Induction of altered states of consciousness during Floatation-REST is associated with the dissolution of body boundaries and the distortion of subjective time.

Floatation-REST (Reduced Environmental Stimulation Therapy) minimizes stimulation of the nervous system by immersing subjects in an environment without sound or light while they effortlessly float in thermoneutral water supersaturated with Epsom salt. Here we investigated the relationship between altered states of consciousness (ASC) and its association with the affective changes induced by Floatation-REST. Using a within-subject crossover design, 50 healthy subjects were randomized to 60 min of Floatation-REST or 60 min of Bed-REST (an active control condition that entailed lying supine on a warm waterbed in a dark and quiet room). Following Floatation-REST, subjects felt significantly more relaxed, less anxious, and less tired than after Bed-REST. Floatation-REST also induced significantly more pronounced ASC characterized by the dissolution of body boundaries and the distortion of subjective time. The loss of body boundaries mediated the loss of anxiety, revealing a novel mechanism by which Floatation-REST exerts its anxiolytic effect.

A case of severe anterograde amnesia in the era of smartphone technology.

A.V. is a young herpes simplex encephalitis (HSE) survivor who suffered extensive bilateral damage to the medial temporal lobe (MTL) leading to a severe and pervasive form of anterograde amnesia. Structural Magnetic Resonance Imaging (MRI) revealed lesions that encompass the hippocampus and amygdala in both hemispheres and that extend more laterally in the right temporal lobe. At the same time, detailed neuropsychological testing showed that the disparity between A.V.'s preserved intellectual functioning (Full Scale IQ: 115) and severe memory deficit (Delayed Memory Index: 42) is one of the largest on record. Despite this deficit, A.V. has regained a higher level of functioning and autonomy compared to previously documented amnesic cases with major bilateral MTL lesions. As a millennial, one advantage which A.V. has over prior amnesic cases is fluency with digital technology - particularly the smartphone. The analysis of his phone and specific app usage showed a pattern that is consistent with the strategy to offload cognitive tasks that would normally be supported by the MTL. A.V.'s behavior is significant in terms of rehabilitation and may have broader implications at the societal level and for public health given the ubiquity of smartphone technology and its potential to become integrated with neural mnemonic functions.

The impact of floatation therapy on body image and anxiety in anorexia nervosa: a randomised clinical efficacy trial.

Background: Body image disturbance and anxiety are core features of anorexia nervosa (AN), a psychiatric disorder with one of the highest mortality rates. This study examined the efficacy of a novel non-pharmacological treatment, floatation-REST (Reduced Environmental Stimulation Therapy) on body image disturbance and anxiety in inpatients with AN. Methods: This parallel group randomised controlled trial compared floatation-REST vs. care as usual in women and girls hospitalised for treatment of AN in Tulsa, Oklahoma, USA. Participants were randomised on a 2:1 ratio to receive eight, twice-weekly, 60-min floatation-REST sessions for 4 weeks, in addition to care as usual, or to receive care as usual. The primary outcome was the average change in body dissatisfaction from pre- to post-float as measured by the Photographic Figure Rating Scale. The secondary outcome was the average change in anxiety from pre- to post-float as measured by the state version of the State Trait Anxiety Inventory. Longitudinal effects of floatation-REST on body dissatisfaction were also examined. All analyses were conducted using the intention-to-treat principle. Planned linear mixed models tested the effect of floatation-REST vs. care as usual. The trial was preregistered (clinicaltrials.govNCT03610451). Findings: Between March 16, 2018 and February 25, 2021, 133 participants were screened for eligibility, and 86 were consented. Eighteen were excluded after consent, for a final randomisation sample of 68 participants (45 floatation-REST; 23 care as usual). There were two session by condition interactions on body dissatisfaction (p = 0.00026) and state anxiety (p < 0.0001), such that the floatation-REST group exhibited acute (i.e., pre- to post-session) reductions in body dissatisfaction (floatation-REST group mean change (Δm) = -0.43; 95% CI -0.56 to -0.30, p < 0.0001, Cohen's d = 0.23), and acute reductions in anxiety (floatation-REST group Δm = -15.75; 95% CI -17.95 to -13.56, p < 0.0001, Cohen's d = 1.52); however, the care as usual group exhibited no significant changes. With regard to longitudinal results, there was a significant time by treatment interaction between baseline and immediately post intervention (p = 0.012) and baseline and six-month follow up (p = 0.0019). At immediately post intervention, there was a trending reduction in body dissatisfaction for the floatation-REST group (Δm = -0.41, 95% CI -0.86 to 0.03, p = 0.068) and care as usual group (Δm = 0.61; 95% CI -0.04 to 1.27, p = 0.070). At six-months post-intervention, the floatation-REST group exhibited lower body dissatisfaction (Δm = -0.91; 95% CI -1.37 to -0.45, p = 0.0020, Cohen's d = 0.53) whereas the care as usual group reported no change in body dissatisfaction (Δm = 0.35; 95% CI -0.28 to 0.98, p = 0.96) relative to baseline. There were no adverse events related to the trial during the study. Interpretation: Our findings suggest that Floatation-REST decreased body dissatisfaction compared to care as usual acutely after each float session and at six-month follow-up. Floatation-REST has potential utility for the treatment of body image disturbance and anxiety in AN. These results may be limited by some generalisability concerns given the recruitment of a modest sample receiving inpatient treatment at a single site. Funding: The William K. Warren Foundation.

