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It is unclear whether deviations in brain and behavioral development, which may underpin elevated substance use during adolescence, are predispositions for or consequences of substance use initiation. Here, we examine behavioral and neuroimaging indices at early and mid-adolescence in drug-naive youths to identify possible predisposing factors for substance use initiation and its possible consequences.Among 304 drug-naive adolescents at baseline (age 14 years) from the IMAGEN dataset, 83 stayed drug-naive, 133 used alcohol on 1 to 9 occasions, 42 on 10 to 19 occasions, 27 on 20 to 39 occasions, and 19 on40 occasions at follow-up (age 16 years). Baseline measures included brain activation during the Monetary Incentive Delay task. Data at both baseline and follow-up included measures of trait impulsivity and delay discounting.From baseline to follow-up, impulsivity decreased in the 0 and 1- to 9-occasions groups (p .004), did not change in the 10- to 19-occasions and 20- to 29-occasions groups (p.294), and uncharacteristically increased in the40-occasions group (p = .046). Furthermore, blunted medial orbitofrontal cortex activation during reward outcome at baseline significantly predicted higher alcohol use frequency at follow-up, above and beyond behavioral and clinical variables (p = .008).These results suggest that the transition from no use to frequent drinking in early to mid-adolescence may disrupt normative developmental changes in behavioral control. In addition, blunted activity of the medial orbitofrontal cortex during reward outcome may underscore a predisposition toward the development of more severe alcohol use in adolescents. This distinction is clinically important, as it informs early intervention efforts in preventing the onset of substance use disorder in adolescents.

Objective Irritable mood, a common and impairing symptom in psychopathology, has been proposed to underlie the developmental link between oppositional problems in youth and depression in adulthood. We examined the neural correlates of adolescent irritability in IMAGEN, a sample of 2,024 14-year-old adolescents from 5 European countries. Method The Development and Well-Being Assessment (DAWBA) was used to assess attention-deficit/hyperactivity disorder, major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder. Three items from the DAWBA, selected as close matches to the Affective Reactivity Index, were used to assess irritability. Structural magnetic resonance imaging was examined using whole-brain voxel-based morphometry analysis, and functional magnetic resonance imaging was examined during a stop signal task of inhibitory control. Imaging data were included in structural equation models to examine the direct and indirect associations between irritable mood and comorbid DSM diagnoses. Results Whole-brain voxelwise analysis showed that adolescent irritable mood was associated with less gray matter volume and less neural activation underlying inhibitory control in frontal and temporal cortical areas (cluster-correction at p Conclusion This study identifies adolescent irritability as an independent construct and points to a neurobiological correlate to irritability that is an important contributing feature to many psychopathological disorders.

Urbanicity is a growing environmental challenge for mental-health. While the impact of urban life on brain and behavior might be distinct in different sociocultural conditions and geographies, there might exist features shared between regions. To investigate correlations of urbanicity with brain structure and function, neuropsychology and mental illness symptoms in young people from China and Europe, we developed a remote-sensing satellite-measure termed ‘UrbanSat’ quantifying population-density, a general measure of urbanicity. UrbanSat is correlated with brain volume, surface area and brain-network-connectivity in the medial prefrontal cortex and cerebellum, which mediate its effect on perspective-taking and depression- symptoms. Susceptibility to high population-density is greatest during childhood for the cerebellum and from childhood to adolescence for the prefrontal cortex. As UrbanSat can be generalized to different geographies, it will enable assessing the impact of urbanicity on mental illness and resilience globally, especially in young people where prevention and early interventions are most effective.

