John K. Chapin

Real-time prediction of hand trajectory by ensembles of cortical neurons in primates.

Signals derived from the rat motor cortex can be used for controlling one-dimensional movements of a robot arm. It remains unknown, however, whether real-time processing of cortical signals can be employed to reproduce, in a robotic device, the kind of complex arm movements used by primates to reach objects in space. Here we recorded the simultaneous activity of large populations of neurons, distributed in the premotor, primary motor and posterior parietal cortical areas, as non-human primates performed two distinct motor tasks. Accurate real-time predictions of one- and three-dimensional arm movement trajectories were obtained by applying both linear and nonlinear algorithms to cortical neuronal ensemble activity recorded from each animal. In addition, cortically derived signals were successfully used for real-time control of robotic devices, both locally and through the Internet. These results suggest that long-term control of complex prosthetic robot arm movements can be achieved by simple real-time transformations of neuronal population signals derived from multiple cortical areas in primates.

Progesterone alters GABA and glutamate responsiveness: a possible mechanism for its anxiolytic action.

In this study, the neuromodulatory effects of progesterone were tested in an intact neuronal circuit of a model extrahypothalamic CNS area. Spontaneous discharge and responses of single cerebellar Purkinje neurons to microiontophoretically applied gamma-aminobutyric acid (GABA) and glutamate were monitored before, during and after either systemic injection, at physiologic doses, or local application of the steroid. By both means of administration, progesterone significantly enhanced inhibitory responses of Purkinje cells to GABA and suppressed glutamate excitation within 3-10 min post-steroid. These results are consistent with the anxiolytic actions of the steroid.

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.

Ceramic-based multisite electrode arrays for chronic single-neuron recording

A method is described for the manufacture of a microelectrode array for chronic, multichannel, single neuron recording. The ceramic-based, multisite electrode array has four recording sites patterned onto a ceramic shaft the size of a single typical microwire electrode. The sites and connecting wires are applied to the ceramic substrate using a reverse photolithographic procedure. Recording sites (22/spl times/80 /spl mu/m) are separated by 200 /spl mu/m along the shaft. A layer of alumina insulation is applied over the whole array (exclusive of recording sites) by ion-beam assisted deposition. These arrays were capable of recording single neuron activity from each of their recording sites for at least three weeks during chronic implantation in the somatosensory cortex of rats, and several sites had recordings that lasted for more than 8 weeks. The vertical arrangement of the recording sites on these electrodes is ideal for simultaneously recording across the different layers of brain areas such as the cerebral cortex and hippocampus in chronic preparations.

Somatotopic maps within the zona incerta relay parallel GABAergic somatosensory pathways to the neocortex, superior colliculus, and brainstem

Neurons located in the zona incerta (ZI) of the ventral thalamus project to several regions of the central nervous system, including the neocortex, superior colliculus, and brainstem. However, whether these projections are functionally segregated remains unknown. This issue was addressed here by combining neuroanatomical tracers with immunohistochemical staining for gamma-aminobutyric acid (GABA) and/or parvalbumin, coupled with neurophysiological mapping. GABAergic projection neurons were found in four distinct subregions of the ZI including: (1) the rostral pole of the ZI, from which neurons project to the supragranular layers of the neocortex (especially layer I); (2) the dorsal subregion of the ZI, where both ascending projections to the neocortex and descending projections to the pretectal area were observed; (3) the ventral subregion of the ZI, whose neurons project to the superior colliculus; and 3) the caudal pole of the ZI, from which descending projections to the lower brainstem and spinal cord were observed. Somatotopic representations of the contralateral cutaneous periphery were also identified in the dorsal and ventral subregions of ZI, both of which were found to receive dense direct afferent projections from the trigeminal complex, and dorsal column nuclei. These results suggest that the rat ZI is a major somatosensory relay in the ventral thalamus, carrying feed-forward inhibitory signals to neocortical and subcortical targets, in parallel with the excitatory somatosensory pathways.

Laminar differences in sizes, shapes, and response profiles of cutaneous receptive fields in the rat SI cortex

SummaryQuantitative techniques were used to demonstrate cortical layer differences in cutaneous receptive fields (RFs) in the rat SI cortex. Two- and three-dimensional (2-D and 3-D) RF maps were constructed showing the responsiveness of single neurons to standardized punctate stimulation of each of a matrix of points on the skin or the mystacial vibrissa pad. These allowed a visualization not only of the overall sizes of such RFs, but also their shape and “response profile”. Initial experiments showed that the sizes and response profiles of such RFs were similar whether they were mapped by sinusoidal mechanical vibration of skin, punctate touch, or direct intracutaneous electrical stimulation. This method was used to quantitatively determine distoproximal lengths of RFs of single units recorded at different depths in the forepaw area of the SI cortex. Plots of these RF lengths as a function of cortical depth showed that the smallest RFs were found in the granular layers (IV and deep III). RFs up to double that size were found in supragranular layers, and up to triple that size in infragranular layers. 3-D maps of RFs in the granular layers showed sharp central response peaks surrounded by very steep dropoffs to the RF boundaries. In the whisker areas, granular layer RFs were typically circular in shape and contained from 1–4 whiskers. By contrast, in supragranular layers they were often elongated in shape, and were oriented along rows or columns of whiskers. RFs in layer V resembled large, high plateaus, often supporting clearly separated peaks. RFs mapped in the fore- and hindpaw areas were similar, but, even in the granular layers, were often slightly elongated along the limb axis. In all regions of the SI, both the locations and shapes of the granular layer RFs appeared to be conserved as subsets of other more topographically heterogeneous RFs encountered elsewhere in the column. These findings may correlate with patterns of axonal connectivity in the rat SI.

