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).

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.

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.

Greater decision uncertainty characterizes a transdiagnostic patient sample during approach-avoidance conflict: a computational modelling approach.

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.

A Bayesian computational model reveals a failure to adapt interoceptive precision estimates across depression, anxiety, eating, and substance use disorders.

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 visceral regulation and interoceptively-guided decision-making.

Oxytocin-enforced norm compliance reduces xenophobic outgroup rejection.

Never before have individuals had to adapt to social environments defined by such magnitudes of ethnic diversity and cultural differentiation. However, neurobiological evidence informing about strategies to reduce xenophobic sentiment and foster altruistic cooperation with outsiders is scarce. In a series of experiments settled in the context of the current refugee crisis, we tested the propensity of 183 Caucasian participants to make donations to people in need, half of whom were refugees (outgroup) and half of whom were natives (ingroup). Participants scoring low on xenophobic attitudes exhibited an altruistic preference for the outgroup, which further increased after nasal delivery of the neuropeptide oxytocin. In contrast, participants with higher levels of xenophobia generally failed to exhibit enhanced altruism toward the outgroup. This tendency was only countered by pairing oxytocin with peer-derived altruistic norms, resulting in a 74% increase in refugee-directed donations. Collectively, these findings reveal the underlying sociobiological conditions associated with outgroup-directed altruism by showing that charitable social cues co-occurring with enhanced activity of the oxytocin system reduce the effects of xenophobia by facilitating prosocial behavior toward refugees.

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.

Cardiorespiratory noise correction improves the ASL signal.

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.

Panic Anxiety in Humans with Bilateral Amygdala Lesions: Pharmacological Induction via Cardiorespiratory Interoceptive Pathways.

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 non-chemosensory 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 ß-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. SIGNIFICANCE STATEMENT: We found that monozygotic twins with focal bilateral amygdala lesions report panic anxiety in response to intravenous infusions of isoproterenol, a ß-adrenergic agonist similar to adrenaline. Heightened anxiety was evident in both twins, with one twin experiencing a panic attack. The twin who did not panic displayed signs of impaired cardiorespiratory interoception, including a complete absence of dyspnea sensation. These findings highlight that the amygdala is not strictly required for the experience of panic anxiety, and suggest that neural systems beyond the amygdala are also involved. Determining these additional systems could provide key neural modulation targets for future anxiolytic treatments.

Dissociable contributions of amygdala and hippocampus to emotion and memory in patients with Alzheimer's disease.

The amygdala and the hippocampus are associated with emotional processing and declarative memory, respectively. Studies have shown that patients with bilateral hippocampal damage caused by anoxia/ischemia, and patients with probable Alzheimer's disease (AD), can experience emotions for prolonged periods of time, even when they cannot remember what caused the emotion in the first place (Feinstein et al. (2010) Proc Natl Acad Sci USA 107:7674-7679; Guzmán-Vélez et al. (2014) Cogn Behav Neurol 27:117-129). This study aimed to investigate, for the first time, the roles of the amygdala and hippocampus in the dissociation between feelings of emotion and declarative memory for emotion-inducing events in patients with AD. Individuals with probable AD (N = 12) and age-matched healthy comparisons participants (HCP; N = 12) completed a high-resolution (0.44 × 0.44 × 0.80 mm) T2-weighted structural MR scan of the medial temporal lobe. Each of these individuals also completed two separate emotion induction procedures (sadness and happiness) using film clips. We collected real-time emotion ratings at baseline and multiple times postinduction, and administered a test of declarative memory shortly after each induction. Consistent with previous research, hippocampal volume was significantly smaller in patients with AD compared with HCP, and was positively correlated with memory for the film clips. Sustained feelings of emotion and amygdala volume did not significantly differ between patients with AD and HCP. Follow-up analyses showed a significant negative correlation between amygdala volume and sustained sadness, and a significant positive correlation between amygdala volume and sustained happiness. Our findings suggest that the amygdala is important for regulating and sustaining an emotion independent of hippocampal function and declarative memory for the emotion-inducing event. © 2015 Wiley Periodicals, Inc.

