Thalamic and extrathalamic mechanisms of consciousness after severe brain injury

Abstract

Objective: What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development. Methods: Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. Results: Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. Interpretation: These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal.ANN NEUROL 2015;00:000-000 T he mechanisms supporting consciousness, as well as its loss and recovery after severe brain injury, remain largely unknown. In the context of disorders of consciousness (DOC) 1 such as the vegetative state (VS) and the minimally conscious state (MCS), the lack of a mechanistic understanding of the relationship between brain damage and neurological condition has direct consequences for our ability to make accurate diagnoses, prognoses, and to develop targeted interventions, thereby raising complicated medical and ethical questions. 2Although information concerning the nature and extent of a patient's brain damage is generally taken into consideration during clinical assessments, current differential diagnosis procedures rely exclusively-as per international guidelines-on behavioral presentation. 3-5 Consequently, although our understanding of DOC is continuously increasing, 6,7 little is known about the connection between behaviorally defined clinical entities and the underlying brain damage, [8][9][10] or the degree to which standard behavior-based clinical assessments (eg, JFK View this article online at wil...

Stratification of unresponsive patients by an independently validated index of brain complexity

“…Several factors, in addition to the extent of structural lesions, may affect the ability of the residual brain to engage in complex interactions. One possibility to be investigated is whether the integrity of some specific structures, such as the precuneus,20, 37 the thalamus,5, 38 and the claustrum,39, 40 or a critical level of overall anatomical connectivity41 may be key in sustaining such interactions. Another non–mutually exclusive possibility is that the complexity of residual thalamocortical networks may be reduced by functional imbalances leading to an excessive degree of neuronal bistability 42.…”

Acute EEG spectra characteristics predict thalamic atrophy after severe TBI

“…A shape analysis of subcortical regions of interest (ROIs: brainstem and bilateral thalamus, globus pallidus, striatum, and hippocampus) was performed using FSL (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/), using a previously published procedure3 (see online supplementary information). Briefly, data were brain-extracted with optiBET, and ROIs were segmented and transformed into three-dimensional meshes which can be compared across time/patients.…”

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“…The reduction is reportedly more pronounced in VS compared with minimally conscious state (MCS) and even more in coma compared to VS and MCS. 1,5 This observation is supported by electrophysiologic findings, 6 suggesting a possible pathophysiologic continuum from coma to recovered consciousness, of which coma and evolution into the arousal/awareness dissociation characterizing VS and MCS would be only transitional phases. The functional core impairment was shared by all DOC conditions in the meta-analyses by Hannawi et al 1 and Lutkenhoff et al, 5 but more complex patterns were common, including associations of clinical measures characterizing VS and MCS with tissue atrophy in subcortical structures.…”

“…1,5 This observation is supported by electrophysiologic findings, 6 suggesting a possible pathophysiologic continuum from coma to recovered consciousness, of which coma and evolution into the arousal/awareness dissociation characterizing VS and MCS would be only transitional phases. The functional core impairment was shared by all DOC conditions in the meta-analyses by Hannawi et al 1 and Lutkenhoff et al, 5 but more complex patterns were common, including associations of clinical measures characterizing VS and MCS with tissue atrophy in subcortical structures. 1,5 Heterogeneities in etiology or in the extension and severity of brain damage (possibly crucial in this regard) would result in preserved neural structures and residual resources 7 and could question the boundaries between the conventional DOC conditions.…”