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Large-scale well-aligned ZnO nanotubes with outer diameters of 100–300 nm and lengths oftens of micrometres have been prepared by a template-based chemical vapour depositionmethod. The photoluminescence spectrum of the ZnO nanotube arrays consists of a strongviolet band at 414 nm, a blue band at 462 nm and a weak shoulder peak at around 480 nm.The field emission of the ZnO nanotube arrays shows a turn-on field of about7.3 V µm−1 at a current densityof 0.1 µA cm−2 and emissioncurrent density up to 1.3 mA cm−2 at a bias field of 11.8 V µm−1. [ABSTRACT FROM AUTHOR]

Mental health problems are common for persons with neurological disorders (PWNDs) and their caregivers (CGs) but often are not adequately treated. Despite this growing need, the training of clinical psychologists typically does not include coursework or practicum experience working with these populations. To address this, a team of faculty, supervisors, and doctoral students in UC Berkeley's Clinical Science program undertook a year-long process that consisted of building a training curriculum that integrated coursework and consultation with visiting experts; providing supervised practicum training with PWNDs and CGs and evaluating training and clinical outcomes. We hoped to prepare students to train other mental health professionals to work with these populations in the future. In this article, we describe the Specialty Clinic with special attention given to the training provided, challenges faced and solutions found, clinic operations and logistics, and lessons learned. We also review key clinical issues and report key indicators of client outcomes. Finally, we evaluate the success of the Specialty Clinic and offer recommendations for others interested in providing these kinds of much needed training and clinical services in this important area.

Empathic accuracy, the ability to accurately understand others' emotions, is typically viewed as beneficial for mental health. However, empathic accuracy may be problematic when a close relational partner is depressed because it promotes shared depression. Across two studies, we measured empathic accuracy using laboratory tasks that capture the ability to rate others' emotional valence accurately over time: first, in a sample of 156 neurotypical married couples (Study 1; Total N=312), and then in a sample of 102 informal caregivers of individuals with dementia (Study 2). Across both studies, the association between empathic accuracy and depressive symptoms varied as a function of a partner's level of depressive symptoms. Greater empathic accuracy was associated with (a) fewer depressive symptoms when a partner lacked depressive symptoms, but (b) more depressive symptoms when a partner had high levels of depressive symptoms. Accurately detecting changes in others' emotional valence may underpin shared depressive symptoms., Competing Interests: Conflict of Interest The authors declare no conflicts of interest with respect to the authorship or the publication of this article.

