Dataset Information

Joint analysis of frontal theta synchrony and white matter following mild traumatic brain injury.

ABSTRACT: Some of the most disabling aspects of mild traumatic brain injury (mTBI) include lingering deficits in executive functioning. It is known that mTBI can damage white matter tracts, but it remains unknown how this structural brain damage translates into cognitive deficits. This experiment utilized theta band phase synchrony to identify the dysfunctional neural operations that contribute to cognitive problems following mTBI. Sub-acute stage (< 2 weeks) mTBI patients (N = 52) and healthy matched controls (N = 32) completed a control-demanding task with concurrent EEG. Structural MRI was also collected. While there were no performance-specific behavioral differences between groups in the dot probe expectancy task, the degree of theta band phase synchrony immediately following injury predicted the degree of symptom recovery two months later. Although there were no differences in fractional anisotropy (FA) between groups, joint independent components analysis revealed that a smaller network of lower FA-valued voxels contributed to a diminished frontal theta phase synchrony network in the mTBI group. This finding suggests that frontal theta band markers of cognitive control are sensitive to sub-threshold structural aberrations following mTBI.

SUBMITTER: Cavanagh JF

PROVIDER: S-EPMC6992511 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Joint analysis of frontal theta synchrony and white matter following mild traumatic brain injury.

Cavanagh James F JF Rieger Rebecca E RE Wilson J Kevin JK Gill Darbi D Fullerton Lynne L Brandt Emma E Mayer Andrew R AR

Brain imaging and behavior 20201201 6

Some of the most disabling aspects of mild traumatic brain injury (mTBI) include lingering deficits in executive functioning. It is known that mTBI can damage white matter tracts, but it remains unknown how this structural brain damage translates into cognitive deficits. This experiment utilized theta band phase synchrony to identify the dysfunctional neural operations that contribute to cognitive problems following mTBI. Sub-acute stage (< 2 weeks) mTBI patients (N = 52) and healthy matched con ...[more]

PMID: 31368085

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Project description:Mild traumatic brain injuries (mTBIs) are a prevalent form of injury that can result in persistent neurological impairments. Microglial activation has become increasingly recognized as a key process regulating the pathology of white matter in a wide range of brain injury and disease contexts. As white matter damage is known to be a major contributor to the impairments that follow mTBI, microglia have rightfully become a common target of investigation for the development of mTBI therapies and biomarkers. Recent work has demonstrated that the efficacy of microglial manipulation as a therapeutic intervention following injury or disease is highly time-sensitive, emphasizing the importance of advancing our understanding of the dynamics of post-mTBI microglial activation from onset to resolution. Current reporting of microglial activation in experimental studies of mTBI is non-standardized, which has limited our ability to identify concrete patterns of post-mTBI microglial activation over time. In this review, we examine preclinical studies of mTBI that report on microglial activation in white matter regions to summarize our current understanding of these patterns. Specifically, we summarize timecourses of post-mTBI microglial activation in white matter regions of the brain, identify factors that influence this activation, examine the temporal relationship between microglial activation and other post-mTBI assessments, and compare the relative sensitivities of various methods for detecting microglial activation. While the lack of replicated experimental conditions has limited the extent of conclusions that can confidently be drawn, we find that microglia are activated over a wide range of timecourses following mTBI and that microglial activation is a long-lasting outcome of mTBI that may resolve after most typical post-mTBI assessments, with the exception of those measuring oligodendrocyte lineage cell integrity. We identify several understudied parameters of post-mTBI microglial activation in white matter, such as the inclusion of female subjects. This review summarizes our current understanding of the progression of microglial activation in white matter structures following experimental mTBI and offers suggestions for important future research directions.

Project description:Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function.

Dataset Information

Joint analysis of frontal theta synchrony and white matter following mild traumatic brain injury.

Publications

Joint analysis of frontal theta synchrony and white matter following mild traumatic brain injury.

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