Specialization of amygdala subregions in emotion processing.

The amygdala is important for human fear processing. However, recent research has failed to reveal specificity, with evidence that the amygdala also responds to other emotions. A more nuanced understanding of the amygdala's role in emotion processing, particularly relating to fear, is needed given the importance of effective emotional functioning for everyday function and mental health. We studied 86 healthy participants (44 females), aged 18-49 (mean 26.12 ± 6.6) years, who underwent multiband functional magnetic resonance imaging. We specifically examined the reactivity of four amygdala subregions (using regions of interest analysis) and related brain connectivity networks (using generalized psycho-physiological interaction) to fear, angry, and happy facial stimuli using an emotional face-matching task. All amygdala subregions responded to all stimuli (p-FDR < .05), with this reactivity strongly driven by the superficial and centromedial amygdala (p-FDR < .001). Yet amygdala subregions selectively showed strong functional connectivity with other occipitotemporal and inferior frontal brain regions with particular sensitivity to fear recognition and strongly driven by the basolateral amygdala (p-FDR < .05). These findings suggest that amygdala specialization to fear may not be reflected in its local activity but in its connectivity with other brain regions within a specific face-processing network.

Cannabis Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. Methods: We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). Results: We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (p<0.001, d=0.32) and with controls (p=0.022, d=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (p=0.002, d=0.37, and p=0.002, d=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. Conclusions: Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.

Cerebrovascular Responses in a Patient with Lundberg B Waves Following Subarachnoid Haemorrhage Assessed with a Novel Non-Invasive Brain Pulse Monitor: A Case Report.

Subarachnoid haemorrhage (SAH) can trigger a range of poorly understood cerebrovascular responses that may play a role in delayed cerebral ischemia. The brain pulse monitor is a novel non-invasive device that detects a brain photoplethysmography signal that provides information on intracranial pressure (ICP), compliance, blood flow and tissue oxygen saturation. We monitored the cerebrovascular responses in a patient with Lundberg B waves following a SAH. The patient presented with a Fischer grade 4 SAH that required urgent left posterior communicating artery aneurysm coiling and ventricular drain insertion. On hospital day 4 oscillations or spikes on the invasive ICP were noted, consistent with Lundberg B waves. Brain pulse monitoring demonstrated concurrent pulse waveform features consistent with reduced brain compliance and raised ICP over both brain hemispheres. Oxygen levels also demonstrated slow oscillations correlated with the ICP spikes. Brief infrequent episodes of reduced and absent brain pulses were also noted over the right hemisphere. Our findings suggest that the brain pulse monitor holds promise for early detection of delayed cerebral ischemia and could offer insights into the vascular mechanisms at play.

Assessment of a Non-Invasive Brain Pulse Monitor to Measure Intra-Cranial Pressure Following Acute Brain Injury.

Background: Intracranial pressure (ICP) monitoring requires placing a hole in the skull through which an invasive pressure monitor is inserted into the brain. This approach has risks for the patient and is expensive. We have developed a non-invasive brain pulse monitor that uses red light to detect a photoplethysmographic (PPG) signal arising from the blood vessels on the brain's cortical surface. The brain PPG and the invasive ICP waveform share morphological features which may allow measurement of the intracranial pressure. Methods: We enrolled critically ill patients with an acute brain injury with invasive ICP monitoring to assess the new monitor. A total of 24 simultaneous invasive ICP and brain pulse monitor PPG measurements were undertaken in 12 patients over a range of ICP levels. Results: The waveform morphologies were similar for the invasive ICP and brain pulse monitor PPG approach. Both methods demonstrated a progressive increase in the amplitude of P2 relative to P1 with increasing ICP levels. An automated algorithm was developed to assess the PPG morphological features in relation to the ICP level. A correlation was demonstrated between the brain pulse waveform morphology and ICP levels, R2=0.66, P < 0.001. Conclusion: The brain pulse monitor's PPG waveform demonstrated morphological features were similar to the invasive ICP waveform over a range of ICP levels, these features may provide a method to measure ICP levels. Trial Registration: ACTRN12620000828921.

The effect of psychological treatment on repetitive negative thinking in youth depression and anxiety: a meta-analysis and meta-regression.

