On the pathophysiology and treatment of akinetic mutism.

• AM represents the far end in the spectrum of disorders of diminished motivation. • AM is caused by damage to several components of the frontal-subcortical system. • Damage results in loss of dopaminergic input: an 'energizing factor' for motivation. • AM is the result of an imbalance between execution and inhibition of behavior. • Treatment depends on the affected brain structures and neurotransmitter systems. Akinetic mutism (AM) is a rare neurological disorder characterized by the presence of an intact level of consciousness and sensorimotor capacity, but with a simultaneous decrease in goal-directed behavior and emotions. Patients are in a wakeful state of profound apathy, seemingly indifferent to pain, thirst, or hunger. It represents the far end within the spectrum of disorders of diminished motivation. In recent years, more has become known about the functional roles of neurocircuits and neurotransmitters associated with human motivational behavior. More specific, there is an increasing body of behavioral evidence that links specific damage of functional frontal-subcortical organization to the occurrence of distinct neurological deficits. In this review, we combine evidence from lesion studies and neurophysiological evidence in animals, imaging studies in humans, and clinical investigations in patients with AM to form an integrative theory of its pathophysiology. Moreover, the specific pharmacological interventions that have been used to treat AM and their rationales are reviewed, providing a comprehensive overview for use in clinical practice. [ABSTRACT FROM AUTHOR]