Profiles of motivational impairment and their relationship to functional decline in frontotemporal dementia.

Motivational disturbances are pervasive in frontotemporal dementia (FTD) and impact negatively on everyday functioning. Despite mounting evidence of anhedonia in FTD, it remains unclear how such changes fit within the broader motivational symptom profile of FTD, or how anhedonia relates to functional outcomes. Here we sought to comprehensively characterize motivational disturbances in FTD and their respective relationships with functional impairment. A cross-sectional study design was used including 211 participants-68 behavioral-variant FTD (bvFTD), 32 semantic dementia (SD), 43 Alzheimer's disease (AD), and 68 healthy older control participants. Anhedonia severity was measured using the Snaith-Hamilton Pleasure Scale while severity of apathy was assessed across Emotional, Executive, and Initiation dimensions using the Dimensional Apathy Scale. Functional impairment was established using the FTD Functional Rating Scale (FRS). Distinct motivational profiles emerged in each dementia syndrome: a domain-general motivational impairment in bvFTD; a predominantly anhedonic profile in SD; and more pronounced initiation and executive apathy in AD. Correlation analyses revealed differential associations between motivational symptoms and severity of functional impairment in each group. Executive apathy was associated with functional impairment in bvFTD, while anhedonia was strongly correlated with functional decline in SD. Finally, executive and emotional apathy were associated with functional decline in AD. Our study indicates distinct profiles of apathy and anhedonia in FTD syndromes, which in turn are differentially associated with functional decline. This detailed characterization of motivational phenotypes can inform patient stratification for targeted interventions to improve functional outcomes.

Establishing the link between motivational disturbances and behavioural rigidity in frontotemporal dementia.

BACKGROUND: Rigid and inflexible behaviours are common in frontotemporal dementia (FTD), manifesting in compulsive pursuit of specific interests, routines, and rituals. Paradoxically, these changes occur alongside profound motivational disturbances including apathy and anhedonia. While posited to be related, no study to date has explored the link between motivational changes and behavioural rigidity in FTD. METHODS: Carer ratings for 71 FTD participants (26 semantic dementia [SD], 45 behavioural variant [bvFTD]) were obtained on the Dimensional Apathy Scale (apathy), the Snaith-Hamilton Pleasure Scale (hedonic tone) and the Cambridge Behavioural Inventory-Revised (CBI-R; behavioural changes). A rigidity index was created from existing items on the CBI-R. Whole-brain voxel-based morphometry was used to explore associations between rigidity and grey matter intensity in the combined FTD group. RESULTS: Behavioural rigidity was significantly related to apathy severity (r = 0.57) and decreased hedonic tone (r = -0.36) in the combined FTD group. Multiple linear regression revealed a significant diagnosis × hedonic tone interaction (ß = -1.40), whereby lower hedonic tone predicted rigidity in SD (r = -0.65) but not in bvFTD (r = -0.18). In contrast, the relationship between rigidity and apathy did not differ between the groups (ß = -0.42). At the neural level, rigidity correlated with degeneration of predominantly right-sided frontostriatal structures including, notably, the nucleus accumbens. CONCLUSIONS: As the first study to demonstrate a link between motivational changes and behavioural rigidity in FTD, our findings have important clinical implications. By identifying candidate mechanisms of behavioural rigidity, our findings can inform targeted interventions to manage inflexible patterns of thought and behaviour in daily life.

The Role of Apathy in Spontaneous Verbal and Nonverbal Behaviors: A Transdiagnostic Pilot Study in Neurodegeneration.

BACKGROUND: Apathy, characterized by a quantifiable reduction in motivation or goal-directed behavior, is a multidimensional syndrome that has been observed across many neurodegenerative diseases. OBJECTIVE: To develop a novel task measuring spontaneous action initiation (ie, a nonverbal equivalent to spontaneous speech tasks) and to investigate the association between apathy and executive functions such as the voluntary initiation of speech and actions and energization (ie, ability to initiate and sustain a response). METHOD: We compared the energization and executive functioning performance of 10 individuals with neurodegenerative disease and clinically significant apathy with that of age-matched healthy controls (HC). We also investigated the association between self-reported scores on the Apathy Evaluation Scale (AES) and performance on energization tasks. RESULTS: The individuals with apathy made significantly fewer task-related actions than the HC on the novel spontaneous action task, and their scores on the AES were negatively correlated with spontaneous task-related actions, providing preliminary evidence for the task's construct validity. In addition, the individuals with apathy performed more poorly than the HC on all of the energization tasks, regardless of task type or stimulus modality, suggesting difficulty in sustaining voluntary responding over time. Most of the tasks also correlated negatively with the AES score. However, the individuals with apathy also performed more poorly on some of the executive function tasks, particularly those involving self-monitoring. CONCLUSION: Our work presents a novel experimental task for measuring spontaneous action initiation-a key symptom of apathy-and suggests a possible contribution of apathy to neuropsychological deficits such as poor energization.

Reconciling profiles of reward-seeking versus reward-restricted behaviours in frontotemporal dementia.

This scientific commentary refers to 'The architecture of abnormal reward behaviour in dementia: multimodal hedonic phenotypes and brain substrate', by Chokesuwattanaskul et al. (https://doi.org/10.1093/braincomms/fcad027).

