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.

Understanding Health Beliefs and Health Behaviors in Older Adults at Risk for Alzheimer's Disease.

Background: There are significant public health benefits to delaying the onset of Alzheimer's disease (AD) in individuals at risk. However, adherence to brain healthy behaviors is low. The Health Belief Model proposes that specific beliefs are mediators of behavior change. Objective: To characterize health belief measures from the Science of Behavior Change Research Network (SBCRN) in an older adult population and associations between health beliefs, AD risk, and current health behaviors. Methods: A total of 172 individuals from the Rhode Island AD Prevention Registry participated. SBCRN health belief measures included assessments of future time perspective, self-efficacy, deferment of gratification, and consideration of future consequences. Outcome measures included individual AD risk index score, dementia risk awareness, and lifestyle behaviors including physical, cognitive, and social activity. Results: Participants who were older had higher scores for AD risk, lower future time perspective, and lower generalized self-efficacy (all at p < 0.001). Higher generalized self-efficacy was related to increased physical activity (p < 0.010). Higher future time perspective (p < 0.001) and generalized self-efficacy (p = 0.48) were associated with lower AD risk score. Subjective cognitive decline (SCD) was associated with lower self-efficacy, ability to delay gratification, and a less expansive future time perspective. Conclusions: Greater self-efficacy and perceived future time remaining were associated with lower AD risk and greater engagement in physical activity. SCD was associated with health beliefs that may negatively affect engagement in positive brain health behaviors. Assessment of and psychoeducation about these intrapersonal health belief constructs may be important targets for behavioral interventions to reduce AD risk.

Rates of diagnosis and service utilization in veterans with hoarding disorder.

Hoarding Disorder (HD) is a prominent and disabling neuropsychiatric condition defined by the inability to discard objects resulting in impairing levels of clutter. The prevalence rate is 2-6 % and increases with age. The aging Veteran population is a high risk group for impairment associated with HD. Medical and psychiatric comorbidities as well as associated rates of disability and poor quality of life are very common in both HD and the related disorder of OCD. We examined rates of HD and OCD diagnoses at the VA San Diego Healthcare System. Data were obtained from medical records for all Veterans with these diagnoses over 8-years and included information on medical and psychiatric care, homelessness services, and Care Assessment Needs (CAN) scores. Rates of diagnosis for both HD and OCD were well below epidemiological estimates. Veterans with HD were older, had higher rates of medical hospital admissions with longer stays; had more cardiac, neurological, and acquired medical conditions; had more psychiatric comorbidities; had more interactions with the suicide prevent team and homelessness services; and had higher CAN scores than Veterans with OCD. The low rate of diagnosis and high services utilization of Veterans with HD demonstrates an area of unmet need.

Subjective cognitive complaints and objective cognitive impairment in hoarding disorder.

Individuals with Hoarding Disorder (HD) frequently complain of problems with attention and memory. These self-identified difficulties are often used as justification for saving and acquiring behaviors. Research using neuropsychological measures to examine verbal and visual memory performance and sustained attention have reported contradictory findings. Here we aim to determine the relationship between self-reported problems with memory and attention, objective memory and attention performance, and self-reported depression and anxiety symptoms in HD. Data was available for 319 individuals who participated in a treatment study of HD. Multiple regression was used to assess the relationship between self-reported complaints and objective measures, with age, education, and measures of depression and anxiety included as covariates. We found no association between self-reported memory difficulties and objective verbal or visual memory performance. Self-reported problems with attention were associated with objective attentional performance, although this relationship was partially accounted for by anxiety symptom severity. There was a small association between visual memory performance at baseline and improvements in hoardingrelated functional abilities following treatment. Improvements in subjective memory complaints pre-to-post treatment were associated with improvements in hoarding symptom severity and hoarding-related functioning. These results demonstrate a dissociation between perceived and objective functioning in HD.

Impact of Hoarding and Obsessive-Compulsive Disorder Symptomatology on Quality of Life and Their Interaction With Depression Symptomatology.

