Active Brain & Nervous System Mental Health

Understanding the neural mechanisms of anhedonia in epilepsy and its response to epilepsy surgery and neural stimulation

In plain English

AI plain-English summary

Up to half of people with drug-resistant epilepsy also suffer from depression, and their suicide risk is five times higher than average—yet the brain mechanisms linking seizures to the loss of pleasure, known as anhedonia, remain poorly understood. This project aims to map those mechanisms directly. The researcher will recruit epilepsy patients with anhedonia who are scheduled for surgery, track their reward behaviour using an online platform, and record whole-brain activity with magnetoencephalography during reward tasks. During surgery, intracranial electrodes will capture direct neural signals from the same tasks, creating a rare multimodal dataset. Advanced computational models will then analyse why anhedonia sometimes persists after surgery. The researcher will also test whether stimulating the amygdala–orbitofrontal circuit can restore reward learning. If successful, this work could transform treatment for a neglected symptom that affects quality of life and suicide risk in epilepsy—and may also illuminate reward-circuit dysfunction in other brain disorders. This is fundamental science with clear clinical potential.

View original technical description
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.

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Researchers

Umesh Vivekananda (EPMC Awardee)

Related Research

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Characterising the neurocomputational basis of motivated behaviour in anhedonic depression

Original classification

Career Development Award

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