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Summary: Glucagon‐like peptide 1 (GLP‐1) receptor agonists are revolutionizing obesity and type 2 diabetes treatment, delivering remarkable weight loss outcomes. These medications, leveraging the effects of the insulin‐regulating hormone GLP‐1 via actions on peripheral and central nervous system targets, have raised hopes with their bariatric surgery‐rivaling results. However, questions remain about their long‐term safety and efficacy. Drawing from our expertise in obesity medicine and psychiatry, we reflect upon our experiences with the clinical use of these medications and delve into the nuanced challenges and risks they pose, particularly for those prone to disordered eating or those diagnosed with rare genetic diseases of obesity. We contend that effectively managing weight loss within this "danger zone" necessitates (1) proactive screening and continuous monitoring for disordered eating, (2) vigilant monitoring for appetite‐related maladaptive responses, including food aversion and dehydration, and (3) ongoing assessment for broader health impacts. A multifaceted, interdisciplinary approach that melds medical, psychological, dietary, and behavioral strategies is crucial to delivering tailored and thorough care to each patient. [ABSTRACT FROM AUTHOR]

A developing area of research suggests that there may be a relationship between interoception and suicidal behavior. For example, it was recently reported that individuals who made a suicide attempt within the previous 5 years exhibit behavioral and neural abnormalities across multiple domains of interoception relative to nonattempters. This included increased tolerance for aversive sensations of pain and dyspnea, reduced heartbeat-perception accuracy, and blunted insula activity during attention to cardiac sensations. However, the degree to which interoceptive deficits persist following a suicidal attempt is unknown. In the current study, we examined differences between individuals with a remote history of suicide attempts (greater than 5 years ago; N = 56) versus those with no history of attempts (N = 240). We found that remote suicide attempters demonstrated greater pain tolerance and lower ratings of stress during a cold-pressor challenge and lower ratings of suffocation during a breath-hold challenge, as compared to nonattempters. In contrast, there were no group differences in breath-hold duration, interoceptive accuracy on a heartbeat-tapping task, or insula activation during cardiac attention. An exploratory resting-state functional connectivity analysis of individuals with suicide attempts in the past 5 years (N = 23), individuals with more remote histories of suicide attempts (N = 39), and nonattempters (N = 232) revealed preliminary and subtle evidence of differences in insula connectivity with areas of the temporal cortex in remote suicide attempters. Taken together, these findings suggest that blunted affective responses to aversive interoceptive sensations is an enduring characteristic of suicide attempters, even when assessed many years after a suicide attempt, whereas differences in the experience of nonaversive interoceptive sensations may be less persistent. [ABSTRACT FROM AUTHOR]

The present paper considers recent progress in our understanding of the afferent/ascending neural pathways and neural circuits of interoception. Of particular note is the extensive role of rostral neural systems, including cortical systems, in the recognition of internal body states, and the reciprocal role of efferent/descending systems in the regulation of those states. Together these reciprocal interacting networks entail interoceptive circuits that play an important role in a broad range of functions beyond the homeostatic maintenance of physiological steady-states. These include the regulation of behavioral, cognitive, and affective processes across conscious and nonconscious levels of processing. We highlight recent advances and knowledge gaps that are important for accelerating progress in the study of interoception. The nervous system receives ascending communication of interoceptive signals originating from the periphery via chemoreceptor, mechanoreceptor, and osmoreceptor pathways, several of which were discovered only recently. Visceral systems and associated interoceptive signals are regulated in part by descending central nervous system (CNS) control of the autonomic nervous system, yielding a reciprocal circuit that regulates bodily organs and a wide array of motor, cognitive, and affective processes. A gap in our understanding of how interoceptive signals are relayed through the CNS from the body centers on inputs to the nucleus tractus solitarius and higher relay pathways. The neural circuits of interoception are important for behavioral, cognitive, and emotional regulation across conscious and nonconscious levels of processing. [ABSTRACT FROM AUTHOR]

Blunted anterior insula activation during interoceptive perturbations has been associated with stimulant (cocaine and amphetamine) use disorder (SUD) and is related to risk for and prognosis of SUD. However, little is known whether these interoceptive alterations extend to opioid use disorder (OUD). This exploratory study used the same experimental probe during functional magnetic resonance imaging (fMRI) to test the hypothesis that SUD and OUD exhibit interoceptive discrepancies characterized by subjective ratings and activation within the insula. Recently, abstinent individuals diagnosed with current SUD (n = 40) or current OUD (n = 20) were compared with healthy individuals (CTL; n = 30) on brain and self-report responses during an interoceptive attention task known to elicit insula activation. Participants selectively attended to interoceptive (heartbeat and stomach) and exteroceptive signals during blood-oxygen-level-dependent fMRI recording. Groups and conditions were compared on (a) activation within probabilistic cytoarchitectonic segmentations of the insula and (b) self-reported stimulus intensity. First, SUD showed amplified ratings of heart-related sensations but attenuation of dorsal dysgranular insula activity relative to CTL. Amplified ratings were linked to drug use recency, while attenuation was normalized with greater past-year stimulant use. Second, SUD and OUD showed attenuation of dorsal dysgranular insula activity during attention to stomach sensations relative to CTL. Taken together, these results are consistent with altered neural processing of interoceptive signals in drug addiction, particularly as a function of SUD. Future studies will need to determine whether interoceptive metrics help to explain substance use disorder pathophysiology and are useful for predicting outcomes. [ABSTRACT FROM AUTHOR]

The parasympathetic nervous system via the vagus nerve exerts profound influence over the heart. Together with the sympathetic nervous system, the parasympathetic nervous system is responsible for fine-tuned regulation of all aspects of cardiovascular function, including heart rate, rhythm, contractility, and blood pressure. In this review, we highlight vagal efferent and afferent innervation of the heart, with a focus on insights from comparative biology and advances in understanding the molecular and genetic diversity of vagal neurons, as well as interoception, parasympathetic dysfunction in heart disease, and the therapeutic potential of targeting the parasympathetic nervous system in cardiovascular disease. [ABSTRACT FROM AUTHOR]

The article describes how a transdiagnostic process called interoception may help to advance the understanding and treatment of eating disorders. Topics discussed include overview of interoception, interoception in anorexia nervosa, and developmental importance of interoception in eating disorders. Treating dysfunctional interoceptive awareness in eating disorders is also mentioned.

