Tuesday, October 17, 2017

Restoring consciousness with vagus nerve stimulation

Corazzol M, Lio G, Lefevre A, Deiana G, Tell L, André-Obadia N, Bourdillon P, Guenot M, Desmurget M, Luauté J, Sirigu A. Restoring consciousness with vagus nerve stimulation. Curr Biol. 2017 Sep 25;27(18):R994-R996.

Patients lying in a vegetative state present severe impairments of consciousness  caused by lesions in the cortex, the brainstem, the thalamus and the white matter. There is agreement that this condition may involve disconnections in long-range cortico-cortical and thalamo-cortical pathways. Hence, in the vegetative state cortical activity is 'deafferented' from subcortical modulation and/or principally disrupted between fronto-parietal regions. Some patients in a vegetative state recover while others persistently remain in such a state. The neural signature of spontaneous recovery is linked to increased thalamo-cortical activity and improved fronto-parietal functional connectivity. The likelihood of consciousness recovery depends on the extent of brain damage and patients' etiology, but after one year of unresponsive behavior, chances become low. There is thus a need to explore novel ways of repairing lost consciousness. Here we report beneficial effects of vagus nerve stimulation on consciousness level of a single patient in a vegetative state, including improved behavioral responsiveness and enhanced brain connectivity patterns.

From the manuscript

Following the hypothesis that vagus nerve stimulation functionally reorganizes the thalamo-cortical network, we tested its effects on the cortical activity of a patient lying in a vegetative state for 15 years following traumatic brain injury. Behavioral, electroencephalographic (EEG) and 18F-FDG PET recordings were performed before and after surgical implantation of a vagus nerve stimulator. Stimulation was gradually increased to a maximum intensity of 1.5 mA, and its effects were monitored over six months post-implantation. After one month of stimulation, when intensity reached 1 mA, clinical examination revealed reproducible and consistent improvements in general arousal, sustained attention, body motility and visual pursuit. Scores on the Coma Recovery Scale-Revised (CRS-R) test improved, mostly in the visual domain, as stimulation increased, from a score of 5 at baseline (last exam) to 10 at highest intensities (1.00–1.25 mA), indicating a transition from a vegetative to minimally conscious state…

These findings show that stimulation of the vagus nerve promoted the spread of cortical signals and caused an increase of metabolic activity leading to behavioral improvement as measured with the CRS-R scale and as reported by clinicians and family members. Thus, potentiating vagus nerve inputs to the brain helps to restore consciousness even after many years of being in a vegetative state, thus challenging the belief that disorders of consciousness persisting after 12 months are irreversible. The direct connection between the NTS where the vagus nerve originates and the thalamus may be at the origin of the significant increase in theta signal recorded at the cortical level. In particular, the parietal cortex appears to be a major player in guiding the expansion of neural activity across brain areas. The enhanced neural activity might also be mediated by neurotransmission changes given that vagus nerve projections target key regions important for the liberation of norepinephrine and serotonin. Finally, since the vagus nerve has bidirectional control over the brain and the body, reactivation of sensory/visceral afferences might have enhanced brain activity within a body/brain closed loop process. Our study demonstrates the therapeutic potential of vagus nerve stimulation to modulate large-scale human brain activity and alleviate disorders of consciousness.

Courtesy of Medscape


  1. A 35-year-old man who had been in a persistent vegetative state (PVS) for 15 years has shown signs of consciousness after receiving a pioneering therapy involving nerve stimulation.

    The treatment challenges a widely-accepted view that there is no prospect of a patient recovering consciousness if they have been in PVS for longer than 12 months.

    Since sustaining severe brain injuries in a car accident, the man had been completely unaware of the world around him. But when fitted with an implant to stimulate the vagus nerve, which travels into the brain stem, the man appeared to flicker back into a state of consciousness.

    He started to track objects with his eyes, began to stay awake while being read a story and his eyes opened wide in surprise when the examiner suddenly moved her face close to the patient’s. He could even respond to some simple requests, such as turning his head when asked – although this took about a minute.

