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


OBJECTIVE
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.


METHODS
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.


METHODS
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
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 and Mind Institute, University of Western Ontario, London, Ontario, Canada2School of Psychology, University of Birmingham, Birmingham, England.
Davinia
D
Fernández-Espejo
School of Psychology, University of East Anglia Norwich, Norwich, England.
Stephanie
S
Rossit
Brain and Mind Institute, University of Western Ontario, London, Ontario, Canada.
Adrian M
AM
Owen
D000328:Adult; D001364:Awareness / Q000502:physiology*; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019018:Imagery, Psychotherapy; D008279:Magnetic Resonance Imaging; D008297:Male; D015233:Models, Statistical; D009044:Motor Cortex / Q000098:blood supply / Q000473:pathology*; D009069:Movement Disorders / Q000209:etiology*; D010100:Oxygen / Q000097:blood; D012189:Retrospective Studies; D013788:Thalamus / Q000098:blood supply / Q000473:pathology*; D055815:Young Adult
D010100:Oxygen