Neural signatures and personalized neuromodulation in a subject experiencing context-dependent inhibitory control deficits

Abstract

The ability to override prepotent actions is critical to control impulses and adjust behavior depending on goals and contextual needs. In this study, we investigate the inhibitory control abilities of a patient diagnosed with Klüver-Bucy Syndrome following a left temporal resection. The patient presented with disruptive hypersexuality symptoms akin to compulsions, leading to the inability to control and suppress inappropriate actions. The patient was recruited for the current research study while undergoing intracranial monitoring for epilepsy, to investigate the cognitive and neural processes underlying the patient’s inhibitory control symptoms. We formulated the hypothesis that a reactive inhibitory control deficit emerges in response to provocative triggers, and we designed a personalized paradigm pairing arousing images with a classic inhibitory control task. We not only confirmed disrupted performance following exposure to triggering, provocative material, but we also leveraged the simultaneously recorded neural data to identify a biomarker reflecting inhibitory control failures. Next, we repeated the experimental paradigm during and after personalized neuromodulation via direct high-frequency stimulation of the right inferior frontal cortex. The patient displayed a marked improvement in his behavior during neuromodulation, mirrored by changes in neural activity, spanning spectral features, event-related potentials and functional connectivity. Altogether, our study revealed that the patient’s symptoms were not due to a global inhibition deficit, but to a specific control issue triggered by exposure to provocative material. Overall, our work showcases a feasible, effective approach towards data-driven personalized neuromodulation, which could be leveraged to mitigate specific inhibitory control deficits and potentially other symptoms of executive dysfunction.