Search

Estimated age from brain MRI data has emerged as a promising biomarker of neurological health. However, the absence of large, diverse, and clinically representative training datasets, along with the complexity of managing heterogeneous MRI data, presents significant barriers to the development of accurate and generalisable models appropriate for clinical use. Here, we present a deep learning framework trained on routine clinical data (N up to 18,890, age range 18–96 years). We trained five separate models for accurate brain age prediction (all with mean absolute error ≤4.0 years, R2 ≥.86) across five different MRI sequences (T2‐weighted, T2‐FLAIR, T1‐weighted, diffusion‐weighted, and gradient‐recalled echo T2*‐weighted). Our trained models offer dual functionality. First, they have the potential to be directly employed on clinical data. Second, they can be used as foundation models for further refinement to accommodate a range of other MRI sequences (and therefore a range of clinical scenarios which employ such sequences). This adaptation process, enabled by transfer learning, proved effective in our study across a range of MRI sequences and scan orientations, including those which differed considerably from the original training datasets. Crucially, our findings suggest that this approach remains viable even with limited data availability (as low as N = 25 for fine‐tuning), thus broadening the application of brain age estimation to more diverse clinical contexts and patient populations. By making these models publicly available, we aim to provide the scientific community with a versatile toolkit, promoting further research in brain age prediction and related areas. [ABSTRACT FROM AUTHOR]

Adolescent subcortical structural brain development might underlie psychopathological symptoms, which often emerge in adolescence. At the same time, sex differences exist in psychopathology, which might be mirrored in underlying sex differences in structural development. However, previous studies showed inconsistencies in subcortical trajectories and potential sex differences. Therefore, we aimed to investigate the subcortical structural trajectories and their sex differences across adolescence using for the first time a single cohort design, the same quality control procedure, software, and a general additive mixed modeling approach. We investigated two large European sites from ages 14 to 24 with 503 participants and 1408 total scans from France and Germany as part of the IMAGEN project including four waves of data acquisition. We found significantly larger volumes in males versus females in both sites and across all seven subcortical regions. Sex differences in age‐related trajectories were observed across all regions in both sites. Our findings provide further evidence of sex differences in longitudinal adolescent brain development of subcortical regions and thus might eventually support the relationship of underlying brain development and different adolescent psychopathology in boys and girls. [ABSTRACT FROM AUTHOR]

Purpose: To develop self‐navigated motion correction for 3D silent zero echo time (ZTE) based neuroimaging and characterize its performance for different types of head motion. Methods: The proposed method termed MERLIN (Motion Estimation & Retrospective correction Leveraging Interleaved Navigators) achieves self‐navigation by using interleaved 3D phyllotaxis k‐space sampling. Low resolution navigator images are reconstructed continuously throughout the ZTE acquisition using a sliding window and co‐registered in image space relative to a fixed reference position. Rigid body motion corrections are then applied retrospectively to the k‐space trajectory and raw data and reconstructed into a final, high‐resolution ZTE image. Results: MERLIN demonstrated successful and consistent motion correction for magnetization prepared ZTE images for a range of different instructed motion paradigms. The acoustic noise response of the self‐navigated phyllotaxis trajectory was found to be only slightly above ambient noise levels (<4 dBA). Conclusion: Silent ZTE imaging combined with MERLIN addresses two major challenges intrinsic to MRI (i.e., subject motion and acoustic noise) in a synergistic and integrated manner without increase in scan time and thereby forms a versatile and powerful framework for clinical and research MR neuroimaging applications. [ABSTRACT FROM AUTHOR]

Purpose: Validation of quantitative MR measures for myelin imaging in the postmortem multiple sclerosis spinal cord. Methods: Four fixed spinal cord samples were imaged first with a 3T clinical MR scanner to identify areas of interest for scanning, and then with a 7T small bore scanner using a multicomponent‐driven equilibrium single‐pulse observation of T1 and T2 protocol to produce apparent proton density, T1, T2, myelin water, intracellular water, and free‐water fraction maps. After imaging, the cords were sectioned and stained with histological markers (hematoxylin and eosin, myelin basic protein, and neurofilament protein), which were quantitatively compared with the MR maps. Results: Excellent correspondence was found between high‐resolution MR parameter maps and histology, particularly for apparent proton density MRI and myelin basic protein staining. Conclusion: High‐resolution quantitative MRI of the spinal cord provides biologically meaningful measures, and could be beneficial to diagnose and track multiple sclerosis lesions in the spinal cord. [ABSTRACT FROM AUTHOR]

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early‐life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion‐processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting‐state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p <.025, FWE‐corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology. [ABSTRACT FROM AUTHOR]

Having the means to share research data openly is essential to modern science. For human research, a key aspect in this endeavor is obtaining consent from participants, not just to take part in a study, which is a basic ethical principle, but also to share their data with the scientific community. To ensure that the participants' privacy is respected, national and/or supranational regulations and laws are in place. It is, however, not always clear to researchers what the implications of those are, nor how to comply with them. The Open Brain Consent (https://open-brain-consent.readthedocs.io) is an international initiative that aims to provide researchers in the brain imaging community with information about data sharing options and tools. We present here a short history of this project and its latest developments, and share pointers to consent forms, including a template consent form that is compliant with the EU general data protection regulation. We also share pointers to an associated data user agreement that is not only useful in the EU context, but also for any researchers dealing with personal (clinical) data elsewhere. [ABSTRACT FROM AUTHOR]

In vivo quantification of glutamate (Glu) and γ‐aminobutyric acid (GABA) using MRS is often achieved using two separate sequences: a short‐echo point resolved spectroscopy (PRESS) acquisition for Glu and a Mescher‐Garwood PRESS (MEGA‐PRESS) acquisition for GABA. The purpose of this study was to examine the agreement of Glu and Glx (the combined signal of glutamate + glutamine) quantified from two different GABA‐edited MEGA‐PRESS acquisitions (GABA plus macromolecules, GABA+, TE = 68 ms, and macromolecule suppressed, MMSup, TE = 80 ms) with Glu and Glx quantified from a short‐echo PRESS (PRESS‐35, TE = 35 ms) acquisition. Fifteen healthy male volunteers underwent a single scan session, in which data were acquired using the three acquisitions (GABA+, MMSup and PRESS‐35) in both the sensorimotor and anterior cingulate cortices using a voxel size of 3 × 3 × 3 cm3. Glx and Glu were quantified from the MEGA‐PRESS data using both the OFF sub‐spectra and the difference (DIFF) spectra. Agreement was assessed using correlation analyses, Bland–Altman plots and intraclass correlation coefficients. Glx quantified from the OFF sub‐spectra from both the GABA+ and MMSup acquisitions showed poor agreement with PRESS‐35 in both brain regions. In the sensorimotor cortex, Glu quantified from the OFF sub‐spectra of GABA+ showed moderate agreement with PRESS‐35 data, but this finding was not replicated in the anterior cingulate cortex. Glx and Glu quantified using the DIFF spectra of either MEGA‐PRESS sequence were in poor agreement with the PRESS‐35 data in both brain regions. In conclusion, Glx and Glu measured from MEGA‐PRESS data generally showed poor agreement with Glx and Glu measured using PRESS‐35. [ABSTRACT FROM AUTHOR]

