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.

Resting-state neuroimaging in social anxiety disorder: a systematic review.

There has been a growing interest in resting-state brain alterations in people with social anxiety disorder. However, the evidence has been mixed and contested and further understanding of the neurobiology of this disorder may aid in informing methods to increase diagnostic accuracy and treatment targets. With this systematic review, we aimed to synthesize the findings of the neuroimaging literature on resting-state functional activity and connectivity in social anxiety disorder, and to summarize associations between brain and social anxiety symptoms to further characterize the neurobiology of the disorder. We systematically searched seven databases for empirical research studies. Thirty-five studies met the inclusion criteria, with a total of 1611 participants (795 people with social anxiety disorder and 816 controls). Studies involving resting-state seed-based functional connectivity analyses were the most common. Individuals with social anxiety disorder (vs. controls) displayed both higher and lower connectivity between frontal-amygdala and frontal-parietal regions. Frontal regions were the most consistently implicated across other analysis methods, and most associated with social anxiety symptoms. Small sample sizes and variation in the types of analyses used across studies may have contributed to the inconsistencies in the findings of this review. This review provides novel insights into established neurobiological models of social anxiety disorder and provides an update on what is known about the neurobiology of this disorder in the absence of any overt tasks (i.e., resting state). The knowledge gained from this body of research enabled us to also provide recommendations for a more standardized imaging pre-processing approach to examine resting-state brain activity and connectivity that could help advance knowledge in this field. We believe this is warranted to take the next step toward clinical translation in social anxiety disorder that may lead to better treatment outcomes by informing the identification of neurobiological targets for treatment.

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.

Age Differences in Emotion Regulation and Facial Muscle Reactivity to Emotional Films.

BACKGROUND: Age-related declines in many cognitive abilities are common in healthy aging. However, the ability to effectively regulate emotions is preserved, and possibly even enhanced, in late adulthood. This capacity has been examined most commonly in relation to low-intensity emotional stimuli that typically involve static pictures. Evidence is suggesting that older adults may become overwhelmed when exposed to emotional cues of heightened intensity. OBJECTIVE: In the current study, we assessed whether older adults retain the ability to regulate emotions successfully when exposed to more emotionally evocative (e.g., dynamic) stimuli. METHODS: Young and older adults were instructed to regulate, using expressive suppression, their outward behavioral expression of emotions while viewing dynamic stimuli involving amusing and sad films. Facial reactivity, as indexed using electromyography, self-rated emotional experience, and memory for the stimuli were assessed. RESULTS: The results showed that, relative to young adults, older adults were unable to suppress zygomaticus (cheek) activity to amusing films or corrugator (brow) reactivity to sad films, which is likely due to their relatively reduced facial muscle reactivity. Expressive suppression did not affect young or older adults' subjective feelings or memory for the stimuli. CONCLUSION: Our findings suggest that there are age differences in facial muscle reactivity to amusing and sad cues of heightened intensity. These findings suggest that older adults' ability to effectively regulate emotions may be limited, at least with expressive suppression, in the context of high-intensity emotional cues. Further research is needed to investigate possible exceptions the preservation of emotion regulation in older adults.

Apathy Associated With Impaired Recognition of Happy Facial Expressions in Huntington's Disease.

OBJECTIVES: Previous research has demonstrated an association between emotion recognition and apathy in several neurological conditions involving fronto-striatal pathology, including Parkinson's disease and brain injury. In line with these findings, we aimed to determine whether apathetic participants with early Huntington's disease (HD) were more impaired on an emotion recognition task compared to non-apathetic participants and healthy controls. METHODS: We included 43 participants from the TRACK-HD study who reported apathy on the Problem Behaviours Assessment - short version (PBA-S), 67 participants who reported no apathy, and 107 controls matched for age, sex, and level of education. During their baseline TRACK-HD visit, participants completed a battery of cognitive and psychological tests including an emotion recognition task, the Hospital Depression and Anxiety Scale (HADS) and were assessed on the PBA-S. RESULTS: Compared to the non-apathetic group and the control group, the apathetic group were impaired on the recognition of happy facial expressions, after controlling for depression symptomology on the HADS and general disease progression (Unified Huntington's Disease Rating Scale total motor score). This was despite no difference between the apathetic and non-apathetic group on overall cognitive functioning assessed by a cognitive composite score. CONCLUSIONS: Impairment of the recognition of happy expressions may be part of the clinical picture of apathy in HD. While shared reliance on frontostriatal pathways may broadly explain associations between emotion recognition and apathy found across several patient groups, further work is needed to determine what relationships exist between recognition of specific emotions, distinct subtypes of apathy and underlying neuropathology. (JINS, 2019, 25, 453-461).