A randomized controlled safety and feasibility trial of floatation-REST in anxious and depressed individuals.

Background: Reduced Environmental Stimulation Therapy via floatation (floatation-REST) is a behavioral intervention designed to attenuate exteroceptive sensory input to the nervous system. Pilot studies in anxious and depressed individuals demonstrated that single sessions of floatation-REST are safe, well-tolerated, and associated with acute anxiolysis. However, there is not sufficient evidence of the feasibility of floatation-REST as a repeated intervention. Methods: We randomized 75 individuals with anxiety and depression to six sessions of floatation-REST in different formats (pool-REST or pool-REST preferred) or an active comparator (chair-REST). Feasibility was assessed via adherence rate to the assigned intervention, tolerability via duration of REST utilization and overall study dropout rate, and safety via incidence of serious or non-serious adverse events. Results: Six-session adherence was 85% for pool-REST, 89% for pool-REST preferred, and 74% for chair-REST. Dropout rates did not differ significantly between the treatment conditions. Mean session durations were consistently above 50 minutes, and when allowed to choose the duration and frequency, participants opted to float for an average of 75 minutes. 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: Taken together, 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.

Parieto-occipital ERP indicators of gut mechanosensation in humans.

Understanding the neural processes governing the human gut-brain connection has been challenging due to the inaccessibility of the body's interior. Here, we investigated neural responses to gastrointestinal sensation using a minimally invasive mechanosensory probe by quantifying brain, stomach, and perceptual responses following the ingestion of a vibrating capsule. Participants successfully perceived capsule stimulation under two vibration conditions (normal and enhanced), as evidenced by above chance accuracy scores. Perceptual accuracy improved significantly during the enhanced relative to normal stimulation, which was associated with faster stimulation detection and reduced reaction time variability. Capsule stimulation induced late neural responses in parieto-occipital electrodes near the midline. Moreover, these 'gastric evoked potentials' showed intensity-dependent increases in amplitude and were significantly correlated with perceptual accuracy. Our results replicated in a separate experiment, and abdominal X-ray imaging localized most capsule stimulations to the gastroduodenal segments. Combined with our prior observation that a Bayesian model is capable of estimating computational parameters of gut-brain mechanosensation, these findings highlight a unique form of enterically-focused sensory monitoring within the human brain, with implications for understanding gut feelings and gut-brain interactions in healthy and clinical populations.

Exploring the acute cardiovascular effects of Floatation-REST.

