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Background As mood dysregulation and hyperarousal are overlapping and prominent features of posttraumatic stress disorder (PTSD), and mood disorders (MD) including bipolar disorder (BD), we aimed to clarify the role of trauma and MD on the resting state functional connectivity (RSFC) of amygdala in MD youth with or without trauma exposure, and healthy controls (HC). Methods Of 23 subjects, 21 completed the magnetic resonance imaging (MRI) protocol, 5 were excluded for subject motion, leaving final sample size of 16: nine subjects with MD (5/9 with trauma), and 7 HC. Youth were assessed with Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL), and other behavioral measures including Young Mania Rating Scale (YMRS). Imaging data were acquired using functional MRI in 3-T scanner. Imaging included T1-weighted structural MRI and 6-min resting state acquisition. Results In between group analysis, the average correlation coefficients between left anterior cingulate cortex (Acc) and left insula cortex with left amygdala regions were significantly larger in HC compared to the patient population. Connectivity between left amygdala and left cingulate cortex shows a significant negative correlation with YMRS severity. Conclusions In this preliminary study, MD with trauma youth had more manic symptoms and difficulties regulating anger. While MD youth showed reduced RSFC of left amygdala with left acc and left insula, no significant difference between the subgroups of children with MD was observed. However, when looking at both clinical groups together, we observed a significant correlation of RSFC of left amygdala to left acc, and YMRS scores.

Background: The degree of reproducibility of the neuroimaging literature in psychiatric application areas has been called into question and the issues that relate to this reproducibility are extremely complex. Some of these complexities have to do with the underlying biology of the disorders that we study and others arise due to the technology we apply to the analysis of the data we collect. Ultimately, the observations we make get communicated to the rest of the community through publications in the scientific literature. Methods: We sought to perform a ‘re-executability survey’ to evaluate the recent neuroimaging literature with an eye toward seeing if the technical aspects of our publication practices are helping or hindering the overall quest for a more reproducible understanding of brain development and aging. The topic areas examined include availability of the data, the precision of the imaging method description and the reporting of the statistical analytic approach, and the availability of the complete results. We applied the survey to 50 publications in the autism neuroimaging literature that were published between September 16, 2017 to October 1, 2018. Results: The results of the survey indicate that for the literature examined, data that is not already part of a public repository is rarely available, software tools are usually named but versions and operating system are not, it is expected that reasonably skilled analysts could approximately perform the analyses described, and the complete results of the studies are rarely available. Conclusions: We have identified that there is ample room for improvement in research publication practices. We hope exposing these issues in the retrospective literature can provide guidance and motivation for improving this aspect of our reporting practices in the future.

This study was to examine cortical thickness in drug naive, first episode schizophrenia patients, and to explore its relationship with serum levels of brain-derived neurotrophic factor (BDNF). Forty-five drug naive schizophrenia patients and 28 healthy controls were enrolled in the study. Freesurfer was used to parcellate cortical regions, and vertex-wise group analysis was used for whole brain cortical thickness. The clusters for the brain regions that demonstrated group differences were extracted, and the mean values of thickness were calculated. Serum levels of BDNF were measured using enzyme-linked immunosorbent assay (ELISA). After controlling for age and gender, significantly thinner cortical thickness was found in left insula and superior temporal gyrus in the patient group compared with the healthy control group (HC group) (p's < 0.001). Lower serum levels of BDNF were also found in the patient group compared with the HC group (p = 0.001). Correlation analysis showed a significant positive relationship between thickness of left insula and serum levels of BDNF within the HC group (r = 0.396, p = 0.037) but there was no such relationship within the patient group (r = 0.035, p = 0.819). Cortical thinning is present in drug naive, first episode schizophrenia patients, indicating neurodevelopmental abnormalities at the onset of schizophrenia. Left insula might be an imaging biomarker in detecting the impaired protective role of neurotrophic factor for the brain development in schizophrenia.