Floatation-REST (Reduced Environmental Stimulation Therapy) reduces sensory input to the nervous system through the act of floating supine in a pool of water saturated with Epsom salt. The float experience is calibrated so that sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational and proprioceptive channels are minimized, as is most movement and speech. This open-label study aimed to examine whether Floatation-REST would attenuate symptoms of anxiety, stress, and depression in a clinical sample. Fifty participants were recruited across a spectrum of anxiety and stress-related disorders (posttraumatic stress, generalized anxiety, panic, agoraphobia, and social anxiety), most (n = 46) with comorbid unipolar depression. Measures of self-reported affect were collected immediately before and after a 1-hour float session, with the primary outcome measure being the pre- to post-float change score on the Spielberger State Anxiety Inventory. Irrespective of diagnosis, Floatation-REST substantially reduced state anxiety (estimated Cohen’s d > 2). Moreover, participants reported significant reductions in stress, muscle tension, pain, depression and negative affect, accompanied by a significant improvement in mood characterized by increases in serenity, relaxation, happiness and overall well-being (p < .0001 for all variables). In reference to a group of 30 non-anxious participants, the effects were found to be more robust in the anxious sample and approaching non-anxious levels during the post-float period. Further analysis revealed that the most severely anxious participants reported the largest effects. Overall, the procedure was well-tolerated, with no major safety concerns stemming from this single session. The findings from this initial study need to be replicated in larger controlled trials, but suggest that Floatation-REST may be a promising technique for transiently reducing the suffering in those with anxiety and depression. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Relapse after treatment for anorexia nervosa (AN) is a significant clinical problem. Given the level of chronicity, morbidity, and mortality experienced by this population, it is imperative to understand the driving forces behind apparently high relapse rates. However, there is a lack of consensus in the field on an operational definition of relapse, which hinders precise and reliable estimates of the severity of this issue. The primary goal of this paper was to review prior studies of AN addressing definitions of relapse, as well as relapse rates. Methods: Data sources included PubMed and PsychINFO through March 19th, 2016. A systematic review was performed following the PRISMA guidelines. A total of (N = 27) peer-reviewed English language studies addressing relapse, remission, and recovery in AN were included. Results: Definitions of relapse in AN as well as definitions of remission or recovery, on which relapse is predicated, varied substantially in the literature. Reported relapse rates ranged between 9 and 52%, and tended to increase with increasing duration of follow-up. There was consensus that risk for relapse in persons with AN is especially high within the first year following treatment. Discussion: Standardized definitions of relapse, as well as remission and recovery, are needed in AN to accelerate clinical and research progress. This should improve the ability of future longitudinal studies to identify clinical, demographic, and biological characteristics in AN that predict relapse versus resilience, and to comparatively evaluate relapse prevention strategies. We propose standardized criteria for relapse, remission, and recovery, for further consideration. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Several case reports of Wernicke's Encephalopathy in anorexia nervosa (AN) caused by thiamine deficiency have described mammillary body (MB) injury, but systematic studies are lacking. Here we evaluated whether underweight and weight-restored individuals with AN demonstrate evidence of abnormal MB morphology, via retrospective examination of a previously collected data set. Method Using standard-resolution T1-weighted magnetic resonance imaging at 3 Tesla, we measured MB volume and fornix area in a cross-sectional study of 12 underweight AN, 20 weight-restored AN, and 30 age- and sex-matched healthy comparisons. Because of the small size of these structures, a manual tracing approach was necessary to obtain accurate measurements. A blinded expert rater manually traced MB and fornix structures in each participant. Results We observed significantly smaller MB volumes in the underweight AN group. However, the weight-restored AN group exhibited significantly larger MB volumes. The right fornix was smaller in the weight-restored AN group only. Discussion These findings suggest the possibility that MB volume and fornix area could represent potential biomarkers of acute weight loss and restoration, respectively. Verification of this finding through prospective studies evaluating MB morphology, cognition, and thiamine levels longitudinally across individual illness trajectories might be warranted. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:920-929) [ABSTRACT FROM AUTHOR]

We previously demonstrated that carbon dioxide inhalation could induce panic anxiety in a group of rare lesion patients with focal bilateral amygdala damage. To further elucidate the amygdala-independent mechanisms leading to aversive emotional experiences, we retested two of these patients (B.G. and A.M.) to examine whether triggering palpitations and dyspnea via stimulation of nonchemosensory interoceptive channels would be sufficient to elicit panic anxiety. Participants rated their affective and sensory experiences following bolus infusions of either isoproterenol, a rapidly acting peripheral β-adrenergic agonist akin to adrenaline, or saline. Infusions were administered during two separate conditions: a panic induction and an assessment of cardiorespiratory interoception. Isoproterenol infusions induced anxiety in both patients, and full-blown panic in one (patient B.G.). Although both patients demonstrated signs of diminished awareness for cardiac sensation, patient A.M., who did not panic, reported a complete lack of awareness for dyspnea, suggestive of impaired respiratory interoception. These findings indicate that the amygdala may play a role in dynamically detecting changes in cardiorespiratory sensation. The induction of panic anxiety provides further evidence that the amygdala is not required for the conscious experience of fear induced via interoceptive sensory channels. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Impaired interoceptive awareness (IA), the subjective perception of internal body sensations, has been proposed as a vulnerability or maintaining factor in anorexia nervosa (AN). We examined whether IA of heartbeat and breathing sensations was impaired in AN across a range of arousal levels, and whether it was influenced by meal anticipation and consumption. Method: IA was assessed using randomized, double-blinded, bolus intravenous infusions of isoproterenol, a peripheral beta-adrenergic sympathetic agonist, and saline. Fifteen women with AN and 15 age-, and sex- matched healthy comparisons (HC) were evaluated before and after consumption of a 1,000 Calorie meal. During each infusion participants rated their moment-to-moment intensity of heartbeat and breathing sensations with a dial. To measure IA we evaluated interoceptive detection thresholds, retrospective ratings of palpitation and dyspnea intensity, and interoceptive accuracy via correlations between subjective dial ratings and observed heart rate responses. Results: Contrary to prediction the AN group was more likely to report detection of interoceptive sensations across all conditions, an effect driven by false discriminations at low arousal levels. Concordant with prediction, meal anticipation was associated with intensified interoceptive sensations, particularly dyspnea. There were no differences in interoceptive accuracy. Discussion: This represents the first demonstration of interoceptive prediction errors in AN. Although IA is unimpaired at high arousal levels in AN, prediction signals are abnormal at low arousal levels, especially during meal anticipation. Altered interoceptive prediction signaling during meal anticipation could contribute to phenotypes of high anxiety in AN or alternatively, might be explained by enhanced meal associated anxiety. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:889-897) [ABSTRACT FROM AUTHOR]

Aging has been shown to increase sensory thresholds for a variety of exteroceptive and proprioceptive stimuli. However, the influence of aging on interoceptive awareness has received relatively little empirical attention. Here we report an inverse association between aging and interoception, as indexed by the ability to sense the heartbeat at rest. In a group of 59 participants ranging in age from 22 to 63 years, age inversely predicted heartbeat detection ability, both within and across several measurement sessions. On average, age accounted for 30% of the variance in heartbeat detection accuracy. Other attribute variables including body mass index and sex were not related to heartbeat detection ability. These findings provide clear empirical evidence that interoception, much like exteroception and proprioception, declines with age. [ABSTRACT FROM AUTHOR]

Attention to internal body sensations is practiced in most meditation traditions. Many traditions state that this practice results in increased awareness of internal body sensations, but scientific studies evaluating this claim are lacking. We predicted that experienced meditators would display performance superior to that of nonmeditators on heartbeat detection, a standard noninvasive measure of resting interoceptive awareness. We compared two groups of meditators (Tibetan Buddhist and Kundalini) to an age- and body mass index-matched group of nonmeditators. Contrary to our prediction, we found no evidence that meditators were superior to nonmeditators in the heartbeat detection task, across several sessions and respiratory modulation conditions. Compared to nonmeditators, however, meditators consistently rated their interoceptive performance as superior and the difficulty of the task as easier. These results provide evidence against the notion that practicing attention to internal body sensations, a core feature of meditation, enhances the ability to sense the heartbeat at rest. [ABSTRACT FROM AUTHOR]

Abstract: Hughlings Jackson’s insightful bedside observations of patients with epilepsy paved the way for the first effective surgical epilepsy treatments. Jackson’s most famous case, that of Doctor Z, concerned a medical doctor with partial complex seizures who was reported to have a discrete and circumscribed medial temporal lobe (mTL) lesion on autopsy. Although integral to Jackson’s argument for mTL resection, the case remains controversial due to inadequate pathological descriptions of Doctor Z’s lesion. This motivated us to describe the case of a patient, whom we call Patient A, who suffered from a form of epilepsy similar to that of Doctor Z, accompanied by a discrete and circumscribed mTL lesion in the exact same location. The lesion, a cavernous hemangioma, spared the hippocampus and was restricted to the lateral aspect of the entorhinal cortex. This finding validates Jackson’s original description and suggests that the entorhinal cortex can play a role in seizure genesis. [Copyright &y& Elsevier]

