Evaluation of an Integrated Psychology Service in a Pediatric Emergency Department and Urgent Care.

OBJECTIVES: Children visiting emergency departments (EDs) are disproportionately affected by mental health disorders. Integrated behavioral health models hold promise for improving care among ED patients. We implemented and evaluated a novel behavioral health service integrated psychology trainees in a safety net hospital's pediatric ED and urgent care. METHODS: Consultations and interventions provided were identified from the service's patient registry. Patients treated by the service were matched based on age, sex, day, and month of presentation to control patients who received a brief assessment by a specialized psychiatric nurse or patients receiving comprehensive management in a psychiatric emergency service. Rates of ED return visits were obtained from local hospital records, and insurance claims were used to identify rates of psychiatric hospitalization and outpatient follow-up care. RESULTS: The most commonly provided interventions among 71 intervention patients were assistance with connection to follow-up behavioral health treatment (65%), relaxation training (41%), and motivational interviewing (31%). These patients were matched with 142 comparison patients. There was no difference among groups in return rates within 90 days among intervention versus nurse assessment or psychiatric emergency service patients (25% vs 23% vs 13%, P = 0.14). Insurance claims data were available for 115 patients (54%): within 90 days, integrated care patients were less likely to have at least 1 outpatient claim (52% vs 78% vs 84%, P < 0.01), and there was no difference in rates of psychiatric hospital admission (18% vs 20% vs 24%, P = 0.83). CONCLUSIONS: Although this psychology-led integrated behavioral health service delivered a range of brief psychotherapeutic interventions, its impact on outpatient, inpatient, and emergency care was mixed. This lower follow-up rate among intervention patients may reflect the success of active psychological treatment in the ED, lower acuity among intervention patients, or implications of the study's safety net setting. The authors discuss this model's potential for enhancing mental health care in pediatric EDs.

Stable Meta-Networks, Noise, and Artifacts in the Human Connectome: Low- to High-Dimensional Independent Components Analysis as a Hierarchy of Intrinsic Connectivity Networks.

Connectivity within the human connectome occurs between multiple neuronal systems-at small to very large spatial scales. Independent component analysis (ICA) is potentially a powerful tool to facilitate multi-scale analyses. However, ICA has yet to be fully evaluated at very low (10 or fewer) and ultra-high dimensionalities (200 or greater). The current investigation used data from the Human Connectome Project (HCP) to determine the following: (1) if larger networks, or meta-networks, are present at low dimensionality, (2) if nuisance sources increase with dimensionality, and (3) if ICA is prone to overfitting. Using bootstrap ICA, results suggested that, at very low dimensionality, ICA spatial maps consisted of Visual/Attention and Default/Control meta-networks. At fewer than 10 components, well-known networks such as the Somatomotor Network were absent from results. At high dimensionality, nuisance sources were present even in denoised high-quality data but were identifiable by correlation with tissue probability maps. Artifactual overfitting occurred to a minor degree at high dimensionalities. Basic summary statistics on spatial maps (maximum cluster size, maximum component weight, and average weight outside of maximum cluster) quickly and easily separated artifacts from gray matter sources. Lastly, by using weighted averages of bootstrap stability, even ultra-high dimensional ICA resulted in highly reproducible spatial maps. These results demonstrate how ICA can be applied in multi-scale analyses, reliably and accurately reproducing the hierarchy of meta-networks, large-scale networks, and subnetworks, thereby characterizing cortical connectivity across multiple spatial scales.

Deep Brain Stimulation for Obsessive-Compulsive Disorder: Real World Experience Post-FDA-Humanitarian Use Device Approval.

Background: While case series have established the efficacy of deep brain stimulation (DBS) in treating obsessive-compulsive disorder (OCD), it has been our experience that few OCD patients present without comorbidities that affect outcomes associated with DBS treatment. Here we present our experience with DBS therapy for OCD in patients who all have comorbid disease, together with the results of our programming strategies. Methods: For this case series, we assessed five patients who underwent ventral capsule/ventral striatum (VC/VS) DBS for OCD between 2015 and 2019 at the University of Colorado Hospital. Every patient in this cohort exhibited comorbidities, including substance use disorders, eating disorder, tic disorder, and autism spectrum disorder. We conducted an IRB-approved, retrospective study of programming modifications and treatment response over the course of DBS therapy. Results: In addition to patients' subjective reports of improvement, we observed significant improvement in the Yale-Brown Obsessive-Compulsive Scale (44%), the Montgomery-Asberg Depression Rating Scale (53%), the Quality of Life Enjoyment and Satisfaction Questionnaire (27%), and the Hamilton Anxiety Rating scales (34.9%) following DBS. With respect to co-morbid disease, there was a significant improvement in a patient with tic disorder's Total Tic Severity Score (TTSS) (p = 0.005). Conclusions: DBS remains an efficacious tool for the treatment of OCD, even in patients with significant comorbidities in whom DBS has not previously been investigated. Efficacious treatment results not only from the accurate placement of the electrodes by the surgeon but also from programming by the psychiatrist.

Effects of acetate on cerebral blood flow, systemic inflammation, and behavior in alcohol use disorder.