In semantic dementia (SD), asymmetric degeneration of the anterior temporal lobes is associated with loss of semantic knowledge and alterations in socioemotional behavior. There are two clinical variants of SD: semantic variant primary progressive aphasia (svPPA), which is characterized by predominant atrophy in the anterior temporal lobe and insula in the left hemisphere, and semantic behavioral variant frontotemporal dementia (sbvFTD), which is characterized by predominant atrophy in those structures in the right hemisphere. Previous studies of behavioral variant frontotemporal dementia, an associated clinical syndrome that targets the frontal lobes and anterior insula, have found impairments in baseline autonomic nervous system activity that correlate with left-lateralized frontotemporal atrophy patterns and disruptions in socioemotional functioning. Here, we evaluated whether there are similar impairments in resting autonomic nervous system activity in SD that also reflect left-lateralized atrophy and relate to diminished affiliative behavior. A total of 82 participants including 33 people with SD (20 svPPA and 13 sbvFTD) and 49 healthy older controls completed a laboratory-based assessment of respiratory sinus arrhythmia (RSA; a parasympathetic measure) and skin conductance level (SCL; a sympathetic measure) during a two-minute resting baseline period. Participants also underwent structural magnetic resonance imaging, and informants rated their current affiliative behavior on the Interpersonal Adjective Scale. Results indicated that baseline RSA and SCL were lower in SD than in healthy controls, with significant impairments present in both svPPA and sbvFTD. Voxel-based morphometry analyses revealed left-greater-than-right atrophy related to diminished parasympathetic and sympathetic outflow in SD. While left-lateralized atrophy in the mid-to-posterior insula correlated with lower RSA, left-lateralized atrophy in the ventral anterior insula correlated with lower SCL. In SD, lower baseline RSA, but not lower SCL, was associated with lower gregariousness/extraversion. Neither autonomic measure related to warmth/agreeableness, however. Through the assessment of baseline autonomic nervous system physiology, the present study contributes to expanding conceptualizations of the biological basis of socioemotional alterations in svPPA and sbvFTD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Focal anterior temporal lobe degeneration often preferentially affects the left or right hemisphere. While patients with left-predominant anterior temporal lobe atrophy show severe anomia and verbal semantic deficits and meet criteria for semantic variant primary progressive aphasia and semantic dementia, patients with early right anterior temporal lobe atrophy are more difficult to diagnose as their symptoms are less well understood. Focal right anterior temporal lobe atrophy is associated with prominent emotional and behavioural changes, and patients often meet, or go on to meet, criteria for behavioural variant frontotemporal dementia. Uncertainty around early symptoms and absence of an overarching clinico-anatomical framework continue to hinder proper diagnosis and care of patients with right anterior temporal lobe disease. Here, we examine a large, well-characterized, longitudinal cohort of patients with right anterior temporal lobe-predominant degeneration and propose new criteria and nosology. We identified individuals from our database with a clinical diagnosis of behavioural variant frontotemporal dementia or semantic variant primary progressive aphasia and a structural MRI (n = 478). On the basis of neuroimaging criteria, we defined three patient groups: right anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 46), frontal-predominant atrophy with relative sparing of the right anterior temporal lobe (n = 79) and left-predominant anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 75). We compared the clinical, neuropsychological, genetic and pathological profiles of these groups. In the right anterior temporal lobe-predominant group, the earliest symptoms were loss of empathy (27%), person-specific semantic impairment (23%) and complex compulsions and rigid thought process (18%). On testing, this group exhibited greater impairments in Emotional Theory of Mind, recognition of famous people (from names and faces) and facial affect naming (despite preserved face perception) than the frontal- and left-predominant anterior temporal lobe-predominant groups. The clinical symptoms in the first 3 years of the disease alone were highly sensitive (81%) and specific (84%) differentiating right anterior temporal lobe-predominant from frontal-predominant groups. Frontotemporal lobar degeneration-transactive response DNA binding protein (84%) was the most common pathology of the right anterior temporal lobe-predominant group. Right anterior temporal lobe-predominant degeneration is characterized by early loss of empathy and person-specific knowledge, deficits that are caused by progressive decline in semantic memory for concepts of socioemotional relevance. Guided by our results, we outline new diagnostic criteria and propose the name, 'semantic behavioural variant frontotemporal dementia', which highlights the underlying cognitive mechanism and the predominant symptomatology. These diagnostic criteria will facilitate early identification and care of patients with early, focal right anterior temporal lobe degeneration as well as in vivo prediction of frontotemporal lobar degeneration-transactive response DNA binding protein pathology., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Researchers typically study physiological responses either after stimulus onset or when the emotional valence of an upcoming stimulus is revealed. Yet, participants