Neurosurgery for treatment-resistant depression: valuation and decision making

Area of Science:

• Neuroscience
• Psychiatry
• Computational Psychiatry

Background:

• Severe and enduring psychiatric illness, including treatment-resistant depression (TRD), causes significant disability.
• Ablative neurosurgery (anterior cingulotomy and anterior capsulotomy) offers sustained response in select TRD patients, but mechanisms remain unclear.

Purpose of the Study:

• To investigate behavioral and neural differences in patients with TRD who have undergone neurosurgery compared to those who have not and healthy controls.
• To explore the underlying neurobiological mechanisms of treatment response in TRD.

Main Methods:

• Sixty-two participants (neurosurgical TRD, non-surgical TRD, healthy controls) completed a probabilistic reward-loss learning task during fMRI.
• Behavioral data were modeled using hierarchical Bayesian reinforcement learning drift-diffusion models.
• Neural activity was analyzed in relation to reward and loss processing.

Main Results:

• TRD patients exhibited impaired value discrimination and blunted reward prediction-error signals.
• Neurosurgical treatment was associated with altered value-related processing, distinct from response slowing.
• Clinical responders showed normalized evidence accumulation and value representation, unlike non-responders.

Conclusions:

• Clinical improvement after neurosurgery for TRD is linked to normalized valuation neurophysiology, not altered response dynamics.
• Valuation processes are central to severe TRD and represent a promising therapeutic target.