Objective: To compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans. Methods: We developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI‐visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG. Results: Seizure‐onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG. Significance: Computational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co‐located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery. [ABSTRACT FROM AUTHOR]

Anatomical brain templates are commonly used as references in neurological MRI studies, for bringing data into a common space for group‐level statistics and coordinate reporting. Given the inherent variability in brain morphology across age and geography, it is important to have templates that are as representative as possible for both age and population. A representative‐template increases the accuracy of alignment, decreases distortions as well as potential biases in final coordinate reports. In this study, we developed and validated a new set of T1w Indian brain templates (IBT) from a large number of brain scans (total n = 466) acquired across different locations and multiple 3T MRI scanners in India. A new tool in AFNI, make_template_dask.py, was created to efficiently make five age‐specific IBTs (ages 6–60 years) as well as maximum probability map (MPM) atlases for each template; for each age‐group's template–atlas pair, there is both a "population‐average" and a "typical" version. Validation experiments on an independent Indian structural and functional‐MRI dataset show the appropriateness of IBTs for spatial normalization of Indian brains. The results indicate significant structural differences when comparing the IBTs and MNI template, with these differences being maximal along the Anterior–Posterior and Inferior–Superior axes, but minimal Left–Right. For each age‐group, the MPM brain atlases provide reasonably good representation of the native‐space volumes in the IBT space, except in a few regions with high intersubject variability. These findings provide evidence to support the use of age and population‐specific templates in human brain mapping studies. [ABSTRACT FROM AUTHOR]

Purpose: To compare the silent rotating ultrafast imaging sequence (RUFIS) to a traditional Cartesian spoiled gradient‐echo (SPGR) acquisition scheme for variable flip angle (VFA) T1 mapping. Methods: A two‐point VFA measurement was performed using RUFIS and Cartesian SPGR in a quantitative phantom and healthy volunteers. To correct for B1 errors, a novel silent magnetization prepared B1 map acquisition (SIMBA) was developed, which combined with RUFIS VFA allows for a completely silent T1 mapping protocol. Results: The silent protocol was found to have comparable repeatability but higher reproducibility in vivo compared to the standard SPGR protocol, and showed no increase in acoustic noise levels above background noise levels compared to a 33 dBA increase for the SPGR acquisition. Conclusions: VFA T1 mapping using RUFIS is a feasible alternative to SPGR, achieving silent T1 mapping with comparable acquisition time. [ABSTRACT FROM AUTHOR]

Objective: Electroencephalography (EEG) features in the alpha band have been shown to differ between people with epilepsy and healthy controls. Here, in a group of patients with mesial temporal lobe epilepsy (mTLE), we seek to confirm these EEG features, and using simultaneous functional magnetic resonance imaging, we investigate whether brain networks related to the alpha rhythm differ between patients and healthy controls. Additionally, we investigate whether alpha abnormalities are found as an inherited endophenotype in asymptomatic relatives. Methods: We acquired scalp EEG and simultaneous EEG and functional magnetic resonance imaging in 24 unrelated patients with unilateral mTLE, 23 asymptomatic first‐degree relatives of patients with mTLE, and 32 healthy controls. We compared peak alpha power and frequency from electroencephalographic data in patients and relatives to healthy controls. We identified brain networks associated with alpha oscillations and compared these networks in patients and relatives to healthy controls. Results: Patients had significantly reduced peak alpha frequency (PAF) across all parietal and occipital electrodes. Asymptomatic relatives also had significantly reduced PAF over 14 of 17 parietal and occipital electrodes. Both patients and asymptomatic relatives showed a combination of increased activation and a failure of deactivation in relation to alpha oscillations compared to healthy controls in the sensorimotor network. Interpretation: Genetic factors may contribute to the shift in PAF and alterations in brain networks related to alpha oscillations. These may not entirely be a consequence of anti‐epileptic drugs, seizures or hippocampal sclerosis and deserve further investigation as mechanistic contributors to mTLE. [ABSTRACT FROM AUTHOR]

Summary: We investigated gray and white matter morphology in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE+HS) and first‐degree asymptomatic relatives of patients with mTLE+HS. Using T1‐weighted magnetic resonance imaging (MRI), we sought to replicate previously reported findings of structural surface abnormalities of the anterior temporal lobe in asymptomatic relatives of patients with mTLE+HS in an independent cohort. We performed whole‐brain MRI in 19 patients with mTLE+HS, 14 first‐degree asymptomatic relatives of mTLE+HS patients, and 32 healthy control participants. Structural alterations in patients and relatives compared to controls were assessed using automated hippocampal volumetry and cortical surface–based morphometry. We replicated previously reported cortical surface area contractions in the ipsilateral anterior temporal lobe in both patients and relatives compared to healthy controls, with asymptomatic relatives showing similar but less extensive changes than patients. These findings suggest morphologic abnormality in asymptomatic relatives of mTLE+HS patients, suggesting an inherited brain structure endophenotype. [ABSTRACT FROM AUTHOR]

The functional neuroanatomy and connectivity of reward processing in adults are well documented, with relatively less research on adolescents, a notable gap given this developmental period's association with altered reward sensitivity. Here, a large sample (n = 1,510) of adolescents performed the monetary incentive delay (MID) task during functional magnetic resonance imaging. Probabilistic maps identified brain regions that were reliably responsive to reward anticipation and receipt, and to prediction errors derived from a computational model. Psychophysiological interactions analyses were used to examine functional connections throughout reward processing. Bilateral ventral striatum, pallidum, insula, thalamus, hippocampus, cingulate cortex, midbrain, motor area, and occipital areas were reliably activated during reward anticipation. Bilateral ventromedial prefrontal cortex and bilateral thalamus exhibited positive and negative activation, respectively, during reward receipt. Bilateral ventral striatum was reliably active following prediction errors. Previously, individual differences in the personality trait of sensation seeking were shown to be related to individual differences in sensitivity to reward outcome. Here, we found that sensation seeking scores were negatively correlated with right inferior frontal gyrus activity following reward prediction errors estimated using a computational model. Psychophysiological interactions demonstrated widespread cortical and subcortical connectivity during reward processing, including connectivity between reward‐related regions with motor areas and the salience network. Males had more activation in left putamen, right precuneus, and middle temporal gyrus during reward anticipation. In summary, we found that, in adolescents, different reward processing stages during the MID task were robustly associated with distinctive patterns of activation and of connectivity. [ABSTRACT FROM AUTHOR]

Abstract: Arterial spin labeling (ASL) provides absolute quantification of resting tissue cerebral blood flow (CBF) as an entirely noninvasive approach with good reproducibility. As a result of neurovascular coupling, ASL provides a useful marker of resting neuronal activity. Recent ASL studies in individuals at clinical high risk of psychosis (CHR) have reported increased resting hippocampal perfusion compared with healthy controls. Schizotypy refers to the presence of subclinical psychotic‐like experiences in healthy individuals and represents a robust framework to study neurobiological mechanisms involved in the extended psychosis phenotype while avoiding potentially confounding effects of antipsychotic medications or disease comorbidity. Here we applied pseudo‐continuous ASL to examine differences in resting CBF in 21 subjects with high positive schizotypy (HS) relative to 22 subjects with low positive schizotypy (LS), as determined by the Oxford and Liverpool Inventory of Feelings and Experiences. Based on preclinical evidence that hippocampal hyperactivity leads to increased activity in mesostriatal dopamine projections, CBF in hippocampus, midbrain, and striatum was assessed. Participants with HS showed higher CBF of the right hippocampus compared to those with LS (p = .031, family‐wise error corrected). No differences were detected in the striatum or midbrain. The association between increased hippocampal CBF and HS supports the notion that hippocampal hyperactivity might be a central characteristic of the extended psychosis phenotype, while hyperactivity in subcortical dopamine pathways may only emerge at a higher intensity of psychotic experiences. [ABSTRACT FROM AUTHOR]

