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Abstract Background Means restriction is an approach to suicide prevention that has been shown to be effective but is underutilized in the United States. For the current study, we sought to determine if a webinar-based education intervention could impact caregiver means restriction knowledge and behaviors. Methods Nine webinars for caregivers were offered by a children’s hospital in conjunction with community groups. Education on raising teenagers was paired with information about suicide prevention, including the importance of securing medications and firearms. Participants completed surveys prior to the presentation, immediately following and two weeks later to measure change in knowledge and storage of medications and firearms. Participants were provided a safety toolkit to secure medications and firearms. Results Of the 327 participants who completed the baseline survey, 299 and 257 completed the second and third surveys. By the conclusion of the study, 46.6% of participants reported they had disposed of unneeded medications and 44.1% had locked up medications. Among firearm owners, use of a cable gun lock rose from 13.7% to 25.8%. In addition, 40.2% of firearm owners reported learning more about how their firearms were stored at the final survey. Most participants (88.3%) strongly agreed that the presentation provided value. Conclusion This study shows that a webinar on safe storage appears to have some impact on behavior changes for caregivers of adolescents. A controlled study could help to clarify if the webinar format or the timing during the Covid-19 pandemic might have played a role in the degree of behavior change reported.

Aberrant reward processing has been predominantly associated with depressive disorders, with evidence that pre-treatment abnormalities in striatal reward responsiveness relates to treatment outcomes. Emerging research also implicates reward processing differences in anxiety disorders, particularly generalized anxiety disorder (GAD). The current study examined whether pre-treatment reward- and loss- related neural activity predicts symptom improvement with behavioral activation (BA) and exposure therapy (EXP) for GAD. In this randomized clinical trial (ClinicalTrials.gov NCT02807480) conducted from 2016 to 2021, treatment-seeking adults with GAD completed the monetary incentive delay task during functional magnetic resonance imaging pre-treatment, then were randomized to 10-session EXP or BA. The primary outcome measure was the GAD-7. Of 101 participants consented, 69 completed treatment, the 46 completers with quality imaging data were included in analyses (22 EXP, 24 BA; mean 32.7 years, 10.9 % male). A priori region-of-interest analysis revealed that greater left caudate activity during loss receipt predicted greater symptom improvement in EXP, and did not relate to symptom change in BA (F(1, 428)= 5.24, p = 0.023), though this was not significant after correction for multiple comparisons. Whole-brain analysis further identified that greater activity during reward receipt in left frontoparietal regions and anterior insula / ventrolateral prefrontal cortex was associated with better outcomes in BA and worse outcomes in EXP. These findings highlight the role of reward and loss reactivity in GAD treatment. In particular, patients with elevated reactivity to reward salience may benefit most from BA or other reward-focused treatments. Future clinical trials are warranted to further elucidate reward-related predictors of anxiety treatment.

Abstract Most growth references for very preterm infants were developed using measurements taken at birth, and were thought to represent intrauterine growth. However, it remains unclear whether the goal of approximating an intrauterine growth rate as stated by the American Academy of Pediatrics is attainable by very preterm infants. Using real-world measurement data from very preterm infants born between 2010 through 2020, we develop models to characterize the patterns of postnatal growth, and compare them to intrauterine growth. By assessing the weight growth rate, we show three phases of postnatal growth not evident in intrauterine growth. Furthermore, postnatal length and head circumference growth exhibit a slow rate after birth, followed by an acceleration. Collectively, postnatal and intrauterine growth are distinctly different. Although postnatal growth models do not represent optimal growth of very preterm infants, they can serve as a practical tool for clinical assessment of growth and for nutrition research.