Background: Regional prefrontal cortex gray matter reductions have been identified in schizophrenia, likely reflecting a combination of genetic vulnerability and disease effects. Few morphometric studies to date have examined regional prefrontal abnormalities in non-psychotic biological relatives who have not passed through the age range of peak risk for onset of psychosis. We conducted a region-of-interest morphometric study of prefrontal subregions in adolescent and young adult relatives of schizophrenia patients. Methods: Twenty-seven familial high-risk (FHR) first-degree relatives of schizophrenia patients and forty-eight control subjects without a family history of psychosis (ages 13–28) underwent high-resolution magnetic resonance imaging at 1.5 Tesla. The prefrontal cortex was parcellated into polar, dorsolateral, ventrolateral, ventromedial and orbital subregions. The Chapman scales measured subpsychotic symptoms. General linear models examined associations of prefrontal subregion volumes with familial risk and subpsychotic symptoms. Results: FHR subjects had significantly reduced bilateral ventromedial prefrontal and frontal pole gray matter volumes compared with controls. Ventromedial volume was significantly negatively correlated with magical ideation and anhedonia scores in FHR subjects. Conclusions: Selective, regional prefrontal gray matter reductions may differentially mark genetic vulnerability and early symptom processes among non-psychotic young adults at familial risk for schizophrenia.

Corpus callosum (CC) area abnormalities have been reported in magnetic resonance imaging (MRI) studies of adults and youths with bipolar disorder (BPD), suggesting interhemispheric communication may be abnormal in BPD and may be present early in the course of illness and affect normal neuromaturation of this structure throughout the lifecycle. Neuroimaging scans from 44 youths with DSM-IV BPD and 22 healthy controls (HC) were analyzed using cross-sectional area measurements and a novel method of volumetric parcellation. Univariate analyses of variance were conducted on CC subregions using both volume and traditional area measurements. Youths with BPD had smaller middle and posterior callosal regions, and reduced typical age-related increases in CC size. The cross-sectional area and novel volumetric methodologies resulted in similar findings. Future longitudinal assessments of CC development would track the evolution of callosal abnormalities in youths with BPD and allow exploration of the functional significance of these findings.

A significant number of children with bipolar disorder (BP) have co-morbid attention-deficit/hyperactivity disorder (ADHD). It is unknown if these children have neuroimaging findings unique to their co-morbid presentation, or if their brain findings are similar to children diagnosed with BP alone.Fifty three children with Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) BP (23 with ADHD, 30 without), 29 healthy controls (HC), and 23 children with ADHD, similar in sex and age, had magnetic resonance imaging (MRI) scans on a 1.5T GE scanner. Volumetric assessments were performed for basal ganglia and limbic subcortical structures.Youths with ADHD had smaller caudate and putamen volumes compared to both BP groups and they had moderately smaller total amygdala volumes compared to the other three groups. Youths with BP + ADHD had moderately larger nucleus accumbens volumes than HC, and females in both BP groups had smaller hippocampal volumes compared to ADHD and HC. No differences were found between the BP and BP + ADHD groups.These data suggest that morphometric subcortical volumes in youths with BP + ADHD are more similar to those in youths with BP. They do not share subcortical neuroanatomic correlates with the ADHD group. These findings suggest that BP + ADHD is a subtype of pediatric BP rather than severe ADHD.

SummaryThe structural effects of cocaine on neural systems mediating cognition and motivation are not well known. By comparing the thickness of neocortical and paralimbic brain regions between cocaine-dependent and matched control subjects, we found that four of 18 a priori regions involved with executive regulation of reward and attention were significantly thinner in addicts. Correlations were significant between thinner prefrontal cortex and reduced keypresses during judgment and decision making of relative preference in addicts, suggesting one basis for restricted behavioral repertoires in drug dependence. Reduced effortful attention performance in addicts also correlated with thinner paralimbic cortices. Some thickness differences in addicts were correlated with cocaine use independent of nicotine and alcohol, but addicts also showed diminished thickness heterogeneity and altered hemispheric thickness asymmetry. These observations suggest that brain structure abnormalities in addicts are related in part to drug use and in part to predisposition toward addiction.

Amygdala volume has been associated with drug craving in cocaine addicts, and amygdala volume reduction is observed in some alcohol-dependent subjects. This study sought an association in alcohol-dependent subjects between volumes of reward-related brain regions, alcohol craving, and the risk of relapse.Besides alcohol craving, the authors assessed amygdala, hippocampus, and ventral striatum volumes in 51 alcohol-dependent subjects and 52 age- and education-matched healthy comparison subjects after detoxification. After imaging and clinical assessment, patients were followed for 6 months and alcohol intake was recorded.Alcohol-dependent subjects showed reduced amygdala, hippocampus, and ventral striatum volumes and reported stronger craving in relation to healthy comparison subjects. However, only amygdala volume and craving differentiated between subsequent relapsers and abstainers. A significant decrease of amygdala volume in alcohol-dependent subjects was associated with increased alcohol craving before imaging and an increased alcohol intake during the 6-month follow-up period.These findings suggest a relationship between amygdala volume reduction, alcohol craving, and prospective relapse into alcohol consumption.

