Effect of coordinated reset deep brain stimulation on aperiodic and high frequency periodic components in subthalamic and motor cortical local field potentials

Abstract

Coordinated Reset (CR) deep brain stimulation (DBS) is a promising alternative to conventional DBS for Parkinson’s disease (PD) that can provide sustained aftereffects for PD. CR DBS is hypothesized to desynchronize pathologically synchronized neuronal networks in the STN, but this mechanism needs to be validated further. Here, we expand on a previous experiment to examine of the impact of CR DBS on the aperiodic spectral parameters and high-frequency power in the local field potentials (LFPs) from the subthalamic nucleus (STN) of a nonhuman primate model of PD. Recordings were taken at four sites (two in the STN, one in the primary motor cortex, and one at the premotor cortex) across sessions using four different CR stimulation frequencies. We found that CR DBS produced significant increases in the aperiodic exponent at the STN, which also exhibited a negative correlation with the severity of motor signs as measured by the modified Unified Parkinson’s Disease Rating Scale (mUPDRS). Both the aperiodic offset and high-frequency power increased at both sites following stimulation, though no clear relationship with mUPDRS scores was found. No clear trend of change or relationship with mUDPRS scores was observed in cortical aperiodic parameters or high frequency power. Based on prior work suggesting that a correlation exists between the aperiodic exponent and the excitation-inhibition balance in a neural population, our findings suggest that CR DBS shifts the excitation-inhibition balance in the STN towards inhibition, resulting in lower sensitivity to excitatory inputs from the cortex. This study enhances our understanding of the underlying sustained therapeutic effects of CR DBS and advances the development of this novel DBS approach for the treatment of PD.