may also respond when they are told that an emotional stimulus is about to be presented even without knowing its valence. Increased physiological responding during this time may reflect a 'preparation for action'. The generation of such physiological responses may be supported by frontotemporal regions of the brain that are vulnerable to damage in frontotemporal lobar degeneration. We examined preparatory physiological responses and their structural and functional neural correlate in five frontotemporal lobar degeneration clinical subtypes (behavioural variant frontotemporal dementia, n  = 67; semantic variant primary progressive aphasia, n  = 35; non-fluent variant primary progressive aphasia, n  = 30; corticobasal syndrome, n  = 32; progressive supranuclear palsy, n  = 30). Comparison groups included patients with Alzheimer's disease ( n  = 56) and healthy controls ( n  = 35). Preparatory responses were quantified as cardiac interbeat interval decreases (i.e. heart rate increases) from baseline to an 'instruction period', during which participants were told to watch the upcoming emotional film but not provided the film's valence. Patients' behavioural symptoms (apathy and disinhibition) were also evaluated via a caregiver-reported measure. Compared to healthy controls and Alzheimer's disease, the frontotemporal lobar degeneration group showed significantly smaller preparatory responses. When comparing each frontotemporal lobar degeneration clinical subtype with healthy controls and Alzheimer's disease, significant group differences emerged for behavioural variant frontotemporal dementia and progressive supranuclear palsy. Behavioural analyses revealed that frontotemporal lobar degeneration patients showed greater disinhibition and apathy compared to Alzheimer's disease patients. Further, these group differences in disinhibition (but not apathy) were mediated by patients' smaller preparatory responses. Voxel-based morphometry and resting-state functional MRI analyses revealed that across patients and healthy controls, smaller preparatory responses were associated with smaller volume and lower functional connectivity in a circuit that included the ventromedial prefrontal cortex and cortical and subcortical regions of the salience network. Diminished preparatory physiological responding in frontotemporal lobar degeneration may reflect a lack of preparation for actions that are appropriate for an upcoming situation, such as approaching or withdrawing from emotional stimuli. The ventromedial prefrontal cortex and salience network are critical for evaluating stimuli, thinking about the future, triggering peripheral physiological responses, and processing and interpreting interoceptive signals. Damage to these circuits in frontotemporal lobar degeneration may impair preparatory responses and help explain often-observed clinical symptoms such as disinhibition in these patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objectives: Caregivers of persons with neurodegenerative disease have high rates of mental health problems compared to noncaregiving adults. Emotion regulation may play an important role in preserving caregivers' mental health. We examined the associations between caregivers' emotion regulation measured in several ways (ability, habitual use, and self-ratings) and their mental health symptoms., Method: Ninety-one caregivers of persons with neurodegenerative disease participated in a laboratory-based assessment of emotion regulation. In two series of tasks, caregivers were given different instructions (no instruction, suppress) regarding altering their emotional behavioral responses to disgusting films and acoustic startle stimuli. Caregivers' emotional behavior was measured via behavioral coding and caregivers rated "how much emotion" they showed during each task. Anxiety, depression, and habitual use of expressive suppression were measured via questionnaires., Results: Poor emotion regulation in the disgust suppression condition (i.e., greater emotional behavior) was associated with greater anxiety. Associations were not found for the startle suppression condition, depression, or self-report measures of emotion regulation., Discussion: Findings suggest that caregivers who are unable to suppress emotional behavior in response to disgusting stimuli may be at greater risk for anxiety. Given high levels of anxiety in caregivers, it may be useful to evaluate interventions that improve ability to downregulate emotional behavior., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Caregiving for a person with dementia or neurodegenerative disease (PWD) is associated with increased rates of depression and anxiety. As the population ages and dementia prevalence increases worldwide, mental health problems related to dementia caregiving will become an even more pressing public health concern. The present study assessed emotional empathy (physiological, behavioral, and self-reported emotional responses to a film depicting others suffering) and two measures of cognitive empathy (identifying the primary emotion experienced by another person; providing continuous ratings of the valence of another person's changing emotions) in relation to mental health (standard questionnaires) in 78 caregivers of PWDs. Greater emotional empathy (self-reported emotional responses) was associated with worse mental health, even after accounting for known risk factors. Neither measure of cognitive empathy was associated with mental health. A relationship between high levels of emotional empathy and poor mental health in caregivers suggests possible risk indicators and intervention targets., Competing Interests: Conflict of Interest The authors declare no conflicts of interest with respect to the authorship or the publication of this article.

