Patterns of change in cortical morphometry following traumatic brain injury in adults.

Progressive cortical volumetric loss following moderate-severe traumatic brain injury (TBI) has been observed; however, regionally specific changes in the structural determinants of cortical volume, namely, cortical thickness (CT) and cortical surface area (CSA), are unknown and may inform the patterns and neural substrates of neurodegeneration and plasticity following injury. We aimed to (a) assess differences in CT and CSA between TBI participants and controls in the early chronic stage post-injury, (b) describe longitudinal changes in cortical morphometry following TBI, and (c) examine how regional changes in CT and CSA are associated. We acquired magnetic resonance images for 67 participants with TBI at up to 4 time-points spanning 5 months to 7 years post-injury, and 18 controls at 2 time-points. In the early chronic stage, TBI participants displayed thinner cortices than controls, predominantly in frontal regions, but no CSA differences. Throughout the chronic period, TBI participants showed widespread CT reductions in posterior cingulate/precuneus regions and moderate CT increase in frontal regions. Additionally, CSA showed a significant decrease in the orbitofrontal cortex and circumscribed increase in posterior regions. No changes were identified in controls. Relationships between regional cortical changes in the same morphological measure revealed coordinated patterns within participants, whereas correlations between regions with CT and CSA change yielded bi-directional relationships. This suggests that these measures may be differentially affected by neurodegenerative mechanisms such as transneuronal degeneration following TBI and that degeneration may be localized to the depths of cortical sulci. These findings emphasize the importance of dissecting morphometric contributions to cortical volume change.

Progressive Neurodegeneration Across Chronic Stages of Severe Traumatic Brain Injury.

OBJECTIVE: To examine the trajectory of structural gray matter changes across 2 chronic periods of recovery in individuals who have sustained severe traumatic brain injury (TBI), adding to the growing literature indicating that neurodegenerative processes occur in the months to years postinjury. PARTICIPANTS: Patients who experienced posttraumatic amnesia of 1 hour or more, and/or scored 12 or less on the Glasgow Coma Scale at the emergency department or the scene of the accident, and/or had positive brain imaging findings were recruited while receiving inpatient care, resulting in 51 patients with severe TBI. METHODS: Secondary analyses of gray matter changes across approximately 5 months, 1 year, and 2.5 years postinjury were undertaken, using an automated segmentation protocol with improved accuracy in populations with morphological anomalies. We compared patients and matched controls on regions implicated in poorer long-term clinical outcome (accumbens, amygdala, brainstem, hippocampus, thalamus). To model brain-wide patterns of change, we then conducted an exploratory principal component analysis (PCA) on the linear slopes of all regional volumes across the 3 time points. Finally, we assessed nonlinear trends across earlier (5 months-1 year) versus later (1-2.5 years) time-windows with PCA to compare degeneration rates across time. Chronic degeneration was predicted cortically and subcortically brain-wide, and within specific regions of interest. RESULTS: (1) From 5 months to 1 year, patients showed significant degeneration in the accumbens, and marginal degeneration in the amygdala, brainstem, thalamus, and the left hippocampus when examined unilaterally, compared with controls. (2) PCA components representing subcortical and temporal regions, and regions from the basal ganglia, significantly differed from controls in the first time-window. (3) Progression occurred at the same rate across both time-windows, suggesting neither escalation nor attenuation of degeneration across time. CONCLUSION: Localized yet progressive decline emphasizes the necessity of developing interventions to offset degeneration and improve long-term functioning.

Changes in Resting-State Connectivity following Melody-Based Therapy in a Patient with Aphasia.

Melody-based treatments for patients with aphasia rely on the notion of preserved musical abilities in the RH, following left hemisphere damage. However, despite evidence for their effectiveness, the role of the RH is still an open question. We measured changes in resting-state functional connectivity following melody-based intervention, to identify lateralization of treatment-related changes. A patient with aphasia due to left frontal and temporal hemorrhages following traumatic brain injuries (TBI) more than three years earlier received 48 sessions of melody-based intervention. Behavioral measures improved and were maintained at the 8-week posttreatment follow-up. Resting-state fMRI data collected before and after treatment showed an increase in connectivity between motor speech control areas (bilateral supplementary motor areas and insulae) and RH language areas (inferior frontal gyrus pars triangularis and pars opercularis). This change, which was specific for the RH, was greater than changes in a baseline interval measured before treatment. No changes in RH connectivity were found in a matched control TBI patient scanned at the same intervals. These results are compatible with a compensatory role for RH language areas following melody-based intervention. They further suggest that this therapy intervenes at the level of the interface between language areas and speech motor control areas necessary for language production.

