Risk and aversion coding in human habenula high gamma activity.

Neurons in the primate lateral habenula fire in response to punishments and are inhibited by rewards. Through its modulation of midbrain monoaminergic activity, the habenula is believed to play an important role in adaptive behavioural responses to punishment and underlie depressive symptoms and their alleviation with ketamine. However, its role in value-based decision-making in humans is poorly understood due to limitations with non-invasive imaging methods which measure metabolic, not neural, activity with poor temporal resolution. Here, we overcome these limitations to more closely bridge the gap between species by recording local field potentials directly from the habenula in 12 human patients receiving deep brain stimulation treatment for bipolar disorder (n = 4), chronic pain (n = 3), depression (n = 3) and schizophrenia (n = 2). This allowed us to record neural activity during value-based decision-making tasks involving monetary rewards and losses. High-frequency gamma (60-240 Hz) activity, a proxy for population-level spiking involved in cognitive computations, increased during the receipt of loss and decreased during receipt of reward. Furthermore, habenula high gamma also encoded risk during decision-making, being larger in amplitude for high compared to low risk. For both risk and aversion, differences between conditions peaked approximately between 400 and 750 ms after stimulus onset. The findings not only demonstrate homologies with the primate habenula but also extend its role to human decision-making, showing its temporal dynamics and suggesting revisions to current models. The findings suggest that habenula high gamma could be used to optimize real-time closed-loop deep brain stimulation treatment for mood disturbances and impulsivity in psychiatric disorders.