The subcortical basis of outcome and cognitive impairment in TBI

Lutkenhoff, Evan S.; Wright, Matthew; Shrestha, Vikesh; Real, Courtney; McArthur, David L.; Buitrago-Blanco, Manuel; Vespa, Paul; Monti, Martin M.

doi:10.1212/wnl.0000000000010825

Cited by 37 publications

(28 citation statements)

References 44 publications

(70 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 57%

Network dynamics scale with levels of awareness

Coppola

Spindler

Luppi

et al. 2021

Preprint

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Small world topologies are thought to provide a valuable insight into human brain organisation and consciousness. However, functional magnetic resonance imaging studies in consciousness have not yielded consistent results. Given the importance of dynamics for both consciousness and cognition, here we investigate how the diversity of brain dynamics pertaining to small world topology (quantified by sample entropy; dSW-E) scales with decreasing levels of awareness (i.e., sedation and disorders of consciousness). Paying particular attention to result reproducibility, we show that dSW-E is a consistent predictor of levels of awareness even when controlling for the underlying functional connectivity dynamics. We find that dSW-E of subcortical and cortical areas are predictive, with the former showing higher and more robust effect sizes across analyses. Consequently, we propose that the dynamic reorganisation of the functional information architecture, in particular of the subcortex, is a characteristic that emerges with awareness and has explanatory power beyond that of the complexity of dynamic functional connectivity.

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Section: Discussionmentioning

confidence: 57%

Network dynamics scale with levels of awareness

Coppola

Spindler

Luppi

et al. 2021

Preprint

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“…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].…”

Section: Sildenafil Exposure and Behavioral Outcomes In Response To Brain Injurymentioning

confidence: 99%

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

Zinni

Pansiot

Leger

et al. 2021

Cells

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Cerebral stroke, traumatic brain injury, and hypoxic ischemic encephalopathy are among the most frequently occurring brain injuries. A complex pathogenesis, characterized by a synergistic interaction between alterations of the cerebrovascular system, cell death, and inflammation, is at the basis of the brain damage that leads to behavioral and neurodevelopmental disabilities in affected subjects. Sildenafil is a selective inhibitor of the enzyme phosphodiesterase 5 (PDE5) that is able to cross the blood–brain barrier. Preclinical data suggest that sildenafil may be a good candidate for the prevention or repair of brain injury in both adults and neonates. The aim of this review is to summarize the evidence supporting the neuroprotective action of sildenafil and discuss the possible benefits of the association of sildenafil with current therapeutic strategies.

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“…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].…”

Section: Dmn To Dmnmentioning

confidence: 99%

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

Coulborn

Taylor

Naçi

et al. 2021

Preprint

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Recent research indicates prolonged disorders of consciousness (PDOC) result from structural and functional impairments to key cortical and subcortical networks including the default mode network (DMN) and the anterior forebrain mesocircuit (AFM). However, the specific mechanisms which underpin such impairments remain unknown. It is known that disruptions in the striatal-pallidal pathway can result in the over inhibition of the thalamus and lack of excitation to the cortex that characterises PDOC. Here, we used spectral dynamic causal modelling and parametric empirical Bayes on rs-fMRI data to assess whether DMN changes in PDOC are caused by disruptions in the AFM. PDOC patients displayed overall reduced coupling within the AFM, and specifically, decreased self-inhibition of the striatum paired with reduced coupling from striatum to thalamus. This led to loss of inhibition from AFM to DMN, mostly driven by posterior areas including the precuneus and inferior parietal cortex. In turn, the DMN showed disruptions in self-inhibition of the precuneus and medial prefrontal cortex. Our results provide support for the anterior mesocircuit model at the subcortical level but highlight an inhibitory role for the AFM over the DMN, which is disrupted in PDOC.

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The subcortical basis of outcome and cognitive impairment in TBI

Cited by 37 publications

References 44 publications

Network dynamics scale with levels of awareness

Network dynamics scale with levels of awareness

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

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

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