Aims Apathy is a neurocognitive syndrome of reduced goal-directed behaviour, which is an important cause of disability in neurodegenerative disorders. We aimed to test the hypothesis that apathy in two disorders would be associated with reduced activation in the dorsolateral prefrontal cortex and supplementary motor area during a novel fMRI paradigm specifically examining volitional behaviour.

Methods A new fMRI paradigm, designed to avoid confounding by working memory and to be easy for patients to perform, was first used in a group of 15 healthy volunteers. 21 patients with Progressive Supranuclear Palsy and 20 patients with Alzheimer's disease provided data for the clinical study. Patients were defined as apathetic or non-apathetic by a Clinical Global Impression of Apathy, based on the use of established rating scales. These sub-groups were well-matched for important demographic and clinical characteristics and all patients were able to perform the task successfully.

Results As expected, healthy volunteers showed increased activation in the DLPFC and SMA during self-initiated compared with cued actions. Using a conservative whole brain analysis, there were no significant differences in activation associated with self-initated action between apathetic and non-apathetic patients. However, using a hypothesis-driven region of interest approach we found significantly reduced activation among apathetic patients in the DLPFC (in both PSP and AD) and in the SMA (in PSP only).

Conclusions These findings support the notion that deficits in self-initiated behaviour are a key part of the cognitive basis of apathy symptoms and that altered function in the DLPFC and SMA may be important in the neurobiology of apathy across different neurological disorders.