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Importance: Mild traumatic brain injury (TBI) may predispose individuals to progressive neurodegeneration., Objective: To identify evidence of neurodegeneration through longitudinal evaluation of changes in retinal layer thickness using optical coherence tomography in veterans with a history of mild TBI., Design, Setting, and Participants: This longitudinal cohort study evaluated veterans who were receiving services at the Minneapolis Veterans Affairs Health Care System. Symptomatic or mild TBI was diagnosed according to the Mayo TBI Severity Classification System. Participants in the age-matched control group had no history of TBI. Participants with any history or evidence of retinal or optic nerve disease that could affect retinal thickness were excluded. Data analysis was performed from July 2019 to February 2020., Exposures: The presence and severity of mild TBI were determined through consensus review of self-report responses during the Minnesota Blast Exposure Screening Tool semistructured interview., Main Outcomes and Measures: Change over time of retinal nerve fiber layer (RNFL) thickness., Results: A total of 139 veterans (117 men [84%]; mean [SD] age, 49.9 [11.1] years) were included in the study, 69 in the TBI group and 70 in the control group. Veterans with mild TBI showed significantly greater RNFL thinning compared with controls (mean [SE] RNFL slope, -1.47 [0.24] μm/y vs -0.31 [0.32] μm/y; F1,122 = 8.42; P = .004; Cohen d = 0.52). Functionally, veterans with mild TBI showed greater declines in visual field mean deviation (mean [SE] slope, -0.09 [0.14] dB/y vs 0.46 [0.23] dB/y; F1,122 = 4.08; P = .046; Cohen d = 0.36) and pattern standard deviation (mean [SE] slope, 0.09 [0.06] dB/y vs -0.10 [0.07] dB/y; F1,122 = 4.78; P = .03; Cohen d = 0.39) and high spatial frequency (12 cycles/degree) contrast sensitivity compared with controls. Cognitively, there was a significantly greater decrease in the number of errors over time during the Groton Maze Learning Test (GMLT) in controls compared with veterans with mild TBI (mean [SE] slope, -9.30 [1.48] errors/y vs -5.23 [1.24] errors/y; F1,127 = 4.43; P = .04; Cohen d = 0.37). RNFL tissue loss was significantly correlated with both worsening performance on the GMLT over time (Spearman ρ = -0.20; P = .03) and mild TBI severity (Spearman ρ = -0.25; P = .006). The more severe the mild TBI (larger Minnesota Blast Exposure Screening Tool severity score), the faster the reduction in RNFL thickness (ie, the more negative the slope) across time., Conclusions and Relevance: This cohort study found longitudinal evidence for significant, progressive neural degeneration over time in veterans with mild TBI, as indicated by greater RNFL tissue loss in patients with mild TBI vs controls, as well as measures of function. These results suggest that these longitudinal measures may be useful biomarkers of neurodegeneration. Changes in this biomarker may provide early detection of subsequent cognitive and functional deficits that may impact veterans' independence and need for care.

Background: This study was a randomized double-blind sham-controlled trial examining the effects of transcranial direct current stimulation (tDCS) augmented cognitive training (CT) in children with Fetal Alcohol Spectrum Disorders (FASD). Prenatal alcohol exposure has profound detrimental effects on brain development and individuals with FASD commonly present with deficits in executive functions including attention and working memory. The most commonly studied treatment for executive deficits is CT, which involves repeated drilling of exercises targeting the impaired functions. As currently implemented, CT requires many hours and the observed effect sizes are moderate. Neuromodulation via tDCS can enhance brain plasticity and prior studies demonstrate that combining tDCS with CT improves efficacy and functional outcomes. TDCS-augmented CT has not yet been tested in FASD, a condition in which there are known abnormalities in neuroplasticity and few interventions., Methods: This study examined the feasibility and efficacy of this approach in 44 children with FASD. Participants were randomized to receive five sessions of CT with either active or sham tDCS targeting the dorsolateral prefrontal cortex, a region of the brain that is heavily involved in executive functioning., Results: The intervention was feasible and well-tolerated in children with FASD. The tDCS group showed nominally significant improvement in attention on a continuous performance test compared to sham (p = .043). Group differences were observed at the third, fourth and fifth treatment sessions. There was no effect of tDCS on working memory (p = .911). Further, we found no group differences on a trail making task (p = .659) or on the verbal fluency test (p = .826). In the active tDCS group, a significant correlation was observed between improvement in attention scores and decrease in parent-reported attention deficits (p = .010)., Conclusions: These results demonstrate that tDCS-augmented CT is well tolerated in children with FASD and potentially offers benefits over and above CT alone., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience. There were significant differences in prevalence of Alzheimer disease neuropathologic change, small vessel vascular brain injury, and Lewy body disease between these 2 studies, suggesting that sex, ethnicity, and lifestyle factors may significantly influence resistance to developing brain injury with age. In contrast, hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive performance, suggesting that hippocampal sclerosis could act sequentially with other diseases to impair cognitive function. Strikingly, despite these observed differences, the proportion of individuals resistant to all 4 diseases of brain or displaying apparent cognitive resilience was virtually identical between HAAS and Nun Study participants. Future in vivo validation of these results awaits comprehensive biomarkers of these 4 brain diseases., (© 2017 American Association of Neuropathologists, Inc. All rights reserved.)