Objectives: Diffusion tensor magnetic resonance imaging (DT-MRI) assesses the integrity of white matter (WM) tracts in the brain. Children with bipolar disorder (BPD) may have WM abnormalities that precede illness onset. To more fully examine this possibility, we scanned children with DSM-IV BPD and compared them to healthy peers and children at risk for BPD (AR-BPD), defined as having a first-degree relative with the disorder. Methods: Ten children with BPD, eight healthy controls (HC), and seven AR-BPD, similar in age, had MRI scans on a 1.5 Tesla GE scanner, including a standard DT-MRI sequence (T2-EPI) with 25 axial slices. Fractional anisotropy (FA) values were compared between groups to determine regions of significant difference (p

Autism spectrum disorder (ASD) affects 1 in 50 children between the ages of 6 and 17 years. The etiology of ASD is not precisely known. ASD is an umbrella term, which includes both low- (IQ70) and high-functioning (IQ70) individuals. A better understanding of the disorder and how it manifests in individual subjects can lead to more effective intervention plans to fulfill the individual's treatment needs.Magnetic resonance imaging (MRI) is a non-invasive investigational tool that can be used to study the ways in which the brain develops or deviates from the typical developmental trajectory. MRI offers insights into the structure, function, and metabolism of the brain. In this article, we review published studies on brain connectivity changes in ASD using either resting state functional MRI or diffusion tensor imaging.The general findings of decreases in white matter integrity and in long-range neural coherence are well known in the ASD literature. Nevertheless, the detailed localization of these findings remains uncertain, and few studies link these changes in connectivity with the behavioral phenotype of the disorder. With the help of data sharing and large-scale analytic efforts, however, the field is advancing toward several convergent themes, including the reduced functional coherence of long-range intra-hemispheric cortico-cortical default mode circuitry, impaired inter-hemispheric regulation, and an associated, perhaps compensatory, increase in local and short-range cortico-subcortical coherence.

An imbalance of excitatory and inhibitory neurotransmission in autism spectrum disorder (ASD) has been proposed. We compared glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) of 13 males with ASD and 14 typically developing (TD) males (ages 13-17), and correlated these levels with intelligence quotient (IQ) and measures of social cognition.Social cognition was evaluated by administration of the Social Responsiveness Scale (SRS) and the Reading the Mind in the Eyes Test (RMET). We acquired proton magnetic resonance spectroscopy ((1)H-MRS) data from the bilateral ACC using the single voxel point resolved spectroscopy sequence (PRESS) to quantify Glu and Gln, and Mescher-Garwood point-resolved spectroscopy sequence (MEGA-PRESS) to quantify GABA levels referenced to creatine (Cr).There were higher Gln levels (p=0.04), and lower GABA/Cre levels (p=0.09) in the ASD group than in the TD group. There was no difference in Glu levels between groups. Gln was negatively correlated with RMET score (rho=-0.62, p=0.001) and IQ (rho=-0.56, p=0.003), and positively correlated with SRS scores (rho=0.53, p=0.007). GABA/Cre levels were positively correlated with RMET score (rho=0.34, p=0.09) and IQ (rho=0.36, p=0.07), and negatively correlated with SRS score (rho=-0.34, p=0.09).These data suggest an imbalance between glutamatergic neurotransmission and GABA-ergic neurotransmission in ASD. Higher Gln levels and lower GABA/Cre levels were associated with lower IQ and greater impairments in social cognition across groups.

The insula is anatomically situated to be critically involved in many bio-behavioral functions impaired in schizophrenia. Furthermore, its total volume has been shown to be reduced in schizophrenia. In the present study, we tested the hypothesis that in schizophrenia it is the anterior insular lobule (aINS(lbl)) rather than the posterior insular lobule (pINS(lbl)) that is smaller, given that limbic system abnormalities are central in schizophrenia and that the affiliations of the limbic system are principally with the anterior insular lobule. We used T1-weighted high resolution magnetic resonance imaging (MRI) to measure the cortical volume of the left and right anterior and posterior insular subdivisions. The subjects included a sample of healthy community controls (N=40) and chronic patients with DSM-III-R schizophrenia (N=41). We correlated insula volumes with positive and negative symptoms. We found that the total aINS(lbl), and the left aINS(lbl) in particular, were significantly volumetrically smaller in schizophrenia compared to controls, and significantly correlated with bizarre behavior. Given that the anterior insular lobule offers anatomic features that allow for MRI-based morphometric analysis, namely its central and circular sulci, this brain structure provides a useful model to test hypotheses regarding genotype-phenotype relationships in schizophrenia using the anterior insular lobule as a candidate endophenotype.

Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities.Forty-three youths 6-16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled.The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen.These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.

Language deficits are among the core impairments of autism. We previously reported asymmetry reversal of frontal language cortex in boys with autism. Specific language impairment (SLI) and autism share similar language deficits and may share genetic links. This study evaluated asymmetry of frontal language cortex in a new, independent sample of right-handed boys, including a new sample of boys with autism and a group of boys with SLI. The boys with autism were divided into those with language impairment (ALI) and those with normal language ability (ALN). Subjects (righthanded, aged 6.2–13.4 years) included 22 boys with autism (16 ALI and 6 ALN), 9 boys with a history of or present SLI, and 11 normal controls. MRI brain scans were segmented into grey and white matter; then the cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere. Group differences in volumetric asymmetry were predicted a priori in language-related regions in inferior lateral frontal (Broca’s area) and posterior superior temporal cortex. Language impaired boys with autism and SLI both had significant reversal of asymmetry in frontal language-related cortex; larger on the right side in both groups of language impaired boys and larger on the left in both unimpaired language groups, strengthening a phenotypic link between ALI and SLI. Thus, we replicated the observation of reversed asymmetry in frontal language cortex reported previously in an independent autism sample, and observed similar reversal in boys with SLI, further strengthening a phenotypic link between SLI and a subgroup of autism. Linguistically unimpaired boys with autism had similar asymmetry compared with the control group, suggesting that Broca’s area asymmetry reversal is related more to language impairment than specifically to autism diagnosis. Ann Neurol 2004;56:757–766

We performed cerebellum segmentation and parcellation on magnetic resonance images from right-handed boys, aged 6-13 years, including 22 boys with autism [16 with language impairment (ALI)], 9 boys with Specific Language Impairment (SLI), and 11 normal controls. Language-impaired groups had reversed asymmetry relative to unimpaired groups in posterior-lateral cerebellar lobule VIIIA (right side larger in unimpaired groups, left side larger in ALI and SLI), contralateral to previous findings in inferior frontal cortex language areas. Lobule VIIA Crus I was smaller in SLI than in ALI. Vermis volume, particularly anterior I-V, was decreased in language-impaired groups. Language performance test scores correlated with lobule VIIIA asymmetry and with anterior vermis volume. These findings suggest ALI and SLI subjects show abnormalities in neurodevelopment of fronto-corticocerebellar circuits that manage motor control and the processing of language, cognition, working memory, and attention.

Objective: The limbic structures in early-onset schizophrenia-spectrum illness (SZ) and bipolar disorder (BPD) were studied to discern patterns associated with diagnosis and sex. Methods: Thirty-five youths with DSM-IV BPD without psychosis, 19 with BPD with psychosis, 20 with SZ, and 29 healthy controls (HC), similar in age (6-17 years) and sex, underwent structured and clinical interviews, neurological examination, and cognitive testing. Structural magnetic resonance images (MRIs) were acquired on a 1.5 Tesla, General Electric Signa Scanner. Differences in subcortical brain volumes, including the amygdala and hippocampus, were evaluated using two-way (diagnosis, sex) univariate analyses covarying for total cerebral volume and age. Results: Youth with SZ and BPD showed no differences in amygdala and hippocampal volumes. However, boys with SZ had smallest left amygdala and girls with BPD had the smallest left hippocampal volumes. In exploratory analyses, SZ showed reduced thalamic volumes bilaterally and both BPD groups had larger right nucleus accumbens (NA) volumes relative to HC. Conclusion: There were no limbic volumetric differences between BPD and SZ. However, there were diagnosis-by-sex interactions in the amygdala and hippocampus, structures that are rich in sex hormone receptors. In addition, smaller thalamus was associated with SZ while larger right NA volumes were most related to BPD. This study underscores the importance of assessing diagnostic effects and sex effects on the brain in future studies and provides evidence that boys and girls with SZ and BPD may have differential patterns of neuropathology associated with disease expression.