Subjective emotional experience that is congruent with a given situation (i.e., target emotions) is critical for human survival (e.g., feeling disgusted in response to contaminated food motivates withdrawal behaviors). Neurodegenerative diseases including frontotemporal dementia and Alzheimer's disease affect brain regions critical for cognitive and emotional functioning, resulting in increased experience of emotions incongruent with the situation (i.e., non-target emotions, such as feeling happy when seeing someone grieving). We examined neuroanatomical correlates of subjective experience of non-target emotions in 147 patients with neurodegenerative diseases and 26 healthy individuals. Participants watched three films intended to elicit particular target emotions and rated their experience of negative and positive target and non-target emotions after watching each film. We found that smaller volume in left hemisphere regions (e.g., caudate, putamen, and dorsal anterior insula) was associated with greater experience of negative non-target emotions. Follow-up analyses confirmed that these effects were left-lateralized. No correlates emerged for positive non-target emotions. These findings suggest that volume loss in left-hemisphere regions produces a more diffuse, incongruent experience of non-target emotions. These findings provide a potential neuroanatomical basis for understanding how subjective emotional experience is constructed in the brain and how this can be disrupted in neurodegenerative disease., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background and Objectives: Motivated by the high rates of health problems found among caregivers of persons with neurodegenerative disease, we examined associations between deficits in two aspects of care recipients' socioemotional functioning and their caregivers' health., Research Design and Methods: In 2 studies with independent samples (N = 171 and 73 dyads), caregivers reported on care recipients' emotion recognition and emotional reactivity. Caregiver health was assessed using both self-report measures (Studies 1 and 2) and autonomic nervous system indices (Study 2)., Results: Lower emotion recognition in care recipients was linearly associated with worse self-reported health, faster resting heart rate, and greater physiological reactivity to an acoustic startle stimulus in caregivers. These effects held after accounting for a variety of risk factors for poor caregiver health, including care recipients' neuropsychiatric symptoms. Emotional reactivity showed a quadratic association with health, such that the lowest and highest levels of emotional reactivity in care recipients were associated with lower self-reported health in caregivers., Discussion and Implications: Results shed light on the unique associations between two aspects of care recipients' emotional functioning and caregivers' health. Findings suggest potential ways to identify and help caregivers at heightened risk for adverse health outcomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Deficits in emotion perception (the ability to infer others' emotions accurately) can occur as a result of neurodegeneration. It remains unclear how different neurodegenerative diseases affect different forms of emotion perception. The present study compares performance on a dynamic tracking task of emotion perception (where participants track the changing valence of a film character's emotions) with performance on an emotion category labeling task (where participants label specific emotions portrayed by film characters) across seven diagnostic groups (N = 178) including Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA), non-fluent variant primary progressive aphasia (nfvPPA), progressive supranuclear palsy (PSP), corticobasal syndrome and healthy controls. Consistent with hypotheses, compared to controls, the bvFTD group was impaired on both tasks. The svPPA group was impaired on the emotion labeling task, whereas the nfvPPA, PSP and AD groups were impaired on the dynamic tracking task. Smaller volumes in bilateral frontal and left insular regions were associated with worse labeling, whereas smaller volumes in bilateral medial frontal, temporal and right insular regions were associated with worse tracking. Findings suggest labeling and tracking facets of emotion perception are differentially affected across neurodegenerative diseases due to their unique neuroanatomical correlates., (© The Author(s) 2020. Published by Oxford University Press.)

