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Transcranial magnetic stimulation (TMS) is currently used for cognitive studies and investigated as a treatment for psychiatric disorders. Because of the cortex variability, the coil positioning stage is difficult and should be improved by using individual neuroimaging data. Sophisticated and expensive neuronavigation systems have been developed to guide the coil to selected regions on the patient''s magnetic resonance images (MRI). Our objective was to develop a triangulation-based MRI-guided method to position manually the TMS coil over the subject''s head, using a cortical target derived from individual MR data. We evaluated both the spatial accuracy and the reproducibility of the method using functional MR activations of two different targets in the motor and parietal cortices. The accuracy of the MRI-guided method, assessed from the Euclidean distance (Dm) between the thumb motor target and the coil position eliciting reproducible thumb motor-evoked potentials with TMS, was Dm = 10 ± 3 mm. The reproducibility of the method, evaluated across two different operators, was Dm = 6.7 ± 1.4 mm for the repositioning in the motor cortex and Dm = 6.0 ± 3.2 mm in the parietal cortex. This novel method could be used clinically to assist positioning of the TMS coil. [Copyright &y& Elsevier]

The article presents a study that focuses on the early-onset schizophrenia (EOS). It reveals that EOS had involved neurodevelopmental deviance across a wide range of brain structural measures. It examines the possibility that the alteration of cortical folding will be applied to EOS. It explores the involvement of EOS to prominent structural aberrations in superior temporal and collateral sulci. It reveals that patients with EOS presented lower global sulcal indices in both hemispheres as well as local sulcal index in the left collateral sulcus.

Abstract: A decreased striatal presynaptic dopaminergic function has been reported in depressed patients with affective flattening and psychomotor retardation, using 18F-fluorodopa positron emission tomography and regions-of-interest. The present study aimed to investigate regional `[18F]dopa uptake in mesolimbic and mesocortical dopaminergic projections with the hypothesis that there should be a decrease in mesolimbic [18F]dopa uptake associated with affective flattening and psychomotor retardation. [18F]Dopa-positron emission tomography and anatomical magnetic resonance imaging datasets from 12 screened depressed patients with either marked affective flattening and psychomotor retardation (n =6) or with marked impulsivity (n =6), and from eight healthy subjects, were analyzed using a voxel-based approach. Regional differences in [18F]dopa uptake rate constant (K i) values between the healthy group and the two depression subgroups were compared using both statistical parametric mapping and cluster-based regions-of-interest. Patients with affective flattening and psychomotor retardation had [18F]dopa K i decreases in the left caudate, bilateral putamen and nucleus accumbens, left parahippocampus and dorsal brainstem. Impulsive depressives had [18F]dopa K i decreases in the anterior cingulate and hypothalamus, and an increase in the right parahippocampal gyrus. These findings support distinct regional dysfunctions of monoamines depending on the depressive symptomatology. [Copyright &y& Elsevier]

Transcranial magnetic stimulation (TMS) is a technique used for investigation of the tics, when repeatedly applied, has a therapeutic potential, notably in psychiatry. The physiological and neuroendocrine effects induced by repeated TMS treatment in an animal model are similar to those caused by antidepressants in man. In particular, TMS appears to modify the release of neuromediators (serotonin, dopamine) involved in depressive states. Because of these properties, repeated TMS has been proposed as a potential treatment for depression. Several randomized studies have now evaluated its effects in this regard and for the most part show statistically significant results, although the findings are sometimes modest at the clinical level. However, the therapeutic effects depend on various parameters which are generally not taken into account, such as cortical excitability and regional cerebral metabolism, Apart from depression, the trials focus on a limited number of disorders. In schizophrenia, the use of TMS has permitted abnormalities in cortical excitability to be demonstated and an improvement of the symptomatology, e.g. by suppressing the perception of auditory hallucinations. Parkinsonˈs disease, nervous twitch and Gilles de la Tourette syndome, obsessive-compulsive disorders and mania have also been the focus of promising albeit preliminary trials. Wider randomized studies should now assess the different parameters involved in the therapeutic effects, so that the treatment procedure can be optimized and the physiopathology of various neuropsychiatric disorders better understood. [Copyright &y& Elsevier]

