Higher emotional granularity relates to greater inferior frontal cortex cortical thickness in healthy, older adults.

Individuals with high emotional granularity make fine-grained distinctions between their emotional experiences. To have greater emotional granularity, one must acquire rich conceptual knowledge of emotions and use this knowledge in a controlled and nuanced way. In the brain, the neural correlates of emotional granularity are not well understood. While the anterior temporal lobes, angular gyri, and connected systems represent conceptual knowledge of emotions, inhibitory networks with hubs in the inferior frontal cortex (i.e., posterior inferior frontal gyrus, lateral orbitofrontal cortex, and dorsal anterior insula) guide the selection of this knowledge during emotions. We investigated the structural neuroanatomical correlates of emotional granularity in 58 healthy, older adults (ages 62-84 years), who have had a lifetime to accrue and deploy their conceptual knowledge of emotions. Participants reported on their daily experience of 13 emotions for 8 weeks and underwent structural magnetic resonance imaging. We computed intraclass correlation coefficients across daily emotional experience surveys (45 surveys on average per participant) to quantify each participant's overall emotional granularity. Surface-based morphometry analyses revealed higher overall emotional granularity related to greater cortical thickness in inferior frontal cortex (pFWE < 0.05) in bilateral clusters in the lateral orbitofrontal cortex and extending into the left dorsal anterior insula. Overall emotional granularity was not associated with cortical thickness in the anterior temporal lobes or angular gyri. These findings suggest individual differences in emotional granularity relate to variability in the structural neuroanatomy of the inferior frontal cortex, an area that supports the controlled selection of conceptual knowledge during emotional experiences.

Neuropsychiatric symptoms and imbalance of atrophy in behavioral variant frontotemporal dementia.

Behavioral variant frontotemporal dementia is characterized by heterogeneous frontal, insular, and anterior temporal atrophy patterns that vary along left-right and dorso-ventral axes. Little is known about how these structural imbalances impact clinical symptomatology. The goal of this study was to assess the frequency of frontotemporal asymmetry (right- or left-lateralization) and dorsality (ventral or dorsal predominance of atrophy) and to investigate their clinical correlates. Neuropsychiatric symptoms and structural images were analyzed for 250 patients with behavioral variant frontotemporal dementia. Frontotemporal atrophy was most often symmetric while left-lateralized (9%) and right-lateralized (17%) atrophy were present in a minority of patients. Atrophy was more often ventral (32%) than dorsal (3%) predominant. Patients with right-lateralized atrophy were characterized by higher severity of abnormal eating behavior and hallucinations compared to those with left-lateralized atrophy. Subsequent analyses clarified that eating behavior was associated with right atrophy to a greater extent than a lack of left atrophy, and hallucinations were driven mainly by right atrophy. Dorsality analyses showed that anxiety, euphoria, and disinhibition correlated with ventral-predominant atrophy. Agitation, irritability, and depression showed greater severity with a lack of regional atrophy, including in dorsal regions. Aberrant motor behavior and apathy were not explained by asymmetry or dorsality. This study provides additional insight into how anatomical heterogeneity influences the clinical presentation of patients with behavioral variant frontotemporal dementia. Behavioral symptoms can be associated not only with the presence or absence of focal atrophy, but also with right/left or dorsal/ventral imbalance of gray matter volume.

Behavioural subphenotypes and their anatomic correlates in neurodegenerative disease.

Patients with neurodegenerative disorders experience a range of neuropsychiatric symptoms. The neural correlates have been explored for many individual symptoms, such as apathy and disinhibition. Atrophy patterns have also been associated with broadly recognized syndromes that bring together multiple symptoms, such as the behavioural variant of frontotemporal dementia. There is substantial heterogeneity of symptoms, with partial overlap of behaviour and affected neuroanatomy across and within dementia subtypes. It is not well established if there are anatomically distinct behavioural subphenotypes in neurodegenerative disease. The objective of this study was to identify shared behavioural profiles in frontotemporal dementia-spectrum and Alzheimer's disease-related syndromes. Additionally, we sought to determine the underlying neural correlates of these symptom clusters. Two hundred and eighty-one patients diagnosed with one of seven different dementia syndromes, in addition to healthy controls and individuals with mild cognitive impairment, completed a 109-item assessment capturing the severity of a range of clinical behaviours. A principal component analysis captured distinct clusters of related behaviours. Voxel-based morphometry analyses were used to identify regions of volume loss associated with each component. Seven components were identified and interpreted as capturing the following behaviours: Component 1-emotional bluntness, 2-emotional lability and disinhibition, 3-neuroticism, 4-rigidity and impatience, 5-indiscriminate consumption, 6-psychosis and 7-Geschwind syndrome-related behaviours. Correlations with structural brain volume revealed distinct neuroanatomical patterns associated with each component, including after controlling for diagnosis, suggesting that localized neurodegeneration can lead to the development of behavioural symptom clusters across various dementia syndromes.

