White Matter Structural Integrity Research Articles

Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia.

Vascular cognitive impairment is the second most common form of dementia. The pathogenic pathways leading to vascular cognitive impairment remain unclear but clinical and experimental data have shown that chronic reactive astrogliosis occurs within white matter lesions, indicating that a sustained pro-inflammatory environment affecting the white matter may contribute towards disease progression. To model vascular cognitive impairment, we induced prolonged mild cerebral hypoperfusion in mice by bilateral common carotid artery stenosis. This chronic hypoperfusion resulted in reactive gliosis of astrocytes and microglia within white matter tracts, demyelination and axonal degeneration, consecutive spatial memory deficits, and loss of white matter integrity, as measured by ultra high-field magnetic resonance diffusion tensor imaging. White matter astrogliosis was accompanied by activation of the pro-inflammatory transcription factor nuclear factor (NF)-kB in reactive astrocytes. Using mice expressing a dominant negative inhibitor of NF-kB under the control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter (GFAP-IkBα-dn), we found that transgenic inhibition of astroglial NF-kB signaling ameliorated gliosis and axonal loss, maintained white matter structural integrity, and preserved memory function. Collectively, our results imply that pro-inflammatory changes in white matter astrocytes may represent an important detrimental component in the pathogenesis of vascular cognitive impairment, and that targeting these pathways may lead to novel therapeutic strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0350-3) contains supplementary material, which is available to authorized users.

Early Shifts of Brain Metabolism By Caloric Restriction Preserve White Matter Integrity and Long‐term Memory in Aging Mice

Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals’ memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between normal aging and CR aging on brain functions - normal aging showed reductions in brain glucose metabolism, white matter integrity, and long-term memory, resembling human brain aging. CR aging, in contrast, displayed an early shift from glucose to ketone bodies metabolism, which was associated with preservations of brain energy production, white matter integrity, and long-term memory in aging mice. Among all the mice, we found a positive correlation between blood glucose level and body weight, but an inverse association between blood glucose level and lifespan. Our findings suggest that CR could slow down brain aging, in part due to the early shift of energy metabolism caused by lower caloric intake, and we were able to identify the age-dependent effects of CR non-invasively using neuroimaging. These results provide a rationale for CR-induced sustenance of brain health with extended longevity.

Higher Blood Pressure Partially Links Greater Adiposity to Reduced Brain White Matter Integrity.

Adiposity and elevated blood pressure (BP) are associated with brain structure abnormalities, but whether these effects are independent is unknown. We tested whether associations between adiposity and white matter integrity were explained by elevated BP. A sample of 209 middle-aged adults underwent diffusion tensor imaging to quantify indirect metrics of white matter structural integrity. These included putative markers of global white matter integrity (fractional anisotropy (FA)), axonal integrity (axial diffusivity), and myelin integrity (radial diffusivity). Participants were either normotensive or prehypertensive. After adjusting for age and sex, regression analyses showed that waist circumference was associated with FA (β = -0.15, P < 0.05) and axial diffusivity (β = -0.24, P < 0.001), and mean arterial pressure (MAP) was associated with FA (β = -0.21, P < 0.05). Direct and indirect effect analyses showed that waist circumference was indirectly associated with whole brain FA through MAP (β = -0.06), and directly related to whole brain axial diffusivity, independent of MAP (β = -0.24). Examination of specific white matter tracts yielded similar results; waist circumference was indirectly related to FA through MAP and radial diffusivity, and directly related to axial diffusivity, independent of MAP. Supplemental analyses using body mass index, systolic BP, and diastolic BP also yielded similar results. These findings suggest at least 2 mechanisms explain the adiposity and white matter association: one pathway through elevated BP impacting global white matter integrity and reducing integrity of the myelin sheath, and at least one other adiposity-specific pathway decreasing axonal integrity.

Diffusion tensor imaging of the corticospinal tract and walking performance in multiple sclerosis

Research has identified a significant relationship between DTI (Diffusion Tensor Imaging) indices in the Corticospinal Tract (CST) and disability status in persons with multiple sclerosis (MS). To date, there is little known about the association between DTI indices of the CST with walking and gait outcomes in MS. This study examined the associations among DTI indices [fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD)] of the CST with walking and gait outcomes in persons with MS. We enrolled 69 persons with MS who underwent 3T brain magnetic resonance imaging (MRI) and examined white matter structural integrity in the CST in the brain with DTI. Participants completed three walking performance assessments: 6-minute walk (6MW), timed 25-foot walk (T25FW), and gait testing. We examined associations using Spearman (rs) and partial Spearman correlation (prs) analyses, using the entire sample and stratifying by disability status after controlling for age and sex. After controlling for age, sex, and disease duration, RD was significantly correlated (p<0.05) with step time (prs=0.30). AD was significantly correlated (p<0.05) with step length (prs=−0.32). MD was significantly associated (p<0.05) with 6MW (prs=−0.35), T25FW (prs=−0.34), gait velocity (prs=−0.31), step time (prs=0.29), and step length (prs=−0.36). FA was not significantly correlated with any of the walking parameters (p>0.05). We provide novel evidence of possible motor pathway damage involved in walking performance in MS. There may be subtle differences in associations between MD, AD, and RD with walking outcomes, and these could be assessed in future longitudinal examinations and clinical trials of motor rehabilitation.

