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Background: An improved understanding of the neurodevelopmental differences between attention deficit hyperactivity disorder with and without prenatal alcohol exposure (ADHD + PAE and ADHD-PAE, respectively) is needed. Herein, we evaluated gyrification (cortical folding) in children with ADHD + PAE compared to that in children with familial ADHD-PAE and typically developing (TD) children., Methods: ADHD + PAE (n = 37), ADHD-PAE (n = 25), and TD children (n = 27), aged 8-13 years, were compared on facial morphological, neurobehavioral, and neuroimaging assessments. Local gyrification index (LGI) maps were compared between groups using general linear modelling. Relationships between LGI and clincobehavioral parameters in children with ADHD ± PAE were evaluated using multivariate partial least squares., Results: ADHD + PAE and ADHD-PAE groups showed significantly lower LGI (relative to TD) in numerous regions, overlapping in medial prefrontal, parietal, and temporo-occipital cortices (p < 0.001). However, LGI in left mid-dorsolateral prefrontal cortex was uniquely lower in the ADHD + PAE group (p < 0.001). Partial least squares analysis identified one significant latent variable (accounting for 59.3 % of the crossblock correlation, p < 0.001), reflecting a significant relationship between a profile of lower LGI in prefrontal (including left mid-dorsolateral), insular, cingulate, temporal, and parietal cortices and a clinicobehavioral profile of PAE, including a flat philtrum and upper vermillion border, lower IQ, poorer behavioral regulation scores, and greater hyperactivity/impulsivity., Conclusions: Children with ADHD + PAE uniquely demonstrate lower mid-dorsolateral LGI, with widespread lower LGI related to more severe facial dysmorphia and neurobehavioral impairments. These findings add insight into the brain bases of PAE symptoms, potentially informing more targeted ADHD treatments based on an objective differential diagnosis of ADHD + PAE vs. ADHD-PAE., (Copyright © 2021. Published by Elsevier B.V.)

Background: Intermittent theta-burst stimulation priming (iTBS-P) can improve clinical outcome of patients with Major Depressive Disorder (MDD) who do not show early benefit from 10 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC), also known as high-frequency left-sided (HFL) stimulation. The intensity and pulse number for iTBS-P needed to induce clinical benefit have not been systematically examined., Objective: To study the effect of intensity and pulse number on the clinical efficacy of iTBS-P., Methods: We conducted a retrospective review of 71 participants who received at least five sessions of HFL with limited clinical benefit and received iTBS-P augmentation for between 5 and 25 sessions. Intensity of iTBS-P priming stimuli ranged from 75 to 120% of motor threshold (MT) and pulse number ranged from 600 to 1800. Associations among intensity, pulse number, and clinical outcome were analyzed using a mixed methods linear model with change in IDS-SR as the primary outcome variable, priming stimulation intensity (subthreshold or suprathreshold), pulse number (<1200 or >1200 pulses), and gender as fixed factors, and number of iTBS-P treatments and age as continuous covariates., Results: Subjects who received subthreshold intensity iTBS-P experienced greater reduction in depressive symptoms than those who received suprathreshold iTBS-P (p = 0.011) with no effect of pulse number after controlling for stimulus intensity., Conclusions: Subthreshold intensity iTBS-P was associated with greater clinical improvement than suprathreshold stimulation. This finding is consistent with iTBS-P acting through homeostatic plasticity mechanisms., Competing Interests: Declaration of competing interest Drs. Corlier, Tadayonnejad, Marder, Krantz, Wilke, Levitt, and Ginder, along with Ms. Doan Ngo have no disclosures, Andrew Wilson has served as a consultant to HeartCloud, Inc within the past 36 months. Dr. Leuchter discloses that within the past 36 months he has received research support from the National Institutes of Health, Neuronetics, Department of Defense, CHDI Foundation, and NeuroSigma, Inc. He has served as a consultant to NeoSync, Inc., Ionis Pharmaceuticals, Inc., and ElMindA. He is Chief Scientific Officer of Brain Biomarker Analytics LLC (BBA). Dr. Leuchter has equity interest in BBA. Jonathan Lee has received in-kind equipment support from Magventure Inc. The authors report no other conflicts of interest in this work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Focal brain metabolic effects detected by proton magnetic resonance spectroscopy (MRS) in obsessive-compulsive disorder (OCD) represent prospective indices of clinical status and guides to treatment design. Sampling bilateral pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and thalamus in 40 adult patients and 16 healthy controls, we examined relationships of the neurometabolites glutamate+glutamine (Glx), creatine+phosphocreatine (Cr), and choline-compounds (Cho) with OCD diagnosis and multiple symptom types. The latter included OC core symptoms (Yale-Brown Obsessive-Compulsive Scale - YBOCS), depressive symptoms (Montgomery-Åsberg Depression Rating Scale - MADRS), and general functioning (Global Assessment Scale - GAS). pACC Glx was 9.7% higher in patients than controls. Within patients, Cr and Cho correlated negatively with YBOCS and MADRS, while Cr correlated positively with the GAS. In aMCC, Cr and Cho correlated negatively with MADRS, while Cr in thalamus correlated positively with GAS. These findings present moderate support for glutamatergic and cingulocentric perspectives on OCD. Based on our prior metabolic model of OCD, we offer one possible interpretation of these group and correlational effects as consequences of a corticothalamic state of elevated glutamatergic receptor activity alongside below-normal glutamatergic transporter activity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Previous voxel-based and regions-of-interest (ROI)-based diffusion tensor imaging (DTI) studies have found above-normal mean diffusivity (MD) and below-normal fractional anisotropy (FA) in subjects with attention-deficit/hyperactivity disorder (ADHD). However, findings remain mixed, and few studies have examined the contribution of ADHD familial liability to white matter microstructure., Method: We used refined DTI tractography methods to examine MD, FA, axial diffusivity (AD), and radial diffusivity (RD) of the anterior thalamic radiation, cingulum, corticospinal tract, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major, forceps minor, superior longitudinal fasciculus, and uncinate fasciculus in children and adolescents with ADHD (n = 56), unaffected siblings of ADHD probands (n = 31), and healthy controls (n = 17)., Results: Subjects with ADHD showed significantly higher MD than controls in the anterior thalamic radiation, forceps minor, and superior longitudinal fasciculus. Unaffected siblings of subjects with ADHD displayed similar differences in MD as subjects with ADHD. Although none of the tested tracts showed a significant effect of FA, the tracts with elevated MD likewise displayed elevated AD both in subjects with ADHD and in unaffected siblings. Differences in RD between subjects with ADHD, unaffected siblings, and controls were not as widespread as differences in MD and AD., Conclusion: Our findings suggest that disruptions in white matter microstructure occur in several large white matter pathways in association with ADHD and indicate a familial liability for the disorder. Furthermore, MD may reflect these abnormalities more sensitively than FA., (Copyright © 2013 American Academy of Child & Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Subjects with autism suffer from impairments of social interaction, deviations in language usage, as well as restricted and stereotyped patterns of behavior. These characteristics are found irrespective of age, IQ, and gender of affected subjects. However, brain changes due to age, IQ, and gender might pose potential confounds in autism neuroimaging analyses., Methods: To investigate gray matter differences in autism that are not related to these potential confounds, we performed a voxel-based morphometry analysis in 52 affected children and adolescents and 52 matched control subjects., Results: We observed diminished gray matter in a region of the hypothalamus, which synthesizes the behaviorally relevant hormones oxytocin and arginine vasopressin., Conclusions: This finding provides support for further investigations of the theory of abnormal functioning of this hormonal system in autism and potentially for experimental therapeutic approaches with oxytocin and related neuropeptides., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: This cross-sectional study sought to confirm the presence and regional profile of previously reported changes in laminar cortical thickness in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) compared with typically developing control subjects., Method: High-resolution magnetic resonance images were obtained from 22 (19 male and 3 female subjects; mean age 11.7 years) children and adolescents with ADHD and 22 age- and sex-matched control subjects (mean age 11.7 years). Brain tissue volumes were estimated for each subject. Cortical pattern matching methods were used to sample measures of laminar thickness at high spatial frequency across homologous regions of the cortex. Volume and thickness measures were compared across diagnostic groups with and without controlling for general intelligence. False discovery rate correction confirmed regional results., Results: The subjects with ADHD exhibited significant reductions in overall brain volume, gray matter volume, and mean cortical thickness compared with the controls, whereas white matter volumes were significantly increased in ADHD. Highly significant cortical thinning (false discovery rate-corrected p < .0006) was observed over large areas of the frontal, temporal, parietal, and occipital association cortices and aspects of motor cortex but not within the primary sensory regions., Conclusions: Cortical thickness reductions present a robust neuroanatomical marker for child and adolescent ADHD. Observations of widespread cortical thinning expand on earlier cross-sectional findings and provide further evidence to support that the neurobiological underpinnings of ADHD extend beyond prefrontal and subcortical circuits.