Enhanced positive emotional reactivity in frontotemporal dementia reflects left-lateralized atrophy in the temporal and frontal lobes.

In frontotemporal dementia (FTD), left-lateralized atrophy patterns have been associated with elevations in certain positive emotions. Here, we investigated whether positive emotional reactivity was enhanced in semantic variant primary progressive aphasia (svPPA), an FTD syndrome that targets the left anterior temporal lobe. Sixty-one participants (16 people with svPPA, 24 people with behavioral variant FTD, and 21 healthy controls) viewed six 90-sec trials that were comprised of a series of photographs; each trial was designed to elicit a specific positive emotion, negative emotion, or no emotion. Participants rated their positive emotional experience after each trial, and their smiling behavior was coded with the Facial Action Coding System. Results indicated that positive emotional experience and smiling were elevated in svPPA in response to numerous affective and non-affective stimuli. Voxel-based morphometry analyses revealed that greater positive emotional experience and greater smiling in the patients were both associated with smaller gray matter volume in the left superior temporal gyrus (pFWE < .05), among other left-lateralized frontotemporal regions. Whereas enhanced positive emotional experience related to atrophy in middle superior temporal gyrus and structures that promote cognitive control and emotion regulation, heightened smiling related to atrophy in posterior superior temporal gyrus and structures that support motor control. Our results suggest positive emotional reactivity is elevated in svPPA and offer new evidence that atrophy in left-lateralized emotion-relevant systems relates to enhanced positive emotions in FTD.

Big smile, small self: Awe walks promote prosocial positive emotions in older adults.

Aging into later life is often accompanied by social disconnection, anxiety, and sadness. Negative emotions are self-focused states with detrimental effects on aging and longevity. Awe-a positive emotion elicited when in the presence of vast things not immediately understood-reduces self-focus, promotes social connection, and fosters prosocial actions by encouraging a "small self." We investigated the emotional benefits of a novel "awe walk" intervention in healthy older adults. Sixty participants took weekly 15-min outdoor walks for 8 weeks; participants were randomly assigned to an awe walk group, which oriented them to experience awe during their walks, or to a control walk group. Participants took photographs of themselves during each walk and rated their emotional experience. Each day, they reported on their daily emotional experience outside of the walk context. Participants also completed pre- and postintervention measures of anxiety, depression, and life satisfaction. Compared with participants who took control walks, those who took awe walks experienced greater awe during their walks and exhibited an increasingly "small self" in their photographs over time. They reported greater joy and prosocial positive emotions during their walks and displayed increasing smile intensity over the study. Outside of the walk context, participants who took awe walks reported greater increases in daily prosocial positive emotions and greater decreases in daily distress over time. Postintervention anxiety, depression, and life satisfaction did not change from baseline in either group. These results suggest cultivating awe enhances positive emotions that foster social connection and diminishes negative emotions that hasten decline. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Enhanced visceromotor emotional reactivity in dyslexia and its relation to salience network connectivity.

Dyslexia is a neurodevelopmental disorder mainly defined by reading difficulties. During reading, individuals with dyslexia exhibit hypoactivity in left-lateralized language systems. Lower activity in one brain circuit can be accompanied by greater activity in another, and, here, we examined whether right-hemisphere-based emotional reactivity may be elevated in dyslexia. We measured emotional reactivity (i.e., facial behavior, physiological activity, and subjective experience) in 54 children ages 7-12 with (n = 32) and without (n = 22) dyslexia while they viewed emotion-inducing film clips. Participants also underwent task-free functional magnetic resonance imaging. Parents of children with dyslexia completed the Behavior Assessment System for Children, which assesses real-world behavior. During film viewing, children with dyslexia exhibited significantly greater reactivity in emotional facial behavior, skin conductance level, and respiration rate than those without dyslexia. Across the sample, greater emotional facial behavior correlated with stronger connectivity between right ventral anterior insula and right pregenual anterior cingulate cortex (pFWE<.05), key salience network hubs. In children with dyslexia, greater emotional facial behavior related to better real-world social skills and higher anxiety and depression. Our findings suggest there is heightened visceromotor emotional reactivity in dyslexia, which may lead to interpersonal strengths as well as affective vulnerabilities.