    Angela Sirigu, who led the work at the Institut des Sciences Cognitives Marc Jeannerod in Lyon, France, said: “He is still paralysed, he cannot talk, but he can respond. Now he is more aware.”

    Niels Birbaumer, of the University of Tübingen and a pioneer of brain-computer interfaces to help patients with neurological disorders communicate, said the findings, published in the journal Current Biology, raised pressing ethical issues. “Many of these patients may and will have been neglected, and passive euthanasia may happen often in a vegetative state,” he said. “This paper is a warning to all those believing that this state is hopeless after a year.”…

    Sirigu and her team now hope to apply the same technique to patients with less serious brain injuries, where even more substantial improvements might be possible. There may even be patients, she said, whose cortex (the part of the brain used for cognitive tasks) is intact, but who have brain stem injuries that have led to limited awareness or consciousness.

    The findings offer hope to the families of patients in PVS that it may one day be possible to re-establish some basic form of communication. However, some might also question whether such patients would wish to be made more acutely aware of being in a severely injured state.

    “I cannot answer to this question,” said Sirigu. “Personally I think it’s better to be aware, even if it’s a bad state, to be conscious of what’s happening. Then you can have a decision if you want to go on or if you want [euthanasia].”

    Damian Cruse, a cognitive neuroscientist at the University of Birmingham, described the findings as “pretty exciting”, adding that in future it might be possible to combine vagal nerve stimulation with other forms of rehabilitation.

    “If you can just push the patient over the threshold so they can start responding to external stimulation you can maybe help them follow speech therapy and get them to a level where they can start to communicate,” he said.

    During the past decade, scientists have made major advances in communicating with “locked in” patients using various forms of brain-computer interface.

    These have allowed paralysed patients, some of whom had been assumed to be in PVS, to answer “yes” or “no” to questions to let their family and friends know their wishes and their state of wellbeing.


    Courtesy of Doximity

  2. French scientists have been criticised for concealing the death of the patient at the centre of a breakthrough in which consciousness was restored to a man in a persistent vegetative state.

    The treatment was hailed as a major advance in the field and suggested that the outlook for these patients and their families might be less bleak than was previously thought.

    However, it has emerged that the scientists behind the research withheld the fact that the man, who remains anonymous, died a few months after receiving the therapy. The team justified the decision, citing the family’s wish to keep the death private and a concern that people might have wrongly linked the therapy, which involved nerve stimulation, to the 35-year-old’s death from a lung infection.

    However, others said the decision had created an over-optimistic narrative of a patient on an upward trajectory.

    Damian Cruse, a cognitive neuroscientist at the University of Birmingham, said: “I do worry that the media coverage of the study gave a more hopeful message to other families in this situation than the message that perhaps would have been delivered with all of the facts … If we protect patient anonymity, then there’s no reason not to be able to tell the full story.”

    When the paper came out last month, Angela Sirigu, who led the work at the Institut des Sciences Cognitives Marc Jeannerod in Lyon, France, told the Guardian: “He is still paralysed, he cannot talk, but he can respond. Now he is more aware.”

    Sirigu appeared to suggest that the team was continuing to monitor the man when, in fact, the patient had already died.

    Of the decision not to report the death, Sirigu told the Guardian: “The patient’s death was not linked to our protocol. He entered in our study in January 2016 and his participation ended [at the] beginning of September 2016. We respected the family decision to not communicate about the event. What was important for us was to keep the event in the privacy of this wonderful family.”

    Prof Jacques Luauté of the University of Lyon, who had followed the patient for several years, told Le Monde: “We discussed it with the family. Together, we thought, wrongly, that it would lead to people linking the stimulation and the death. We concluded that the death, which wasn’t linked to the study, was a private family event. This was a mistake, because it was obvious that we’d be asked what became of the patient.”


    Courtesy of Doximity