Apathy: a neurocircuitry model based on frontotemporal dementia

Abstract

Apathy is a symptom shared among many neurological and psychiatric disorders. However, the underlying neurocircuitry remains incompletely understood. Apathy is one of the core features of behavioural variant frontotemporal dementia (bvFTD), a neurodegenerative disease presenting with heterogeneous combinations of socioaffective symptoms and executive dysfunction. We reviewed all neuroimaging studies of apathy in frontotemporal dementia (FTD) attempting to refine a neurocircuitry model and inform clinical definitions. Levels of apathy have been consistently shown to correlate with the severity of executive dysfunctions across a wide range of diseases, including FTD. Some authors view 'energisation'-the loss of which is central in apathy-as a core executive function. Apathy in FTD is most robustly associated with atrophy, hypometabolism and/or hypoperfusion in the dorsolateral prefrontal cortex, the anterior and middle cingulate cortex, the orbitofrontal cortex and the medial and ventromedial superior frontal gyri. Data also suggest that abnormalities in connecting white matter pathways and functionally connected more posterior cortical areas could contribute to apathy. There is a lack of consistency across studies due to small samples, lenient statistical thresholds, variable measurement scales and the focus on apathy as a unitary concept. Integrating findings across studies, we revise a neurocircuitry model of apathy divided along three subcomponents (cognition/planning, initiation, emotional-affective/motivation) with specific neuroanatomical and cognitive substrates. To increase consistency in clinical practice, a recommendation is made to modify the bvFTD diagnostic criteria of apathy/inertia. More generally, we argue that bvFTD constitutes a disease model to study the neurocircuitry of complex behaviours as a 'lesion-based' approach to neuropsychiatric symptoms observed across diagnostic categories.

Keywords: neuroimaging.

Figure 1

Neurocircuitry model of the three components of apathy and associated cognitive deficits. (A) Hypothesised main neuroanatomical areas related to three subcomponents of apathy and associated cognitive deficits. (B) Striatal connections of key cortical nodes based on monkey tract tracing. pSMA/SMA has main connections with the medial putamen, DLPFC and DMPFC to dorsal caudate and VMPFC to ventral caudate (nucleus accumbens). (C) Resting state fMRI intrinsic connectivity of key cortical nodes with the striatum in humans corroborating anatomical findings in monkeys. (D) Main resting state intrinsic connectivity networks associated with cortical nodes and related striatal connections. DLPFC, DMPFC and pSMA/SMA are mainly integrated as part of the frontoparietal control network. The VMPFC is integrated within the limbic network. (B–D) Adapted with permission from Choi et al. Organisation of the human striatum estimated by intrinsic functional connectivity. DLPFC, dorsolateral prefrontal cortex; pSMA/SMA, presupplementary motor area/supplementary motor area; DMPFC, dorsal medial prefrontal cortex; fMRI, functional MRI; pSMA, presupplementary motor area; VMPFC, ventromedial prefrontal cortex.