BACKGROUND: Alcohol use disorders (AUDs) are associated with altered regulation of physiological processes in the brain. Acetate, a metabolite of ethanol, has been implicated in several processes that are disrupted in AUDs including transcriptional regulation, metabolism, inflammation, and neurotransmission. To further understand the effects of acetate on brain function in AUDs, we investigated the effects of acetate on cerebral blood flow (CBF), systemic inflammatory cytokines, and behavior in AUD. METHODS: Sixteen participants with AUD were recruited from a nonmedical, clinically managed detoxification center. Each participant received acetate and placebo in a randomly assigned order of infusion and underwent 3T MR scanning using quantitative pseudo-continuous arterial spin labeling. Participants and the study team were blinded to the infusion. CBF values (ml/100 g/min) extracted from thalamus were compared between placebo and acetate using a mixed effect linear regression model accounting for infusion order. Voxel-wise CBF comparisons were set at threshold of p < 0.05 cluster-corrected for multiple comparisons, voxel-level p < 0.0001. Plasma cytokine levels and behavior were also assessed between infusions. RESULTS: Fifteen men and 1 woman were enrolled with Alcohol Use Disorders Identification Test (AUDIT) scores between 13 and 38 with a mean of 28.3 ± 9.1. Compared to placebo, acetate administration increased CBF in the thalamus bilaterally (Left: 51.2 vs. 68.8, p < 0.001; Right: 53.7 vs. 69.6, p = 0.001), as well as the cerebellum, brainstem, and cortex. Older age and higher AUDIT scores were associated with increases in acetate-induced thalamic blood flow. Cytokine levels and behavioral measures did not differ between placebo and acetate infusions. CONCLUSIONS: This pilot study in AUD suggests that during the first week of abstinence from alcohol, the brain's response to acetate differs by brain region and this response may be associated with the severity of alcohol dependence.

In Utero Exposure to Maternal Overweight or Obesity is Associated with Altered Offspring Brain Function in Middle Childhood.

OBJECTIVE: The impact of in utero exposure to maternal overweight and obesity on offspring metabolic health is well documented. Neurodevelopmental outcomes among these children are, however, less well studied. To address this gap, the current study investigated brain function among 4- to 6-year-old children exposed to maternal overweight or obesity during gestation compared with that of children born to mothers with healthy BMI in pregnancy. METHODS: Resting-state functional magnetic resonance imaging was used to study neuronal activity and connectivity during a passive viewing task (movie) among 101 typically developing children enrolled in the Healthy Start study, a longitudinal prebirth cohort in Colorado. RESULTS: Forty-nine children (48%) were exposed to maternal overweight or obesity in utero (mean age = 5 years, SD = 0.9). Children born to mothers with overweight or obesity demonstrated hyperactivity in the left posterior cingulate cortex and hypoactivity in the dorsal anterior cingulate and the supplementary motor area (P < 0.05 for all). Children born to mothers with overweight or obesity also showed ubiquitously weaker brain connectivity (P < 0.05 for all). CONCLUSIONS: These novel results suggest altered brain function among children exposed to maternal overweight and obesity in utero.

Hemodynamic responses are abnormal in isolated cervical dystonia.

Neuroimaging studies using functional magnetic resonance imaging (fMRI), which measures brain activity by detecting the changes in blood oxygenation levels, are advancing our understanding of the pathophysiology of dystonia. Neurobiological disturbances in dystonia, however, may affect neurovascular coupling and impact the interpretability of fMRI studies. We evaluated here whether the hemodynamic response patterns during a behaviorally matched motor task are altered in isolated cervical dystonia (CD). Twenty-five CD patients and 25 healthy controls (HCs) underwent fMRI scanning during a paced finger tapping task (nondystonic task in patients). Imaging data were analyzed using a constrained principal component analysis-a statistical method that combines regression analysis and principal component analysis and enables the extraction of task-related functional networks and determination of the spatial and temporal hemodynamic response patterns associated with the task performance. Data from three patients and two controls were removed due to excessive movement. No significant differences in demographics or motor performance were observed. Three task-associated functional brain networks were identified. During task performance, reduced hemodynamic responses were seen in a sensorimotor network and in a network that included key nodes of the default mode, executive control and visual networks. During rest, reductions in hemodynamic responses were seen in the cognitive/visual network. Lower hemodynamic responses within the primary sensorimotor network in patients were correlated with the increased dystonia severity. Pathophysiological disturbances in isolated CD, such as alterations in inhibitory signaling and dopaminergic neurotransmission, may impact neurovascular coupling. Not accounting for hemodynamic response differences in fMRI studies of dystonia could lead to inaccurate results and interpretations.

Effects of Alcohol and Acetate on Cerebral Blood Flow: A Pilot Study.

