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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.

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.

Background Hoasca (also called ayahuasca ) is a N , N -dimethyltryptamine (DMT) – containing psychedelic brew originally used for magico-religious purposes by Amerindian populations of the Amazon Basin. Recently, Brazilian syncretic churches have helped spread the ritual use of hoasca to Western societies. The aim of this study was to evaluate substance use, and neuropsychological and psychological functioning of regular hoasca users within a religious setting. Methods Assessment of socio-economic status, mood, personality traits, impulsiveness, drug use, quality of life, extrinsic and intrinsic religiosity, and neuropsychological function was performed on 30 volunteers from a U.S. branch of Uniao do Vegetal (UDV), a Brazilian religion which uses hoasca ritually. We also assessed 27 non-hoasca-using control subjects matched by socio-demographic profile and church attendance. Mann–Whitney U , chi-squared and Fisher tests were used to analyze differences between groups. Spearman's association and simple logistic regression tests were used to analyze the impact of frequency of hoasca use on dependent variables. Results Relative to the control group, the UDV group demonstrated lower scores for depression ( p = 0.043, r = .27) and confusion ( p = 0.032, r = .29) as assessed by the Profile of Mood States (POMS); higher scores on the instrument Big Five Inventory (BFI) for the personality traits agreeableness ( p = 0.028, r = .29) and openness ( p = 0.037, r = .28); higher scores on the quality life domain role limitations due to physical health as determined by the instrument Medical Outcomes Study Short Form-36 – SF-36 ( p = 0.035, r = .28); less recent use of alcohol ( p φ c = .57), greater past use of alcohol to intoxication ( p = 0.007, φ c = .36) and past use of cannabis ( p = 0.001, φ c = .45) as measured by the Addiction Severity Index (ASI), 5th edition; better score on a measure of memory vulnerability to proactive interference as measured by the California Verbal Learning Test – CVLT ( p = 0.040, r = .27). Lifetime use of hoasca was positively correlated with role limitations due to physical health ( p = 0.032, r s = .39) and negatively associated with lifetime heavy alcohol use ( p = 0.034, OR = 0.979). Conclusions The findings indicate that religious use of hoasca does not adversely affect neuropsychological functioning and may have positive effects on substance abuse and mood.

The developmental roots of individual variation in general cognitive ability (GCA) are the subject of intense scientific interest. One unique perspective is offered by developmental instability theory, which suggests that variation in GCA in part reflects the ability to buffer brain development from key environmental and genetic perturbations. Support for this approach comes mainly from assessment of fluctuating asymmetry, or deviations from symmetry of body features that are symmetric at the population level. In this study of healthy young adults (N = 244) we assessed fluctuating asymmetry (FA) of total cortical surface area (CSFA) from 33 regions using automated analysis. Overall CSFA was negatively related to GCA, consistent with meta-analytic results from body FA studies. A correlated vectors analysis indicated that the CSFA-cognition relationship varied systematically with a test's g loading. Further, FA of frontoparietal regions was a significant predictor of GCA, but FA non-frontoparietal regions was not, consistent with the Parieto-Frontal Integration Theory (P-FIT) model of intelligence. Frontoparietal FA was less than non-frontoparietal FA, i.e., consistent with the hypothesis that regions linked with GCA are better buffered from perturbation, perhaps a reflection of the importance of GCA for important life outcomes.

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.

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.

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.