Bilateral cardiac sympathetic denervation (BCSD) is a surgical treatment for refractory ventricular arrhythmias. Although the procedure has shown efficacy at reducing cardiac arrhythmias, its impact on mental health is unknown. In the current study we examined associations between the BCSD procedure and mental health. 10 ventricular arrhythmia patients undergoing BCSD completed assessments of anxiety, depression, and posttraumatic stress symptoms at pre- and post-BCSD time points. Wilcoxon signed rank and Mann-Whitney U tests were used to examine differences in mental health symptoms in the pre- and post-BSCD states. Point biserial correlations were used to explore associations between BCSD response and mental health symptoms. A significant reduction of anxiety symptoms was observed from pre- to post-BCSD. At the post-BCSD assessment, participants who successfully responded to the BCSD procedure exhibited lower anxiety symptoms compared to non-responders. However, no significant relationships were identified for depressive or PTSD symptoms. The BCSD procedure is associated with reduced anxiety shortly after successful treatment for refractory ventricular arrhythmias in a small sample. Longitudinal surveillance of mental health symptoms after BCSD may be warranted to monitor the impact of this procedure on mental health. • Stellate ganglia removal was associated with lower anxiety in cardiac arrhythmias. • Successful arrhythmia response to denervation was associated with lower anxiety. • Stellate ganglia removal was not associated with lower depression or PTSD symptoms. [ABSTRACT FROM AUTHOR]

Background: Reduced Environmental Stimulation Therapy via floatation (floatation-REST) is a behavioral intervention designed to attenuate exteroceptive sensory input to the nervous system. Prior studies in anxious and depressed individuals demonstrated that single sessions of floatation-REST are safe, well-tolerated, and associated with an acute anxiolytic and antidepressant effect that persists for over 48 hours. However, the feasibility of using floatation-REST as a repeated intervention in anxious and depressed populations has not been well-investigated. Methods: In this single-blind safety and feasibility trial, 75 individuals with anxiety and depression were randomized to complete six sessions of floatation-REST in different formats: pool-REST (weekly 1-hour float sessions), pool-REST preferred (float sessions with flexibility of duration and frequency), or an active comparator (chair-REST; weekly 1-hour sessions in a Zero Gravity chair). Feasibility (primary outcome) was assessed via an 80% rate of adherence to the assigned intervention; tolerability via study dropout and duration/frequency of REST utilization; and safety via incidence of adverse events and ratings about the effects of REST. Results: Of 1,715 individuals initially screened, 75 participants were ultimately randomized. Six-session adherence was 85% for pool-REST (mean, M = 5.1 sessions; standard deviation, SD = 1.8), 89% for pool-REST preferred (M = 5.3 sessions; SD = 1.6), and 74% for chair-REST (M = 4.4 sessions; SD = 2.5). Dropout rates at the end of the intervention did not differ significantly between the treatment conditions. Mean session durations were 53.0 minutes (SD = 12.3) for pool-REST, 75.4 minutes (SD = 29.4) for pool-REST preferred, and 58.4 minutes (SD = 4.3) for chair-REST. There were no serious adverse events associated with any intervention. Positive experiences were endorsed more commonly than negative ones and were also rated at higher levels of intensity. Conclusions: Six sessions of floatation-REST appear feasible, well-tolerated, and safe in anxious and depressed individuals. Floatation-REST induces positively-valenced experiences with few negative effects. Larger randomized controlled trials evaluating markers of clinical efficacy are warranted. Clinical Trial Registration Identifier: NCT03899090. [ABSTRACT FROM AUTHOR]

A network of cortical brain regions, including the insula and anterior cingulate cortex (ACC), has been proposed as the critical and sole substrate for interoceptive awareness. Combining lesion and pharmacological approaches in humans, we found that the insula and ACC were not critical for awareness of heartbeat sensations. Instead, this awareness was mediated by both somatosensory afferents from the skin and a network that included the insula and ACC. Together, these pathways enable the core human experience of the cardiovascular state of the body. [ABSTRACT FROM AUTHOR]

Meditation is commonly assumed to be associated with enhanced interoceptive accuracy. We previously found that experienced meditators did not exhibit a greater ability than nonmeditators to detect heartbeat sensations at rest, despite the meditators' reported subjective ratings of higher accuracy and lower difficulty. Here, attempting to overcome previous methodological limitations, we assessed interoceptive awareness of heartbeat and breathing sensations across physiological arousal levels using infusions of isoproterenol, a beta‐adrenergic agonist similar to adrenaline. We hypothesized that meditators would display greater interoceptive awareness than nonmeditators, as evidenced by higher interoceptive detection rates, increased interoceptive accuracy, and differences in localization of heartbeat sensations. We studied 15 meditators and 15 nonmeditators, individually matched on age, gender, and body mass index, using randomized, double‐blinded, and placebo‐controlled bolus infusions of isoproterenol. Participants reported their experience of heartbeat and breathing sensations using a dial during infusions and the location of heartbeat sensations on a two‐dimensional manikin afterward. There was no evidence of higher detection rates or increased accuracy across any dose, although meditators showed a tendency to report cardiorespiratory sensation changes sooner at higher doses. Relative to nonmeditators, meditators exhibited prominent geographical differences in heartbeat localization, disproportionally reporting sensations throughout central regions of the chest, abdomen, neck, back, and head. To further assess indications of potential differences in cardiac interoceptive accuracy between meditators and nonmeditators, we conducted a meta‐analysis including 724 participants and found little evidence for such differences. We conclude that the practice of meditation is not associated with improved cardiac interoceptive awareness. Despite the fact that one in seven U.S. adults report using meditation, we know little about the underlying mechanisms. We investigated whether meditators exhibit greater awareness of interoceptive (internal body) sensations of the heartbeat and breath. We found that meditators were not more accurate at perceiving these sensations. Moreover, meditators processed the heartbeat sensation differently, experiencing it more broadly throughout the body in regions overlying prominent arteries. A meta‐analysis of cardiac interoceptive accuracy including 724 meditators and nonmeditators also found no differences. Contrary to popular belief, meditation does not enhance the accuracy of interoceptive awareness for the heartbeat. [ABSTRACT FROM AUTHOR]

