Synchronized low-frequency BOLD fluctuations are observed in dissociable large-scale, distributed networks with functional specialization. Two such networks, referred to as the task-positive network (TPN) and the task-negative network (TNN) because they tend to be active or inactive during cognitively demanding tasks, show reproducible anticorrelation of resting BOLD fluctuations after removal of the global brain signal. Because global signal regression mandates that anticorrelated regions to a given seed region must exist, it is unclear whether such anticorrelations are an artifact of global regression or an intrinsic property of neural activity. In this study, we demonstrate from simulated data that spurious anticorrelations are introduced during global regression for any two networks as a linear function of their size. Using actual resting state data, we also show that both the TPN and TNN become anticorrelated with the orbits when soft tissues are included in the global regression algorithm. Finally, we propose a technique using phase-shifted soft tissue regression (PSTCor) that allows improved correction of global physiological artifacts without global regression that shows improved anatomic specificity to global regression but does not show significant network anticorrelations. These results imply that observed anticorrelations between TNN and TPN may be largely or entirely artifactual in the resting state. These results also imply that differences in network anticorrelations attributed to pathophysiological or behavioral states may be due to differences in network size or recruitment rather than actual anticorrelations.

The presence of morphometric abnormalities of the lateral ventricles, which can reflect focal or diffuse atrophic changes of nearby brain structures, is not well characterized in methamphetamine dependence. The current study was aimed to examine the size and shape alterations of the lateral ventricles in methamphetamine-dependent subjects.

The prevalence of comorbid cannabis and tobacco use has been increasing among adolescents and adults and has been shown to be associated with a range of changes or deficits in physical, psychological and behavioral outcomes. Moreover, comorbid use has been shown to have a differential effect on the structure and function of the brain, especially as it relates to the reward circuitry and learning and memory. This interaction might be mediated by the involvement of the endocannabinoid system and alterations in dopamine signaling in regions associated with reward and cognitive functioning. While current findings demonstrate a differential effect of comorbid use on neurobiological and behavioral correlates compared with single substance use, additional studies are needed controlling for potential psychiatric comorbidities, age of onset of use and use of other substances. Understanding the neurobiological mechanisms associated with comorbid cannabis and tobacco use will be important in developing successful treatment outcomes in the future.

To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes.

The aim of the current study was to evaluate the relationship between quetiapine's effect on the improvement of mood symptoms in bipolar patients and brain metabolite level changes as measured by proton magnetic resonance spectroscopy ((1)H-MRS). Rapid cycling bipolar patients in the manic state were recruited and treated with quetiapine for 12 weeks. Clinical assessment was performed using the Young Mania Rating Scale (YMRS), the 17-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Severity scale (CGI-S) at baseline and weekly intervals during the 12-week period. In order to evaluate metabolite level changes over time, (1)H-MRS scans were acquired at baseline and week 12. There were significant reductions in YMRS scores (by 43.0%), HDRS scores (by 27.5%) and CGI-S score (by 44.6%) over the 12 week-period. Lactate levels significantly decreased over the 12-week study period (22.4%). This change in lactate levels was more prominent in quetiapine responders than in non-responders. Additionally, there was a positive correlation between changes in lactate levels and those in YMRS scores (r=0.52, p=0.003). Our findings suggest that quetiapine's antimanic and antidepressant efficacy in patients with rapid cycling bipolar disorder may potentially be related to decreased lactate levels in frontal regions of the brain.

To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.

Adolescent marijuana (MJ) use has been associated with alterations in brain structure and function as well as behavior. Examination of neurochemical correlates such as GABA (gamma-aminobutyric acid) and Glx (glutamate + glutamine) in MJ users remains limited. Impulsivity, identified as a risk factor and consequence of MJ use, has been associated with GABA and Glx levels in healthy and clinical populations. However, this relationship has not been investigated in MJ users. In this study, we examined levels of GABA and Glx in the anterior cingulate cortex (ACC) and its relationship with impulsive behavior in MJ-using adolescents and healthy controls.

Adolescent-onset exposure to highly addictive substances such as opiates may induce far-reaching deleterious effects on later mental and physical health. However, little is known about the neurodevelopmental basis for adolescent-onset opiate dependence. Here we examined whether having an abnormally large cavum septum pellucidum (CSP), a putative marker of limbic structural maldevelopment, is associated with opiate dependence particularly beginning in adolescence.