Abstract: The hippocampal formation is a complex brain structure that is important in cognitive processes such as memory, mood, reward processing and other executive functions. Histological and neuroimaging studies have implicated the hippocampal region in neuropsychiatric disorders as well as in neurodegenerative diseases. This highly plastic limbic region is made up of several subregions that are believed to have different functional roles. Therefore, there is a growing interest in imaging the subregions of the hippocampal formation rather than modelling the hippocampus as a homogenous structure, driving the development of new automated analysis tools. Consequently, there is a pressing need to understand the stability of the measures derived from these new techniques. In this study, an automated hippocampal subregion segmentation pipeline, released as a developmental version of Freesurfer (v6.0), was applied to T1‐weighted magnetic resonance imaging (MRI) scans of 22 healthy older participants, scanned on 3 separate occasions and a separate longitudinal dataset of 40 Alzheimer's disease (AD) patients. Test–retest reliability of hippocampal subregion volumes was assessed using the intra‐class correlation coefficient (ICC), percentage volume difference and percentage volume overlap (Dice). Sensitivity of the regional estimates to longitudinal change was estimated using linear mixed effects (LME) modelling. The results show that out of the 24 hippocampal subregions, 20 had ICC scores of 0.9 or higher in both samples; these regions include the molecular layer, granule cell layer of the dentate gyrus, CA1, CA3 and the subiculum (ICC > 0.9), whilst the hippocampal fissure and fimbria had lower ICC scores (0.73–0.88). Furthermore, LME analysis of the independent AD dataset demonstrated sensitivity to group and individual differences in the rate of volume change over time in several hippocampal subregions (CA1, molecular layer, CA3, hippocampal tail, fissure and presubiculum). These results indicate that this automated segmentation method provides a robust method with which to measure hippocampal subregions, and may be useful in tracking disease progression and measuring the effects of pharmacological intervention. [ABSTRACT FROM AUTHOR]

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. Real-time functional magnetic resonance neurofeedback (rtfMRI-NF) allows participants to gain self-control over dysregulated brain regions. Despite evidence for beneficial effects of electrophysiological-NF on ADHD symptoms, no study has applied the spatially superior rtfMRI-NF neurotherapy to ADHD. A randomized controlled trial tested the efficacy of rtfMRI-NF of right inferior prefrontal cortex (rIFG), a key region that is compromised in ADHD and upregulated with psychostimulants, on improvement of ADHD symptoms, cognition, and inhibitory fMRI activation. To control for region-specificity, an active control group received rtfMRI-NF of the left parahippocampal gyrus (lPHG). Thirty-one ADHD boys were randomly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI-NF runs over 2 weeks. Feedback was provided through a video-clip of a rocket that had to be moved up into space. A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life. Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11-month follow-up. Only the group targeting rIFG, however, showed a transfer effect, which correlated with ADHD symptom reductions, improved at trend level in sustained attention, and showed increased IFG activation during an inhibitory fMRI task. This proof-of-concept study demonstrates for the first time feasibility, safety, and shorter- and longer-term efficacy of rtfMRI-NF of rIFG in adolescents with ADHD. Hum Brain Mapp 38:3190-3209, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose Diffusion spectrum imaging (DSI) is an imaging technique that has been successfully applied to resolve white matter crossings in the human brain. However, its accuracy in complex microstructure environments has not been well characterized. Theory and Methods Here we have simulated different tissue configurations, sampling schemes, and processing steps to evaluate DSI performances' under realistic biophysical conditions. A novel approach to compute the orientation distribution function (ODF) has also been developed to include biophysical constraints, namely integration ranges compatible with axial fiber diffusivities. Results Performed simulations identified several DSI configurations that consistently show aliasing artifacts caused by fast diffusion components for both isotropic diffusion and fiber configurations. The proposed method for ODF computation showed some improvement in reducing such artifacts and improving the ability to resolve crossings, while keeping the quantitative nature of the ODF. Conclusion In this study, we identified an important limitation of current DSI implementations, specifically the presence of aliasing due to fast diffusion components like those from pathological tissues, which are not well characterized, and can lead to artifactual fiber reconstructions. To minimize this issue, a new way of computing the ODF was introduced, which removes most of these artifacts and offers improved angular resolution. Magn Reson Med 76:1837-1847, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. [ABSTRACT FROM AUTHOR]

Background: Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification. Methods: 1,870 European adolescents (Mage = 14.56 years, SDage = 0.44 years, 51.5% female) underwent MRI scanning and completed behavioral and psychological measures of stressful life events, academic competence, social competence, rule-abiding conduct, personality, and alcohol use. Results: The interaction of competence and adversity identified two regions centered on the right middle and superior frontal gyri; grey matter volumes in these regions were larger in adolescents experiencing adversity who showed positive adaptation. Differences in these regions among competence/adversity subgroups were maintained after controlling for several covariates and were robust to alternative operationalization decisions for key constructs. Conclusions: We demonstrate structural brain correlates of adolescent resilience, and suggest that right prefrontal structures are implicated in adaptive functioning for youth who have experienced adversity. [ABSTRACT FROM AUTHOR]

Adolescence is a common time for initiation of alcohol use and alcohol use disorders. Importantly, the neuro-anatomical foundation for later alcohol-related problems may already manifest pre-natally, particularly due to smoking and alcohol consumption during pregnancy. In this context, cortical gyrification is an interesting marker of neuronal development but has not been investigated as a risk factor for adolescent alcohol use. On magnetic resonance imaging scans of 595 14-year-old adolescents from the IMAGEN sample, we computed whole-brain mean curvature indices to predict change in alcohol-related problems over the following 2 years. Change of alcohol use-related problems was significantly predicted from mean curvature in left orbitofrontal cortex (OFC). Less gyrification of OFC was associated with an increase in alcohol use-related problems over the next 2 years. Moreover, lower gyrification in left OFC was related to pre-natal alcohol exposure, whereas maternal smoking during pregnancy had no effect. Current alcohol use-related problems of the biological mother had no effect on offsprings' OFC gyrification or drinking behaviour. The data support the idea that alcohol consumption during pregnancy mediates the development of neuro-anatomical phenotypes, which in turn constitute a risk factor for increasing problems due to alcohol consumption in a vulnerable stage of life. Maternal smoking during pregnancy or current maternal alcohol/nicotine consumption had no significant effect. The OFC mediates behaviours known to be disturbed in addiction, namely impulse control and reward processing. The results stress the importance of pre-natal alcohol exposure for later increases in alcohol use-related problems, mediated by structural brain characteristics. [ABSTRACT FROM AUTHOR]

