Faculty Bibliography

Sleep plays a crucial role in brain development, sensory information processing, and consolidation. Sleep spindles are markers of these mechanisms as they mirror the activity of the thalamocortical circuits. Spindles can be subdivided into two groups, slow (10-13 Hz) and fast (13-16 Hz), which are each associated with different functions. Specifically, fast spindles oscillate in the high-sigma band and are associated with sensorimotor processing, which is affected by visual deprivation. However, how blindness influences spindle development has not yet been investigated. We recorded nap video-EEG of 50 blind/severely visually impaired (BSI) and 64 sighted children aged 5 months to 6 years old. We considered aspects of both macro- and micro-structural spindles. The BSI children lacked the evolution of developmental spindles within the central area. Specifically, young BSI children presented low central high-sigma and high-beta (25-30 Hz) event-related spectral perturbation and showed no signs of maturational decrease. High-sigma and high-beta activity in the BSI group correlated with clinical indices predicting perceptual and motor disorders. Our findings suggest that fast spindles are pivotal biomarkers for identifying an early developmental deviation in BSI children. These findings are critical for initial therapeutic intervention.

IMPORTANCE/UNASSIGNED:Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose escalation beyond US Food and Drug Administration recommendations is associated with positive risk benefits is unclear. OBJECTIVE/UNASSIGNED:To investigate the impact, based on averages, of stimulant doses on treatment outcomes in adults with ADHD and to determine, based on averages, whether unlicensed doses are associated with positive risk benefits compared with licensed doses. DATA SOURCES/UNASSIGNED:Twelve databases, including published (PubMed, Cochrane Library, Embase, Web of Sciences) and unpublished (ClinicalTrials.gov) literature, up to February 22, 2023, without language restrictions. STUDY SELECTION/UNASSIGNED:Two researchers independently screened records to identify double-blinded randomized clinical trials of stimulants against placebo in adults (18 years and older) with ADHD. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Aggregate data were extracted and synthesized in random-effects dose-response meta-analyses and network meta-analyses. MAIN OUTCOME MEASURES/UNASSIGNED:Change in ADHD symptoms and discontinuations due to adverse events. RESULTS/UNASSIGNED:A total of 47 randomized clinical trials (7714 participants; mean age, 35 (SD, 11) years; 4204 male [56%]) were included. For methylphenidate, dose-response curves indicated additional reductions of symptoms with increments in doses, but the gains were progressively smaller and accompanied by continued additional risk of adverse events dropouts. Network meta-analyses showed that unlicensed doses were associated with greater reductions of symptoms compared with licensed doses (standardized mean difference [SMD], -0.23; 95% CI, -0.44 to -0.02; very low certainty of evidence), but the additional gain was small and accompanied by increased risk of adverse event dropouts (odds ratio, 2.02; 95% CI, 1.19-3.43; moderate certainty of evidence). For amphetamines, the dose-response curve approached a plateau and increments in doses did not indicate additional reductions of symptoms, but there were continued increments in the risk of adverse event dropouts. Network meta-analysis did not identify differences between unlicensed and licensed doses for reductions of symptoms (SMD, -0.08; 95% CI, -0.24 to 0.08; very low certainty of evidence). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Based on group averages, unlicensed doses of stimulants may not have positive risk benefits compared with licensed doses for adults with ADHD. In general, practitioners should consider unlicensed doses cautiously. Practitioners may trial unlicensed doses if needed and tolerated but should be aware that there may not be large gains in the response to the medication with those further increments in dose. However, the findings are averages and will not generalize to every patient.

Prenatal alcohol exposure is the leading nongenetic cause of human intellectual impairment. The long-term impacts of prenatal alcohol exposure on health and well-being are diverse, including neuropathology leading to behavioral, cognitive, and emotional impairments. Additionally negative effects also occur on the physiological level, such as the endocrine, cardiovascular, and immune systems. Among these diverse impacts is sleep disruption. In this review, we describe how prenatal alcohol exposure affects sleep, and potential mechanisms of those effects. Furthermore, we outline the evidence that sleep disruption across the lifespan may be a mediator of some cognitive and behavioral impacts of developmental alcohol exposure, and thus may represent a promising target for treatment.