Methamphetamine (MA) use rates in the United States (US) have consistently demonstrated geographical variation and have been higher in the West and Midwest. This uneven pattern of use could be explained by regional differences in MA manufacturing and distribution, but may also result from differences in altitude. The hypobaric hypoxia found at high altitude alters neurotransmitter synthesis in the brain, which may contribute to MA use. The present study investigated the relationship between mean altitude and MA use rate in the 48 contiguous US states and the District of Columbia.

Internet use and on-line game play stimulate corticostriatal-limbic circuitry in both healthy subjects and subjects with Internet gaming disorder (IGD). We hypothesized that increased fractional anisotropy (FA) with decreased radial diffusivity (RD) would be observed in IGD subjects, compared with healthy control subjects, and that these white matter indices would be associated with clinical variables including duration of illness and executive function. We screened 181 male patients in order to recruit a large number (n = 58) of IGD subjects without psychiatric co-morbidity as well as 26 male healthy comparison subjects. Multiple diffusion-weighted images were acquired using a 3.0 Tesla magnetic resonance imaging scanner. Tract-based spatial statistics was applied to compare group differences in diffusion tensor imaging (DTI) metrics between IGD and healthy comparison subjects. IGD subjects had increased FA values within forceps minor, right anterior thalamic radiation, right corticospinal tract, right inferior longitudinal fasciculus, right cingulum to hippocampus and right inferior fronto-occipital fasciculus (IFOF) as well as parallel decreases in RD value within forceps minor, right anterior thalamic radiation and IFOF relative to healthy control subjects. In addition, the duration of illness in IGD subjects was positively correlated with the FA values (integrity of white matter fibers) and negatively correlated with RD scores (diffusivity of axonal density) of whole brain white matter. In IGD subjects without psychiatric co-morbidity, our DTI results suggest that increased myelination (increased FA and decreased RD values) in right-sided frontal fiber tracts may be the result of extended game play.

Observational neuroimaging studies with children and adolescents may identify neurological anomalies and other clinically relevant findings. Planning for the management of this information involves ethical considerations that may influence informed consent, confidentiality, and communication with participants about assessment results. Biomedical ethics principles include respect for autonomy, beneficence, non-maleficence, and justice. Each project presents unique challenges. The Adolescent Brain and Cognitive Development study (ABCD) collaborators have systematically developed recommendations with written guidelines for identifying and responding to potential risks that adhere to biomedical ethics principles. To illustrate, we will review the ABCD approach to three areas: (1) hazardous substance use; (2) neurological anomalies; and (3) imminent potential for self-harm or harm to others. Each ABCD site is responsible for implementing procedures consistent with these guidelines in accordance with their Institutional Review Board approved protocols, state regulations, and local resources. To assure that each site has related plans and resources in place, site emergency procedures manuals have been developed, documented and reviewed for adherence to ABCD guidelines. This article will describe the principles and process used to develop these ABCD bioethics and medical oversight guidelines, the concerns and options considered, and the resulting approaches advised to sites.

Background and aims Given the similarities in clinical symptoms, Internet gaming disorder (IGD) is thought to be diagnostically similar to Internet-based gambling disorder (ibGD). However, cognitive enhancement and educational use of Internet gaming suggest that the two disorders derive from different neurobiological mechanisms. The goal of this study was to compare subjects with ibGD to those with IGD. Methods Fifteen patients with IGD, 14 patients with ibGD, and 15 healthy control subjects were included in this study. Resting-state functional magnetic resonance imaging data for all participants were acquired using a 3.0 Tesla MRI scanner (Philips, Eindhoven, The Netherlands). Seed-based analyses, the three brain networks of default mode, cognitive control, and reward circuitry, were performed. Results Both IGD and ibGD groups demonstrated decreased functional connectivity (FC) within the default-mode network (DMN) (family-wise error p < .001) compared with healthy control subjects. However, the IGD group demonstrated increased FC within the cognitive network compared with both the ibGD (p < .01) and healthy control groups (p < .01). In contrast, the ibGD group demonstrated increased FC within the reward circuitry compared with both IGD (p < .01) and healthy control subjects (p < .01). Discussion and conclusions The IGD and ibGD groups shared the characteristic of decreased FC in the DMN. However, the IGD group demonstrated increased FC within the cognitive network compared with both ibGD and healthy comparison groups.

