Clinical Research Directory

Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Patients With Disorders of Consciousness

Consciousness disorders following severe brain injury refer to a series of disturbances in arousal and cognition secondary to organic brain diseases, including Unresponsive Wakefulness Syndrome (UWS) (also termed Vegetative State, VS) and Minimally Conscious State (MCS). Disorders of consciousness(DoC) is listed in the International Statistical Classification of Diseases and Related Health Problems, though it is not currently recognized as an independent and consistent diagnostic category. According to epidemiological surveys, conservative estimates suggest that 70,000 to 100,000 new cases of DoC are reported annually in China, posing significant challenges for clinical diagnosis and treatment. Accurately assessing DoC, understanding its neurobiological underpinnings, and developing effective rehabilitation strategies remain subjects requiring further investigation through both clinical and basic neuroscience research. Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) is a non-invasive brain stimulation technique that delivers electrical impulses to the auricular branch of the vagus nerve. Substantial evidence indicates that taVNS serves as a therapeutic intervention for various neurological and psychiatric disorders, such as epilepsy, treatment-resistant depression, migraines, and cognitive impairments. As an emerging neurostimulation technique, taVNS has been investigated for its potential to promote the recovery of awareness in patients with DoC. However, clinical evidence remains limited, underscoring the need for further trials to substantiate its efficacy. Developed from traditional implanted Vagus Nerve Stimulation(VNS), taVNS offers high safety and minimal to negligible side effects, presenting a promising therapeutic avenue for patients with severe traumatic brain injury and disorders of consciousness. Methods: This study is a single-arm trial. A total of 20 patients are planned to be enrolled. Each patient will receive taVNS twice daily over a period of 10 consecutive days, totaling 20 sessions. Primary and secondary outcome measures will be assessed at baseline and after the completion of taVNS treatment. The primary efficacy endpoint will be the change in behavioral responses as evaluated by the Coma Recovery Scale-Revised (CRS-R). Additionally, resting-state high-density electroencephalography (EEG) and combined transcranial magnetic stimulation with EEG (TMS-EEG) recordings will be utilized to investigate the neurophysiological correlates of taVNS intervention. Discussion: This study will provide valuable insights to inform the selection of treatment approaches for patients with disorders of consciousness. By employing a pre-post within-subject comparison design, it aims to validate the therapeutic role of Closed-Loop Transcutaneous Auricular Vagus Nerve Stimulation (CL-taVNS) in this patient population.

fNIRS for Disorders of Consciousness

The goal of this observational study is to learn whether functional near-infrared spectroscopy (fNIRS) can measure brain activity in healthy adults and in people with disorders of consciousness (DoC) in the neuro-intensive care unit (Neuro-ICU). DoC include conditions such as coma and minimally conscious state that occur after severe brain injury. These conditions make it difficult to assess a person's level of awareness because many clinical tests rely on observable behaviors such as speaking or moving, which are commonly impaired after brain injury. The main questions the study aims to answer are: * Can fNIRS detect changes in brain activity in healthy adults when they receive sensory stimulation or perform mental tasks? * Can the same fNIRS protocol be used in patients with disorders of consciousness in the Neuro-ICU to measure brain responses and determine whether the method is feasible in this clinical setting? The investigators will first study healthy adult volunteers to establish baseline brain responses and determine which tasks produce the most reliable signals. The protocol will then be applied to patients with disorders of consciousness admitted to the Neuro-ICU. Participants will take part in a single research session lasting about 30 to 45 minutes while wearing the lightweight fNIRS headband that measures brain oxygen levels using near-infrared light. During the session, participants will: * Wear a non-invasive fNIRS headband placed on the forehead * Receive gentle sensory stimulation (for example, compression devices on the legs or hands) * Listen to sounds or spoken sentences * Perform guided mental tasks such as imagining walking through their home or imagining moving a limb The study does not test a treatment and will not change medical care. The goal is to determine whether fNIRS can safely and reliably measure brain activity at the bedside and provide preliminary information that may help guide future research on improving the assessment of consciousness after brain injury.