Negative life events (NLEs) increase the risk for externalizing behaviors (EBs) and internalizing behaviors (IBs) in adolescence and adult psychopathology. DNA methylation associated with behavioral problems may reflect this risk and long-lasting effects of NLEs. To identify consistent associations between blood DNA methylation and EBs or IBs across adolescence, we conducted longitudinal epigenome-wide association studies (EWASs) using data from the IMAGEN cohort, collected at ages 14 and 19 years (n = 506). Significant findings were validated in a separate subsample (n = 823). Methylation risk scores were generated by 10-fold cross-validation and further tested for their associations with gray matter volumes and NLEs. No significant findings were obtained for the IB-EWAS. The EB-EWAS identified a genome-wide significant locus in a gene linked to attention-deficit/hyperactivity disorder (ADHD) (IQSEC1 , cg01460382; p = 1.26 × 10−8). Other most significant CpG sites were near ADHD-related genes and enriched for genes regulating tumor necrosis factor and interferon-γ signaling, highlighting the relevance of EB-EWAS findings for ADHD. Analyses with the EB methylation risk scores suggested that it partly reflected comorbidity with IBs in late adolescence. Specific to EBs, EB methylation risk scores correlated with smaller gray matter volumes in medial orbitofrontal and anterior/middle cingulate cortices, brain regions known to associate with ADHD and conduct problems. Longitudinal mediation analyses indicated that EB-related DNA methylation were more likely the outcomes of problematic behaviors accentuated by NLEs, and less likely the epigenetic bases of such behaviors. Our findings suggest that novel epigenetic mechanisms through which NLEs exert short and longer-term effects on behavior may contribute to ADHD. [ABSTRACT FROM AUTHOR]

Adolescence is a critical period for circadian rhythm, with a strong shift toward eveningness around age 14. Also, eveningness in adolescence has been found to predict later onset of depressive symptoms. However, no previous study has investigated structural variations associated with chronotype in early adolescence and how this adds to the development of depressive symptoms. Assessment of 128 community-based adolescents (51% girls) at age 14 and 19 years was performed. Using whole-brain voxel-based morphometry, baseline (at age 14) regional gray matter volumes (GMVs), follow-up (at age 19) regional GMVs, and longitudinal changes (between 14 and 19) associated with Morningness/Eveningness Scale in Children score and sleep habits at baseline were measured. The association of GMV with depressive symptoms at 19 years was studied, and the role of potential clinical and genetic factors as mediators and moderators was assessed. Higher eveningness was associated with larger GMV in the right medial prefrontal cortex at ages 14 and 19 in the whole sample. GMV in this region related to depressive symptoms at age 19 in catechol-O-methyltransferase (COMT) Val/Val, but not in Met COMT , carriers. Larger GMV also was observed in the right fusiform gyrus at age 14, which was explained by later wake-up time during weekends. In adolescence, eveningness and its related sleep habits correlated with distinct developmental patterns. Eveningness was specifically associated with GMV changes in the medial prefrontal cortex; this could serve as a brain vulnerability factor for later self-reported depressive symptoms in COMT Val/Val carriers. [ABSTRACT FROM AUTHOR]

Objective: Children experiencing attention-deficit/hyperactivity disorder (ADHD) symptoms may retain symptoms into adulthood, but little is known about the underlying mechanism.Method: To identify biomarkers of persistent ADHD symptom development, we carried out whole-brain analyses of neuroimaging data during the anticipation phase of the Monetary-Incentive-Delay (MID) task in 1,368 adolescents recruited by the IMAGEN Consortium at age 14 years, whose behavioral measurements were followed up longitudinally at age 16. In particular, we focused on comparing individuals with persistent high ADHD symptoms at both ages 14 and 16 years to unaffected control individuals, but also exploring which individuals demonstrating symptom remission (with high ADHD symptoms at age 14 but much reduced at age 16).Results: We identified reduced activations in the medial frontal cortex and the thalamus during reward anticipation as neuro-biomarkers for persistent ADHD symptoms across time. The genetic relevance of the above findings was further supported by the associations of the polygenic risk scores of ADHD with both the persistent and control status and the activations of both brain regions. Furthermore, in an exploratory analysis, the thalamic activation might also help to distinguish persons with persistent ADHD from those remitted in both an exploratory sample (odds ratio = 9.43, p < .001) and an independent generalization sample (odds ratio = 4.64, p = .003).Conclusion: Using a well-established and widely applied functional magnetic resonance imaging task, we have identified neural biomarkers that could discriminate ADHD symptoms that persist throughout adolescence from controls and potentially those likely to remit during adolescent development as well. [ABSTRACT FROM AUTHOR]

