Patients with chronic disorders of consciousness face a significant lack of treatment options.
We aimed at investigating the feasibility and the behavioral effects of home-based transcranial direct ...current stimulation (tDCS), applied by relatives or caregivers, in chronic patients in minimally conscious state (MCS).
Each participant received, in a randomized order, 20 sessions of active and 20 sessions of sham tDCS applied over the prefrontal cortex for 4 weeks; separated by 8 weeks of washout. Level of consciousness was assessed using the Coma Recovery Scale-Revised before the first stimulation (baseline), at the end of the 20 tDCS sessions (direct effects) and 8 weeks after the end of each stimulation period (long-term effects). Reported adverse events and data relative to the adherence (i.e., amount of sessions effectively received) were collected as well.
Twenty-seven patients completed the study and 22 patients received at least 80% of the stimulation sessions. All patients tolerated tDCS well, no severe adverse events were noticed after real stimulation and the overall adherence (i.e., total duration of stimulation) was good. A moderate effect size (0.47 and 0.53, for modified intention to treat and per protocol analysis, respectively) was observed at the end of the 4 weeks of tDCS in favor of the active treatment.
We demonstrated that home-based tDCS can be used adequately outside a research facility or hospital by patients' relatives or caregivers. In addition, 4 weeks of tDCS moderately improved the recovery of signs of consciousness in chronic MCS patients.
•Feasibility, efficiency and safety of tDCS in minimally conscious state patients are investigated.•Repeated tDCS shows moderate efficacy along with excellent feasibility and safety.•tDCS is a valuable treatment option for patients with chronic minimally conscious state.
Thermosensation is crucial for humans to probe the environment and detect threats arising from noxious heat or cold. Over the last years, EEG frequency-tagging using long-lasting periodic radiant ...heat stimulation has been proposed as a means to study the cortical processes underlying tonic heat perception. This approach is based on the notion that periodic modulation of a sustained stimulus can elicit synchronized periodic activity in the neuronal populations responding to the stimulus, known as a steady-state response (SSR). In this paper, we extend this approach using a contact thermode to generate both heat- and cold-evoked SSRs. Furthermore, we characterize the temporal dynamics of the elicited responses, relate these dynamics to perception, and assess the effects of displacing the stimulated skin surface to gain insight on the heat- and cold-sensitive afferents conveying these responses. Two experiments were conducted in healthy volunteers. In both experiments, noxious heat and innocuous cool stimuli were applied during 75 seconds to the forearm using a Peltier-based contact thermode, with intensities varying sinusoidally at 0.2 Hz. Displacement of the thermal stimulation on the skin surface was achieved by independently controlling the Peltier elements of the thermal probe. Continuous intensity ratings to sustained heat and cold stimulation were obtained in the first experiment with 14 subjects, and the EEG was recorded in the second experiment on 15 subjects. Both contact heat and cool stimulation elicited periodic EEG responses and percepts. Compared to heat stimulation, the responses to cool stimulation had a lower magnitude and shorter latency. All responses tended to habituate along time, and this response attenuation was most pronounced for cool compared to warm stimulation, and for stimulation delivered using a fixed surface compared to a variable surface.
Background
With the emergence of Brain Computer Interfaces (BCI), clinicians have been facing a new group of patients with severe acquired brain injury who are unable to show any behavioral sign of ...consciousness but respond to active neuroimaging or electrophysiological paradigms. However, even though well documented, there is still no consensus regarding the nomenclature for this clinical entity.
Objectives
This systematic review aims to 1) identify the terms used to indicate the presence of this entity through the years, and 2) promote an informed discussion regarding the rationale for these names and the best candidates to name this fascinating disorder.
Methods
The Disorders of Consciousness Special Interest Group (DoC SIG) of the International Brain Injury Association (IBIA) launched a search on Pubmed and Google scholar following PRISMA guidelines to collect peer-reviewed articles and reviews on human adults (>18 years) published in English between 2006 and 2021.
Results
The search launched in January 2021 identified 4,089 potentially relevant titles. After screening, 1,126 abstracts were found relevant. Finally, 161 manuscripts were included in our analyses. Only 58% of the manuscripts used a specific name to discuss this clinical entity, among which 32% used several names interchangeably throughout the text. We found 25 different names given to this entity. The five following names were the ones the most frequently used: covert awareness, cognitive motor dissociation, functional locked-in, non-behavioral MCS (MCS
*
) and higher-order cortex motor dissociation.
Conclusion
Since 2006, there has been no agreement regarding the taxonomy to use for unresponsive patients who are able to respond to active neuroimaging or electrophysiological paradigms. Developing a standard taxonomy is an important goal for future research studies and clinical translation. We recommend a Delphi study in order to build such a consensus.
