Disconnection of the Ascending Arousal System in Traumatic Coma

Abstract

Traumatic coma is associated with disruption of axonal pathways throughout the brain but the specific pathways involved in humans are incompletely understood. In this study, we used high angular resolution diffusion imaging (HARDI) to map the connectivity of axonal pathways that mediate the 2 critical components of consciousness – arousal and awareness – in the postmortem brain of a 62-year-old woman with acute traumatic coma and in 2 control brains. HARDI tractography guided tissue sampling in the neuropathological analysis. HARDI tractography demonstrated complete disruption of white matter pathways connecting brainstem arousal nuclei to the basal forebrain and thalamic intralaminar and reticular nuclei. In contrast, hemispheric arousal pathways connecting the thalamus and basal forebrain to the cerebral cortex were only partially disrupted, as were the cortical “awareness pathways.” Neuropathologic examination, which utilized β-amyloid precursor protein and fractin immunomarkers, revealed axonal injury in the white matter of the brainstem and cerebral hemispheres that corresponded to sites of HARDI tract disruption. Axonal injury was also present within the grey matter of the hypothalamus, thalamus, basal forebrain, and cerebral cortex. We propose that traumatic coma may be a subcortical disconnection syndrome related to the disconnection of specific brainstem arousal nuclei from the thalamus and basal forebrain.

Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations

“…GBO are strongly reduced and abnormal in coma and vegetative states (14). Increasing the activity of BF PV neurons may be an interesting strategy to improve cortical function in traumatic brain injury, because recent brain imaging studies in traumatic coma revealed a complete disruption of the axonal pathways connecting brainstem arousal centers to the BF, whereas BF axonal projections to the cerebral cortex are partially preserved (43).…”

Aneurysmal Subarachnoid Hemorrhage Causes Injury of the Ascending Reticular Activating System: Relation to Consciousness

“…In 2013, Yeo et al 5 reported a method for reconstruction of the lower portion of the ARAS from the pontine reticular formation to the thalamus in healthy subjects. Subsequently, Edlow et al in 2013 13 reported on a patient with coma who showed disruptions of white matter pathways connecting brain stem arousal nuclei to the basal forebrain and thalamic intralaminar and reticular nuclei and the pathways connecting the thalamus and basal forebrain to the cerebral cortex following traumatic brain injury. Recently, Jang et al in 2014 12 demonstrated injury of the ARAS between the pontine reticular formation and the thalamus in patients with impaired arousal after hypoxic-ischemic brain injury.…”

“…8,[37][38][39][40][41] Since the introduction of DTI, several studies have reported on the lower portion of the ARAS in healthy subjects and patients with brain injury. 5,6,12,13 In 2012, Edlow et al 6 reconstructed the ARAS connecting the brain stem to the thalamus, hypothalamus, and the basal forebrain in healthy subjects. In 2013, Yeo et al 5 reported a method for reconstruction of the lower portion of the ARAS from the pontine reticular formation to the thalamus in healthy subjects.…”

“…5,6 In addition, a few studies have reported injury of the ARAS in patients with traumatic brain injury and hypoxic-ischemic brain injury by using diffusion tensor tractography. 12,13 However, no study on injury of the ARAS in patients with SAH has been reported, to our knowledge. In this study, we hypothesized that injury of the lower portion of the ARAS between the reticular formation of the brain stem and the intralaminar thalamic nuclei would be observed in patients with spontaneous SAH and that injury of the lower ARAS might be correlated with consciousness level.…”

Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study

“…Injury to the thalamus and brainstem and extensive cerebral injury are among the most frequent observations in DOC in post-mortem [19][20][21][22][23][24][25][26] and MRI studies [25][26][27][28][29][30]. Equally little is known about brain atrophy secondary to the injury causing DOC [31,32].…”