Convergent and discriminant validity of the ImPACT with traditional neuropsychological measures.

Neuropsychological assessment of cognitive sequelae secondary to sports concussion is limited by lengthy administration times and lack of readily available neuropsychologists. Brief computerized test batteries are now under development to address this, but the validity of these measures is not yet established. The validity of one such computerized test battery, the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), was administered to 93 healthy NCAA Division I athletes, aged 18-24, along with a battery of traditional, well-described neuropsychological tests. Convergent and discriminant validity between the ImPACT and traditional measures was investigated using multitrait-multimethod matrix (MTMM) analysis. As an example, the ImPACT Visual Motor Speed composite demonstrated reasonably good convergent validity secondary to moderate correlations with traditional measures of processing speed, but it demonstrated relatively poor discriminant validity as it significantly correlated with the Reaction Time composite score. MTMM results were variable across ImPACT composites and data for each are presented. The ImPACT composite's validity was further investigated using exploratory factor analysis (EFA). Six principal components were termed processing speed, visual memory, verbal memory, attention & working memory, and verbal fluency, based upon traditional test loadings, and a sixth loaded only on the ImPACT Reaction Time composite. EFA indicated content validity of moderate strength for the Visual Motor Speed and Visual Memory composites, but revealed problems with specificity for the other composites. Based upon the present findings, validity problems render the interpretability of the ImPACT composites somewhat questionable, and more research is necessary prior to using the ImPACT for assessment of clinical populations.

Risk of Concussion During Sports Versus Physical Education Among New Mexico Middle and High School Students.

OBJECTIVES: To measure the risk of concussion among New Mexico middle and high school students during both sports and physical education. METHODS: Athletic directors or athletic trainers in 147 schools were asked to report the number of concussions occurring during sports and physical education in the 2013 to 2014 school year. We calculated 1-year cumulative incidence rates. RESULTS: Of the 147 schools, 99 responded (67%). During the school year, 598 students were removed from athletics because of a concussion, a 1-year cumulative incidence of 3.5 per 100. The concussion rate during sports was 3.0: 3.5 for boys and 2.4 for girls (relative risk [RR] = 1.5; 95% confidence interval [CI] = 1.2, 1.7). An additional 335 students experienced concussions during physical education. Concussion rates during physical education were 60% higher than during sports (RR = 1.6; 95% CI = 1.4, 1.8). CONCLUSIONS: In our data, the risk of concussion was higher in physical education than in sports. This suggests that concussions should be tracked for a wide range of youth athletic activities, not just for sports. Monitoring cumulative incidence, in addition to other measures, may allow comparisons across schools and regions. More prevention efforts are needed.

Diminished auditory sensory gating during active auditory verbal hallucinations.

Auditory sensory gating, assessed in a paired-click paradigm, indicates the extent to which incoming stimuli are filtered, or "gated", in auditory cortex. Gating is typically computed as the ratio of the peak amplitude of the event related potential (ERP) to a second click (S2) divided by the peak amplitude of the ERP to a first click (S1). Higher gating ratios are purportedly indicative of incomplete suppression of S2 and considered to represent sensory processing dysfunction. In schizophrenia, hallucination severity is positively correlated with gating ratios, and it was hypothesized that a failure of sensory control processes early in auditory sensation (gating) may represent a larger system failure within the auditory data stream; resulting in auditory verbal hallucinations (AVH). EEG data were collected while patients (N=12) with treatment-resistant AVH pressed a button to indicate the beginning (AVH-on) and end (AVH-off) of each AVH during a paired click protocol. For each participant, separate gating ratios were computed for the P50, N100, and P200 components for each of the AVH-off and AVH-on states. AVH trait severity was assessed using the Psychotic Symptoms Rating Scales AVH Total score (PSYRATS). The results of a mixed model ANOVA revealed an overall effect for AVH state, such that gating ratios were significantly higher during the AVH-on state than during AVH-off for all three components. PSYRATS score was significantly and negatively correlated with N100 gating ratio only in the AVH-off state. These findings link onset of AVH with a failure of an empirically-defined auditory inhibition system, auditory sensory gating, and pave the way for a sensory gating model of AVH.