Background: Immune mechanisms have been implicated in the pathogenesis of depression. Translocator protein (TSPO)–targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to 1) test the hypothesis of significant case-control differences in TSPO binding in the anterior cingulate cortex, prefrontal cortex, and insula regions; and 2) explore the relationship between cerebral TSPO binding and peripheral blood C-reactive protein (CRP) concentration. Methods: A total of 51 depressed subjects with Hamilton Depression Rating Scale score >13 (median 17; interquartile range, 16–22) and 25 healthy control subjects underwent dynamic brain 11C-PK11195 PET and peripheral blood immune marker characterization. Depressed subjects were divided into high CRP (>3 mg/L; n = 20) and low CRP (2 p = .09; F 1,71 = 6.97, p = .01), which was not influenced by body mass index. The case-control difference was greatest in the anterior cingulate cortex (d = 0.49; t 74 = 2.00, p = .03) and not significant in the prefrontal cortex or insula (d = 0.27 and d = 0.36, respectively). Following CRP stratification, significantly higher TSPO binding was observed in low-CRP depression compared with controls (d = 0.53; t 54 = 1.96, p = .03). These effect sizes are comparable to prior major depressive disorder case-control TSPO PET data. No significant correlations were observed between TSPO and CRP measures. Conclusions: Consistent with previous findings, there is a modest increase in TSPO binding in depressed patients compared with healthy control subjects. The lack of a significant correlation between brain TSPO binding and blood CRP concentration or body mass index poses questions about the interactions between central and peripheral immune responses in the pathogenesis of depression.

Background 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. Methods 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). Results 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. Conclusions 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.

BACKGROUND: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms.METHODS: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14.RESULTS: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003).CONCLUSIONS: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores.

International audience; Objective: Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described.Method: A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs.Results: We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p = .002 at the cluster level, p = .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b = 0.069, 95% CI = 0.04−0.1, p =2 × 10−16), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI = 0.0004−0.01, p = .026).Conclusion: We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents

Objective: To characterize the structural and functional neurobiology of a large group of adolescents exhibiting a behaviorally and emotionally dysregulated phenotype. Method: Adolescents aged 14 years from the IMAGEN study were investigated. Latent class analysis (LCA) on the Strengths and Difficulties Questionnaire (SDQ) was used to identify a class of individuals with elevated behavioral and emotional difficulties (“dysregulated”; n = 233) who were compared to a matched sample from a low symptom class (controls, n = 233). Whole-brain gray matter volume (GMV) images were compared using a general linear model with 10,000 random label permutations. Regional GMV findings were then probed for functional differences from three functional magnetic resonance imaging (fMRI) tasks. Significant brain features then informed mediation path models linking the likelihood of psychiatric disorders (DSM-IV) with dysregulation. Results: Whole-brain differences were found in the right orbitofrontal cortex (R.OFC; p < .05; k = 48), with dysregulated individuals exhibiting lower GMV. The dysregulated group also exhibited higher activity in this region during successful inhibitory control (F1,429 = 7.53, p < .05). Path analyses indicated significant direct effects between the likelihood of psychopathologies and dysregulation. Modeling the R.OFC as a mediator returned modest partial effects, suggesting that the path linking the likelihood of an anxiety or conduct disorder diagnoses to dysregulation is partially explained by this anatomical feature. Conclusion: A large sample of dysregulated adolescents exhibited lower GMV in the R.OFC relative to controls. Dysregulated individuals also exhibited higher regional activations when exercising inhibitory control at performance levels comparable to those of controls. These findings suggest a neurobiological marker of dysregulation and highlight the role of the R.OFC in impaired emotional and behavioral control.

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.

It has been proposed that blending of Navan Conglomerate Group Ore (CGO) with Pale Beds Ore (PBO), the latter which floats well in isolation, results in sub-optimal Pb recovery with increased abundance of pyrite reporting to the concentrate and increased abundance of galena reporting to the tails. QEMSCAN data indicate that poor liberation of galena particles is not the primary cause of sub-optimal recovery of galena. Rather, principal component analysis (PCA) of time of flight secondary ion mass spectrometry (ToF-SIMS) reveals that chemically altered surface species interfere with the selectivity and recovery of froth flotation indicating that there is some poisoning of galena mineral surfaces particularly with Fe-containing species possibly leading to loss of recovery. Analysis of the Pb-circuit cleaner tails indicates Pb-species association with sphalerite surfaces, as was observed for the flotation feed and rougher tails but with insufficient induced hydrophobicity by Pb–collector interaction for flotation. A small population of relatively clean galena surfaces is also observed which may result from low bubble–particle collision efficiency or insufficient liberation. Fine-grained framboidal pyrite is the main diluting phase in the cleaner concentrate and is likely present due to entrainment. The presence of framboidal pyrite in CGO is of particular significance as its large surface area increases the rate of galvanic interaction with other metal sulfide minerals. We propose that increased abundance of refractory framboidal pyrite in CGO is the critical factor affecting the performance of the Navan Pb flotation circuit rather than purely high pyrite abundance. Irish Research Council Boliden Tara Mines Ltd Enterprise Partnership Scheme PhD scholarship

