Neurobiology of Positive Emotion Disruption in Neurodegenerative Disease

Alterations in emotion are common in neurodegenerative disease. Although often associated with diminished functioning, neurodegeneration of emotion circuits can lead to both losses and gains in a range of emotional functions, including reactivity, regulation, appraisal, and empathy. Most previous research in this area has focused on the impact of neurodegeneration on negative emotions; however, there has recently been increasing interest in the degree to which neurodegenerative diseases may also alter positive emotions. This chapter reviews how different neurodegenerative diseases (e.g., frontotemporal dementia, amyotrophic lateral sclerosis, and Alzheimer’s disease) impact positive emotions and the neural basis of positive emotion alterations. We will also discuss how decreases and increases in positive emotional reactivity can lead to specific behavioral symptoms in neurodegenerative disease and can impact patients’ family members and caregivers

Emotional and behavioral symptoms in neurodegenerative disease: a model for studying the neural bases of psychopathology.

Disruptions in emotional, cognitive, and social behavior are common in neurodegenerative disease and in many forms of psychopathology. Because neurodegenerative diseases have patterns of brain atrophy that are much clearer than those of psychiatric disorders, they may provide a window into the neural bases of common emotional and behavioral symptoms. We discuss five common symptoms that occur in both neurodegenerative disease and psychopathology (i.e., anxiety, dysphoric mood, apathy, disinhibition, and euphoric mood) and their associated neural circuitry. We focus on two neurodegenerative diseases (i.e., Alzheimer's disease and frontotemporal dementia) that are common and well characterized in terms of emotion, cognition, and social behavior and in patterns of associated atrophy. Neurodegenerative diseases provide a powerful model system for studying the neural correlates of psychopathological symptoms; this is supported by evidence indicating convergence with psychiatric syndromes (e.g., symptoms of disinhibition associated with dysfunction in orbitofrontal cortex in both frontotemporal dementia and bipolar disorder). We conclude that neurodegenerative diseases can play an important role in future approaches to the assessment, prevention, and treatment of mental illness

Authenticity and brain health: a values-based perspective and cultural education approach

This perspective paper discusses the concept of authenticity in relation to brain health and neurodegenerative diseases. We define authenticity as being true to oneself and consider it a social value of relevance to neuroscientists, clinicians, and caregivers. From a biological perspective, behaviors that can be interpreted as expressions of authenticity are produced by distributed brain networks. By understanding it as a dynamic process, we argue that harnessing authenticity across the lifespan can be protective by promoting resilience. We discuss the idea of authentic aging, which appreciates the complexity of human life within the world and can enhance positive views of later life. Authenticity is additionally applicable to caring for people with neurodegenerative diseases, both when understanding the behavior of people with dementia and the response of caregivers. Tailoring care to an individual’s personality and strengths may improve their brain health. Finally, we describe an interdisciplinary learning event, themed around masks, designed to engage participants in identifying authenticity in their own work. For scientists, care professionals, and caregivers, reflecting upon authenticity can aid understanding of the person with dementia and therefore improve care

Early affective changes and increased connectivity in preclinical Alzheimer's disease.

IntroductionAffective 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.MethodsOne 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.ResultsIn 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.ConclusionsAffective 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

Neuroanatomy of expressive suppression: The role of the insula.

