Thalamic and extrathalamic mechanisms of consciousness after severe brain injury

Thalamic and extrathalamic mechanisms of consciousness after severe brain injury Lutkenhoff Chiang Tshibanda Kamau Kirsch Pickard Laureys Owen Monti

Tag layer of the DHSS Meta-Tagging Project. The article text is reproduced from the staged copy named in sourceDesc and is not altered; the tags are held separately in standOff so that overlapping and nested spans are preserved.

Thalamic and extrathalamic mechanisms of consciousness after severe brain injury 2015 Annals of Neurology 10.1002/ana.24423 lutkenhoff2015-thalamic-and-extrathalamic-mechani lutkenhoff2015-thalamic-and-extrathalamic-mechani.txt, the project's staged copy c088f71fda59a63f365015f89042644691f86d91 open-access neuroscience

the paper's own words

the tag layer; a sentence written by the tagger about the paper, always anchored to a quotation but not itself a quotation

0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them mechanism Quotation withheld because this record is not cleared for redistribution. disorders of consciousness after severe brain injury Quotation withheld because this record is not cleared for redistribution. observational-study observational-study Quotation withheld because this record is not cleared for redistribution. mechanisms Willful behaviour and arousal are supported by separate circuits, so thalamic damage removes organised willful behaviour while extrathalamic (basal ganglia) damage removes behavioural and electrocortical arousal Quotation withheld because this record is not cleared for redistribution. mechanisms Loss of corticopetal thalamo-prefrontal projections (the mesocircuit) removes the drive that sustains organised behaviour and integrates information across cortex Quotation withheld because this record is not cleared for redistribution. mechanisms Partial basal forebrain atrophy spares the coma-inducing threshold but impairs the fast cortical disinhibition that transiently amplifies sensory processing Quotation withheld because this record is not cleared for redistribution. Structural neuroimaging is descriptive, so the findings cannot be given a causal interpretation what this limits: any causal reading of the neuroanatomical findings: THE USE OF STRUCTURAL NEUROIMAGING, A DESCRIPTIVE METHODOLOGY ... DOES NOT ALLOW A CAUSAL INTERPRETATION OF OUR FINDINGS Quotation withheld because this record is not cleared for redistribution. The atlas-based segmentation relies on priors estimated mostly from healthy volunteers what this limits: every segmentation and volume in patients: THE ATLAS-BASED COMPONENT ... IS BOTH AN ASSET ... AND A LIABILITY, GIVEN ITS RELIANCE ON PRIORS ESTIMATED MOSTLY FROM HEALTHY VOLUNTEERS Quotation withheld because this record is not cleared for redistribution. The proposed model is an approximation that omits corticosubcortical connectivity, temporal dynamics, neurotransmitter action and further arousal-related regions what this limits: the mechanistic model offered: OUR PROPOSAL, AS WELL AS THE MESOCIRCUIT MODEL OF DOC, ARE TO BE UNDERSTOOD AS APPROXIMATIONS THAT DO NOT TAKE INTO FULL ACCOUNT THE EXTENT OF CORTICOSUBCORTICAL CONNECTIVITY, TEMPORAL DYNAMICS Quotation withheld because this record is not cleared for redistribution. Additional clinical factors that shape a given patient's atrophy pattern could not be addressed and would need larger samples what this limits: any individual patient's atrophy pattern: THERE ARE A NUMBER OF ADDITIONAL FACTORS THAT MIGHT WELL PLAY AN IMPORTANT ROLE ... THAT WE COULD NOT ADDRESS Quotation withheld because this record is not cleared for redistribution. A structure the literature calls crucial could not be assessed by the technique used. what this limits: any map of which structures support this process drawn from this study: the parabrachial/precoeruleus complex has previously been shown to be crucial for it and could not be assessed with the present technique Quotation withheld because this record is not cleared for redistribution. The outcome analysed is a set of rotated components, not the clinical subscales themselves. what this limits: any statement here relating a brain region to a clinical function: because of correlations between the CRS-R subscales and the effects of multicollinearity on regression, the authors performed a data reduction by principal component analysis with varimax rotation Quotation withheld because this record is not cleared for redistribution. One region entered the analysis on the strength of evidence from animal models. what this limits: the set of subcortical regions examined here: this region was added to the analysis because of its causal role in the maintenance of cortical and behavioral arousal in animal models Quotation withheld because this record is not cleared for redistribution. a multiple-regression approach across a deliberately HETEROGENEOUS patient sample, controlling the factors known to drive variability in disorders of consciousness eliminates: aetiology, time since injury and the other known sources of between-patient variance, so that what remains is the 'minimum common denominator' the paper is after rather than a property of whichever patients were available · outcome: partial Quotation withheld because this record is not cleared for redistribution. parabrachial/precoeruleus complex parabrachial/precoeruleus complex Quotation withheld because this record is not cleared for redistribution. CRS-R subscales CRS-R subscales Quotation withheld because this record is not cleared for redistribution. multicollinearity multicollinearity Quotation withheld because this record is not cleared for redistribution. basal forebrain basal forebrain Quotation withheld because this record is not cleared for redistribution. arousal arousal Quotation withheld because this record is not cleared for redistribution. the region set - BOUNDED BY THE INSTRUMENT, NOT BY THE BIOLOGY: one structure previously shown to be crucial for the process under study could not be assessed with the technique used, so the map of which regions matter is drawn from the regions the method can see Quotation withheld because this record is not cleared for redistribution. the clinical outcome - COMPONENTS, NOT SUBSCALES: the six CRS-R subscales are correlated, so a principal component analysis with varimax rotation was performed and the regression is run on the components; every later claim linking a region to a function is a claim about a component Quotation withheld because this record is not cleared for redistribution. the basal