Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) antidromically activates the motor cortex (M1), and this cortical activation appears to play a role in the treatment of hypokinetic motor behaviors (Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K. Science 324: 354-359, 2009; Yu C, Cassar IR, Sambangi J, Grill WM. J Neurosci 40: 4323-4334, 2020). The synchronous antidromic activation takes the form of a short-latency cortical evoked potential (cEP) in electrocorticography (ECoG) recordings of M1. We assessed the utility of the cEP as a biomarker for STN DBS in unilateral 6-hydroxydopamine-lesioned female Sprague Dawley rats, with stimulating electrodes implanted in the STN and the ECoG recorded above M1. We quantified the correlations of the cEP magnitude and latency with changes in motor behavior from DBS and compared them to the correlation between motor behaviors and several commonly used spectral-based biomarkers. The cEP features correlated strongly with motor behaviors and were highly consistent across animals, whereas the spectral biomarkers correlated weakly with motor behaviors and were highly variable across animals. The cEP may thus be a useful biomarker for assessing the therapeutic efficacy of DBS parameters, as its features strongly correlate with motor behavior, it is consistent across time and subjects, it can be recorded under anesthesia, and it is simple to quantify with a large signal-to-noise ratio, enabling rapid, real-time evaluation. Additionally, our work provides further evidence that antidromic cortical activation mediates changes in motor behavior from STN DBS and that the dependence of DBS efficacy on stimulation frequency may be related to antidromic spike failure.NEW & NOTEWORTHY We characterize a new potential biomarker for deep brain stimulation (DBS), the cortical evoked potential (cEP), and demonstrate that it exhibits a robust correlation with motor behaviors as a function of stimulation frequency. The cEP may thus be a useful clinical biomarker for changes in motor behavior. This work also provides insight into the cortical mechanisms of DBS, suggesting that motor behaviors are strongly affected by the rate of antidromic spike failure during DBS.