• Evaluation of two paradigms measuring anticipation and experience as well as the detection of discrepancies between anticipated and experienced interoceptive states. • 52 participants (of which 10 took part in a retest) conducted both paradigms on two modalities: respiroception and nociception. • Results show both paradigms to be valid and reliable tools for assessing the anticipation of future interoceptive states across different interoceptive domains. • Paradigms offer the possibility for implementation in further studies using imaging techniques. As the sense of the body's internal state, interoception represents the afferent component of the brain-body feedback loop essential for linking internal sensation with body regulation, thereby minimizing erroneous feedback and maintaining homeostasis. The anticipation of potential future interoceptive states enables organisms to take regulatory actions to meet demands before they arise, and alterations of anticipation have been implicated in the pathophysiology of medical and psychiatric conditions. However, laboratory approaches operationalizing the anticipation of interoceptive states are missing. Therefore, we developed two interoceptive awareness paradigms, the Accuracy of Interoceptive Anticipation paradigm, and the Interoceptive Discrepancy paradigm, which we tested in 52 healthy participants on two sensory modalities: nociception and respiroception. Ten participants took part in a retest. The Accuracy of Interoceptive Anticipation paradigm focused on assessing how individuals anticipate and experience interoceptive stimuli of varying strengths. The Interoceptive Discrepancy paradigm extended this measure by manipulating previously learned expectations to induce discrepancies between anticipated and experienced stimuli. We found that anticipation and experience ratings successfully related to stimulus strength in both paradigms and modalities and were stable between test-retest. Furthermore, the Interoceptive Discrepancy paradigm successfully induced the expected discrepancies between anticipation and experience conditions, and discrepancy values were correlated across sensory modalities. Thus, both paradigms are valid and reliable tools for assessing the anticipation of future interoceptive states, and the Interoceptive Discrepancy paradigm is additionally suited to evaluate discrepancy awareness. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to test whether there are sex differences in the relationship between impulsivity and amphetamine use disorder (AMP). Design: A naturalistic cross‐sectional design was used. Setting: The Tulsa 1000 study was held in Tulsa, OK, USA. Participants: There were two groups in this study: AMP+ (29F, 20M) and AMP– (57F, 33M). Measurements This project focuses on data related to impulsivity: UPPS‐P impulsive behavior scale and a stop signal task (SST) during functional magnetic resonance imaging (fMRI) recording. Group, sex and their interaction were compared for UPPS‐P ratings and SST fMRI and behavioral responses. Findings AMP+ reported higher UPPS‐P positive and negative urgency scores (Ps < 0.001; r = 0.56 and 0.51) and displayed greater bilateral insula and amygdala responses across correct SST trials (Ps < 0.001, g range = 0.57–0.81) than AMP–. fMRI results indicated that AMP+ exhibited larger right anterior/middle insula, amygdala and nucleus accumbens signals during successful difficult stop trials than AMP– (Ps < 0.01; g = 0.63, 0.54 and 0.44, respectively). Crucially, two group × sex effects emerged: (a) within females, AMP+ reported larger UPPS‐P lack of premeditation scores than AMP– (P < 0.001, r = 0.51), and (b) within males, AMP+ showed greater left middle insula signals than AMP– across correct SST trials (P = 0.01, g = 0.78). Conclusions: Both female and male amphetamine users appear to be characterized by rash action in the presence of positive and negative mood states as well as heightened recruitment of right hemisphere regions during behavioral inhibition. In contrast, planning ahead may be particularly difficult for female amphetamine users, whereas male amphetamine users may need to recruit additional left hemisphere resources during inhibitory processing. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is associated with immunologic and metabolic alterations linked to central processing dysfunctions, including attenuated reward processing. This study investigated the associations between inflammation, metabolic hormones (leptin, insulin, adiponectin), and reward-related brain processing in MDD patients with high (MDD-High) and low (MDD-Low) C-reactive protein (CRP) levels compared to healthy comparison subjects (HC). Participants completed a blood draw and a monetary incentive delay task during functional magnetic resonance imaging. Although groups did not differ in insulin or adiponectin concentrations, both MDD-High (Wilcoxon p = 0.004, d = 0.65) and MDD-Low (Wilcoxon p = 0.046, d = 0.53) showed higher leptin concentrations than HC but did not differ from each other. Across MDD participants, higher leptin levels were associated with lower brain activation during reward anticipation in the left insula (r = − 0.30, p = 0.004) and left dorsolateral putamen (r = -− 0.24, p = 0.025). In contrast, within HC, higher leptin concentrations were associated with higher activation during reward anticipation in the same regions (insula: r = 0.40, p = 0.007; putamen: r = 0.37, p = 0.014). Depression may be characterized by elevated pro-inflammatory signaling via leptin concentrations through alternate inflammatory pathways distinct to CRP. [ABSTRACT FROM AUTHOR]

Differences in the correlated activity of networked brain regions have been reported in individuals with generalized anxiety disorder (GAD) but an overreliance on null-hypothesis significance testing (NHST) limits the identification of disorder-relevant relationships. In this preregistered study, we applied both a Bayesian statistical framework and NHST to the analysis of resting-state fMRI scans from females with GAD and matched healthy comparison females. Eleven a-priori hypotheses about functional connectivity (FC) were evaluated using Bayesian (multilevel model) and frequentist (t-test) inference. Reduced FC between the ventromedial prefrontal cortex (vmPFC) and the posterior-mid insula (PMI) was confirmed by both statistical approaches and was associated with anxiety sensitivity. FC between the vmPFC-anterior insula, the amygdala-PMI, and the amygdala-dorsolateral prefrontal cortex (dlPFC) region pairs did not survive multiple comparison correction using the frequentist approach. However, the Bayesian model provided evidence for these region pairs having decreased FC in the GAD group. Leveraging Bayesian modeling, we demonstrate decreased FC of the vmPFC, insula, amygdala, and dlPFC in females with GAD. Exploiting the Bayesian framework revealed FC abnormalities between region pairs excluded by the frequentist analysis and other previously undescribed regions in GAD, demonstrating the value of applying this approach to resting-state FC data in clinical investigations. [ABSTRACT FROM AUTHOR]

Repetitive negative thinking (RNT) is a symptom that can negatively impact the treatment and course of common psychiatric disorders such as depression and anxiety. We aimed to characterize behavioral and genetic correlates of RNT to infer potential contributors to its genesis and maintenance. We applied a machine learning (ML) ensemble method to define the contribution of fear, interoceptive, reward, and cognitive variables to RNT, along with polygenic risk scores (PRS) for neuroticism, obsessive compulsive disorder (OCD), worry, insomnia, and headaches. We used the PRS and 20 principal components of the behavioral and cognitive variables to predict intensity of RNT. We employed the Tulsa-1000 study, a large database of deeply phenotyped individuals recruited between 2015 and 2018. PRS for neuroticism was the main predictor of RNT intensity (R 2 = 0.027 , p < 0.001). Behavioral variables indicative of faulty fear learning and processing, as well as aberrant interoceptive aversiveness, were significant contributors to RNT severity. Unexpectedly, we observed no contribution of reward behavior and diverse cognitive function variables. This study is an exploratory approach that must be validated with a second, independent cohort. Furthermore, this is an association study, limiting causal inference. RNT is highly determined by genetic risk for neuroticism, a behavioral construct that confers risk to a variety of internalizing disorders, and by emotional processing and learning features, including interoceptive aversiveness. These results suggest that targeting emotional and interoceptive processing areas, which involve central autonomic network structures, could be useful in the modulation of RNT intensity. • A machine learning ensemble method identified behavioral and genetic predictors of repetitive negative thinking (RNT). • Heightened response to aversive and fear inducing stimuli are associated with RNT. • The only genetic trait associated with RNT was polygenic risk score for neuroticism. • Our results warrant the exploration of interventions that target fear learning and interoceptive aversiveness. • Our results indicate that RNT is either a component of neuroticism or a contributor to the development and stability of it. [ABSTRACT FROM AUTHOR]

The neurovisceral integration (NVI) model was originally proposed to account for observed relationships between peripheral physiology, cognitive performance, and emotional/physical health. This model has also garnered a considerable amount of empirical support, largely from studies examining cardiac vagal control. However, recent advances in functional neuroanatomy, and in computational neuroscience, have yet to be incorporated into the NVI model. Here we present an updated/expanded version of the NVI model that incorporates these advances. Based on a review of studies of structural/functional anatomy, we first describe an eight - level hierarchy of nervous system structures, and the contribution that each level plausibly makes to vagal control. Second, we review recent work on a class of computational models of brain function known as “predictive coding” models. We illustrate how the computational dynamics of these models, when implemented within our proposed vagal control hierarchy, can increas e understanding of the relationship between vagal control and both cognitive performance and emotional/physical health. We conclude by discussing novel implications of this updated NVI model for future research. [ABSTRACT FROM AUTHOR]

Background: Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive–compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of exposure-based therapy. Growing evidence links orexin system activity to deficits in fear extinction and we have demonstrated that reactivity to an inhaled carbon dioxide (CO2) challenge—a safe, affordable, and easy-to-implement procedure—can serve as a proxy for orexin system activity and predicts fear extinction deficits in rodents. Building upon this basic research, the goal for the proposed study is to validate CO2 reactivity as a biomarker of exposure-based therapy non-response. Methods: We will assess CO2 reactivity in 600 adults meeting criteria for one or more fear- or anxiety-related disorders prior to providing open exposure-based therapy. By incorporating CO2 reactivity into a multivariate model predicting treatment non-response that also includes reactivity to hyperventilation as well as a number of related predictor variables, we will establish the mechanistic specificity and the additive predictive utility of the potential CO2 reactivity biomarker. By developing models independently within two study sites (University of Texas at Austin and Boston University) and predicting the other site's data, we will validate that the results are likely to generalize to future clinical samples. Discussion: Representing a necessary stage in translating basic research, this investigation addresses an important public health issue by testing an accessible clinical assessment strategy that may lead to a more effective treatment selection (personalized medicine) for patients with anxiety- and fear-related disorders, and enhanced understanding of the mechanisms governing exposure-based therapy. Trial registration: ClinicalTrials.gov Identifier: NCT05467683 (20/07/2022). [ABSTRACT FROM AUTHOR]