Window On the Brain

Disorders of consciousness (DOC) diagnosis suffers from the difficulty to measure the level of consciousness due to the variability associated with behavioural assessments and the difficulty in detecting the residual level of consciousness in patients who do not show any behavioural signs during the behavioural assessment. This issue could be overcome by using instrumental tools, that are expensive and not always available in clinical settings. The ultrasound-based techniques could represent a valid low-cost and more feasible alternative to deep the knowledge about physio-pathological mechanisms underlying DOC and their chronicization. These techniques could be tailored to treat acute and chronic DOC patients from a personalised medicine perspective. Improving the knowledge, management and care pathways of DOC patients and finding new therapeutic options would benefit not only patients but also public health systems.

Spontaneous Eye Blinking Evaluation for Cognitive Assessment of Individuals With Severe Acquired Brain Injury

Assessment of consciousness and attention in individuals with severe Acquired Brain Injury (sABI) is crucial for planning rehabilitation, but it is often hindered by coexisting sensory-motor and/or cognitive-behavioural disorders. This project aims at evaluating the value of spontaneous eye blinking features to assess patients' attentional abilities and to distinguish patients with unresponsive wakefulness syndrome (UWS) from those in minimally conscious state (MCS). Patients will undergo an EEG-EOG recording at rest and during an auditory oddball task. Eye blinking features on EOG will be analysed and compared to that of healthy individuals. A machine-learning-based algorithm using blinking features for the diagnosis of patients with sABI will be studied and validated preliminarily. This project will help to stratify patients with sABI using easy-to-detect clinical markers, supporting clinicians' decision-making about patient's management. Additionally, blinking patterns related to residual attentional abilities in patients emerged from disorders of consciousness will be investigated.

mindBEAGLE: Unlocking Functional Communication for Patients With Disorders of Consciousness

The goal of this clinical trial is to test how effective the mindBEAGLE device is in allowing people who are unconscious (due to a brain injury or other condition) to communicate using brain waves to answer Yes/No questions. Participants will wear a cap that will be connected to a computer that measures brain waves, wrist bands that vibrate at different strengths, and ear phones that create different levels of loud tones and will be asked to associate Yes/No answers with the vibrations or tones. They will also be asked to "think about" moving different parts of their body to answer Yes or No. The mindBEAGLE device has already been proven effective for this kind of communication in a previous study, and the study team would like to trial it on a population of unconscious people who enter the UPMC Rehabilitation Institute to see if patients are able to be trained to use the device as part of their everyday inpatient rehabilitation until they are discharged, or until they are able to regain consciousness.

REstoring CONsciousness With NEurostimulation of the Central Thalamus: The RECONNECT Study

The RE-CONNECT study is an early feasibility study to establish the safety, feasibility, and efficacy of two central thalamic deep brain stimulation targets in patients with chronic disorders of consciousness.

Diagnosis Value of Interoceptive EEG Indicators by Rectal Stimulation in DoC

Study on the Significance and Value of Interoception-Related Indicators in the Classification of Patients with Disorders of Consciousness (DoC) via Rectal Stimulation

Spontaneous Eye Blinking in Disorders of Consciousness

Differential diagnosis between Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) is complicated due to severe cognitive and/or sensorimotor deficits in these patients. In this study the investigators aimed at exploring the diagnostic and prognostic validity of spontaneous eye blinking parameters (rate, amplitude, duration, variability) in a sample of patients with Disorders of Consciousness (DoC). This is a multi-center prospective observational study conducted in patients with Severe Acquired Brain Injury (sABI) and DoC admitted to 8 European participating centers, with clinical data collection not deviating from routine practice. The study is non-commercial and will have a maximum total duration of 24 months.

Advancing Assessment for Disorders of Consciousness

Over the past two decades, major progress has been made in detecting, predicting and promoting recovery of consciousness in patients with disorders of consciousness (DOC) caused by severe brain injuries. This study will aim to establish innovative standards and intelligent diagnostic system based on multi-source heterogeneous information including clinical signs, advanced neuroimaging and electrophysiological techniques, thus raising hope for more accurate diagnosis and prognosis.

