Emerging data support the benefits of creative arts interventions for addressing depression in adolescents, but the neural mechanisms are poorly understood. This study examined changes in connectivity among large-scale brain networks implicated in both depression and creativity, before and after an arts intervention for adolescents with depression. Thirty-nine adolescents with depression completed resting-state functional magnetic resonance imaging scans before and after completing a two-week arts intervention called Creativity Camp. To approximate a “waitlist” control, half the sample also completed scanning 2 weeks before camp. Using a graph theory approach, we calculated the strength of connectivity between four networks at the “nexus” of mood and creativity: Default, Control, Salience, and Limbic. For these between-network connection strength indices, we (1) measured pre- to post-camp changes across the whole sample; (2) compared changes during waitlist versus during camp for the rest of the sample; and (3) explored correlations between changes in connectivity and changes in depression. In the whole sample, the strength of connectivity between three network pairs increased significantly from pre- to post-camp: Default–Control, Limbic–Control, and Salience–Default (all p < 0.05, corrected). The waitlist control comparison revealed that pre-to-post camp changes were greater than those observed during the waitlist for two of these network pairs (uncorrected). Connectivity changes did not significantly correlate with changes in depressive symptoms. Intensive engagement in creative arts may contribute to increases in connections between large-scale neural networks that are implicated in both mood and creative thinking. Future research is needed with larger samples using randomized control trials to further understand how creative arts engagement confers its mental health benefits for adolescents.

Aim: To quantify regional subcortical brain volume anomalies in youth with fetal alcohol spectrum disorder (FASD), assess the relative sensitivity and specificity of abnormal volumes in FASD vs. a comparison group, and examine associations with cognitive function. Method: Participants: 47 children with FASD and 39 typically-developing comparison participants, ages 8-17 years, who completed physical evaluations, cognitive and behavioral testing, and an MRI brain scan. A large normative MRI dataset that controlled for sex, age, and intracranial volume was used to quantify the developmental status of 7 bilateral subcortical regional volumes. Z-scores were calculated based on volumetric differences from the normative sample. T-tests compared subcortical volumes across groups. Percentages of atypical volumes are reported as are sensitivity and specificity in discriminating groups. Lastly, Pearson correlations examined the relationships between subcortical volumes and neurocognitive performance. Results: Participants with FASD demonstrated lower mean volumes across a majority of subcortical regions relative to the comparison group with prominent group differences in the bilateral hippocampi and bilateral caudate. More individuals with FASD (89%) had one or more abnormally small volume compared to 72% of the comparison group. The bilateral hippocampi, bilateral putamen, and right pallidum were most sensitive in discriminating those with FASD from the comparison group. Exploratory analyses revealed associations between subcortical volumes and cognitive functioning that differed across groups. Conclusion: In this sample, youth with FASD had a greater number of atypically small subcortical volumes than individuals without FASD. Findings suggest MRI may have utility in identifying individuals with structural brain anomalies resulting from PAE.

BackgroundPrenatal alcohol exposure (PAE) impacts hippocampal structure and function, contributing to deficits in memory and decision-making in affected individuals. Here, we evaluate hippocampal anomalies in children with PAE and an unexposed comparison group using advanced MRI methods that characterize hippocampal curvature and thickness.MethodsParticipants, ages 8 to 16 years, included children with PAE (n = 48) and an unexposed comparison group (n = 46) who underwent a dysmorphology exam, neuropsychological assessment, and an MRI scan. Height, weight, head circumference, and dysmorphic facial features were evaluated. Of those with PAE, 4.2% had fetal alcohol syndrome (FAS), 22.9% had partial FAS, and 72.9% had alcohol-related neurodevelopmental disorder. Neuropsychological testing included measures of intelligence and memory functioning. T1-weighted anatomical data were processed with the Hippunfold pipeline, which "unfolds" the complex hippocampal structure onto a template surface and provides measures of thickness and gyrification/curvature at each vertex. Permutation Analysis of Linear Models (PALM) was used to test for group differences (PAE vs. comparison) in hippocampal thickness and gyrification at each vertex and also to assess correlations with cognitive functioning.ResultsThere were significant regional differences in thickness and gyrification across bilateral hippocampi, with the PAE group showing substantially thinner tissue and less curvature than the comparison group, especially in CA1 and subiculum regions. For those with PAE, thinner subicular tissue (bilateral) was associated with lower IQ. Also in the PAE group, lower episodic memory performance was associated with thinness in the right hippocampus, especially in the subiculum region. There were no significant regional hippocampal patterns that were associated with cognitive functioning for individuals in the unexposed comparison group.ConclusionsWe used a novel MRI method to evaluate hippocampal structure in children with PAE and an unexposed comparison group. The data suggest that PAE disrupts hippocampal development, impacting both the early-stage folding of the structure and its ultimate thickness. The data also demonstrate that these developmental anomalies have functional consequences in terms of core memory functions as well as global intellectual functioning in children with PAE.