BACKGROUND: Depression and anxiety are prevalent in youth populations and typically emerge during adolescence. Repetitive negative thinking (RNT) is a putative transdiagnostic mechanism with consistent associations with depression and anxiety. Targeting transdiagnostic processes like RNT for youth depression and anxiety may offer more targeted, personalised and effective treatment. METHODS: A meta-analysis was conducted to examine the effect of psychological treatments on RNT, depression and anxiety symptoms in young people with depression or anxiety, and a meta-regression to examine relationships between outcomes. RESULTS: Twenty-eight randomised controlled trials examining 17 different psychological interventions were included. Effect sizes were small to moderate across all outcomes (Hedge's g depression = -0.47, CI -0.77 to -0.17; anxiety = -0.42, CI -0.65 to -0.20; RNT = -0.45, CI -0.67 to -0.23). RNT-focused and non-RNT focused approaches had comparable effects; however, those focusing on modifying the process of RNT had significantly larger effects on RNT than those focusing on modifying negative thought content. Meta-regression revealed a significant relationship between RNT and depression outcomes only across all intervention types and with both depression and anxiety for RNT focused interventions only. CONCLUSION: Consistent with findings in adults, this review provides evidence that reducing RNT with psychological treatment is associated with improvements in depression and anxiety in youth. Targeting RNT specifically may not lead to better outcomes compared to general approaches; however, focusing on modifying the process of RNT may be more effective than targeting content. Further research is needed to determine causal pathways.

Childhood maltreatment and trauma is common and severe in body dysmorphic disorder.

BACKGROUND: Childhood maltreatment and trauma may be risk factors for the development of body dysmorphic disorder (BDD). However, the limited research to date on these topics has been constrained by either the absence of a matched healthy control group or non-comprehensive assessments. METHODS: This study assessed the prevalence and severity of childhood maltreatment and other traumatic events in 52 BDD participants (56% female) and 57 matched controls (51% female) with no history of mental illness, using the Childhood Trauma Questionnaire and a checklist assessing broader traumatic events. RESULTS: In comparison with controls, participants with BDD showed a higher prevalence of emotional abuse (61.5% vs. 33.3%) and physical neglect (59.6% vs. 28.1%), as well as more severe overall maltreatment, emotional abuse, and emotional and physical neglect. BDD participants were also more likely to meet cut-offs for multiple types of maltreatment and reported an elevated number and variety of broader traumatic childhood events (e.g., life-threatening illness). In BDD, increasingly severe maltreatment was correlated with greater severity of BDD symptoms, anxiety and suicidal ideation. CONCLUSIONS: These data suggest that childhood maltreatment and exposure to other traumatic events are common and severe in BDD and are cross-sectionally associated with the severity of clinical symptoms. Adversity linked to maladaptive family functioning during childhood may therefore be especially relevant to people with BDD and could relate to social and emotional processing problems in the disorder.

Sex differences in the neuroanatomy of alcohol dependence: hippocampus and amygdala subregions in a sample of 966 people from the ENIGMA Addiction Working Group.

Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We examined hippocampal and amygdala subregions in a large sample of 966 people from the ENIGMA Addiction Working Group. This comprised 643 people with alcohol dependence (225 females), and a comparison group of 323 people without alcohol dependence (98 females). Males with alcohol dependence had smaller volumes of the total amygdala and its basolateral nucleus than male controls, that exacerbated with alcohol dose. Alcohol dependence was also associated with smaller volumes of the hippocampus and its CA1 and subiculum subfield volumes in both males and females. In summary, hippocampal and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females.

Empirical evidence for cognitive subgroups in body dysmorphic disorder.

