DCCN Colloquium by Sanjay Manohar

Motivation enables us to overcome effort and pursue goals according to internal needs. Conversely, clinical apathy represents a disabling deficit in motivation across various neurological conditions. Although traditionally viewed as opposite constructs, apathy and impulsivity surprisingly co-occur and positively correlate. To resolve this paradox, we decomposed motivation into distinct dimensions—including effort sensitivity, reward processing, arousal, and goal selection. Evaluating clinical profiles across Parkinson’s disease, cerebrovascular disease, and focal frontal lesion cohorts reveals distinct patterns of motivational impairment. Furthermore, neuropharmacological investigations demonstrate that these specific dimensions are differentially modulated by dopamine and acetylcholine across healthy and clinical populations. Together, these findings establish a multidimensional framework showing how distinct neurotransmitter systems and frontostriatal circuits govern the computations underlying motivation in health and disease.