Binge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB. The study used prospective longitudinal data from the European IMAGEN study adolescent cohort. Participants completed baseline assessments (questionnaires and a brain scan [functional magnetic resonance imaging]) at 14 years of age and a follow-up assessment (questionnaires) at 16 years of age. Self-reported binge eating and/or purging were used to indicate presence of DEB. Neural correlates of failed inhibition were assessed using the stop signal task. Participants were categorized as healthy control subjects (reported no DEB at both time points), maintainers (reported DEB at both time points), recoverers (reported DEB at baseline only), and developers (reported DEB at follow-up only). Forty-three individuals per group with complete scanning data were matched on gender, age, puberty, and intelligence (N = 172). At baseline, despite similar task performance, incorrectly responding to stop signals (failed inhibitory control) was associated with greater recruitment of the medial prefrontal cortex and anterior cingulate cortex in the developers compared with healthy control subjects and recoverers. Greater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to DEB development. As this precedes symptom onset and is evident despite normal task performance, neural responses during failed inhibition may be a useful biomarker of vulnerability for DEB. This study highlights the potential value of prospective neuroimaging studies for identifying markers of illness before the emergence of behavior changes. [ABSTRACT FROM AUTHOR]

Background Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood. Methods Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of temporal discounting in a large cohort ( n = 1830) of 14- to 15-year-old children. Mediation analysis was then used to determine whether the volumes of brain regions associated with temporal discounting mediate the relation between adverse life events (e.g., family conflict, serious accidents) and antisocial behaviors (e.g., precocious sexual activity, bullying, illicit substance use). Results Greater temporal discounting (more impulsivity) was associated with 1) lower volume in frontomedial cortex and bilateral insula and 2) greater volume in a subcortical region encompassing the ventral striatum, hypothalamus and anterior thalamus. The volume ratio between these cortical and subcortical regions was found to partially mediate the relation between adverse life events and antisocial behavior. Conclusions Temporal discounting is related to regions of the brain involved in reward processing and interoception. The results support a developmental imbalance model of impulsivity and are consistent with the idea that negative environmental factors can alter the developing brain in ways that promote antisocial behavior. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by deficits in reward sensitivity and response inhibition. The relative contribution of these frontostriatal mechanisms to ADHD symptoms and their genetic determinants is largely unexplored. Methods: Using functional magnetic resonance imaging and genetic analysis of the monoamine oxidase A (MAOA) gene, we investigated how striatal and inferior frontal activation patterns contribute to ADHD symptoms depending on MAOA genotype in a sample of adolescent boys (n = 190). Results: We demonstrate an association of ADHD symptoms with distinct blood oxygen level–dependent (BOLD) responses depending on MAOA genotype. In A hemizygotes of the expression single nucleotide polymorphism rs12843268, which express lower levels of MAOA, ADHD symptoms are associated with lower ventral striatal BOLD response during the monetary incentive delay task and lower inferior frontal gyrus BOLD response during the stop signal task. In G hemizygotes, ADHD symptoms are associated with increased inferior frontal gyrus BOLD response during the stop signal task in the presence of increased ventral striatal BOLD response during the monetary incentive delay task. Conclusions: Depending on MAOA genotype, ADHD symptoms in adolescent boys are associated with either reward deficiency or insufficient response inhibition. Apart from its mechanistic interest, our finding may aid in developing pharmacogenetic markers for ADHD. [Copyright &y& Elsevier]

Objective: In a recent genomewide association study of subcortical brain volumes, a common genetic variation at rs945270 was identified as having the strongest effect on putamen volume, a brain measurement linked to familial risk for attention-deficit/hyperactivity disorder (ADHD). To determine whether rs945270 might be a genetic determinant of ADHD, its effects on ADHD-related symptoms and neural mechanisms of ADHD, such as response inhibition and reward sensitivity, were explored.Method: A large population sample of 1,834 14-year-old adolescents was used to test the effects of rs945270 on ADHD symptoms assessed through the Strengths and Difficulties Questionnaire and region-of-interest analyses of putamen activation by functional magnetic resonance imaging using the stop signal and monetary incentive delay tasks, assessing response inhibition and reward sensitivity, respectively.Results: There was a significant link between rs945270 and ADHD symptom scores, with the C allele associated with lower symptom scores, most notably hyperactivity. In addition, there were sex-specific effects of this variant on the brain. In boys, the C allele was associated with lower putamen activity during successful response inhibition, a brain response that was not associated with ADHD symptoms. In girls, putamen activation during reward anticipation increased with the number of C alleles, most significantly in the right putamen. Remarkably, right putamen activation during reward anticipation tended to negatively correlate with ADHD symptoms.Conclusion: These results indicate that rs945270 might contribute to the genetic risk of ADHD partly through its effects on hyperactivity and reward processing in girls. [ABSTRACT FROM AUTHOR]