Local field potentials and single unit dynamics in motor cortex of unconstrained macaques during different behavioral states.

Different sleep stages have been shown to be vital for a variety of brain functions, including learning, memory, and skill consolidation. However, our understanding of neural dynamics during sleep and the role of prominent LFP frequency bands remain incomplete. To elucidate such dynamics and differences between behavioral states we collected multichannel LFP and spike data in primary motor cortex of unconstrained macaques for up to 24 h using a head-fixed brain-computer interface (Neurochip3). Each 8-s bin of time was classified into awake-moving (Move), awake-resting (Rest), REM sleep (REM), or non-REM sleep (NREM) by using dimensionality reduction and clustering on the average spectral density and the acceleration of the head. LFP power showed high delta during NREM, high theta during REM, and high beta when the animal was awake. Cross-frequency phase-amplitude coupling typically showed higher coupling during NREM between all pairs of frequency bands. Two notable exceptions were high delta-high gamma and theta-high gamma coupling during Move, and high theta-beta coupling during REM. Single units showed decreased firing rate during NREM, though with increased short ISIs compared to other states. Spike-LFP synchrony showed high delta synchrony during Move, and higher coupling with all other frequency bands during NREM. These results altogether reveal potential roles and functions of different LFP bands that have previously been unexplored.

Responses of Cortical Neurons to Intracortical Microstimulation in Awake Primates.

Intracortical microstimulation (ICMS) is commonly used in many experimental and clinical paradigms; however, its effects on the activation of neurons are still not completely understood. To document the responses of cortical neurons in awake nonhuman primates to stimulation, we recorded single-unit activity while delivering single-pulse stimulation via Utah arrays implanted in primary motor cortex (M1) of three macaque monkeys. Stimuli between 5 and 50 µA delivered to single channels reliably evoked spikes in neurons recorded throughout the array with delays of up to 12 ms. ICMS pulses also induced a period of inhibition lasting up to 150 ms that typically followed the initial excitatory response. Higher current amplitudes led to a greater probability of evoking a spike and extended the duration of inhibition. The likelihood of evoking a spike in a neuron was dependent on the spontaneous firing rate as well as the delay between its most recent spike time and stimulus onset. Tonic repetitive stimulation between 2 and 20 Hz often modulated both the probability of evoking spikes and the duration of inhibition; high-frequency stimulation was more likely to change both responses. On a trial-by-trial basis, whether a stimulus evoked a spike did not affect the subsequent inhibitory response; however, their changes over time were often positively or negatively correlated. Our results document the complex dynamics of cortical neural responses to electrical stimulation that need to be considered when using ICMS for scientific and clinical applications.

Neurochip3: An Autonomous Multichannel Bidirectional Brain-Computer Interface for Closed-Loop Activity-Dependent Stimulation.

Toward addressing many neuroprosthetic applications, the Neurochip3 (NC3) is a multichannel bidirectional brain-computer interface that operates autonomously and can support closed-loop activity-dependent stimulation. It consists of four circuit boards populated with off-the-shelf components and is sufficiently compact to be carried on the head of a non-human primate (NHP). NC3 has six main components: (1) an analog front-end with an Intan biophysical signal amplifier (16 differential or 32 single-ended channels) and a 3-axis accelerometer, (2) a digital control system comprised of a Cyclone V FPGA and Atmel SAM4 MCU, (3) a micro SD Card for 128 GB or more storage, (4) a 6-channel differential stimulator with ±60 V compliance, (5) a rechargeable battery pack supporting autonomous operation for up to 24 h and, (6) infrared transceiver and serial ports for communication. The NC3 and earlier versions have been successfully deployed in many closed-loop operations to induce synaptic plasticity and bridge lost biological connections, as well as deliver activity-dependent intracranial reinforcement. These paradigms to strengthen or replace impaired connections have many applications in neuroprosthetics and neurorehabilitation.

Cortical Stimulation Paired With Volitional Unimanual Movement Affects Interhemispheric Communication.

Cortical stimulation (CS) of the motor cortex can cause excitability changes in both hemispheres, showing potential to be a technique for clinical rehabilitation of motor function. However, previous studies that have investigated the effects of delivering CS during movement typically focus on a single hemisphere. On the other hand, studies exploring interhemispheric interactions typically deliver CS at rest. We sought to bridge these two approaches by documenting the consequences of delivering CS to a single motor cortex during different phases of contralateral and ipsilateral limb movement, and simultaneously assessing changes in interactions within and between the hemispheres via local field potential (LFP) recordings. Three macaques were trained in a unimanual reaction time (RT) task and implanted with epidural or intracortical electrodes over bilateral motor cortices. During a given session CS was delivered to one hemisphere with respect to movements of either the contralateral or ipsilateral limb. Stimulation delivered before contralateral limb movement onset shortened the contralateral limb RT. In contrast, stimulation delivered after the end of contralateral movement increased contralateral RT but decreased ipsilateral RT. Stimulation delivered before ipsilateral limb movement decreased ipsilateral RT. All other stimulus conditions as well as random stimulation and periodic stimulation did not have consistently significant effects on either limb. Simultaneous LFP recordings from one animal revealed correlations between changes in interhemispheric alpha band coherence and changes in RT, suggesting that alpha activity may be indicative of interhemispheric communication. These results show that changes caused by CS to the functional coupling within and between precentral cortices is contingent on the timing of CS relative to movement.

Embedding a Panoramic Representation of Infrared Light in the Adult Rat Somatosensory Cortex through a Sensory Neuroprosthesis.

Can the adult brain assimilate a novel, topographically organized, sensory modality into its perceptual repertoire? To test this, we implemented a microstimulation-based neuroprosthesis that rats used to discriminate among infrared (IR) light sources. This system continuously relayed information from four IR sensors that were distributed to provide a panoramic view of IR sources, into primary somatosensory cortex (S1). Rats learned to discriminate the location of IR sources in <4 d. Animals in which IR information was delivered in spatial register with whisker topography learned the task more quickly. Further, in animals that had learned to use the prosthesis, altering the topographic mapping from IR sensor to stimulating electrode had immediate deleterious effects on discrimination performance. Multielectrode recordings revealed that S1 neurons had multimodal (tactile/IR) receptive fields, with clear preferences for those stimuli most likely to be delivered during the task. Neuronal populations predicted, with high accuracy, which stimulation pattern was present in small (75 ms) time windows. Surprisingly, when identical microstimulation patterns were delivered during an unrelated task, cortical activity in S1 was strongly suppressed. Overall, these results show that the adult mammalian neocortex can readily absorb completely new information sources into its representational repertoire, and use this information in the production of adaptive behaviors.