Frontotemporal dementia (FTD), a neurodegenerative disease broadly characterized by socioemotional impairments, includes three clinical subtypes: behavioral variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non-fluent variant primary progressive aphasia (nfvPPA). Emerging evidence has shown emotional reactivity impairments in bvFTD and svPPA, whereas emotional reactivity in nfvPPA is far less studied. In 105 patients with FTD (49 bvFTD, 31 svPPA and 25 nfvPPA) and 27 healthy controls, we examined three aspects of emotional reactivity (physiology, facial behavior and subjective experience) in response to a sad film. In a subset of the sample, we also examined the neural correlates of diminished aspects of reactivity using voxel-based morphometry. Results indicated that all three subtypes of FTD showed diminished physiological responding in respiration rate and diastolic blood pressure; patients with bvFTD and svPPA also showed diminished subjective experience, and no subtypes showed diminished facial behavior. Moreover, there were differences among the clinical subtypes in brain regions where smaller volumes were associated with diminished sadness reactivity. These results show that emotion impairments extend to sadness reactivity in FTD and underscore the importance of considering different aspects of sadness reactivity in multiple clinical subtypes for characterizing emotional deficits and associated neurodegeneration in FTD., (© The Author(s) 2020. Published by Oxford University Press.)

Objective: To test the hypothesis that a functional polymorphism of the serotonin transporter gene (serotonin-transporter-linked polymorphic region [5-HTTLPR]), which is thought to be associated with differential environmental sensitivity, moderates the association between low levels of empathic accuracy (i.e., ability to recognize emotions in others) in patients with neurodegenerative disease and caregivers' well-being., Methods: Participants were 54 patients with neurodegenerative disease and their caregivers. Patients' empathic accuracy was measured using a dynamic tracking task in which they continuously rated the emotions of a character in a film; accuracy was determined by comparing patient ratings with those made by an expert panel. Caregivers provided a saliva sample for genotyping. Caregivers' well-being was measured as a latent construct indicated by validated measures of depression, anxiety, and negative affect., Results: Lower levels of patients' empathic accuracy were associated with lower levels of caregivers' well-being. Importantly, caregivers' 5-HTTLPR genotype moderated this association such that lower empathic accuracy in patients predicted lower well-being for caregivers with the short/short genotype (standardized β = 0.66), but not for caregivers with the short/long (standardized β = 0.05) or long/long genotypes (standardized β = -0.21)., Conclusion: Consistent with previous findings that the short/short variant of 5-HTTLPR is associated with greater sensitivity to environmental influences, caregivers with the short/short variant manifest lower well-being when caring for a patient with low levels of empathic accuracy than caregivers with the other variants. This finding contributes to the authors' understanding of biological factors associated with individual differences in caregiver vulnerability and resilience., (Copyright © 2019. Published by Elsevier Inc.)

Background: Caregivers of patients with neurodegenerative diseases are at heightened risk for serious health problems, but health differences between individual caregivers abound., Aims: To determine whether atrophy in patient brains could be used to identify caregivers at heightened risk for health problems and which patient variables mediate this relationship., Methods: In 162 patient-caregiver dyads, we assessed patient atrophy using structural MRI, caregiver health, and patient behavior and cognitive symptoms., Results: Patient atrophy in the right insula and medial frontal gyrus was associated with worse caregiver health; this relationship was partially mediated by patient neuropsychiatric symptoms, and assessing atrophy in these regions improved predictions of poor caregiver health above and beyond patient behavioral symptoms., Conclusions: This study shows the value of patients' brain data in identifying caregivers at risk for becoming sick themselves., (© 2019 S. Karger AG, Basel.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The salience network is a distributed neural system that maintains homeostasis by regulating autonomic nervous system activity and social-emotional function. Here we examined how within-network connectivity relates to individual differences in human (including males and females) baseline parasympathetic and sympathetic nervous activity. We measured resting autonomic nervous system physiology in 24 healthy controls and 23 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease characterized by baseline autonomic deficits. Participants also underwent structural and task-free fMRI. First, we used voxel-based morphometry to determine whether salience network atrophy was associated with lower baseline respiratory sinus arrhythmia (a parasympathetic measure) and skin conductance level (a sympathetic measure) in bvFTD. Next, we examined whether functional connectivity deficits in 21 autonomic-relevant, salience network node-pairs related to baseline autonomic dysfunction. Lower baseline respiratory sinus arrhythmia was associated with smaller volume in left ventral anterior insula (vAI), weaker connectivity between bilateral vAI and bilateral anterior cingulate cortex (ACC), and stronger connectivity between bilateral ACC and bilateral hypothalamus/amygdala. Lower baseline skin conductance level, in contrast, was associated with smaller volume in inferior temporal gyrus, dorsal mid-insula, and hypothalamus; weaker connectivity between bilateral ACC and right hypothalamus/amygdala; and stronger connectivity between bilateral dorsal anterior insula and periaqueductal gray. Our results suggest that baseline parasympathetic and sympathetic tone depends on the integrity of lateralized salience network hubs (left vAI for parasympathetic and right hypothalamus/amygdala for sympathetic) and highly calibrated ipsilateral and contralateral network connections. In bvFTD, deficits in this system may underlie resting parasympathetic and sympathetic disruption. SIGNIFICANCE STATEMENT The salience network maintains homeostasis and regulates autonomic nervous system activity. Whether within-network connectivity patterns underlie individual differences in resting parasympathetic and sympathetic nervous system activity, however, is not well understood. We measured baseline autonomic nervous system activity in healthy controls and patients with behavioral variant frontotemporal dementia, a neurodegenerative disease characterized by resting autonomic deficits, and probed how salience network dysfunction relates to diminished parasympathetic and sympathetic outflow. Our results indicate that baseline parasympathetic and sympathetic tone are the product of complex, opposing intranetwork nodal interactions and depend on the integrity of highly tuned, lateralized salience network hubs (i.e., left ventral anterior insula for parasympathetic activity and right hypothalamus/amygdala for sympathetic activity)., (Copyright © 2018 the authors 0270-6474/18/388944-13$15.00/0.)