Magnetoencephalographic and functional MRI connectomics in schizophrenia via intra- and inter-network connectivity.

Examination of intrinsic functional connectivity using functional MRI (fMRI) has provided important findings regarding dysconnectivity in schizophrenia. Extending these results using a complementary neuroimaging modality, magnetoencephalography (MEG), we present the first direct comparison of functional connectivity between schizophrenia patients and controls, using these two modalities combined. We developed a novel MEG approach for estimation of networks using MEG that incorporates spatial independent component analysis (ICA) and pairwise correlations between independent component timecourses, to estimate intra- and intern-network connectivity. This analysis enables group-level inference and testing of between-group differences. Resting state MEG and fMRI data were acquired from a large sample of healthy controls (n=45) and schizophrenia patients (n=46). Group spatial ICA was performed on fMRI and MEG data to extract intrinsic fMRI and MEG networks and to compensate for signal leakage in MEG. Similar, but not identical spatial independent components were detected for MEG and fMRI. Analysis of functional network connectivity (FNC; i.e., pairwise correlations in network (ICA component) timecourses) revealed a differential between-modalities pattern, with greater connectivity among occipital networks in fMRI and among frontal networks in MEG. Most importantly, significant differences between controls and patients were observed in both modalities. MEG FNC results in particular indicated dysfunctional hyperconnectivity within frontal and temporal networks in patients, while in fMRI FNC was always greater for controls than for patients. This is the first study to apply group spatial ICA as an approach to leakage correction, and as such our results may be biased by spatial leakage effects. Results suggest that combining these two neuroimaging modalities reveals additional disease-relevant patterns of connectivity that were not detectable with fMRI or MEG alone.

Functional MRI Evaluation of Multiple Neural Networks Underlying Auditory Verbal Hallucinations in Schizophrenia Spectrum Disorders.

Functional MRI studies have identified a distributed set of brain activations to be associated with auditory verbal hallucinations (AVH). However, very little is known about how activated brain regions may be linked together into AVH-generating networks. Fifteen volunteers with schizophrenia or schizoaffective disorder pressed buttons to indicate onset and offset of AVH during fMRI scanning. When a general linear model was used to compare blood oxygenation level dependence signals during periods in which subjects indicated that they were versus were not experiencing AVH ("AVH-on" versus "AVH-off"), it revealed AVH-related activity in bilateral inferior frontal and superior temporal regions; the right middle temporal gyrus; and the left insula, supramarginal gyrus, inferior parietal lobule, and extranuclear white matter. In an effort to identify AVH-related networks, the raw data were also processed using independent component analyses (ICAs). Four ICA components were spatially consistent with an a priori network framework based upon published meta-analyses of imaging correlates of AVH. Of these four components, only a network involving bilateral auditory cortices and posterior receptive language areas was significantly and positively correlated to the pattern of AVH-on versus AVH-off. The ICA also identified two additional networks (occipital-temporal and medial prefrontal), not fully matching the meta-analysis framework, but nevertheless containing nodes reported as active in some studies of AVH. Both networks showed significant AVH-related profiles, but both were most active during AVH-off periods. Overall, the data suggest that AVH generation requires specific and selective activation of auditory cortical and posterior language regions, perhaps coupled to a release of indirect influence by occipital and medial frontal structures.

Associations of White Matter Microstructure with Clinical and Demographic Characteristics in Heavy Drinkers.

