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Biomedical subjects

Miguel A L Nicolelis

Publications and source records attributed to Miguel A L Nicolelis.

At least 19 recordsLinked to original sources
PubMed2006

Rapid alterations in corticostriatal ensemble coordination during acute dopamine-dependent motor dysfunction.

Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex during hyperdopaminergia ( approximately 500% of controls) with hyperkinesia, and after rapid and profound dopamine depletion (<0.2%) with akinesia in the same animal. Surprisingly, although most cortical and striatal neurons ( approximately 70%) changed firing rate during the transition between dopamine-related hyperkinesia and akinesia, the overall cortical firing rate remained unchanged. Conversely, neuronal oscillations and ensemble activity coordination within and between cortex and striatum did change rapidly between these periods. During hyperkinesia, corticostriatal activity became largely asynchronous, while during dopamine-depletion the synchronicity increased. Thus, dopamine-related disorders like Parkinson's disease may not stem from changes in the overall levels of cortical activity, but from dysfunctional activity coordination in corticostriatal circuits.

Action Potentials↗
PubMed2006

Dopaminergic control of sleep-wake states.

Dopamine depletion is involved in the pathophysiology of Parkinson's disease, whereas hyperdopaminergia may play a fundamental role in generating endophenotypes associated with schizophrenia. Sleep disturbances are known to occur in both schizophrenia and Parkinson's disease, suggesting that dopamine plays a role in regulating the sleep-wake cycle. Here, we show that novelty-exposed hyperdopaminergic mice enter a novel awake state characterized by spectral patterns of hippocampal local field potentials that resemble electrophysiological activity observed during rapid-eye-movement (REM) sleep. Treatment with haloperidol, a D2 dopamine receptor antagonist, reduces this abnormal intrusion of REM-like activity during wakefulness. Conversely, mice acutely depleted of dopamine enter a different novel awake state characterized by spectral patterns of hippocampal local field potentials that resemble electrophysiological activity observed during slow-wave sleep (SWS). This dopamine-depleted state is marked by an apparent suppression of SWS and a complete suppression of REM sleep. Treatment with D2 (but not D1) dopamine receptor agonists recovers REM sleep in these mice. Altogether, these results indicate that dopamine regulates the generation of sleep-wake states. We propose that psychosis and the sleep disturbances experienced by Parkinsonian patients result from dopamine-mediated disturbances of REM sleep.

Animals↗
PubMed2006

Fast modulation of prefrontal cortex activity by basal forebrain noncholinergic neuronal ensembles.

Traditionally, most basal forebrain (BF) functions have been attributed to its cholinergic neurons. However, the majority of cortical-projecting BF neurons are noncholinergic and their in vivo functions remain unclear. We investigated how BF modulates cortical dynamics by simultaneously recording </=50 BF single neurons along with local field potentials (LFPs) from the prefrontal cortex (PFCx) in different wake-sleep states of adult rats. Using stereotypical spike time correlations, we identified a large (roughly 70%) subset of BF neurons, which we named BF tonic neurons (BFTNs). BFTNs fired tonically at 2-8 Hz without significantly changing their average firing rate across wake-sleep states. As such, these cannot be classified as cholinergic neurons. BFTNs substantially increased the spiking variability during waking and rapid-eye-movement sleep, by exhibiting frequent spike bursts with <50-ms interspike interval. Spike bursts among BFTNs were highly correlated, leading to transient population synchronization events of BFTN ensembles that lasted on average 160 ms. Most importantly, BFTN synchronization occurred preferentially just before the troughs of PFCx LFP oscillations, which reflect increased cortical activity. Furthermore, BFTN synchronization was accompanied by transient increases in prefrontal cortex gamma oscillations. These results suggest that synchronization of BFTN ensembles, which are likely to be formed by cortical-projecting GABAergic neurons from the BF, could be primarily responsible for fast cortical modulations to provide transient amplification of cortical activity.

Animals↗
PubMed2006

Neural ensemble coding of satiety states.