Recent neuropsychological studies have distinguished deficits in verbal working memory, verbal memory, and confrontation naming from other neuropsychological domains as specifically related to the severity of auditory verbal hallucinations (AVH) in schizophrenia (Gisselgard et al., 2014; Siddi et al., 2017). To extend this research, it was hypothesized that AVH severity would be related only to measures within the language domain and the test battery was augmented with the [CTOPP2 and COWAT…define?] to more comprehensively define the language processing functions most predictive of AVH. A neuropsychological test battery was administered to a group of adult patients diagnosed with schizophrenia and schizoaffective disorder (N = 30), who continued to experience AVH despite clinical treatment. Multiple regression analyses demonstrated that poorer performance on measures of verbal working memory and verbal immediate memory significantly predicted greater AVH severity. Going beyond the prior studies, it was also shown that greater impairment of semantic fluency and lesser impairment in delayed general memory were also significant predictors of AVH. Intellectual ability and executive functioning, considered as covariates, were not significant predictors and their inclusion in regression analyses did not affect the pattern of results. Lastly, when cognitive predictors were accounted for, a trend toward an effect of medication (assessed as olanzapine equivalents) emerged such that higher dose predicted less severe AVH. Taken together, better performance on measures of linguistic processes associated with verbal working memory, semantic fluency and verbal learning predicts less severe AVH, perhaps most consistent with limited capacity language processing models. The finding that better delayed memory predicted more severe AVH is consistent with AVH memory models suggesting that AVH are dependent upon information recalled from memory storage.

Posttraumatic stress (PTSD) and alcohol use (AUD) disorders are associated with abnormal anterior cingulate cortex/ventromedial prefrontal cortex, thalamus, and amygdala function, yet microstructural white matter (WM) differences in executive-limbic tracts are likely also involved. Investigating WM in limbic-thalamo-cortical tracts, this study hypothesized (1) fractional anisotropy (FA) in dorsal cingulum, parahippocampal cingulum, and anterior corona radiata (ACR) would be lower in individuals with comorbid PTSD/AUD compared to in individuals with AUD-only and (2) that FA would be related to both AUD and PTSD severity. 22 combat veterans with comorbid PTSD/AUD or AUD-only completed DTI scans. ANCOVAs indicated lower FA in right (F(df= 1,19)=9.091, P=0.0071) and left (F(df= 1,19) = 10.375, P=0.0045) dorsal cingulum and right ACR (F(df= 1,19) = 18.914, P= 0.0003) for individuals with comorbid PTSD/AUD vs. individuals with AUD-only, even controlling for alcohol use. Multiple linear regressions revealed that FA in the right ACR was inversely related to PTSD severity (r= −0.683, P=0.004). FA was not significantly related to alcohol severity. Reduced WM integrity in limbic-thalamo-cortical tracts is implicated in PTSD, even in the presence of comorbid AUD. These findings suggest that diminished WM integrity in tracts important for top-down control may be an important anomaly in PTSD and/or comorbid PTSD/AUD.

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.

Chronic, heavy alcohol consumption may affect the concentration of neurometabolites assessed with proton magnetic resonance spectroscopy (1H-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.

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.

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 Language: en

Auditory sensory gating deficits have been reported in subjects with post-traumatic stress disorder (PTSD), but the hemispheric and neuronal origins of this deficit are not well understood. The objectives of this study were to: (1) investigate auditory sensory gating of the 50-ms response (M50) in patients diagnosed with PTSD by utilizing magnetoencephalography (MEG); (2) explore the relationship between M50 sensory gating and cortical thickness of the superior temporal gyrus (STG) measured with structural magnetic resonance imaging (MRI); and (3) examine the association between PTSD symptomatology and bilateral sensory gating. Seven participants with combat-related PTSD and eleven controls underwent the paired-click sensory gating paradigm. MEG localized M50 neuronal generators to the STG in both groups. The PTSD group displayed impaired M50 gating in the right hemisphere. Thinner right STG cortical thickness was associated with worse right sensory gating in the PTSD group. The right S1 M50 source strength and gating ratio were correlated with PTSD symptomatology. These findings suggest that the structural integrity of right hemisphere STG cortices play an important role in auditory sensory gating deficits in PTSD.

