LFP Analysis of Brain Injured Anesthetized Animals Undergoing Closed-Loop Intracortical Stimulation

Abstract

Activity dependent stimulation (ADS) is a closed loop stimulation technique whose neurophysiological effects have not been deeply investigated. Here we explored how Local field Potentials (LFP) are impacted by a focal ischemic lesion and, subsequently, by ADS treatment. Intracortical microelectrode arrays were implanted in the rostral forelimb area (RFA) and in the primary somatosensory area (S1) of anaesthetized rats. An ischemic injury was induced in the caudal forelimb area through microinjections of Endothelin-1. The lesion induced an acute depressive trend in LFP power in RFA (evaluated in 6 bands of interest: Delta (1–4Hz), Theta (4–8Hz), Alpha (8–11Hz), Beta (11–30Hz), LowGamma (30–55Hz) and HighGamma (55–80)) followed by a noticeable significant rebound in both areas. Applying ADS induced an overall decrease of power. The lesion impacted the connectivity in a frequency specific manner, resulting in widespread increase in connectivity in Delta both between and within areas. Two hours after the lesion, without stimulation, correlated activity between areas increased in Beta and Gamma. After stimulation, inter-area connectivity increased in Delta, Theta and Alpha, while considerably dropping within RFA in highGamma. By computing phase-amplitude coupling, we found that the lesion produced an incremental increase in the coupling between (Theta) Alpha phase and (lowGamma) highGamma amplitude within RFA, while S1 had a more generalized increase. Likewise, coupling between Theta phase and lowGamma/highGamma amplitudes increased between areas after lesion. ADS induced a similar increase, but greater in magnitude both within and between RFA and S1. These results have important implications on the emerging field of closed-loop adaptive stimulation promoting ADS as an innovative tool for the treatment of neurological disorders.

Repetitive Transcranial Alternating Current Stimulation to Improve Working Memory: An EEG-fNIRS Study

“…Determining proper imaging features is essential to a closedloop stimulation system, which requires high accessibility to the actual brain state [70]. Functional brain imaging can establish the correlation between the brain state and behavioral performance by investigating the direct/indirect neuronal activity of the circumscribed brain region and brain network [71].…”

Personalized strategies of neurostimulation: from static biomarkers to dynamic closed-loop assessment of neural function

“…To better understand the mechanistic properties of ADS for modulating activity, other studies investigated its effect on neuronal firing patterns in rats with focal ischemic lesion in the motor cortex (i.e., M1 or CFA). Their findings suggest that ADS can rapidly alter intrinsic neural activity after an injury, which could be effective for modulating activity in the acute periods after injury ( Averna et al, 2022 ; Carè et al, 2022 ). Additional evidence supporting the use of ADS as a viable therapeutic method also after a spinal cord injury (i.e., SCI) were shown in Borrell et al (2020) , after demonstration that it could enhance synaptic efficacy in remaining pathways between the motor cortex and spinal cord.…”