The motivation to start or terminate a meal involves the continual updating of information on current body status by central gustatory and reward systems. Previous electrophysiological and neuroimaging investigations revealed region-specific decreases in activity as the subject's state transitions from hunger to satiety. By implanting bundles of microelectrodes in the lateral hypothalamus, orbitofrontal cortex, insular cortex, and amygdala of hungry rats that voluntarily eat to satiety, we have measured the behavior of neuronal populations through the different phases of a complete feeding cycle (hunger-satiety-hunger). Our data show that while most satiety-sensitive units preferentially responded to a unique hunger phase within a cycle, neuronal populations integrated single-unit information in order to reflect the animal's motivational state across the entire cycle, with higher activity levels during the hunger phases. This distributed population code might constitute a neural mechanism underlying meal initiation under different metabolic states.

Action Potentials↗
PubMed2006

Brain-machine interfaces: past, present and future.

Since the original demonstration that electrical activity generated by ensembles of cortical neurons can be employed directly to control a robotic manipulator, research on brain-machine interfaces (BMIs) has experienced an impressive growth. Today BMIs designed for both experimental and clinical studies can translate raw neuronal signals into motor commands that reproduce arm reaching and hand grasping movements in artificial actuators. Clearly, these developments hold promise for the restoration of limb mobility in paralyzed subjects. However, as we review here, before this goal can be reached several bottlenecks have to be passed. These include designing a fully implantable biocompatible recording device, further developing real-time computational algorithms, introducing a method for providing the brain with sensory feedback from the actuators, and designing and building artificial prostheses that can be controlled directly by brain-derived signals. By reaching these milestones, future BMIs will be able to drive and control revolutionary prostheses that feel and act like the human arm.

Animals↗
PubMed2006

Rapid taste responses in the gustatory cortex during licking.

Rapid tastant detection is necessary to prevent the ingestion of potentially poisonous compounds. Behavioral studies have shown that rats can identify tastants in approximately 200 ms, although the electrophysiological correlates for fast tastant detection have not been identified. For this reason, we investigated whether neurons in the primary gustatory cortex (GC), a cortical area necessary for tastant identification and discrimination, contain sufficient information in a single lick cycle, or approximately 150 ms, to distinguish between tastants at different concentrations. This was achieved by recording neural activity in GC while rats licked four times without a liquid reward, and then, on the fifth lick, received a tastant (FR5 schedule). We found that 34% (61 of 178) of GC units were chemosensitive. The remaining neurons were activated during some phase of the licking cycle, discriminated between reinforced and unreinforced licks, or processed task-related information. Chemosensory neurons exhibited a latency of 70-120 ms depending on concentration, and a temporally precise phasic response that returned to baseline in tens of milliseconds. Tastant-responsive neurons were broadly tuned and responded to increasing tastant concentrations by either increasing or decreasing their firing rates. In addition, some responses were only evoked at intermediate tastant concentrations. In summary, these results suggest that the gustatory cortex is capable of processing multimodal information on a rapid timescale and provide the physiological basis by which animals may discriminate between tastants during a single lick cycle.

Animals↗
PubMed2006

The neural mechanisms of gustation: a distributed processing code.

Whenever food is placed in the mouth, taste receptors are stimulated. Simultaneously, different types of sensory fibre that monitor several food attributes such as texture, temperature and odour are activated. Here, we evaluate taste and oral somatosensory peripheral transduction mechanisms as well as the multi-sensory integrative functions of the central pathways that support the complex sensations that we usually associate with gustation. On the basis of recent experimental data, we argue that these brain circuits make use of distributed ensemble codes that represent the sensory and post-ingestive properties of tastants.

Afferent Pathways↗
PubMed2006

Continuous shared control for stabilizing reaching and grasping with brain-machine interfaces.