Abstract Background Intake-balance assessments measure energy intake (EI) by summing energy expenditure (EE) with concurrent change in energy storage (ΔES). Prior work has not examined the validity of such calculations when EE is estimated via open-source techniques for research-grade accelerometry devices. The purpose of this study was to test the criterion validity of accelerometry-based intake-balance methods for a wrist-worn ActiGraph device. Methods Healthy adults (n = 24) completed two 14-day measurement periods while wearing an ActiGraph accelerometer on the non-dominant wrist. During each period, criterion values of EI were determined based on ΔES measured by dual X-ray absorptiometry and EE measured by doubly labeled water. A total of 11 prediction methods were tested, 8 derived from the accelerometer and 3 from non-accelerometry methods (e.g., diet recall; included for comparison). Group-level validity was assessed through mean bias, while individual-level validity was assessed through mean absolute error, mean absolute percentage error, and Bland–Altman analysis. Results Mean bias for the three best accelerometry-based methods ranged from -167 to 124 kcal/day, versus -104 to 134 kcal/day for the non-accelerometry-based methods. The same three accelerometry-based methods had mean absolute error of 323–362 kcal/day and mean absolute percentage error of 18.1-19.3%, versus 353–464 kcal/day and 19.5-24.4% for the non-accelerometry-based methods. All 11 methods demonstrated systematic bias in the Bland–Altman analysis. Conclusions Accelerometry-based intake-balance methods have promise for advancing EI assessment, but ongoing refinement is necessary. We provide an R package to facilitate implementation and refinement of accelerometry-based methods in future research (see paulhibbing.com/IntakeBalance).

ObjectiveYouth unmet behavioral health needs are at public health crisis status and have worsened since the onset of the coronavirus disease 2019 pandemic (Covid-19). Integrating behavioral health services into pediatric primary care has shown efficacy in addressing youth behavioral health needs. However, there is limited guidance on facilitating equitable access to care in this setting, including in triaging access to co-located services (i.e., onsite outpatient behavioral health services with only the behavioral health provider) or to specialty behavioral health services in other clinics within larger health systems.MethodsA retrospective, comparative study was conducted to examine variability in access to co-located and specialty behavioral health (SBH) services for a pre-Covid-19 cohort (April 2019 to March 2020; n = 367) and a mid-Covid-19 cohort (April 2020 to March 2021; n = 328), while accounting for integrated primary care consultation services. The sample included children 1-18 years old served through a large, inner-city primary care clinic. Logistic regression models were used to examine the association between scheduled and attended co-located and SBH visits, pre- and mid-Covid-19 effects, and sociodemographic factors of race and ethnicity, language, health insurance (SES proxy), age, and sex.ResultsThe majority of youth were not directly scheduled for a co-located or SBH visit but the majority of those scheduled attended their visit(s). The odds of not being directly scheduled for a co-located or SBH visit were greater for the mid-Covid-19 cohort, Black youth, and older youth. Accounting for integrated primary care consultation visits addressed these disparities, with the exception of persisting significant differences in scheduled and attended co-located and SBH visits for Black youth even while accounting for IPC consultation.ImplicationFindings from the current study highlight the effective role of integrated primary care consultation services as facilitating access to initial behavioral health services, especially given that referrals to integrated primary care co-located and SBH services within the larger health system often involve barriers to care such as longer wait-times and increased lack of referral follow through. Ongoing research and equitable program development are needed to further this work.

Abstract Background The new bronchopulmonary dysplasia (BPD) grading system was developed based on its correlation with long-term respiratory and neurodevelopmental outcomes and may provide better personalized prognostication. Identifying early-life predictors for accurate BPD grade prediction may allow interventions to be tailored to individual needs. This study aimed to assess whether oxygenation index (OI) dynamics in the first three weeks of life are a predictor of BPD grade. Methods A single-center retrospective study was performed. Generalized additive mixed modeling was used to model OI trajectories for each BPD grade subgroup. A multinomial regression model was then developed to quantify the association between OI dynamics and BPD grade. Results Two hundred fifty-four infants were identified for inclusion in the trajectory modeling. A total of 6,243 OI data points were available for modeling. OI trajectory estimates showed distinct patterns in the three groups, most prominent during the third week of life. The average daily OI change was -0.33 ± 0.52 (n = 85) in the No-BPD group, -0.04 ± 0.75 (n = 82) in the Low-Grade BPD group, and 0.22 ± 0.65 (n = 75) in the High-Grade BPD group (p