Increased oxidative stress has been postulated to contribute to the pathogenesis of autism spectrum disorder (ASD). However, reports of alterations in oxidation markers including glutathione (GSH), the major endogenous antioxidant, are indirect, coming from blood plasma level measurements and postmortem studies. Therefore we used in-vivo 3 Tesla proton magnetic resonance spectroscopy ([1H]MRS) to directly measure GSH concentrations in the basal ganglia (BG) and the dorsomedial prefrontal cortex of 21 normally intelligent adult males with ASD and 29 controls who did not differ in age or IQ. There was no difference in brain GSH between patients and controls in either brain area; neither did GSH levels correlate with measures of clinical severity in patients. Thus [1H]MRS measures of cortical and subcortical GSH are not a biomarker for ASD in intellectually able adult men. Autism Res 2016, 9: 429-435. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. [ABSTRACT FROM AUTHOR]

Purpose To design hyperbolic secant (HS) excitation pulses to reduce signal dropout in the orbitofrontal and inferior temporal regions in gradient-echo echo-planar imaging (GE-EPI) for functional MRI (fMRI) applications. Methods An algorithm based on Bloch simulations optimizes the HS pulse parameters needed to give the desired signal response across the range of susceptibility gradients observed in the human head (approximately ±250 μT·m−1). The impact of the HS pulse on the signal, temporal signal-to-noise ratio, blood oxygen level-dependent (BOLD) sensitivity, and ability to detect resting state BOLD signal changes was assessed in six healthy male volunteers at 3T. Results The optimized HS pulse (μ = 4.25, β = 3040 Hz, A0 = 12.3 μT, Δf = 4598 Hz) had a near uniform signal response for through-plane susceptibility gradients in the range ±250 μT·m−1. Signal, temporal signal-to-noise ratio, BOLD sensitivity, and the detectability of resting state networks were all partially recovered in the orbitofrontal and inferior temporal regions; however, there were signal losses of up to 50% in regions of homogeneous field (and signal loss from in-plane susceptibility gradients remained). Conclusion The HS pulse reduced signal dropout and could be used to acquire task and resting state fMRI data without loss of spatial coverage or temporal resolution. Magn Reson Med 74:661-672, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Individuals with alcohol-dependent parents show an elevated risk of developing alcohol-related problems themselves. Modulations of the mesolimbic reward circuit have been postulated as a pre-existing marker of alcoholism. We tested whether a positive family history of alcoholism is correlated with ventral striatum functionality during a reward task. All participants performed a modified version of the monetary incentive delay task while their brain responses were measured with functional magnetic resonance imaging. We compared 206 healthy adolescents (aged 13-15) who had any first- or second-degree relative with alcoholism to 206 matched controls with no biological relative with alcoholism. Reward anticipation as well as feedback of win recruited the ventral striatum in all participants, but adolescents with a positive family history of alcoholism did not differ from their matched peers. Also we did not find any correlation between family history density and reward anticipation or feedback of win. This finding of no differences did not change when we analyzed a subsample of 77 adolescents with at least one parent with alcohol use disorder and their matched controls. Because this result is in line with another study reporting no differences between children with alcohol-dependent parents and controls at young age, but contrasts with studies of older individuals, one might conclude that at younger age the effect of family history has not yet exerted its influence on the still developing mesolimbic reward circuit. [ABSTRACT FROM AUTHOR]

fMRI is increasingly implemented in the clinic to assess memory function. There are multiple approaches to memory fMRI, but limited data on advantages and reliability of different methods. Here, we compared effect size, activation lateralisation, and between-sessions reliability of seven memory fMRI protocols: Hometown Walking (block design), Scene encoding (block design and event-related design), Picture encoding (block and event-related), and Word encoding (block and event-related). All protocols were performed on three occasions in 16 patients with temporal lobe epilepsy (TLE). Group T-maps showed activity bilaterally in medial temporal lobe for all protocols. Using ANOVA, there was an interaction between hemisphere and seizure-onset lateralisation ( P = 0.009) and between hemisphere, protocol and seizure-onset lateralisation ( P = 0.002), showing that the distribution of memory-related activity between left and right temporal lobes differed between protocols and between patients with left-onset and right-onset seizures. Using voxelwise intraclass Correlation Coefficient, between-sessions reliability was best for Hometown and Scenes (block and event). The between-sessions spatial overlap of activated voxels was also greatest for Hometown and Scenes. Lateralisation of activity between hemispheres was most reliable for Scenes (block and event) and Words (event). Using receiver operating characteristic analysis to explore the ability of each fMRI protocol to classify patients as left-onset or right-onset TLE, only the Words (event) protocol achieved a significantly above-chance classification of patients at all three sessions. We conclude that Words (event) protocol shows the best combination of between-sessions reliability of the distribution of activity between hemispheres and reliable ability to distinguish between left-onset and right-onset patients. Hum Brain Mapp 36:1595-1608, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Key points Nausea is a highly individual and variable experience. The reasons for this variability are incompletely understood although psychophysiological factors have been proposed., Herein we describe objective psychophysiological changes induced by the subjective sensation of motion sickness., In comparison to subjects who did not develop nausea, nausea-sensitive subjects demonstrated electrogastrographic and autonomic changes, which included an increase in sympathetic nervous system activity with a concomitant reduction in parasympathetic activity. Furthermore, differences were also evident in plasma ghrelin, and subcortical and cortical activity., These data have a number of important implications for future research examining the physiological mechanisms that underlie nausea: The physiological, hormonal and cortical patterns identified herein represent potential biomarkers of the physiological mechanisms of nausea., Reverse translation of the physiological factors identified may facilitate refinement of animal models used to investigate novel anti-emetic agents and emetic liability of candidate drugs, increasing their validity and translation of finding to humans., , Abstract An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea-sensitive subjects had lower normogastria/tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea-sensitive subjects had decreased plasma ghrelin and demonstrated increased activity of the left anterior cingulate cortex. Nausea VAS scores correlated positively with plasma vasopressin and left inferior frontal and middle occipital gyri activity and correlated negatively with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Purpose Idiopathic generalized epilepsies (IGE) comprise a group of clinical syndromes associated with spike wave discharges, putatively linked to alterations in neurotransmission. The purpose of this study was to investigate whether patients with IGE have altered glutamine and γ-aminobutyric acid (GABA) levels indicative of altered excitatory and inhibitory neurotransmission in frontal regions. Materials and Methods Single-voxel MEGA-edited PRESS magnetic resonance imaging (MRI) spectra were acquired from a 30-mL voxel in the dorsolateral prefrontal cortex in 13 patients with IGE (8 female) and 16 controls (9 female) at 3T. Metabolite concentrations were derived using LCModel. Differences between groups were investigated using an unpaired t-test. Results Patients with IGE were found to have significantly higher glutamine than controls ( P = 0.02). GABA levels were also elevated in patients with IGE ( P = 0.03). Conclusion Patients with IGE have increased frontal glutamine and GABA compared with controls. Since glutamine has been suggested to act as a surrogate for metabolically active glutamate, it may represent a marker for excitatory neurotransmission. J. Magn. Reson. Imaging 2015;41:694-699. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background It has been reported that mania may be associated with superior cognitive performance. In this study, we test the hypothesis that manic symptoms in youth separate along two correlated dimensions and that a symptom constellation of high energy and cheerfulness is associated with superior cognitive performance. Method We studied 1755 participants of the IMAGEN study, of average age 14.4 years ( SD = 0.43), 50.7% girls. Manic symptoms were assessed using the Development and Wellbeing Assessment by interviewing parents and young people. Cognition was assessed using the Wechsler Intelligence Scale For Children ( WISC- IV) and a response inhibition task. Results Manic symptoms in youth formed two correlated dimensions: one termed exuberance, characterized by high energy and cheerfulness and one of undercontrol with distractibility, irritability and risk-taking behavior. Only the undercontrol, but not the exuberant dimension, was independently associated with measures of psychosocial impairment. In multivariate regression models, the exuberant, but not the undercontrolled, dimension was positively and significantly associated with verbal IQ by both parent- and self-report; conversely, the undercontrolled, but not the exuberant, dimension was associated with poor performance in a response inhibition task. Conclusions Our findings suggest that manic symptoms in youth may form dimensions with distinct correlates. The results are in keeping with previous findings about superior performance associated with mania. Further research is required to study etiological differences between these symptom dimensions and their implications for clinical practice. [ABSTRACT FROM AUTHOR]