Introduction: Recovery from stroke has been correlated with specific anatomical lesions in the brain, however much of the variability in recovery remains unexplained. Recent research has indicated that the peri-infarct tissue plays a crucial role in recovery. We hypothesised that N-acetyl aspartate (NAA) can serve as a marker of neural integrity in the structurally intact peri-infarct region following stroke, with the potential to predict recovery. The objective of our study was to measure NAA in a longitudinal MR spectroscopy study in stroke patients, and to correlate these findings with functional outcome. Methods: Six patients (age 53±10 y) with a non-lacunar ischemic stroke in the left middle cerebral artery territory underwent MR spectroscopy on a 3.0 T MRI scanner. Patients were scanned at 3 and 15 weeks after stroke onset. Proton spectra were acquired from the structurally intact peri-infarct thalamus, the contralesional thalamus, and the anterior cingulate cortex (ACC) using a point resolved spectroscopy sequence with an echo time of 30 ms. NAA concentrations were calculated with LCModel. Clinical assessment included the Fugl-Meyer (FM) scale for the motor performance of the right arm and the NIHSS. Seven healthy controls (age 53±7 y) were also recruited. Results: At baseline, NAA was significantly lower in the patients in the structurally intact ipsilesional thalamus (9.0±2.1 vs 11.3±1.2, p=0.030), but not in the other 2 voxels. Baseline NAA was also significantly lower in the ipsilesional thalamus than in the ACC (9.0±2.1 vs 12.7±1.2, p=0.016) in the patients, but not in the controls. NAA decreased significantly between the 2 visits (9.0±2.1 vs 7.2±1.7, p=0.021) in the patients in the ipsilesional thalamus, but not in the other 2 voxels. The patients demonstrated significant clinical improvement during the course of follow up (median 15-point gain on the FM scale, p=0.042; and a 7-point decline on the NIHSS, p=0.026). NAA in the ipsilateral thalamus at baseline significantly correlated with the final FM (r s =0.81, p=0.025) and NIHSS scores (r s =-0.84, p=0.018). Conclusions: Stroke disturbs neuronal integrity in the structurally intact peri-infarct tissue. Despite clinical improvement, neural damage in the peri-infarct area appears to progress during the first 3-4 months following a non-lacunar ischemic stroke. This decreased neuronal integrity is associated with impaired recovery and may therefore represent a therapeutic target. Peri-infarct NAA is a potential biomarker not only for the prediction of recovery, but also for the monitoring of therapeutic interventions.

Background: The glutamate model of schizophrenia proposes that altered glutamatergic neurotransmission is fundamental to the development of the disorder. In addition, its potential to mediate neurotoxicity raises the possibility that glutamate dysfunction could underlie neuroanatomic changes in schizophrenia. Here we determine whether changes in brain glutamate are present in subjects at ultra high risk of developing psychosis and whether these changes are related to reductions in cortical gray matter volume.Methods: Twenty-seven individuals with an at-risk mental state and a group of 27 healthy volunteers underwent proton magnetic resonance spectroscopy and volumetric proton magnetic resonance imaging using a 3-Tesla scanner. Glutamate and glutamine levels were measured in anterior cingulate, left hippocampus, and left thalamus. These measures were then related to cortical gray matter volume.Results: At-risk mental state (ARMS) subjects had significantly lower levels of glutamate than control subjects in the thalamus (p Conclusions: This study provides the first evidence that brain glutamate function is perturbed in people with prodromal signs of schizophrenia and that glutamatergic dysfunction is associated with a reduction in gray matter volume in brain regions thought to be critical to the pathogenesis of the disorder. These findings support the hypothesis that drugs affecting the glutamate system may be of benefit in the early stages of psychotic illness.

