Probing frontostriatal reward circuits with rTMS

Anhedonia is a debilitating symptom in depression and while treatment with repetitive transcranial magnetic stimulation (rTMS) targeting frontostriatal circuits is effective many continue to suffer from anhedonia, prompting the need to understand its mechanisms.

In healthy, reward learning is thought to depend on frontostriatal brain circuits that are modulated by dopamine for optimal functioning. Reduced dopamine in these circuits has sometimes been found in depression and may be associated with anhedonia.

However, direct evidence that dopamine signaling drives frontostriatal activity to enable reward learning in humans, and that failure to do this contributes to anhedonia, is lacking.

Here, 40 healthy participants and 40 patients with anhedonia will be randomized to either active or sham rTMS during a session of concurrent [11C]raclopride positron emission tomography (PET) and magnetic resonance imaging (MRI) to assess the simultaneous effect of rTMS on striatal dopamine release and functional frontostriatal connectivity and its association with reward learning performance and anhedonia symptoms.

Understanding how reward processing is implemented in the brain and affected in anhedonia will be key to optimization and individualization of treatment in many psychiatric disorders where this symptom is pervasive.