The relationship between episodic future thinking and prospective memory in middle childhood: Mechanisms depend on task type.

Episodic future thinking (EFT), the ability to imagine experiencing a future event, and prospective memory (PM), the ability to remember and carry out a planned action, are core aspects of future-oriented cognition that have individually been the focus of research attention in the developmental literature. However, the relationship between EFT and PM, including the extent to which it varies with PM task type, remains poorly delineated, particularly in middle childhood. The current study tested this relationship in 62 typically developing children aged 8-12 years. Results indicated that EFT ability was significantly related to performance on three types of PM tasks (regular and irregular event based and regular time based). Age was not found to moderate the relationship. Children's performance on the retrospective memory component of the PM tasks mediated the relationship between EFT ability and their performance on three types of PM tasks. For irregular event-based tasks, however, EFT made an additional significant contribution. This study adds to the limited empirical literature supporting a relationship between EFT and PM in this age band and supports theoretical models arguing that EFT ability may support PM performance by strengthening the encoding of PM task details in retrospective memory. However, additional mechanisms were also indicated for irregular event-based PM tasks, possibly involving strengthening of cue-context associations. These data show for the first time that the contribution of EFT to children's PM performance varies across task types. This study provides an important and novel contribution to current understanding of the processes that underlie PM development.

Intranasal oxytocin does not reduce age-related difficulties in social cognition.

Oxytocin is a neuropeptide that plays a key role in social processing and there are several studies suggesting that intranasally administered oxytocin may enhance social cognitive abilities and visual attention in healthy and clinical groups. However, there are very few studies to date that have investigated the potential benefits of intranasal oxytocin (iOT) on older adults' social cognitive abilities. This is a surprising omission, because relative to their younger counterparts, older adults also exhibit a range of social cognitive difficulties and also show differences in the way they visually attend to social information. Therefore, we tested the effect of iOT (24 IU) versus a placebo spray on 59 older and 61 younger adults' social cognitive abilities and visual attention using a double-blind placebo-controlled within-groups design. While iOT provided no overall age-related benefit on social cognitive abilities, the key finding to emerge was that iOT improved ToM ability in both age-groups when the task had minimal contextual information, but not when the task had enriched contextual information. Interestingly, iOT had gender specific effects during a ToM task with minimal context. For males in both age-groups, iOT reduced gazing to the social aspects of the scenes (i.e., faces & bodies), and for females, iOT eliminated age differences in gaze patterns that were observed in the placebo condition. These effects on eye-gaze were not observed in a very similar ToM task that included more enriched contextual information. Overall, these findings highlight the interactive nature of iOT with task related factors (e.g., context), and are discussed in relation to the social salience hypothesis of oxytocin.

The relationship between body dysmorphic disorder and obsessive-compulsive disorder: A systematic review of direct comparative studies.

OBJECTIVE: Current nosology conceptualises body dysmorphic disorder as being related to obsessive-compulsive disorder, but the direct evidence to support this conceptualisation is mixed. In this systematic review, we aimed to provide an integrated overview of research that has directly compared body dysmorphic disorder and obsessive-compulsive disorder. METHOD: The PubMed database was searched for empirical studies which had directly compared body dysmorphic disorder and obsessive-compulsive disorder groups across any subject matter. Of 379 records, 31 met inclusion criteria and were reviewed. RESULTS: Evidence of similarities between body dysmorphic disorder and obsessive-compulsive disorder was identified for broad illness features, including age of onset, illness course, symptom severity and level of functional impairment, as well as high perfectionism and high fear of negative evaluation. However, insight was clearly worse in body dysmorphic disorder than obsessive-compulsive disorder, and preliminary data also suggested unique visual processing features, impaired facial affect recognition, increased social anxiety severity and overall greater social-affective dysregulation in body dysmorphic disorder relative to obsessive-compulsive disorder. CONCLUSION: Limitations included a restricted number of studies overall, an absence of studies comparing biological parameters (e.g. neuroimaging), and the frequent inclusion of participants with comorbid body dysmorphic disorder and obsessive-compulsive disorder. Risks of interpreting common features as indications of shared underlying mechanisms are explored, and evidence of differences between the disorders are placed in the context of broader research findings. Overall, this review suggests that the current nosological status of body dysmorphic disorder is somewhat tenuous and requires further investigation, with particular focus on dimensional, biological and aetiological elements.