Internal states and interoception along a spectrum of eating disorder symptomology.

OBJECTIVE: Recent studies on atypical interoceptive capabilities have focused on clinical populations, including anorexia nervosa[1,2]. The present exploratory study aims to characterize the influence of disordered eating symptomology on interoceptive capabilities in college students, a population for which dangerous dieting behaviors may emerge. METHOD: Ninety-nine participants were randomized to consume a blinded high calorie or low calorie midday shake. Participants reported frequency of eating disorder cognitions and behaviors; indicated changes in satiety, happiness, and energy pre- and post-consumption; and guessed the calories in their shake. Outcomes (perceived satiety, changes in mood, and caloric guess) were regressed on eating disorder symptoms scores, the high/low calorie shake condition, and the interaction between these predictors. RESULTS: Those randomized to receive the high calorie shake reported feeling fuller, but only when endorsing lower levels of eating concern. Those randomized to the high calorie shake reported greater post-meal happiness, but only at greater levels of eating concerns. Lastly, those with lower levels of eating restraint reported an expected positive association between level of fullness and calorie guess, but those with higher levels of eating restraint did not exhibit any relationship between perceived fullness and calorie guess. DISCUSSION: Results of this exploratory suggest that irregular eating habits (e.g., not eating a sufficient amount for lunch) may have direct consequences on interoceptive capabilities. Further, these capacities may be impacted by individual differences in eating concern and restraint. Preliminary findings suggest that impairment in deciphering visceral signals may be associated with the degree of eating disorder symptomology; such impairment may occur at lower levels of symptomatology than normative data would indicate.

Meal skipping and cognition along a spectrum of restrictive eating.

OBJECTIVE: Inadequate nutrition adversely impacts brain development and cognitive functioning (Pollitt et al., 1983). Studies examining the acute impact of eating regular meals on cognition have reported inconsistent findings, necessitating the exploration of individual differences in samples contributing to equivocal results. The present study examines the impact of skipping lunch on cognitive ability in college-aged students by including eating restraint as a moderator. METHODS: Participants were 99 college-aged students (M = 19.7 years, SD = 1.5) randomized to a blinded 'lunch' or 'lunch-omission' condition, and assessed on memory, attention, processing speed, set shifting, and eating disorder symptomology. RESULTS: Regressing long and short-term memory on the lunch manipulation, eating restraint scores, and their interaction revealed significant interactions: those who had lunch had superior memory performance, but only for those reporting lower levels of eating restraint. Regressing set shifting speed on the manipulation, those who had lunch had slower set shifting speed than those who skipped, but only for those reporting lower levels of eating restraint. CONCLUSIONS: Results suggest that skipping lunch may have immediate consequences on cognition, however, cognitive enhancing effects may be diminished in the presence of even low levels of eating restraint. Findings highlight the significance of purported subclinical levels of eating restraint and may inform health education strategies.

Factors that predict diagnostic stability in neurodegenerative dementia.

OBJECTIVE: To determine the frequency and characteristics of clinical diagnostic change in frontotemporal dementia (FTD)-spectrum syndromes and Alzheimer's disease (AD)-type dementia. METHODS: We reviewed records and categorized diagnostic changes in patients seen ≥ 2 times with behavioral variant FTD (bvFTD, n = 99), nonfluent and semantic variant primary progressive aphasia (nfvPPA, n = 32; svPPA, n = 59), corticobasal syndrome (CBS, n = 40), progressive supranuclear palsy-Richardson syndrome (PSP-RS, n = 34), and AD-type dementia (n = 49). For bvFTD, we compared patients with and without diagnostic change, and assessed predictors of diagnostic change by logistic regression. RESULTS: Initial diagnoses changed infrequently at subsequent visits in svPPA (6.8%), PSP-RS (8.8%), and nfvPPA (12.5%), with rare changes largely involving clinicopathological overlap or diagnostic ambiguity. Changes in AD-type dementia (30.6%) and CBS (37.5%) were more common, but reflected greater specificity, predicted co-pathology, or overlapping syndromes. Diagnostic change in bvFTD was also common (32.3%), but more diverse, including motor neuron disease development, alternative neurodegenerative syndromes, and non-neurodegenerative diseases. Diagnostic change occurred more often in those who met possible rather than probable bvFTD criteria (70.6% vs 15.3%, p < 0.001). Patients with stable diagnoses showed greater overall impairment, bvFTD behavioral severity, and atrophy in core right-hemisphere bvFTD regions. Patients with diagnostic change had more severe depression (p < 0.05) and more frequent contributing, secondary diagnoses (p = 0.01), such as cerebrovascular disease. By logistic regression, the accuracy of predicting stable bvFTD diagnoses using first-visit data was 80%. CONCLUSION: bvFTD displays more diverse diagnostic change than other neurodegenerative syndromes. First-visit bvFTD diagnoses may waver if based on meeting possible criteria only.