Repetitive negative thinking (RNT) is a transdiagnostic symptom associated with poor outcomes in major depressive disorder (MDD). MDD is characterized by altered interoception, which has also been associated with poor outcomes. The present study investigated whether RNT is directly associated with altered interoceptive processing. Interoceptive awareness toward the heart and stomach was probed on the Visceral Interoceptive Attention (VIA) task with fMRI in MDD individuals who were propensity-matched on the severity of depression and anxiety symptoms and relevant demographics but different in RNT intensity (High RNT [H-RNT, n = 48] & Low RNT [L-RNT, n = 49]), and in matched healthy volunteers (HC, n = 27). Both H-RNT and L-RNT MDD individuals revealed reduced stomach interoceptive processing compared to HC in the left medial frontal region and insular cortex (H-RNT: β = −1.04, L-RNT: β = −0.97), perirhinal cortex (H-RNT: β = −0.99, L-RNT: β = −1.03), and caudate nucleus (H-RNT: β = −1.06, L-RNT: β = −0.89). However, H-RNT was associated with decreased right medial temporal lobe activity including the hippocampus and amygdala during stomach interoceptive trials (β = −0.61) compared to L-RNT. Insular interoceptive processing was similar in H-RNT and L-RNT participants (β = −0.07, p = 0.92). MDD individuals with high RNT exhibited altered gastric interoceptive responses in brain areas that are important for associating the information with specific contexts and emotions. Attenuated interoceptive processing may contribute to RNT generation, non-adaptive information processing, action selection, and thus poor treatment outcome. [ABSTRACT FROM AUTHOR]

• Serum C-Reactive Protein (CRP) was negatively correlated with white matter integrity (fractional anisotropy, FA) in participants with major depressive disorder (MDD). • CRP was inversely associated with FA of the cingulum and fornix. • The ratio of kynurenic acid to quinolinic acid (KynA/QA) in serum was positively correlated with FA in participants with MDD. • KynA/QA was positively associated with FA in the fornix, superior thalamic radiations, corpus callosum, and cingulum bundles. • The effect of KynA/QA was equally driven by KynA and QA so that their ratio provided the greatest sensitivity. Kynurenic acid (KynA) and quinolinic acid (QA) are neuroactive kynurenine pathway (KP) metabolites that have neuroprotective and neurotoxic properties, respectively. At least partly as a result of immune activation, the ratio of KynA to QA in the blood is reduced in major depressive disorder (MDD) and has been reported to be positively correlated with gray matter volume in depression. This study examined whether the inflammatory mediator, C-reactive protein (CRP) and the putative neuroprotective index, KynA/QA, were associated with white matter integrity in MDD, and secondly, whether any such associations were independent of each other or whether the effect of CRP was mediated by KynA/QA. One hundred and sixty-six participants in the Tulsa 1000 study with a DSM-V diagnosis of MDD completed diffusion tensor imaging and provided a serum sample for the quantification of CRP, KynA, and QA. Correlational tractography was performed using DSI Studio to map the specific white matter pathways that correlated with CRP and KynA/QA. CRP was negatively related to KynA/QA (standardized beta coefficient, SBC = -0.35 with standard error, Std.E = 0.13, p < 0.01) after controlling for nine possible confounders, i.e., age, sex, body mass index (BMI), medication status, lifetime alcohol use, severity of depression, severity of anxiety, length of illness, and smoking status. Higher concentrations of CRP were associated with decreased white matter integrity (fractional anisotropy, FA) of the bilateral cingulum and fornix after controlling for the nine potential confounders (SBC = -0.43, Std.E = 0.13, p = 0.002). Greater serum KynA/QA was associated with increased white matter integrity of the bilateral fornix, bilateral superior thalamic radiations, corpus callosum, and bilateral cingulum bundles after controlling for the same possible confounders (SBC = 0.26, Std.E = 0.09, p = 0.005). The relationship between CRP and FA was not mediated by KynA/QA. Exploratory analyses also showed that KynA/QA but not CRP was associated with self-reported positive affect, attentiveness, and fatigue measured with the PANASX (SBCs = 0.17–0.23). Taken together, these results are consistent with the hypothesis that within a subgroup of MDD patients, a higher level of systemic inflammation alters the balance of KP metabolism but also raise the possibility that CRP and neuroactive KP metabolites represent independent molecular mechanisms underlying white matter alterations in MDD. [ABSTRACT FROM AUTHOR]

Empathic communication between a patient and therapist is an essential component of psychotherapy. However, finding objective neural markers of the quality of the psychotherapeutic relationship have been elusive. Here we conceptualize how a neuroscience-informed approach involving real-time neurofeedback, facilitated via existing functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) technologies, could provide objective information for facilitating therapeutic rapport. We propose several neurofeedback-assisted psychotherapy (NF-AP) approaches that could be studied as a way to optimize the experience of the individual patient and therapist across the spectrum of psychotherapeutic treatment. Finally, we consider how the possible strengths of these approaches are balanced by their current limitations and discuss the future prospects of NF-AP. • Biomarkers of empathy and rapport may be evaluated using neurofeedback. • Neurofeedback can be used to measure therapeutic alliance between patients and therapists. • The application of neurofeedback in psychotherapy is an innovative approach. [ABSTRACT FROM AUTHOR]

Although the amygdala plays an important part in the pathogenesis of anxiety and generation of exteroceptive fear, recent discoveries have challenged the directionality of this brain-behavior relationship with respect to interoceptive fear. Here we highlight several paradoxical findings including: (1) amygdala lesion patients who experience excessive fear and panic following inhalation of carbon dioxide (CO 2), (2) clinically anxious patients who have significantly smaller (rather than larger) amygdalae and a pronounced hypersensitivity toward CO 2 , and (3) epilepsy patients who exhibit apnea immediately following stimulation of their amygdala yet have no awareness that their breathing has stopped. The above findings elucidate an entirely novel role for the amygdala in the induction of apnea and inhibition of CO 2 -induced fear. Such a role is plausible given the strong inhibitory connections linking the central nucleus of the amygdala with respiratory and chemoreceptive centers in the brainstem. Based on this anatomical arrangement, we propose a model of Apnea-induced Anxiety (AiA) which predicts that recurring episodes of apnea are being unconsciously elicited by amygdala activation, resulting in transient spikes in CO 2 that provoke fear and anxiety, and lead to characteristic patterns of escape and avoidance behavior in patients spanning the spectrum of anxiety. If this new conception of AiA proves to be true, and activation of the amygdala can repeatedly trigger states of apnea outside of one's awareness, then it remains possible that the chronicity of anxiety disorders is being interoceptively driven by a chemoreceptive system struggling to maintain homeostasis in the midst of these breathless states. • The causal role of the amygdala with regard to fear and anxiety remains controversial. • Research is reviewed across lesion studies, intracranial stimulation, and volumetric MRI. • The amygdala inhibits fear evoked by elevations in CO 2. • Stimulation of the amygdala triggers a state of apnea outside of one's awareness. • We propose a model of apnea-induced anxiety that can be tested in future studies. [ABSTRACT FROM AUTHOR]

