Differential Effects of Open- and Closed-Loop Intracortical Microstimulation on Firing Patterns of Neurons in Distant Cortical Areas

Abstract

Intracortical microstimulation can be used successfully to modulate neuronal activity. Activity-dependent stimulation (ADS), in which action potentials recorded extracellularly from a single neuron are used to trigger stimulation at another cortical location (closed-loop), is an effective treatment for behavioral recovery after brain lesion, but the related neurophysiological changes are still not clear. Here, we investigated the ability of ADS and random stimulation (RS) to alter firing patterns of distant cortical locations. We recorded 591 neuronal units from 23 Long-Evan healthy anesthetized rats. Stimulation was delivered to either forelimb or barrel field somatosensory cortex, using either RS or ADS triggered from spikes recorded in the rostral forelimb area (RFA). Both RS and ADS stimulation protocols rapidly altered spike firing within RFA compared with no stimulation. We observed increase in firing rates and change of spike patterns. ADS was more effective than RS in increasing evoked spikes during the stimulation periods, by producing a reliable, progressive increase in stimulus-related activity over time and an increased coupling of the trigger channel with the network. These results are critical for understanding the efficacy of closed-loop electrical microstimulation protocols in altering activity patterns in interconnected brain networks, thus modulating cortical state and functional connectivity.

The impact of closed-loop intracortical stimulation on neural activity in brain-injured, anesthetized animals

“…For each recording phase of the two groups (i.e., CTR and ADS), we quantified a significant deviation from a null (zero centered) distribution of the differences in firing rates between two time-points for a given unit. Using a bootstrapping method (Slomowitz E 2015 , Averna, Pasquale et al 2020 ) two time-segments were divided into 1-min bins and then randomly shuffled 10′000 times into two groups. Subsequently, a null-distribution was produced by differences between the means of the two randomly shuffled groups.…”

“…Further, we observed a shift in the neural activity within RFA that was not present with random stimulation (Guggenmos ( 2013 )). To further characterize ADS, we have investigated its ability to rapidly alter firing characteristics in both anesthetized and ambulatory rats without brain injury (Averna, Pasquale et al 2020 , Averna, Hayley et al 2021 ). However, due to the nature of cortical injury and the subsequent global disruption in activity and communication, it was unknown what impact ADS would have on the ability to facilitate changes in activity within the trigger and target regions.…”

“…Neurophysiological activity of both the rostral forelimb area (RFA) and the somatosensory cortex (S1) was recorded by using micro-electrode arrays. ADS was utilized following the same procedures as previous studies (Averna, Pasquale et al 2020 , Averna, Hayley et al 2021 ), by pairing the occurrence of the single-unit activity on a selected channel within RFA with ICMS applied to S1 after CFA ischemic injury.…”

Activity dependent stimulation increases synaptic efficacy in spared pathways in an anesthetized rat model of spinal cord contusion injury

“…Bonferroni correction for multiple comparisons was used to control for multiple comparisons. ICMS-evoked spiking activity analyses followed the rationale of a comparable study ( Averna et al., 2020 ). The current study was designed to assess the effect and interactions of various ADS parameters in separate dorsoventral sectors over time on neuronal activity.…”

SANTIA: a Matlab-based open-source toolbox for artifact detection and removal from extracellular neuronal signals

“…The toolbox was tested using LFP recorded from rats as previously described in [37,76]. The LFP were downsampled to 1017.3 Hz and low-pass filtered (with a 0-500 Hz cut-off frequency).…”