A Thalamocortical Mechanism for the Absence of Overt Motor Behavior in Covertly Aware Patients

Abstract

IMPORTANCE It is well accepted that a significant number of patients in a vegetative state are covertly aware and capable of following commands by modulating their neural responses in motor imagery tasks despite remaining nonresponsive behaviorally. To date, there have been few attempts to explain this dissociation between preserved covert motor behavior and absent overt motor behavior. OBJECTIVES To investigate the differential neural substrates of overt and covert motor behavior and assess the structural integrity of the underlying networks in behaviorally nonresponsive patients. DESIGN, SETTING, AND PARTICIPANTS A case-control study was conducted at an academic center between February 7, 2012, and November 6, 2014. Data analysis was performed between March 2014 and June 2015. Participants included a convenience sample of 2 patients with severe brain injury: a paradigmatic patient who fulfilled all clinical criteria for the vegetative state but produced repeated evidence of covert awareness (patient 1) and, as a control case, a patient with similar clinical variables but capable of behavioral command following (patient 2). Fifteen volunteers participated in the study as a healthy control group. MAIN OUTCOMES AND MEASURES We used dynamic causal modeling of functional magnetic resonance imaging to compare voluntary motor imagery and motor execution. We then used fiber tractography to assess the structural integrity of the fibers that our functional magnetic resonance imaging study revealed as essential for successful motor execution. RESULTS The functional magnetic resonance imaging study revealed that, in contrast to mental imagery, motor execution was associated with an excitatory coupling between the thalamus and primary motor cortex (Bayesian model selection; winning model Bayes factors >17). Moreover, we detected a selective structural disruption in the fibers connecting these 2 regions in patient 1 (fractional anisotropy, 0.294; P = .047) but not in patient 2 (fractional anisotropy, 0.413; P = .35). CONCLUSIONS AND RELEVANCE These results suggest a possible biomarker for the absence of intentional movement in covertly aware patients (ie, specific damage to motor thalamocortical fibers), highlight the importance of the thalamus for the execution of intentional movements, and may provide a target for restorative therapies in behaviorally nonresponsive patients.

Brain imaging reveals covert consciousness during behavioral unresponsiveness induced by propofol

“…Hence, a reasonable argument could be made that if someone demonstrated evidence of consciousness via motor imagery that they should be able to engage intentional motor acts 13 . However, a recent study suggested that a possible biomarker for absent intentional movement in covertly aware patients was the selective structural damage to thalamocortical motor circuits 16 . In line with this proposition, we found that voluntary motor imagery and execution were dissociable (one could be present in the absence of the other).…”

“…Finally, we also lack a precise neural account for the paradoxical impairment of purposeful motor behavior in covertly aware patients 13–15 . A previous study examined the importance of selective structural damage to thalamocortical motor fibers as an explanation for the lack of intentional movement in a single VS/UWS patient with identified covert consciousness 16 . Thus, whether structural damage is a necessary condition for the dissociation between covert (i.e.…”

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

“…However, some patients may become unable to respond to stimuli despite still having conscious experiences 2, 3. This may happen because of motor or executive function impairments4, 5 and/or because of sensory disconnection from the environment 6. States of disconnected consciousness can occur in healthy subjects during dreaming7 and some forms of anesthesia,8 and may result from severe brain injury 9.…”

Komunikacja w grupie pacjentów z zaburzeniami świadomości – wnioskiz projektu InteRDoCTor

“…They are able to follow command(s) by modulating their neural responses in motor imagery (MI) tasks reflected in fMRI findings. Study by Fernadez-espejo et al showed, that they have intacted thalamus, but damaged excitatory coupling between the thalamus and primary motor cortex [52]. But role of certain brain areas (bilateral occipital areas, left parahippocampus, other temporal and frontal areas, etc.)…”