Hoarding disorder (HD) is a psychiatric condition characterized by difficulty discarding items and accumulation of clutter. Although studies have established the negative impact of HD and compulsive hoarding behavior, fewer have examined the impact on quality of life (QoL) of hoarding behavior independent of obsessive-compulsive disorder (OCD). Moreover, specific aspects of QoL such as success in work/academics or satisfaction with interpersonal relationships have not been well-investigated. In this study, we examined, in a sample of 2100 adult participants obtained from Amazon Mechanical Turk, the relationships between hoarding, OCD, and depression symptomatology and four QoL domains (success, enrichment, environment, and family) derived from a factor analysis of the Quality of Life Inventory (QoLI). We performed linear regressions to examine associations between psychiatric symptomatology and QoL domains and then conducted mediation analyses to investigate the role of depressive symptomatology in the identified relationships. We found that while hoarding and obsessive-compulsive symptoms were both negatively associated with QoL, they were associated with different domains [hoarding was significantly associated (p < 0.05) with total QoL and all domains and uniquely associated with environment and family QoL compared to obsessive-compulsive symptoms], whereas obsessive-compulsive symptoms were only significantly associated with total, success, and enrichment QoL. However, when depressive symptoms were included in the model, hoarding no longer accounted for significant variance in the total, environment, or family QoL domains (p > 0.05), and was less strongly associated with success or enrichment. Mediation analyses confirmed the role of depression as a complete mediator of hoarding's effect on total, environment, and family QoL, and as a partial mediator of hoarding's effect on success and enrichment QoL. Further examination of the relationship between hoarding symptoms and QoL in those with mild, moderate, and severe depression indicated that in those with more severe depression, hoarding was associated with improved QoL, indicating a possible buffering or compensatory effect. The findings suggest a differential impact of hoarding and obsessive-compulsive symptoms on QoL and emphasize the importance of considering co-morbid depressive symptoms in designing more targeted interventions. Future studies should continue to investigate these complex relationships, given the high co-morbidity of hoarding and depression.

Self-reporting of psychiatric illness in an online patient registry is a good indicator of the existence of psychiatric illness.

Online registries offer many advantages for research, including the ability to efficiently assess large numbers of individuals and identify potential participants for clinical trials and genetic studies. Of particular interest is the validity and utility of self-endorsement of psychiatric disorders in online registries, which, while increasingly more common, remain understudied. We thus assessed the comparability of prevalence estimated from self-endorsement of psychiatric disorders in one such registry, the Brain Health Registry (BHR) to prevalence computed from large US-based epidemiological studies and the degree to which BHR participants report psychiatric disorders consistently. We also examined the concordance between self-report and clinically determined diagnoses of various DSM-5 psychiatric disorders in a subset of participants who underwent direct assessments and identified possible reasons for discordance. Rates of self-reported psychiatric disorders were closest to previously reported population prevalence rates when endorsed at multiple timepoints, and accuracy was at least 70% for all except Hoarding Disorder as compared to the clinical diagnoses. Clinical data suggested that self-endorsement of a given psychiatric diagnosis was indicative of the presence of a closely related condition, although not necessarily for the specific disorder, with the exception of major depressive disorder, panic disorder, and hoarding disorder, which had high positive predictive values (85%, 73%, 100%, respectively). We conclude that self-reporting of psychiatric conditions in an online setting is a fair indicator of psychopathology, but should be accompanied by more in-depth interviews if using data from a participant for a specific disorder.

Identifying psychiatric and neurological comorbidities associated with hoarding disorder through network analysis.

BACKGROUND: The relationships between hoarding disorder (HD) and other neurological and psychiatric disorders remain largely unknown. Although psychiatric burden in those with HD is high, less is known about neurological disorders. Furthermore, which disorders are primarily associated with HD vs which can be better explained via a relationship with another disorder has not been determined. To address these questions, we examined comorbidity patterns of psychiatric and neurological disorders in a large online registry of adults using network analyses. METHODS: We first examined psychiatric comorbidity among 252 participants completing clinician administered psychiatric assessments. Using the Brain Health Registry (BHR) (N = 15,978), we next analyzed prevalence of self-reported neurological and psychiatric disorders among participants with no/minimal hoarding, subclinical hoarding, and clinically significant hoarding and used network analyses to identify direct and indirect relationships between HD and the assessed psychiatric and neurological disorders. RESULTS: The most prevalent comorbidity in clinically assessed participants with HD was major depressive disorder (MDD, 62%), followed by generalized anxiety disorder (GAD, 32%). Network analyses in the BHR indicated that the strongest direct relationships with HD were attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD). The relationships between HD and neurological disorders, including mild cognitive impairment, were weak or non-existent after controlling for other disorders. CONCLUSIONS: ADHD, MDD, and OCD form a triad of psychiatric disorders directly associated with HD. Despite their high comorbidity rates, the associations among anxiety disorders and HD were weak or indirect.

Electrophysiological dynamics of visuocortical processing in hoarding disorder.