Damage to the brain's white matter is a signature injury of alcohol use disorders (AUDs), yet understanding of risks associated with clinical and demographic characteristics is incomplete. This study investigated alcohol problem severity, recent drinking behavior, and demographic factors in relation to white matter microstructure in heavy drinkers. Magnetic resonance imaging (MRI) scans, including diffusion tensor imaging (DTI), were collected from 324 participants (mean age = 30.9 ± 9.1 years; 30% female) who reported five or more heavy drinking episodes in the past 30 days. Drinking history and alcohol problem severity were assessed. A common white matter factor was created from fractional anisotropy (FA) values of five white matter tracts: body of corpus callosum, fornix, external capsule, superior longitudinal fasciculus, and cingulate gyrus. Previous research has implicated these tracts in heavy drinking. Structural equation modeling (SEM) analyses tested the hypothesis that, after controlling for duration of alcohol exposure, clinical and behavioral measures of alcohol use severity would be associated with lower white matter factor scores. Potential interactions with smoking status, gender, age, treatment-seeking status, and depression or anxiety symptoms also were tested. Controlling for number of years drinking, greater alcohol problem severity and recent drinking frequency were significantly associated with lower white matter factor scores. The effect of drinking frequency differed significantly for men and women, such that higher drinking frequency was linked to lower white matter factor scores in women but not in men. In conclusion, alcohol problem severity was a significant predictor of lower white matter FA in heavy drinkers, after controlling for duration of alcohol exposure. In addition, more frequent drinking contributed to lower FA in women but not men, suggesting gender-specific vulnerability to alcohol neurotoxicity.

Reliable activation to novel stimuli predicts higher fluid intelligence.

The ability to reliably respond to stimuli could be an important biological determinant of differences in fluid intelligence (Gf). However, most electrophysiological studies of Gf employ event-related potential (ERP) measures that average brain activity over trials, and hence have limited power to quantify neural variability. Time-frequency analyses can capture cross-trial variation in the phase of neural activity, and thus can help address the importance of neural reliability to differences in Gf. This study recruited a community sample of healthy adults and measured inter-trial phase clustering (ITPC), total spectral power, and ERP amplitudes elicited by Repeated and Novel non-target stimuli during two visual oddball tasks. Condition effects, relations among the EEG measures, and relations with Gf were assessed. Early visual responses to Repeated stimuli elicited higher ITPC, yet only ITPC elicited by Novel stimuli was associated with Gf. Analyses of spectral power further highlighted the contribution of phase consistency to the findings. The link between Gf and reliable responding to changing inputs suggests an important role for flexible resource allocation in fluid intellectual skills.

The effect of days since last concussion and number of concussions on cognitive functioning in Division I athletes.

OBJECTIVE: Cognitive recovery from sports concussion may be incomplete after resolution of other symptoms. It was hypothesized that independent effects of the number of days since last concussion (Days) and total number of concussions (Number) would predict poorer cognitive functioning. METHODS AND PROCEDURES: Cognition was assessed in an NCAA Division I student-athlete population (n = 87) using the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery. In a MANOVA, the five ImPACT Composite scores were dependent variables, with Group (Concussion, Unaffected) as the independent variable and prior number of concussions (Number) and days since last concussion (Days; 68-2495 days) entered as covariates. OUTCOMES AND RESULTS: The hypothesis that Days and Number would each independently affect cognitive functioning (as assessed by ImPACT Composite scores) was only partly supported. A significant, multivariate, main effect of Days (p = 0.01) indicated that more Days predicted better cognitive functioning overall (p = 0.01). Univariate effects emerged such that more Days specifically predicted better visual memory (p = 0.004) and faster reaction times (p = 0.02). A trend toward a Group*Days*Number three-way interaction for reaction time emerged (p = 0.06), such that smaller Number and more Days each predicted slower reaction time. CONCLUSIONS: Cognitive recovery following sports concussion may take far longer than was previously thought, the aetiology of cognitive reductions may be very complex and the ImPACT appears to be sensitive to subtle changes in cognition across time.

1H-MRS glutamate level predicts auditory sensory gating in alcohol dependence: Preliminary results.