The assessment and management of pain and nociception is very challenging in patients unable to communicate functionally such as patients with disorders of consciousness (DoC) or in locked-in ...syndrome (LIS). In a clinical setting, the detection of signs of pain and nociception by the medical staff is therefore essential for the wellbeing and management of these patients. However, there is still a lot unknown and a lack of clear guidelines regarding the assessment, management and treatment of pain and nociception in these populations. The purpose of this narrative review is to examine the current knowledge regarding this issue by covering different topics such as: the neurophysiology of pain and nociception (in healthy subjects and patients), the source and impact of nociception and pain in DoC and LIS and, finally, the assessment and treatment of pain and nociception in these populations. In this review we will also give possible research directions that could help to improve the management of this specific population of severely brain damaged patients.
•Behavioral and EEG effects of multifocal frontoparietal tDCS are investigated in patients with severe brain injury.•No behavioral treatment effect was identified at the group level while EEG ...complexity increased in low frequency bands.•Electrophysiological changes were not translated into behavioral changes at the group level.
Transcranial direct current stimulation (tDCS) may promote the recovery of severely brain-injured patients with disorders of consciousness (DOC). Prior tDCS studies targeted single brain regions rather than brain networks critical for consciousness recovery.
Investigate the behavioral and electrophysiological effects of multifocal tDCS applied over the frontoparietal external awareness network in patients with chronic acquired DOC.
Forty-six patients were included in this randomized double-blind sham-controlled crossover trial (median interquartile range: 46 35 – 59 years old; 12 5 – 47 months post injury; 17 unresponsive wakefulness syndrome, 23 minimally conscious state (MCS) and 6 emerged from the MCS). Multifocal tDCS was applied for 20 min using 4 anodes and 4 cathodes with 1 mA per electrode. Coma Recovery Scale-Revised (CRS-R) assessment and 10 min of resting state electroencephalogram (EEG) recordings were acquired before and after the active and sham sessions.
At the group level, there was no tDCS behavioral treatment effect. However, following active tDCS, the EEG complexity significantly increased in low frequency bands (1–8 Hz). CRS-R total score improvement was associated with decreased baseline complexity in those bands. At the individual level, after active tDCS, new behaviors consistent with conscious awareness emerged in 5 patients. Conversely, 3 patients lost behaviors consistent with conscious awareness.
The behavioral effect of multifocal frontoparietal tDCS varies across patients with DOC. Electrophysiological changes were observed in low frequency bands but not translated into behavioral changes at the group level.
Improving the functional recovery of patients with DoC remains one of the greatest challenges of the field. Different theories exist about the role of the anterior (prefrontal areas) versus posterior ...(parietal areas) parts of the brain as hotspots for the recovery of consciousness. Repetitive transcranial magnetic stimulation (rTMS) is a powerful non-invasive brain stimulation technique for the treatment of DoC. However, a direct comparison of the effect of TMS treatment on the front versus the back of the brain has yet to be performed. In this study, we aim to assess the short- and long-term effects of frontal and parietal rTMS on DoC recovery and characterize responders phenotypically.
Ninety patients with subacute and prolonged DoC will be included in a two-part multicenter prospective study. In the first phase (randomized controlled trial, RCT), patients will undergo four rTMS sessions in a crossover design over 10 days, targeting (i) the left dorsolateral prefrontal cortex (DLPFC) and (ii) the left angular gyrus (AG), as well as (iii & iv) their sham alternatives. In the second phase (longitudinal personalized trial), patients will receive personalized stimulations for 20 working days targeting the brain area that showed the best results in the RCT and will be randomly assigned to either active or sham intervention. The effects of rTMS on neurobehavioral and neurophysiological functioning in patients with DoC will be evaluated using clinical biomarkers of responsiveness (i.e., the Coma Recovery Scale-Revised; CRS-R), and electrophysiological biomarkers (e.g., power spectra, functional and effective connectivity, perturbational complexity index before and after intervention). Functional long-term outcomes will be assessed at 3 and 6 months post-intervention. Adverse events will be recorded during the treatment phase.
This study seeks to identify which brain region (front or back) is best to stimulate for the treatment of patients with DoC using rTMS, and to characterize the neural correlates of its action regarding recovery of consciousness and functional outcome. In addition, we will define the responders' profile based on patients' characteristics and functional impairments; and develop biomarkers of responsiveness using EEG analysis according to the clinical responsiveness to the treatment.
https://clinicaltrials.gov/ct2/show/NCT04401319, Clinicaltrials.gov, n° NCT04401319.
