| Abstract/Results: | ABSTRACT:
After a severe brain injury leading to a period of coma, a possible scenario is that the patient remains with an altered state of consciousness for a prolonged period. These disorders of consciousness (DOC) encompass the unresponsive wakefulness syndrome (UWS); a state of awakening with only reflexive movements and the minimally conscious state (MCS); where fluctuating but reproducible signs of consciousness are observed. The
ability to functionally use objects or communicate then marks the transition to the emergence of the MCS (EMCS). The management of patient with DOC represents a medical challenge from both diagnostic and treatment perspectives. Given the absence of subjective report, the brain injury-associated cognitive and motor deficits and the fluctuations in vigilance that characterize them, the misdiagnosis rates can go up to 40%, with dramatic impact on their care. Furthermore, therapeutic approaches to increase their level of consciousness and ameliorate their functional status are lacking and poorly investigated. The present thesis had therefore two aims: i) better characterizing the path to recovery from a behavioral perspective (Part One) and ii) investigate the use of non-invasive brain stimulation, more specifically transcranial direct current
stimulation (tDCS), and its different application parameters, as a treatment option (Part Two).
In Part One, we present two retrospectives studies using data collected by therapists in a specialized rehabilitation setting. We used repeated administrations of the Coma Recovery Scale-Revised (CRS-R), the current gold standard for behavioral assessment of DOC patients, to pin down the initial transition from unconscious states (i.e., coma or UWS) to recovery of consciousness (i.e., MCS or EMCS). Among the 13 CRS-R behaviors depicting consciousness, visual pursuit most often marked the transition while the time to recovery of consciousness was approximately six weeks after injury. We then focused on a specific and highly clinically relevant behavior that is the recovery of communication; anticipated by both relatives and therapists as it substantially ameliorates the interactions and the care. Within our 8-week observation period, the ability to answer some close-ended questions, despite of accuracy (i.e., intentional communication) was usually recovered within 40 days after injury
while correctly answering six out of six close-ended questions (i.e., functional communication) reappeared about nine days later. In Part Two, we develop four studies: a pilot trial, two randomized controlled trials and a study protocol, aiming at answering the following questions regarding the use of tDCS as a therapeutic option: In what kind of setting can we apply it? Where should we stimulate? When? Which setting – In a feasibility and efficacy randomized controlled trial, we investigated the home-based application of tDCS, applied for a prolonged period of 20 days over the left prefrontal cortex of 27 chronic MCS patients following traumatic or nontraumatic insult. There was a significant behavioral treatment effect at the group level, as long as at least 80% of the planned sessions were applied. No severe adverse events were reported. Where – The first pilot study investigated the effects of a single session of tDCS applied over the motor cortex in ten UWS and MCS patients, with traumatic and non-traumatic etiologies. No behavioral treatment effect was identified at the group level while at the individual level, two patients responded to tDCS by showing a new sign of consciousness for the first time after active and not sham stimulation. In a randomized controlled trial performed on 46 patients in UWS, MCS or EMCS with traumatic or non-traumatic etiologies, we used multifocal network-based tDCS to stimulate the frontoparietal network, also known as the external awareness network. Again, there was no group level behavioral treatment effect while at the individual level, seven patients responded positively to tDCS. Seven other patients negatively responded by losing a sign of
consciousness after active stimulation that was present before. These patients presented an initial significantly higher complexity of the EEG signal in the theta band. When – Finally, we developed an original study protocol based on brain-state dependent application of tDCS, in a closed-loop fashion. Based on electroencephalographic entropy patterns as markers of vigilance, we aim to compare the behavioral and electrophysiological effects of tDCS applied at high and low levels of vigilance and hypothesize this approach will significantly impact the individual response to tDCS. Overall, the present findings show that patients with DOC have a strong potential for recovery in the subacute phase of their injury, and that false despair should be avoided in the early stages. These patients could benefit from tDCS, which has a proven efficacy when applied over the prefrontal cortex and when repeating the amount of sessions. Caregivers and relatives can be safely involved to apply this type of treatment and there is a potential in determining the timing of stimulations based on the brain’s spontaneous activity.
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