BACKGROUND: Impairment in auditory sensory gating (ASG) has been documented in alcohol dependence [1]. Likewise, it has been shown that ASG becomes abnormal during alcohol administration in otherwise healthy individuals [2]. Patterns of gating abnormality associated with alcohol use are likely associated with an alcohol responsive neurochemical like glutamate (Glu), particularly since it is well-established that alcohol affects NMDA receptors and that glutamatergic functioning is abnormal in both acute alcohol use and in alcohol dependence [3]. Hence, a link between Glu metabolite levels and ASG was hypothesized. It was first hypothesized that Glu and ASG abnormality would be found in groups with alcohol dependence. A second hypothesis was that across groups, greater Glu would predict reduced ASG. METHODS: Groups were comprised of healthy, non-drinking controls (Controls, N = 4), individuals with current alcohol dependence (AUD-current, N = 6), and with alcohol dependence in remission for at least 1 year (AUD-remission, N = 6). Participants underwent a diagnostic assessment for alcohol consumption, MRI, 1H-MRS for in vivo assessment of Glu and other metabolites, and MEG scanning during a paired click protocol. ASG was computed as the ratio of the source strength of the 50 ms component in the event related field (ERF) to the second click in the pair divided by the source strength of the 50 ms component to the first click in the pair. RESULTS: Univariate MANOVAs controlling for age and gender revealed a significant effect for group on Glu and ASG, such that ASG ratios were significantly elevated, implying weakened gating. Glu concentration was reduced in AUD-current relative to the other two groups. Further analysis revealed that when additionally controlling for the group effect, reduced Glu predicted increasing impairment in ASG. CONCLUSIONS: The overall results were consistent with the hypothesis that differences in Glu metabolite levels associated with alcohol dependence result in impaired ASG.

Studying hallucinations within the NIMH RDoC framework.

We explore how hallucinations might be studied within the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) framework, which asks investigators to step back from diagnoses based on symptoms and focus on basic dimensions of functioning. We start with a description of the objectives of the RDoC project and its domains and constructs. Because the RDoC initiative asks investigators to study phenomena across the wellness spectrum and different diagnoses, we address whether hallucinations experienced in nonclinical populations are the same as those experienced by people with psychotic diagnoses, and whether hallucinations studied in one clinical group can inform our understanding of the same phenomenon in another. We then discuss the phenomenology of hallucinations and how different RDoC domains might be relevant to their study. We end with a discussion of various challenges and potential next steps to advance the application of the RDoC approach to this area of research.

Electroconvulsive therapy response in major depressive disorder: a pilot functional network connectivity resting state FMRI investigation.

Major depressive disorder (MDD) is associated with increased functional connectivity in specific neural networks. Electroconvulsive therapy (ECT), the gold-standard treatment for acute, treatment-resistant MDD, but temporal dependencies between networks associated with ECT response have yet to be investigated. In the present longitudinal, case-control investigation, we used independent component analysis to identify distinct networks of brain regions with temporally coherent hemodynamic signal change and functional network connectivity (FNC) to assess component time course correlations across these networks. MDD subjects completed imaging and clinical assessments immediately prior to the ECT series and a minimum of 5 days after the last ECT treatment. We focused our analysis on four networks affected in MDD: the subcallosal cingulate gyrus, default mode, dorsal lateral prefrontal cortex, and dorsal medial prefrontal cortex (DMPFC). In an older sample of ECT subjects (n = 12) with MDD, remission associated with the ECT series reverses the relationship from negative to positive between the posterior default mode (p_DM) and two other networks: the DMPFC and left dorsal lateral prefrontal cortex (l_DLPFC). Relative to demographically healthy subjects (n = 12), the FNC between the p_DM areas and the DMPFC normalizes with ECT response. The FNC changes following treatment did not correlate with symptom improvement; however, a direct comparison between ECT remitters and non-remitters showed the pattern of increased FNC between the p_DM and l_DLPFC following ECT to be specific to those who responded to the treatment. The differences between ECT remitters and non-remitters suggest that this increased FNC between p_DM areas and the left dorsolateral prefrontal cortex is a neural correlate and potential biomarker of recovery from a depressed episode.

Neurometabolite concentration and clinical features of chronic alcohol use: a proton magnetic resonance spectroscopy study.