Cognitive Deficits Correlate with White Matter Deterioration in Spinocerebellar Ataxia Type 2.

The aim of this study was to explore the relationship between cognitive and white matter deterioration in a group of participants with spinocerebellar ataxia type 2 (SCA2). Fourteen genetically confirmed participants with SCA2 and 14 aged-matched controls participated in the study. Diffusion tensor imaging tract-based spatial statistics were performed to analyze structural white matter integrity. Significant group differences in the mean diffusivity were correlated with SCA2 cognitive deficits. Our analysis revealed higher mean diffusivity in the SCA2 group in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Cognitive scores correlated with white matter mean diffusivity in the parahippocampal area, inferior frontal and supramarginal gyri and the stria terminalis. Our findings show significant correlations between white matter microstructural damage in key areas affected in SCA2 and cognitive deficits. These findings result in a more comprehensive understanding of the effect of the neurodegenerative process in people with SCA2.

Tobacco Smoke-Induced Brain White Matter Myelin Dysfunction: Potential Co-Factor Role of Smoking in Neurodegeneration.

Meta-analysis studies showed that smokers have increased risk for developing Alzheimer's disease (AD) compared with non-smokers, and neuroimaging studies revealed that smoking damages white matter structural integrity. The present study characterizes the effects of side-stream (second hand) cigarette smoke (CS) exposures on the expression of genes that regulate oligodendrocyte myelin-synthesis, maturation, and maintenance and neuroglial functions. Adult male A/J mice were exposed to air (8 weeks; A8), CS (4 or 8 weeks; CS4, CS8), or CS8 followed by 2 weeks recovery (CS8 + R). The frontal lobes were used for histology and qRT-PCR analysis. Luxol fast blue, Hematoxylin and Eosin stained histological sections revealed CS-associated reductions in myelin staining intensity and narrowing of the corpus callosum. CS exposures broadly decreased mRNA levels of immature and mature oligodendrocyte myelin-associated, neuroglial, and oligodendrocyte-related transcription factors. These effects were more prominent in the CS8 compared with CS4 group, suggesting that molecular abnormalities linked to white matter atrophy and myelin loss worsen with duration of CS exposure. Recovery normalized or upregulated less than 25% of the suppressed genes; in most cases, inhibition of gene expression was either sustained or exacerbated. CS exposures broadly inhibit expression of genes needed for myelin synthesis and maintenance. These adverse effects often were not reversed by short-term CS withdrawal. The results support the hypothesis that smoking contributes to white matter degeneration, and therefore could be a key risk factor for a number of neurodegenerative diseases, including AD.

Effects of white matter microstructure lesions on language and memory function in magnetic resonance imaging-negative temporal lobe epilepsy determined by diffusion tensor imaging.

This study was conducted to investigate the associations between white matter lesions and language and memory dysfunctions in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy. This study included 26 patients with temporal lobe epilepsy, who did not have significant findings on conventional MRI scanning, and 17 healthy subjects as control. Diffusion tensor imaging data was obtained with a 3Tesla (T) MRI scanner. Neuropsychological scores of language and memory functions were measured. One-way analysis of variance was used to analyze abnormal fractional anisotropy and mean diffusivity values. Correlations were performed to evaluate the relationship between fractional anisotropy/mean diffusivity of each fiber tract and neuropsychological measures. Regression analysis was performed to determine the contribution of each fiber tract to cognitive performance. Our data showed significantly decreased neuropsychological scores in the left and right temporal lobe epilepsy groups compared with control; it however, failed to show a statistical difference between the two groups. For the left temporal lobe epilepsy group, the mean diffusivity of the left parahippocampal and cingulate cortex, right arcuate fasciculus, and left fornix were significantly higher than control. Fractional anisotropy of the right fornix and mean diffusivity of the left uncinate fasciculus were significantly related to confrontational naming scores. There were significant correlations between the fractional anisotropy of the left fornix and verbal delayed memory scores and between the fractional anisotropy of the left fornix and nonverbal delayed memory scores. The mean diffusivity of left fractional anisotropy and the fractional anisotropy of the left uncinate fasciculus were significantly related to confrontational naming and verbal fluency scores, and seizure frequency was significantly related to nonverbal delayed memory scores. Language and memory function impairment was correlated with white matter structural integrity.