The central nervous system (CNS) exerts a strong regulatory influence over the cardiovascular system in response to environmental demands. Floatation-REST (Reduced Environmental Stimulation Therapy) is an intervention that minimizes stimulation from the environment, yet little is known about the autonomic consequences of reducing external sensory input to the CNS. We recently found that Floatation-REST induces a strong anxiolytic effect in anxious patients while paradoxically enhancing their interoceptive awareness for cardiorespiratory sensations. To further investigate the physiologic nature of this anxiolytic effect, the present study measured acute cardiovascular changes during Floatation-REST using wireless and waterproof equipment that allowed for concurrent measurement of heart rate, heart rate variability (HRV), breathing rate, and blood pressure. Using a within-subjects crossover design, 37 clinically anxious participants with high levels of anxiety sensitivity and 20 non-anxious comparison participants were randomly assigned to undergo a 90-min session of either Floatation-REST or an exteroceptive comparison condition that entailed watching a relaxing nature film. Measures of state anxiety and serenity were collected before and after each session, while indices of autonomic activity were measured throughout each session. HRV was calculated using both time-series and frequency domain analyses. Linear mixed-effects modeling revealed a significant main effect of condition such that relative to the film condition, Floatation-REST elicited significant decreases (p < 0.001) in diastolic blood pressure, systolic blood pressure, breathing rate, and certain metrics of HRV including the standard deviation of the interbeat interval (SDNN), low-frequency HRV, and very low-frequency HRV. Heart rate showed a non-significant trend (p = 0.073) toward being lower in the float condition, especially toward the beginning of the session. The only metric that showed a significant increase during Floatation-REST was normalized high-frequency HRV (p < 0.001). The observed physiological changes were consistent across both anxious and non-anxious participants, and there were no significant group by condition interactions. Blood pressure was the only cardiac metric significantly associated with float-related reductions in state anxiety and increases in serenity. These findings suggest that Floatation-REST lowers sympathetic arousal and alters the balance of the autonomic nervous system toward a more parasympathetic state. Clinical trial registration: [https://clinicaltrials.gov/show/NCT03051074], identifier [NCT03051074].

CO2 reactivity as a biomarker of exposure-based therapy non-response: study protocol.

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).

Amygdala-driven apnea and the chemoreceptive origin of anxiety.

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 (CO2), (2) clinically anxious patients who have significantly smaller (rather than larger) amygdalae and a pronounced hypersensitivity toward CO2, 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 CO2-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 CO2 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.

Association of Generalized Anxiety Disorder With Autonomic Hypersensitivity and Blunted Ventromedial Prefrontal Cortex Activity During Peripheral Adrenergic Stimulation: A Randomized Clinical Trial.

IMPORTANCE: ß-Adrenergic stimulation elicits heart palpitations and dyspnea, key features of acute anxiety and sympathetic arousal, yet no neuroimaging studies have examined how the pharmacologic modulation of interoceptive signals is associated with fear-related neurocircuitry in individuals with generalized anxiety disorder (GAD). OBJECTIVE: To examine the neural circuitry underlying autonomic arousal induced via isoproterenol, a rapidly acting, peripheral ß-adrenergic agonist akin to adrenaline. DESIGN, SETTING, AND PARTICIPANTS: This crossover randomized clinical trial of 58 women with artifact-free data was conducted from January 1, 2017, to November 31, 2019, at the Laureate Institute for Brain Research in Tulsa, Oklahoma. EXPOSURES: Functional magnetic resonance imaging was used to assess neural responses during randomized intravenous bolus infusions of isoproterenol (0.5 and 2.0 µg) and saline, each administered twice in a double-blind fashion. MAIN OUTCOMES AND MEASURES: Blood oxygen level-dependent responses across the whole brain during isoproterenol administration in patients with GAD vs healthy comparators. Cardiac and respiratory responses, as well as interoceptive awareness and anxiety, were also measured during the infusion protocol. RESULTS: Of the 58 female study participants, 29 had GAD (mean [SD] age, 26.9 [6.8] years) and 29 were matched healthy comparators (mean [SD] age, 24.4 [5.0] years). During the 0.5-µg dose of isoproterenol, the GAD group exhibited higher heart rate responses (b = 5.34; 95% CI, 2.06-8.61; P = .002), higher intensity ratings of cardiorespiratory sensations (b = 8.38; 95% CI, 2.05-14.71; P = .01), higher levels of self-reported anxiety (b = 1.04; 95% CI, 0.33-1.76; P = .005), and significant hypoactivation in the ventromedial prefrontal cortex (vmPFC) that was evident throughout peak response (Cohen d = 1.55; P < .001) and early recovery (Cohen d = 1.52; P < .001) periods. Correlational analysis of physiological and subjective indexes and percentage of signal change extracted during the 0.5-µg dose revealed that vmPFC hypoactivation was inversely correlated with heart rate (r56 = -0.51, adjusted P = .001) and retrospective intensity of both heartbeat (r56 = -0.50, adjusted P = .002) and breathing (r56 = -0.44, adjusted P = .01) sensations. Ventromedial prefrontal cortex hypoactivation correlated inversely with continuous dial ratings at a trend level (r56 = -0.38, adjusted P = .051), whereas anxiety (r56 = -0.28, adjusted P = .27) and chronotropic dose 25 (r56 = -0.14, adjusted P = .72) showed no such association. CONCLUSIONS AND RELEVANCE: In this crossover randomized clinical trial, women with GAD exhibited autonomic hypersensitivity during low levels of adrenergic stimulation characterized by elevated heart rate, heightened interoceptive awareness, increased anxiety, and a blunted neural response localized to the vmPFC. These findings support the notion that autonomic hyperarousal may be associated with regulatory dysfunctions in the vmPFC, which could serve as a treatment target to help patients with GAD more appropriately appraise and regulate signals of sympathetic arousal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02615119.