Chronic, heavy alcohol consumption may affect the concentration of neurometabolites assessed with proton magnetic resonance spectroscopy ((1)H-MRS). We investigated the largest sample reported to date (N=213) with the primary goal of determining how specific clinical features impact neurometabolite concentrations in an anterior cingulate gray matter voxel. This community-dwelling sample included both treatment-seeking and non-treatment-seeking individuals. A healthy control group (N=66) was matched for age and education. In multivariate analyses predicting neurometabolite concentrations, the heavy drinking group had greater concentrations overall. An age by group interaction was noted, as group difference across neurometabolites increased with age. More years drinking, but not more drinks per drinking day (DPDD), predicted greater concentrations of choline-containing compounds (Cho), creatine-phosphocreatine (Cre), glutamate-glutamine (Glx), and N-acetyl-aspartate (NAA). The effects of other clinical variables (depression, cigarette smoking, marijuana use) were negligible. After controlling for DPDD and years drinking, treatment-seeking status had no impact on neurometabolites. In the very oldest portion of the sample (mean age=50), however, a negative relationship was seen between NAA and years drinking. These results suggest that the nature of neurometabolite abnormalities in chronic heavy drinkers may vary as a function of duration of abuse.

White matter volume in alcohol use disorders: a meta-analysis.

Atrophy of brain white matter (WM) often is considered a signature injury of alcohol use disorders (AUDs). However, investigations into AUD-related changes in WM volume have yielded complex findings that are difficult to synthesize in a narrative review. The objective of this study was to obtain an averaged effect size (ES) for WM volume reduction associated with AUD diagnosis and to test potential moderators of ES. Study inclusion criteria were: (1) English language; (2) peer reviewed; (3) published before December 2011; (4) use of magnetic resonance imaging (MRI); (5) human participants; (6) inclusion of AUD group; (7) inclusion of non-AUD comparison group; and (8) reporting or testing of total or cerebral WM volume. Moderators included study design, MRI methodology and AUD characteristics. Nineteen studies with a total of 1302 participants (70% male) were included, and calculated ESs were confirmed by the corresponding author for 12 studies. The magnitude of the averaged ES adjusted for small sample bias (Hedges' g) for WM reduction in AUDs was 0.304 (standard error = 0.134, range = -0.57-1.21). Hierarchical linear modeling indicated that the overall ES differed significantly from 0, t(18) = 2.257, P = 0.037, and that the distribution of the 19 ESs showed significant heterogeneity beyond sampling error, χ(2) (18) = 52.400, P < 0.001. Treatment-seeking status and length of abstinence were significant moderators of ES distribution. These results are suggestive of WM recovery with sustained abstinence and point to the need for further investigation of factors related to treatment-seeking status.

The impact of copy number deletions on general cognitive ability and ventricle size in patients with schizophrenia and healthy control subjects.

BACKGROUND: General cognitive ability is usually lower in individuals with schizophrenia, partly due to genetic influences. However, the specific genetic features related to general cognitive ability are poorly understood. Individual variation in a specific type of mutation, uncommon genetic deletions, has recently been linked with both general cognitive ability and risk for schizophrenia. METHODS: We derived measures of the aggregate number of "uncommon" deletions (i.e., those occurring in 3% or less of our combined samples) and the total number of base pairs affected by these deletions in individuals with schizophrenia (n = 79) and healthy control subjects (n = 110) and related each measure to the first principal component of a large battery of cognitive tests, a common technique for characterizing general cognitive ability. These two measures of mutation load were also evaluated for relationships with total brain gray matter, white matter, and lateral ventricle volume. RESULTS: The groups did not differ on genetic variables. Multivariate general linear models revealed a group (control subjects vs. patients) × uncommon deletion number interaction, such that the latter variable was associated with lower general cognitive ability and larger ventricles in patients but not control subjects. CONCLUSIONS: These data suggest that aggregate uncommon deletion burden moderates central features of the schizophrenia phenotype.

Diffusion tensor imaging of white matter networks in individuals with current and remitted alcohol use disorders and comorbid conditions.