Metabolite-specific, scalar spin-spin coupling constant (J)-editing 1H MRS methods have become gold-standard for measuring brain γ-amino butyric acid (GABA) levels in human brain. Localized, two-dimensional (2D) 1H MRS technology offers an attractive alternative as it significantly alleviates the problem of severe metabolite signal overlap associated with standard 1D MRS and retains spectroscopic information for all MRS-detectable species. However, for metabolites found at low concentration, a direct, in vivo, comprehensive methods comparison is challenging and has not been reported to date. Here, we document an assessment of comparability between 2D 1H MRS and J-editing methods for measuring GABA in human brain. This clinical study is unique in that it involved chronic administration a GABA-amino transferase (AT) inhibitor (CPP-115), which induces substantial increases in brain GABA concentration, with normalization after washout. We report a qualitative and quantitative comparison between these two measurement techniques. In general, GABA concentration changes detected using J-editing were closely mirrored by the 2D 1H MRS time courses. The data presented are particularly encouraging considering recent 2D 1H MRS methodological advances are continuing to improve temporal resolution and spatial coverage for achieving whole-brain, multi-metabolite mapping.

Introduction. This paper focuses on the application of Magnetic Resonance Spectroscopy (MRS) to the study of Major Depressive Disorder (MDD) in children and adolescents. Method. A literature search using the National Institutes of Health's PubMed database was conducted to identify indexed peer-reviewed MRS studies in pediatric patients with MDD. Results. The literature search yielded 18 articles reporting original MRS data in pediatric MDD. Neurochemical alterations in Choline, Glutamate, and N-Acetyl Aspartate are associated with pediatric MDD, suggesting pathophysiologic continuity with adult MDD. Conclusions. The MRS literature in pediatric MDD is modest but growing. In studies that are methodologically comparable, the results have been consistent. Because it offers a noninvasive and repeatable measurement of relevant in vivo brain chemistry, MRS has the potential to provide insights into the pathophysiology of MDD as well as the mediators and moderators of treatment response.

Magnetic Resonance Imaging (MRI) has high spatial resolution, but low sensitivity for visualization of molecular targets in the central nervous system (CNS). Our goal was to develop a new MRI method with the potential for non-invasive molecular brain imaging. We herein introduce new bio-nanotechnology approaches for designing CNS contrast media based on the ubiquitous clathrin cell protein.

The purpose of this study was to develop a functional MRI method to examine overt speech in stroke patients with aphasia. An fMRI block design for overt picture naming was utilized which took advantage of the hemodynamic response delay where increased blood flow remains for 4-8 s after the task [(Friston, K.J., Jezzard, P., Turner, R., 1994. Analysis of functional MRI time-series. Hum. Brain Mapp. 1, 153-171)]. This allowed task-related information to be obtained after the task, minimizing motion artifact from overt speech (Eden, G.F., Joseph, J., Brown, H.E., Brown, C.P., Zeffiro, T.A., 1999. Utilizing hemodynamic delay and dispersion to detect fMRI signal change without auditory interference: the behavior interleaved gradients technique. Magn. Reson. Med. 41, 13-20; Birn, RM., Bandettini, P.A., Cox, R.W., Shaker, R., 1999. Event-related fMRI of tasks involving brief motion. Hum. Brain Mapp. 7, 106-114; Birn, R.M., Cox, R.W., Bandettini, P.A., 2004. Experimental designs and processing strategies for fMRI studies involving overt verbal responses. NeuroImage 23, 1046-1058). Five chronic aphasia patients participated (4 mild-moderate and 1 severe nonfluent/global). The four mild-moderate patients who correctly named 88-100% of the pictures during fMRI, had a greater number of suprathreshold voxels in L supplementary motor area (SMA) than R SMA (P < 0.07). Three of these four mild-moderate patients showed activation in R BA 45 and/or 44; along with L temporal and/or parietal regions. The severe patient, who named no pictures, activated almost twice as many voxels in R SMA than L SMA. He also showed activation in R BA 44, but had remarkably extensive L and R temporal activation. His poor naming and widespread temporal activation may reflect poor modulation of the bi-hemispheric neural network for naming. Results indicate that this fMRI block design utilizing hemodynamic response delay can be used to study overt naming in aphasia patients, including those with mild-moderate or severe aphasia. This method permitted verification that the patients were cooperating with the task during fMRI. It has application for future fMRI studies of overt speech in aphasia.

