Brain Mechanisms Underlying Motivation & Apathy in Health and Disease

Apathy is a condition associated with pathological lack of motivation for which there is currently no definitive treatment. It is a common, disabling symptom associated with many brain diseases. Typically, apathetic patients show a reduction in self-initiated actions but are nevertheless able to perform behaviours when requested to do so by others.

Recent developments have led to a new theoretical framework for understanding the condition which builds on animal and human models of motivated behaviour (Husain & Roiser, Nature Rev Neurosci 2018). This provides a common, trans-diagnostic context to understand apathy, across neurological diseases.

I’ll review the findings which have led to the formulation of core fronto-striatal circuitry which is crucial for motivated behavior. Investigations in different patient groups suggest a common, fundamental deficit in apathy may be blunting of sensitivity to rewards which leads to reduced self-initiated actions. Both dopamine and serotonin may be important modulators of motivated behavior, with dopamine enhancing reward sensitivity and improving movement initiation and vigour.