Emotion processing in persons who respond vicariously towards others in pain: Disinhibited left-lateralized neural activity for threatening expressions.

We investigated emotional processing in vicarious pain (VP) responders. VP responders report an explicit sensory and emotional feeling of pain when they witness another in pain, which is greater in magnitude than the empathic processing of pain in the general population. In Study 1, 31 participants completed a chimeric faces task, judging whether emotional chimera in the left, or right, visual field was more intense. VP responders took longer to judge emotionality than non-responders, and fixated more on the angry hemiface in the right visual field, whereas non-responder controls had no lateralized fixation bias. In Study 2, blood-oxygen level-dependent signals were recorded during an emotional face matching task. VP intensity was correlated with increased insula activity and reduced middle frontal gyrus activity for angry faces, and with reduced activity in the inferior and middle frontal gyri for sad faces. Together, these findings suggest that VP responders are more reactive to negative emotional expressions. Specifically, emotional judgements involved altered left-hemisphere activity in VP responders, and reduced engagement of regions involved in emotion regulation.

The Wisdom to Know the Difference.

The ability to regulate emotions is central to well-being, but healthy emotion regulation may not merely be about using the "right" strategies. According to the strategy-situation-fit hypothesis, emotion-regulation strategies are conducive to well-being only when used in appropriate contexts. This study is the first to test the strategy-situation-fit hypothesis using ecological momentary assessment of cognitive reappraisal-a putatively adaptive strategy. We expected people who used reappraisal more in uncontrollable situations and less in controllable situations to have greater well-being than people with the opposite pattern of reappraisal use. Healthy participants ( n = 74) completed measures of well-being in the lab and used a smartphone app to report their use of reappraisal and perceived controllability of their environment 10 times a day for 1 week. Results supported the strategy-situation-fit hypothesis. Participants with relatively high well-being used reappraisal more in situations they perceived as lower in controllability and less in situations they perceived as higher in controllability. In contrast, we found little evidence for an association between greater well-being and greater mean use of reappraisal across situations.

Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington's Disease.

OBJECTIVES: Visuospatial processing deficits have been reported in Huntington's disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. METHODS: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. RESULTS: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation ("same") was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. CONCLUSIONS: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595-608).

Differential effects of social stress on laboratory-based decision-making are related to both impulsive personality traits and gender.

Urgency is the tendency to make impulsive decisions under extreme positive or negative emotional states. Stress, gender and impulsive personality traits are all known to influence decision-making, but no studies have examined the interplay of all of these factors. We exposed 78 men and women to a stress or a non-stress condition, and then administered the Balloon Analogue Risk Task. We found that stress effects varied as a function of gender and urgency traits. Under stress, women low in negative urgency and men high in negative urgency made fewer risky decisions. Positive urgency yielded a similar pattern. Thus, decisions under stress depend on a complex interplay between gender and impulsive personality traits. These findings have implications for clinical disorders, such as substance use disorders, in which there are known deficits in decision-making and high levels of impulsive traits.

The cognitive burden in Huntington's disease: pathology, phenotype, and mechanisms of compensation.

Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder. The most prominent sign of HD is the presence of involuntary motor movements. However, HD is also characterized by marked cognitive decline, which often precedes the onset of motor symptoms and is generally considered to be more debilitating to the patients and their families, compared to motor symptoms. Cognitive decline is widespread across most faculties of cognition in later stages of the disease, but seems to be selective in preclinical and early stages of the disease, with deficits in the HD patients' ability to multitask, their speed of processing, and executive function. It is now well established that preceding clinical diagnosis there is a preclinical stage, during which HD gene mutation carriers are relatively symptom free, despite disease pathological onset and the presence of neurodegeneration. Evidence from functional brain imaging studies suggests the presence of neural compensation in preclinical stages of HD, whereby the brain undergoes functional reorganization in response to neurodegeneration to preserve motor and cognitive performance. In this review, we will describe the underlying HD pathology with a focus on how it links to the cognitive phenotype. We will also present evidence regarding the presence of neural compensation in HD and the possible mechanisms supporting it. Finally, we will discuss current research in the field of cognitive interventions that aim to support and enhance neural compensation in HD. These research efforts could, one day, prolong the preclinical stage and assist with symptom management of those affected with HD.

