.5 +/- 12.6%; difference from controls significant at P < 0.01) despite the fact that much more widely spaced stimulus targets were used and even when up to 20 neurons were included in the ensemble. Overall, these results suggest that neonatal damage to peripheral sense organs may produce marked changes in the physiology of individual neurons in the somatosensory thalamus. Moreover, the present demonstration that these changes can profoundly alter sensory discrimination at the level of neural populations in the thalamus provides important evidence that the well-known perceptual effects of chronic peripheral deprivation may be partially attributable to plastic reorganization at subcortical levels.

Animals↗
PubMed1996

Calbindin-containing non-specific thalamocortical projecting neurons in the rat.

Immunoreactivity for calcium binding proteins was used to demonstrate the neurochemical profiles of non-specific thalamocortical neurons located in the ventromedial nucleus, the centrolateral nucleus, and the nucleus reuniens that project to the somatosensory cortex in the adult rat. Cortical injections of fluorescent tracers combined with immunohistochemistry for calcium binding proteins revealed that retrogradely labeled neurons in these three thalamic nuclei are immunoreactive for calbindin. The present results suggest the presence of a chemically distinct non-specific thalamocortical system which terminates in the neocortex.

Animals↗
PubMed1996

Active tactile exploration influences the functional maturation of the somatosensory system.

1. The hypothesis that active exploration of objects is required for the functional maturation of neuronal circuits subserving tactile perception was tested by subjecting 8- to 11-day old rats to a complete unilateral section of the facial nerve. This procedure selectively abolished whisker protraction movements without affecting the sensory innervation of the facial vibrissae, the tactile organs used by rats to discriminate object texture and shape. 2. Six to 14 mo after the facial nerve section, simultaneous recordings of neuronal ensembles located in the ventral posterior medial nucleus (VPM) of the thalamus revealed a marked reduction in receptive field (RF) size (in terms of number of whiskers), and the formation of abnormal RF surrounds, spanning the face and contiguous body regions. In addition, the directional organization of VPM RFs, represented by caudal to rostral shifts in RF centers over 30 ms following whisker stimulation, was greatly reduced in these animals. 3. These results suggest that neonatal active tactile exploration is required to establish normal spatiotemporal patterning of neuronal RFs within the somatosensory system, and consequently, to develop normal tactile perception.

Animals↗
PubMed1996

Beyond maps: a dynamic view of the somatosensory system.

Current theories on how tactile information is processed by the mammalian somatosensory system are based primarily on data obtained in studies in which the physiological properties of single neurons were characterized, one at a time, in behaving or anesthetized animals. Yet, the central nervous system relies on the concurrent activation of large populations of neurons to process the variety of sensory stimuli that contribute to normal tactile perception. The recent introduction of electrophysiological methods for chronic and simultaneous recordings of the extracellular activity of large numbers of single neurons per animal has allowed us to investigate, for the first time, how populations of neurons, located at multiple processing stages of the somatosensory system, interact following passive and active tactile stimulation. The rat trigeminal somatosensory system was used as a model for this investigation. Our results revealed the existence of highly dynamic and distributed representations of tactile information, not only in the somatosensory cortex, but also in the thalamus and even in the brainstem. In these structures, we identified broadly tuned neurons with multiwhisker receptive fields (RFs). In the thalamus, a large percentage of neurons exhibited shifts in the spatial domain of their RFs as a function of post-stimulus time. During these shifts, the center of the neuron's RF moved across the whisker pad from caudal to rostral whiskers, but not in the opposite direction, suggesting that these spatiotemporal RFs may encode directional information. Further studies revealed that somatosensory representations were maintained by dynamic interactions between multiple convergent afferents, since they could be altered in a matter of seconds by reversible sensory deprivations. Overall, these results suggest that the rat somatosensory system relies on both spatial and temporal interactions between populations of cortical and subcortical neurons to process multiple attributes of tactile stimuli.

Animals↗
PubMed1995

Sensorimotor encoding by synchronous neural ensemble activity at multiple levels of the somatosensory system.

Neural ensemble processing of sensorimotor information during behavior was investigated by simultaneously recording up to 48 single neurons at multiple relays of the rat trigeminal somatosensory system. Cortical, thalamic, and brainstem neurons exhibited widespread 7- to 12-hertz synchronous oscillations, which began during attentive immobility and reliably predicted the imminent onset of rhythmic whisker twitching. Each oscillatory cycle began as a traveling wave of neural activity in the cortex that then spread to the thalamus. Just before the onset of rhythmic whisker twitching, the oscillations spread to the spinal trigeminal brainstem complex. Thereafter, the oscillations at all levels were synchronous with whisker protraction. Neural structures manifesting these rhythms also exhibited distributed spatiotemporal patterns of neuronal ensemble activity in response to tactile stimulation. Thus, multilevel synchronous activity in this system may encode not only sensory information but also the onset and temporal domain of tactile exploratory movements.

Animals↗