Neural Prostheses for Restoration of Sensory and Motor Function

Sensory and Motor Prostheses Auditory Prostheses, B.E. Pfingst Advances in Upper Extremity Functional Restoration Employing Neuroprostheses, P.H. Peckham, K.L. Kilgore, and M.W. Keith BION(TM) Implants for Therapeutic and Functional Electrical Stimulation, G.E. Loeb and J.R. Richmond Intraspinal Chord Microstimulation: Techniques, Perspectives, and Prospects for FES, S.F. Giszter, W. Grill, M. Lemay, V. Mushahwar, and A. Prochazka How to Use Nerve Cuffs to Stimulate, Record, or Modulate Neural Activity, J.-A. Hoffer and K. Klaus Brain Control of Neural Prostheses Engineering the Brain-Machine Interface for Neural Prosthetic Devices, K.A. Moxon, J. Morizio, J.K. Chapin, M.A.L. Nicolelis, and P.D. Wolf. Dynamic Interplay of Neural Signals During the Emergence of Cursor-Related Cortex in a Human Implanted with the Neurotrophic Electrode, P.R. Kennedy and B. King Brain Control of Sensorimotor Prosthesis, J.K. Chapin and M.A.L. Nicolelis Drug Deliveries into the Microenvironment of Electrophysiologically Monitored Neurons in the brain of Behaving Rats and Monkeys, N. Ludvig

Somatic sensory transmission to the cortex during movement: Phasic modulation over the locomotor step cycle

Abstract We determined whether or not information transmitted through sensory pathways to the primary somatosensory (SI) cortex is selectively gated over the step cycle in locomotion. Moment-to-moment changes in the potential for sensory transmission through the afferent pathways to these cells were tested by delivering test stimuli through electrodes chronically implanted in the skin of the palm during different phases of the step cycle. The averaged intensities of these neural responses were calculated and plotted sequentially in a “perifootfall sensory gating histogram.” The results showed that the sensory responsiveness of all cells studied was strongly diminished when averaged for the whole step cycle, but most cells also exhibited short, phasic periods of facilitation (or “disinhibition”) of afferent input. We found that the group of neurons (described in the previous paper) that responded strongly when the forepaw touched the ground at footfall did so because they were phasically facilitated just before the footfall event, but were suppressed during all other phases. Conversely, the sensory inputs to the group of cells which did not respond to footfall were either tonically suppressed throughout the whole step cycle or were facilitated during the early swing phase. For this reason, these latter cells responded to touch of the area of their forepaw receptive fields with a hand-held probe during the swing phase of locomotion but did not respond to footfall. These results suggest that the afferent sensory pathways arising to the rat SI cortex may be subject to a gating process which is temporally specific.

Controlling Robots with the Mind.

Belle, our tiny owl monkey, was seated in her special chair inside a soundproof chamber at our Duke University laboratory. Her right hand grasped a joystick as she watched a horizontal series of lights on a display panel. She knew that if a light suddenly shone and she moved the joystick left or right to correspond to its position, a dispenser would send a drop of fruit juice into her mouth. She loved to play this game. And she was good at it.

DEVELOPMENT OF DIRECT GABAERGIC PROJECTIONS FROM THE ZONA INCERTA TO THE SOMATOSENSORY CORTEX OF THE RAT

The postnatal development of direct thalamocortical projections from the zona incerta of the ventral thalamus to the whisker representation area of the rat primary somatosensory cortex was investigated. Cytoarchitectonic analysis based on Nissl staining, cytochrome oxidase histochemistry and immunohistochemistry for glutamic acid decarboxylase, GABA, parvalbumin and calbindin D28K revealed that the zona incerta can be clearly distinguished from surrounding diencephalic structures from the day of birth. Moreover, four distinct anatomical subdivisions of this nucleus were identified: the rostral, dorsal, ventral and caudal. Of these, the ventral subdivision is by far the most conspicuous, containing the highest density of neurons, and the highest levels of cytochrome oxidase, glutamate decarboxylase, GABA, parvalbumin and calbindin D28K. In contrast, the dorsal, rostral and caudal subdivisions contain fewer cells, lower levels of glutamic acid decarboxylase and GABA and very few parvalbumin-positive and calbindin-positive neurons. Small injections of rhodamine coated microspheres or Fluoro-gold in the primary somatosensory cortex of animals at different stages of development revealed the existence of retrogradely labeled neurons in the rostral and dorsal subdivisions of the zona incerta from postnatal day 1. At this age, retrogradely labeled cells were also found in the ventral lateral, ventral posterior medial, posterior medial, centrolateral, ventral medial and magnocellular subdivision of the medial geniculate nuclei of the dorsal thalamus. The density of the incertocortical projection reaches its maximum between the first and second postnatal weeks, decreasing subsequently, until an adult pattern of labeling is achieved. Tracer injections combined with immunohistochemistry revealed that the majority of the incertocortical projection derives from GABAergic neurons, implying a potentially inhibitory role for the incertocortical projection. These results demonstrate that the rat trigeminal system contains parallel thalamocortical pathways of opposite polarity, emerging from both the dorsal (glutamatergic, excitatory) and ventral (GABAergic, inhibitory) thalamus since the day of birth. As such, these findings suggest that, contrary to the classical notion, not only the dorsal but also the ventral thalamus may play a special role in both cortical maturation and function.