Altered delay discounting in neurodegeneration: insight into the underlying mechanisms and perspectives for clinical applications.

Steeper delay discounting (i.e., the extent to which future rewards are perceived as less valuable than immediate ones) has been proposed as a transdiagnostic process across different health conditions, in particular psychiatric disorders. Impulsive decision-making is a hallmark of different neurodegenerative conditions but little is known about delay discounting in the domain of neurodegenerative conditions. We reviewed studies on delay discounting in patients with Parkinson's disease (PD) and in patients with dementia (Alzheimer's disease / AD or frontotemporal dementia / FTD). We proposed that delay discounting could be an early marker of the neurodegenerative process. We developed the idea that altered delay discounting is associated with overlapping but distinct neurocognitive mechanisms across neurodegenerative diseases: dopaminergic-related disorders of reward processing in PD, memory/projection deficits due to medial temporal atrophy in AD, modified reward processing due to orbitofrontal atrophy in FTD. Neurodegeneration could provide a framework to decipher the neuropsychological mechanisms of value-based decision-making. Further, delay discounting could become a marker of interest in clinical practice, in particular for differential diagnosis.

Disentangling Clinical Profiles of Apathy in Behavioral Variant Frontotemporal Dementia.

BACKGROUND: Apathy is highly frequent in behavioral variant frontotemporal dementia (bvFTD). It is presumed to involve different pathophysiological mechanisms and neuroanatomical regions. OBJECTIVE: We explored the hypothesis that subgroups showing distinct profiles of apathy and distinct patterns of atrophy within frontal lobes could be disentangled in bvFTD. METHODS: Using data-driven clustering applied to 20 bvFTD patients, we isolated subgroups according to their profiles on the three subscales of the Dimensional Apathy Scale (DAS). We explored their apathy profiles and atrophy patterns. Apathy profiles were characterized through both subjective measures of apathy by questionnaires and measures including objective behavioral metrics. Atrophy patterns were obtained by voxel-based morphometry, contrasting each bvFTD subgroup with healthy controls (N = 16). RESULTS: By clustering based on DAS dimensions, we disentangled three subgroups of bvFTD patients, with distinct apathy profiles and atrophy patterns. One subgroup, which presented the smallest pattern of atrophy (including orbitofrontal cortex) with a right asymmetry, was characterized by high self-reported emotional and initiation apathy and by a self-initiation deficit reversible by external guidance. In other subgroups showing more diffuse bilateral atrophies extending to lateral prefrontal cortex, apathy was not reversible by external guidance and more difficulty to focus on goal-management was observed, especially in the subgroup with the largest atrophy and highest levels of executive apathy. CONCLUSION: Distinct clinical profiles of apathy, corresponding to distinct anatomical subtypes of bvFTD, were identified. These findings have implications for clinicians in a perspective of precision medicine as they could contribute to personalize treatments of apathy.

Resting-state fMRI functional connectivity and mindfulness in clinical and non-clinical contexts: A review and synthesis.

This review synthesizes relations between mindfulness and resting-state fMRI functional connectivity of brain networks. Mindfulness is characterized by present-moment awareness and experiential acceptance, and relies on attention control, self-awareness, and emotion regulation. We integrate studies of functional connectivity and (1) trait mindfulness and (2) mindfulness meditation interventions. Mindfulness is related to functional connectivity in the default mode (DMN), frontoparietal (FPN), and salience (SN) networks. Specifically, mindfulness-mediated functional connectivity changes include (1) increased connectivity between posterior cingulate cortex (DMN) and dorsolateral prefrontal cortex (FPN), which may relate to attention control; (2) decreased connectivity between cuneus and SN, which may relate to self-awareness; (3) increased connectivity between rostral anterior cingulate cortex region and dorsomedial prefrontal cortex (DMN) and decreased connectivity between rostral anterior cingulate cortex region and amygdala region, both of which may relate to emotion regulation; and lastly, (4) increased connectivity between dorsal anterior cingulate cortex (SN) and anterior insula (SN) which may relate to pain relief. While further study of mindfulness is needed, neural signatures of mindfulness are emerging.

Improvement of Tardive Dyskinesia during Mindfulness Meditation.

BACKGROUND: We report the case of a patient presenting with orofacial tardive dyskinesia (TD), following administration of a first-generation antipsychotic (Loxapine). INTERVENTION: Four weeks of repeated sessions of mindfulness-based cognitive therapy (MBCT) and mindfulness-based stress reduction (MBSR) protocols were administered, with TD hetero-quantified before and during each session via the Abnormal Involuntary Movement Scale (AIMS). RESULTS: The dyskinesia ameliorated quantitatively and qualitatively (1) during each session, and (2) at resting conditions in the long term. During some sessions, after which patients' compliance was auto-evaluated as maximal, complete arrest of the TD was observed. Hypothesis and Conclusion: We suggest mindfulness meditation as a novel adjunctive therapeutic approach for tardive dyskinesia, and invite for further clinical and neurological investigations.

Frontotemporal dementia subtypes based on behavioral inhibition deficits.

INTRODUCTION: We aimed to investigate phenotypic heterogeneity in the behavioral variant of frontotemporal dementia (bvFTD) through assessment of inhibition deficits. METHODS: We assessed occurrences of 16 behavioral inhibition deficits from video recordings of 15 bvFTD patients (early stage) and 15 healthy controls (HC) in an ecological setting. We extracted dimensions of inhibition deficit and analyzed their correlations with cognitive and clinical measures. Using these dimensions, we isolated patient clusters whose atrophy patterns were explored. RESULTS: After identifying two patterns of inhibition deficit (compulsive automatic behaviors and socially unconventional behaviors), we isolated three behavioral clusters with distinct atrophy patterns. BvFTD-G0 (N = 3), an outlier group, showed severe behavioral disturbances and more severe ventromedial prefrontal cortex/orbitofrontal cortex atrophy. Compared to bvFTD-G1 (N = 6), bvFTD-G2 (N = 6) presented higher anxiety and depression along with less diffuse atrophy especially in midline regions. DISCUSSION: Identifying clinico-anatomical profiles through behavior observation could help to stratify bvFTD patients for adapted treatments.

Cognitive and behavioural inhibition deficits in neurodegenerative dementias.

Disinhibition, mainly caused by damage in frontotemporal brain regions, is one of the major causes of caregiver distress in neurodegenerative dementias. Behavioural inhibition deficits are usually described as a loss of social conduct and impulsivity, whereas cognitive inhibition deficits refer to impairments in the suppression of prepotent verbal responses and resistance to distractor interference. In this review, we aim to discuss inhibition deficits in neurodegenerative dementias through behavioural, cognitive, neuroanatomical and neurophysiological exploration. We also discuss impulsivity and compulsivity behaviours as related to disinhibition. We will therefore describe different tests available to assess both behavioural and cognitive disinhibition and summarise different manifestations of disinhibition across several neurodegenerative diseases (behavioural variant of frontotemporal dementia, Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, Huntington's disease). Finally, we will present the latest findings about structural, metabolic, functional, neurophysiological and also neuropathological correlates of inhibition impairments. We will briefly conclude by mentioning some of the latest pharmacological and non pharmacological treatment options available for disinhibition. Within this framework, we aim to highlight i) the current interests and limits of tests and questionnaires available to assess behavioural and cognitive inhibition in clinical practice and in clinical research; ii) the interpretation of impulsivity and compulsivity within the spectrum of inhibition deficits; and iii) the brain regions and networks involved in such behaviours.