PURPOSE: To implement and validate methods for producing calculated coronal T2 maps with complete coverage of the hippocampus and the rest of the brain. METHODS: T2 relaxation times were estimated on three occasions for 12 quality assessment test objects with the use of fast spin-echo (FSE) and conventional spin-echo (CSE) sequences. Hippocampal T2 relaxation times were measured in 15 healthy subjects with FSE and CSE sequences. Ten of these subjects were scanned twice with CSE imaging. Twenty-two patients with temporal lobe epilepsy, in whom hippocampal T2 relaxation times were previously estimated by means of a multiecho sequence, were studied with CSE. RESULTS: CSE data were more reliable than FSE data. Reliability of hippocampal T2 measures on repeated acquisitions was superior for the CSE sequence with echo time 30,120 than for the 30,80 sequence (test-retest reliability, 4.0%; interrater reliability, 4.6%). CSE images were suitable for qualitative reporting, so additional T2-weighted sequences were not required. There was good correlation between these hippocampal T2 data and values obtained on a previously validated multiecho technique, with reliable identification of hippocampal sclerosis. CONCLUSION: T2 mapping with CSE 30/120 sequences may be readily applied, produces reliable T2 values in contiguous 5-mm sections, and may be useful in the assessment of the hippocampus and other cerebral structures.

In certain situations in magnetic resonance imaging the digital resolution in the frequency encode direction may be compromised by hardware limits on data digitization rates. We demonstrate a method of overcoming this restriction, without hardware modifications, by interleaving data from several acquisitions to produce a higher resolution composite data set. © 1992 Academic Press, Inc.

Magnetization transfer (MT) techniques may be applied to magnetic resonance imaging (MRI) to evaluate the inherent relaxation properties of heterogeneous tissues. In addition to providing a unique contrast mechanism for the purpose of qualitative imaging, the MT effect may be quantified by various means to provide useful data that relate either to the pathological or associated clinical features of multiple sclerosis (MS) and other neurological disorders. The variable and relatively unpredictable course of neurological disorders such as MS often necessitates the study of large patient cohorts in multiple MRI centers to define either the natural history of the disease or its modification by potential therapies. For multicenter studies, precision (reproducibility, or lack of random error) and accuracy (closeness to the truth, or lack of systematic error) are important requirements for the acquisition of standardized and comparable data. For serial studies, quality assurance is important to determine pathological change from fluctuation in scanner performance. This review addresses how MT imaging techniques may be utilized to provide standardized and clinically relevant measures.

MR magnetization transfer ratio was measured in both hippocampi of three patients with temporal lobe epilepsy, and in two control subjects. The magnetization transfer ratio in each section was significantly lower on the affected side than on the contralateral side and in control subjects. Magnetization transfer ratio measurements are relatively fast and precise, this preliminary study shows that they may provide useful presurgical information.

BACKGROUND AND PURPOSE: The purpose of our study was to investigate the effect of section thickness on MR detection of brain lesion volume and measurement precision in patients with multiple sclerosis (MS). METHODS: Eight subjects with known MS were studied on a 1.5-T MR system. We used a 3D fast fluid-attenuated inversion-recovery sequence to obtain contiguous axial brain images at section thicknesses of 5 mm, 3 mm, and 1 mm. Two sets of images were acquired at each section thickness during two sessions, between which the patient was removed from the scanner. Lesion volumes were measured at each section thickness using a semiautomated local thresholding technique. RESULTS: We found that progressive reduction in section thickness led to detection of smaller lesions, resulting in a significant (8%) increase in lesion volume on MR images as section thickness was reduced from 5 mm to 3 mm. However, despite a further increase in lesion detection at a section thickness of 1 mm, this did not result in an increase in total lesion volume. This finding indicates that the relationship between section thickness and lesion volume on MR images is not linear. Scan-rescan reproducibility was improved by reducing section thickness, at the cost of increased analysis time. CONCLUSION: This study shows that acquisition of very thin sections increases the sensitivity and precision of MS lesion measurement. Serial studies assessing lesion changes over time are needed to define the impact of this increase on sample size requirements for MS treatment trials.