forebrain's role - ESTABLISHED ELSEWHERE, MEASURED HERE: the paper reports its own negative association with sensory responsiveness and, in the next clause, that the region is well known to play a causal role in arousal and to induce a comalike state when extensively lesioned - the causal claim is inherited, the association is measured Quotation withheld because this record is not cleared for redistribution. builds-on → the mesocircuit theory of disorders of consciousness Quotation withheld because this record is not cleared for redistribution. replicates → postmortem examinations of thalamic damage after nontraumatic brain injury Quotation withheld because this record is not cleared for redistribution. basal forebrain —causes→ arousal basal forebrain arousal strength of the relation: 0.7 Audit 2026-09-28: DOUBTFUL - read against its span and kept, but the span says the basal forebrain is associated with responsiveness and known for arousal; causes is loose. Quotation withheld because this record is not cleared for redistribution. principal component analysis principal component analysis Quotation withheld because this record is not cleared for redistribution. permutation test permutation test Quotation withheld because this record is not cleared for redistribution. multiple regression multiple regression Quotation withheld because this record is not cleared for redistribution. t-statistic t-statistic Quotation withheld because this record is not cleared for redistribution. p-value p-value Quotation withheld because this record is not cleared for redistribution. correlation correlation Quotation withheld because this record is not cleared for redistribution. Bayesian estimation Bayesian estimation Quotation withheld because this record is not cleared for redistribution. standard deviation standard deviation Quotation withheld because this record is not cleared for redistribution. Compared with healthy volunteers, patients with disorders of consciousness showed significant atrophy in every subcortical structure examined. Quotation withheld because this record is not cleared for redistribution. The behaviourally defined diagnostic categories were not distinguishable by subcortical pathology: vegetative-state, MCS-minus and MCS-plus patients did not differ from one another in any region. Quotation withheld because this record is not cleared for redistribution. Total CRS-R score varied inversely with atrophy in the left globus pallidus, left putamen and small ventromedial parts of the basal forebrain. Quotation withheld because this record is not cleared for redistribution. Motor and communication ability tracked thalamic pathology: the Motor-Communication component correlated negatively with atrophy in bilateral anterior and dorsomedial thalamus, left putamen and right hippocampus. Quotation withheld because this record is not cleared for redistribution. Arousal tracked basal ganglia rather than thalamic pathology: the Arousal component correlated negatively with atrophy in bilateral putamen and globus pallidus. Quotation withheld because this record is not cleared for redistribution. Patients' level of arousal showed no association with thalamic atrophy. Quotation withheld because this record is not cleared for redistribution. Sensory (audiovisual) responsiveness was associated specifically with atrophy of small ventromedial segments of the basal forebrain. Quotation withheld because this record is not cleared for redistribution. Patients with nontraumatic injury had more widespread and left-lateralised thalamic atrophy than patients with traumatic injury, mirroring the worse prognosis of nontraumatic aetiology. Quotation withheld because this record is not cleared for redistribution. Vegetative-state patients showed more atrophy than eMCS patients in left putamen, globus pallidus and a small part of right hippocampus. Quotation withheld because this record is not cleared for redistribution. shape (or vertex) analysis shape (or vertex) analysis Quotation withheld because this record is not cleared for redistribution. minimum common denominator minimum common denominator Quotation withheld because this record is not cleared for redistribution. total CRS-R score total CRS-R score Quotation withheld because this record is not cleared for redistribution. injury etiology injury etiology Quotation withheld because this record is not cleared for redistribution. local brain atrophy local brain atrophy Quotation withheld because this record is not cleared for redistribution. total normalized brain volume total normalized brain volume Quotation withheld because this record is not cleared for redistribution. age age Quotation withheld because this record is not cleared for redistribution. gender gender Quotation withheld because this record is not cleared for redistribution. 143 — consecutive patients with disorders of consciousness recruited Quotation withheld because this record is not cleared for redistribution. 96 — healthy volunteers providing control images Quotation withheld because this record is not cleared for redistribution. 28 — patient datasets discarded for low image quality before any analysis Quotation withheld because this record is not cleared for redistribution. 115 / 38 / 63 / 14 — patients analysed, split into vegetative state, minimally conscious state and emerging-from-MCS Quotation withheld because this record is not cleared for redistribution. 90% — total variance in the CRS-R subscales explained by the four retained PCA components Quotation withheld because this record is not cleared for redistribution. 100% and 99% — proportion of right and left globus pallidus vertices showing significant atrophy in patients versus volunteers Quotation withheld because this record is not cleared for redistribution. 47% — share of patients whose injury was nontraumatic Quotation withheld because this record is not cleared for redistribution. 56% of vertices — extent of left thalamus showing extra atrophy in nontraumatic relative to traumatic injury Quotation withheld because this record is not cleared for redistribution. 84% vs 9.6% and 6% — proportions of bilateral, left- and right-lateralised injuries in the sample, used to rule out a trivial explanation of the left-lateralised thalamic finding Quotation withheld because this record is not cleared for redistribution.

The full text of this article is not redistributable, so it is not included here. The evidence sentences are withheld with it; the tag layer and its grounding status remain. The article itself is at https://doi.org/10.1002/ana.24423.