Understanding the neural mechanisms of anhedonia in epilepsy and its response to epilepsy surgery and neural stimulation (360G-Wellcome-307306_Z_23_Z)

Up to half of patients with medication refractory epilepsy suffer from depression, with a 5 fold increase in suicide risk compared to the general population. Anhedonia, the inability to feel pleasure or learn about reward, is a major component of epilepsy associated depression. The link between epilepsy and anhedonia is unsurprising given the shared disruption to key brain networks thought to underlie emotion, reward processing and seizure generation. However mechanistically anhedonia remains poorly understood, resulting in unfocussed treatments. This is a unique opportunity to advance our mechanistic understanding of the brain circuitry underlying anhedonia, using state-of-the-art multilevel neural recording. I will recruit patients with medication refractory epilepsy and comorbid anhedonia who are undergoing epilepsy surgery. Prior to surgery, I will track anhedonia state and reward behaviour in patients using an online platform. They will have magnetoencephalography to perform whole brain activity analysis during validated reward processing tasks. Patients will then undergo intracranial electroencephalography, which will provide unprecedented insights into direct brain activity during the same tasks. This multimodal dataset will drive advanced computational modelling to understand presence of persistent anhedonia following surgical intervention. I will also trial cortical stimulation of the amygdala-orbitofrontal circuit to potentially remediate reward learning.