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How Some Patients in a Vegetative State Can Retain Awareness, Despite Appearing Unresponsive

New insight into a vital cerebral pathway has explained how some patients in a vegetative state are aware despite appearing to be unconscious and being behaviourally unresponsive.

The findings, published in JAMA Neurology, identify structural damage between the thalamus and primary motor cortex as the obstacle between covert awareness and intentional movement.

The team of researchers hope that their study, the first to understand the phenomenon, will pave the way for the development of restorative therapies for thousands of patients.

Dr. Davinia Fernández-Espejo, from the University of Birmingham, explained, “A number of patients who appear to be in a vegetative state are actually aware of themselves and their surroundings, able to comprehend the world around them, create memories and imagine events as with any other person.”

“However, before we take the crucial step of developing targeted therapies to help these patients, we needed to identify the reason for the dissociation between their retained awareness and their inability to respond with intentional movement.”

“In highlighting damage to the pathways that physically connect the thalamus, one of the hubs of consciousness if you will, and the motor cortex, which drives our voluntary muscular activity, as the reason behind the dissociation we have provided an important explanation”.

A patient who produced repeated evidence of covert awareness across multiple examinations, despite being in a vegetative state for over 12 years, was observed in a case study at the imaging centre at the Brain and Mind Institute, at Western University (Canada).

A fellow patient with similar clinical variables, but capable of intentional movement, and 15 healthy control volunteers were also monitored using functional magnetic resonance imaging (fMRI) and fiber tractography.

Participants were asked to respond to commands, for example, asking them to imagine moving their hand in response to the keyword “move”, while their brain activity was measured. Additionally, the researchers assessed the integrity of the structural pathways that were revealed as essential for successful motor execution (those connecting the thalamus with the motor cortex).

Dr. Fernández-Espejo added, “The ultimate aim is to use this information in targeted therapies that can drastically improve the quality of life of patients. For example, with the advances being made in assistive technology, if we can help a patient to regain even limited movement in one finger it opens up so many possibilities for communication and control of their environment.”

Image shows the location of the thalamus and pmc in the brain.

Image of brain showing the location of the thalamus (green) and primary motor cortex (blue). Credit: University of Birmingham/Dr. Davinia Fernández-Espejo.

Though it may be a number of years before an effective therapy is developed, the team believe that a significant milestone has been reached with the discovery.

Dr. Fernández-Espejo is working to consolidate this research at Birmingham, which is the ideal setting due to the regional concentration of academic and clinical expertise, care homes who monitor the long term care of severe brain injury patients and world class facilities available between the University and University Hospitals Birmingham NHS Foundation Trust; including the Birmingham University Imaging Centre and Institute of Translational Medicine.

About this neurology research

Source of Article: NeuroscienceNews.com would like to thank Angela Ronson for sharing this article with us. Angela’s blog, “The Thoughtful Vegetable”, is available here.

Original Source: Luke Harrison – University of Birmingham
Image Source: The image is credited to University of Birmingham/Dr. Davinia Fernández-Espejo
Original Research: Full open access research for “A Thalamocortical Mechanism for the Absence of Overt Motor Behavior in Covertly Aware Patients” by Davinia Fernández-Espejo, PhD; Stephanie Rossit, PhD; and Adrian M. Owen, PhD in JAMA Neurology. Published online October 19 2015 doi:10.1001/jamaneurol.2015.2614


Abstract

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

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.

“A Thalamocortical Mechanism for the Absence of Overt Motor Behavior in Covertly Aware Patients” by Davinia Fernández-Espejo, PhD; Stephanie Rossit, PhD; and Adrian M. Owen, PhD in JAMA Neurology. Published online October 19 2015 doi:10.1001/jamaneurol.2015.2614

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