Background: Affective bias toward negativity is associated with depression and may represent a promising treatment target. Stimulating the dorsolateral prefrontal cortex (dlPFC) with deep Transcranial Magnetic Stimulation (dTMS) could lead to shifts in affective bias. The current study examined behavioral and neural correlates of affective bias in the context of dTMS in adolescents with treatment-resistant depression (TRD). Methods: Adolescents completed a Word-Face Stroop (WFS) task during an fMRI scan before and after 30 sessions of dTMS targeting the left dlPFC. In the task, participants were shown words superimposed on faces in either a "congruent" (both word and face were positive or both negative) or an "incongruent" fashion; in both cases, participants identified whether the words were positive or negative. We examined pre-post intervention neural and behavioral WFS changes and their correlations with clinical improvement. Results: Usable pre- and post-intervention WFS data were available for 10 adolescents with TRD (Age, years: M = 16.3, SD = 1.09) for behavioral data; 9 for neuroimaging data. After treatment, although changes in behavioral performance did not suggest improved affective bias, amygdala activation decreased during the negative word/ happy face condition, which correlated with clinical improvement. Overall, clinical improvement correlated with decreased neural activation during congruent conditions. Limitations: Major limitations include the small sample size, lack of a sham control group, and unknown psychometric properties. Conclusions: Preliminary findings suggesting improving neural efficiency and normalizing affective bias in those with the most clinical improvement highlight the potential importance of targeting affective bias in treating adolescents with TRD.

The Adolescent Brain Cognitive Development (ABCD) study offers a unique opportunity to identify neural correlates of mental health problems in young people. Here we applied a Hidden Markov Modeling (HMM) approach to characterize dynamic functional network connectivity in the baseline resting-state fMRI data of the ABCD dataset. We tested whether depression and suicidal thinking in children were associated with neural inflexibility as characterized by fewer state transitions during rest.

Background Executive dysfunction such as inattention or forgetfulness can lead to disruptions in a person's daily functioning and quality of life. Objective/Hypothesis This triple-blinded randomized clinical trial assessed the efficacy of bifrontal (over the forehead) transcranial direct current stimulation (tDCS) concurrent with cognitive training to improve cognitive performance in a healthy sample. Methods Fifty-eight participants were randomly assigned to one of three stimulation conditions (2mA left anode-right cathode, 2mA right anode-left cathode, or sham), which was administered with cognitive training tasks 3x/week over 12 weeks with assessments at baseline, midpoint (6 weeks), and post-training (12 weeks). We assessed cognitive performance, functional connectivity, and the influence of individual differences in training advancement. Results Forty participants completed training. We found that at midpoint and post, all groups improved significantly on overall cognitive performance. The left anode group's attention & vigilance score improved significantly at post, but the other two groups did not. Greater attention training advancement predicted attention improvement by post, most notably in the left anode group. Finally, within-network connectivity decreased in the control network and increased in the somatomotor network across all groups. Conclusions These results suggest that, given cognitive training, the left anode montage is more effective at improving attention than the right anode montage and sham. Future research may focus on the application of the left anode montage during cognitive training to assess its effectiveness in improving cognition in neuropsychiatric disorders.