Longitudinal multimodal imaging and clinical endpoints for frontotemporal dementia clinical trials.

Frontotemporal dementia refers to a group of progressive neurodegenerative syndromes usually caused by the accumulation of pathological tau or TDP-43 proteins. The effects of these proteins in the brain are complex, and each can present with several different clinical syndromes. Clinical efficacy trials of drugs targeting these proteins must use endpoints that are meaningful to all participants despite the variability in symptoms across patients. There are many candidate clinical measures, including neuropsychological scores and functional measures. Brain imaging is another potentially attractive outcome that can be precisely quantified and provides evidence of disease modification. Most imaging studies in frontotemporal dementia have been cross-sectional, and few have compared longitudinal changes in cortical volume with changes in other measures such as perfusion and white matter integrity. The current study characterized longitudinal changes in 161 patients with three frontotemporal dementia syndromes: behavioural variant frontotemporal dementia (n = 77) and the semantic (n = 45) and non-fluent (n = 39) variants of primary progressive aphasia. Visits included comprehensive neuropsychological and functional assessment, structural MRI (3 T), diffusion tensor imaging, and arterial spin labelled perfusion imaging. The goal was to identify measures that are appropriate as clinical trial outcomes for each group, as well as those that might be appropriate for trials that would include more than one of these groups. Linear mixed effects models were used to estimate changes in each measure, and to examine the correlation between imaging and clinical changes. Sample sizes were estimated based on the observed effects for theoretical clinical trials using bootstrapping techniques to provide 95% confidence intervals for these estimates. Declines in functional and neuropsychological measures, as well as frontal and temporal cortical volumes and white matter microstructure were detected in all groups. Imaging changes were statistically significantly correlated with, and explained a substantial portion of variance in, the change in most clinical measures. Perfusion and diffusion tensor imaging accounted for variation in clinical decline beyond volume alone. Sample size estimates for atrophy and diffusion imaging were comparable to clinical measures. Corpus callosal fractional anisotropy led to the lowest sample size estimates for all three syndromes. These findings provide further guidance on selection of trial endpoints for studies in frontotemporal dementia and support the use of neuroimaging, particularly structural and diffusion weighted imaging, as biomarkers. Diffusion and perfusion imaging appear to offer additional utility for explaining clinical change beyond the variance explained by volume alone, arguing for considering multimodal imaging in treatment trials.

Resting parasympathetic dysfunction predicts prosocial helping deficits in behavioral variant frontotemporal dementia.

In the behavioral variant of frontotemporal dementia (bvFTD), left-lateralized salience network dysfunction reduces basal activity in the parasympathetic nervous system, a branch of the autonomic nervous system that reduces arousal and fosters empathy and prosociality. Here we examined whether resting parasympathetic deficits in bvFTD related to diminished prosocial behavior. Eighty participants [30 with bvFTD, 25 with Alzheimer's disease (AD), and 25 healthy controls] completed a "helping task" in which we quantified participants' spontaneous reactions to an experimenter who struggled to find a lost key. Participants also underwent an assessment of baseline autonomic nervous system activity and structural magnetic resonance imaging. An exploratory factor analysis of participants' behaviors during the helping task revealed four factors: empathic concern, consolation, disengagement, and impatience. Patients with bvFTD had lower empathic concern and greater disengagement and impatience than the AD and healthy control groups. Patients with bvFTD had lower resting respiratory sinus arrhythmia and faster respiration and heart rates than patients with AD and healthy controls, a pattern consistent with parasympathetic dysfunction. Skin conductance level was also lower in bvFTD than in the other groups. Lower baseline respiratory sinus arrhythmia and faster baseline respiration rates, but not skin conductance level, predicted lower prosocial helping behaviors. Voxel-based morphometry analyses revealed that atrophy in the bilateral medial pulvinar nucleus of the thalamus, midcingulate cortex, and caudate was associated with lower empathic concern and consolation, and atrophy in the bilateral medial pulvinar nucleus of the thalamus, left frontoinsula, and left ventral striatum was associated with greater disengagement and impatience. Left-lateralized frontoinsula atrophy was associated with not only lower respiratory sinus arrhythmia but also with lower consolation and greater disengagement. This study offers evidence for prosocial behavior deficits in bvFTD and suggests that left-lateralized salience network atrophy reduces patients' resting parasympathetic activity and motivation to help others in need.

