A nonlinear relationship of evoked responses following charge-balanced single-pulse electrical stimulation with varying pulse widths

BACKGROUND: Single-pulse electrical stimulation (SPES) can help guide neuromodulation therapy in an iterative process to reveal ideal circuits and degrees of engagement. Understanding the relationship between parameter input and neural output will be necessary both to build informative models of the brain's functional connectivity and to improve responses to stimulation-based neuromodulation therapies. Modulating pulse width alters the total charge delivered to neural tissue and is thought to selectively activate fibers with different diameters, potentially shifting therapeutic thresholds. The anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) are of great clinical relevance to the pathophysiology and treatment of neuropsychiatric disorders. OBJECTIVE: To provide empirical evidence for the impact of pulse width on pulse-evoked responses and promote the ability to modify specific circuits. METHODS: We measured evoked response robustness, peak amplitude, and latency to peak amplitude from depth electrode contacts in 20 epilepsy patients undergoing intracranial monitoring for treatment-refractory epilepsy. RESULTS: A nonlinear relationship between pulse width with evoked potential robustness was determined. Pulse width modulation is further shown to be distance-dependent, with distant connections responding maximally to a shorter pulse width. CONCLUSION: These results emphasize the importance of input stimulation parameters on cerebro-cerebral evoked potential (CCEP) response magnitude and consistency and are a step towards guiding selective engagement of specific fiber populations for both research and clinical settings.