Human intracortical responses to varying electrical stimulation conditions are separable in low-dimensional subspaces

Electrical stimulation is a powerful tool for targeted neurorehabilitation, and recent work in adaptive stimulation where stimulation can be adjusted in real-time has shown promise in improving stimulation outcomes and reducing stimulation-induced side effects. Mapping the relationship between electrical stimulation input and neural activity response can help reveal their interactions and can give us tools to iterate and improve on our stimulation protocols. Here, we introduce methods for identifying low-dimensional subspaces of human intracortical responses to electrical stimulation in invasive electroencephalography. In epilepsy patients (n=4) undergoing clinical monitoring, we applied a stimulation protocol of varying amplitude and frequency in 5-second intervals to capture a range of responses to different stimulation conditions. We characterized these responses using time-frequency spectral power, applied baseline subtraction and outlier removal procedures, and performed principal component analysis across frequencies. We identified that intracortical responses to different stimulation conditions can be represented in a 3-dimensional subspace, accounting for more than 95% of the variance. Using support vector machine classification, we demonstrated separability of intracortical responses in different stimulation conditions across subjects, where this separability was contingent on applying baseline subtraction and outlier removal. Our results represent a first step towards building a predictive model of neural response from stimulation input, an important prerequisite for adaptive closed-loop stimulation for targeted neurorehabilitation. © 2022 IEEE.