Background: Adolescence is a period in which cognition and brain undergo dramatic parallel development. Whereas chronic use of alcohol and marijuana is known to cause cognitive impairments in adults, far less is known about the effect of these substances of abuse on adolescent cognition, including possible interactions with developmental processes. Methods: Neuropsychological performance, alcohol use, and marijuana use were assessed in 48 adolescents (ages 12 to 18), recruited in 3 groups: a healthy control group (HC, n = 15), a group diagnosed with substance abuse or dependence (SUD, n = 19), and a group with a family history positive for alcohol use disorder (AUD) but no personal substance use disorder (FHP, n = 14). Age, drinks per drinking day (DPDD), percentage days drinking, and percentage days using marijuana were considered as covariates in a MANCOVA in which 6 neuropsychological composites (Verbal Reasoning, Visuospatial Ability, Executive Function, Memory, Attention, and Processing Speed) served as dependent variables. Results: More DPDD predicted poorer performance on Attention and Executive Function composites, and more frequent use of marijuana was associated with poorer Memory performance. In separate analyses, adolescents in the SUD group had lower scores on Attention, Memory, and Processing Speed composites, and FHP adolescents had poorer Visuospatial Ability. Conclusions: In combination, these analyses suggest that heavy alcohol use in adolescence leads to reduction in attention and executive functioning and that marijuana use exerts an independent deleterious effect on memory. At the same time, premorbid deficits associated with family history of AUD appeared to be specific to visuospatial ability. Language: en

Abnormal 50- and 100-msec event-related brain activity derived from paired-click procedures are well established in schizophrenia. There is little agreement on whether group differences in the ratio score, i.e., the ratio of EEG amplitude after the second stimulus (S2) to the amplitude after the first stimulus (S1), reflect an encoding or gating abnormality. In addition, the functional implications remain unclear. In the present study, EEG and magnetoencephalography (MEG) were used to examine paired-click measures and cognitive correlates of paired-click activity.EEG and whole-cortex MEG data were acquired during the standard paired-click paradigm in 73 comparison subjects and 79 schizophrenia patients. Paired-click ratio scores were obtained at 50 msec (P50 evoked potential at Cz, M50 at left and right superior temporal gyrus [STG]) and 100 msec (N100 at Cz, M100 at left and right STG). A cognitive battery assessing attention, working memory, and long-delay memory was administered. IQ was also estimated.Groups differed on ratio score and amplitude of S1 response. Ratio scores at 50 msec and 100 msec and S1 amplitude predicted variance in attention (primarily S1 amplitude), working memory, and long-delay memory. The attention findings remained after removal of variance associated with IQ.Associations between paired-click measures and cognitive performance in patients support 50-msec and 100-msec ratio and amplitude scores as clinically significant biomarkers of schizophrenia. In general, cognitive performance was better predicted by the ability to encode auditory information than the ability to filter redundant information.

While the reliability of assessment instruments designed for use with adults is well established, much less is known about the adequacy of these instruments for adolescent substance abusers. As part of a comprehensive intake evaluation, the Inventory of Drug Use Consequences (InDUC) was administered both to forty adolescents assigned to a probationary substance abuse treatment program and to one of their parents. The correlation was statistically significant between Parent and Adolescent InDUC score(s), but the interrater reliability was relatively low. IQ scores and level of substance use were considered as moderator variables, but neither showed a significant effect. History of head injury, however, significantly moderated this relationship; those adolescents reporting no history of head injury showed little correspondence with Parent InDUC Score(s), whereas those adolescents with a history of head injury showed significant correlations with parent InDUC scores. This suggests that a history of head injury may affect the way in which adolescents perceive substance-related consequences.