Background: Adherence to treatment, i.e. the extent to which a patient's therapeutic engagement coincides with the prescribed treatment, is among the most important problems in mental health care. The current study investigated the influence of pairing an acute positive reinforcing dopaminergic/noradrenergic effect (methylphenidate, MPH) with a standard antidepressant on the rates of adherence to medication treatment. The primary objective of this study was to determine whether MPH + escitalopram resulted in higher rates of medication adherence relative to placebo + escitalopram. Methods: Twenty participants with moderate to severe depression were 1–1 randomized to either (1) 5 mg MPH + 10 mg escitalopram or (2) placebo + 10 mg escitalopram with the possibility for a dose increase at 4 weeks. A Bayesian analysis was conducted to evaluate the outcomes. Results: First, neither percent Pill count nor Medication Electronic Monitoring System adherence showed that MPH was superior to placebo. In fact, placebo showed slightly higher adherence rates on the primary (7.82% better than MPH) and secondary (7.07% better than MPH) outcomes. There was a less than 25% chance of MPH augmentation showing at least as good or better adherence than placebo. Second, both groups showed a significant effect of treatment on the QIDS-SR with a median effect of an 8.6-point score reduction. Third, neither subjective measures of adherence attitudes nor socio-demographic covariates had a significant influence on the primary or secondary outcome variables. Conclusions: These data do not support the use of MPH to increase adherence to antidepressant medication in individuals with moderate to severe depression. ClinicalTrials.gov identifier NCT03388164, registered on 01/02/2018. [ABSTRACT FROM AUTHOR]

It has been proposed that self-awareness (SA), a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). Such a proposal predicts that damage to these regions should disrupt or even abolish SA. We tested this prediction in a rare neurological patient with extensive bilateral brain damage encompassing the insula, ACC, mPFC, and the medial temporal lobes. In spite of severe amnesia, which partially affected his "autobiographical self", the patient's SA remained fundamentally intact. His Core SA, including basic self-recognition and sense of self-agency, was preserved. His Extended SA and Introspective SA were also largely intact, as he has a stable self-concept and intact higher-order metacognitive abilities. The results suggest that the insular cortex, ACC and mPFC are not required for most aspects of SA. Our findings are compatible with the hypothesis that SA is likely to emerge from more distributed interactions among brain networks including those in the brainstem, thalamus, and posteromedial cortices. [ABSTRACT FROM AUTHOR]

• Ibuprofen acts as a PPARγ agonist and thus may confer antidepressant effects. • We examined the impact of ibuprofen and PPARγ on emotion-related neural activity. • At the doses used, ibuprofen did not significantly change PPARγ gene expression. • Ibuprofen dose negatively related to activation in the dlPFC and fusiform gyrus. • PPARγ gene expression positively related to activation in the insula. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have shown initial promise in producing antidepressant effects. This is perhaps due to these drugs being peroxisome proliferator-activated receptor gamma (PPARγ) agonists, in addition to their inhibition of cyclooxygenase enzymes. Some, albeit mixed, evidence suggests that PPARγ agonists have antidepressant effects in humans and animals. This double-blind, placebo-controlled, pharmacologic functional magnetic resonance imaging (ph-fMRI) study aimed to elucidate the impact of ibuprofen on emotion-related neural activity and determine whether observed effects were due to changes in PPARγ gene expression. Twenty healthy volunteers completed an emotional face matching task during three fMRI sessions, conducted one week apart. Placebo, 200 mg, or 600 mg ibuprofen was administered 1 h prior to each scan in a pseudo-randomized order. Peripheral blood mononuclear cells were collected at each session to isolate RNA for PPARγ gene expression. At the doses used, ibuprofen did not significantly change PPARγ gene expression. Ibuprofen dose was associated with decreased blood oxygen level-dependent (BOLD) activation in the dorsolateral prefrontal cortex and fusiform gyrus during emotional face processing (faces-shapes). Additionally, PPARγ gene expression was associated with increased BOLD activation in the insula and transverse and superior temporal gyri (faces-shapes). No interaction effects between ibuprofen dose and PPARγ gene expression on BOLD activation were observed. Thus, results suggest that ibuprofen and PPARγ may have independent effects on emotional neurocircuitry. Future studies are needed to further delineate the roles of ibuprofen and PPARγ in exerting antidepressant effects in healthy as well as clinical populations. [ABSTRACT FROM AUTHOR]

Floatation‐Reduced Environmental Stimulation Therapy (REST) is a procedure that reduces stimulation of the human nervous system by minimizing sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational, and proprioceptive channels, in addition to minimizing musculoskeletal movement and speech. Initial research has found that Floatation‐REST can elicit short‐term reductions in anxiety, depression, and pain, yet little is known about the brain networks impacted by the intervention. This study represents the first functional neuroimaging investigation of Floatation‐REST, and we utilized a data‐driven exploratory analysis to determine whether the intervention leads to altered patterns of resting‐state functional connectivity (rsFC). Healthy participants underwent functional magnetic resonance imaging (fMRI) before and after 90 min of Floatation‐REST or a control condition that entailed resting supine in a zero‐gravity chair for an equivalent amount of time. Multivariate Distance Matrix Regression (MDMR), a statistically‐stringent whole‐brain searchlight approach, guided subsequent seed‐based connectivity analyses of the resting‐state fMRI data. MDMR identified peak clusters of rsFC change between the pre‐ and post‐float fMRI, revealing significant decreases in rsFC both within and between posterior hubs of the default‐mode network (DMN) and a large swath of cortical tissue encompassing the primary and secondary somatomotor cortices extending into the posterior insula. The control condition, an active form of REST, showed a similar pattern of reduced rsFC. Thus, reduced stimulation of the nervous system appears to be reflected by reduced rsFC within the brain networks most responsible for creating and mapping our sense of self. [ABSTRACT FROM AUTHOR]

Body image disturbance (BID) is a core feature of eating disorders, for which there are few objective markers. We examined the feasibility of a novel digital tool, "Somatomap", to index BID related to anorexia nervosa (AN) severity. Fifty-five AN inpatients and 55 healthy comparisons (HC) outlined their body concerns on a 2-Dimensional avatar. Next, they indicated sizes/shapes of body parts for their current and ideal body using sliders on a 3-Dimensional avatar. Physical measurements of corresponding body parts, in cm, were collected for reference. We evaluated regional differences in BID using proportional z-scores to generate statistical body maps, and multivariate analysis of covariance to assess perceptual discrepancies for current body, ideal body, and body dissatisfaction. The AN group demonstrated greater regional perceptual inaccuracy for their current body than HC, greater discrepancies between their current and ideal body, and higher body dissatisfaction than HCs. AN body concerns localized disproportionately to the chest and lower abdomen. The number of body concerns and perceptual inaccuracy for individual body parts was strongly associated with Eating Disorder Examination Questionnaire (Global EDE-Q) scores across both groups. Somatomap demonstrated feasibility to capture multidimensional aspects of BID. Several implicit measures were significantly associated with illness severity, suggesting potential utility for identifying objective BID markers. [ABSTRACT FROM AUTHOR]

Maladaptive behavior during approach-avoidance conflict (AAC) is common to multiple psychiatric disorders. Using computational modeling, we previously reported that individuals with depression, anxiety, and substance use disorders (DEP/ANX; SUDs) exhibited differences in decision uncertainty and sensitivity to negative outcomes versus reward (emotional conflict) relative to healthy controls (HCs). However, it remains unknown whether these computational parameters and group differences are stable over time. We analyzed 1-year follow-up data from a subset of the same participants (N = 325) to assess parameter stability and relationships to other clinical and task measures. We assessed group differences in the entire sample as well as a subset matched for age and IQ across HCs (N = 48), SUDs (N = 29), and DEP/ANX (N = 121). We also assessed 2–3 week reliability in a separate sample of 30 HCs. Emotional conflict and decision uncertainty parameters showed moderate 1-year intra-class correlations (.52 and.46, respectively) and moderate to excellent correlations over the shorter period (.84 and.54, respectively). Similar to previous baseline findings, parameters correlated with multiple response time measures (ps <.001) and self-reported anxiety (r =.30, p <.001) and decision difficulty (r =.44, p <.001). Linear mixed effects analyses revealed that patients remained higher in decision uncertainty (SUDs, p =.009) and lower in emotional conflict (SUDs, p =.004, DEP/ANX, p =.02) relative to HCs. This computational modelling approach may therefore offer relatively stable markers of transdiagnostic psychopathology. [ABSTRACT FROM AUTHOR]

