The subcortical basis of outcome and cognitive impairment in TBI

Abstract

Objective:To understand how, biologically, the acute event of traumatic brain injury gives rise to a long-term disease, we address the relationship between evolving cortical and subcortical brain damage and measures of functional outcome and cognitive functioning at six months post-injury.Methods:Longitudinal analysis of clinical and MRI data collected, in a tertiary neurointensive care setting, in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient we collected T1- and T2-weighted MRI data, acutely and at a six-months follow-up, as well as acute measures of injury severity (Glasgow Coma Scale) and follow-up measures of functional impairment (Glasgow Outcome Scale extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory.Results:In the final cohort of 113 subcortical and 92 cortical datasets that survived (blind) quality control, extensive atrophy was observed over the first six months post-injury across the brain. Nonetheless, only atrophy within subcortical regions, particularly in left thalamus, were associated with functional outcome and neuropsychological measures of attention, executive functions, and episodic memory. Furthermore, when brought together in an analytical model, longitudinal brain measurements could distinguish good versus bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could only achieve 20% accuracy.Conclusion.Despite great injury heterogeneity, secondary thalamic pathology is a measurable minimum common denominator mechanism directly relating biology to clinical measures of outcome and cognitive functioning, potentially linking the acute “event” and the longer-term “disease” of TBI.

Network dynamics scale with levels of awareness

“…see, Shewmon, Holmes, & Byrne, 1999). In fact, the present results suggest that investigating subcortical information may aid finer differentiation of different conscious states (Lutkenhoff, Johnson, et al, 2020;Lutkenhoff, Wright, et al, 2020;Panksepp, 2011) for clinical purposes.…”

Sildenafil-Mediated Neuroprotection from Adult to Neonatal Brain Injury: Evidence, Mechanisms, and Future Translation

“…Cognitive disabilities including memory deficit and language deficits are indeed reported in the 60% of children with perinatal stroke and are identified in the 30% of adult stroke patients within the first year after the brain injury event [72,73]. Similarly cognitive and behavioral alterations are reported in the 30% of patients surviving to TBI [74].…”

Disruptions in effective connectivity within and between default mode network and anterior forebrain mesocircuit in prolonged disorders of consciousness

“…Previous research suggests that structural differences are more prominent in the left hemisphere in PDOC [51,52], and atrophy in the left thalamus predicts functional outcome in post-traumatic brain injury survivors [53]. Furthermore, the metabolic integrity of the left hemisphere better predicts clinical diagnosis (vegetative versus minimally conscious state) [54].…”