The adolescent brain may be susceptible to the influences of illicit drug use. While compensatory network reorganization is a unique developmental characteristic that may restore several brain disorders, its association with methamphetamine (MA) use-induced damage during adolescence is unclear.

The adolescent brain, with ongoing prefrontal maturation, may be more vulnerable to drug use-related neurotoxic changes as compared to the adult brain. We investigated whether the use of methamphetamine (MA), a highly addictive psychostimulant, during adolescence affect metabolic and cognitive functions of the anterior cingulate cortex (ACC). In adolescent MA users (n = 44) and healthy adolescents (n = 53), the levels of N-acetyl aspartate (NAA), a neuronal marker, were examined in the ACC using proton magnetic resonance spectroscopy. The Stroop color-word task was used to assess Stroop interference, which may reflect cognitive functions of behavior monitoring and response selection that are mediated by the ACC. Adolescent MA users had lower NAA levels in the ACC (t = -2.88, P = 0.005) and relatively higher interference scores (t = 2.03, P = 0.045) than healthy adolescents. Moreover, there were significant relationships between lower NAA levels in the ACC and worse interference scores in adolescent MA users (r = -0.61, P < 0.001). Interestingly, early onset of MA use, as compared to late onset, was related to both lower NAA levels in the ACC (t = -2.24, P = 0.03) as well as lower performance on interference measure of the Stroop color-word task (t = 2.25, P = 0.03). The current findings suggest that metabolic dysfunction in the ACC and its related cognitive impairment may play an important role in adolescent-onset addiction, particularly during early adolescence.

Creatine monohydrate is actively being researched for its antidepressant effects, yet little is known about the link between dietary creatine and depression risk. This study examines the association between dietary creatine and depression in U.S. adults, using data from the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES). Patient health questionnaire, dietary creatine intake and covariates were obtained on 22,692 NHANES participants ≥20 years of age. Depression prevalence was calculated within quartiles of dietary creatine intake. Adjusted logistic regression models were formulated to determine the relationship between dietary creatine intake and depression risk. Additional covariates included income to poverty ratio, race/ethnicity, sex, age, education level, body mass index, healthcare access, smoking status, physical activity, and antidepressant/anxiolytic medication use. Models were further stratified by sex, age group, and antidepressant/anxiolytic medication use. Depression prevalence was 10.23/100 persons (95% CI: 8.64-11.83) among NHANES participants in the lowest quartile of dietary creatine intake compared with 5.98/100 persons (95% CI: 4.97-6.98) among participants in the highest quartile (p < 0.001). An inverse association was measured between dietary creatine and depression (adjusted odds ratio (AOR) = 0.68, 95% CI: 0.52-0.88). Dietary creatine's negative association with depression was strongest in females (AOR = 0.62, 95% CI: 0.40-0.98), participants aged 20-39 years (AOR = 0.52, 95% CI: 0.34-0.79) and participants not taking antidepressant/anxiolytic medication (AOR = 0.58, 95% CI: 0.43-0.77). Study results indicate a significant negative relationship between dietary creatine and depression in a nationally representative adult cohort. Further research is warranted to investigate the role creatine plays in depression, particularly among women and across the lifespan.

Physical health in childhood is crucial for neurobiological as well as overall development, and can shape long-term outcomes into adulthood. The landmark, longitudinal Adolescent Brain Cognitive Development StudySM (ABCD study®), was designed to investigate brain development and health in almost 12,000 youth who were recruited when they were 9-10 years old and will be followed through adolescence and early adulthood. The overall goal of this paper is to provide descriptive analyses of physical health measures in the ABCD study at baseline, including but not limited to sleep, physical activity and sports involvement, and body mass index. Further this summary will describe how physical health measures collected from the ABCD cohort compare with current normative data and clinical guidelines. We propose this data set has the potential to facilitate clinical recommendations and inform national standards of physical health in this age group. This manuscript will also provide important information for ABCD users and help guide analyses investigating physical health including new avenues for health disparity research as it pertains to adolescent and young adult development.