Schizophrenia neurocognitive domain profiles are predominantly based on paper-and-pencil batteries. This study presents the first schizophrenia domain profile based on the Computerized Multiphasic Interactive Neurocognitive System (CMINDS(®)). Neurocognitive domain z-scores were computed from computerized neuropsychological tests, similar to those in the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), administered to 175 patients with schizophrenia and 169 demographically similar healthy volunteers. The schizophrenia domain profile order by effect size was Speed of Processing (d=-1.14), Attention/Vigilance (d=-1.04), Working Memory (d=-1.03), Verbal Learning (d=-1.02), Visual Learning (d=-0.91), and Reasoning/Problem Solving (d=-0.67). There were no significant group by sex interactions, but overall women, compared to men, showed advantages on Attention/Vigilance, Verbal Learning, and Visual Learning compared to Reasoning/Problem Solving on which men showed an advantage over women. The CMINDS can readily be employed in the assessment of cognitive deficits in neuropsychiatric disorders; particularly in large-scale studies that may benefit most from electronic data capture., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: The phenotype of attenuated mucopolysaccharidosis type II (MPS II), also called Hunter syndrome, has not been previously studied in systematic manner. In contrast to the "severe" phenotype, the "attenuated" phenotype does not present with behavioral or cognitive impairment; however, the presence of mild behavior and cognitive impairment that might impact long-term functional outcomes is unknown. Previously, significant MRI abnormalities have been found in MPS II. Recent evidence suggests white matter abnormalities in many MPS disorders., Methods: As the initial cross-sectional analysis of a longitudinal study, we studied the association of brain volumes and somatic disease burden with neuropsychological outcomes, including measures of intelligence, memory, and attention in 20 patients with attenuated MPS II with a mean age of 15.8. MRI volumes were compared to 55 normal controls., Results: While IQ and memory were average, measures of attention were one standard deviation below the average range. Corpus callosum volumes were significantly different from age-matched controls, differing by 22%. Normal age-related volume increases in white matter were not seen in MPS II patients as they were in controls. Somatic disease burden and white matter and corpus callosum volumes were significantly associated with attention deficits. Neither age at evaluation nor age at starting treatment predicted attention outcomes., Conclusions: Despite average intelligence, attention is compromised in attenuated MPS II. Results confirm an important role of corpus callosum and cortical white matter abnormality in MPS II as well as the somatic disease burden in contributing to attention difficulties. Awareness by the patient and caregivers with appropriate management and symptomatic support will benefit the attenuated MPS II patient., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The N-methyl-D-aspartate glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). However, evaluation of ketamine's neurocognitive aspects in TRD has started to be explored. This study aims to (1) examine baseline neurocognitive performance and change in severity of depressive symptoms through six ketamine infusions, (2) examine the neurocognitive effects after completion of serial infusions and whether changes were associated to relapse to depression. Six IV infusions of 0.5 mg/Kg ketamine over 40 min were conducted on a Monday-Wednesday-Friday schedule during a 12-d period on 15 patients with TRD followed by a 4-wk observational period. Neurocognitive functioning was assessed using the CogState battery at baseline and at each follow-up visit. Tasks were designed to test attention, memory (working, visual, and verbal), speed of processing, and set shifting. The likelihood of response through six infusions was greater among depressed subjects with lower attention at baseline (F(1,13)=5.59, p=0.034). Significant improvement was found in scores of visual memory (F(4,33.82)=5.12, p=0.002), simple working memory (F(4, 24.85)=3.29, p=0.027) and complex working memory (F(4, 32.76)=4.18, p=0.008) after the last ketamine infusion. However, neurocognitive changes were accounted for by improvement in the severity of depressive symptom. The acute neurocognitive effect after completion of repeated infusions was not associated with the likelihood of subsequent relapse during follow-up. Our findings suggest a potential baseline neurocognitive predictor of ketamine response and the apparently lack of short-term neurocognitive impairment after completion of six ketamine infusions in TRD.