Background: Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have revealed structural abnormalities in the brains of affected individuals. One of the most replicated alterations is a significantly smaller corpus callosum (CC), for which conflicting reports exist with respect to the affected callosal segments., Methods: We applied novel surface-based geometrical modeling methods to establish the presence, direction, and exact location of callosal alterations in ADHD at high spatial resolution. For this purpose, we calculated the thickness of the CC at 100 equidistant midsagittal points in an age-matched male sample of 19 individuals with ADHD and 19 typically developing control subjects., Results: In close agreement with many prior observations, the CC was shown to be significantly thinner in ADHD subjects in anterior and, particularly, posterior callosal sections. Covarying for intelligence did not significantly alter the observed ADHD effects. However, group differences were no longer present in anterior sections when covarying for brain volume and after excluding ADHD subjects comorbid for oppositional defiant disorder., Conclusions: Decreased callosal thickness may be associated with fewer fibers or a decrease in the myelination of fibers connecting the parietal and prefrontal cortices. This might affect interhemispheric communication channels that are necessary to sustain attention or motor control, thus contributing to symptoms of hyperactivity and impulsivity, or inattention, observed in ADHD. Future studies are necessary to determine whether callosal abnormalities reflect maturational delays or persist into adulthood.

Background: Autism is a developmental disorder of unknown neurologic basis. Based on prior work, we used proton magnetic resonance spectroscopic imaging ((1)H- MRSI) to investigate brain structures, including cingulate and caudate, that we hypothesized would reveal metabolic abnormalities in subjects with autism., Methods: In 22 children with autism, 5 to 16 years old, and 20 age-matched healthy control subjects, (1)H-MRSI assessed levels of N-acetyl compounds (NAA), choline compounds (Cho), and creatine plus phosphocreatine (Cr) at 272 msec echo-time and 1.5 T., Results: In subjects with autism compared with control subjects, Cho was 27.2% lower in left inferior anterior cingulate and 19.1% higher in the head of the right caudate nucleus; Cr was 21.1% higher in the head of the right caudate nucleus, but lower in the body of the left caudate nucleus (17.9%) and right occipital cortex (16.6%)., Conclusions: Results are consistent with altered membrane metabolism, altered energetic metabolism, or both in the left anterior cingulate gyrus, both caudate nuclei, and right occipital cortex in subjects with autism compared with control subjects.