Eating disorder and body dysmorphic disorder symptoms overlap and frequently co-occur clinically, yet whether they represent one or more underlying constructs in the general population is unknown. We examined relationships between these symptoms on underlying factor structures and dimensional distributions in a young adult sample of 328 students using the Eating Disorder Examination-Questionnaire (EDE-Q 6.0) and the Dysmorphic Concern Questionnaire (DCQ). We performed factor and hierarchical cluster analyses on pooled items and Gaussian mixture modeling on score distributions. EDE-Q 6.0 and DCQ total scores were correlated (r = 0.53, p <.001). Pooled items demonstrated a three-factor solution; DCQ items separating from two EDE-Q 6.0 factors. Hierarchical clustering yielded a two-cluster solution that separated the two scales. Mixture modeling demonstrated that more than one underlying distribution best fit the data for each scale. These results suggest that the EDE-Q 6.0 and DCQ measure different sets of psychopathological features, despite their tendency to track together. Moreover, eating disorder and body dysmorphic phenotypes each show nonuniform variation from normal to abnormal. This argues against using linear dimensional applications of these scales to assess individuals ranging from mild to severe in symptom severity. Separate scales may be necessary to characterize lower and higher ranges of clinical severity. [ABSTRACT FROM AUTHOR]

• Higher BMI is associated with worse eating disorder symptoms in models and nonmodels. • Most models and nonmodels with clinically significant eating disorder symptoms had normal BMIs. • Using a <18.5 BMI cutoff is likely to miss female models with eating disorders. Low body mass index (BMI<18/18.5) is utilized as a mandated cutoff for professional fashion model employment, based on assumptions that low BMI indicates eating disorder pathology. No previous studies have examined the association between experimenter-measured BMI and eating disorder symptomatology in professional fashion models. We measured BMI and Eating Disorder Examination Questionnaire (EDE-Q) responses in United Kingdom (UK) professional fashion models, and nonmodels. Characteristics were compared using robust standardized mean difference (rSMD) obtained via probability of superiority. Associations between BMI and eating disorder symptomatology were examined using robust regression, controlling for age. Models exhibited lower BMI but higher fat-percentage and muscle mass. On the EDE-Q, models had higher Restraint, Global, Eating, and Weight Concerns, and similar Shape Concern scores compared to nonmodels. BMI was positively associated with eating disorder symptoms in both groups, and all but one of the eight models with clinically significant EDE-Q level had ≥18.5 measured BMI. Lower BMI was not indicative of worse eating disorder symptomatology in models or nonmodels. Thus, using a low BMI cutoff (<18.5) may not be an appropriate single index of health for detecting elevated eating disorder symptoms in models. Different policies to protect models' health should be considered. [ABSTRACT FROM AUTHOR]

Background: Imbalances in approach-avoidance conflict (AAC) decision-making (e.g., sacrificing rewards to avoid negative outcomes) are considered central to multiple psychiatric disorders. We used computational modelling to examine 2 factors that are often not distinguished in descriptive analyses of AAC: decision uncertainty and sensitivity to negative outcomes versus rewards (emotional conflict). Methods: A previously validated AAC task was completed by 478 participants, including healthy controls (n = 59), people with substance use disorders (n = 159) and people with depression and/or anxiety disorders who did not have substance use disorders (n = 260). Using an active inference model, we estimated individual-level values for a model parameter that reflected decision uncertainty and another that reflected emotional conflict. We also repeated analyses in a subsample (59 healthy controls, 161 people with depression and/or anxiety disorders, 56 people with substance use disorders) that was propensity-matched for age and general intelligence. Results: The model showed high accuracy (72%). As further validation, parameters correlated with reaction times and self-reported task motivations in expected directions. The emotional conflict parameter further correlated with self-reported anxiety during the task (r = 0.32, p < 0.001), and the decision uncertainty parameter correlated with self-reported difficulty making decisions (r = 0.45, p < 0.001). Compared to healthy controls, people with depression and/or anxiety disorders and people with substance use disorders showed higher decision uncertainty in the propensity-matched sample (t = 2.16, p = 0.03, and t = 2.88, p = 0.005, respectively), with analogous results in the full sample; people with substance use disorders also showed lower emotional conflict in the full sample (t = 3.17, p = 0.002). Limitations: This study was limited by heterogeneity of the clinical sample and an inability to examine learning. Conclusion: These results suggest that reduced confidence in how to act, rather than increased emotional conflict, may explain maladaptive approach-avoidance behaviours in people with psychiatric disorders. [ABSTRACT FROM AUTHOR]

To survive, organisms must effectively respond to the challenge of maintaining their physiological integrity in the face of an ever-changing environment. Preserving this homeostasis critically relies on adaptive behavior. In this review, we consider recent frameworks that extend classical homeostatic control via reflex arcs to include more flexible forms of adaptive behavior that take interoceptive context, experiences, and expectations into account. Specifically, we define a landscape for computational models of interoception, body regulation, and forecasting, address these models' unique challenges in relation to translational research efforts, and discuss what they can teach us about cognition as well as physical and mental health. The sensory-control loop can be used as a guiding principle to align different computational models of interoception and body regulation. Recent computational frameworks focus on formulating body regulation via flexible, adaptive control mechanisms that extend classical reflex arcs. The perception and regulation of interoceptive signals pose tangible and unique challenges for computational modeling. Concrete computational frameworks of brain–body interactions hold great potential for translational research. Modeling approaches could be applied to develop testable 'computational biomarkers' to support diagnostic, prognostic, or treatment efforts, particularly in individuals with symptoms originating from maladaptive brain–body interactions. [ABSTRACT FROM AUTHOR]

Recent neurocomputational theories have hypothesized that abnormalities in prior beliefs and/or the precision-weighting of afferent interoceptive signals may facilitate the transdiagnostic emergence of psychopathology. Specifically, it has been suggested that, in certain psychiatric disorders, interoceptive processing mechanisms either over-weight prior beliefs or under-weight signals from the viscera (or both), leading to a failure to accurately update beliefs about the body. However, this has not been directly tested empirically. To evaluate the potential roles of prior beliefs and interoceptive precision in this context, we fit a Bayesian computational model to behavior in a transdiagnostic patient sample during an interoceptive awareness (heartbeat tapping) task. Modelling revealed that, during an interoceptive perturbation condition (inspiratory breath-holding during heartbeat tapping), healthy individuals (N = 52) assigned greater precision to ascending cardiac signals than individuals with symptoms of anxiety (N = 15), depression (N = 69), co-morbid depression/anxiety (N = 153), substance use disorders (N = 131), and eating disorders (N = 14)–who failed to increase their precision estimates from resting levels. In contrast, we did not find strong evidence for differences in prior beliefs. These results provide the first empirical computational modeling evidence of a selective dysfunction in adaptive interoceptive processing in psychiatric conditions, and lay the groundwork for future studies examining how reduced interoceptive precision influences body regulation and interoceptively-guided decision-making. Author summary: Interoception is the process by which the nervous system senses the internal state of the body. It provides the brain with important information to adaptively guide the regulation of both internal body states and behavior. Interoceptive dysfunction is thought to play a role in multiple psychiatric disorders. Theoretical models propose that the computational mechanisms of interoceptive dysfunction are caused by overly precise prior beliefs about body states ("hyperprecise priors") or underestimates of the reliability of the information carried by ascending signals from the body ("low sensory precision"). Our empirical approach tested for evidence of these mechanisms across several psychiatric disorders, using a computational model of perception during performance of a heartbeat perception task. We found evidence of low sensory precision within individuals with anxiety, depression, eating disorders, and/or substance use disorders, relative to healthy individuals. This difference occurred only during a breath-holding condition designed to enhance heartbeat signals. We did not find strong evidence for hyperprecise priors in the patient groups. The data from this study support the argument for computational mechanisms of interoceptive dysfunction across several psychiatric disorders, and suggest that these conditions may be characterized by an inability to adjust sensory precision when signals from the body change. [ABSTRACT FROM AUTHOR]