What is the Perceived Role of Risk in DOC Healthcare.

Critical ethnography exploring how decisions are made on behalf of people in disorder of consciousness (DOC). Prospective longitudinal case study design including observation, field interview and video reflexive ethnography.

Investigation of Mnesic Capacities in Patients With a Disorder of Consciousness

Following severe brain damage, some individuals lose partial or total awareness of themselves and their environment, falling into a coma that can evolve towards a Disorder of Consciousness (DoC). Accurately diagnosing the depth of consciousness alteration, and thus characterizing the patient's residual state of consciousness, is a real medical challenge, yet crucial for establishing a neurological prognosis, predicting cognitive outcome, and guiding medical decisions. Clinicians attempt to classify DoC patients into different global states (e.g. coma, Unresponsive Wakefulness Syndrome (UWS), Minimally Conscious State (MCS)) depending on their residual level of arousal and awareness. In recent years, the improvement of diagnostic tools and the use of a multimodal approach combining clinical, neurophysiological and neuroimaging examinations, have greatly refined this assessment and revealed the existence of possible discrepancies between clinical observation (e.g. poor consciousness state like UWS) and brain activity (richer, MCS+ type, or even conscious) so-called Cognitive-Motor Dissociation, making it essential to search for any 'hidden cognition' not revealed by the clinical behavioral examination. It is therefore essential to have tools that can not only probe consciousness level, but also provide a detailed profile of patients' residual cognitive abilities - such as language, attention or memory - which are essential dimmensions of conscious experience and shape waking cognitive life. This could crucially improve the neurological diagnostic and prognostic' accuracy of these disorders, as well as allowing to infer the eventual subjective experience of these patients. Indeed, we still know very little about the possible conscious 'contents' involved in these states. What does the possible 'mental life' of DoC patients look like? A multidimensional exploration of their cognition is needed, requiring the development of innovative methods capable of probing cognitive functions in the absence of any communication with the patient. Thus, the general aim of this study lies in the development of tools for the cognitive exploration of DoC patients and their application at patients' bedside in the Intensive Care Unit (ICU). We're particularly interested in assessing memory capacities in these patients, as exploration of memory has immediate clinical implications, since memory encoding during DoC could impact patients' quality of life and be implicated in the occurrence of post-traumatic stress disorder (PTSD) in case of consciousness recovery. More specifically, we want to tackle the following questions: Are patients suffering from a DoC able to form, consolidate and retrieve new memories (anterograde memory)? Are they able to recall memories from their 'past life' (retrograde memory)? Previous research suggests that some DoC patients retain the ability to reactivate old autobiographical memory traces, and to present automatic short-term sensory memory processes, or residual working memory. Nevertheless, DoC patients' memory abilities have been little studied to date, despite their clinical relevance. We postulate that memory could be differentially preserved between different clinical states of DoC such as UWS and MCS. At the group level, we expect MCS patients to have better learning and memory retrieval abilities than UWS patients. We therefore expect memory functions to be affected by brain lesions and, consequently, by consciousness alteration, although we envisage the preservation of unconscious memory processes (e.g. in non-declarative memory subtypes such as perceptual memory) in UWS patients. We hypothesize that the presence of robust markers of memory processes will vary, at the single-patient level, according to the types and stages of memory tested, informing the cognitive profile of the patient suffering from a DoC. By providing information on the potential presence of memory capacities that cannot be revealed by clinical examination, the physiological tools we are developing in this study will open a crucial window onto non-communicating patients' cognition. Defining DoC patients' memory profile could not only improve their care during and after the disorder (reflection on the quality of life in ICU; better understanding of cognitive and psychological symptoms occurring after a DoC (e.g. amnesia, PTSD); orientation of rehabilitation strategies), but also improve the diagnostic accuracy of these troubles if memory proves to be differentially preserved between different DoC states such as UWS and MCS. Ultimately, we aim to refine the neurological prognosis of these non-responsive patients, by predicting their cognitive outcome thanks to these innovative physiological tools. On a more fundamental level, this project questions the interplay of memory and consciousness, exploring which forms of memory do and do not require a conscious state.