BackgroundEating Disorders (ED) affect up to 5% of youth and are associated with reward system alterations and compulsive behaviors. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and/or purging. The presumed mechanism of action is blockade of reward activation; however, not all patients respond, and the optimal dose is unknown. Developing a tool to detect objective drug response in the brain will facilitate drug development and therapeutic optimization. This pilot study evaluated neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED.MethodsYouth aged 13–21 with binge/purge ED completed functional magnetic resonance imaging (fMRI) pre- and post-oral naltrexone. fMRI detected blood oxygenation-level dependent (BOLD) signal at rest and during two reward probes (monetary incentive delay, MID, and passive food view, PFV) in predefined regions of interest associated with reward and inhibitory control. Effect sizes for Δ%BOLD (post-naltrexone vs. baseline) were estimated using linear mixed effects modeling.ResultsIn 12 youth (16–21 years, 92% female), BOLD signal changes were detected following naltrexone in the nucleus accumbens during PFV (Δ%BOLD −0.08 ± 0.03; Cohen’s d −1.06, p = 0.048) and anterior cingulate cortex during MID (Δ%BOLD 0.06 ± 0.03; Cohen’s d 1.25, p = 0.086).ConclusionfMRI detected acute reward pathway modulation in this small sample of adolescents with binge/purge ED. If validated in future, larger trials, task-based Δ%BOLD detected by fMRI may serve as a pharmacodynamic biomarker of opioid antagonism to facilitate the development of novel therapeutics targeting the reward pathway, enable quantitative pharmacology trials, and inform drug dosing.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04935931, NCT#04935931.

Abstract Elevated serum concentrations (>3 mg/L) of the acute-phase protein, C-reactive protein (CRP), is used as a clinical marker of inflammation and is reported to be a strong risk factor for cardiovascular disease. In psychiatric populations, CRP concentration is reported to be higher in depressed versus healthy individuals. Positive associations between CRP and depression have been established in both clinical and community samples, but effect sizes are attenuated after controlling for confounding variables. Similarly, emerging research has begun to draw a link between inflammation, symptoms of anxiety, and substance abuse. Given the high level of comorbid anxiety and substance use disorders in many depressed populations, this study examined whether depression (Patient Health Questionnaire 9 [PHQ-9]) and substance use-related (Drug Abuse Screening Test [DAST]) symptoms were associated with CRP concentrations in the blood after adjusting for relevant medical, social, and demographic covariates in a large sample undergoing screening for several transdiagnostic psychiatric research studies. A total of 1,724 participants were analyzed for association of CRP with variables using multivariate linear regression. An unadjusted model with no covariates showed that PHQ-9 was significantly associated with CRP in All (β = 0.125), Female (β = 0.091), and Male (β = 0.154) participants, but DAST was significantly associated with CRP in males only (β = 0.120). For the adjusted model, in both males and females, mood-stabilizer treatment (β = 0.630), opioid medication (β = 0.360), body mass index (β = 0.244), percent body fat (β = 0.289), nicotine use (β = 0.063), and self-reported sleep disturbance (β = 0.061) were significantly associated with increased CRP concentrations. In females, oral contraceptive use (β = 0.576), and waist-to-hip ratio (β = 0.086), and in males, non-steroidal anti-inflammatory drug use (β = 0.367) were also associated with increased CRP concentrations. There was no significant association between CRP and individual depressive, anxiety, or substance use-related symptoms when covariates were included in the regression models. These results suggest that associations between circulating CRP and the severity of psychiatric symptoms are dependent on the type of covariates controlled for in statistical analyses.

BackgroundA variety of quality control (QC) approaches are employed in resting-state functional magnetic resonance imaging (rs-fMRI) to determine data quality and ultimately inclusion or exclusion of a fMRI data set in group analysis. Reliability of rs-fMRI data can be improved by censoring or “scrubbing” volumes affected by motion. While censoring preserves the integrity of participant-level data, including excessively censored data sets in group analyses may add noise. Quantitative motion-related metrics are frequently reported in the literature; however, qualitative visual inspection can sometimes catch errors or other issues that may be missed by quantitative metrics alone. In this paper, we describe our methods for performing QC of rs-fMRI data using software-generated quantitative and qualitative output and trained visual inspection.ResultsThe data provided for this QC paper had relatively low motion-censoring, thus quantitative QC resulted in no exclusions. Qualitative checks of the data resulted in limited exclusions due to potential incidental findings and failed pre-processing scripts.ConclusionVisual inspection in addition to the review of quantitative QC metrics is an important component to ensure high quality and accuracy in rs-fMRI data analysis.

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].