Feelings without memory in Alzheimer disease.

BACKGROUND: Patients with Alzheimer disease (AD) typically have impaired declarative memory as a result of hippocampal damage early in the disease. Far less is understood about AD's effect on emotion. OBJECTIVE: We investigated whether feelings of emotion can persist in patients with AD, even after their declarative memory for what caused the feelings has faded. METHODS: A sample of 17 patients with probable AD and 17 healthy comparison participants (case-matched for age, sex, and education) underwent 2 separate emotion induction procedures in which they watched film clips intended to induce feelings of sadness or happiness. We collected real-time emotion ratings at baseline and at 3 post-induction time points, and we administered a test of declarative memory shortly after each induction. RESULTS: As expected, the patients with AD had severely impaired declarative memory for both the sad and happy films. Despite their memory impairment, the patients continued to report elevated levels of sadness and happiness that persisted well beyond their memory for the films. This outcome was especially prominent after the sadness induction, with sustained elevations in sadness lasting for more than 30 minutes, even in patients with no conscious recollection for the films. CONCLUSIONS: These findings indicate that patients with AD can experience prolonged states of emotion that persist well beyond the patients' memory for the events that originally caused the emotion. The preserved emotional life evident in patients with AD has important implications for their management and care, and highlights the need for caretakers to foster positive emotional experiences.

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 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. 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.

Sustained experience of emotion after loss of memory in patients with amnesia.

Can the experience of an emotion persist once the memory for what induced the emotion has been forgotten? We capitalized on a rare opportunity to study this question directly using a select group of patients with severe amnesia following circumscribed bilateral damage to the hippocampus. The amnesic patients underwent a sadness induction procedure (using affectively-laden film clips) to ascertain whether their experience of sadness would persist beyond their memory for the sadness-inducing films. The experiment showed that the patients continued to experience elevated levels of sadness well beyond the point in time at which they had lost factual memory for the film clips. A second experiment using a happiness induction procedure yielded similar results, suggesting that both positive and negative emotional experiences can persist independent of explicit memory for the inducing event. These findings provide direct evidence that a feeling of emotion can endure beyond the conscious recollection for the events that initially triggered the emotion.

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.

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.

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.

Reduced Environmental Stimulation Therapy (REST) in anxiety and depression: An experience sampling study.

Background: Reduced Environmental Stimulation Therapy (REST) is a behavioral intervention that systematically attenuates external sensory input to the nervous system. Previous studies have demonstrated acute anxiolytic and antidepressant effects of single sessions of REST in anxious individuals, however the duration and time course of these effects is unknown. In the current study, we used experience sampling and multiple sessions of REST to explore the time course of the anxiolytic and antidepressant effects over a 48-hour time period. Methods: 75 adults with anxiety and/or depression were randomized to complete 6 sessions of REST (either pool-REST, pool-REST preferred, or chair-REST). Post-REST effects were tracked using experience sampling on a smartphone with a ten-item survey administered at 6 time points for each session (i.e., immediately before and after REST and then 4, 8, 24, and 48 hours later). Using principal component analysis, responses to survey items at baseline were reduced to broad symptom clusters of anxiety, depression, and serenity and were utilized in linear mixed effects models to determine the magnitude and time course of post-REST effects. Results: REST was associated with significant decreases in anxiety and depression, and significant increases in serenity, with effects lasting for 48 hours. Repeated exposure to REST was associated with lower baseline levels of anxiety at later sessions. Conclusion: These initial findings suggest that the anxiolytic and antidepressant effects of REST persist for at least two days, and that repeated REST sessions may have additive effects on lowering anxiety-related symptoms. These findings could help to determine the optimal intervention frequency of REST and facilitate future investigations focused on the combination of REST with standard treatments for anxiety and depression.