The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer's disease and mild cognitive impairment are evident in their performance on the semantic verbal fluency test. In addition to the semantic verbal fluency test score, several other performance characteristics sensitive to disease status and predictive of future cognitive decline have been defined in terms of words generated from semantically related categories (clustering) and shifting between categories (switching). However, the traditional assessment of clustering and switching has been performed manually in a qualitative fashion resulting in subjective scoring with limited reproducibility and scalability. Our approach uses word definitions and hierarchical relations between the words in WordNet(®), a large electronic lexical database, to quantify the degree of semantic similarity and relatedness between words. We investigated the novel semantic fluency indices of mean cumulative similarity and relatedness between all pairs of words regardless of their order, and mean sequential similarity and relatedness between pairs of adjacent words in a sample of patients with clinically diagnosed probable (n=55) or possible (n=27) Alzheimer's disease or mild cognitive impairment (n=31). The semantic fluency indices differed significantly between the diagnostic groups, and were strongly associated with neuropsychological tests of executive function, as well as the rate of global cognitive decline. Our results suggest that word meanings and relations between words shared across individuals and computationally modeled via WordNet and large text corpora provide the necessary context to account for the variability in language-based behavior and relate it to cognitive dysfunction observed in mild cognitive impairment and Alzheimer's disease., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Diffusion tensor imaging was used to investigate white matter (WM) integrity in adults with traumatic brain injury (TBI) and healthy adults as controls. Adults with TBI had sustained severe vehicular injuries on the average of 7 years earlier. A multivariate analysis of covariance with verbal IQ as the covariate revealed that adults with TBI had lower fractional anisotropy and higher mean diffusivity than controls, specifically in the three regions of interest (ROIs), the centrum semiovale (CS), the superior frontal (SPF), and the inferior frontal (INF). Adults with TBI averaged in the normal range in motor speed and two of three executive functions and were below average in delayed verbal recall and inhibition, whereas controls were above average. Time since injury, but not age, was associated with WM changes in the SPF ROI, whereas age, but not time since injury, was associated with WM changes in the INF ROI, suggesting that the effects of WM on time since injury may interact with age. To understand the utility of WM changes in chronic recovery, larger sample sizes are needed to investigate associations between cognition and WM integrity of severely injured individuals who have substantial cognitive impairment compared to severely injured individuals with little cognitive impairment. (JINS, 2009, 15, 130-136.).

Objective: Long-standing type 1 diabetes is associated with deficits on neurocognitive testing that suggest central white matter dysfunction. This study investigated whether diffusion tensor imaging (DTI), a type of magnetic resonance imaging that measures white matter integrity quantitatively, could identify white matter microstructural deficits in patients with long-standing type 1 diabetes and whether these differences would be associated with deficits found by neurocognitive tests., Research Design and Methods: Twenty-five subjects with type 1 diabetes for at least 15 years and 25 age- and sex-matched control subjects completed DTI on a 3.0 Tesla scanner and a battery of neurocognitive tests. Fractional anisotropy was calculated for the major white matter tracts of the brain., Results: Diabetic subjects had significantly lower mean fractional anisotropy than control subjects in the posterior corona radiata and the optic radiation (P < 0.002). In type 1 diabetic subjects, reduced fractional anisotropy correlated with poorer performance on the copy portion of the Rey-Osterreith Complex Figure Drawing Test and the Grooved Peg Board Test, both of which are believed to assess white matter function. Reduced fractional anisotropy also correlated with duration of diabetes and increased A1C. A history of severe hypoglycemia did not correlate with fractional anisotropy., Conclusions: DTI can detect white matter microstructural deficits in subjects with long-standing type 1 diabetes. These deficits correlate with poorer performance on selected neurocognitive tests of white matter function.

BackgroundSchizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.MethodsHippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.ResultsThis study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = -0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = -0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10-8, 95% CI 7.0-14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.ConclusionsThis study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.

ObjectivesPrecise characterization of cognitive outcomes and factors that contribute to cognitive variability will enable better understanding of disease progression and treatment effects in mucopolysaccharidosis type I (MPS I). We examined the effects on cognition of phenotype, genotype, age at evaluation and first treatment, and somatic disease burden.MethodsSixty patients with severe MPS IH (Hurler syndrome treated with hematopoietic cell transplant and 29 with attenuated MPS I treated with enzyme replacement therapy), were studied with IQ measures, medical history, genotypes. Sixty-seven patients had volumetric MRI. Subjects were grouped by age and phenotype and MRI and compared to 96 normal controls.ResultsPrior to hematopoietic cell transplant, MPS IH patients were all cognitively average, but post-transplant, 59% were below average, but stable. Genotype and age at HCT were associated with cognitive ability. In attenuated MPS I, 40% were below average with genotype and somatic disease burden predicting their cognitive ability. White matter volumes were associated with IQ for controls, but not for MPS I. Gray matter volumes were positively associated with IQ in controls and attenuated MPS I patients, but negatively associated in MPS IH.ConclusionsCognitive impairment, a major difficulty for many MPS I patients, is associated with genotype, age at treatment and somatic disease burden. IQ association with white matter differed from controls. Many attenuated MPS patients have significant physical and/or cognitive problems and receive insufficient support services. Results provide direction for future clinical trials and better disease management.

ObjectiveTo identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF).DesignCross-sectional brain Magnetic Resonance I (MRI) study.SettingCommunity based cohort in three U.S. sites.ParticipantsA Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study.Primary and secondary outcomes3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function.ResultsAdjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all

Background: The glutamate N-methyl-d-aspartate (NMDA) receptor antagonist ketamine rapidly ameliorates posttraumatic stress disorder (PTSD) and depression symptoms in individuals with comorbid PTSD and major depressive disorder (MDD). However, concerns over ketamine's potential neurocognitive side effects have yet to be assessed in this population. The current study investigated 1) changes in neurocognitive performance after a repeated ketamine dosing regimen and 2) baseline neurocognitive performance as a predictor of ketamine treatment effect.Method: Veterans with comorbid PTSD and MDD (N = 15) received six infusions of 0.5 mg/kg ketamine over a 12-day period. Neurocognitive and clinical outcomes assessments occurred at baseline and within 7 days of infusion-series completion using the CogState battery.Results: Repeated ketamine infusions did not significantly worsen any measures of cognition. Rather, significant improvement was observed in working memory following completion of the infusion series. In addition, greater improvements in PTSD and MDD symptoms were associated with lower working memory, slower processing speed and faster set shifting at baseline. Lower verbal learning was also predictive of improvement in depression.Limitations: This study applied an open-label design without a placebo control. As such, it is not known to what extent the correlations or improvement in neurocognitive performance may have occurred under placebo conditions.Conclusion: This is the first study to examine the neurocognitive effects of repeated ketamine in participants with comorbid PTSD and MDD. Our findings suggest potential baseline neurocognitive predictors of ketamine response for comorbid PTSD and MDD symptoms. [ABSTRACT FROM AUTHOR]

Wavelet methods are widely used to decompose fMRI, EEG, or MEG signals into time series representing neurophysiological activity in fixed frequency bands. Using these time series, one can estimate frequency-band specific functional connectivity between sensors or regions of interest, and thereby construct functional brain networks that can be examined from a graph theoretic perspective. Despite their common use, however, practical guidelines for the choice of wavelet method, filter, and length have remained largely undelineated. Here, we explicitly explore the effects of wavelet method (MODWT vs. DWT), wavelet filter (Daubechies Extremal Phase, Daubechies Least Asymmetric, and Coiflet families), and wavelet length (2 to 24)—each essential parameters in wavelet-based methods—on the estimated values of graph metrics and in their sensitivity to alterations in psychiatric disease. We observe that the MODWT method produces less variable estimates than the DWT method. We also observe that the length of the wavelet filter chosen has a greater impact on the estimated values of graph metrics than the type of wavelet chosen. Furthermore, wavelet length impacts the sensitivity of the method to detect differences between health and disease and tunes classification accuracy. Collectively, our results suggest that the choice of wavelet method and length significantly alters the reliability and sensitivity of these methods in estimating values of metrics drawn from graph theory. They furthermore demonstrate the importance of reporting the choices utilized in neuroimaging studies and support the utility of exploring wavelet parameters to maximize classification accuracy in the development of biomarkers of psychiatric disease and neurological disorders. [ABSTRACT FROM AUTHOR]