Attention-deficit/hyperactivity disorder (ADHD) is hypothesized to be due, in part, to structural defects in brain networks influencing cognitive, affective, and motor behaviors. Although the current literature on fiber tracts is limited in ADHD, gray matter abnormalities suggest that white matter (WM) connections may be altered selectively in neural systems. A prior study (Ashtari et al. 2005), using diffusion tensor magnetic resonance imaging (DT-MRI), showed alterations within the frontal and cerebellar WM in children and adolescents with ADHD. In this study of adults with childhood ADHD, we hypothesized that fiber pathways subserving attention and executive functions (EFs) would be altered. To this end, the cingulum bundle (CB) and superior longitudinal fascicle II (SLF II) were investigated in vivo in 12 adults with childhood ADHD and 17 demographically comparable unaffected controls using DT-MRI. Relative to controls, the fractional anisotropy (FA) values were significantly smaller in both regions of interest in the right hemisphere, in contrast to a control region (the fornix), indicating an alteration of anatomical connections within the attention and EF cerebral systems in adults with childhood ADHD. The demonstration of FA abnormalities in the CB and SLF II in adults with childhood ADHD provides further support for persistent structural abnormalities into adulthood.

Background Basal ganglia (BG) enlargement has been found in studies of adults with bipolar disorder (BPD), while the few studies of BPD youths have had mixed findings. The BG (caudate, putamen, globus pallidus, nucleus accumbens) is interconnected with limbic and prefrontal cortical structures and therefore may be implicated in BPD. Methods Sixty-eight youths (46 with BPD, 22 healthy controls) received neurological and psychiatric assessment, semi-structured interviews, and neuropsychological testing, followed by anatomic magnetic resonance imaging on a 1.5 Tesla scanner. After image segmentation, log BG volumes and asymmetry indices were analyzed using MANOVAs controlling for the effects of cerebral volume, age, sex, and diagnosis. These omnibus tests were followed by univariate linear regression models of each BG structure. Results Youths with BPD had a trend for larger right nucleus accumbens (NA) volumes ( p = 0.089). There were no significant group asymmetry differences, nor volume differences in the caudate, putamen, and globus pallidus. When analyzed separately by pubertal status, the prepubertal group had significantly larger total NA ( p = 0.035) versus healthy controls, while the pubertal group did not show significant differences in the NA versus healthy controls. Limitations The size of the control group is relatively small, possibly limiting our power to detect significant group differences. The inter-rater reliability for the NA is not as strong as the other structures; the finding of volume differences in this structure is preliminary and warrants replication. Conclusions Youths with BPD had larger right NA volumes; this enlargement was most pronounced in the prepubertal group. The differences between these findings and those seen in adult BPD imply a neurodevelopmental phenomenon.

Objective To test whether lesion site patterns in patients with chronic, severe aphasia who have no meaningful spontaneous speech are predictive of outcome following treatment with a nonverbal, icon-based computer-assisted visual communication (C-ViC) program. Design Retrospective study in which computed tomographic scans performed 3 months after onset of stroke and aphasia test scores obtained before C-ViC therapy were reviewed for patients after receiving C-ViC treatment. Setting A neurology department and speech pathology service of a Department of Veterans Affairs medical center and a university aphasia research center. Patients Seventeen patients with stroke and severe aphasia who began treatment with C-ViC from 3 months to 10 years after onset of stroke. Main Outcome Measure Level of ability to use C-ViC on a personal computer to communicate. Results All patients with bilateral lesions failed to learn C-ViC. For patients with unilateral left hemisphere lesion sites, statistical analyses accurately discriminated between those who could initiate communication with C-ViC from those who were only able to answer directed questions. The critical lesion areas involved temporal lobe structures (Wernicke cortical area and the subcortical temporal isthmus), supraventricular frontal lobe structures (supplementary motor area or cingulate gyrus 24), and the subcortical medial subcallosal fasciculus, deep to the Broca area. Specific lesion sites were also identified for appropriate candidacy for C-ViC. Conclusions Lesion site patterns on computed tomographic scans are helpful to define candidacy for C-ViC training, and to predict outcome level. A practical method is presented for clinical application of these lesion site results in combination with aphasia test scores.

The amygdala is instrumental to a set of brain processes that lead to cocaine consumption, including those that mediate reward and drug craving. This study examined the volumes of the amygdala and hippocampus in cocaine-addicted subjects and matched healthy controls and determined that the amygdala but not the hippocampus was significantly reduced in volume. The right-left amygdala asymmetry in control subjects was absent in the cocaine addicts. Topological analysis of amygdala isosurfaces (population averages) revealed that the isosurface of the cocaine-dependent group undercut the anterior and superior surfaces of the control group, implicating a difference in the corticomedial and basolateral nuclei. In cocaine addicts, amygdala volume did not correlate with any measure of cocaine use. The amygdala symmetry coefficient did correlate with baseline but not cocaine-primed craving. These findings argue for a condition that predisposes the individual to cocaine dependence by affecting the amygdala, or a primary event early in the course of cocaine use.