Network neuroscience of apathy in cerebrovascular disease

Abstract

Apathy is a reduction in motivated goal-directed behavior (GDB) that is prevalent in cerebrovascular disease, providing an important opportunity to study the mechanistic underpinnings of motivation in humans. Focal lesions, such as those seen in stroke, have been crucial in developing models of brain regions underlying motivated behavior, while studies of cerebral small vessel disease (SVD) have helped define the connections between brain regions supporting such behavior. However, current lesion-based models cannot fully explain the neurobiology of apathy in stroke and SVD. To address this, we propose a network-based model which conceptualizes apathy as the result of damage to GDB-related networks. A review of the current evidence suggests that cerebrovascular disease-related pathology can lead to network changes outside of initially damaged territories, which may propagate to regions that share structural or functional connections. The presentation and longitudinal trajectory of apathy in stroke and SVD may be the result of these network changes. Distinct subnetworks might support cognitive components of GDB, the disruption of which results in specific symptoms of apathy. This network-based model of apathy may open new approaches for investigating its underlying neurobiology, and presents novel opportunities for its diagnosis and treatment. Recent research on the fundamental neuroanatomical and neurocognitive mechanisms underlying apathy has broadened our understanding of apathy in cerebrovascular disease and across neurological disorders. Despite this, theoretical work has primarily focused on linking neurodegenerative pathology to apathy, such as in Alzheimer's disease or Parkinson's disease (e.g., Lanctôt et al., 2017; Pagonabarraga et al., 2015). This has left the mechanisms underlying apathy in cerebrovascular disease comparably under-explored. Given the high prevalence of comorbid vascular pathology in neurodegenerative

Apathy, but not depression, predicts all-cause dementia in cerebral small vessel disease

“…Indeed, recent theoretical work proposed that certain symptoms of apathy are synonymous with defined cognitive deficits. 33 If this is the case, then apathy may manifest early as a reduction in attention towards reward stimuli, then later, as an inability to learn or remember rewarding behaviours.…”

“…Indeed, recent theoretical work proposed that certain symptoms of apathy are synonymous with defined cognitive deficits. 33 If this is the case, then apathy may manifest early as a reduction in attention towards reward stimuli, then later, as an inability to learn or remember rewarding behaviours. This would be consistent with initial executive deficits that are followed by declining episodic memory, which may be a cognitive phenotype of SVD patients that develop vascular or mixed dementia.…”

Cognitive Reserve, Leisure Activity, and Neuropsychological Profile in the Early Stage of Cognitive Decline

“…Apathy and a low positive affect are known to be the main behavioral and psychological symptoms of dementia commonly observed in various types of dementia (Gilley et al, 1991;Harrison et al, 2016;Breitve et al, 2018). Lower mood, motivation, activity, and affect can be manifested as the prodromal or initial symptoms in the dementia continuum (van Dalen et al, 2018;Tay et al, 2020). Apathy is also known to persist during the course of the disease (van der Linde et al, 2016) and is highly associated with impaired cognitive function (Reichman et al, 1996;Brown and Pluck, 2000;Breitve et al, 2018).…”

Early apathetic, but not depressive, symptoms are associated with poor outcome after stroke

“…Despite substantial overlap in clinical presentation between poststroke depressive and apathetic symptoms, there is evidence that these two syndromes have different neuroanatomical and neurobiological backgrounds [29,30]. Radiological studies have shown dissociable brain networks related to apathetic and depressive symptoms.…”