Introduction: Affective changes precede cognitive decline in mild Alzheimer's disease and may relate to increased connectivity in a "salience network" attuned to emotionally significant stimuli. The trajectory of affective changes in preclinical Alzheimer's disease, and its relationship to this network, is unknown., Methods: One hundred one cognitively normal older adults received longitudinal assessments of affective symptoms, then amyloid-PET. We hypothesized amyloid-positive individuals would show enhanced emotional reactivity associated with salience network connectivity. We tested whether increased global connectivity in key regions significantly related to affective changes., Results: In participants later found to be amyloid positive, emotional reactivity increased with age, and interpersonal warmth declined in women. These individuals showed higher global connectivity within the right insula and superior temporal sulcus; higher superior temporal sulcus connectivity predicted increasing emotional reactivity and decreasing interpersonal warmth., Conclusions: Affective changes should be considered an early preclinical feature of Alzheimer's disease. These changes may relate to higher functional connectivity in regions critical for social-emotional processing.

Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disease characterized by profound changes in emotions and empathy. Although most patients with bvFTD become less sensitive to negative emotional cues, some patients become more sensitive to positive emotional stimuli. We investigated whether dysregulated positive emotions in bvFTD undermine empathy by making it difficult for patients to share (emotional empathy), recognize (cognitive empathy), and respond (real-world empathy) to emotions in others. Fifty-one participants (26 patients with bvFTD and 25 healthy controls) viewed photographs of neutral, positive, negative, and self-conscious emotional faces and then identified the emotions displayed in the photographs. We used facial electromyography to measure automatic, sub-visible activity in two facial muscles during the task: Zygomaticus major ( ZM ), which is active during positive emotional reactions (i.e., smiling), and Corrugator supercilii ( CS ), which is active during negative emotional reactions (i.e., frowning). Participants rated their baseline positive and negative emotional experience before the task, and informants rated participants' real-world empathic behavior on the Interpersonal Reactivity Index. The majority of participants also underwent structural magnetic resonance imaging. A mixed effects model found a significant diagnosis X trial interaction: patients with bvFTD showed greater ZM reactivity to neutral, negative (disgust and surprise), self-conscious (proud), and positive (happy) faces than healthy controls. There was no main effect of diagnosis or diagnosis X trial interaction on CS reactivity. Compared to healthy controls, patients with bvFTD had impaired emotion recognition. Multiple regression analyses revealed that greater ZM reactivity predicted worse negative emotion recognition and worse real-world empathy. At baseline, positive emotional experience was higher in bvFTD than healthy controls and also predicted worse negative emotion recognition. Voxel-based morphometry analyses found that smaller volume in the thalamus, midcingulate cortex, posterior insula, anterior temporal pole, amygdala, precentral gyrus, and inferior frontal gyrus-structures that support emotion generation, interoception, and emotion regulation-was associated with greater ZM reactivity in bvFTD. These findings suggest that dysregulated positive emotional reactivity may relate to reduced empathy in bvFTD by making patients less likely to tune their reactions to the social context and to share, recognize, and respond to others' feelings and needs.

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.

