Microstructural abnormalities in deep and superficial white matter in youths with mild traumatic brain injury

BACKGROUND: Diffusion Tensor Imaging (DTI) studies of traumatic brain injury (TBI) have focused on alterations in microstructural features of deep white matter fibers (DWM), though post-mortem studies have demonstrated that injured axons are often observed at the gray-white matter interface where superficial white matter fibers (SWM) mediate local connectivity. OBJECTIVES: To examine microstructural alterations in SWM and DWM in youths with a history of mild TBI and examine the relationship between white matter alterations and attention. METHODS: Using DTIDWM fractional anisotropy (FA) and SWM FA in youths with mild TBI (TBI, n=63) were compared to typically developing and psychopathology matched control groups (n=63 each). Following tract-based spatial statistics, SWM FA was assessed by applying a probabilistic tractography derived SWM mask, and DWM FA was captured with a white matter fiber tract mask. Voxel-wise z-score calculations were used to derive a count of voxels with abnormally high and low FA for each participant. Analyses examined DWM and SWM FA differences between TBI and control groups, the relationship between attention and DWM and SWM FA and the relative susceptibility of SWM compared to DWM FA to alterations associated with mild TBI. RESULTS: Case-based comparisons revealed more voxels with low FA and fewer voxels with high FA in SWM in youths with mild TBI compared to both control groups. Equivalent comparisons in DWM revealed a similar pattern of results, however, no group differences for low FA in DWM were found between mild TBI and the control group with matched psychopathology. Slower processing speed on the attention task was correlated with the number of voxels with low FA in SWM in youths with mild TBI. CONCLUSIONS: Within a sample of youths with a history of mild TBI, this study identified abnormalities in SWM microstructure associated with processing speed. The majority of DTI studies of TBI have focused on long-range DWM fiber tracts, often overlooking the SWM fiber type

Relationship of neurite architecture to brain activity during task-based fMRI

Functional MRI (fMRI) has been widely used to examine changes in neuronal activity during cognitive tasks. Commonly used measures of gray matter macrostructure (e.g., cortical thickness, surface area, volume) do not consistently appear to serve as structural correlates of brain function. In contrast, gray matter microstructure, measured using neurite orientation dispersion and density imaging (NODDI), enables the estimation of indices of neurite density (neurite density index; NDI) and organization (orientation dispersion index; ODI) in gray matter. Our study explored the relationship among neurite architecture, BOLD (blood-oxygen-level-dependent) fMRI, and cognition, using a large sample (n = 750) of young adults of the human connectome project (HCP) and two tasks that index more cortical (working memory) and more subcortical (emotion processing) targeting of brain functions. Using NODDI, fMRI, structural MRI and task performance data, hierarchical regression analyses revealed that higher working memory- and emotion processing-evoked BOLD activity was related to lower ODI in the right DLPFC, and lower ODI and NDI values in the right and left amygdala, respectively. Common measures of brain macrostructure (i.e., DLPFC thickness/surface area and amygdala volume) did not explain any additional variance (beyond neurite architecture) in BOLD activity. A moderating effect of neurite architecture on the relationship between emotion processing task-evoked BOLD response and performance was observed. Our findings provide evidence that neuro-/social-affective cognition-related BOLD activity is partially driven by the local neurite organization and density with direct impact on emotion processing. In vivo gray matter microstructure represents a new target of investigation providing strong potential for clinical translation

Sex and Diffusion Tensor Imaging of White Matter in Schizophrenia: A Systematic Review Plus Meta-analysis of the Corpus Callosum

Sex is considered an understudied variable in health research. Schizophrenia is a brain disorder with known sex differences in epidemiology and clinical presentation. We systematically reviewed the literature for sex-based differences of diffusion properties of white matter tracts in schizophrenia. We then conducted a meta-analysis examining sex-based differences in the genu and splenium of the corpus callosum in schizophrenia. Medline and Embase were searched to identify relevant papers. Studies fulfilling the following criteria were included: (1) included individuals with a diagnosis of schizophrenia, (2) included a control group of healthy individuals, (3) included both sexes in the patient and the control groups, (4) used diffusion tensor imaging, and (5) involved analyzing metrics of white matter microstructural integrity. Fractional anisotropy (FA) was used as the measure of interest in the meta-analysis. Of 730 studies reviewed, 75 met the inclusion criteria. Most showed no effect of sex, however, those that did found either that females have lower FA than males, or that the effect of disease in females is larger than that in males. The findings of the meta-analysis in the corpus callosum supported this result. There is a recognized need for studies on schizophrenia with a sufficient sample of female patients. Lack of power undermines the ability to detect sex-based differences. Understanding the sex-specific impact of illness on neural circuits may help inform development of new treatments, and improvement of existing interventions

The role of untreated psychosis in neurodegeneration: A review of hypothesized mechanisms of neurotoxicity in first-episode psychosis

For over 20 years, studies have tried to measure the association between the duration of untreated psychosis (DUP) and changes in brain morphology. A hypothesis that untreated psychosis is neurotoxic has been postulated, but the mechanisms of that toxicity have not been described. We re-analyzed papers collected for a systematic review to extract data on the hypotheses that have been generated on the potential mechanisms by which DUP could impact brain morphology in first-episode psychosis. Dopaminergic hyperactivity, prolonged hypothalamic-pituitary-adrenal activation, and persistent activity of catecholamines have been hypothesized as mechanisms to explain these associations. However, the question remains as to whether the observed structural changes are permanent or may be reversed via antipsychotic treatment