IntroductionThe complexity of brain signals may hold clues to understand brain-based disorders. Sample entropy, an index that captures the predictability of a signal, is a promising tool to measure signal complexity. However, measurement of sample entropy from fMRI signals has its challenges, and numerous questions regarding preprocessing and parameter selection require research to advance the potential impact of this method. For one example, entropy may be highly sensitive to the effects of motion, yet standard approaches to addressing motion (e.g., scrubbing) may be unsuitable for entropy measurement. For another, the parameters used to calculate entropy need to be defined by the properties of data being analyzed, an issue that has frequently been ignored in fMRI research. The current work sought to rigorously address these issues and to create methods that could be used to advance this field.MethodsWe developed and tested a novel windowing approach to select and concatenate (ignoring connecting volumes) low-motion windows in fMRI data to reduce the impact of motion on sample entropy estimates. We created utilities (implementing autoregressive models and a grid search function) to facilitate selection of the matching length m parameter and the error tolerance r parameter. We developed an approach to apply these methods at every grayordinate of the brain, creating a whole-brain dense entropy map. These methods and tools have been integrated into a publicly available R package (“powseR”). We demonstrate these methods using data from the ABCD study. After applying the windowing procedure to allow sample entropy calculation on the lowest-motion windows from runs 1 and 2 (combined) and those from runs 3 and 4 (combined), we identified the optimal m and r parameters for these data. To confirm the impact of the windowing procedure, we compared entropy values and their relationship with motion when entropy was calculated using the full set of data vs. those calculated using the windowing procedure. We then assessed reproducibility of sample entropy calculations using the windowed procedure by calculating the intraclass correlation between the earlier and later entropy measurements at every grayordinate.ResultsWhen applying these optimized methods to the ABCD data (from the subset of individuals who had enough windows of continuous “usable” volumes), we found that the novel windowing procedure successfully mitigated the large inverse correlation between entropy values and head motion seen when using a standard approach. Furthermore, using the windowed approach, entropy values calculated early in the scan (runs 1 and 2) are largely reproducible when measured later in the scan (runs 3 and 4), although there is some regional variability in reproducibility.DiscussionWe developed an optimized approach to measuring sample entropy that addresses concerns about motion and that can be applied across datasets through user-identified adaptations that allow the method to be tailored to the dataset at hand. We offer preliminary results regarding reproducibility. We also include recommendations for fMRI data acquisition to optimize sample entropy measurement and considerations for the field.

Background Adolescence is a critical period for brain development, consolidation of self-understanding, and onset of non-suicidal self-injury (NSSI). This study evaluated the RDoC (Research Domain Criteria) sub-construct of Self-Knowledge in relation to adolescent NSSI using multiple units of analysis.Methods One hundred and sixty-four adolescents assigned female at birth (AFAB), ages 12-16 years with and without a history of NSSI entered a study involving clinical assessment and magnetic resonance imaging (MRI), including structural, resting-state functional MRI (fMRI), and fMRI during a self-evaluation task. For imaging analyses, we used an a priori defined Self Network (anterior cingulate, orbitofrontal, and posterior cingulate cortices; precuneus). We first examined interrelationships among multi-level Self variables. We then evaluated the individual relationships between NSSI severity and multi-level Self variables (self-report, behavior, multi-modal brain Self Network measures), then conducted model testing and multiple regression to test how Self variables (together) predicted NSSI severity.Results Cross-correlations revealed key links between self-reported global self-worth and self-evaluation task behavior. Individually, greater NSSI severity correlated with lower global self-worth, more frequent and faster negative self-evaluations, lower anterior Self Network activation during self-evaluation, and lower anterior and posterior Self Network resting-state connectivity. Multiple regression analysis revealed the model including multi-level Self variables explained NSSI better than a covariate-only model; the strongest predictive variables included self-worth, self-evaluation task behavior, and resting-state connectivity.Conclusions Disruptions in Self-Knowledge across multiple levels of analysis relate to NSSI in adolescents. Findings suggest potential neurobiological treatment targets, potentially enhancing neuroplasticity in Self systems to facilitate greater flexibility (more frequently positive) of self-views in AFAB adolescents.

BACKGROUND:Despite preliminary evidence that links impulsivity to suicide risk among Native American youth, impulsivity has not been directly studied in relation to suicide ideation (SI) or behaviors in this population. We examined indexes of rapid-response impulsivity (RRI) across multiple levels of analysis (self-report, behavioral, neurobiological) and associations with SI among Native American youth ages 9-10 in the Adolescent Brain Cognitive Development Study. METHODS:Data from the sample (n = 284) included self-report (UPPS-P), behavioral (Stop Signal Task), and neurobiological (right inferior frontal gyrus activation) indicators of RRI. RRI indicators were modeled using variable-centered (i.e., traditional multivariable regression) and person-centered (i.e., clustering analyses) approaches in measuring their association with SI. RESULTS:Logistic regression analysis demonstrated that higher negative urgency was associated with higher odds of SI (Adjusted Odds Ratio = 1.23, p = 0.015). Latent profile analysis clustered youth into five profiles based on within-individual variation in RRI indicators. Youth with an elevated self-reported negative and positive urgency profile had higher odds of reporting SI than "normative" youth (Adjusted Odds Ratio = 2.38, p = 0.019). LIMITATIONS:Limitations of this study include the modest sample size particularly regarding SI (14.1 %), potential bias in estimates of lifetime SI, and generalizability to youth from specific Native American communities. CONCLUSIONS:Negative urgency may increase risk for SI among Native American youth in late childhood. Clinical implications, including the potential for person-centered RRI profiles to act as candidate markers of suicide risk and resilience in adolescence and inform safety assessments and planning, are discussed.

