Mishler, J. | bioRxiv Science

bioRxiv2022

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

Different sleep states have been shown to be vital for a variety of brain function, 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 changes between different behavioral states we collected multichannel LFP and spike data in primary motor cortex of unconstrained macaques for up to 24 hours using the Neurochip3. Each 8 second bin of time was classified into awake and moving (Move), awake and at rest (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 for deeper sleep 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. Sorted single units showed decreased firing rate with deeper sleep, though with higher "bursty" patterns during NREM compared to other states. Spike-LFP synchrony showed high delta synchrony during Move, and higher coupling with all other frequency bands with deeper sleep. These results altogether are consistent with previous findings showing reactivation of cortical circuitry during sleep, which may be moderated by delta band LFP.

neuroscience↗

bioRxiv2022

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 non-human primates to stimulation, we recorded single unit activity while delivering single-pulse stimulation via Utah arrays implanted in primary motor cortex of three macaque monkeys. Stimuli between 5-50 A delivered to single channels reliably evoked spikes in neurons recorded throughout the array with delays of up to 12 milliseconds. 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, although high frequency stimulation in particular 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 frequently positively or negatively correlated. Our results document the complex dynamics of cortical neural responses to electrical stimulation that need to be considered when utilizing ICMS for scientific and clinical applications. Significance statementIntracortical microstimulation (ICMS) is commonly used to probe the cortex, and previous studies have characterized the responses of single neurons to ICMS. However, these studies typically explored the averaged effects of ICMS throughout each experimental session, rather than by a trial-by-trial basis for each stimulation pulse. By shifting the approach, we explored the dependence of neural responses to ICMS on the spontaneous neural activity as well as the dynamics of responses over time due to repetitive stimulation. Our results highlight how the responses of neurons to ICMS are likely the result of interactions between local excitatory and inhibitory cortical circuits. These results will help inform the design of ICMS for both basic research and clinically relevant stimulation protocols.

neuroscience↗