Modulation of functional network properties in major depressive disorder following electroconvulsive therapy (ECT): a resting-state EEG analysis

Electroconvulsive therapy (ECT) is a highly effective neuromodulatory intervention for treatment-resistant major depressive disorder (MDD). Presently, however, understanding of its neurophysiological effects remains incomplete. In the present study, we utilised resting-state electroencephalography (RS-EEG) to explore changes in functional connectivity, network topology, and spectral power elicited by an acute open-label course of ECT in a cohort of 23 patients with treatment-resistant MDD. RS-EEG was recorded prior to commencement of ECT and again within 48 h following each patient’s final treatment session. Our results show that ECT was able to enhance connectivity within lower (delta and theta) frequency bands across subnetworks largely confined to fronto-central channels, while, conversely, more widespread subnetworks of reduced connectivity emerged within faster (alpha and beta) bands following treatment. Graph-based topological analyses revealed changes in measures of functional segregation (clustering coefficient), integration (characteristic path length), and small-world architecture following ECT. Finally, post-treatment enhancement of delta and theta spectral power was observed, which showed a positive association with the number of ECT sessions received. Overall, our findings indicate that RS-EEG can provide a sensitive measure of dynamic neural activity following ECT and highlight network-based analyses as a promising avenue for furthering mechanistic understanding of the effects of convulsive therapies

Personality Goes a Long a Way: An Interhemispheric Connectivity Study

Throughout the development of psychology the delineation of personality has played a central role. Together with the NEO-PI-R, a questionnaire derived from the Five Factor Model of Personality, and recent advances in research technology it is now possible to investigate the relationship between personality features and neurophysiological brain processes. The NEO-FFI, the short version of the NEO-PI-R, reliably measures five main personality traits: Neuroticism, Extraversion, Openness to experience, Agreeableness, and Conscientiousness. As behavior and some psychiatric disorders have been related to interhemispheric connectivity, the present study used the combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to measure frontal interhemispheric connectivity and its association with personality as indexed by the NEO-FFI. Results demonstrated that prefrontal interhemispheric connectivity between the left and right dorsolateral prefrontal cortex correlates with Agreeableness in healthy subjects. This is the first study to relate personality features to interhemispheric connectivity through TMS–EEG and suggests that Agreeableness relates to the effectiveness of prefrontal communication between hemispheres

Myelin-Associated Glycoprotein Gene and Brain Morphometry in Schizophrenia

Myelin and oligodendrocyte disruption may be a core feature of schizophrenia pathophysiology. The purpose of the present study was to localize the effects of previously identified risk variants in the myelin-associated glycoprotein (MAG) gene on brain morphometry in schizophrenia patients and healthy controls. Forty-five schizophrenia patients and 47 matched healthy controls underwent clinical, structural magnetic resonance imaging, and genetics procedures. Gray and white matter cortical lobe volumes along with hippocampal volumes were calculated from T1-weighted MRI scans. Each subject was also genotyped for the two disease-associated MAG single nucleotide polymorphisms (rs720308 and rs720309). Repeated measures general linear model (GLM) analysis found significant region by genotype and region by genotype by diagnosis interactions for the effects of MAG risk variants on lobar gray matter volumes. No significant associations were found with lobar white matter volumes or hippocampal volumes. Follow-up univariate GLMs found the AA genotype of rs720308 predisposed schizophrenia patients to left temporal and parietal gray matter volume deficits. These results suggest that the effects of the MAG gene on cortical gray matter volume in schizophrenia patients can be localized to temporal and parietal cortices. Our results support a role for MAG gene variation in brain morphometry in schizophrenia, align with other lines of evidence implicating MAG in schizophrenia, and provide genetically based insight into the heterogeneity of brain imaging findings in this disorder

Meta-analysis and systematic review of skin graft donor-site dressings with future guidelines.

Background: Many types of split-thickness skin graft (STSG) donor-site dressings are available with little consensus from the literature on the optimal dressing type. The purpose of this systematic review was to analyze the most recent outcomes regarding moist and nonmoist dressings for STSG donor sites. Methods: A comprehensive systematic review was conducted across PubMed/MEDLINE, EMBASE, and Cochrane Library databases to search for comparative studies evaluating different STSG donor-site dressings in adult subjects published between 2008 and 2017. The quality of randomized controlled trials was assessed using the Jadad scale. Data were collected on donor-site pain, rate of epithelialization, infection rate, cosmetic appearance, and cost. Meta-analysis was performed for reported pain scores. Results: A total of 41 articles were included comparing 44 dressings. Selected studies included analysis of donor-site pain (36 of 41 articles), rate of epithelialization (38 of 41), infection rate (25 of 41), cosmetic appearance (20 of 41), and cost (10 of 41). Meta-analysis revealed moist dressings result in lower pain (pooled effect size = 1.44). A majority of articles (73%) reported better reepithelialization rates with moist dressings. Conclusion: The literature on STSG donor-site dressings has not yet identified an ideal dressing. Although moist dressings provide superior outcomes with regard to pain control and wound healing, there continues to be a lack of standardization. The increasing commercial availability and marketing of novel dressings necessitates the development of standardized research protocols to design better comparison studies and assess true efficacy.R01 EB021308 - NIBIB NIH HHSPublished versio

Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research