Research on brain-machine interfaces (BMI's) is directed toward enabling paralyzed individuals to manipulate their environment through slave robots. Even for able-bodied individuals, using a robot to reach and grasp objects in unstructured environments can be a difficult telemanipulation task. Controlling the slave directly with neural signals instead of a hand-master adds further challenges, such as uncertainty about the intended trajectory coupled with a low update rate for the command signal. To address these challenges, a continuous shared control (CSC) paradigm is introduced for BMI where robot sensors produce reflex-like reactions to augment brain-controlled trajectories. To test the merits of this approach, CSC was implemented on a 3-degree-of-freedom robot with a gripper bearing three co-located range sensors. The robot was commanded to follow eighty-three reach-and-grasp trajectories estimated previously from the outputs of a population of neurons recorded from the brain of a monkey. Five different levels of sensor-based reflexes were tested. Weighting brain commands 70% and sensor commands 30% produced the best task performance, better than brain signals alone by more than seven-fold. Such a marked performance improvement in this test case suggests that some level of machine autonomy will be an important component of successful BMI systems in general.

Arm↗
PubMed2005

Stable ensemble performance with single-neuron variability during reaching movements in primates.

Significant variability in firing properties of individual neurons was observed while two monkeys, chronically implanted with multielectrode arrays in frontal and parietal cortical areas, performed a continuous arm movement task. Although the degree of correlation between the firing of single neurons and movement parameters was nonstationary, stable predictions of arm movements could be obtained from the activity of neuronal ensembles. This result adds support to the idea that movement parameters are redundantly encoded in the motor cortex, such that brain networks can achieve the same behavioral goals through different patterns and relative contribution of individual neuron activity. This has important implications for neural prosthetics, suggesting that accurate operation of a brain-machine interface requires recording from large neuronal ensembles to minimize the effect of variability and ensuring stable performance over long periods of time.

Action Potentials↗
PubMed2005

Orbitofrontal ensemble activity monitors licking and distinguishes among natural rewards.

The classification of rhythmic licking into clusters has proved to be useful for characterizing brain mechanisms that modulate the ingestion of natural rewards (sucrose and water). One cortical area that is responsive to rewarding stimuli is the orbitofrontal cortex (OFC). However, it is not presently known how OFC neurons respond while rodents freely lick for natural rewards and whether these responses are related to the structure of licking clusters. We addressed these issues by showing that temporary inactivation of the OFC decreases the duration and increases the number of clusters and that the activity of OFC neurons changed at precise times before, during, and after the cluster terminates. Furthermore, analysis of the activity of OFC neuronal ensembles showed that they could discriminate cluster onset from termination, predict when a behaving animal will begin a cluster, and distinguish and anticipate between natural rewards. These results provide a new role for the OFC in influencing licking clusters and anticipating specific rewards.

Animals↗
PubMed2005

Cortical ensemble adaptation to represent velocity of an artificial actuator controlled by a brain-machine interface.

Monkeys can learn to directly control the movements of an artificial actuator by using a brain-machine interface (BMI) driven by the activity of a sample of cortical neurons. Eventually, they can do so without moving their limbs. Neuronal adaptations underlying the transition from control of the limb to control of the actuator are poorly understood. Here, we show that rapid modifications in neuronal representation of velocity of the hand and actuator occur in multiple cortical areas during the operation of a BMI. Initially, monkeys controlled the actuator by moving a hand-held pole. During this period, the BMI was trained to predict the actuator velocity. As the monkeys started using their cortical activity to control the actuator, the activity of individual neurons and neuronal populations became less representative of the animal's hand movements while representing the movements of the actuator. As a result of this adaptation, the animals could eventually stop moving their hands yet continue to control the actuator. These results show that, during BMI control, cortical ensembles represent behaviorally significant motor parameters, even if these are not associated with movements of the animal's own limb.

Adaptation, Physiological↗
PubMed2005

Computing with thalamocortical ensembles during different behavioural states.

A series of recent studies have indicated that ensembles of neurones, distributed within the neural structures that form the primary thalamocortical loop (TCL) of the trigeminal component of the rat somatosensory system, change the way they respond to similar tactile stimuli, according to both the behavioural strategy employed by animals to gather information and the animal's internal brain states. These findings suggest that top-down influences, which are more likely to play a role during active discrimination than during passive whisker stimulation, may alter the pattern of neuronal firing within both the distinct layers of the primary somatosensory cortex (S1) and the ventral posterior medial nucleus (VPM). We propose that through this physiological process, which involves concurrent dynamic modulations at both cellular and circuit levels in the TCL, rats can either optimize the detection of novel or hard to sense stimuli or they can analyse complex patterns of multi-whisker stimulation, during natural exploration of their surrounding environment.

