Thalamic integrity underlies executive dysfunction in traumatic brain injury

Abstract

Objective: To quantify the effects of traumatic brain injury on integrity of thalamocortical projection fibers and to evaluate whether damage to these fibers accounts for impairments in executive function in chronic traumatic brain injury.Methods: High-resolution (voxel size: 0.78 mm ϫ 0.78 mm ϫ 3 mm 3 ) diffusion tensor MRI of the thalamus was conducted on 24 patients with a history of single, closed-head traumatic brain injury (TBI) (12 each of mild TBI and moderate to severe TBI) and 12 age-and education-matched controls. Detailed neuropsychological testing with an emphasis on executive function was also conducted. Fractional anisotropy was extracted from 12 regions of interest in cortical and corpus callosum structures and 7 subcortical regions of interest (anterior, ventral anterior, ventral lateral, dorsomedial, ventral posterior lateral, ventral posterior medial, and pulvinar thalamic nuclei). Results:Relative to controls, patients with a history of brain injury showed reductions in fractional anisotropy in both the anterior and posterior corona radiata, forceps major, the body of the corpus callosum, and fibers identified from seed voxels in the anterior and ventral anterior thalamic nuclei. Fractional anisotropy from cortico-cortico and corpus callosum regions of interest did not account for significant variance in neuropsychological function. However, fractional anisotropy from the thalamic seed voxels did account for variance in executive function, attention, and memory. Conclusions:The data provide preliminary evidence that traumatic brain injury and resulting diffuse axonal injury results in damage to the thalamic projection fibers and is of clinical relevance to cognition. Neurology ® 2010;74:558 -564 GLOSSARY ACR ϭ anterior corona radiata; AN ϭ anterior thalamic nucleus; bCC ϭ body of the corpus callosum; CST ϭ cortical-spinal tract; DAI ϭ diffuse axonal injury; DM ϭ dorsomedial nucleus; DTI ϭ diffusion tensor imaging; FA ϭ fractional anisotropy; fMaj ϭ forceps major; fMin ϭ forceps minor; FOV ϭ field of view; FSE ϭ fast spin echo; gCC ϭ genu of the corpus callosum; IC ϭ internal capsule; IFOF ϭ inferior frontal occipital fasciculus; LOC ϭ loss of consciousness; miTBI ϭ mild TBI; msTBI ϭ moderate to severe TBI; NEX ϭ number of excitations; PCR ϭ posterior corona radiata; PTA ϭ posttraumatic amnesia; PU ϭ pulvinar; ROI ϭ region of interest; sCC ϭ splenium of the corpus callosum; SLF ϭ superior longitudinal fasciculus; SS ϭ sagittal stratum; TBI ϭ traumatic brain injury; TE ϭ echo time; TR ϭ repetition time; VA ϭ ventral anterior thalamic nucleus; VL ϭ ventral lateral thalamic nucleus; VPL ϭ ventral posterior lateral nucleus; VPM ϭ ventral posterior medial nucleus. Traumatic brain injury (TBI) is a serious public health problem with a high incidence 1-3 which can result in structural damage to the cerebrum including contusions, edema, and diffuse axonal injury (DAI).4 DAI has been demonstrated in all stages and severities [5][6][7] and is often the only significant pathology in milder injury...

A prospective study of gray matter abnormalities in mild traumatic brain injury

“…Supplemental 2 3 2 (group 3 time) ANCOVA analyses were also conducted to examine the effects of mTBI on voxel-wise subcortical diffusion metrics and vertex-wise cortical thickness measurements in light of previous results from patients with chronic mTBI. 3,4 However, no significant effects were detected for any analyses following appropriate corrections for false positives. Finally, a recent publication 25 identified significant longitudinal differences (within-subject) in regional brain volume over a 1-year period in patients with mTBI using paired t tests.…”

“…Previous studies reported nonsignificant trends 3 and reduced 4 anisotropic diffusion after mTBI. However, both studies were conducted with chronically symptomatic and/or mixed patient populations.…”

Principal Component Analysis of Diffusion Tensor Images to Determine White Matter Injury Patterns Underlying Postconcussive Headache

“…20 Similarly, attempts to correlate structural injuries with postconcussive cognitive perfor- mance have shown mixed results without a strong anatomic/ pathologic correlation, with deficits detected in regions as diverse as the occipital cortex and corticospinal tracts. [21][22][23][24][25] This finding suggests that not all regions with differences in FA between patients and controls are necessarily symptomatic. 1 Reduced FA in 1 region alone may not, in and of itself, be clinically relevant.…”

MRI Characterization of Progressive Brain Alterations After Experimental Traumatic Brain Injury: Region Specific Tissue Damage, Hemodynamic Changes and Axonal Injury

“…Our study did not yield any correlations between CBF changes and memory and learning impairment, but poor performance in the Morris water maze was found to correlate with enhanced thalamic vessel density (r = -0.81, p < 0.01). The thalamus is often found to be damaged in moderate and severely injured TBI patients as well as in animal models (Pierce et al 1998, Maxwell et al 2004, Tollard et al 2009, Little et al 2010, but the role of the thalamic pathology in epileptogenesis after acquired etiologies like TBI is poorly understood (Bonilha et al 2004, Blumenfeld et al 2009). We also found that a high vessel density in the ipsilateral thalamus was associated with increased CBF and enhanced seizure susceptibility in injured rats.…”