The amplitude of low-frequency fluctuations (ALFF) in the blood oxygenation level-dependent (BOLD) signal during resting-state fMRI reflects the magnitude of local low-frequency BOLD oscillations, rather than interregional connectivity. ALFF is of interest to studies of cognition because fluctuations in spontaneous intrinsic brain activity relate to, and possibly even constrain, task-evoked brain responses in healthy people. Lower ALFF has been reported in schizophrenia, but the cognitive correlates of these reductions remain unknown. Here, we assess relationships between ALFF and attention and working memory in order to establish the functional relevance of intrinsic BOLD oscillatory power alterations with respect to specific cognitive impairments in schizophrenia. As part of the multisite FBIRN study, resting-state fMRI data were collected from schizophrenia subjects (SZ; n=168) and healthy controls (HC; n=166). Voxelwise fractional ALFF (fALFF), a normalized ALFF measure, was regressed on neuropsychological measures of sustained attention and working memory in SZ and HC to identify regions showing either common slopes across groups or slope differences between groups (all findings p<0.01 height, p<0.05 family-wise error cluster corrected). Poorer sustained attention was associated with smaller fALFF in the left superior frontal cortex and bilateral temporoparietal junction in both groups, with additional relationships in bilateral posterior parietal, posterior cingulate, dorsal anterior cingulate (ACC), and right dorsolateral prefrontal cortex (DLPFC) evident only in SZ. Poorer working memory was associated with smaller fALFF in bilateral ACC/mPFC, DLPFC, and posterior parietal cortex in both groups. Our findings indicate that smaller amplitudes of low-frequency BOLD oscillations during rest, measured by fALFF, were significantly associated with poorer cognitive performance, sometimes similarly in both groups and sometimes only in SZ, in regions known to subserve sustained attention and working memory. Taken together, these data suggest that the magnitude of resting-state BOLD oscillations shows promise as a biomarker of cognitive function in health and disease. [ABSTRACT FROM AUTHOR]

Background: Addiction is a complex phenotype, though it consistently includes characteristics of impulsivity. A number of brain regions are suggested to be involved in cocaine addiction, including the insula, which serves diverse functions including interoceptive awareness and integration of neural signals from sensory, subcortical and frontal regions. Malfunction of this integration links impulsive behavior to the insula. Objectives: This study examines intrinsic connectivity of the insula in chronic cocaine users to investigate abnormal insular circuitry, its role in cocaine addiction, and relationships to measure of impulsivity. Methods: Cocaine-dependent individuals ( n = 33) and healthy controls ( n = 32) completed a resting-state fMRI scan. An intrinsic connectivity network (ICN) approach generated metrics of mean network connectivity and inter-network connectivity from fMRI data. Metrics pertaining to ICNs involving insula and other structures repeatedly involved in addiction (e.g. striatum) were selected for analysis, which included the capacity to discriminate groups. Relationships between group discriminating connectivity metrics and behavioral impulsivity were examined. Results: Models demonstrated group prediction accuracy up to 75%. Accuracy of 69% was obtained by a parsimonious model of six inter-network connectivity metrics. The inter-network connectivity between an ICN involving the anterior insula and ACC, and an ICN involving the striatum, was significantly weaker in cocaine users relative to controls. The degree of reduced inter-network connectivity was significantly related to greater non-planning impulsivity in cocaine users. Conclusions: Aberrant insula-derived intrinsic connectivity patterns are observed in cocaine users and include dysfunctions in insula to striatal connectivity, which is furthermore linked to increased impulsivity pertaining to forethought. [ABSTRACT FROM AUTHOR]

