Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset¹. Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals^2,3,4, but this approach has not been applied in depression. Here, using precision functional mapping and several samples of deeply sampled individuals, we found that the frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression. This effect was replicable in several samples and caused primarily by network border shifts, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was stable over time, unaffected by mood state and detectable in children before the onset of depression later in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in frontostriatal circuits that tracked fluctuations in specific symptoms and predicted future anhedonia symptoms. Together, these findings identify a trait-like brain network topology that may confer risk for depression and mood-state-dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.

Background: Transcranial direct current stimulation (tDCS) is a safe, tolerable, and acceptable technique in adults. However, there is limited evidence for its safety in youth. Although limited, there are a handful of important empirical articles that have evaluated safety and tolerability outcomes in youth. However, a synthesis of pediatric safety studies is not currently available. Objective: To synthesize objective evidence regarding the safety and tolerability of pediatric tDCS based on the current state of the literature. Methods: Our search and report used PRISMA guidelines. Our method systematically examined investigations purposefully designed to evaluate the safety, tolerability, and acceptability of tDCS in healthy and atypical youth that were submitted to three databases, from the beginning of the database to November 2019. Safety considerations were evaluated by studies utilizing neuroimaging, physiological changes, performance on tasks, and by analyzing reported and objective side effects; tolerability via rate of adverse events; and acceptability via rate of dropouts. Results: We report on 203 sham sessions, 864 active sessions up to 2 mA, and 303 active hours of stimulation in 156 children. A total of 4.4% of the active sessions were in neurotypical controls, with the other 95.6% in clinical subjects. Conclusion: In spite of the fact that the current evidence is sporadic and scarce, the presently reviewed literature provides support for the safety, tolerability, and acceptability, of tDCS in youth for 1–20 sessions of 20 min up to 2 mA. Future pediatric tDCS research is encouraged.

(1) Background: Mild traumatic brain injury produces significant changes in neurotransmission including brain oscillations. We investigated potential quantitative electroencephalography biomarkers in 57 patients with post-concussive syndrome and chronic pain following motor vehicle collision, and 54 healthy nearly age- and sex-matched controls. (2) Methods: Electroencephalography processing was completed in MATLAB, statistical modeling in SPSS, and machine learning modeling in Rapid Miner. Group differences were calculated using current-source density estimation, yielding whole-brain topographical distributions of absolute power, relative power and phase-locking functional connectivity. Groups were compared using independent sample Mann–Whitney U tests. Effect sizes and Pearson correlations were also computed. Machine learning analysis leveraged a post hoc supervised learning support vector non-probabilistic binary linear kernel classification to generate predictive models from the derived EEG signatures. (3) Results: Patients displayed significantly elevated and slowed power compared to controls: delta (p = 0.000000, r = 0.6) and theta power (p < 0.0001, r = 0.4), and relative delta power (p < 0.00001) and decreased relative alpha power (p < 0.001). Absolute delta and theta power together yielded the strongest machine learning classification accuracy (87.6%). Changes in absolute power were moderately correlated with duration and persistence of symptoms in the slow wave frequency spectrum (<15 Hz). (4) Conclusions: Distributed increases in slow wave oscillatory power are concurrent with post-concussive syndrome and chronic pain.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with substantial evidence for its safety and tolerability in adults. However, less than 5% of published tDCS research is in pediatrics. Our primary objective was to investigate tDCS safety, tolerability, and acceptability in a sample of children and adults. We hypothesized that children and adults would be equal with regard to tDCS safety, tolerability, and acceptability. We tested this hypothesis using a Bayesian approach. Sixty participants aged 6–45 (balanced for sex) participated in a randomized double-blind controlled trial. They were randomly assigned to two ten-minute tDCS sessions with varying amperages and electrode locations. The primary outcome measure of this study was the intensity of 13 potential side effects evaluated at six different time points spanning two weeks. Independent sample Bayes factor tests were conducted between children/adults, males/females, clinical/healthy, and low/high amperage groups. As predicted, there was moderate support for the null hypothesis in all between-group analyses. There were no serious adverse events or dropouts, and the number needed to treat for an additional harmful outcome was 23. This study provided evidence supporting the overall short-term safety, tolerability, and acceptability of tDCS including amperages up to 2 mA and different electrode placements.

Transcranial direct current stimulation (tDCS) is a novel treatment option for attention deficit hyperactivity disorder. To facilitate translation into clinical practice, we interviewed parents of children who have experienced experimental tDCS. A grounded theory approach using open, axial, and selective coding provided seven emergent themes for acceptability: tDCS provides hope for parents, safety tolerability and side effects of tDCS versus medication, burden of treatment, education and trust with care providers, cost and coverage, unestablished tDCS efficacy versus established medication effectiveness, perceived compliance of tDCS versus medication. Results suggest tDCS is acceptable but depends on evidence of effectiveness and regular availability.