Post-stroke apathy: A case series investigation of neuropsychological and lesion characteristics.

Apathy is a multi-dimensional syndrome associated with reduced initiation, executive function and emotion toward goal-directed behaviour. Affecting ∼30% of stroke patients, apathy can negatively impact rehabilitation outcomes and increase caregiver burden. However, relatively little is known about the multi-dimensional nature of post-stroke apathy and whether these dimensions map onto neuropsychological and neuroanatomical correlates. The present study aimed to address this question in a case series of stroke patients with apathy. 65 patients with acute stroke were assessed on a comprehensive battery of neuropsychological tasks and 12 patients were identified as having clinically significant apathy on one or more domains on the Dimensional Apathy Scale. Individual scores were compared to a group of healthy controls and normative data where available. Lesion mapping was completed from clinical CT and MRI scans to characterise the extent and locations of each patient's lesion. All participants performed significantly poorer than controls on one or more tasks. Difficulties with inhibition were observed across all dimensions. Prospective memory deficits were also common, while speed and social cognition were only reduced in initiation and emotional apathy, respectively. Verbal fluency was not impaired in any of the patients, despite previously established relationships with apathy. Lesions were predominantly located in right subcortical regions, with some additional frontal, temporal and cerebellar/brainstem involvement. There was substantial overlap in lesion locations within and between dimensions, such that similar apathy symptoms occurred in patients with very different lesion sites. Overall, our results suggest that neuropsychological and lesion profiles of apathy in stroke patients may be more complex and heterogenous than in neurodegenerative disease, possibly due to functional changes occurring beyond the lesion site.

Evidence against benefits from cognitive training and transcranial direct current stimulation in healthy older adults.

Cognitive training and brain stimulation show promise for ameliorating age-related neurocognitive decline. However, evidence for this is controversial. In a Registered Report, we investigated the effects of these interventions, where 133 older adults were allocated to four groups (left prefrontal cortex anodal transcranial direct current stimulation (tDCS) with decision-making training, and three control groups) and trained over 5 days. They completed a task/questionnaire battery pre- and post-training, and at 1- and 3-month follow-ups. COMT and BDNF Val/Met polymorphisms were also assessed. Contrary to work in younger adults, there was evidence against tDCS-induced training enhancement on the decision-making task. Moreover, there was evidence against transfer of training gains to untrained tasks or everyday function measures at any post-intervention time points. As indicated by exploratory work, individual differences may have influenced outcomes. But, overall, the current decision-making training and tDCS protocol appears unlikely to lead to benefits for older adults.

Structural and functional brain correlates of theory of mind impairment post-stroke.

The ability to understand the mental states of others - also known as Theory of Mind (ToM) - is critical for normal social interactions. We combine behavioural probes with structural and functional brain imaging to provide the first comprehensive analysis of ToM deficits following stroke using the Reading the Mind in the Eyes Test (RMET). First, fMRI was used to identify the functional brain network involved in a non-clinical cohort. Results indicated that, relative to a control task, the RMET increased activity in a widespread functional bilateral network comprising frontal and temporo-parietal areas. To investigate how damage to grey and white matter components of this network can lead to ToM impairment, parcel-based lesion-symptom mapping (PLSM), white-matter tract-wise statistical analysis (TSA) and disconnectome symptom mapping (DSM) were performed using structural images from 64 stroke patients. PLSM results revealed that low scores on the RMET were associated with damage centered around the right posterior frontal gyrus and insula. TSA and DSM results further revealed that low RMET scores were associated with damage to white-matter tracts connecting frontal and temporo-parietal components of the RMET functional network. Together, these findings suggest that making judgements about the mental states of others imposes demands on a large functional network that can easily be disrupted, both by damage to grey matter areas that form part of the network directly, or the white-matter pathways that connect them.

Do implicit and explicit belief processing share neural substrates?

Humans rely on their ability to infer another person's mental state to understand and predict others' behavior ("theory of mind," ToM). Multiple lines of research suggest that not only are humans able to consciously process another person's belief state, but also are able to do so implicitly. Here we explored how general implicit belief states are represented in the brain, compared to those substrates involved in explicit ToM processes. Previous work on this topic has yielded conflicting results, and thus, the extent to which the implicit and explicit ToM systems draw on common neural bases is unclear. Participants were presented with "Sally-Anne" type movies in which a protagonist was falsely led to believe a ball was in one location, only for a puppet to later move it to another location in their absence (false-belief condition). In other movies, the protagonist had their back turned the entire time the puppet moved the ball between the two locations, meaning that they had no opportunity to develop any pre-existing beliefs about the scenario (no-belief condition). Using a group of independently localized explicit ToM brain regions, we found greater activity for false-belief trials, relative to no-belief trials, in the right temporoparietal junction, right superior temporal sulcus, precuneus, and left middle prefrontal gyrus. These findings extend upon previous work on the neural bases of implicit ToM by showing substantial overlap between this system and the explicit ToM system, suggesting that both abilities might recruit a common set of mentalizing processes/functional brain regions. Hum Brain Mapp 38:4760-4772, 2017. © 2017 Wiley Periodicals, Inc.