Resting-state amygdala subregion and precuneus connectivity provide evidence for a dimensional approach to studying social anxiety disorder.

Social anxiety disorder (SAD) is a prevalent and disabling mental health condition, characterized by excessive fear and anxiety in social situations. Resting-state functional magnetic resonance imaging (fMRI) paradigms have been increasingly used to understand the neurobiological underpinnings of SAD in the absence of threat-related stimuli. Previous studies have primarily focused on the role of the amygdala in SAD. However, the amygdala consists of functionally and structurally distinct subregions, and recent studies have highlighted the importance of investigating the role of these subregions independently. Using multiband fMRI, we analyzed resting-state data from 135 participants (42 SAD, 93 healthy controls). By employing voxel-wise permutation testing, we examined group differences of fMRI connectivity and associations between fMRI connectivity and social anxiety symptoms to further investigate the classification of SAD as a categorical or dimensional construct. Seed-to-whole brain functional connectivity analysis using multiple 'seeds' including the amygdala and its subregions and the precuneus, revealed no statistically significant group differences. However, social anxiety severity was significantly negatively correlated with functional connectivity of the precuneus - perigenual anterior cingulate cortex and positively correlated with functional connectivity of the amygdala (specifically the superficial subregion) - parietal/cerebellar areas. Our findings demonstrate clear links between symptomatology and brain connectivity in the absence of diagnostic differences, with evidence of amygdala subregion-specific alterations. The observed brain-symptom associations did not include disturbances in the brain's fear circuitry (i.e., disturbances in connectivity between amygdala - prefrontal regions) likely due to the absence of threat-related stimuli.

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.

Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex.

The neuropeptide oxytocin (OXT) plays an important role in complex socio-affective behaviours such as affiliation, attachment, stress and anxiety. Previous studies have focused on the amygdala as an important target of OXT's effects. However, the effects of OXT on connectivity of the amygdala with cortical regions such as medial frontal cortex, an important mediator of social cognition and emotion regulation, remain unexplored. In a randomized, double-blind, cross-over design, 15 volunteers received intranasal OXT or placebo prior to resting-state functional magnetic resonance imaging. OXT significantly increased connectivity between both amygdalae and rostral medial frontal cortex (rmFC), while having only negligible effects on coupling with other brain regions. These results demonstrate that OXT is a robust and highly selective enhancer of amygdala connectivity with rmFC, a region critical to social cognition and emotion regulation, and add to our understanding of the neural mechanisms by which OXT modulates complex social and cognitive behaviours.

Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin.

Generalized social anxiety disorder (GSAD) is associated with heightened limbic and prefrontal activation to negative social cues conveying threat (e.g. fearful faces), but less is known about brain response to negative non-threatening social stimuli. The neuropeptide oxytocin (Oxt) has been shown to attenuate (and normalize) fear-related brain activation and reactivity to emotionally negative cues. Here, we examined the effects of intranasal Oxt on cortical activation to non-threatening sad faces in patients with GSAD and matched controls (Con). In a double-blind placebo-controlled within-subjects design, the cortical activation to sad and happy (vs. neutral) faces was examined using functional magnetic resonance imaging following acute intranasal administration of 24 IU Oxt and placebo. Relative to the Con group, GSAD patients exhibited heightened activity to sad faces in the medial prefrontal cortex (mPFC/BA 10) extending into anterior cingulate cortex (ACC/BA 32). Oxt significantly reduced this heightened activation in the mPFC/ACC regions to levels similar to that of controls. These findings suggest that GSAD is associated with cortical hyperactivity to non-threatening negative but not positive social cues and that Oxt attenuates this exaggerated cortical activity. The modulation of cortical activity by Oxt highlights a broader mechanistic role of this neuropeptide in modulating socially negative cues in GSAD.

Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease.