Individuals with hoarding disorder (HD) typically perform worse than peers on neuropsychological tasks involving visual perception. Functional neuroimaging shows diffusely increased activity in the visual cortex, consistent with inefficient visual processing in HD. The temporal locus of these inefficiencies in HD is unknown. This study examined the temporal unfolding of visual event-related brain potentials (ERPs) to help better define the neurophysiological mechanisms underlying visual dysfunction in HD. Thirty-three individuals with HD and 35 healthy controls (HC) were assessed using a 64-channel EEG during a modified flanker task. Permutation-controlled analyses were conducted to detect group differences in visual evoked ERPs on a millisecond-to-millisecond basis. Bayesian ANCOVAs and linear regressions that included hoarding and age were conducted to identify the best-fit model for the identified VEPs, compared to a null model that included depression and anxiety severity. Three temporal regions (175 ms, 270 ms, and 440 ms), showed differences in amplitude between HD and HC and were consistent with ERP components N1, P1/N2, and a late negative slow wave (LNSW), respectively. After controlling for depression and anxiety, HD demonstrated an enhanced ERP amplitude at N1 and an attenuated amplitude in LNSW compared to HC but did not show differences at P1/N2. For the N1 and LNSW, there was also a primary effect of the interaction between hoarding and age. This study indicates that altered visuocortical reactivity in HD first occurs at the level of visuocortical processing after 170 ms, indicating alterations of middle and later, but not early, processing in occipitotemporal visual cortex.

Internet-based hoarding assessment: The reliability and predictive validity of the internet-based Hoarding Rating Scale, Self-Report.

The Hoarding Rating Scale, Self Report (HRS-SR) is a 5-item assessment developed to ascertain the presence and severity of hoarding symptoms. This study aimed to evaluate the validity of an online adaptation of the HRS-SR in a remote, unsupervised internet sample of 23,214 members of the Brain Health Registry (BHR), an online research registry that evaluates and longitudinally monitors cognition, medical and psychiatric health status. Convergent validity was assessed among a sub-sample of 1,183 participants who completed additional, remote measures of self-reported hoarding behaviors. Structured clinical interviews conducted in-clinic and via video conferencing tools were conducted among 230 BHR participants; ROC curves were plotted to assess the diagnostic performance of the internet-based HRS-SR using best estimate hoarding disorder (HD) diagnoses as the gold standard. The area under the curve indicated near-perfect model accuracy, and was confirmed with 10-fold cross validation. Sensitivity and specificity for distinguishing clinically relevant hoarding were optimized using an HRS-SR total score cut-off of 5. Longitudinal analyses indicated stability of HRS-SR scores over time. Findings indicate that the internet-based HRS-SR is a useful and valid assessment of hoarding symptoms, though additional research using samples with more diverse hoarding behavior is needed to validate optimal cut-off values.

Visually mediated functioning improves following treatment of hoarding disorder.

BACKGROUND: Hoarding disorder (HD) is a highly debilitating psychiatric disorder that affects 2-6% of adults. Neuropsychological deficits in visual memory, detection, and categorization have been reported in HD. To date, no study has examined the relationship between neurocognitive functioning and treatment for HD. We aim to determine the association between neurocognitive functioning and treatment outcomes, as well as the impact of HD-specific treatment on cognitive functioning. METHODS: 323 individuals with HD were randomized to 20 weeks of peer- or clinician-led group behavioral treatment. 242 participants completed pre- and post-treatment neuropsychological testing covering eight neurocognitive domains. Rates of cognitive impairment (CI) were assessed for each neurocognitive domain. The association of baseline neurocognitive function on treatment response was examined using multiple regression. MANOVA and post-hoc tests were used to determine neurocognitive performance change pre- to post treatment. RESULTS: Sixty-seven percent of participants had CI on ≥1 cognitive domain. There was no significant effect of pre-treatment neurocognitive functioning on treatment outcome. Post-treatment improvements were observed in visual memory, visual detection, decision making, information processing speed, visuospatial processing, attention/working memory (p≤.001). Declines in performance were found in visual reaction time and categorization. LIMITATIONS: This was a non-inferiority trial to examine two treatment types with no normative comparison group. Treatment seeking individuals are more likely to be insightful, motivated, and have other features which limit generalizability. CONCLUSIONS: Patterns of cognitive impairment in HD are similar to previous reports. Pre-treatment neurocognitive functioning did not impact treatment response. Neuropsychological functioning improved across multiple domains following targeted treatment.

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.

Recruiting under-represented populations into psychiatric research: Results from the help for hoarding study.

This study compares the effectiveness of approaches used to recruit a diverse sample for a randomized clinical trial for Hoarding Disorder (HD) in the San Francisco Bay Area. Of the 632 individuals who inquired about the study, 313 were randomized and 231 completed treatment. Most participants heard about the study via flyering (N = 161), followed by advocacy groups (N = 113), word of mouth (N = 84), health care professionals (N = 78), online (N = 68), and media (N = 11). However, those that heard about the study via advertising methods, such as flyers, were less likely to complete the study, p = .01, while those recruited via advocacy groups were most likely to be randomized, p = .03. No source proved more effective in recruiting underrepresented groups such as men, p = .60; non-whites, p = .49; or Hispanics, p = .97. Advertising recruited the youngest individuals, p < 0.001, and word of mouth was most likely to recruit unemployed, disabled, or retired individuals, p = .01. Thus, results suggest an ongoing multimodal approach is likely to be most effective in both soliciting and retaining a diverse sample. Future studies should compare recruitment methods across greater geographical regions too, as well as in terms of financial and human costs.

