Abstract
The past few decades have seen growing interest in the
neuropsychiatric syndrome of apathy, conceptualised as a loss of motivation
manifesting as a reduction of goal-directed behaviour. Apathy occurs
frequently, and with substantial impact on quality of life, in a broad range of
neurological and psychiatric conditions. Apathy is also consistently associated
with neuroimaging changes in specific medial frontal cortex and subcortical
structures, suggesting that disruption of a common systems-level mechanism may
underlie its development, irrespective of the condition that causes it. In
parallel with this growing recognition of the clinical importance of apathy,
significant advances have been made in understanding normal motivated behaviour
in humans and animals. These developments have occurred at several different
conceptual levels, from work linking neural structures and neuromodulatory
systems to specific aspects of motivated behaviour, to higher order
computational models that aim to unite these findings within frameworks for
normal goal-directed behaviour. In this review we develop a conceptual
framework for understanding pathological apathy based on this current
understanding of normal motivated behaviour. We first introduce prominent
theories of motivated behaviour—which often involves sequences of actions
towards a goal that needs to be maintained across time. Next, we outline the
behavioural effects of disrupting these processes in animal models,
highlighting the specific effects of these manipulations on different
components of motivated behaviour. Finally, we relate these findings to
clinical apathy, demonstrating the homologies between this basic neuroscience
work and emerging behavioural and physiological evidence from patient studies
of this syndrome.