The etiologic factors underlying schizophrenia have been conceptualized as reflecting two largely genetic components — those unique to schizophrenia and those representing vulnerability to neurodevelopmental deviation in general. The Developmental Instability (DI) approach suggests that the latter can be indexed by minor physical anomalies (MPAs), which assess early prenatal growth abnormalities, and fluctuating anatomic asymmetries (FA), which reflects later deviations. Individuals with schizophrenia ( N = 19) had elevated scores on both measures as compared to healthy controls ( N = 23). Further, MPAs and FA were very highly correlated in the sample of individuals with schizophrenia but not in controls. In order to identify neuroanatomic variation linked with the unique factor, we conducted gray matter Voxel Based Morphometry analyses of group membership, with and without treating a composite measure of DI (based on FA, and MPAs) as a covariate. When DI was treated as a covariate, many more gray matter regions were found to statistically differ as a function of diagnosis. These results support the DI approach and suggest that the unique etiologic factors associated with schizophrenia lead to widespread gray matter volume reductions.

Although many studies have compared the brains of normal controls and individuals with autism, especially older, higher-functioning individuals with autism, little is known of the neural correlates of the vast clinical heterogeneity characteristic of the disorder. In this study, we used voxel-based morphometry (VBM) to examine gray matter correlates of variation in communication skill and symptom severity within a heterogeneous group of 33 children with autism ranging in age from 3.4 to 11.4 years. Greater gray matter (GM) volume was associated with better communication skills in numerous frontal regions, especially in the left middle frontal gyrus. Further, greater GM volume in the right inferior frontal gyrus was associated with reduced severity of symptoms of autism. However, increased total GM volume was correlated with more severe symptoms of autism at a trend level, consistent with other studies, suggesting that while increased total GM volume is generally predictive of greater autistic severity, specific local increases in GM volume result in a reduction in symptoms. Our results suggest that communication and symptom severity have distinct neuroanatomic correlates and draw attention to the importance of studying the neuroanatomy of clinical heterogeneity within the autistic population.

One of the most consistent electrophysiological deficits reported in the schizophrenia literature is the failure to inhibit, or properly gate, the neuronal response to the second stimulus of an identical pair (i.e., sensory gating). Although animal and invasive human studies have consistently implicated the auditory cortex, prefrontal cortex and hippocampus in mediating the sensory gating response, localized activation in these structures has not always been reported during non-invasive imaging modalities. In the current experiment, event-related FMRI and a variant of the traditional gating paradigm were utilized to examine how the gating network differentially responded to the processing of pairs of identical and non-identical tones. Two single-tone conditions were also presented so that they could be used to estimate the HRF for paired stimuli, reconstructed based on actual hemodynamic responses, to serve as a control non-gating condition. Results supported an emerging theory that the gating response for both paired-tone conditions was primarily mediated by auditory and prefrontal cortex, with potential contributions from the thalamus. Results also indicated that the left auditory cortex may play a preferential role in determining the stimuli that should be inhibited (gated) or receive further processing due to novelty of information. In contrast, there was no evidence of hippocampal involvement, suggesting that future work is needed to determine what role it may play in the gating response.

Impaired P50 gating is thought to reflect a core deficit in schizophrenia, but the relevant neural network is not well understood. The present study used EEG and MEG to assess sensory gating and volumetric MRI to measure hippocampal volume to investigate relationships between them in 22 normal controls and 22 patients with schizophrenia. In the schizophrenia group, anterior but not posterior hippocampal volume was smaller, and both the P50 and M50 gating ratios were larger (worse) than in controls. Independent of group, left-hemisphere M50 gating ratio correlated negatively with left anterior hippocampal volume, and right-hemisphere M50 gating ratio correlated negatively with right anterior hippocampal volume. Schizophrenia diagnosis predicted M50 gating independent of hippocampal volume. These results are consistent with the finding that hippocampus is a critical part of a fronto-temporal circuit involved in auditory gating.

