Abnormal visual scanning of emotionally evocative natural scenes in Huntington's disease

Huntington’s disease (HD) is a neurodegenerative movement disorder associated with deficits in the processing of emotional stimuli, including alterations in the self-reported subjective experience of emotion when presented with pictures of emotional scenes. The aim of this study was to determine whether individuals with HD, compared to unaffected controls, display abnormal visual scanning of emotionally evocative natural scenes. Using eye-tracking, we recorded eye-movements of 25 HD participants (advanced pre-symptomatic and early symptomatic) and 25 age-matched unaffected control participants during a picture viewing task. Participants viewed pictures of natural scenes associated with different emotions: anger, fear, disgust, happiness, or neutral, and evaluated those pictures on a valence rating scale. Individuals with HD displayed abnormal visual scanning patterns, but did not differ from controls with respect to their valence ratings. Specifically, compared to controls, HD participants spent less time fixating on the pictures and made longer scan paths. This finding highlights the importance of taking visual scanning behavior into account when investigating emotion processing in HD. The visual scanning patterns displayed by HD participants could reflect a heightened, but possibly unfocussed, search for information, and might be linked to attentional deficits or to altered subjective emotional experiences in HD. Another possibility is that HD participants may have found it more difficult than controls to evaluate the emotional valence of the scenes, and the heightened search for information was employed as a compensatory strategy

Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study

Background: Hypothalamic pathology is a well-documented feature of Huntington's disease (HD) and is believed to contribute to circadian rhythm and habitual sleep disturbances. Currently, no therapies exist to combat hypothalamic changes, nor circadian rhythm and habitual sleep disturbances in HD. Objective: To evaluate the effects of multidisciplinary rehabilitation on hypothalamic volume, brain-derived neurotrophic factor (BDNF), circadian rhythm and habitual sleep in individuals with preclinical HD. Methods: Eighteen individuals with HD (ten premanifest and eight prodromal) undertook a nine-month multidisciplinary rehabilitation intervention (intervention group), which included exercise, cognitive and dual task training and social events, and were compared to a community sample of eleven individuals with premanifest HD receiving no intervention (control group). Hypothalamic volume, serum BDNF, salivary cortisol and melatonin concentrations, subjective sleep quality, daytime somnolence, habitual sleep-wake patterns, stress and anxiety and depression symptomatology were evaluated. Results: Hypothalamus grey matter volume loss was significantly attenuated in the intervention group compared to the control group after controlling for age, gender, Unified Huntington's Disease Rating Scale-Total Motor Score and number of cytosine-adenine-guanine repeats. Serum BDNF levels were maintained in the intervention group, but decreased in the control group following the study period. Both groups exhibited decreases in cortisol and melatonin concentrations. No changes were observed in sleep or mood outcomes. Conclusions: This exploratory study provides evidence that multidisciplinary rehabilitation can reduce hypothalamic volume loss and maintain peripheral BDNF levels in individuals with preclinical HD but may not impact on circadian rhythm. Larger, randomised controlled trials are required to confirm these findings

Beyond emotion recognition deficits: A theory guided analysis of emotion processing in Huntington's disease

Deficits in facial emotion recognition in Huntington’s disease (HD) have been extensively researched, however, a theory-based integration of these deficits into the broader picture of emotion processing is lacking. To describe the full extent of emotion processing deficits we reviewed the clinical research literature in HD, including a consideration of research in Parkinson’s disease, guided by a theoretical model on emotion processing, the Component Process Model. Further, to contribute to understanding the mechanisms underlying deficient emotion recognition, we discussed the literature in light of specific emotion recognition theories. Current evidence from HD studies indicates deficits in the production of emotional facial expressions and alterations in subjective emotional experiences, in addition to emotion recognition deficits. Conceptual understanding of emotions remains relatively intact. Impaired recognition and expression of emotion in HD might be linked, whereas altered emotional experiences appear to be unrelated to emotion recognition. A key implication of this review is the need to take all the components of emotion processing into account to understand specific deficits in neurodegenerative diseases