Abstract 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 Background Neurocognitive deficits (NCDs) and associated meta-cognition difficulties associated with chronic substance use often delay the learning and change process necessary for addiction recovery and relapse prevention. However, very few cognitive remediation programs have been developed to target NCDs and meta-cognition for substance users. The study described herein aims to investigate the efficacy of a multi-component neurocognitive rehabilitation and awareness program termed “Neurocognitive Empowerment for Addiction Treatment” (NEAT). NEAT is a fully manualized, cartoon-based intervention involving psychoeducation, cognitive practice, and compensatory strategies relevant across 10 major cognitive domains, including aspects of attention, memory, executive functions, and decision-making. Method/design In a single-blind randomized controlled trial (RCT), 80 female opioid and/or methamphetamine users will be recruited from an addiction recovery program providing an alternative to incarceration for women with substance use-related offenses. Eight groups of 9–12 participants will be randomized into NEAT or treatment-as-usual (TAU). NEAT involves 14 90-min sessions, delivered twice weekly. The primary outcome is change in self-reported drug craving from before to after intervention using Obsessive Compulsive Drug Use Scale. Secondary and exploratory outcomes include additional psychological, neurocognitive, and structural and functional neuroimaging measures. Clinical measures will be performed at five time points (pre- and post-intervention, 3-, 6-, and 12-month follow-up); neuroimaging measures will be completed at pre- and post-intervention. Discussion The present RCT is the first study to examine the efficacy of an adjunctive neurocognitive rehabilitation and awareness program for addiction. Results from this study will provide initial information concerning potential clinical efficacy of the treatment, as well as delineate neural mechanisms potentially targeted by this novel intervention. Trial registration ClinicalTrials.gov NCT03922646 . Registered on 22 April 2019

Neuroticism as a personality trait represents a heritable risk for psychiatric disorders. The polygenic risk score for neuroticism (N-PRS) is used to study genetic vulnerability to neuroticism. The current data present the association of the genetic risk for neuroticism to neural reward-punishment processing using functional magnetic resonance imaging. N-PRS was computed based on the individual's genotype information and a genome-wide association study on the UK Biobank data. While individuals performed a monetary incentive delay task, their neural activations for upcoming incentives (reward: gain, punishment: loss) were measured in blood oxygen level dependent (BOLD) signals during the delay phase. Multivariate ANCOVAs were used to analyze BOLD signals for finding the association between N-PRS and reward-punishment processing by the incentive valence (Related research article: H. Park, K.L. Forthman, R. Kuplicki, T.A. Victor, Tulsa 1000 Investigators, H.W. Yeh, W.K. Thompson, M.P. Paulus, Polygenic risk for neuroticism modulates response to gains and losses in the amygdala and caudate: evidence from a clinical cohort. J. Affect. Disord. 293 (2021) 124–132. https://doi.org/10.1016/j.jad.2021.06.016). These data can be used as reference data for future studies examining the role of the genetic propensity for personality traits in the context of psychiatric disorders.

Summary Introduction Obesity is linked to altered activation in reward and control brain circuitry; however, the associated brain activity related to successful or unsuccessful weight loss (WL) is unclear. Methods Adults with obesity (N = 75) completed a baseline functional magnetic resonance imaging (fMRI) scan before entering a WL intervention (ie,3‐month diet and physical activity [PA] program). We conducted an exploratory analysis to identify the contributions of baseline brain activation, adherence behavior patterns, and the associated connections to WL at the conclusion of a 3‐month WL intervention. Food cue‐reactivity brain regions were functionally identified using fMRI to index brain activation to food vs nonfood cues. Food consumption, PA, and class attendance were collected weekly during the 3‐month intervention. Results The left middle frontal gyrus (L‐MFG, BA 46) and right middle frontal gyrus (R‐MFG; BA 9) were positively activated when viewing food compared with nonfood images. Structural equation modeling with bootstrapping was used to investigate a hypothesized path model and revealed the following significant paths: (1) attendance to 3‐month WL, (2) R‐MFG to attendance, and (3) indirect effects of R‐MFG through attendance on WL. Conclusion Findings suggest that brain activation to appetitive food cues predicts future WL through mediating session attendance, diet, and PA. This study contributes to the growing evidence of the importance of food cue reactivity and self‐regulation brain regions and their impact on WL outcomes.

