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The impact of adverse childhood experiences (ACEs) differs between individuals and depends on the type and timing of the ACE. The aim of this study was to assess the relation between various recently occurred ACEs and morphology in the developing brain of children between 8 and 11 years of age. We measured subcortical volumes, cortical thickness, cortical surface area and fractional anisotropy in regions of interest in brain scans acquired in 1,184 children from the YOUth cohort. ACEs were based on parent-reports of recent experiences and included: financial problems; parental mental health problems; physical health problems in the family; substance abuse in the family; trouble with police, justice or child protective services; change in household composition; change in housing; bereavement; divorce or conflict in the family; exposure to violence in the family and bullying victimization. We ran separate linear models for each ACE and each brain measure. Results were adjusted for the false discovery rate across regions of interest. ACEs were reported for 83% of children in the past year. Children were on average exposed to two ACEs. Substance abuse in the household was associated with larger cortical surface area in the left superior frontal gyrus, t(781) = 3.724, pFDR = 0.0077, right superior frontal gyrus, t(781) = 3.409, pFDR = 0.0110, left pars triangularis, t(781) = 3.614, pFDR = 0.0077, left rostral middle frontal gyrus, t(781) = 3.163, pFDR = 0.0195 and right caudal anterior cingulate gyrus, t(781) = 2.918, pFDR = 0.0348. Household exposure to violence (was associated with lower fractional anisotropy in the left and right cingulum bundle hippocampus region t(697) = −3.154, pFDR = 0.0101 and t(697) = −3.401, pFDR = 0.0085, respectively. Lower household incomes were more prevalent when parents reported exposure to violence and the mean parental education in years was lower when parents reported substance abuse in the family. No other significant associations with brain structures were found. Longer intervals between adversity and brain measurements and longitudinal measurements may reveal whether more evidence for the impact of ACEs on brain development will emerge later in life.

BackgroundIndividuals at ultra-high risk for psychosis (UHR) present with subtle alterations in cerebral white matter (WM), which appear to be associated with clinical and functional outcome. The effect of cognitive remediation on WM organization in UHR individuals has not been investigated previously.MethodsIn a randomized, clinical trial, UHR individuals aged 18 to 40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation for 20 weeks. Cognitive remediation comprised 20 x 2-h sessions of neurocognitive and social-cognitive training. Primary outcome was whole brain fractional anisotropy derived from diffusion weighted imaging, statistically tested as an interaction between timepoint and treatment group. Secondary outcomes were restricted to five predefined region of interest (ROI) analyses on fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. For significant timepoint and treatment group interactions within these five ROIs, we explored associations between longitudinal changes in WM and cognitive functions/clinical symptoms. Finally, we explored dose-response effects of cognitive remediation on WM.ResultsA total of 111 UHR individuals were included. Attrition-rate was 26%. The cognitive remediation group completed on average 12 h of neurocognitive training, which was considerably lower than per protocol. We found no effect of cognitive remediation on whole-brain FA when compared to treatment as usual. Secondary ROI analyses revealed a nominal significant interaction between timepoint*treatment of AD in left medial lemniscus (P=0.016) which did not survive control for multiple comparisons. The exploratory test showed that this change in AD correlated to improvements of mental flexibility in the cognitive remediation group (p=0.001). We found no dose-response effect of neurocognitive training on WM.ConclusionsCognitive remediation comprising 12 h of neurocognitive training on average did not improve global or regional WM organization in UHR individuals. Further investigations of duration and intensity of cognitive training as necessary prerequisites of neuroplasticity-based changes are warranted.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02098408.

Intelligence is a measure of general cognitive functioning capturing a wide variety of different cognitive functions. It has been hypothesized that the brain works to minimize the resources allocated toward higher cognitive functioning. Thus, for the intelligent brain, it may be that not simply more is better, but rather, more efficient is better. Energy metabolism supports both inhibitory and excitatory neurotransmission processes. Indeed, in glutamatergic and GABAergic neurons, the primary energetic costs are associated with neurotransmission. We tested the hypothesis that minimizing resources through the excitation–inhibition balance encompassing gamma-aminobutyric acid (GABA) and glutamate may be beneficial to general cognitive functioning using 7 T 1H-MRS in 23 healthy individuals (male/female = 16/7, 27.7 ± 5.3 years). We find that a higher working memory index is significantly correlated with a lower GABA to glutamate ratio in the frontal cortex and with a lower glutamate level in the occipital cortex. Thus, it seems that working memory performance is associated with the excitation–inhibition balance in the brain.

PurposeTo assess reproducibility of glutamate measurement in the human brain by two short echo time (TE) 1H-MRS sequences [stimulated echo acquisition mode (STEAM) and semi-localized by adiabatic selective refocusing (sLASER)] at 7 T. Reliable assessment of glutamate is important when studying a variety of neurological and neuropsychiatric disorders. At 7 T, the glutamate signal can be separated from the glutamine signal and hence more accurately measured as compared to lower field strengths. A sLASER sequence has been developed for 7 T, using field focusing at short TE, resulting in twice as much signal as can be obtained using STEAM and improved localization accuracy due to a decreased chemical shift artifact.Materials and methodsEight subjects were scanned twice using both STEAM and sLASER. Data were acquired from the frontal and occipital brain region. Subsequently, intraclass correlations were computed for the estimated metabolite concentrations.ResultssLASER has higher ICC’s for glutamate concentration as compared to STEAM in both the frontal and occipital VOI, which is probably due to the higher sensitivity and localization accuracy.ConclusionWe conclude that sLASER 1H-MRS at 7 T is a reliable method to obtain reproducible measures of glutamate levels in the human brain at such high accuracy that individual variability, even between age-matched subjects, is measured.