Background: Electroencephalography (EEG) studies suggest that major depressive disorder (MDD) is associated with lower left than right frontal brain activity (asymmetry), a pattern appearing stronger in women than men, and when elicited during emotionally-relevant paradigms versus an uncontrolled resting state. However, it is unclear whether this asymmetry pattern generalizes to the common presentation of MDD with co-occurring anxiety. Moreover, asymmetry may differ for anxiety subtypes, wherein anxious apprehension (AnxApp: worry characteristic of generalized anxiety disorder) appears left-lateralized, but anxious arousal (AnxAro: panic characteristic of social anxiety, posttraumatic stress, and panic disorders) may be right-lateralized.Methods: This analysis attempted to replicate frontal EEG asymmetry patterns using functional magnetic resonance imaging (fMRI). Participants completed clinical interviews and a monetary incentive delay (MID) task during fMRI recording. We compared five groups of right-handed women from the Tulsa 1000 study, MDD (n=40), MDD-AnxApp (n=26), MDD-AnxAro (n=34), MDD-Both (with AnxApp and AnxAro; n=26), and healthy controls (CTL; n=24), as a function of MID anticipation condition (no win/loss, win, loss) and hemisphere on frontal blood oxygen-level-dependent (BOLD) signal.Results: CTL exhibited higher bilateral superior, middle, and inferior middle frontal gyrus BOLD signal than the four MDD groups for high arousal (win and loss) conditions. However, frontal attenuations were unrelated to current depression/anxiety symptoms, suggestive of a trait as opposed to a state marker.Limitations: This was a cross-sectional analysis restricted to women.Conclusions: Reduced prefrontal cortex recruitment during processing of both positively and negatively valenced stimuli is consistent with the emotion context insensitivity theory of MDD. [ABSTRACT FROM AUTHOR]

Several studies have recently suggested that an abnormal processing of respiratory interoceptive and nociceptive (painful) stimuli may contribute to eating disorder (ED) pathophysiology. Mood and anxiety disorders (MA) are also characterized by abnormal respiratory symptoms, and show substantial comorbidity with ED. However, no studies have examined both respiratory and pain processing simultaneously within ED and MA. The present study systematically evaluated responses to perturbations of respiratory and nociceptive signals across the levels of physiology, behavior, and symptom report in a transdiagnostic ED sample (n = 51) that was individually matched to MA individuals (n = 51) and healthy comparisons (HC; n = 51). Participants underwent an inspiratory breath-holding challenge as a probe of respiratory interoception and a cold pressor challenge as a probe of pain processing. We expected both clinical groups to report greater stress and fear in response to respiratory and nociceptive perturbation than HCs, in the absence of differential physiological and behavioral responses. During breath-holding, both the ED and MA groups reported significantly more stress, feelings of suffocation, and suffocation fear than HC, with the ED group reporting the most severe symptoms. Moreover, anxiety sensitivity was related to suffocation fear only in the ED group. The heightened affective responses in the current study occurred in the absence of group differences in behavioral (breath hold duration, cold pressor duration) and physiological (end-tidal carbon dioxide, end-tidal oxygen, heart rate, skin conductance) responses. Against our expectations, there were no group differences in the response to cold pain stimulation. A matched-subgroup analysis focusing on individuals with anorexia nervosa (n = 30) produced similar results. These findings underscore the presence of abnormal respiratory interoception in MA and suggest that hyperreactivity to respiratory signals may be a potentially overlooked clinical feature of ED. [ABSTRACT FROM AUTHOR]

It has recently been proposed that measures of the perception of the state of one's own body ("interoception") can be categorised as one of several types depending on both how an assessment is obtained (objective measurement vs. self-report) and what is assessed (degree of interoceptive attention vs. accuracy of interoceptive perception). Under this model, a distinction is made between beliefs regarding the degree to which interoceptive signals are the object of attention and beliefs regarding one's ability to perceive accurately interoceptive signals. This distinction is difficult to test, however, because of the paucity of measures designed to assess self-reported perception of one's own interoceptive accuracy. This article therefore reports on the development of such a measure, the Interoceptive Accuracy Scale (IAS). Use of this measure enables assessment of the proposed distinction between beliefs regarding attention to, and accuracy in perceiving, interoceptive signals. Across six studies, we report on the development of the IAS and, importantly, its relationship with measures of trait self-reported interoceptive attention, objective interoceptive accuracy, confidence in the accuracy of specific interoceptive percepts, and metacognition with respect to interoceptive accuracy. Results support the distinction between individual differences in perceived attention towards interoceptive information and the accuracy of interoceptive perception. [ABSTRACT FROM AUTHOR]

Abstract: Cardiorespiratory fluctuations such as changes in heart rate or respiration volume influence the temporal dynamics of cerebral blood flow (CBF) measurements during arterial spin labeling (ASL) fMRI. This “physiological noise” can confound estimates of resting state network activity, and it may lower the signal‐to‐noise ratio of ASL during task‐related experiments. In this study we examined several methods for minimizing the contributions of both synchronized and non‐synchronized physiological noise in ASL measures of CBF, by combining the RETROICOR approach with different linear deconvolution models. We evaluated the amount of variance in CBF that could be explained by each method during physiological rest, in both resting state and task performance conditions. To further demonstrate the feasibility of this approach, we induced low‐frequency cardiorespiratory deviations via peripheral adrenergic stimulation with isoproterenol, and determined how these fluctuations influenced CBF, before and after applying noise correction. By suppressing physiological noise, we observed substantial improvements in the signal‐to‐noise ratio at the individual and group activation levels. Our results suggest that variations in cardiac and respiratory parameters can account for a large proportion of the variance in resting and task‐based CBF, and indicate that regressing out these non‐neuronal signal variations improves the intrinsically low signal‐to‐noise ratio of ASL. This approach may help to better identify and control physiologically driven activations in ASL resting state and task‐based analyses. [ABSTRACT FROM AUTHOR]

Prominent theories emphasize key roles for the insular cortex in the central representation of interoceptive sensations, but how this brain region responds dynamically to changes in interoceptive state remains incompletely understood. Here, we systematically modulated cardiorespiratory sensations in humans using bolus infusions of isoproterenol, a rapidly acting peripheral beta-adrenergic agonist similar to adrenaline. To identify central neural processes underlying these parametrically modulated interoceptive states, we used pharmacological functional magnetic resonance imaging (phMRI) to simultaneously measure blood-oxygenation-level dependent (BOLD) and arterial spin labelling (ASL) signals in healthy participants. Isoproterenol infusions induced dose-dependent increases in heart rate and cardiorespiratory interoception, with all participants endorsing increased sensations at the highest dose. These reports were accompanied by increased BOLD and ASL activation of the right insular cortex at the highest dose. Different responses across insula subregions were also observed. During anticipation, insula activation increased in more anterior regions. During stimulation, activation increased in the mid-dorsal and posterior insula on the right, but decreased in the same regions on the left. This study demonstrates the feasibility of phMRI for assessing brain activation during adrenergic interoceptive stimulation, and provides further evidence supporting a dynamic role for the insula in representing changes in cardiorespiratory states. This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'. [ABSTRACT FROM AUTHOR]

The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of neuroscience-based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases. [ABSTRACT FROM AUTHOR]