Altered nucleus accumbens functional connectivity precedes apathy in Parkinson's disease.

Work in animal and human neuroscience has identified neural regions forming a network involved in the production of motivated, goal-directed behaviour. In particular, the nucleus accumbens and anterior cingulate cortex are recognized as key network nodes underlying decisions of whether to exert effort for reward, to drive behaviour. Previous work has convincingly shown that this cognitive mechanism, known as effort-based decision making, is altered in people with Parkinson's disease with a syndrome of reduced goal-directed behaviour-apathy. Building on this work, we investigated whether the neural regions implementing effort-based decision-making were associated with apathy in Parkinson's disease, and more importantly, whether changes to these regions were evident prior to apathy development. We performed a large, multimodal neuroimaging analysis in a cohort of people with Parkinson's disease (n = 199) with and without apathy at baseline. All participants had ∼2-year follow-up apathy scores, enabling examination of brain structure and function specifically in those with normal motivation who converted to apathy by ∼2-year follow-up. In addition, of the people with normal motivation, a subset (n = 56) had follow-up neuroimaging data, allowing for examination of the 'rate of change' in key nodes over time in those who did, and did not, convert to apathy. Healthy control (n = 54) data were also included to aid interpretation of findings. Functional connectivity between the nucleus accumbens and dorsal anterior cingulate cortex was higher in people with normal motivation who later converted to apathy compared to those who did not, whereas no structural differences were evident between these groups. In contrast, grey matter volume in these regions was reduced in the group with existing apathy. Furthermore, of those with normal motivation who had undergone longitudinal neuroimaging, converters to apathy showed a higher rate of change in grey matter volume within the nucleus accumbens. Overall, we show that changes in functional connectivity between nucleus accumbens and anterior cingulate cortex precedes apathy in people with Parkinson's disease, with conversion to apathy associated with higher rate of grey matter volume loss in nucleus accumbens, despite no baseline differences. These findings significantly add to an accumulating body of transdiagnostic evidence that apathy arises from disruption to key nodes within a network in which normal goal-directed behaviour is instantiated, and raise the possibility of identifying those at risk for developing apathy before overt motivational deficits have arisen.

Disordered Decision Making: A Cognitive Framework for Apathy and Impulsivity in Huntington's Disease.

A caregiver's all-too-familiar narrative - "He doesn't think through what he does, but mostly he does nothing." Apathy and impulsivity, debilitating and poorly understood, commonly co-occur in Huntington's disease (HD). HD is a neurodegenerative disease with manifestations bridging clinical neurology and psychiatry. In addition to movement and cognitive symptoms, neurobehavioral disturbances, particularly apathy and impulsivity, are prevalent features of HD, occurring early in the disease course, often worsening with disease progression, and substantially reducing quality of life. Treatments remain limited, in part because of limited mechanistic understanding of these behavioral disturbances. However, emerging work within the field of decision-making neuroscience and beyond points to common neurobiological mechanisms underpinning these seemingly disparate problems. These insights bridge the gap between underlying disease pathology and clinical phenotype, offering new treatment strategies, novel behavioral and physiological biomarkers of HD, and deeper understanding of human behavior. In this review, we apply the neurobiological framework of cost-benefit decision making to the problems of apathy and impulsivity in HD. Through this decision-making lens, we develop a mechanistic model that elucidates the occurrence of these behavioral disturbances and points to potential treatment strategies and crucial research priorities. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Characterising spoken responses to an intelligent virtual agent by persons with mild cognitive impairment.

The diagnosis of Mild Cognitive Impairment (MCI) characterises patients at risk of dementia and may provide an opportunity for disease-modifying interventions. Identifying persons with MCI (PwMCI) from adults of a similar age without cognitive complaints is a significant challenge. The main aims of this study were to determine whether generic speech differences were evident between PwMCI and healthy controls (HC), whether such differences were identifiable in responses to recent or remote memory questions, and to determine which speech variables showed the clearest between-group differences. This study analysed recordings of 8 PwMCI (5 females, 3 males) and 14 HC of a similar age (8 females, 6 males). Participants were recorded interacting with an intelligent virtual agent: a computer-generated talking head on a computer screen which asks pre-recorded questions when prompted by the interviewee through pressing the next key on a computer keyboard. Responses to recent and remote memory questions were analysed. Mann-Whitney U tests were used to test for statistically significant differences between PwMCI and HC on each of 12 speech variables, relating to temporal characteristics, number of words produced and pitch. It was found that compared to HC, PwMCI produce speech for less time and in shorter chunks, they pause more often and for longer, take longer to begin speaking and produce fewer words in their answers. It was also found that the PwMCI and HC were more alike when responding to remote memory questions than when responding to recent memory questions. These findings show great promise and suggest that detailed speech analysis can make an important contribution to diagnostic and stratification systems in patients with memory complaints.