Magnetic resonance imaging evidence of progression of subacute brain atrophy in moderate to severe traumatic brain injury.

OBJECTIVE: To demonstrate subacute progression of brain atrophy (from 4.5-29mo postinjury) in moderate to severe traumatic brain injury (TBI) using structural magnetic resonance imaging (MRI). DESIGN: Within-subjects, repeated-measures design. SETTING: Inpatient neurorehabilitation program and teaching hospital (MRI department). PARTICIPANTS: Adults (N=14) with moderate to severe TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Neuroradiologist readings and volumetric measurements (total brain cerebrospinal fluid and hippocampus) at 4.5 months and 2.5 years postinjury. RESULTS: Ten of 14 patients showed visible atrophy progression. Significant increase in cerebrospinal fluid (CSF) volume (t(13)=-4.073, P<.001) and decrease in right and left hippocampal volumes (t(13)=4.221, P<.001 and t(13)=3.078, P<.005, respectively) were observed from 4.5 months to 2.5 years. Compared with published normative data, patients with TBI showed significantly more pathologic percent annual volume change for the hippocampi (t(26)=-3.864, P<.001, right; and t(26)=-2.737, P<.01, left), and a trend for CSF (t(26)=1.655, P=.059). CONCLUSIONS: This study provides strong MRI evidence for subacute progression of atrophy, as distinct from early, acute neurologic changes observed.

Scale and pattern of atrophy in the chronic stages of moderate-severe TBI.

BACKGROUND: Moderate-severe traumatic brain injury (TBI) is increasingly being understood as a progressive disorder, with growing evidence of reduced brain volume and white matter (WM) integrity as well as lesion expansion in the chronic phases of injury. The scale of these losses has yet to be investigated, and pattern of change across structures has received limited attention. OBJECTIVES: (1) To measure the percentage of patients in our TBI sample showing atrophy from 5 to 20 months post-injury in the whole brain and in structures with known vulnerability to acute TBI, and (2) To examine relative vulnerability and patterns of volume loss across structures. METHODS: Fifty-six TBI patients [complicated mild to severe, with mean Glasgow Coma Scale (GCS) in severe range] underwent MRI at, on average, 5 and 20 months post-injury; 12 healthy controls underwent MRI twice, with a mean gap between scans of 25.4 months. Mean monthly percent volume change was computed for whole brain (ventricle-to-brain ratio; VBR), corpus callosum (CC), and right and left hippocampi (HPC). RESULTS: (1) Using a threshold of 2 z-scores below controls, 96% of patients showed atrophy across time points in at least one region; 75% showed atrophy in at least 3 of the 4 regions measured. (2) There were no significant differences in the proportion of patients who showed atrophy across structures. For those showing decline in VBR, there was a significant association with both the CC and the right HPC (P < 0.05 for both comparisons). There were also significant associations between those showing decline in (i) right and left HPC (P < 0.05); (ii) all combinations of genu, body and splenium of the CC (P < 0.05), and (iii) head and tail of the right HPC (P < 0.05 all sub-structure comparisons). CONCLUSIONS: Atrophy in chronic TBI is robust, and the CC, right HPC and left HPC appear equally vulnerable. Significant associations between the right and left HPC, and within substructures of the CC and right HPC, raise the possibility of common mechanisms for these regions, including transneuronal degeneration. Given the 96% incidence rate of atrophy, a genetic explanation is unlikely to explain all findings. Multiple and possibly synergistic mechanisms may explain findings. Atrophy has been associated with poorer functional outcomes, but recent findings suggest there is potential to offset this. A better, understanding of the underlying mechanisms could permit targeted therapy enabling better long-term outcomes.