OBJECTIVE: Current understanding of cognitive functioning in body dysmorphic disorder is limited, owing to few studies, small sample sizes and assessment across only limited cognitive domains. Existing research has also shown inconsistent findings, with both intact and impaired cognition reported in body dysmorphic disorder, which might point towards cognitive heterogeneity in the disorder. This study aimed to examine the cognitive profile of body dysmorphic disorder in a large sample across eight cognitive domains, and to explore whether cognitive subgroups might be identified within body dysmorphic disorder. METHOD: Cognitive domains of inhibition/flexibility, working memory, speed of processing, reasoning and problem-solving, visual and verbal learning, attention/vigilance and social cognition were assessed and compared between 65 body dysmorphic disorder patients and 70 healthy controls. Then, hierarchical clustering analysis was conducted on the body dysmorphic disorder group's cognitive data. RESULTS: Group-average comparisons demonstrated significantly poorer cognitive functioning in body dysmorphic disorder than healthy controls in all domains except for attention/vigilance and social cognition. Cluster analysis identified two divergent cognitive subgroups within our body dysmorphic disorder cohort characterised by (1) broadly intact cognitive function with mild selective impairments (72.3%), and (2) broadly impaired cognitive function (27.7%). However, the clusters did not significantly differ on clinical parameters or most sociodemographic characteristics. CONCLUSION: Our findings demonstrate considerable cognitive heterogeneity among persons with body dysmorphic disorder, rather than uniform deficits. Poor performances in the broadly impaired subgroup may have driven group-level differences. However, our findings also suggest a dissociation between cognitive functioning and clinical characteristics in body dysmorphic disorder that has implications for current aetiological models. Additional research is needed to clarify why some people with body dysmorphic disorder demonstrate cognitive deficits while others do not.

Advances in the field of intranasal oxytocin research: lessons learned and future directions for clinical research.

Reports on the modulatory role of the neuropeptide oxytocin on social cognition and behavior have steadily increased over the last two decades, stimulating considerable interest in its psychiatric application. Basic and clinical research in humans primarily employs intranasal application protocols. This approach assumes that intranasal administration increases oxytocin levels in the central nervous system via a direct nose-to-brain route, which in turn acts upon centrally-located oxytocin receptors to exert its behavioral effects. However, debates have emerged on whether intranasally administered oxytocin enters the brain via the nose-to-brain route and whether this route leads to functionally relevant increases in central oxytocin levels. In this review we outline recent advances from human and animal research that provide converging evidence for functionally relevant effects of the intranasal oxytocin administration route, suggesting that direct nose-to-brain delivery underlies the behavioral effects of oxytocin on social cognition and behavior. Moreover, advances in previously debated methodological issues, such as pre-registration, reproducibility, statistical power, interpretation of non-significant results, dosage, and sex differences are discussed and integrated with suggestions for the next steps in translating intranasal oxytocin into psychiatric applications.

The influence of COMT rs4680 on functional connectivity in healthy adults: A systematic review.

The aim of this systematic review was to qualitatively synthesise the available research that investigated the influence of COMT genotype at SNP rs4680 on both task-based and resting-state connectivity in healthy adults. Thirty-five studies were identified that met inclusion criteria. Of the included studies, 20 studies reported resting-state findings and 16 studies reported task-based findings (emotion-processing, memory, working memory, reward-based learning and executive function). Studies were highly heterogeneous but an overall trend towards an association of the Val allele with greater resting-state connectivity and the Met allele with greater task-based connectivity is reported. A possible interpretation of current findings is discussed, whereby the Val allele is associated with improved cognitive flexibility allowing integration of novel relevant stimuli, and the Met allele allows improved sustained attention and targeted neural processing, particularly between limbic regions and prefrontal cortex. The most promising brain regions implicated in a COMT genotype influence on functional connectivity include prefrontal regions, amygdala and hippocampus.

Body parts of clinical concern in anorexia nervosa versus body dysmorphic disorder: a cross-diagnostic comparison.

OBJECTIVES: Anorexia nervosa and body dysmorphic disorder share a hallmark clinical feature of severe body image disturbance. This study aimed to document major demographic and clinical characteristics in anorexia nervosa versus body dysmorphic disorder, and it was the first to compare specific body parts related to body image dissatisfaction across these disorders directly. METHODS: Anorexia nervosa (n=26) and body dysmorphic disorder (n=24) patients were administered a range of clinical measures, including key questions about the specificities of their body image concerns. RESULTS: Results revealed increased psychiatric and personality co-morbidities in anorexia nervosa relative to body dysmorphic disorder. The anorexia nervosa group was mostly preoccupied with three body zones typically linked to weight concerns, whereas the body dysmorphic disorder group fixated on facial features, hair and skin. CONCLUSIONS: These findings may help inform differential diagnosis in complex cases and aid in the formulation of targeted interventions.