ABSTRACT Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesized to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluA2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluA2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluA2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective Thalamic abnormality in temporal lobe epilepsy ( TLE) is well known from imaging studies, but evidence is lacking regarding connectivity profiles of the thalamus and their involvement in the disease process. We used a novel multisequence magnetic resonance imaging ( MRI) protocol to elucidate the relationship between mesial temporal and thalamic pathology in TLE. Methods For 23 patients with TLE and 23 healthy controls, we performed T1-weighted (for analysis of tissue structure), diffusion tensor imaging (tissue connectivity), and T1 and T2 relaxation (tissue integrity) MRI across the whole brain. We used connectivity-based segmentation to determine connectivity patterns of thalamus to ipsilateral cortical regions (occipital, parietal, prefrontal, postcentral, precentral, and temporal). We subsequently determined volumes, mean tractography streamlines, and mean T1 and T2 relaxometry values for each thalamic segment preferentially connecting to a given cortical region, and of the hippocampus and entorhinal cortex. Results As expected, patients had significant volume reduction and increased T2 relaxation time in ipsilateral hippocampus and entorhinal cortex. There was bilateral volume loss, mean streamline reduction, and T2 increase of the thalamic segment preferentially connected to temporal lobe, corresponding to anterior, dorsomedial, and pulvinar thalamic regions, with no evidence of significant change in any other thalamic segments. Left and right thalamotemporal segment volume and T2 were significantly correlated with volume and T2 of ipsilateral (epileptogenic), but not contralateral (nonepileptogenic), mesial temporal structures. Significance These convergent and robust data indicate that thalamic abnormality in TLE is restricted to the area of the thalamus that is preferentially connected to the epileptogenic temporal lobe. The degree of thalamic pathology is related to the extent of mesial temporal lobe damage in TLE. [ABSTRACT FROM AUTHOR]

Objective Patients with juvenile myoclonic epilepsy ( JME) often present with risk-taking behavior, suggestive of frontal lobe dysfunction. Recent studies confirm functional and microstructural changes within the frontal lobes in JME. This study aimed at characterizing decision-making behavior in JME and its neuronal correlates using functional magnetic resonance imaging (fMRI). Methods We investigated impulsivity in 21 JME patients and 11 controls using the Iowa Gambling Task ( IGT), which measures decision making under ambiguity. Performance on the IGT was correlated with activation patterns during an fMRI working memory task. Results Both patients and controls learned throughout the task. Post hoc analysis revealed a greater proportion of patients with seizures than seizure-free patients having difficulties in advantageous decision making, but no difference in performance between seizure-free patients and controls. Functional imaging of working memory networks showed that overall poor IGT performance was associated with an increased activation in the dorsolateral prefrontal cortex (DLPFC) in JME patients. Impaired learning during the task and ongoing seizures were associated with bilateral medial prefrontal cortex ( PFC) and presupplementary motor area, right superior frontal gyrus, and left DLPFC activation. Significance Our study provides evidence that patients with JME and ongoing seizures learn significantly less from previous experience. Interictal dysfunction within 'normal' working memory networks, specifically, within the DLPFC and medial PFC structures, may affect their ability to learn. [ABSTRACT FROM AUTHOR]

Despite advances in the treatment of patients with human immunodeficiency virus (HIV), HIV-associated neurocognitive disorder occurs in 15-50% of HIV-infected individuals, and may become more apparent as ageing advances. In the present study we investigated regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose uptake (rCMRglc) in medically and psychiatrically stable HIV-1-infected participants in two age-groups. Positron emission tomography (PET) and magnetic resonance imaging (MRI)-based arterial spin labeling (ASL) were used to measure rCMRglc and rCBF, respectively, in 35 HIV-infected participants and 37 HIV-negative matched controls. All participants were currently asymptomatic with undetectable HIV-1 viral loads, without medical or psychiatric comorbidity, alcohol or substance misuse, stable on medication for at least 6 months before enrolment in the study. We found significant age effects on both ASL and PET with reduced rCBF and rCMRglc in related frontal brain regions, and consistent, although small, reductions in rCBF and rCMRglc in the anterior cingulate cortex (ACC) in HIV, a finding of potential clinical significance. There was no significant interaction between HIV status and the ageing process, and no significant HIV-related changes elsewhere in the brain on PET or ASL. This is the first paper to combine evidence from ASL and PET method in HIV participants. These finding provide evidence of crossvalidity between the two techniques, both in ageing and a clinical condition (HIV). Hum Brain Mapp 34:2484-2493, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Recently, genome-wide association between schizophrenia and an intronic variant in AMBRA1 (rs11819869) was reported. Additionally, in a reverse genetic approach in adult healthy subjects, risk allele carriers showed a higher medial prefrontal cortex blood oxygen level-dependent ( BOLD) response during a flanker task examining motor inhibition as an aspect of impulsivity. To test whether this finding can be expanded to further aspects of impulsivity, we analysed the effects of the rs11819869 genotype on impulsivity-related traits on a behavioral, temperament and neural level in a large sample of healthy adolescents. We consider this reverse genetic approach specifically suited for use in a healthy adolescent sample, as these individuals comprise those who will eventually develop mental disorders in which impulsivity is implicated. Healthy adolescents from the IMAGEN study were included in the neuropsychological analysis ( n = 848) and a functional magnetic resonance imaging ( fMRI) task ( n = 512). Various aspects of impulsivity were assessed using the Temperament and Character Inventory- Revised, the Substance Use Risk Profile Scale, the Cambridge Cognition Neuropsychological Test Automated Battery, and the Stop Signal Task ( SST) in the fMRI paradigm. On a behavioral level, increased delay aversion was observed in risk allele carriers. Furthermore, risk allele carriers showed a higher BOLD response in an orbito-frontal target region during the SST, which declined to trend status after Family Wise Error correction. Our findings support the hypothesis that the schizophrenia-related risk variant of rs11819869 is involved in various aspects of impulsivity, and that this involvement occurs on a behavioral as well as an imaging genetics level. [ABSTRACT FROM AUTHOR]