OBJECTIVE:We aimed to quantify the clinical utility of continuous performance tests (CPTs) for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) compared to a clinical diagnosis in children and adolescents. METHOD/METHODS:Four databases (MEDLINE, PsycINFO, EMBASE, and PubMed) were screened until January 2023. Risk of bias of included results was judged with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We statistically pooled the area under the curve, the sensitivity, and the specificity of 3 commonly used CPTs subscales: omission/inattention, commission/impulsivity, and total number of errors/ADHD subscales (PROSPERO registration: CRD42020168091). RESULTS:A total of 19 studies using commercially available CPTs were identified. Results from up to 835 control individuals and 819 cases were combined in the summary receiver operating characteristic (ROC) curve analyses (sensitivity and specificity pooling), and up to 996 cases and 1,083 control individuals in the area under the curve (AUC) analyses. Clinical utility as measured by AUCs could be considered as barely acceptable (between 0.7 and 0.8) for the most part, with the best results for the total/ADHD score, followed by omissions/inattention, and poorest for commission/impulsivity scores. A similar pattern was found when pooling sensitivity and specificity: 0.75 (95% CI = 0.66-0.82) and 0.71 (0.62-0.78) for the total/ADHD score; 0.63 (0.49-0.75) and 0.74 (0.65-0.81) for omissions; and 0.59 (0.38-0.77) and 0.66 (CI = 0.50-0.78) for commissions. CONCLUSION/CONCLUSIONS:At the clinical level, CPTs as a stand-alone tool have only a modest to moderate ability to differentiate ADHD from non-ADHD samples. Hence, they should be used only within a more comprehensive diagnostic process.

Although the availability of virtual care technologies in the Veterans Health Administration (VHA) continues to expand, ensuring engagement with these technologies among Veterans remains a challenge. VHA Health Services Research & Development convened a Virtual Care State of The Art (SOTA) conference in May 2022 to create a research agenda for improving virtual care access, engagement, and outcomes. This article reports findings from the Virtual Care SOTA engagement workgroup, which comprised fourteen VHA subject matter experts representing VHA clinical care, research, administration, and operations. Workgroup members reviewed current evidence on factors and strategies that may affect Veteran engagement with virtual care technologies and generated key questions to address evidence gaps. The workgroup agreed that although extensive literature exists on factors that affect Veteran engagement, more work is needed to identify effective strategies to increase and sustain engagement. Workgroup members identified key priorities for research on Veteran engagement with virtual care technologies through a series of breakout discussion groups and ranking exercises. The top three priorities were to (1) understand the Veteran journey from active service to VHA enrollment and beyond, and when and how virtual care technologies can best be introduced along that journey to maximize engagement and promote seamless care; (2) utilize the meaningful relationships in a Veteran's life, including family, friends, peers, and other informal or formal caregivers, to support Veteran adoption and sustained use of virtual care technologies; and (3) test promising strategies in meaningful combinations to promote Veteran adoption and/or sustained use of virtual care technologies. Research in these priority areas has the potential to help VHA refine strategies to improve virtual care user engagement, and by extension, outcomes.

OBJECTIVE:This pilot study compared a novel communication strategy, the positive approach to the psychiatric interview, with the traditional approach to see if the positive approach can be taught to psychiatric residents; reproduced with standardized patients; measured with a structured scale, the "Positive Approach Outcome Measure," by blinded raters; and used to improve rapport (assessed with the Bond score), a key driver of engagement. METHODS:Thirty psychiatric residents were randomly assigned to conduct two psychiatric interviews with standardized patients. The standardized patients completed the Working Alliance Inventory-Short Revised, an assessment of the therapeutic alliance. T tests and linear regression examined the effect of the training on the outcome of interest, the Bond score. RESULTS:The Bond scores for the positive approach group (M = 19.27, SD = 2.87) and the traditional approach group (M = 16.90, SD = 3.44) were statistically significantly different (p = 0.05). All residents trained in the positive approach received a positive score on the Positive Approach Outcome Measure while none of the traditional approach-trained residents attained the threshold. The inter-rater reliability for the blinded raters was high (0.857), as was the intra-rater reliability (1.0). CONCLUSIONS:The positive approach can be taught to residents and reproduced consistently and was associated with improvement in a key driver of treatment engagement: rapport. The positive approach may be an important, inexpensive intervention to improve treatment engagement and ultimately treatment outcomes.