Intranasal oxytocin alters amygdala-temporal resting-state functional connectivity in body dysmorphic disorder: A double-blind placebo-controlled randomized trial.

The aetiology of body dysmorphic disorder (BDD) is poorly understood. Recent evidence from functional brain imaging studies suggests that BDD is associated with aberrant task-based functional connectivity and that intranasal oxytocin (OXT) may improve network connectivity in BDD patients. Thus, the aim of this study was to investigate the effect of intranasal OXT on amygdala resting-state functional connectivity (rsFC) in BDD. In a randomized, double-blind, cross-over design, 19 BDD participants and 17 demographically matched healthy control participants received intranasal OXT (24 IU) or placebo prior to resting-state functional magnetic resonance imaging. The left and right amygdala were seeded as regions of interest, and temporal correlations between the amygdalae and all other voxels comprising cortical and subcortical grey matter were investigated. Compared to healthy controls, BDD patients showed greater baseline (placebo) rsFC between the left amygdala and two clusters within the left temporal lobe and one cluster within the superior frontal gyrus which was reversed following OXT administration. The control group also showed significantly greater rsFC between the left amygdala and anterior prefrontal cortex in the OXT session compared to placebo. Whilst preliminary, these findings suggest that BDD patients exhibit abnormal amygdala-temporal connectivity at rest, and OXT might have a role in changing this functional relationship.

Impaired Recognition of Negative Facial Emotions in Body Dysmorphic Disorder.

OBJECTIVES: Patients with body dysmorphic disorder (BDD) have difficulty in recognising facial emotions, and there is evidence to suggest that there is a specific deficit in identifying negative facial emotions, such as sadness and anger. METHODS: This study investigated facial emotion recognition in 19 individuals with BDD compared with 21 healthy control participants who completed a facial emotion recognition task, in which they were asked to identify emotional expressions portrayed in neutral, happy, sad, fearful, or angry faces. RESULTS: Compared to the healthy control participants, the BDD patients were generally less accurate in identifying all facial emotions but showed specific deficits for negative emotions. The BDD group made significantly more errors when identifying neutral, angry, and sad faces than healthy controls; and were significantly slower at identifying neutral, angry, and happy faces. CONCLUSIONS: These findings add to previous face-processing literature in BDD, suggesting deficits in identifying negative facial emotions. There are treatment implications as future interventions would do well to target such deficits.

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.

The neurobiology of body dysmorphic disorder: A systematic review and theoretical model.

There has been an increase in neuroimaging research in body dysmorphic disorder (BDD), yet little is known about the underlying neurobiological basis of the disorder. We aimed to provide a systematic overview of the literature on the neurobiology of BDD. Two reviewers undertook a search of three electronic research databases: PubMed, PsycINFO, and Google Scholar. The search consisted of synonyms commonly associated with BDD and methods to evaluate brain structure, function, and network organisation. Out of an initial yield of 175 articles, 19 fulfilled inclusion criteria and were reviewed. We identified differences in brain activity, structure, and connectivity in BDD participants in frontostriatal, limbic, and visual system regions when compared to healthy control and other clinical groups. We put forth a neurobiological model of BDD pathophysiology that involves wide-spread disorganisation in neural networks involved in cognitive control and the interpretation of visual and emotional information. This review considers how this model might aid in the development of future research and understanding of BDD.

Reduced cortical thickness in body dysmorphic disorder.

Recent neuroimaging studies in body dysmorphic disorder (BDD) have implicated abnormal structure and function of occipito-temporal and fronto-limbic regions in the potential pathophysiology of the disorder. To date, morphometric investigations have yielded inconsistent results, and have suggested that clinical symptoms may mediate structural brain abnormalities in BDD. We measured Grey Matter (GM) cortical thickness in 20 participants with BDD and 20 healthy control participants matched on age, gender, estimated IQ and handedness. We observed cortical thinning in BDD patients compared with healthy control participants within the left middle temporal and left inferior parietal gyrus. No significant relationships between cortical thickness and BDD symptom severity, insight, social anxiety and depression were observed within the BDD group. Thinning within left temporal and left inferior parietal regions supports the involvement of these regions in the pathophysiology of BDD.