Visual scanning of the eye region of human faces predicts emotion recognition performance in Huntington's disease

Objective: Previous research has consistently shown that the ability to recognize emotions from facial expressions is impaired in Huntington’s disease (HD). The aim of this study was to examine whether people with the gene expansion for HD visually scan the most emotionally informative features of human faces less than unaffected individuals, and whether altered visual scanning predicts emotion recognition in HD beyond general disease-related decline. Method: We recorded eye movements of 25 participants either in the late premanifest or early stage of HD and 25 age-matched healthy control participants during a face-viewing task. The task involved the viewing of pictures depicting human faces with angry, disgusted, fearful, happy, and neutral expressions, and evaluating each face on a valence rating scale. For data analysis, we defined 2 regions of interest (ROIs) on each picture, including an eye-ROI and a nose/mouth-ROI. Emotion recognition abilities were measured using an established emotion-recognition task and general disease-related decline was measured using the UHDRS motor score. Results: Compared to the control participants, the HD participants spent less time looking at the ROIs relative to the total time spent looking at the pictures (partial η2 = 0.10), and made fewer fixations on the ROIs (partial η2 = 0.16). Furthermore, visual scanning of the eye-ROI, but not the nose/mouth-ROI, predicted emotion recognition performance in the HD group, over and beyond general disease-related decline. Conclusion: The emotion recognition deficit in HD may partly be explained by general disease-related decline in cognition and motor functioning and partly by a social-emotional deficit, which is reflected in reduced eye-viewing

Diminished facial EMG responses to disgusting scenes and happy and fearful faces in Huntington's disease

Huntington's disease (HD) is a neurodegenerative disorder associated with impaired facial emotion recognition and altered subjective experience of emotion. These impairments likely result from the effects of the disease on underlying neurobiological mechanisms. Studies using self-report to examine emotional experiences have been ambiguous regarding whether experiences are diminished or exaggerated, possibly due to cognitive impairment and lack of insight in HD. To infer affective states more objectively and overcome the limitations of self-report, we used facial EMG to measure muscle responses to emotionally-evocative scenes. Further, we examined muscle responses to emotionally-expressive faces, because facial mimicry is thought to facilitate emotion recognition and social affiliation. Twenty-three HD participants (late pre-manifest and early symptomatic) were compared to twenty-five healthy controls in a scene condition and a face condition. EMG activity was measured from facial muscles associated with expressing particular emotions: 1) corrugator supercilii for anger, 2) frontalis for fear, 3) levator labii for disgust, and 4) both zygomaticus major and orbicularis oculi for happiness. Compared to controls, HD participants showed diminished responses to disgusting scenes, and to happy and fearful faces. Our findings provide evidence for a loss of disgust experience in HD. Further, consistent with the alleged affiliative function of facial mimicry, diminished mimicry responses may be relevant to social-emotional changes in HD. Our findings help understand the neural mechanisms underlying emotion processing impairments in HD

Oxytocin and brain activity in humans: A systematic review and coordinate-based meta-analysis of functional MRI studies

Oxytocin (OXT) is a neuropeptide which has a critical role in human social behaviour and cognition. Research investigating the role of OXT on functional brain changes in humans has often used task paradigms that probe socioemotional processes. Preliminary evidence suggests a central role of the amygdala in the social cognitive effects of intranasal OXT (IN-OXT), however, inconsistencies in task-design and analysis methods have led to inconclusive findings regarding a cohesive model of the neural mechanisms underlying OXT’s actions. The aim of this meta-analysis was to systematically investigate these findings. A systematic search of PubMed, PsycINFO, and Scopus databases was conducted for fMRI studies which compared IN-OXT to placebo in humans. First, we systematically reviewed functional magnetic resonance imaging (fMRI) studies of IN-OXT, including studies of healthy humans, those with clinical disorders, and studies examining resting-state fMRI (rsfMRI). Second, we employed a coordinate-based meta-analysis for task-based neuroimaging literature using activation likelihood estimation (ALE), whereby, coordinates were extracted from clusters with significant differences in IN-OXT versus placebo in healthy adults. Data were included for 39 fMRI studies that reported a total of 374 distinct foci. The meta-analysis identified task-related IN-OXT increases in activity within a cluster of the left superior temporal gyrus during tasks of emotion processing. These findings are important as they implicate regions beyond the amygdala in the neural effects of IN-OXT. The outcomes from this meta-analysis can guide a priori predictions for future OXT research, and provide an avenue for targeted treatment interventions