Developmental neurotoxicity of inhaled ambient ultrafine particle air pollution: Parallels with neuropathological and behavioral features of autism and other neurodevelopmental disorders

Accumulating evidence from both human and animal studies show that brain is a target of air pollution. Multiple epidemiological studies have now linked components of air pollution to diagnosis of autism spectrum disorder (ASD), a linkage with plausibility based on the shared mechanisms of inflammation. Additional plausibility appears to be provided by findings from our studies in mice of exposures from postnatal day (PND) 4–7 and 10–13 (human 3rd trimester equivalent), to concentrated ambient ultrafine (UFP) particles, considered the most reactive component of air pollution, at levels consistent with high traffic areas of major U.S. cities and thus highly relevant to human exposures. These exposures, occurring during a period of marked neuro- and gliogenesis, unexpectedly produced a pattern of developmental neurotoxicity notably similar to multiple hypothesized mechanistic underpinnings of ASD, including its greater impact in males. UFP exposures induced inflammation/microglial activation, reductions in size of the corpus callosum (CC) and associated hypomyelination, aberrant white matter development and/or structural integrity with ventriculomegaly (VM), elevated glutamate and excitatory/inhibitory imbalance, increased amygdala astrocytic activation, and repetitive and impulsive behaviors. Collectively, these findings suggest the human 3rd trimester equivalent as a period of potential vulnerability to neurodevelopmental toxicity to UFP, particularly in males, and point to the possibility that UFP air pollution exposure during periods of rapid neuro- and gliogenesis may be a risk factor not only for ASD, but also for other neurodevelopmental disorders that share features with ASD, such as schizophrenia, attention deficit disorder, and periventricular leukomalacia.

White matter structural integrity differs between people with schizophrenia and healthy groups as a function of cognitive control

A behavioral hallmark of schizophrenia is poor cognitive control. Recent evidence suggests that problems with cognitive control in schizophrenia are related to disconnectivity along major white matter fibers. Although deficits of cognitive control are common in schizophrenia, a proportion of otherwise healthy subjects show poor cognitive control performance. The present study sought to address this potential confound by comparing white matter integrity between a group with schizophrenia and otherwise healthy individuals with either high or low levels of cognitive control (based on working memory span performance). Diffusion tensor imaging was used to evaluate white matter integrity in 24 participants with schizophrenia, 24 healthy participants with high cognitive control (HCC), and 25 healthy participants with low cognitive control (LCC). To test for differences in fractional anisotropy (FA) across major white matter fiber tracts, a voxelwise region of interest analysis was conducted in standardized brain space. In a separate analysis, regions of interest were manually drawn in native brain space to isolate superior longitudinal fasciculus (SLF), a tract implicated in cognitive control performance. The voxelwise analysis demonstrated widespread lower FA in the schizophrenia group compared to the HCC group. With a high degree of concordance, the manual ROI analysis revealed lower FA in the schizophrenia group compared to the HCC group. Taken together, these results provide evidence to suggest that structural differences identified between healthy groups and schizophrenia may not be entirely specific to the disease process and can vary as a function of cognitive control capacity in the comparison group.

Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice.

Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals’ memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between normal aging and CR aging on brain functions – normal aging showed reductions in brain glucose metabolism, white matter integrity, and long-term memory, resembling human brain aging. CR aging, in contrast, displayed an early shift from glucose to ketone bodies metabolism, which was associated with preservations of brain energy production, white matter integrity, and long-term memory in aging mice. Among all the mice, we found a positive correlation between blood glucose level and body weight, but an inverse association between blood glucose level and lifespan. Our findings suggest that CR could slow down brain aging, in part due to the early shift of energy metabolism caused by lower caloric intake, and we were able to identify the age-dependent effects of CR non-invasively using neuroimaging. These results provide a rationale for CR-induced sustenance of brain health with extended longevity.