MRI studies, including recent diffusion tensor imaging (DTI) studies, have shown corpus callosum abnormalities in children prenatally exposed to alcohol, especially in the posterior regions. These abnormalities appear across the range of fetal alcohol spectrum disorders (FASD). Several studies have demonstrated cognitive correlates of callosal abnormalities in FASD including deficits in visual-motor skill, verbal learning, and executive functioning. The goal of this study was to determine whether inter-hemispheric structural connectivity abnormalities in FASD are associated with disrupted inter-hemispheric functional connectivity and disrupted cognition. Twenty-one children with FASD and 23 matched controls underwent a 6-minute resting-state functional MRI scan as well as anatomical imaging and DTI. Using a semi-automated method, we parsed the corpus callosum and delineated 7 inter-hemispheric white matter tracts with DTI tractography. Cortical regions of interest (ROIs) at the distal ends of these tracts were identified. Right-left correlations in resting fMRI signal were computed for these sets of ROIs, and group comparisons were made. Correlations with facial dysmorphology, cognition, and DTI measures were computed. A significant group difference in inter-hemispheric functional connectivity was seen in a posterior set of ROIs, the para-central region. Children with FASD had functional connectivity that was 12% lower than in controls in this region. Subgroup analyses were not possible owing to small sample size, but the data suggest that there were effects across the FASD spectrum. No significant association with facial dysmorphology was found. Para-central functional connectivity was significantly correlated with DTI mean diffusivity, a measure of microstructural integrity, in posterior callosal tracts in controls but not in FASD. Significant correlations were seen between these structural and functional measures, and Wechsler perceptual reasoning ability. Inter-hemispheric functional connectivity disturbances were observed in children with FASD relative to controls. The disruption was measured in medial parietal regions (para-central) that are connected by posterior callosal fiber projections. We have previously shown microstructural abnormalities in these same posterior callosal regions, and the current study suggests a possible relationship between the two. These measures have clinical relevance as they are associated with cognitive functioning. [ABSTRACT FROM AUTHOR]

• This clinical trial examined tDCS with concurrent cognitive training over 12 weeks. • Left anode–right cathode tDCS improved attention; training improved overall cognition. • Improvements in attention were predicted by cognitive training advancement. • Normal electric field strength in bilateral dlPFC predicted changes in attention. • Training altered connectivity in the control (↓) and somatomotor networks (↑). Executive dysfunction such as inattention or forgetfulness can lead to disruptions in a person's daily functioning and quality of life. This triple-blinded randomized clinical trial assessed the efficacy of bifrontal (over the forehead) transcranial direct current stimulation (tDCS) concurrent with cognitive training to improve cognitive performance in a healthy sample. Fifty-eight participants were randomly assigned to one of three stimulation conditions (2 mA left anode–right cathode, 2 mA right anode–left cathode, or sham), which was administered with cognitive training tasks 3x/week over 12 weeks with assessments at baseline, midpoint (6 weeks), and post-training (12 weeks). We assessed cognitive performance, functional connectivity, and the influence of individual differences in training advancement. Forty participants completed training. We found that at midpoint and post, all groups improved significantly on overall cognitive performance. The left anode group's attention & vigilance score improved significantly at post, but the other two groups did not. Greater attention training advancement predicted attention improvement by post, most notably in the left anode group. Finally, within-network connectivity decreased in the control network and increased in the somatomotor network across all groups. These results suggest that, given cognitive training, the left anode montage is more effective at improving attention than the right anode montage and sham. Future research may focus on the application of the left anode montage during cognitive training to assess its effectiveness in improving cognition in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

• Question: are schizophrenia white matter tract abnormalities confounded by head motion or smoking habits, and correlated with cognitive performance and symptom severity?. • Findings: individuals with schizophrenia have white matter abnormalities that are associated with cognitive performance and negative symptom severity. • Meaning: white matter tract abnormalities in schizophrenia contribute in part to cognitive abnormalities and symptom expression in schizophrenia. Schizophrenia is associated with robust white matter (WM) abnormalities but influences of potentially confounding variables and relationships with cognitive performance and symptom severity remain to be fully determined. This study was designed to evaluate WM abnormalities based on diffusion tensor imaging (DTI) in individuals with schizophrenia, and their relationships with cognitive performance and symptom severity. Data from individuals with schizophrenia (SZ; n=138, mean age ± SD=39.02 ± 11.82; 105 males) and healthy controls (HC; n=143, mean age ± SD=37.07 ± 10.84; 102 males) were collected as part of the Function Biomedical Informatics Research Network Phase 3 study. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were compared between individuals with schizophrenia and healthy controls, and their relationships with neurocognitive performance and symptomatology assessed. Individuals with SZ had significantly lower FA in forceps minor and the left inferior fronto-occipital fasciculus compared to HC. FA in several tracts were associated with speed of processing and attention/vigilance and the severity of the negative symptom alogia. This study suggests that regional WM abnormalities are fundamentally involved in the pathophysiology of schizophrenia and may contribute to cognitive performance deficits and symptom expression observed in schizophrenia. [ABSTRACT FROM AUTHOR]