OBJECTIVE:Although evidence suggests significant cross-sectional relationships between attention-deficit/hyperactivity disorder (ADHD) and several physical health conditions, less is known about their longitudinal associations. We investigated the cumulative effect of childhood physical health conditions on ADHD symptoms at age 17 years, controlling for environmental factors, ADHD medication status, and ADHD symptoms at age 3 years. METHOD/METHODS:Using Millennium Cohort Study data (weighted n = 8,059), we assessed whether 4 physical health clusters (sensory, neurological, atopic, and cardio-metabolic) were associated with scores on the ADHD subscale from the Strengths and Difficulties Questionnaire at age 17 years. Environmental factors were grouped into 5 cumulative risk indices: prenatal, perinatal, postnatal environment, postnatal maternal well-being, and sociodemographic factors. Regression analyses determined whether each physical health cluster was associated with ADHD score while controlling for environmental factors, ADHD medication, and earlier symptoms. RESULTS: = 0.06), but the cardio-metabolic cluster was no longer a significant predictor. CONCLUSION/CONCLUSIONS:Sensory or neurological conditions in childhood were associated with higher ADHD symptoms aged 17 after adjustment of confounders. This was not the case for atopic or cardio-metabolic conditions. These findings have implications for the care of children with sensory/neurological conditions and future research examining ADHD etiopathophysiology.

BACKGROUND:Sleep restriction (SR) has been shown to upregulate neuronal reward networks in response to food stimuli but prior studies were short-term and employed severe SR paradigms. OBJECTIVE:Our goal was to determine whether mild SR, achieved by delaying bedtimes by 1.5h, influences neuronal networks responsive to food stimuli compared to maintained adequate sleep (AS) >7h/night. METHODS:A randomized controlled crossover study with two 6-wk phases, AS (≥7h sleep/night) and SR (-1.5h/night relative to screening), was conducted. Adults with adequate sleep duration, measured using wrist-actigraphy over a 2-wk screening period, and self-reported good sleep quality were enrolled. Resting-state and food-stimulated functional neuroimaging (fMRI) was performed at endpoint of each phase. Resting-state fMRI data analyses included a priori region-of-interest seed-based functional connectivity, whole-brain voxel-wise analyses, and network analyses. Food-task fMRI analyses compared brain activity patterns in response to food cues between conditions. Paired-sample t-tests tested differences between conditions. RESULTS:Twenty-six participants (16 males; age 29.6±5.3y, body mass index 26.9±4.0kg/m2) contributed complete data. Total sleep time was 7h30±28min/night during AS vs. 6h12±26min/night during SR. We employed different statistical approaches to replicate prior studies in the field and to apply more robust approaches that are currently advocated in the field. Using uncorrected P<0.01, cluster ≥10 voxels thresholds, we replicate prior findings of increased activation in response to foods in reward networks after SR vs. AS (right insula, right inferior frontal gyrus, and right supramarginal gyrus). These findings did not survive more rigorous analytical approaches (Gaussian Random Field theory correction at two-tailed voxel P<0.001, cluster P<0.05). CONCLUSIONS:Results suggest that mild SR leads to increased reward responsivity to foods but with low confidence given failure to meet significance from rigorous statistical analyses. Further research is necessary to inform the mechanisms underlying the role of sleep on food intake regulation. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT02960776; https://clinicaltrials.gov/ct2/show/NCT02960776.