The oligodendrocyte lineage transcription factor 2 (OLIG2) regulates the genesis of oligodendrocytes, the brain cells responsible for axonal myelination. Although it has been associated with psychiatric and neurological disorders, the impact of this gene on white matter integrity has never been investigated in humans. Using diffusion tensor imaging, we examined the effect of a single nucleotide polymorphism (rs1059004) in OLIG2 previously associated with reduced gene expression, and with psychiatric disorders on fractional anisotropy in 78 healthy subjects. We found that the risk allele (A) was associated with reduced white matter integrity in the corona radiata bilaterally. This is consistent with evidence that it is a schizophrenia susceptibility gene, and suggests that it may confer increased risk through an effect on neuroanatomical connectivity. Hum Brain Mapp 34:2025-2031, 2013. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Key points Perirhinal cortex (Prh) is critically involved in visual recognition memory and synaptic plasticity., Nitric oxide and endocannabinoids (eCBs) have been shown to act as retrograde messengers in synaptic plasticity in several brain areas, but no study has yet investigated their role in synaptic plasticity in Prh., Evidence is still lacking of a retrograde messenger involved in synaptic plasticity in Prh., In this study, we show that NO is involved in long-term depression (LTD) but not in long-term potentiation (LTP). Conversely, eCBs are involved in LTP but not in LTD. Crucially, inhibiition of NO signalling prevents visual recognition memory acquisition, whilst inhibition of eCB signalling does not affect recognition memory., These results suggest that LTD but not LTP is a neuronal correlate of visual recognition memory., Abstract Synaptic plasticity in perirhinal cortex is essential for recognition memory. Nitric oxide and endocannabinoids (eCBs), which are produced in the postsynaptic cell and act on the presynaptic terminal, are implicated in mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in other brain regions. In this study, we examine these two retrograde signalling cascades in perirhinal cortex synaptic plasticity and in visual recognition memory in the rat. We show that inhibition of NO-dependent signalling prevented both carbachol- and activity (5 Hz)-dependent LTD but not activity (100 Hz theta burst)-dependent LTP in the rat perirhinal cortex in vitro. In contrast, inhibition of the eCB-dependent signalling prevented LTP but not the two forms of LTD in vitro. Local administration into perirhinal cortex of the nitric oxide synthase inhibitor NPA (2 μ m) disrupted acquisition of long-term visual recognition memory. In contrast, AM251 (10 μ m), a cannabinoid receptor 1 antagonist, did not impair visual recognition memory. The results of this study demonstrate dissociation between putative retrograde signalling mechanisms in LTD and LTP in perirhinal cortex. Thus, LTP relies on cannabinoid but not NO signalling, whilst LTD relies on NO- but not eCB-dependent signalling. Critically, these results also establish, for the first time, that NO- but not eCB-dependent signalling is important in perirhinal cortex-dependent visual recognition memory. [ABSTRACT FROM AUTHOR]

Objectives A broad range of subtle and markedly heterogenous neuroanatomical abnormalities of grey matter and white matter have been reported in bipolar disorder. Euthymic bipolar disorder patients represent a clinically homogenous group in which to identify trait-based biomarkers of bipolar disorder. In this study, we sought to clarify the nature and extent of neuroanatomical differences in a large, clinically homogeneous group of euthymic bipolar disorder patients. Methods Structural magnetic resonance imaging ( sMRI) was obtained for 60 patients with prospectively confirmed euthymic bipolar I disorder and 60 individually age- and gender-matched healthy volunteers. High angular resolution diffusion tensor imaging (DTI) scans were obtained for a subset of this sample comprising 35 patients and 43 controls. Voxel-based analysis of both sMRI and DTI data sets was performed. Results Bipolar disorder patients displayed global reductions in white matter volume and fractional anisotropy reductions in the corpus callosum, posterior cingulum, and prefrontal white matter compared with controls. There were corresponding increases in radial diffusivity in the callosal splenium in patients compared with controls. No significant group differences were detected in grey matter. In patients, lithium was associated with a bilateral increase in grey matter volume in the temporal lobes, but not with any DTI parameter. Conclusions Euthymic bipolar I disorder is characterized by both diffuse global white matter deficits and potential regional disorganization in interhemispheric and longitudinal tracts, while grey matter appears to be preserved. [ABSTRACT FROM AUTHOR]

Objectives Bipolar disorder is a severe mood disorder, which normally begins during adolescence or early adulthood and has a heritability of up to 80%. The largest genome-wide association analysis of bipolar disorder recently identified a new genome-wide associated variant in OZD4 (rs12576775). The aim of the present study was to further elucidate the role of this risk variant in the disease process using an imaging genetics approach. As increased amygdala and striatal responses during the processing of reward and emotion are characteristic for bipolar disorder patients, it was tested whether the risk variant has an influence on this endophenotype in healthy adolescents. Methods We examined the impact of the risk variant rs12576775 on functional magnetic resonance imaging data in an adolescent sample (N = 485). Differential activation between carriers of the risk allele (G-allele) and homozygous A-allele carriers in the amygdala and the striatum during a modification of the monetary incentive delay task (examining reward) and a face task (examining emotion) was analyzed. Results Carriers of the risk allele showed an increased blood oxygen level-dependent response in the amygdala during reward sensitivity (p = 0.05) and reward expectation (p < 0.05) but not during the face task. No significant group differences were found in the striatum during both reward and emotion processing. Conclusion Our results indicate that the ODZ4 risk variant influences reward processing in the amygdala. Alterations in the processing of emotion may have different underlying mechanisms and need to be further examined. [ABSTRACT FROM AUTHOR]

Background: Trait impulsiveness is a potential factor that predicts both substance use and certain psychiatric disorders. This study investigates whether there are common structural cerebral correlates of trait impulsiveness and cognitive functioning in a large sample of healthy adolescents from the IMAGEN project. Methods: Clusters of gray matter (GM) volume associated with trait impulsiveness, Cloningers' revised temperament, and character inventory impulsiveness (TCI-R-I) were identified in a whole brain analysis using optimized voxel-based morphometry in 115 healthy 14-year-olds. The clusters were tested for correlations with performance on the nonverbal tests (Block Design, BD; Matrix Reasoning, MT) of the Wechsler Scale of Intelligence for Children IV reflecting perceptual reasoning. Results: Cloningers' impulsiveness (TCI-R-I) score was significantly inversely associated with GM volume in left orbitofrontal cortex (OFC). Frontal clusters found were positively correlated with performance in perceptual reasoning tasks (Bonferroni corrected). No significant correlations between TCI-R-I and perceptual reasoning were observed. Conclusions: The neural correlate of trait impulsiveness in the OFC matches an area where brain function has previously been related to inhibitory control. Additionally, orbitofrontal GM volume was associated with scores for perceptual reasoning. The data show for the first time structural correlates of both cognitive functioning and impulsiveness in healthy adolescent subjects. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: Focal epilepsies are often associated with structural and functional changes that may extend beyond the area of seizure onset. In this study we investigated the functional anatomy of memory in patients with frontal lobe epilepsy (FLE), focusing on the local and remote effects of FLE on the networks supporting memory encoding. Methods: We studied 32 patients with drug-resistant FLE and 18 controls using a functional magnetic resonance imaging (fMRI) memory encoding paradigm. Key Findings: During encoding of stimuli, patients with FLE recruited more widely distributed areas than healthy controls, in particular within the frontal lobe contralateral to the seizure onset. Normal memory performance was associated with increased recruitment of frontal areas, and conversely a poor performance was associated with an absence of this increased recruitment and decreased activation in mesial temporal lobe areas. Significance: In patients with FLE, recruitment of wider areas, particularly in the contralateral frontal lobe, appears to be an effective compensatory mechanism to maintain memory function. Impaired hippocampal activation is relatively rare and, in turn, associated with poor recognition memory. [ABSTRACT FROM AUTHOR]