· Schizophrenia is associated with hypoactivation to auditory oddball targets. · This hypoactivation replicates in an independent sample. · Precuneus activation correlates positively with cognitive performance. · Schizophrenia PRS correlates negatively with right supramarginal gyrus activation. · Genes SLC16A10, RPL36 , and C19orf70 are associated with brain activation. Individuals with schizophrenia (SZ) show aberrant activations, assessed via functional magnetic resonance imaging (fMRI), during auditory oddball tasks. However, associations with cognitive performance and genetic contributions remain unknown. This study compares individuals with SZ to healthy volunteers (HVs) using two cross-sectional data sets from multi-center brain imaging studies. It examines brain activation to auditory oddball targets, and their associations with cognitive domain performance, schizophrenia polygenic risk scores (PRS), and genetic variation (loci). Both sample 1 (137 SZ vs. 147 HV) and sample 2 (91 SZ vs. 98 HV), showed hypoactivation in SZ in the left-frontal pole, and right frontal orbital, frontal pole, paracingulate, intracalcarine, precuneus, supramarginal and hippocampal cortices, and right thalamus. In SZ, precuneus activity was positively related to cognitive performance. Schizophrenia PRS showed a negative correlation with brain activity in the right-supramarginal cortex. GWA analyses revealed significant single-nucleotide polymorphisms associated with right-supramarginal gyrus activity. RPL36 also predicted right-supramarginal gyrus activity. In addition to replicating hypoactivation for oddball targets in SZ, this study identifies novel relationships between regional activity, cognitive performance, and genetic loci that warrant replication, emphasizing the need for continued data sharing and collaborative efforts. [ABSTRACT FROM AUTHOR]

Abstract: Diffusion tensor imaging was used to evaluate cerebral white matter in eight patients (ages 10–17), with myotonic dystrophy type 1 (3 congenital-onset, 5 juvenile-onset) compared to eight controls matched for age and sex. Four regions of interest were examined: inferior frontal, superior frontal, supracallosal, and occipital. The myotonic dystrophy group showed white matter abnormalities compared to controls in all regions. All indices of white matter integrity were abnormal: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. With no evidence of regional variation, correlations between whole cerebrum white matter fractional anisotropy and neurocognitive functioning were examined in the patients. Strong correlations were observed between whole cerebrum fractional anisotropy and full-scale intelligence and a measure of executive functioning. Results indicate that significant white matter abnormality is characteristic of young patients with myotonic dystrophy type 1 and that the white matter abnormality seen with neuroimaging has implications for cognitive functioning. [ABSTRACT FROM AUTHOR]

Abstract: Schizophrenia and Attention-Deficit/Hyperactivity Disorder (ADHD) are associated with similar deficits in working memory, attention, and inhibition. Both disorders also involve abnormalities of white matter integrity, possibly reflecting neural communication disruptions. There are likely some regional white matter abnormalities that underlie the common cognitive impairment, though also some regional abnormalities unique to each disorder. We used diffusion tensor imaging (DTI) to compare white matter integrity, as indicated by fractional anisotropy (FA), in adolescents with schizophrenia (n =15) or ADHD (n =14) and healthy controls (n =26). Schizophrenia patients had uniquely low FA, relative to the other two groups, in bilateral cerebral peduncles, anterior and posterior corpus callosum, right anterior corona radiata, and right superior longitudinal fasciculus. ADHD patients had uniquely high FA in left inferior and right superior frontal regions. Both clinical groups had lower FA than controls in left posterior fornix. The two disorders generally demonstrated distinct patterns of abnormal connectivity suggesting that common cognitive and behavioral deficits derive from distinct sources, though the posterior fornix may be involved in both disorders. Schizophrenia was associated with abnormally low FA in widespread circuitry indicative of general connectivity disruptions, whereas ADHD was associated with abnormally high FA in frontal networks that may indicate impaired branching of fibers. [Copyright &y& Elsevier]