Background: The Monetary Incentive Delay task (MID) has been used extensively to probe anticipatory reward processes. However, individual differences evident during this task may relate to other constructs such as general arousal or valence processing (i.e., anticipation of negative versus positive outcomes). This investigation used a latent variable approach to parse activation patterns during the MID within a transdiagnostic clinical sample. Methods: Participants were drawn from the first 500 individuals recruited for the Tulsa-1000 (T1000), a naturalistic longitudinal study of 1000 participants aged 18–55 (n = 476 with MID data). We employed a multiview latent analysis method, group factor analysis, to characterize factors within and across variable sets consisting of: (1) region of interest (ROI)-based blood oxygenation level-dependent (BOLD) contrasts during reward and loss anticipation; and (2) self-report measures of positive and negative valence and related constructs. Results: Three factors comprised of ROI indicators emerged to accounted for >43% of variance and loaded on variables representing: (1) general arousal or general activation; (2) valence, with dissociable responses to anticipation of win versus loss; and (3) region-specific activation, with dissociable activation in salience versus perceptual brain networks. Two additional factors were comprised of self-report variables, which appeared to represent arousal and valence. Conclusions: Results indicate that multiview techniques to identify latent variables offer a novel approach for differentiating brain activation patterns during task engagement. Such approaches may offer insight into neural processing patterns through dimension reduction, be useful for probing individual differences, and aid in the development of optimal explanatory or predictive frameworks.

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 RegistrationClinicalTrials.gov; Identifier: NCT02801084 (April 01, 2016).

Purpose: Head and neck surgery and radiation cause tissue fibrosis that leads to functional limitations and lymphedema. The objective of this study was to determine whether lymphedema therapy after surgery and radiation for head and neck cancer decreases neck circumference, increases cervical range of motion, and improves pain scores. Methods and materials: A retrospective review of all patients with squamous cell carcinoma of the oral cavity, oropharynx, or larynx who were treated with high-dose radiation therapy at a single center between 2011 and 2012 was performed. Patients received definitive or postoperative radiation for squamous cell carcinoma of the oral cavity, oropharynx, or larynx. Patients were referred to a single, certified, lymphedema therapist with specialty training in head and neck cancer after completion of radiation treatment and healing of acute toxicity (typically 1-3 months). Patients underwent at least 3 months of manual lymphatic decongestion and skilled fibrotic techniques. Circumferential neck measurements and cervical range of motion were measured clinically at 1, 3, 6, 9, and 12 months after completion of radiation therapy. Pain scores were also recorded. Results: Thirty-four consecutive patients were eligible and underwent a median of 6 months of lymphedema therapy (Range, 3-12 months). Clinically measured total neck circumference decreased in all patients with 1 month of treatment. Cervical rotation increased by 30.2% on the left and 27.9% on the right at 1 month and continued to improve up to 44.6% and 55.3%, respectively, at 12 months. Patients undergoing therapy had improved pain scores from 4.3 at baseline to 2.0 after 1 month. Conclusions: Lymphedema therapy is associated with objective improvements in range of motion, neck circumference, and pain scores in the majority of patients.

Survey-based studies show that neighborhood disadvantage is associated with community reported mental health problems. However, fewer studies have examined whether neighborhood characteristics have measurable impact on mental health status of individuals in general and whether neighborhood characteristics impact positive/negative valence processing at both behavioral and brain levels. This study addressed these questions by investigating effects of census-based neighborhood affluence on self-reported symptoms, brain functions, and structures associated with positive/negative valence processing in a sample of individuals with mood and anxiety disorders (n = 262). Employing a Bayesian inference approach, our investigation demonstrates that neighborhood affluence fails to be associated with positive/negative valence processing measured across multiple modalities, with the only effects of neighborhood affluence identified in trait anxiety scores. These findings highlight that while community-based relationships between neighborhood characteristics and mental health problems are strong, it is much less clear that these characteristics have a measurable impact on the individual. Keywords: Neighborhood, Positive and negative valence systems, Mood and anxiety disorder, Bayes factor, Brain function and structure, Monetary incentive delay task