Covert cognition in patients with disorders of consciousness represents a real diagnostic conundrum for clinicians. In this meta-analysis, our main objective was to identify clinical and demographic ...variables that are more likely to be associated with responding to an active paradigm. Among 2018 citations found on PubMed, 60 observational studies were found relevant. Based on the QUADAS-2, 49 studies were considered. Data from 25 publications were extracted and included in the meta-analysis. Most of these studies used electrophysiology as well as counting tasks or mental imagery. According to our statistical analysis, patients clinically diagnosed as being in a vegetative state and in a minimally conscious state minus (MCS-) show similar likelihood in responding to active paradigm and responders are most likely suffering from a traumatic brain injury. In the future, multi-centric studies should be performed in order to increase sample size, with similar methodologies and include structural and functional neuroimaging in order to identify cerebral markers related to such a challenging diagnosis.
In the context of managing persistent post-concussive symptoms (PPCS), existing treatments like pharmacotherapy, cognitive behavioral therapy, and physical rehabilitation show only moderate ...effectiveness. The emergence of neuromodulation techniques in PPCS management has led to debates regarding optimal stimulation parameters and their overall efficacy.
this scoping review involved a comprehensive search of PubMed and ScienceDirect databases, focusing on controlled studies examining the therapeutic potential of non-invasive brain stimulation (NIBS) techniques in adults with PPCS.
Among the 940 abstracts screened, only five studies, encompassing 103 patients (12 to 29 per study), met the inclusion criteria. These studies assessed the efficacy of transcranial direct current stimulation (tDCS), or repetitive transcranial magnetic stimulation (rTMS), applied to specific brain regions (i.e., the left dorsolateral pre-frontal cortex (DLPFC) or left motor cortex (M1)) for addressing cognitive and psychological symptoms, headaches, and general PPCSs. The results indicated improvements in cognitive functions with tDCS. In contrast, reductions in headache intensity and depression scores were observed with rTMS, while no significant findings were noted for general symptoms with rTMS.
although these pilot studies suggest promise for rTMS and tDCS in PPCS management, further research with larger-scale investigations and standardized protocols is imperative to enhance treatment outcomes for PPCS patients.
Background and Objectives:
Persistent post-concussive symptoms (PCS) consist of neurologic and psychological complaints persisting after a mild traumatic brain injury (mTBI). It affects up to 50% of ...mTBI patients, may cause long-term disability, and reduce patients' quality of life. The aim of this review was to examine the possible use of different neuroimaging modalities in PCS.
Methods:
Articles from Pubmed database were screened to extract studies that investigated the relationship between any neuroimaging features and symptoms of PCS. Descriptive statistics were applied to report the results.
Results:
A total of 80 out of 939 papers were included in the final review. Ten examined conventional MRI (30% positive finding), 24 examined diffusion weighted imaging (54.17% positive finding), 23 examined functional MRI (82.61% positive finding), nine examined electro(magneto)encephalography (77.78% positive finding), and 14 examined other techniques (71% positive finding).
Conclusion:
MRI was the most widely used technique, while functional techniques seem to be the most sensitive tools to evaluate PCS. The common functional patterns associated with symptoms of PCS were a decreased anti-correlation between the default mode network and the task positive network and reduced brain activity in specific areas (most often in the prefrontal cortex).
Significance:
Our findings highlight the importance to use functional approaches which demonstrated a functional alteration in brain connectivity and activity in most studies assessing PCS.
Epileptic seizures/post-traumatic epilepsy (ES/PTE) are frequent in persons with brain injuries, particularly for patients with more severe injuries including ones that result in disorders of ...consciousness (DoC). Surprisingly, there are currently no best practice guidelines for assessment or management of ES in persons with DoC. This study aimed to identify clinician attitudes toward epilepsy prophylaxis, diagnosis and treatment in patients with DoC as well as current practice in regards to the use of amantadine in these individuals. A cross-sectional online survey was sent to members of the International Brain Injury Association (IBIA). Fifty physician responses were included in the final analysis. Withdrawal of antiepileptic drug/anti-seizure medications (AED/ASM) therapy was guided by the absence of evidence of clinical seizure whether or not the AED/ASM was given prophylactically or for actual seizure/epilepsy treatment. Standard EEG was the most frequent diagnostic method utilized. The majority of respondents ordered an EEG if there were concerns regarding lack of neurological progress. AED/ASM prescription was reported to be triggered by the first clinically evident seizure with levetiracetam being the AED/ASM of choice. Amantadine was frequently prescribed although less so in patients with epilepsy and/or EEG based epileptic abnormalities. A minority of respondents reported an association between amantadine and seizure. Longitudinal studies on epilepsy management, epilepsy impact on neurologic prognosis, as well as potential drug effects on seizure risk in persons with DoC appear warranted with the goal of pushing guideline development forward and improving clinical assessment and management of seizures in this unique, albeit challenging, population.
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