Large-scale magnetic resonance (MR) studies of the human brain offer unique opportunities for identifying genetic and environmental factors shaping the human brain. Here, we describe a dataset collected in the context of a multi-centre study of the adolescent brain, namely the IMAGEN Study. We focus on one of the functional paradigms included in the project to probe the brain network underlying processing of ambiguous and angry faces. Using functional MR (fMRI) data collected in 1,110 adolescents, we constructed probabilistic maps of the neural network engaged consistently while viewing the ambiguous or angry faces; 21 brain regions responding to faces with high probability were identified. We were also able to address several methodological issues, including the minimal sample size yielding a stable location of a test region, namely the fusiform face area (FFA), as well as the effect of acquisition site (eight sites) and scanner (four manufacturers) on the location and magnitude of the fMRI response to faces in the FFA. Finally, we provided a comparison between male and female adolescents in terms of the effect sizes of sex differences in brain response to the ambiguous and angry faces in the 21 regions of interest. Overall, we found a stronger neural response to the ambiguous faces in several cortical regions, including the fusiform face area, in female (vs. male) adolescents, and a slightly stronger response to the angry faces in the amygdala of male (vs. female) adolescents. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To investigate if placental volume in the second trimester of pregnancy is related to uterine artery blood flow and neonatal birth weight. Materials and Methods: In 83 singleton pregnancies at 24-29 weeks' gestation, uterine artery pulsatility index (PI) was measured by Doppler ultrasound and placental volume was calculated from images obtained by magnetic resonance imaging (MRI) at 1.5T. The significance of the association between placental volume, uterine artery PI, and birth weight was examined. Results: In 37 normal pregnancies resulting in delivery of neonates with birth weight at or above the 10th percentile, the median placental volume increased with gestational age from 363 cm3 at 24 weeks to 515 cm3 at 29 weeks. In 46 pregnancies that resulted in delivery of small for gestational age (SGA) neonates with birth weight below the 10th percentile the median placental volume, corrected for gestational age, was significantly decreased by 120 cm3 ( P < 0.0001) and median uterine artery PI was increased (1.87 vs. 1.59, P < 0.0001). There were significant associations between placental volume and both uterine artery PI ( r = −0.677, P < 0.0001) and birth weight percentile ( r = 0.658, P < 0.0001). Conclusion: Placental volume during the second trimester is smaller in pregnancies that subsequently deliver SGA neonates and the measurement is related to placental perfusion. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Autistic Spectrum Disorder (ASD), including Asperger syndrome and autism, is a highly genetic neurodevelopmental disorder. There is a consensus that ASD has a biological basis, and it has been proposed that it is a 'connectivity' disorder. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) allows measurement of the microstructural integrity of white matter (a proxy measure of 'connectivity'). However, nobody has investigated the microstructural integrity of whole brain white matter in people with Asperger syndrome. Methods: We measured the fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) of white matter, using DT-MRI, in 13 adults with Asperger syndrome and 13 controls. The groups did not differ significantly in overall intelligence and age. FA, MD and RD were assessed using whole brain voxel-based techniques. Results: Adults with Asperger syndrome had a significantly lower FA than controls in 13 clusters. These were largely bilateral and included white matter in the internal capsule, frontal, temporal, parietal and occipital lobes, cingulum and corpus callosum. Conclusions: Adults with Asperger syndrome have widespread significant differences from controls in white matter microstructural integrity. [ABSTRACT FROM AUTHOR]

Unfixed and fixed postmortem multiple sclerosis (MS) brain is being used to probe pathology underlying quantitative MR (qMR) changes. Effects of fixation on qMR indices in MS brain are unknown. In 15 postmortem MS brain slices T1, T2, MT ratio (MTR), macromolecular proton fraction (fB), fractional anisotropy (FA), and mean, axial, and radial diffusivity (MD, Dax, and Drad) were assessed in white matter (WM) lesions (WML) and normal appearing WM (NAWM) before and after fixation in formalin. Myelin content, axonal count, and gliosis were quantified histologically. Student's t-test and regression were used for analysis. T1, T2, MTR, and fB obtained in unfixed MS brain were similar to published values obtained in patients with MS in vivo. Following fixation T1, T2 (NAWM, WML) and MTR (NAWM) dropped, whereas fB (NAWM, WML) increased. Compared to published in vivo data all diffusivity measures were lower in unfixed MS brain, and dropped further following fixation (except for FA). MTR was the best predictor of Tmyelin (inversely related to myelin) in unfixed MS brain ( r = −0.83; P < 0.01) whereas postfixation T2 ( r = 0.92; P < 0.01), T1 ( r = 0.89; P < 0.01), and fB ( r = −0.86; P < 0.01) were superior. All diffusivity measures (except for Dax in unfixed tissue) were predictors of myelin content. Magn Reson Med 59:268-277, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Global effects in functional MRI are temporal modulations in signal intensity resulting from various scanner and subject phenomena. These effects contribute to the overall variance, reducing the effect size associated with an experimental paradigm. Statistical estimations that include an approximation for concurrent global effects will reduce the residual error within the model and so improve statistical power of the study. Conventionally, estimates of global effects are derived from mean intracerebral signal intensities, but these may be prone to contributions from localised experimentally evoked signal changes. In such cases, inaccurate estimates of global effects may result in erroneous inferences of neural modulations based on statistical artefact. A novel, computationally simple, method of estimating global effects is proposed using muscle tissue acquired within the same acquisition volume. Quantitative improvements in sensitivity are reported for a somatosensory stimulation paradigm using global muscle signal intensities as a covariate of no-interest. The method is independent of local neurogenic signal changes and, under particular experimental conditions, may be more representative of true global effects. The utility of this strategy to applications in small-animal functional MRI that evoke systemic physiological changes as a result of the experimental manipulation is critically discussed. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Multislice MR images obtained using a fast spin-echo (FSE) readout are strongly affected by magnetization transfer (MT) effects, which will cause a decrease in the observed longitudinal relaxation times for tissues with a large bound water component. This is pertinent for FSE-based inversion-recovery (IR) sequences, as it would be expected to cause a change in the required inversion times. Furthermore, the effect will be greater as the number of slices that are acquired within the repetition time (TR) is increased. A pseudo-3D IR-FSE sequence was used to obtain images of a phantom consisting of thermally crosslinked bovine serum albumin. It was found that increasing the number of slabs acquired per TR period led to a decrease in the inversion time that maximally suppressed the signal from the MT phantom; this was not the case for water. This has important consequences for any IR imaging sequence that uses an FSE readout. Magn Reson Med 58:825-829, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship of myelin content, axonal density, and gliosis with the fraction of macromolecular protons (fB) and T2 relaxation of the macromolecular pool (T2B) acquired using quantitative magnetization transfer (qMT) MRI in postmortem brains of subjects with multiple sclerosis (MS).Materials and Methods: fB and T2B were acquired in unfixed postmortem brain slices of 20 subjects with MS. The myelin content, axonal count, and severity of gliosis were all quantified histologically. t-Tests and multiple regression were used for analysis.Results: MR indices obtained in unfixed postmortem MS brains were consistent with in vivo values reported in the literature. A significant correlation was detected between Tr(myelin) (inversely proportional to myelin content) and 1) fB (r = -0.80, P < 0.001) and 2) axonal count (r = -0.79, P < 0.001). fB differed between 1) normal-appearing white matter (NAWM) and remyelinated WM lesions (rWMLs) (mean: fB 6.9 [SD 2] vs. 4.0 [1.8], P = 0.01), and 2) rWMLs and demyelinated WMLs (mean: 4.2 [2.2] vs. 2.5 [1.3], P = 0.016). No association was detected between T2B and any of the histological measures.Conclusion: fB in MS WM is dependent on myelin content and may be a tool to monitor patients with this condition. [ABSTRACT FROM AUTHOR]

