Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making

Abstract

Patients with small vessel cerebrovascular disease frequently suffer from apathy, a debilitating neuropsychiatric syndrome, the underlying mechanisms of which remain to be established. Here we investigated the hypothesis that apathy is associated with disrupted decision making in effort-based decision making, and that these alterations are associated with abnormalities in the white matter network connecting brain regions that underpin such decisions. Eighty-two patients with MRI evidence of small vessel disease were assessed using a behavioural paradigm as well as diffusion weighted MRI. The decision-making task involved accepting or rejecting monetary rewards in return for performing different levels of physical effort (hand grip force). Choice data and reaction times were integrated into a drift diffusion model that framed decisions to accept or reject offers as stochastic processes approaching a decision boundary with a particular drift rate. Tract-based spatial statistics were used to assess the relationship between white matter tract integrity and apathy, while accounting for depression. Overall, patients with apathy accepted significantly fewer offers on this decision-making task. Notably, while apathetic patients were less responsive to low rewards, they were also significantly averse to investing in high effort. Significant reductions in white matter integrity were observed to be specifically related to apathy, but not to depression. These included pathways connecting brain regions previously implicated in effort-based decision making in healthy people. The drift rate to decision parameter was significantly associated with both apathy and altered white matter tracts, suggesting that both brain and behavioural changes in apathy are associated with this single parameter. On the other hand, depression was associated with an increase in the decision boundary, consistent with an increase in the amount of evidence required prior to making a decision. These findings demonstrate altered effort-based decision making for reward in apathy, and also highlight dissociable mechanisms underlying apathy and depression in small vessel disease. They provide clear potential brain and behavioural targets for future therapeutic interventions, as well as modelling parameters that can be used to measure the effects of treatment at the behavioural level.

Heightened effort discounting is a common feature of both apathy and fatigue

“…Here, we confirmed strong relationships between effort discounting, and responses on all three rating scales. This replicates previous studies that have reported a relationship between heightened effort discounting and apathy 28 , 29 , 72 – 74 . Less work has been done examining the relationship between effort discounting and fatigue, although this is an area of increasing interest 16 , 21 , 31 .…”

Mechanisms Underlying Motivational Dysfunction in Schizophrenia

“…Negative symptoms are associated with specific changes within a fronto-striatal network that is closely associated with EBDM (Moran et al, 2019;Shukla et al, 2019;Xu et al, 2019). This is particularly interesting as this network is also associated with clinical apathy in neurological diseases (Hollocks et al, 2015;Saleh et al, 2021). Exploring the neural and behavioural differences between negative symptoms across diseases is an exciting future area of research.…”

“…Further, clinical apathy as defined in this manner contains several symptom dimensions (e.g., behavioural, social, and emotional) which overlap with MAP symptoms (Marin et al, 1991;Kirkpatrick et al, 2006;Sockeel et al, 2006;Ang et al, 2017). Behaviourally, apathetic patients with cerebrovascular (Le Heron et al, 2018a;Saleh et al, 2021), and Parkinson's disease (Le Heron et al, 2018b) display reward processing deficits when performing an EBDM task. Specifically, they accept less monetary offers at low reward compared to their motivated counterparts (Le Heron et al, 2018a,b;Saleh et al, 2021).…”

“…Behaviourally, apathetic patients with cerebrovascular (Le Heron et al, 2018a;Saleh et al, 2021), and Parkinson's disease (Le Heron et al, 2018b) display reward processing deficits when performing an EBDM task. Specifically, they accept less monetary offers at low reward compared to their motivated counterparts (Le Heron et al, 2018a,b;Saleh et al, 2021). This is a slightly different behavioural pattern to that demonstrated in schizophrenia patients with negative symptoms, where less offers are accepted at the highest reward levels (Gold et al, 2013(Gold et al, , 2015.…”

“…Clinical apathy in neurological conditions like Parkinson's disease (Baggio et al, 2015) and cerebrovascular small vessel disease (Hollocks et al, 2015;Saleh et al, 2021) is also associated with structural and functional deficits within the medial forebrain regions and the basal ganglia, including the VS (Hollocks et al, 2015;Le Heron et al, 2018a;Saleh et al, 2021). This suggests that some negative symptoms, like apathy/motivation may have similar underlying neural origins, across different diseases (Husain and Roiser, 2018).…”