Differential motor and prefrontal cerebello-cortical network development: Evidence from multimodal neuroimaging

While our understanding of cerebellar structural development through adolescence and young adulthood has expanded, we still lack knowledge of the developmental patterns of cerebellar networks during this critical portion of the lifespan. Volume in lateral posterior cerebellar regions associated with cognition and the prefrontal cortex develops more slowly, reaching their peak volume in adulthood, particularly as compared to motor Lobule V. We predicted that resting state functional connectivity of the lateral posterior regions would show a similar pattern of development during adolescence and young adulthood. That is, we expected to see changes over time in Crus I and Crus II connectivity with the cortex, but no changes in Lobule V connectivity. Additionally, we were interested in how structural connectivity changes in cerebello-thalamo-cortical white matter are related to changes in functional connectivity. A sample of 23 individuals between 12 and 21years old underwent neuroimaging scans at baseline and 12months later. Functional networks of Crus I and Crus II showed significant connectivity decreases over 12months, though there were no differences in Lobule V. Furthermore, these functional connectivity changes were correlated with increases in white matter structural integrity in the corresponding cerebello-thalamo-cortical white matter tract. We suggest that these functional network changes are due to both later pruning in the prefrontal cortex as well as further development of the white matter tracts linking these brain regions.

Altered contralateral sensorimotor system organization after experimental hemispherectomy: a structural and functional connectivity study.

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.

Abnormal hippocampal-thalamic white matter tract development and positive symptom course in individuals at ultra-high risk for psychosis.

Background/Objectives:Abnormal development of the hippocampus has been reported in adolescents at ultra-high risk (UHR) for psychosis and thalamic abnormalities have been found. However, the white matter connections between the hippocampus and the thalamus have not been studied. The connections between these regions are of key importance to our understanding of the pathophysiology of psychosis.Methods:Twenty-six UHR and 21 healthy age-matched controls were tested at a baseline assessment and 12 months later. Symptoms were assessed at both the time points and all the participants underwent diffusion tensor imaging scans. We used tractography to trace the white matter connections in each individual between the thalamus and hippocampus and then extracted fractional anisotropy (FA) to assess white matter structural integrity.Results:There was a significant group by time interaction indicating that FA decreased in UHR, and increased in controls over 12 months. Across both groups, baseline FA of the thalamic–hippocampal tract was predictive of positive symptoms at 12-month follow-up. Critically, this pattern remained significant in UHR individual group alone. At baseline, those with higher FA, indicative of abnormal white matter development, show higher positive symptoms 1 year later.Conclusions:Here, we provide evidence to indicate that there are differences in white matter development in hippocampal–thalamic connections, both of which are important nodes in networks associated with schizophrenia. Furthermore, abnormal developmental patterns in UHR individuals are associated with positive symptom course.

Memory binding and white matter integrity in familial Alzheimer's disease.

Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to be markers for Alzheimer's disease.

A Comparative Study of White Matter Structural Integrity Through Diffusion Tensor Imaging Tractography in Bipolar Disorder Patients Compared to First Degree Relatives and Healthy Controls

Objective To compare the white matter structural changes in specific axonal tracts detailed by diffusion tensor imaging (DTI) tractography in patients of bipolar disorder I, non-ill first degree relatives of the patients, and healthy controls in Indian population. Methods In a cross sectional study, we studied right-handed subjects consisting of 15 euthymic bipolar disorder I patients, 15 first degree relatives and 15 healthy controls. White matter tracts, including the anterior thalamic radiation, uncinate fasciculus, corpus callosum, and cingulum bundle were reconstructed by DTI tractography. Mean fractional anisotropy (FA) values were compared for group differences followed by post hoc analysis. Results The three groups did not differ in terms of socio-demographic variables. There were significant group differences in the FA values between the bipolar disorder I, first degree relatives and the healthy control groups for corpus callosum (H=35.922, p Conclusion The findings suggest that bipolar disorder patients and their first degree relatives show alterations in microstructural integrity of white matter tracts, compared to healthy population.

Quantifying white matter structural integrity with high-definition fiber tracking in traumatic brain injury.

There is an urgent, unmet demand for definitive biological diagnosis of traumatic brain injury (TBI) to pinpoint the location and extent of damage. We have developed High-Definition Fiber Tracking, a 3 T magnetic resonance imaging-based diffusion spectrum imaging and tractography analysis protocol, to quantify axonal injury in military and civilian TBI patients. A novel analytical methodology quantified white matter integrity in patients with TBI and healthy controls. Forty-one subjects (23 TBI, 18 controls) were scanned with the High-Definition Fiber Tracking diffusion spectrum imaging protocol. After reconstruction, segmentation was used to isolate bilateral hemisphere homologues of eight major tracts. Integrity of segmented tracts was estimated by calculating homologue correlation and tract coverage. Both groups showed high correlations for all tracts. TBI patients showed reduced homologue correlation and tract spread and increased outlier count (correlations>2.32 SD below control mean). On average, 6.5% of tracts in the TBI group were outliers with substantial variability among patients. Number and summed deviation of outlying tracts correlated with initial Glasgow Coma Scale score and 6-month Glasgow Outcome Scale-Extended score. The correlation metric used here can detect heterogeneous damage affecting a low proportion of tracts, presenting a potential mechanism for advancing TBI diagnosis.