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.

Damage to left frontal regulatory circuits produces greater positive emotional reactivity in frontotemporal dementia.

Positive emotions foster social relationships and motivate thought and action. Dysregulation of positive emotion may give rise to debilitating clinical symptomatology such as mania, risk-taking, and disinhibition. Neuroanatomically, there is extensive evidence that the left hemisphere of the brain, and the left frontal lobe in particular, plays an important role in positive emotion generation. Although prior studies have found that left frontal injury decreases positive emotion, it is not clear whether selective damage to left frontal emotion regulatory systems can actually increase positive emotion. We measured happiness reactivity in 96 patients with frontotemporal dementia (FTD), a neurodegenerative disease that targets emotion-relevant neural systems and causes alterations in positive emotion (i.e., euphoria and jocularity), and in 34 healthy controls. Participants watched a film clip designed to elicit happiness and a comparison film clip designed to elicit sadness while their facial behavior, physiological reactivity, and self-reported emotional experience were monitored. Whole-brain voxel-based morphometry (VBM) analyses revealed that atrophy in predominantly left hemisphere fronto-striatal emotion regulation systems including left ventrolateral prefrontal cortex, orbitofrontal cortex, anterior insula, and striatum was associated with greater happiness facial behavior during the film (pFWE < .05). Atrophy in left anterior insula and bilateral frontopolar cortex was also associated with higher cardiovascular reactivity (i.e., heart rate and blood pressure) but not self-reported positive emotional experience during the happy film (p < .005, uncorrected). No regions emerged as being associated with greater sadness reactivity, which suggests that left-lateralized fronto-striatal atrophy is selectively associated with happiness dysregulation. Whereas previous models have proposed that left frontal injury decreases positive emotional responding, we argue that selective disruption of left hemisphere emotion regulating systems can impair the ability to suppress positive emotions such as happiness.

Metacognition in the behavioral variant of frontotemporal dementia and Alzheimer's disease.

OBJECTIVE: Impaired self-awareness is characteristic of nearly all dementias, including Alzheimer's disease (AD), but the deficit is most severe in the behavioral variant of frontotemporal dementia (bvFTD). The prominence of frontal pathology in bvFTD suggests that failure of online monitoring, the process by which individuals monitor their own cognitive processing in real time, is an important contributor. Metacognitive research offers several approaches to measure self-assessment, some more and others less sensitive to online monitoring. The goal of this study was to assess metacognition in bvFTD using several approaches, and to compare the results with those in AD. METHOD: We examined metacognition in 12 patients with bvFTD, 14 with AD, and 35 healthy controls using feeling of knowing (FOK), ease of learning (EOL), judgment of learning (JOL), and retrospective confidence rating (CR) tasks, as well as response to feedback about performance. RESULTS: BvFTD and AD were both impaired at FOK compared with controls, although AD showed some sparing. Both groups were similarly impaired at CR and neither group was impaired at JOL after accounting for memory performance. Most striking, bvFTD patients failed to appropriately adjust their predictions about future memory performance even after receiving explicit feedback that they had performed worse than they expected. CONCLUSIONS: Both bvFTD and AD show deficits in online monitoring, although the deficit appears more severe in bvFTD. The insensitivity of bvFTD patients to overt feedback may point to unique mechanisms, possibly frontally mediated, that add to their severe lack of self-awareness.

The neural basis of conceptual-emotional integration and its role in major depressive disorder.

The importance of differentiating between social concepts when appraising actions (e.g., understanding behavior as critical vs. fault-finding) and its contribution to vulnerability to major depressive disorder (MDD) is unknown. We predicted poor integration of differentiated conceptual knowledge when people with MDD appraise their social actions, contributing to their tendency to grossly overgeneralize self-blame (e.g., "I am unlikable rather than critical"). To test this hypothesis, we used a neuropsychological test measuring social conceptual differentiation and its relationship with emotional biases in a remitted MDD and a control group. During fMRI, guilt- and indignation-evoking sentences were presented. As predicted, conceptual overgeneralization was associated with increased emotional intensity when appraising social actions. Interdependence of conceptual overgeneralization and negative emotional biases was stronger in MDD (reproducible in the subgroup without medication) and was associated with overgeneralized self-blame. This high conceptual-emotional interdependence was associated with functional disconnection between the right superior anterior temporal lobe (ATL) and right dorsolateral prefrontal cortex (PFC) as well as a septal region across groups when experiencing guilt (SPM8). Strong coupling of conceptual information (ATL) with information about the context of actions and emotions (frontal-subcortical regions) is thus associated with appraisal being less dependent on conceptual overgeneralization, thereby protecting against excessive self-blame.