Considerable evidence indicates early auditory stimulus processing abnormalities in schizophrenia, but the mechanisms are unclear. The present study examined oscillatory phenomena during a paired-click paradigm in the superior temporal gyrus (STG) as a possible core problem. The primary question addressed is whether first click and/or second click group differences in the time-domain evoked response in patients with schizophrenia are due to (1) group differences in the magnitude of poststimulus oscillatory activity, (2) group differences in poststimulus phase-locking, and/or (3) group differences in the magnitude of ongoing background oscillatory activity. Dense-array magnetoencephalography from 45 controls and 45 patients with schizophrenia produced left- and right-hemisphere STG 50- and 100-ms time-frequency evoked, phase-locking, and total power measures. Whereas first click 100-ms evoked theta and alpha abnormalities were observed bilaterally, evoked low beta-band differences were specific to the left hemisphere. Compared to controls, patients with schizophrenia showed more low-frequency phase variability, and the decreased 100-ms S1 evoked response observed in patients was best predicted by the STG phase-locking measure.

Research on the origin of neurodevelopmental disorders has traditionally been pursued within a constrained, disorder-specific perspective. The developmental instability (DI) model described here offers a broader approach based on the evolutionary genetics of normal variation, reflecting our understanding that the processes generating genetic diversity are not unique to any specific disorder. The DI model helps account for shared features, including atypical functional and anatomic asymmetries, reduced general intellectual functioning, and complex patterns of heritability, across different types of neural variation. The model suggests research strategies that may help illuminate the specific and unique causal factors characterizing different types of neural variation.

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.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.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.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.

Recent evidence suggests that changes in brain structure associated with alcohol abuse are compounded in individuals dually diagnosed with alcohol abuse and schizophrenia. To investigate the separate, and possibly interacting, effects of these diagnoses, an event-related brain potential (ERP) measure of auditory information processing (P50 sensory gating paradigm) and neuropsychological measures were administered to healthy control participants with either (1a) no history of alcohol abuse/dependence, or (1b) a remote history of alcohol abuse/dependence, and patients with schizophrenia with either (2a) no history of alcohol abuse/dependence, or (2b) a remote history of alcohol abuse/dependence. Schizophrenia was associated with impaired P50 sensory gating and poorer performance across neuropsychological scores compared to measurements in healthy control participants. Those with a positive alcohol history had impaired gating ratios in contrast to those with a negative alcohol history. There were additive effects of schizophrenia diagnosis and alcohol history for P50 sensory gating and for neuropsychological scores: attention, working memory, and behavioral inhibition. For executive attention and general memory there was an interaction, suggesting that the combination of schizophrenia and history of alcohol abuse results in greater impairment than that predicted by the presence of either diagnosis alone. (JINS, 2006, 12, 34–44.)

Previous studies using functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) of the brain have found that a distributed parietal-frontal neuronal network is activated in normals during both auditory and visual oddball tasks. The common cortical regions in this network are inferior parietal lobule (IPL)/supramarginal gyrus (SMG), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). It is not clear whether the same network is activated by oddball tasks during somatosensory stimulation. The present study addressed this question by testing healthy adults as they performed a novel median-nerve oddball paradigm while undergoing magnetoencephalography (MEG). An automated multiple dipole analysis technique, the Multi-Start Spatio-Temporal (MSST) algorithm, localized multiple neuronal generators, and identified their time-courses. IPL/SMG, ACC, and DLPFC were reliably localized in the MEG median-nerve oddball responses, with IPL/SMG activation significantly preceding ACC and DLPFC activation. Thus, the same parietal-frontal neuronal network that shows activation during auditory and visual oddball tests is activated in a median-nerve oddball paradigm. Regions uniquely related to somatosensory oddball responses (e.g., primary and secondary somatosensory, dorsal premotor, primary motor, and supplementary motor areas) were also localized. Since the parietal-frontal network supports attentional allocation during performance of the task, this study may provide a novel method, as well as normative baseline data, for examining attention-related deficits in the somatosensory system of patients with neurological or psychiatric disorders.