Who Are You? The Study of Personality in Patients With Anterograde Amnesia.

Little is known about the role of declarative memory in the ongoing perception of one's personality. Seven individuals who developed a rare and severe type of anterograde amnesia following damage to their medial temporal lobes were identified from our neurological patient registry. We examined the stability of their personality ratings on the Big Five Inventory over five retest periods and assessed the accuracy of their ratings via analyses of self-caregiver agreement. The patients portrayed a stable sense of self over the course of 1 year. However, their self-ratings differed from those provided by the caregivers. Intriguingly, these discrepancies diminished when caregivers retrospectively rated the patients' personalities prior to their brain injury, suggesting that patients' perceptions of themselves were stuck in the past. We interpret our findings to indicate that the ability to form new declarative memories is not required for maintaining a stable sense of self but may be important for updating one's sense of self over time.

Taking the body off the mind: Decreased functional connectivity between somatomotor and default-mode networks following Floatation-REST.

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.

Perceptual insensitivity to the modulation of interoceptive signals in depression, anxiety, and substance use disorders.

This study employed a series of heartbeat perception tasks to assess the hypothesis that cardiac interoceptive processing in individuals with depression/anxiety (N = 221), and substance use disorders (N = 136) is less flexible than that of healthy individuals (N = 53) in the context of physiological perturbation. Cardiac interoception was assessed via heartbeat tapping when: (1) guessing was allowed; (2) guessing was not allowed; and (3) experiencing an interoceptive perturbation (inspiratory breath hold) expected to amplify cardiac sensation. Healthy participants showed performance improvements across the three conditions, whereas those with depression/anxiety and/or substance use disorder showed minimal improvement. Machine learning analyses suggested that individual differences in these improvements were negatively related to anxiety sensitivity, but explained relatively little variance in performance. These results reveal a perceptual insensitivity to the modulation of interoceptive signals that was evident across several common psychiatric disorders, suggesting that interoceptive deficits in the realm of psychopathology manifest most prominently during states of homeostatic perturbation.

Reduced Environmental Stimulation in Anorexia Nervosa: An Early-Phase Clinical Trial.

Reduced Environmental Stimulation Therapy (REST) alters the balance of sensory input to the nervous system by systematically attenuating sensory signals from visual, auditory, thermal, tactile, vestibular, and proprioceptive channels. Previous research from our group has shown that REST via floatation acutely reduces anxiety and blood pressure (BP) while simultaneously heightening interoceptive awareness in clinically anxious populations. Anorexia nervosa (AN) is an eating disorder characterized by elevated anxiety, distorted body representation, and abnormal interoception, raising the question of whether REST might positively impact these symptoms. However, this approach has never been studied in eating disorders, and it is unknown whether exposure to floatation REST might worsen AN symptoms. To examine these possibilities, we conducted an open-label study to investigate the safety and tolerability of REST in AN. We also explored the acute impact of REST on BP, affective symptoms, body image disturbance, and interoception. Twenty-one partially weight-restored AN outpatients completed a protocol involving four sequential sessions of REST: reclining in a zero-gravity chair, floating in an open pool, and two sessions of floating in an enclosed pool. All sessions were 90 min, approximately 1 week apart. We measured orthostatic BP before and immediately after each session (primary outcome), in addition to collecting BP readings every 10 min during the session using a wireless waterproof system as a secondary outcome measure. Each participant's affective state, awareness of interoceptive sensations, and body image were assessed before and after every session (exploratory outcomes). There was no evidence of orthostatic hypotension following floating, and no adverse events (primary outcome). Secondary analyses revealed that REST induced statistically significant reductions in BP (p < 0.001; Cohen's d, 0.2-0.5), anxiety (p < 0.001; Cohen's d, >1) and negative affect (p < 0.01; Cohen's d, >0.5), heightened awareness of cardiorespiratory (p < 0.01; Cohen's d, 0.2-0.5) but not gastrointestinal sensations, and reduced body image dissatisfaction (p < 0.001; Cohen's d, >0.5). The findings from this initial trial suggest that individuals with AN can safely tolerate the physical effects of REST via floatation. Future randomized controlled trials will need to investigate whether these initial observations of improved anxiety, interoception, and body image disturbance occur in acutely ill AN populations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT02801084 (April 01, 2016).