Predicting Prodromal Alzheimer's Disease in Subjects with Mild Cognitive Impairment Using Machine Learning Classification of Multimodal Multicenter Diffusion-Tensor and Magnetic Resonance Imaging Data.

Alzheimer's disease (AD) patients show early changes in white matter (WM) structural integrity. We studied the use of diffusion tensor imaging (DTI) in assessing WM alterations in the predementia stage of mild cognitive impairment (MCI). We applied a Support Vector Machine (SVM) classifier to DTI and volumetric magnetic resonance imaging data from 35 amyloid-β42 negative MCI subjects (MCI-Aβ42-), 35 positive MCI subjects (MCI-Aβ42+), and 25 healthy controls (HC) retrieved from the European DTI Study on Dementia. The SVM was applied to DTI-derived fractional anisotropy, mean diffusivity (MD), and mode of anisotropy (MO) maps. For comparison, we studied classification based on gray matter (GM) and WM volume. We obtained accuracies of up to 68% for MO and 63% for GM volume when it came to distinguishing between MCI-Aβ42- and MCI-Aβ42+. When it came to separating MCI-Aβ42+ from HC we achieved an accuracy of up to 77% for MD and a significantly lower accuracy of 68% for GM volume. The accuracy of multimodal classification was not higher than the accuracy of the best single modality. Our results suggest that DTI data provide better prediction accuracy than GM volume in predementia AD.

The Evolution of Schizophrenia Research and Treatment

About 100 years after Kraepelin laid the foundation of the current concept of schizophrenia (Falkai et al., 2015), sadly, much remains to be understood about this disease. As the research domain criteria (Buckley & Miller, 2015) are gradually being utilized, perhaps significantly altering our understanding of schizophrenia, work continues, increasingly using novel approaches – particularly the application of genetics and new technologies. Many markers have been linked with schizophrenia but findings do not support a full genetic “profile.” (Chen et al., 2015) Neuroimaging technologies in particular have illuminated common areas of abnormalities including altered structural integrity of white matter in frontal and temporal brain regions and altered structural relationships among regional morphology in the thalamus, frontal, temporal and parietal cortices (Wheeler & Voineskos, 2014), while more research is needed to further define progressive changes and response to medication. Pharmacologically, we have progressed to a third generation of antipsychotics (Kelleher, 2004), although the challenges of balancing efficacy and side effects, particularly within the framework of cost efficient care is a significant issue. Clozapine remains the most efficacious antipsychotic although its most essential pharmacologic characteristic remains inadequately understood (Dold & Leucht, 2014). The best treatment of patients with schizophrenia involves not only psychopharmacology and psychotherapy but also attention to nonpsychiatric medical issues (Shulman, Miller, Misher & Tentler, 2014).

Neuroscience 2014 Showcases Advances in Mental Health Research

Knowledge about structure, development, health, and diseases of the brain and nervous system is advancing rapidly, according to research by some of the world’s leading neuroscientists.

White matter integrity and cognitive performance in children with prenatal methamphetamine exposure

There is emerging evidence on the harmful effects of prenatal methamphetamine (MA) exposure on the structure and function of the developing brain. However, few studies have assessed white matter structural integrity in the presence of prenatal MA exposure, and results are inconsistent. This investigation thus used diffusion tensor imaging (DTI) to investigate white matter microstructure and cognitive performance in a group of prenatal MA exposed (or MA) children and controls of similar age. Seventeen MA children and 15 healthy controls (aged 6–7 years) underwent DTI and assessment of motor function and general cognitive ability. Whole brain analyses of white matter structure were performed using FSL's tract-based spatial statistics comparing fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Mean diffusion values were extracted from white matter regions shown to differ across groups to determine whether variations in FA predicted cognitive performance. Analyses were controlled for maternal nicotine use. MA children showed significantly lower FA as well as higher MD, RD and AD in tracts that traverse striatal, limbic and frontal regions. Abnormal FA levels in MA children were significantly associated with poorer motor coordination and general cognitive ability sub-items that relate to aspects of executive function. Our findings suggest that, consistent with previous studies in older children, there are disruptions of white matter microstructural integrity in striatal, limbic and frontal regions of young MA exposed children, with prominent cognitive implications. Future longitudinal studies may clarify how prenatal MA exposure affects white matter structural connectivity at different stages of brain maturation.