Several imaging modalities, including T1-weighted structural imaging, diffusion tensor imaging, and functional MRI can show chronological age related changes. Employing machine learning algorithms, an individual's imaging data can predict their age with reasonable accuracy. While details vary according to modality, the general strategy is to: (1) extract image-related features, (2) build a model on a training set that uses those features to predict an individual's age, (3) validate the model on a test dataset, producing a predicted age for each individual, (4) define the “Brain Age Gap Estimate” (BrainAGE) as the difference between an individual's predicted age and his/her chronological age, (5) estimate the relationship between BrainAGE and other variables of interest, and (6) make inferences about those variables and accelerated or delayed brain aging. For example, a group of individuals with overall positive BrainAGE may show signs of accelerated aging in other variables as well. There is inevitably an overestimation of the age of younger individuals and an underestimation of the age of older individuals due to “regression to the mean.” The correlation between chronological age and BrainAGE may significantly impact the relationship between BrainAGE and other variables of interest when they are also related to age. In this study, we examine the detectability of variable effects under different assumptions. We use empirical results from two separate datasets [training = 475 healthy volunteers, aged 18–60 years (259 female); testing = 489 participants including people with mood/anxiety, substance use, eating disorders and healthy controls, aged 18–56 years (312 female)] to inform simulation parameter selection. Outcomes in simulated and empirical data strongly support the proposal that models incorporating BrainAGE should include chronological age as a covariate. We propose either including age as a covariate in step 5 of the above framework, or employing a multistep procedure where age is regressed on BrainAGE prior to step 5, producing BrainAGE Residualized (BrainAGER) scores.

Objective: The brain age gap estimate (BrainAGE) is the difference between the estimated age and the individual chronological age. BrainAGE was studied primarily using MRI techniques. EEG signals in combination with machine learning (ML) approaches were not commonly used for the human age prediction, and BrainAGE. We investigated whether age-related changes are affecting brain EEG signals, and whether we can predict the chronological age and obtain BrainAGE estimates using a rigorous ML framework with a novel and extensive EEG features extraction.Methods: EEG data were obtained from 468 healthy, mood/anxiety, eating and substance use disorder participants (297 females) from the Tulsa-1000, a naturalistic longitudinal study based on Research Domain Criteria framework. Five sets of preprocessed EEG features across channels and frequency bands were used with different ML methods to predict age. Using a nested-cross-validation (NCV) approach and stack-ensemble learning from EEG features, the predicted age was estimated. The important features and their spatial distributions were deduced.Results: The stack-ensemble age prediction model achieved R2 = 0.37 (0.06), Mean Absolute Error (MAE) = 6.87(0.69) and RMSE = 8.46(0.59) in years. The age and predicted age correlation was r = 0.6. The feature importance revealed that age predictors are spread out across different feature types. The NCV approach produced a reliable age estimation, with features consistent behavior across different folds.Conclusion: Our rigorous ML framework and extensive EEG signal features allow a reliable estimation of chronological age, and BrainAGE. This general framework can be extended to test EEG association with and to predict/study other physiological relevant responses.

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 NCT03051074.

Pressure application to the lumbar spine is an important assessment and treatment method of low back pain. However, few studies have characterized brain activation patterns in response to mechanical pressure. The objective of this study was to map brain activation associated with various levels of mechanical pressure to the lumbar spine in healthy subjects. Fifteen healthy subjects underwent functional magnetic resonance imaging (fMRI) scanning while mechanical pressure was applied to their lumbar spine with a custom-made magnetic resonance imaging (MRI)-compatible pressure device. Each subject received three levels of pressure (low/medium/high) based on subjective ratings determined prior to the scan using a block design (pressure/rest). Pressure rating was assessed with an 11-point scale (0 = no touch; 10 = max pain-free pressure). Brain activation differences between pressure levels and rest were analyzed. Subjective pressure ratings were significantly different across pressure levels (p < 0.05). The overall brain activation pattern was not different across pressure levels (all p > 0.05). However, the overall effect of pressure versus rest showed significant decreases in brain activation in response to the mechanical stimulus in regions associated with somatosensory processing including the precentral gyri, left hippocampus, left precuneus, left medial frontal gyrus, and left posterior cingulate. There was increase in brain activation in the right inferior parietal lobule and left cerebellum. This study offers insight into the neural mechanisms that may relate to manual mobilization intervention used for managing low back pain.