Heightened affective response to perturbation of respiratory but not pain signals in eating, mood, and anxiety disorders.

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.

Women with Major Depressive Disorder, Irrespective of Comorbid Anxiety Disorders, Show Blunted Bilateral Frontal Responses during Win and Loss Anticipation.

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.

An Active Inference Approach to Interoceptive Psychopathology.

Interoception refers to the process by which the nervous system senses and integrates signals originating from within the body, providing a momentary mapping of the body's internal landscape and its relationship to the outside world. Active inference is based on the premise that afferent sensory input to the brain is constantly shaped and modified by prior expectations. In this review we propose that interoceptive psychopathology results from two primary interoceptive dysfunctions: First, individuals have abnormally strong expectations of the situations that elicit bodily change (i.e., hyperprecise priors), and second, they have great difficulty adjusting these expectations when the environment changes (i.e., context rigidity). Here we discuss how these dysfunctions potentially manifest in mental illness and how interventions aimed at altering interoceptive processing can help the brain create a more realistic model of its internal state.

Interoception and Mental Health: A Roadmap.

Interoception refers to the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body's internal landscape across conscious and unconscious levels. Interoceptive signaling has been considered a component process of reflexes, urges, feelings, drives, adaptive responses, and cognitive and emotional experiences, highlighting its contributions to the maintenance of homeostatic functioning, body regulation, and survival. Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders. However, a number of conceptual and methodological challenges have made it difficult for interoceptive constructs to be broadly applied in mental health research and treatment settings. In November 2016, the Laureate Institute for Brain Research organized the first Interoception Summit, a gathering of interoception experts from around the world, with the goal of accelerating progress in understanding the role of interoception in mental health. The discussions at the meeting were organized around four themes: interoceptive assessment, interoceptive integration, interoceptive psychopathology, and the generation of a roadmap that could serve as a guide for future endeavors. This review article presents an overview of the emerging consensus generated by the meeting.

The Neural Bases of Interoceptive Encoding and Recall in Healthy Adults and Adults With Depression.

BACKGROUND: Theoretical models assert that the brain's interoceptive network links external stimuli with their interoceptive consequences, thereby supporting later recall of these associations to guide the selection of healthy behaviors. If these accounts are correct, previously reported interoceptive abnormalities in major depressive disorder (MDD) should lead to altered recall of associations between external stimuli and their interoceptive (somatic) consequences. To date, the processes underlying interoceptive recall have never been experimentally investigated. METHODS: We designed and implemented the Interoceptive Encoding and Recall task to compare interoceptive and exteroceptive recall among subjects with MDD (n = 24) and healthy comparison subjects (n = 21). During the encoding phase, subjects learned to pair neutral visual cues (geometric shapes) with aversive interoceptive and exteroceptive stimuli. Later, while undergoing functional magnetic resonance imaging, subjects were prompted to recall the stimulus associated with each shape. RESULTS: Interoceptive recall, relative to exteroceptive recall, was associated with bilateral mid-to-posterior insula activation. Relative to the healthy control participants, participants with depression exhibited marked hypoactivation of the right dorsal mid-insula during interoceptive recall. CONCLUSIONS: In healthy control subjects, simply recalling a stimulus associated with a previous interoceptive challenge activated a key region in the brain's interoceptive network. Although previous research has linked MDD with aberrant processing of interoceptive stimuli, the current study is the first to demonstrate that individuals with MDD exhibit decreased insula activity while recalling interoceptive memories. It is possible that insula hypoactivation during interoceptive recall may affect the representation of prior interoceptive experiences in ways that contribute to depressive symptomology and the relationship between depression and systemic health.