Purpose: Conventional optimal MRI is unremarkable in 20%–30% of patients with intractable focal epilepsy. These MRI-negative patients are the most challenging in surgical programs. Our aim was to evaluate the yield and utility of quantitative MRI with novel contrasts in MRI-negative patients with refractory focal epilepsy, who were potential surgical candidates. Methods: Ninety-three consecutive potential surgical candidates with refractory focal epilepsy, 44 with temporal lobe epilepsy, and 49 with frontal lobe epilepsy as determined with ictal scalp video-EEG; and normal optimal conventional MRI, including hippocampal volumes and T2 measures were investigated with quantitative MRI contrasts. The contrasts comprised fast fluid attenuated inversion recovery based T2 measurement (FFT2), double inversion recovery (DIR), magnetization transfer ratio (MTR), and voxel-based morphometry of gray matter (VBM). Voxel-based analyses of whole brain data were used to compare each patient with a control group. Results: In patients with a putative single focus on scalp video-EEG telemetry, 16% had concordant FFT2 abnormalities, as did 16% with DIR, 5% with MTR and 9% with VBM. The greatest agreement in the localization of abnormalities was between FFT2 and DIR. Altogether, 31% patients had a focal abnormality with at least one contrast in the lobe of seizure onset. Signal changes outside the lobe of the putative focus were found with FFT2 in 36% patients, with DIR in 42%, with MTR in 6% and with VBM in 7%. Discussion: Quantitative analysis of MRI contrasts had a low yield of identifying focal abnormalities concordant with putative epileptic foci in patients with unremarkable conventional MRI. Specificity was low for FFT2 and DIR. With the low specificity, data must be interpreted with caution, but in some patients may assist in creating a hypothesis for testing with intracranial electrodes. [ABSTRACT FROM AUTHOR]

The concentrations and magnetization transfer ratios (MTRs) in gray matter (GM) and white matter (WM) of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), myo-inositol (Ins), and glutamate plus glutamine (Glx) were investigated using magnetic resonance spectroscopic imaging (MRSI). The macromolecule (MM) baseline was studied separately using a metabolite-nulling inversion. Three data sets were collected from a point-resolved spectroscopy (PRESS)-selected volume (TE/TR = 30/3000 ms) of human frontal lobe in vivo: one with MT pulses applied, one with an inversion pulse to null small metabolites, and one with no inversion or MT pulses. The MM signal, which was analyzed by integrating the metabolite-nulled spectrum between 0 and 3 ppm, was estimated to be 38% higher in GM than in WM. MM subtraction decreased the signal-to-noise ratio (SNR) and also decreased the reliability of LCModel quantification of most metabolites, but may have improved the accuracy of quantification of Glx. Glx and Cr were both found to correlate strongly with the GM volume fraction of the voxels. Cr showed the highest MTR, but the other metabolites also showed some attenuation of signal when the MT pulses were applied. The MTRs did not correlate with the GM volume fraction, which implies that the local environment of metabolites does not differ markedly between GM and WM. Magn Reson Med 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A pulse sequence was implemented to observe the magnetization transfer (MT) effect on metabolites, water, and macromolecules in human frontal lobes in vivo at 1.5 Tesla. Signals were compared following the application of three hard pulses of 0.745 μT amplitude, applied at frequency offsets of either 2500 Hz or 30 kHz, preceding a conventional point-resolved spectroscopy (PRESS)-localized acquisition with an echo time (TE) of 30 ms and repetition time (TR) of 3 s. This gave an MT effect on water in vivo of 46%, while direct saturation by the MT pulses at 2.5 kHz offset was confirmed to be under 4% for all metabolites. We observed significant MT saturation in vivo for N-acetylated compounds, choline (Cho), myo-inositol, and lactate (Lac); a trend of an effect on glutamate + glutamine (Glx); and the typically observed effect on creatine (Cr). No significant MT effect was seen on the macromolecule signal, which was observed using metabolite nulling. Magn Reson Med, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The fast spin-echo (FSE) sequence is frequently used as a fast data-readout technique in conjunction with other pulse sequence elements, such as in fluid-attenuated inversion-recovery (FLAIR) and double inversion-recovery (DIR) sequences. In order to implement those pulse sequences, an understanding is required of how the longitudinal magnetization evolves during the FSE part of the sequence. This evolution has been addressed to a certain extent by previous publications, but the DIR literature in particular appears to be replete with approximations to the exact expression for the longitudinal magnetization, and several papers contain errors. Equations are therefore presented here for the evolution of the longitudinal magnetization for a FSE readout. These are then applied to calculate the magnetization available immediately prior to the 90° imaging pulse for the FLAIR-FSE and DIR-FSE pulse sequences. Magn Reson Med 54:241-245, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Summary: Purpose: γ-Amino butyric acid (GABA) and glutamate, respectively the principal inhibitory and excitatory neurochemicals in the brain, are visible to proton magnetic resonance spectroscopy (MRS). We report a study of GABA+ (GABA plus homocarnosine) and GLX (glutamate plus glutamine) concentrations in the occipital lobes in patients with idiopathic generalised epilepsy (IGE) and in patients with occipital lobe epilepsy (OLE). Methods: Fifteen patients with IGE, 15 patients with OLE, and 15 healthy volunteers were studied. A single voxel was prescribed in the occipital lobes for each subject. PRESS localised short-echo-time MRS was performed to measure GLX by using LCModel. A double quantum GABA filter was used to measure GABA+. Segmented T1 -weighted images gave the tissue composition of the prescribed voxel. Results: Grey-matter proportion, GLX, and GABA+ were all elevated in IGE. However, analysis using grey-matter proportion as a covariable showed no significant group differences. No correlation was observed between GABA+ concentration and either seizure frequency or time since last seizure. Conclusions: GLX and GABA+ were elevated in IGE. Elevated grey-matter content in the IGE group despite normal MRI appearance can be expected to account for some or all of this observed elevation of GLX and GABA+. GABA+ concentration did not correlate with seizure control or duration since most recent seizure. [ABSTRACT FROM AUTHOR]