Purpose: Previous studies have suggested that the hypopituitarism following traumatic brain injury (TBI) is more prevalent than traditionally thought. The objective of this study was to characterize longitudinal MRI morphometric changes of pituitary gland in patients with severe TBI. Materials and methods: Fourteen patients who had suffered a severe TBI (Glasgow Coma Score=3 - 8) underwent MRI at three time points: Time 1 (mean=31. 5 days), Time 2 (98. 0) and Time 3 (185. 5). The pituitary gland volume was quantified by manually tracing on T1-weighted magnetic resonance images. Data from TBI patients were compared to 14 age- and sex-matched uninjured controls. The relationships between pituitary volumetric measures and patient demographics, length of respiratory support and coma, and presence of intracranial hemorrhage or skull fractures were also analyzed. Results: Following TBI, the pituitary volumes were significantly greater at all three time points: Time 1: median=665mm3, range=460-830mm3, p=0. 007; Time 2: 694mm3, 467-866mm3, 0. 007; and Time 3: 655mm3, 444-795mm3, 0. 015, compared with controls (504mm3, 433-591mm3). At Time 1, pituitary volume was increased in 10 out of 14 patients. Of these, early pituitary enlargements persisted up to six months in nine patients. Pituitary enlargements were negatively correlated with GCS, but not with other variables. Conclusion: Following a severe TBI, early pituitary enlargement found in most of our patients persisted in the chronic phases. Our data suggest a potential role of MRI morphometry in early prediction of pituitary dysfunction following head trauma, but further studies including hormonal measurements are necessary for validation.

We link some equivalent forms of the arithmetic-geometric mean inequality in probability and mathematical statistics.

Objective: Youth unmet behavioral health needs are at public health crisis status and have worsened since the onset of the coronavirus disease 2019 pandemic (Covid-19). Integrating behavioral health services into pediatric primary care has shown efficacy in addressing youth behavioral health needs. However, there is limited guidance on facilitating equitable access to care in this setting, including in triaging access to co-located services (i.e., onsite outpatient behavioral health services with only the behavioral health provider) or to specialty behavioral health services in other clinics within larger health systems. Methods: A retrospective, comparative study was conducted to examine variability in access to co-located and specialty behavioral health (SBH) services for a pre-Covid-19 cohort (April 2019 to March 2020; n = 367) and a mid-Covid-19 cohort (April 2020 to March 2021; n = 328), while accounting for integrated primary care consultation services. The sample included children 1-18 years old served through a large, inner-city primary care clinic. Logistic regression models were used to examine the association between scheduled and attended co-located and SBH visits, pre- and mid-Covid-19 effects, and sociodemographic factors of race and ethnicity, language, health insurance (SES proxy), age, and sex. Results: The majority of youth were not directly scheduled for a co-located or SBH visit but the majority of those scheduled attended their visit(s). The odds of not being directly scheduled for a co-located or SBH visit were greater for the mid-Covid-19 cohort, Black youth, and older youth. Accounting for integrated primary care consultation visits addressed these disparities, with the exception of persisting significant differences in scheduled and attended co-located and SBH visits for Black youth even while accounting for IPC consultation. Implication: Findings from the current study highlight the effective role of integrated primary care consultation services as facilitating access to initial behavioral health services, especially given that referrals to integrated primary care co-located and SBH services within the larger health system often involve barriers to care such as longer wait-times and increased lack of referral follow through. Ongoing research and equitable program development are needed to further this work. [ABSTRACT FROM AUTHOR]

Background: A variety of quality control (QC) approaches are employed in resting-state functional magnetic resonance imaging (rs-fMRI) to determine data quality and ultimately inclusion or exclusion of a fMRI data set in group analysis. Reliability of rs-fMRI data can be improved by censoring or "scrubbing" volumes affected by motion. While censoring preserves the integrity of participant-level data, including excessively censored data sets in group analyses may add noise. Quantitative motion-related metrics are frequently reported in the literature; however, qualitative visual inspection can sometimes catch errors or other issues that may be missed by quantitative metrics alone. In this paper, we describe our methods for performing QC of rs-fMRI data using software-generated quantitative and qualitative output and trained visual inspection. Results: The data provided for this QC paper had relatively low motion-censoring, thus quantitative QC resulted in no exclusions. Qualitative checks of the data resulted in limited exclusions due to potential incidental findings and failed preprocessing scripts. Conclusion: Visual inspection in addition to the review of quantitative QC metrics is an important component to ensure high quality and accuracy in rs-fMRI data analysis. [ABSTRACT FROM AUTHOR]