Progressive supranuclear palsy syndrome (PSP-S) results from neurodegeneration within a network of brainstem, subcortical, frontal and parietal cortical brain regions. It is unclear how network dysfunction progresses and relates to longitudinal atrophy and clinical decline. In this study, we evaluated patients with PSP-S (n = 12) and healthy control subjects (n = 20) at baseline and 6 months later. Subjects underwent structural MRI and task-free functional MRI (tf-fMRI) scans and clinical evaluations at both time points. At baseline, voxel based morphometry (VBM) revealed that patients with mild-to-moderate clinical symptoms showed structural atrophy in subcortex and brainstem, prefrontal cortex (PFC; supplementary motor area, paracingulate, dorsal and ventral medial PFC), and parietal cortex (precuneus). Tf-fMRI functional connectivity (FC) was examined in a rostral midbrain tegmentum (rMT)-anchored intrinsic connectivity network that is compromised in PSP-S. In healthy controls, this network contained a medial parietal module, a prefrontal-paralimbic module, and a subcortical-brainstem module. Baseline FC deficits in PSP-S were most severe in rMT network integrative hubs in the prefrontal-paralimbic and subcortical-brainstem modules. Longitudinally, patients with PSP-S had declining intermodular FC between the subcortical-brainstem and parietal modules, while progressive atrophy was observed in subcortical-brainstem regions (midbrain, pallidum) and posterior frontal (perirolandic) cortex. This suggested that later-stage subcortical-posterior cortical change may follow an earlier-stage subcortical-anterior cortical disease process. Clinically, patients with more severe baseline impairment showed greater subsequent prefrontal-parietal cortical FC declines and posterior frontal atrophy rates, while patients with more rapid longitudinal clinical decline showed coupled prefrontal-paralimbic FC decline. VBM and FC can augment disease monitoring in PSP-S by tracking the disease through stages while detecting changes that accompany heterogeneous clinical progression.

Although laboratory procedures are designed to produce specific emotions, participants often experience mixed emotions (i.e., target and non-target emotions). We examined non-target emotions in patients with frontotemporal dementia (FTD), Alzheimer's disease (AD), other neurodegenerative diseases, and healthy controls. Participants watched film clips designed to produce three target emotions. Subjective experience of non-target emotions was assessed and emotional facial expressions were coded. Compared to patients with other neurodegenerative diseases and healthy controls, FTD patients reported more positive and negative non-target emotions, whereas AD patients reported more positive non-target emotions. There were no group differences in facial expressions of non-target emotions. We interpret these findings as reflecting deficits in processing interoceptive and contextual information resulting from neurodegeneration in brain regions critical for creating subjective emotional experience.

The brain continuously influences and perceives the physiological condition of the body. Related cortical representations have been proposed to shape emotional experience and guide behavior. Although previous studies have identified brain regions recruited during autonomic processing, neurological lesion studies have yet to delineate the regions critical for maintaining autonomic outflow. Even greater controversy surrounds hemispheric lateralization along the parasympathetic-sympathetic axis. The behavioral variant of frontotemporal dementia (bvFTD), featuring progressive and often asymmetric degeneration that includes the frontoinsular and cingulate cortices, provides a unique lesion model for elucidating brain structures that control autonomic tone. Here, we show that bvFTD is associated with reduced baseline cardiac vagal tone and that this reduction correlates with left-lateralized functional and structural frontoinsular and cingulate cortex deficits and with reduced agreeableness. Our results suggest that networked brain regions in the dominant hemisphere are critical for maintaining an adaptive level of baseline parasympathetic outflow.

Approximately 80% of smokers initiate tobacco use during adolescence, suggesting that nicotine initiation and nicotine dependence have a substantial age component. There also is a substantial genetic influence on smoking behaviors such as age of initiation and the development of nicotine dependence. The goal of this study was to examine both genetic background and age dependent effects on oral nicotine self-administration and anxiety-like behaviors in mice. Two inbred mouse strains (C3H/Ibg and C57BL/6J) were assessed for oral nicotine preference during early adolescence (postnatal day 24-35), middle adolescence (postnatal day 36-47), late adolescence (postnatal day 48-59), adulthood (postnatal day 60+) and 2 months following their initial exposure to nicotine. Mice also were assessed for innate anxiety using an elevated zero maze to determine if age and/or genetic background influenced anxiety-like behaviors. Results indicated that initial nicotine preference and nicotine preference two months after an initial exposure are both strain and age dependent. Age also had an effect on some baseline anxiety measures but strain differences for most zero maze measures were present throughout all age groups. In general, early adolescent C3H mice exhibited greater nicotine preference while C57 mice displayed greater preference during middle adolescence and upon a second exposure to nicotine. In contrast, C57 mice exhibited reduced anxiety across all ages tested. These studies indicate that genetic background should be considered when evaluating age-dependent effects of drugs of abuse and baseline anxiety-like behaviors., (Copyright © 2012 Elsevier B.V. All rights reserved.)