Introduction Fetal alcohol spectrum disorder (FASD), a life-long condition resulting from prenatal alcohol exposure (PAE), is associated with structural brain anomalies and neurobehavioral differences. Evidence from longitudinal neuroimaging suggest trajectories of white matter microstructure maturation are atypical in PAE. We aimed to further characterize longitudinal trajectories of developmental white matter microstructure change in children and adolescents with PAE compared to typically-developing Controls using diffusion-weighted Neurite Orientation Dispersion and Density Imaging (NODDI). Materials and methods Participants: Youth with PAE ( n = 34) and typically-developing Controls ( n = 31) ages 8–17 years at enrollment. Participants underwent formal evaluation of growth and facial dysmorphology. Participants also completed two study visits (17 months apart on average), both of which involved cognitive testing and an MRI scan (data collected on a Siemens Prisma 3 T scanner). Age-related changes in the orientation dispersion index (ODI) and the neurite density index (NDI) were examined across five corpus callosum (CC) regions defined by tractography. Results While linear trajectories suggested similar overall microstructural integrity in PAE and Controls, analyses of symmetrized percent change (SPC) indicated group differences in the timing and magnitude of age-related increases in ODI (indexing the bending and fanning of axons) in the central region of the CC, with PAE participants demonstrating atypically steep increases in dispersion with age compared to Controls. Participants with PAE also demonstrated greater increases in ODI in the mid posterior CC (trend-level group difference). In addition, SPC in ODI and NDI was differentially correlated with executive function performance for PAE participants and Controls, suggesting an atypical relationship between white matter microstructure maturation and cognitive function in PAE. Discussion Preliminary findings suggest subtle atypicality in the timing and magnitude of age-related white matter microstructure maturation in PAE compared to typically-developing Controls. These findings add to the existing literature on neurodevelopmental trajectories in PAE and suggest that advanced biophysical diffusion modeling (NODDI) may be sensitive to biologically-meaningful microstructural changes in the CC that are disrupted by PAE. Findings of atypical brain maturation-behavior relationships in PAE highlight the need for further study. Further longitudinal research aimed at characterizing white matter neurodevelopmental trajectories in PAE will be important.

Despite being disproportionately burdened by suicide, mechanisms of suicidality among Native American youths remain unclear. Impulsivity is suggested as a risk factor in Native American young people, though impulsivity has not been examined explicitly in quantitative research. This project aims to examine impulsivity across multiple modes of analysis to better understand how this construct might contribute to risk for suicide ideation (SI) among this population.

OBJECTIVE:To evaluate the use of a large magnetic resonance imaging (MRI) normative dataset to quantify structural brain anomalies that may improve diagnostic sensitivity for atypical brain volume in youth with fetal alcohol spectrum disorder (FASD). STUDY DESIGN:Participants included 48 children with prenatal alcohol exposure (PAE) and 43 controls, ages 8-17 years, from the longitudinal Collaborative Initiative on FASD s. Recently published lifespan brain charts were used to quantify participants' (per)centile for brain volumes (cortical and subcortical gray matter and cortical white matter), providing an index of (dis)similarity to typically developing individuals of the same age and sex. RESULTS:Participants with PAE demonstrated lower mean centile scores compared with controls. Participants with PAE and scores ≤ 10th centile on at least 1 brain volume metric demonstrated significantly lower performance on measures of intellectual function and aspects of executive functioning compared with participants with PAE and "typical" volumes (>10th centile). Brain volume centiles explained a greater amount of variance in IQ and improved sensitivity to brain volume anomalies in FASD compared with the most commonly used diagnostic criterion of occipitofrontal circumference (OFC) ≤ 10th. CONCLUSION:Age- and sex-adjusted brain volumes based on a large normative dataset may be useful predictors of functional outcomes and may identify a greater number of individuals with FASD than the currently used criterion of OFC.