Individuals with alcohol use disorders show white matter abnormality relative to normal samples, but differences in white matter profiles have not yet been investigated as a function of abstinence. Individuals with current alcohol use disorders (AUD-C; n = 10), individuals with alcohol use disorders in remission for at least 1 year (AUD-R; n = 9), and healthy control participants (HC; n = 15) matched to alcohol groups on age and smoking status underwent MRI. Diffusion tensor imaging (DTI) data were analyzed using tract-based spatial statistics (TBSS). Compared with HC, AUD-C showed reduced axial diffusivity in bilateral frontal and temporal white matter. In AUD-R, lower fractional anisotropy relative to HC was widespread in bilateral parietal regions. A combined AUD-C and AUD-R group had decreased fractional anisotropy primarily in the fornix and thalamus. In conclusion, AUD-R manifested damage in parietal regions integral to processing of visuospatial information and self-awareness whereas AUD-C showed abnormal diffusivity in fronto-temporal regions that regulate impulsivity, attention, and memory. As a combined group, AUD individuals exhibited abnormality in subcortical areas associated with sensory processing and memory. White matter differences in individuals with AUD may be attributable to premorbid vulnerability or persisting effects of alcohol abuse, but the pattern of abnormality across groups suggests that these abnormalities may be secondary to alcohol use.

Bilateral hippocampal dysfunction in schizophrenia.

The hippocampus has long been known to be important for memory, with the right hippocampus particularly implicated in nonverbal/visuo-spatial memory and the left in verbal/narrative or episodic memory. Despite this hypothesized lateralized functional difference, there has not been a single task that has been shown to activate both the right and left hippocampi differentially, dissociating the two, using neuroimaging. The transverse patterning (TP) task is a strong candidate for this purpose, as it has been shown in human and nonhuman animal studies to theoretically and empirically depend on the hippocampus. In TP, participants choose between stimuli presented in pairs, with the correct choice being a function of the specific pairing. In this project, TP was used to assess lateralized hippocampal function by varying its dependence on verbal material, with the goal of dissociating the two hippocampi. Magnetoencephalographic (MEG) data were collected while controls performed verbal and nonverbal versions of TP in order to verify and validate lateralized activation within the hippocampi. Schizophrenia patients were evaluated to determine whether they exhibited a lateralized hippocampal deficit. As hypothesized, patients' mean level of behavioral performance was poorer than controls' on both verbal and nonverbal TP. In contrast, patients had no decrement in performance on a verbal and nonverbal non-hippocampal-dependent matched control task. Also, controls but not patients showed more right hippocampal activation during nonverbal TP and more left hippocampal activation during verbal TP. These data demonstrate the capacity to assess lateralized hippocampal function and suggest a bilateral hippocampal behavioral and activation deficit in schizophrenia.

Rare copy number deletions predict individual variation in human brain metabolite concentrations in individuals with alcohol use disorders.

BACKGROUND: Although variations in neurometabolite concentrations occur in diverse neuropsychiatric and neurodegenerative disorders, little is known about the nature of underlying genetic influences. The current study investigated the importance of a specific type of genetic mutation, copy number variation (CNV), for neurometabolite concentrations in a bilateral anterior cingulate voxel. METHODS: These neurometabolic signals were quantified using proton magnetic resonance spectroscopy ((1)H-MRS): N-acetylaspartate (NAA), creatine-phosphocreatine (Cre), glutamate/glutamine (Glx), myoinositol (mI), and phosphorylcholine-glycerol phosphorylcholine (Cho). Genetic data were collected using the Illumina 1MDuoBeadChip Array from a sample adults with alcohol use disorders (n = 146). RESULTS: The number of base pairs lost through rare copy number deletions (occurring in less than 5% of our sample) predicted lower NAA, Cre, mI, and Glx. More total rare deletions also predicted lower NAA, Cre, and Glx. Principal components analyses of the five neurometabolites identified two correlated components, the first comprised of NAA, Glx, and Cre, and the second comprised of Cho, mI, and to a lesser extent, Cre. The number and length of rare deletions were correlated with the first component, capturing approximately 10% of phenotypic variance, but not the second component. CONCLUSIONS: These results suggest that mutation load affects neurometabolite concentrations, potentially increasing risk for neuropsychiatric disorders. The greater effect of CVNs on NAA, Glx, and Cre may reflect a greater sensitivity to the effects of mutations (i.e., reduced canalization) for neurometabolites related to metabolic activity and cellular energetics, due to extensive recent selection pressure on these phenotypes in the human lineage.

A baseline for the multivariate comparison of resting-state networks.

As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12-71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.