Exploring the longitudinal associations of functional network connectivity and psychiatric symptom changes in youth.

BACKGROUND: Functional connectivity has been associated with psychiatric problems, both in children and adults, but inconsistencies are present across studies. Prior research has mostly focused on small clinical samples with cross-sectional designs. METHODS: We adopted a longitudinal design with repeated assessments to investigate associations between functional network connectivity (FNC) and psychiatric problems in youth (9- to 17-year-olds, two time points) from the general population. The largest single-site study of pediatric neurodevelopment was used: Generation R (N = 3,131 with data at either time point). Psychiatric symptoms were measured with the Child Behavioral Checklist as broadband internalizing and externalizing problems, and its eight specific syndrome scales (e.g., anxious-depressed). FNC was assessed with two complementary approaches. First, static FNC (sFNC) was measured with graph theory-based metrics. Second, dynamic FNC (dFNC), where connectivity is allowed to vary over time, was summarized into 5 states that participants spent time in. Cross-lagged panel models were used to investigate the longitudinal bidirectional relationships of sFNC with internalizing and externalizing problems. Similar cross-lagged panel models were run for dFNC. RESULTS: Small longitudinal relationships between dFNC and certain syndrome scales were observed, especially for baseline syndrome scales (i.e., rule-breaking, somatic complaints, thought problems, and attention problems) predicting connectivity changes. However, no association between any of the psychiatric problems (broadband and syndrome scales) with either measure of FNC survived correction for multiple testing. CONCLUSION: We found no or very modest evidence for longitudinal associations between psychiatric problems with dynamic and static FNC in this population-based sample. Differences in findings may stem from the population drawn, study design, developmental timing, and sample sizes.

Network topology changes in chronic mild traumatic brain injury (mTBI).

BACKGROUND: In mild traumatic brain injury (mTBI), diffuse axonal injury results in disruption of functional networks in the brain and is thought to be a major contributor to cognitive dysfunction even years after trauma. OBJECTIVE: Few studies have assessed longitudinal changes in network topology in chronic mTBI. We utilized a graph theoretical approach to investigate alterations in global network topology based on resting-state functional connectivity in veterans with chronic mTBI. METHODS: 50 veterans with chronic mTBI (mean of 20.7 yrs. from trauma) and 40 age-matched controls underwent two functional magnetic resonance imaging scans 18 months apart. Graph theory analysis was used to quantify network topology measures (density, clustering coefficient, global efficiency, and modularity). Hierarchical linear mixed models were used to examine longitudinal change in network topology. RESULTS: With all network measures, we found a significant group × time interaction. At baseline, brain networks of individuals with mTBI were less clustered (p = 0.03) and more modular (p = 0.02) than those of HC. Over time, the mTBI networks became more densely connected (p = 0.002), with increased clustering (p = 0.001) and reduced modularity (p < 0.001). Network topology did not change across time in HC. CONCLUSION: These findings demonstrate that brain networks of individuals with mTBI remain plastic decades after injury and undergo significant changes in network topology even at the later phase of the disease.

A randomized controlled trial of transcranial direct-current stimulation and cognitive training in children with fetal alcohol spectrum disorder.

BACKGROUND: This study was a randomized double-blind sham-controlled trial examining the effects of transcranial direct current stimulation (tDCS) augmented cognitive training (CT) in children with Fetal Alcohol Spectrum Disorders (FASD). Prenatal alcohol exposure has profound detrimental effects on brain development and individuals with FASD commonly present with deficits in executive functions including attention and working memory. The most commonly studied treatment for executive deficits is CT, which involves repeated drilling of exercises targeting the impaired functions. As currently implemented, CT requires many hours and the observed effect sizes are moderate. Neuromodulation via tDCS can enhance brain plasticity and prior studies demonstrate that combining tDCS with CT improves efficacy and functional outcomes. TDCS-augmented CT has not yet been tested in FASD, a condition in which there are known abnormalities in neuroplasticity and few interventions. METHODS: This study examined the feasibility and efficacy of this approach in 44 children with FASD. Participants were randomized to receive five sessions of CT with either active or sham tDCS targeting the dorsolateral prefrontal cortex, a region of the brain that is heavily involved in executive functioning. RESULTS: The intervention was feasible and well-tolerated in children with FASD. The tDCS group showed nominally significant improvement in attention on a continuous performance test compared to sham (p = .043). Group differences were observed at the third, fourth and fifth treatment sessions. There was no effect of tDCS on working memory (p = .911). Further, we found no group differences on a trail making task (p = .659) or on the verbal fluency test (p = .826). In the active tDCS group, a significant correlation was observed between improvement in attention scores and decrease in parent-reported attention deficits (p = .010). CONCLUSIONS: These results demonstrate that tDCS-augmented CT is well tolerated in children with FASD and potentially offers benefits over and above CT alone.

Transcranial direct current stimulation (tDCS) elicits stimulus-specific enhancement of cortical plasticity.

BACKGROUND: Deficits in plasticity underlie many severe psychiatric disorders. Transcranial direct current stimulation (tDCS) is a promising method for modulating plasticity. However, given its non-focal nature, there are open questions as to how targeting and outcome specificity can best be achieved. OBJECTIVE: Understanding how tDCS interacts with concurrent brain activity is necessary for the rational advancement of tDCS. In the present study, we use an event-related potential (ERP) paradigm to assess the stimulus-specific effects of tDCS on cortical plasticity. METHODS: 22 healthy volunteers underwent a blinded, sham-controlled plasticity paradigm in a crossover design. High frequency presentation of auditory stimuli was used to induce potentiation in specific components of the ERP. We investigated whether anodal tDCS targeting the auditory cortex would modulate plasticity induction across time. Two pure tones were used as stimuli, only one of the tones, the target tone, was used for plasticity induction. Plasticity was quantified as change in the mean amplitude of the N100 component relative to baseline. RESULTS: TDCS significantly modulated plasticity in the target tone compared to sham (p â€‹= â€‹0.02) but had no effect on the control tone (p â€‹= â€‹0.73). This effect was time dependent, with tDCS effects no longer apparent 30 â€‹min after stimulation. CONCLUSIONS: Our results indicate that tDCS can modulate cortical plasticity in the auditory cortex in an activity-dependent manner. These findings bolster the idea that tDCS can be an effective tool to target and modulate plasticity both for research and therapeutic purposes.

Transcranial Direct Current Stimulation over the Dorsolateral Prefrontal Cortex in Schizophrenia: A Quantitative Review of Cognitive Outcomes.

Cognitive deficits are a core and disabling feature of psychotic disorders, specifically schizophrenia. Current treatments for impaired cognition in schizophrenia remain insufficient. Recent research suggests transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex can potentiate cognitive improvements in healthy individuals and those with psychiatric conditions, such as schizophrenia. However, this burgeoning literature has not been quantitatively evaluated. Through a literature search and quantitative review, we identified 194 papers on tDCS, psychosis, and cognition. Selection criteria included pre/post design and sham control to achieve specific sham-adjusted effect sizes. The 6 retained studies all address schizophrenia populations and include single and repeated stimulation, as well as within and between subject designs. Small positive effects were found for anodal stimulation on behavioral measures of attention and working memory, with tentative findings for cognitive ability and memory. Cathodal stimulation yielded a small positive effect on behaviorally measured cognitive ability. Neurophysiological measures of attention showed a small to medium down-modulation effect for anodal stimulation. Implications of these findings and guidelines for future research are discussed. As revealed by this report, due to the paucity of data available, much remains unknown regarding the clinical efficacy of tDCS in schizophrenia.