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Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.

ABSTRACT: Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can engage in rapid causal interactions (effective connectivity). Here, we employ transcranial magnetic stimulation together with high-density electroencephalography to evaluate effective connectivity at the bedside of severely brain injured, non-communicating subjects. In patients in a vegetative state, who were open-eyed, behaviourally awake but unresponsive, transcranial magnetic stimulation triggered a simple, local response indicating a breakdown of effective connectivity, similar to the one previously observed in unconscious sleeping or anaesthetized subjects. In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment.

SUBMITTER: Rosanova M

PROVIDER: S-EPMC3326248 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.

Rosanova Mario M Gosseries Olivia O Casarotto Silvia S Boly Mélanie M Casali Adenauer G AG Bruno Marie-Aurélie MA Mariotti Maurizio M Boveroux Pierre P Tononi Giulio G Laureys Steven S Massimini Marcello M

Brain : a journal of neurology 20120105 Pt 4

Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to devel ...[more]

PMID: 22226806

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Project description:Background and objectivesIn patients with severe coronavirus disease 2019 (COVID-19), disorders of consciousness (DoC) have emerged as a serious complication. The prognosis and pathophysiology of COVID-DoC remain unclear, complicating decisions about continuing life-sustaining treatment. We describe the natural history of COVID-DoC and investigate its associated brain connectivity profile.MethodsIn a prospective longitudinal study, we screened consecutive patients with COVID-19 at our institution. We enrolled critically ill adult patients with a DoC unexplained by sedation or structural brain injury and who were planned to undergo a brain MRI. We performed resting-state fMRI and diffusion MRI to evaluate functional and structural connectivity compared to healthy controls and patients with DoC resulting from severe traumatic brain injury (TBI). We assessed the recovery of consciousness (command following) and functional outcomes (Glasgow Outcome Scale Extended [GOSE] and the Disability Rating Scale [DRS]) at hospital discharge and 3 and 6 months after discharge. We also explored whether clinical variables were associated with recovery from COVID-DoC.ResultsAfter screening 1,105 patients with COVID-19, we enrolled 12 with COVID-DoC. The median age was 63.5 years (interquartile range 55-76.3 years). After the exclusion of 1 patient who died shortly after enrollment, all of the remaining 11 patients recovered consciousness 0 to 25 days (median 7 [5-14.5] days) after the cessation of continuous IV sedation. At discharge, all surviving patients remained dependent: median GOSE score 3 (1-3) and median DRS score 23 (16-30). Ultimately, however, except for 2 patients with severe polyneuropathy, all returned home with normal cognition and minimal disability: at 3 months, median GOSE score 3 (3-3) and median DRS score 7 (5-13); at 6 months, median GOSE score 4 (4-5), median DRS score 3 (3-5). Ten patients with COVID-DoC underwent advanced neuroimaging; functional and structural brain connectivity in those with COVID-DoC was diminished compared to healthy controls, and structural connectivity was comparable to that in patients with severe TBI.DiscussionPatients who survived invariably recovered consciousness after COVID-DoC. Although disability was common after hospitalization, functional status improved over the ensuing months. While future research is necessary, these prospective findings inform the prognosis and pathophysiology of COVID-DoC.Trial registration informationClinicalTrials.gov identifier: NCT04476589.

Project description:We apply a comprehensive suite of graph theoretic metrics to illustrate how landscape connectivity can be effectively incorporated into conservation status assessments and in setting conservation objectives. These metrics allow conservation practitioners to evaluate and quantify connectivity in terms of representation, resiliency, and redundancy and the approach can be applied in spite of incomplete knowledge of species-specific biology and dispersal processes. We demonstrate utility of the graph metrics by evaluating changes in distribution and connectivity that would result from implementing two conservation plans for three endangered plant species (Erigeron parishii, Acanthoscyphus parishii var. goodmaniana, and Eriogonum ovalifolium var. vineum) relative to connectivity under current conditions. Although distributions of the species differ from one another in terms of extent and specific location of occupied patches within the study landscape, the spatial scale of potential connectivity in existing networks were strikingly similar for Erigeron and Eriogonum, but differed for Acanthoscyphus. Specifically, patches of the first two species were more regularly distributed whereas subsets of patches of Acanthoscyphus were clustered into more isolated components. Reserves based on US Fish and Wildlife Service critical habitat designation would not greatly contribute to maintain connectivity; they include 83-91% of the extant occurrences and >92% of the aerial extent of each species. Effective connectivity remains within 10% of that in the whole network for all species. A Forest Service habitat management strategy excluded up to 40% of the occupied habitat of each species resulting in both range reductions and loss of occurrences from the central portions of each species' distribution. Overall effective network connectivity was reduced to 62-74% of the full networks. The distance at which each CHMS network first became fully connected was reduced relative to the full network in Erigeron and Acanthoscyphus due to exclusion of peripheral patches, but was slightly increased for Eriogonum. Distances at which networks were sensitive to loss of connectivity due to presence non-redundant connections were affected mostly for Acanthoscyphos. Of most concern was that the range of distances at which lack of redundancy yielded high risk was much greater than in the full network. Through this in-depth example evaluating connectivity using a comprehensive suite of developed graph theoretic metrics, we establish an approach as well as provide sample interpretations of subtle variations in connectivity that conservation managers can incorporate into planning.

Dataset Information

Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.

Publications

Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.

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