Deficits in physiological and self-conscious emotional response to errors in hoarding disorder.

Hoarding disorder (HD) has been hypothesized to arise from deficits in error monitoring and abnormalities in emotional processing, but the relationship between error monitoring and emotional processing has not been examined. We examined measures of self-report, as well as behavioral, physiological, and facial responses to errors during a Stop-Change Task. 25 participants with HD and 32 healthy controls (HC) were recruited. Participants reported on number of errors committed and pre/post emotional response to errors. Skin conductance response (SCR) during correct and error commission trials was examined. Facial expression during task performance was coded for self-conscious and negative emotions. HD and HC participants had significantly different error rates but comparable error correction and post-error slowing. SCR was significantly lower for HD during error commission than for HC. During error trials, HD participants showed a significant deficit in displays of self-conscious emotions compared to HC. Self-reported emotions were increased in HD, with more negative and self-conscious emotion reported than was reported for HC participants. These findings suggest that hypoactive emotional responding at a physiological level may play a role in how errors are processed in individuals with HD.

Mistakes, Too Few to Mention? Impaired Self-conscious Emotional Processing of Errors in the Behavioral Variant of Frontotemporal Dementia.

Anosognosia, or lack of awareness of one's deficits, is a core feature of the behavioral variant of frontotemporal dementia (bvFTD). We hypothesized that this deficit has its origins in failed emotional processing of errors. We studied autonomic and facial emotional reactivity to errors in patients with bvFTD (n = 17), Alzheimer's disease (AD, n = 20), and healthy controls (HC, n = 35) during performance of a timed two-alternative-choice button press task. Performance-related behavioral responses to errors were quantified using rates of error correction and post-error slowing of reaction times. Facial emotional responses were measured by monitoring facial reactivity via video and subsequently coding the type, duration and intensity of all emotional reactions. Skin conductance response (SCR) was measured via noninvasive sensors. SCR and total score for each facial emotion expression were quantified for each trial. Facial emotions were grouped into self-conscious (amusement, embarrassment) and negative (fear, sadness, anger, disgust, contempt) emotions. HCs corrected 99.4% of their errors. BvFTD patients corrected 94% (not statistically different compared with HC) and AD corrected 74.8% of their errors (p < 0.05 compared with HC and bvFTD). All groups showed similar post-error slowing. Errors in HCs were associated with greater facial reactivity and SCRs compared with non-error trials, including both negative and self-conscious emotions. BvFTD patients failed to produce self-conscious emotions or an increase in SCR for errors, although they did produce negative emotional responses to a similar degree as HCs. AD showed no deficit in facial reactivity to errors. Although, SCR was generally reduced in AD during error trials, they showed a preserved increase in SCR for errors relative to correct trials. These results demonstrate a specific deficit in emotional responses to errors in bvFTD, encompassing both physiological response and a specific deficit in self-conscious emotions, despite intact awareness and correction of errors. The findings provide a potential mechanism for anosognosia and possibly other behavioral abnormalities in bvFTD and highlight the importance of studying multiple channels of reactivity to errors, including performance related responses and emotional responses, in order to understand how impaired error processing could influence behavior.

Reward deficits in behavioural variant frontotemporal dementia include insensitivity to negative stimuli.