BACKGROUND: Acute alcohol produces effects on cerebral metabolism and blood flow. Alcohol is converted to acetate, which serves as a source of energy for the brain and is an agonist at G protein-coupled receptors distributed in different cell types in the body including neurons. Acetate has been hypothesized to play a role in the cerebral blood flow (CBF) response after alcohol ingestion. We tested whether administration of acetate would alter CBF in a pattern similar to or different from that of alcohol ingestion in healthy individuals. METHODS: Twenty-four healthy participants were assigned by convenience to receive either 0.6 g/kg alcohol orally (n = 12) or acetate intravenously (n = 12). For each participant, CBF maps were acquired using an arterial spin labeling sequence on a 3T magnetic resonance scanner after placebo and after drug administration. Whole-brain CBF maps were compared between placebo and drug using a paired t-test, and set at a threshold of p < 0.05 corrected for multiple comparisons (k ≥ 142 voxels, ≥3.78 cm3 ), voxel-level p < 0.005. Intoxication was measured after placebo and drug administration with a Subjective High Assessment Scale (SHAS-7). RESULTS: Compared to placebo, alcohol and acetate were associated with increased CBF in the medial thalamus. Alcohol, but not acetate, was associated with increased CBF in the right orbitofrontal, medial prefrontal and cingulate cortex, and hippocampus. Plasma acetate levels increased following administration of alcohol and acetate and did not differ between the 2 arms. Alcohol, but not acetate, was associated with an increase in SHAS-7 scores (p < 0.001). CONCLUSIONS: Increased thalamic CBF associated with either alcohol or acetate administration suggests that the thalamic CBF response after alcohol could be mediated by acetate. Compared to other brain regions, thalamus may differ in its ability to metabolize acetate or expression of receptors responsive to acetate. Increased prefrontal and limbic CBF associated with alcohol may be linked to alcohol's behavioral effects.

Associations Between School-Based Substance Use Treatment and Academic Outcomes.

Objectives: Evaluate the association between school-based treatment of substance use disorders and academic outcomes by developing a system of simple and easily tracked academic performance metrics coinciding with an established substance use treatment program. Methods: This study provided treatment to 75 high school students enrolled without exclusion who voluntarily sought care for substance use disorders. Participants were enrolled in a 12-week program of individual motivational interviewing, acceptance and commitment therapy, family sessions, case management, contingency management, and psychiatric consultation at school-based health centers. We tracked distinct metrics of substance use treatment, including urine drug screens and self-reported use, along with three key metrics of academic performance referred to as the ABCs: attendance (No. of missed classes and percentage of days attended), behavior (No. of behavioral incidents per semester), and credits (grade-point average). Results: Participants in the study attended an average of 6.4 sessions and nearly 50% attained a negative urine drug screen. Participants demonstrated a significant reduction in behavioral incidents with an average decrease from 1.2 to 0.41 incidents per semester (p < 0.01). In addition, there was a reduction in the mean number of missed classes from 148 per semester to 127 (p = 0.001). Conclusions: School-based substance use treatment appears to be associated with a reduction in behavioral incidents and improved class attendance. This study provides the foundation for development of a robust school-based substance treatment program that can be rigorously evaluated against a control group for students with substance use disorders.

Kernel machine tests of association between brain networks and phenotypes.

Applications of quantitative network analysis to functional brain connectivity have become popular in the last decade due to their ability to describe the general topological principles of brain networks. However, many issues arise when standard statistical analysis techniques are applied to functional magnetic resonance imaging (fMRI) connectivity maps. Frequently, summary measures of these maps, such as global efficiency and clustering coefficients, collapse the changing structures of graph topology from many scales to one. This can result in a loss of whole-brain spatio-temporal pattern information that may be significant in association and prediction analyses. Drawing from the electrical engineering field, the resistance perturbation distance is a quantification of similarity between graphs on the same vertex set that has been shown to identify changes in dynamic graphs, such as those from fMRI, while not being computationally expensive or result in a loss of information. This work proposes a novel kernel-based regression scheme that incorporates the resistance perturbation distance to better understand the association with biological phenotypes from fMRI using both simulated and real datasets.

Eating in the absence of hunger in young children is related to brain reward network hyperactivity and reduced functional connectivity in executive control networks.

BACKGROUND: Recent work has implicated disinhibited eating behaviours (DEB) as a potential pathway toward obesity development in children. However, the underlying neurobiology of disinhibited eating behaviours in young, healthy weight children, prior to obesity development, remains unknown. OBJECTIVES: This study tested the relationship between DEB and intrinsic neuronal activity and connectivity in young children without obesity. METHODS: Brain networks implicated in overeating including reward, salience and executive control networks, and the default mode network were investigated. DEB was measured by the eating in the absence of hunger (EAH) paradigm with postlunch kilocalories consumed from highly palatable foods (EAH kcal) used as the predictor. Intrinsic neuronal activity within and connectivity between specified networks were measured via resting-state functional magnetic resonance imaging. Eighteen typically developing children (mean age = 5.8 years) were included. RESULTS: EAH kcal was positively associated with activity of the nucleus accumbens, a major reward network hub (P < 0.05, corrected). EAH kcal was negatively associated with intrinsic prefrontal cortex connectivity to the striatum (P < 0.01, corrected). CONCLUSIONS: These results suggest that neural aspects of DEB are detectable in young children without obesity, providing a potential tool to better understand the development of obesity in this population.