Animals↗
PubMed2005

Interpreting spatial and temporal neural activity through a recurrent neural network brain-machine interface.

We propose the use of optimized brain-machine interface (BMI) models for interpreting the spatial and temporal neural activity generated in motor tasks. In this study, a nonlinear dynamical neural network is trained to predict the hand position of primates from neural recordings in a reaching task paradigm. We first develop a method to reveal the role attributed by the model to the sampled motor, premotor, and parietal cortices in generating hand movements. Next, using the trained model weights, we derive a temporal sensitivity measure to asses how the model utilized the sampled cortices and neurons in real-time during BMI testing.

Algorithms↗
PubMed2005

Frontal and parietal cortical ensembles predict single-trial muscle activity during reaching movements in primates.

Previously we have shown that the kinematic parameters of reaching movements can be extracted from the activity of cortical ensembles. Here we used cortical ensemble activity to predict electromyographic (EMG) signals of four arm muscles in New World monkeys. The overall shape of the EMG envelope was predicted, as well as trial-to-trial variations in the amplitude and timing of bursts of muscle activity. Predictions of EMG patterns exhibited during reaching movements could be obtained not only from primary motor cortex, but also from dorsal premotor, primary somatosensory and posterior parietal cortices. These results suggest that these areas represent signals correlated to EMGs of arm muscles in a distributed manner, and that the larger the population sampled, the more reliable the predictions. We propose that, in the future, recordings from multiple cortical areas and the extraction of muscle patterns from these recordings will help to restore limb mobility in paralysed patients.

Algorithms↗
PubMed2004

Global forebrain dynamics predict rat behavioral states and their transitions.

The wake-sleep cycle, a spontaneous succession of global brain states that correspond to major overt behaviors, occurs in all higher vertebrates. The transitions between these states, at once rapid and drastic, remain poorly understood. Here, intracranial local field potentials (LFPs) recorded in the cortex, hippocampus, striatum, and thalamus were used to characterize the neurophysiological correlates of the rat wake-sleep cycle. By way of a new method for the objective classification and quantitative investigation of all major brain states, we demonstrate that global brain state transitions occur simultaneously across multiple forebrain areas as specific spectral trajectories with characteristic path, duration, and coherence bandwidth. During state transitions, striking changes in neural synchronization are effected by the prominent narrow-band LFP oscillations that mark state boundaries. Our results demonstrate that distant forebrain areas tightly coordinate the processing of neural information during and between global brain states, indicating a very high degree of functional integration across the entire wake-sleep cycle. We propose that transient oscillatory synchronization of synaptic inputs, which underlie the rapid switching of global brain states, may facilitate the exchange of information within and across brain areas at the boundaries of very distinct neural processing regimens.

Animals↗
PubMed2004

Heterogeneous integration of bilateral whisker signals by neurons in primary somatosensory cortex of awake rats.

Bilateral single-unit recordings in primary somatosensory cortex (S1) of anesthetized rats have revealed substantial cross talk between cortical hemispheres, suggesting the possibility that behaviorally relevant bilateral integration could occur in S1. To determine the extent of bilateral neural responses in awake animals, we recorded S1 multi- and single-unit activity in head-immobilized rats while stimulating groups of 4 whiskers from the same column on both sides of the head. Results from these experiments confirm the widespread presence of single units responding to tactile stimuli on either side of the face in S1 of awake animals. Quantification of bilateral integration by multiunits revealed both facilitative and suppressive integration of bilateral inputs. Varying the interval between left and right whisker stimuli between 0 and 120 ms showed the temporal integration of bilateral stimuli to be dominated on average by suppression at intervals around 30 ms, in agreement with comparable recordings in anesthetized animals. Contrary to the anesthetized data, in the awake animals we observed a high level of heterogeneity of bilateral responses and a strong interaction between synchronous bilateral stimuli. The results challenge the traditional conception of highly segregated hemispheric processing channels in the rat S1 cortex, and support the hypothesis that callosal cross-projections between the two hemispheres mediate rats' known ability to integrate bilateral whisker signals.

Action Potentials↗