Oxytocin selectively modulates brain processing of disgust in Huntington's disease gene carriers

People with Huntington's disease (HD) exhibit altered processing of emotional information, especially disgust and other negative emotions. These impairments are likely due to the effects of the disease on underlying brain networks. We examined whether oxytocin, when given intranasally, would normalise aberrant brain reactivity to emotional faces in participants with the gene-expansion for HD. In a double-blind placebo-controlled cross-over design, we measured brain activity, using functional magnetic resonance imaging, whilst nine medication-free HD carriers, and ten control participants viewed emotional (disgust, fear, angry, sad, surprise, happy) and neutral faces, following acute intranasal oxytocin (24 IU) and placebo. Subjective mood changes were assessed before and after the neuroimaging on each visit. Permutation-based non-parametric statistical testing for the whole brain, showed significant group × drug interactions (p's < 0.05, TFCE corrected) in areas of the left frontal pole, superior frontal, and middle frontal gyri cortically, and left putamen and thalamus sub-cortically. Parameter estimates extracted from the middle frontal gyrus and putamen showed that, under placebo, the HD group had lower brain activity to disgust stimuli, compared with controls. After intranasal oxytocin, the pattern of activation to disgust stimuli was normalised in the HD group to similar levels as controls; eight of the nine HD carriers showed increased response in the middle frontal gyrus, and seven of the nine HD carriers showed increased response in the putamen. The observed effects of oxytocin occurred in the absence of changes in subjective mood or state anxiety. These findings provide early evidence for a physiological role of oxytocin in the neuropathology of HD. Our findings are the first reported oxytocin effects in a neurodegenerative disease. Further research should examine the therapeutic benefits of oxytocin in alleviating emotional and social cognition deficits in HD and related disorders

Oxytocin selectively modulates brain processing of disgust in Huntington's disease gene carriers

People with Huntington's disease (HD) exhibit altered processing of emotional information, especially disgust and other negative emotions. These impairments are likely due to the effects of the disease on underlying brain networks. We examined whether oxytocin, when given intranasally, would normalise aberrant brain reactivity to emotional faces in participants with the gene-expansion for HD. In a double-blind placebo-controlled cross-over design, we measured brain activity, using functional magnetic resonance imaging, whilst nine medication-free HD carriers, and ten control participants viewed emotional (disgust, fear, angry, sad, surprise, happy) and neutral faces, following acute intranasal oxytocin (24 IU) and placebo. Subjective mood changes were assessed before and after the neuroimaging on each visit. Permutation-based non-parametric statistical testing for the whole brain, showed significant group × drug interactions (p's < 0.05, TFCE corrected) in areas of the left frontal pole, superior frontal, and middle frontal gyri cortically, and left putamen and thalamus sub-cortically. Parameter estimates extracted from the middle frontal gyrus and putamen showed that, under placebo, the HD group had lower brain activity to disgust stimuli, compared with controls. After intranasal oxytocin, the pattern of activation to disgust stimuli was normalised in the HD group to similar levels as controls; eight of the nine HD carriers showed increased response in the middle frontal gyrus, and seven of the nine HD carriers showed increased response in the putamen. The observed effects of oxytocin occurred in the absence of changes in subjective mood or state anxiety. These findings provide early evidence for a physiological role of oxytocin in the neuropathology of HD. Our findings are the first reported oxytocin effects in a neurodegenerative disease. Further research should examine the therapeutic benefits of oxytocin in alleviating emotional and social cognition deficits in HD and related disorders