During reward processing individuals weigh positive and negative features of a stimulus to determine whether they will pursue or avoid it. Though patients with behavioural variant frontotemporal dementia display changes in their pursuit of rewards, such as food, alcohol, money, and sex, the basis for these shifts is not clearly established. In particular, it is unknown whether patients' behaviour results from excessive focus on rewards, insensitivity to punishment, or to dysfunction in a particular stage of reward processing, such as anticipation, consumption, or action selection. Our goal was to determine the nature of the reward deficit in behavioural variant frontotemporal dementia and its underlying anatomy. We devised a series of tasks involving pleasant, unpleasant, and neutral olfactory stimuli, designed to separate distinct phases of reward processing. In a group of 25 patients with behavioural variant frontotemporal dementia and 21 control subjects, diagnosis by valence interactions revealed that patients with behavioural variant frontotemporal dementia rated unpleasant odours as less aversive than did controls and displayed lower skin conductance responses when anticipating an upcoming aversive odour. Subjective pleasantness ratings and skin conductance responses did not differ between behavioural variant frontotemporal dementia and controls for pleasant or neutral smells. In a task designed to measure the effort subjects would expend to smell or avoid smelling a stimulus, patients with behavioural variant frontotemporal dementia were less motivated, and therefore less successful than control subjects, at avoiding what they preferred not to smell, but had equivalent success at obtaining stimuli they found rewarding. Voxel-based morphometry of patients with behavioural variant frontotemporal dementia revealed that the inability to subjectively differentiate the valence of pleasant and unpleasant odours correlated with atrophy in right ventral mid-insula and right amygdala. High pleasantness ratings of unpleasant stimuli correlated with left dorsal anterior insula and frontal pole atrophy. These findings indicate that insensitivity to negative information may be a key component of the reward-seeking behaviours in behavioural variant frontotemporal dementia, and may relate to degeneration of structures that are involved in representing the emotional salience of sensory information.

Clinicopathological correlations in behavioural variant frontotemporal dementia.

Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical for the success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations in a large bvFTD cohort. Among 438 patients in whom bvFTD was either the top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 with a primary pathological diagnosis of frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related pathology outside of the motor system. Patients with FTLD were distributed between FTLD-tau (34 patients: 10 corticobasal degeneration, nine progressive supranuclear palsy, eight Pick's disease, three frontotemporal dementia with parkinsonism associated with chromosome 17, three unclassifiable tauopathy, and one argyrophilic grain disease); FTLD-TDP (55 patients: nine type A including one with motor neuron disease, 27 type B including 21 with motor neuron disease, eight type C with right temporal lobe presentations, and 11 unclassifiable including eight with motor neuron disease), FTLD-FUS (eight patients), and one patient with FTLD-ubiquitin proteasome system positive inclusions (FTLD-UPS) that stained negatively for tau, TDP-43, and FUS. Alzheimer's disease was uncommon (6%) among patients whose only top diagnosis during follow-up was bvFTD. Seventy-nine per cent of FTLD-tau, 86% of FTLD-TDP, and 88% of FTLD-FUS met at least 'possible' bvFTD diagnostic criteria at first presentation. The frequency of the six core bvFTD diagnostic features was similar in FTLD-tau and FTLD-TDP, suggesting that these features alone cannot be used to separate patients by major molecular class. Voxel-based morphometry revealed that nearly all pathological subgroups and even individual patients share atrophy in anterior cingulate, frontoinsula, striatum, and amygdala, indicating that degeneration of these regions is intimately linked to the behavioural syndrome produced by these diverse aetiologies. In addition to these unifying features, symptom profiles also differed among pathological subtypes, suggesting distinct anatomical vulnerabilities and informing a clinician's prediction of pathological diagnosis. Data-driven classification into one of the 10 most common pathological diagnoses was most accurate (up to 60.2%) when using a combination of known predictive factors (genetic mutations, motor features, or striking atrophy patterns) and the results of a discriminant function analysis that incorporated clinical, neuroimaging, and neuropsychological data.

Prosocial deficits in behavioral variant frontotemporal dementia relate to reward network atrophy.

INTRODUCTION: Empathy and shared feelings of reward motivate individuals to share resources with others when material gain is not at stake. Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disease that affects emotion- and reward-relevant neural systems. Although there is diminished empathy and altered reward processing in bvFTD, how the disease impacts prosocial behavior is less well understood. METHODS: A total of 74 participants (20 bvFTD, 15 Alzheimer's disease [AD], and 39 healthy controls) participated in this study. Inspired by token-based paradigms from animal studies, we developed a novel task to measure prosocial giving (the "Giving Game"). On each trial of the Giving Game, participants decided how much money to offer to the experimenter, and prosocial giving was the total amount that participants gave to the experimenter when it cost them nothing to give. Voxel-based morphometry was then used to identify brain regions that were associated with prosocial giving. RESULTS: Prosocial giving was lower in bvFTD than in healthy controls; prosocial giving in AD did not differ significantly from either of the other groups. Whereas lower prosocial giving was associated with atrophy in the right pulvinar nucleus of the thalamus, greater prosocial giving was associated with atrophy in the left ventral striatum. CONCLUSION: These findings suggest that simple acts of generosity deteriorate in bvFTD due to lateralized atrophy in reward-relevant neural systems that promote shared feelings of positive affect.