BACKGROUND: Deterioration of cognitive functioning is a debilitating symptom in many neurodegenerative diseases, such as Huntington's disease (HD). To date, there are no effective treatments for the cognitive problems associated with HD. Cognitive assessment outcomes will have a central role in the efforts to develop treatments to delay onset or slow the progression of the disease. The TRACK-HD study was designed to build a rational basis for the selection of cognitive outcomes for HD clinical trials. METHODS: There were a total of 349 participants, including controls (n=116), premanifest HD (n=117) and early HD (n=116). A standardised cognitive assessment battery (including nine cognitive tests comprising 12 outcome measures) was administered at baseline, and at 12 and 24 months, and consisted of a combination of paper and pencil and computerised tasks selected to be sensitive to cortical-striatal damage or HD. Each cognitive outcome was analysed separately using a generalised least squares regression model. Results are expressed as effect sizes to permit comparisons between tasks. RESULTS: 10 of the 12 cognitive outcomes showed evidence of deterioration in the early HD group, relative to controls, over 24 months, with greatest sensitivity in Symbol Digit, Circle Tracing direct and indirect, and Stroop word reading. In contrast, there was very little evidence of deterioration in the premanifest HD group relative to controls. CONCLUSIONS: The findings describe tests that are sensitive to longitudinal cognitive change in HD and elucidate important considerations for selecting cognitive outcomes for clinical trials of compounds aimed at ameliorating cognitive decline in HD.

Is resting-state functional connectivity altered in regular cannabis users? A systematic review of the literature.

RATIONALE: Regular cannabis use has been associated with brain functional alterations within frontal, temporal, and striatal pathways assessed during various cognitive tasks. Whether such alterations are consistently reported in the absence of overt task performance needs to be elucidated to uncover the core neurobiological mechanisms of regular cannabis use. OBJECTIVES: We aim to systematically review findings from studies that examine spontaneous fluctuations of brain function using functional Magnetic Resonance Imaging (fMRI) resting-state functional connectivity (rsFC) in cannabis users versus controls, and the association between rsFC and cannabis use chronicity, mental health symptoms, and cognitive performance. METHODS: We conducted a PROSPERO registered systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched eight databases. RESULTS: Twenty-one studies were included for review. Samples comprised 1396 participants aged 16 to 42 years, of which 737 were cannabis users and 659 were controls. Most studies found greater positive rsFC in cannabis users compared to controls between frontal-frontal, fronto-striatal, and fronto-temporal region pairings. The same region pairings were found to be preliminarily associated with varying measures of cannabis exposure. CONCLUSIONS: The evidence to date shows that regular cannabis exposure is consistently associated with alteration of spontaneous changes in Blood Oxygenation Level-Dependent signal without any explicit cognitive input or output. These findings have implications for interpreting results from task-based fMRI studies of cannabis users, which may additionally tax overlapping networks. Future longitudinal rsFC fMRI studies are required to determine the clinical relevance of the findings and their link to the chronicity of use, mental health, and cognitive performance.

Concordance in salivary cortisol and subjective anxiety to the trier social stress test in social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) is characterised by an excessive fear of negative social evaluation. There is a limited understanding of how individuals with SAD react physiologically and subjectively to social stress. METHOD: The Trier Social Stress Test (TSST), an acute social stress task, was completed by 40 SAD individuals (50% female) and 41 healthy controls (matched on age, sex, and education) to examine salivary cortisol and self-reported stress reactivity. Salivary cortisol concentrations and self-reported affect (anxiety, sadness, tiredness, withdrawal, and happiness) were assessed at baseline and across nine-time points during the TSST. RESULTS: Bayesian salivary cortisol analyses revealed no group differences in salivary cortisol levels at baseline or during the TSST, with results comparative after the removal of 17 cortisol non-responders (21%). Contrastingly, the groups significantly differed on self-reported affect. At baseline, the SAD group (vs. controls) reported heightened negative affect and diminished happiness. In response to the TSST, the SAD group (vs. controls) displayed greater negative affect reactivity and diminished happiness reactivity, and significantly higher rates of change in their anxiety and sadness over time. After accounting for differences in the temporal resolution of self-reported versus cortisol responses, a moderate positive association was found between salivary cortisol and anxiety reactivity to social stress that was comparable between the groups. CONCLUSIONS: Despite elevated subjective anxiety, our findings suggest concordance in psychobiological stress reactivity in SAD and healthy controls. We discuss the possibility of heightened subjective sensitivity to social evaluative stress as a core treatment target for SAD.