Auditory P50/M50 paired-click studies have established an association between schizophrenia and impaired sensory gating in the auditory modality. However, the presumed cross-modal generality of the gating deficit has received little study. The present study examined gating in area 3b of primary somatosensory cortex to evaluate patients' somatosensory gating at this first stage of cortical processing. One hundred twenty-two channels of magnetoencephalography (MEG) data were collected from 27 subjects with chronic schizophrenia and 21 controls during a somatosensory paired-pulse paradigm with a 75- or 500-ms interstimulus interval. M20 somatosensory responses were localized using magnetic source imaging, and a gating ratio was calculated. In a subset of these subjects, MEG was also done for the standard auditory paradigm to assess M50 gating. Patients showed abnormal auditory M50 gating but normal somatosensory M20 gating. Results argue against a cross-modal gating deficit in primary somatosensory cortex.

Impaired auditory sensory gating is considered characteristic of schizophrenia and a marker of the information processing deficit inherent to that disorder. Predominance of negative symptoms also reflects the degree of deficit in schizophrenia and is associated with poorer pre-morbid functioning, lower IQ, and poorer outcomes. However, a consistent relationship between auditory sensory gating and negative symptoms in schizophrenia has yet to be demonstrated. The absence of such a finding is surprising, since both impaired auditory gating and negative symptoms have been linked with impaired fronto-temporal cortical function. The present study measured auditory gating using the P50 event related potential (ERP) in a paired-click paradigm and capitalized on the relative localization advantage of magnetoencephalography (MEG) to assess auditory sensory gating in terms of the event related field (ERF) M50 source dipoles on bilateral superior temporal gyrus (STG). The primary hypothesis was that there would be a positive correlation between lateralized M50 auditory sensory gating measures and negative symptoms in patients with schizophrenia. A standard paired-click paradigm was used during simultaneous EEG and MEG data collection to determine S2/S1 sensory gating ratios in a group of 20 patients for both neuroimaging techniques. Participants were administered the Schedule for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale (PANSS), and the Calgary Depression Scale for Schizophrenia. Consistent with previous reports, there was no relationship between ERP P50 sensory gating and negative symptoms. However, right (not left) hemisphere ERF M50 sensory gating ratio was significantly and positively correlated with negative symptoms. This finding is compatible with information processing theories of negative symptoms and with more recent findings of fronto-temporal abnormality in patients with predominantly negative symptoms.

Measures of developmental instability (DI) reflect developmental disruptions due to genetic and environmental perturbations during normal development. DI might be expected to influence the developmental course of brain development and hence intelligence, and several studies indicate this to be the case. The factors that mediate this relationship are unknown. One possibility is that DI affects intelligence through effects on cortical size. To investigate this possibility, we assessed a measure of DI, body fluctuating asymmetry (FA), the Raven's Advanced Progressive Matrices (RAPM), and other cognitive tests on a group of 19 healthy male volunteers on whom cortical volume, white matter, overall brain volume, and cross-sectional areas of the corpus callosum and planum temporale were measured. Both FA and cortical volume significantly predicted RAPM scores, but were not significantly correlated themselves. Multiple regression analyses yielded effects of FA on RAPM scores and a general intelligence principal component independent of cortical volume. Hence, it appears that developmental instability affects intellectual functioning through pathways not involving cortical volume. Possible mediators include macro-organizational structure, neural integrity, or metabolic efficiency.

Sensory gating assessed via EEG in a paired-click paradigm has often served as a neurophysiological metric of attentional function in schizophrenia. However, the standard EEG measure of sensory gating using the P50 component at electrode Cz does not foster differential assessment of left and right hemisphere contributions. Magnetoencephalography (MEG) is complementary to EEG, and its analogous M50 component may be better suited for localization and analysis of such lateralized cortical generators. The authors hypothesized that 1) auditory gating would be evident in M50 sources in superior temporal gyrus, demonstrating ratios similar to P50; 2) M50 would resemble P50 in distinguishing gating in comparison subjects and patients with schizophrenia, but M50 would show lateralization of the gating deficit; and 3) P50 and M50 sensory gating ratios would predict neuropsychological measures in patients and comparison subjects, with the MEG identification of left and right hemisphere sources allowing for the evaluation of lateralization in brain-behavior relationships.Event-related EEG and MEG recordings were simultaneously obtained from 20 patients with schizophrenia and 15 comparison subjects. P50 amplitudes, M50 dipole source strengths, and P50 and M50 gating ratios were compared and assessed with respect to scores on neuropsychological performance measures.M50 dipoles localizing to superior temporal gyrus demonstrated gating similar to that of P50. As expected, patients demonstrated less P50 gating than did comparison subjects. Left (but not right) hemisphere M50 gating 1) correlated with EEG gating, 2) differentiated patients and comparison subjects, and 3) correlated with neuropsychological measures of sustained attention and working memory.Converging evidence from EEG, MEG, and neuropsychological measures points to left hemisphere dysfunction as strongly related to the well-established sensory gating deficit in schizophrenia.