Tickle Stimulation in Disorders of Consciousness (DoC)

The aim of this project is to investigate whether tickling stimulations can have a short-term effect on the responsiveness of patients with Disorders of Consciousness due to Severe Acquired Brain Injury and to compare this effect with that of neutral tactile stimulations that do not induce tickling.

Tactile Stimulation in Disorders of Consciousness (DoC)

The aim of this project is to evaluate the behavioural and neurophysiological responses to pleasant touch in patients with disorders of consciousness (DoC) and to determine whether these responses are related to the level of consciousness. Specifically, the study aims to: 1. explore the relationship between pleasant tactile stimulation and behavioural and neurophysiological responses in patients with DoC; 2. determine whether behavioural responses to pleasant touch stimulation correlate with the level of consciousness; 3. assess whether behavioural responses vary depending on the valence of the stimulus (pleasant, neutral, or unpleasant); 4. examine neurophysiological responses to tactile stimulation using functional near-infrared spectroscopy (fNIRS), and evaluate whether brain activation patterns are associated with behavioural responses; 5. improve diagnostic accuracy in patients with DoC by exploring the value of somatosensory responses in distinguishing unresponsive wakefulness syndrome (UWS) from minimally conscious state (MCS) or conscious patients; 6. explore the potential usefulness of implementing this type of stimulation within rehabilitation programs to support better recovery of consciousness.

Transcranial Temporal Interference Stimulation In Severely Brain Injured Patients With Disorders of Consciousness

The purpose of this academic lead study is to explore the effect of noninvasive neuromodulation of the CM-pf via tTIS for patients with disorders of consciousness.

The Temporally Interfering in Patients with Disorders of Consciousness

This project will help the patient recover consciousness by giving TI (temporally interfering) treatment

The Effects of Psilocybin on Shared Experience in Film Processing

The goal of this clinical trial is to learn whether certain methods of detecting awareness in vegetative or minimally conscious patients (using neuroimaging) are sensitive to the effects of psilocybin (a psychedelic drug). One of these methods includes scanning peoples\' brains while they watch a film. When different individuals watch a film, their brains become synchronized with each other as they watch the plot unfold. Most importantly, if a seemingly unconscious patient also shows the same brain-synchronization, it means they might actually be conscious and aware. To approach this goal, the investigators will be carrying out this trial in healthy volunteers. This will help better understand whether psilocybin may be a potential treatment for restoring awareness in these patients. The main questions it aims to answer are: * Does psilocybin enhance or diminish brain synchrony during a film? * Do changes in brain synchrony reflect differences in each individual\'s conscious experience? Participants will be asked to: * Attend two brain scanning sessions and watch a series of film clips, perform a brief mental imagery task, and listen to music - once under a placebo, and once under psilocybin. * Play a series of games that assess their cognition (memory, reasoning, planning, etc.). * Perform a series of visual illusions tasks.

Brain Network Analysis of Anesthesia Characteristics in Patients With pDoC Based on PSG

The goal of this prospective, exploratory and observational study is to learn about in healthy volunteers and patients with prolonged disorders of consciousness(pDoC). The main questions it aims to answer are: 1. Observe the similarities and differences of polysomnography between pDoC patients and healthy volunteers, and analyze the characteristic brain network changes based on polysomnography 2. To observe the similarities and differences of polysomnography in pDoC patients before and after Insertion of spinal cord electric stimulator under general anesthesia,and analyze the changes of anesthesia characteristic brain network in patients with consciousness disorders based on polysomnography. 3. To observe the similarities and differences of polysomnography in pDoC patients before and after spinal cord stimulation,and analyze the characteristic changes of brain network after spinal cord stimulation. We will record the 8h polysomnography of healthy volunteers,record the polysomnography of DOC patients before and 24 hours after operation;and record the 24h polysomnography of patients with spinal cord electric stimulator.