Expressive suppression is a response-focused regulatory strategy aimed at concealing the outward expression of emotion that is already underway. Expressive suppression requires the integration of interoception, proprioception, and social awareness to guide behavior in alignment with personal and interpersonal goals-all processes known to involve the insular cortex. Frontotemporal dementia (FTD) provides a useful patient model for studying the insula's role in socioemotional regulation. The insula is a key target of early atrophy in FTD, causing patients to lose the ability to represent the salience of internal and external conditions and to use these representations to guide behavior. We examined a sample of 59 patients with FTD, 52 patients with Alzheimer's disease (AD), and 38 neurologically healthy controls. Subjects viewed 2 disgust-eliciting films in the laboratory. During the first film, subjects were instructed to simply watch (emotional reactivity trial); during the second, they were instructed to hide their emotions (expressive suppression trial). Structural images from a subsample of participants (n = 42; 11 FTD patients, 11 AD patients, and 20 controls) were examined in conjunction with behavior. FreeSurfer was used to quantify regional gray matter volume in 41 empirically derived neural regions in both hemispheres. Of the 3 groups studied, FTD patients showed the least expressive suppression and had the smallest insula volumes, even after controlling for age, gender, and emotional reactivity. Among the brain regions examined, the insula was the only significant predictor of expressive suppression ability, with lower insula gray matter volume in both hemispheres predicting less expressive suppression. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

The 5-HTTLPR variant in the serotonin transporter gene modifies degeneration of brain regions important for emotion in behavioral variant frontotemporal dementia

AbstractThe serotonin transporter length polymorphism (5-HTTLPR) short allele (5-HTTLPR-s) has been associated with differential susceptibility for anxiety and depression in multiple psychiatric disorders. 5-HTTLPR-s modifies the serotonergic systems that support emotion and behavioral regulation by reducing gene expression, which slows the reuptake of serotonin, and is associated with distinct morphological and functional effects. Serotonergic systems are also shown to be dysfunctional in behavioral variant frontotemporal dementia (bvFTD), a disease characterized by marked socioemotional dysfunction. However, studies of 5-HTTLPR-s effects in bvFTD have been inconsistent. Our objective was to investigate the patterns of gray matter volume by 5-HTTLPR-s genotype in both healthy older controls and bvFTD patients. We performed voxel-based morphometry of 179 cognitively normal older adults and 24 bvFTD cases to determine brain changes associated with dose (0/1/2) of 5-HTTLPR-s allele. 5-HTTLPR-s frequency did not differ between controls and bvFTD. We found a significant interaction effect whereby carrying more 5-HTTLPR-s alleles in bvFTD was associated with smaller volume in left inferior frontal gyrus (T = 4.86, PFWE = 0.03) and larger volume in right temporal lobe (T = 5.01, PFWE = 0.01). These results suggest that the 5-HTTLPR-s allele differentially influences brain morphology in bvFTD. We propose that patients with bvFTD and 5-HTTLPR-s have altered volumes in regions that support socioemotional behavior, which may be a developmental or disease-related compensation for altered serotonergic activity

Emotion recognition in frontotemporal dementia and Alzheimer's disease: A new film-based assessment.

Deficits in recognizing others' emotions are reported in many psychiatric and neurological disorders, including autism, schizophrenia, behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). Most previous emotion recognition studies have required participants to identify emotional expressions in photographs. This type of assessment differs from real-world emotion recognition in important ways: Images are static rather than dynamic, include only 1 modality of emotional information (i.e., visual information), and are presented absent a social context. Additionally, existing emotion recognition batteries typically include multiple negative emotions, but only 1 positive emotion (i.e., happiness) and no self-conscious emotions (e.g., embarrassment). We present initial results using a new task for assessing emotion recognition that was developed to address these limitations. In this task, respondents view a series of short film clips and are asked to identify the main characters' emotions. The task assesses multiple negative, positive, and self-conscious emotions based on information that is multimodal, dynamic, and socially embedded. We evaluate this approach in a sample of patients with bvFTD, AD, and normal controls. Results indicate that patients with bvFTD have emotion recognition deficits in all 3 categories of emotion compared to the other groups. These deficits were especially pronounced for negative and self-conscious emotions. Emotion recognition in this sample of patients with AD was indistinguishable from controls. These findings underscore the utility of this approach to assessing emotion recognition and suggest that previous findings that recognition of positive emotion was preserved in dementia patients may have resulted from the limited sampling of positive emotion in traditional tests

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

Comparing two facets of emotion perception across multiple neurodegenerative diseases.

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