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 x 0.78 mm x 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.

Figure 1 Thalamic nuclei Seed regions for the ventral posterior lateral nucleus (VPL) (green), anterior thalamic nucleus (AN) (purple), ventral anterior thalamic nucleus (VA) (red), dorsomedial nucleus (DM) (orange), ventral lateral thalamic nucleus (VL) (blue), ventral posterior medial nucleus (VPM) (yellow), and pulvinar (PU) (pink) overlaid on the T2-weighted images.

Figure 2 Average cortical and subcortical fractional anisotropy (FA) Mean FA extracted from the anterior corona radiata (ACR), posterior corona radiata (PCR), forceps major (fMaj), and body of the corpus callosum (body of the corpus callosum) as well as from the thalamus and from fibers identified from seed regions in the anterior thalamic nucleus (AN) and ventral anterior thalamic nucleus (VA). Significant post hoc comparisons between groups are indicated (*p < 0.05; **p < 0.01). Cortical in this figure refers to regions of interest that include cortico-cortico tracts and regions in the corpus callosum.

Figure 3 Relationship between thalamic fractional anisotropy (FA) and cognition Scatterplots of FA from thalamic seed voxels relative to executive (A), attention (B), and memory (C) domain scores for traumatic brain injury (TBI) patients. Best-fit lines are indicated in black.