A number of beamformers have been introduced to localize neuronal activity using magnetoencephalography (MEG) and electroencephalography (EEG). However, currently available information about the major aspects of existing beamformers is incomplete. In the present study, detailed analyses are performed to study the commonalities and differences among vectorized versions of existing beamformers in both theory and practice. In addition, a novel beamformer based on higher-order covariance analysis is introduced. Theoretical formulas are provided on all major aspects of each beamformer; to examine their performance, computer simulations with different levels of correlation and signal-to-noise ratio are studied. Then, an empirical data set of human MEG median-nerve responses with a large number of neuronal generators is analyzed using the different beamformers. The results show substantial differences among existing MEG/EEG beamformers in their ways of describing the spatial map of neuronal activity. Differences in performance are observed among existing beamformers in terms of their spatial resolution, false-positive background activity, and robustness to highly correlated signals. Superior performance is obtained using our novel beamformer with higher-order covariance analysis in simulated data. Excellent agreement is also found between the results of our beamformer and the known neurophysiology of the median-nerve MEG response.

The purpose of this study was to explore the relationship between combat-related posttraumatic stress disorder (PTSD) and specific augmentation versus reduction patterns for the N100 and P200 components of auditory event-related potentials evoked by tones of increasing intensity.Event-related potentials of subjects with PTSD (N=36), subjects with no psychopathology (N=20), subjects with major depression but no PTSD (N=10), and subjects with a history of chronic alcohol abuse but no PTSD (N=8) were recorded. Brain responses were evoked by a 2000-Hz tone presented in intensity blocks of 65, 72.5, 80, 87.5, and 95 dB (SPL).Evoked data from five PTSD subjects were of poor quality and excluded from further analyses. For all but one subject with no psychopathology and for all subjects with a history of alcohol abuse or major depression (but no PTSD), the Cz amplitude of the P200 response component showed augmentation as a nearly linear function of tone intensity. As a group, subjects with PTSD showed no such increase in P200 response magnitude. Examination of the data from individual subjects with PTSD showed that 42% exhibited augmentation patterns similar to those seen for subjects in the comparison groups. However, 58% showed evidence of P200 reduction, with the response to the loudest tone being smaller than responses to tones of intermediate intensity.The data suggest that there is a significant subgroup of patients with combat-related PTSD who enter into a state of protective inhibition at relatively low stimulus intensities. It is hypothesized that this is an appropriate adaptive mechanism for these subjects rather than an indication of a core neurobiological abnormality.

Adaptive development requires the organism to resist genetic and environmental stresses that disrupt the genetic plan for growth, a buffering capacity termed developmental stability. Developmental instability is revealed by fluctuating asymmetry (FA), which has been demonstrated in many species to reflect phenotypic and genetic quality. We report (1) that a measure of developmental instability based on body FA predicts deviation from typical brain asymmetry, (2) that a combined measure of atypical brain asymmetry and body FA correlated negatively with the area of the corpus callosum, especially the portion connecting the left and right planum temporale, and (3) that this combined measure also predicted atypical asymmetry of the size of the somatosensory representation of the two hands, as determined from magnetic source imaging.