Periodic Reporting for period 1 - ComAlive (Diagnosis, prediction, communication and rehabilitation for patients with disorders of consciousness)
Reporting period: 2019-07-01 to 2021-06-30
Comalive project aimed to contribute to the research on diagnosis, communication and rehabilitation of the disorders of consciousness (DOC).
DOC are neurological conditions in which awareness and responsivity to environmental stimuli are compromised.
The DOCs include the Coma, characterised by closed eyes and no volitional responses to commands or sensory stimulation. When eye-opening appears, without other changes in responsivity, the Unresponsive Wakefulness Syndrome (UWS) is recognised. Consistent voluntary reactions to external stimuli characterise the Minimal Conscious State (MCS). The Complete Locked-in Syndrome (CLIS) is contiguous to the DOC. The affected patients present anarthria and quadriplegia, with impossible verbal language and voluntary movements. Consequently, they can’t communicate by any means with the external environment, despite preserving intact cognitive functioning, according to the evidence of preservation of cortical circuits (Fig. 1).
The bedside diagnosis of the DOCs and CLIS represents a challenge even for expert physicians. It has been estimated that up to 43 % of clinically diagnosed UWS preserve a minimal consciousness, which can’t be recognised because of motor impairment, attention fluctuations, severe hypertonus and other clinical characteristics.
The diagnostic precision of the DOC has relevant ethical implications. UWS patients don’t have access to life-prolonging treatments and rehabilitation programs in most countries due to a reduced possibility of recovery.
From these premises arises the need for instrumental support to the clinical diagnosis to detect covert awareness in patients unresponsive at the bedside. For this purpose, we applied EEG-based brain-computer interface (BCI) paradigms to record non-invasively the cortical activity and directly measure the execution of mental tasks. Besides the diagnostic application, we explored the potential use of these devices to establish communication with these vulnerable patients, possibly directed to collecting their needs and wishes. Finally, we studied the potential role of EEG-based BCIs on the rehabilitation of DOC.
Key scientific objectives of Comalive included:
I. Use of EEG-based brain-computer interfaces for diagnosis, prediction and communication with patients with disorders of consciousness
II. Use of EEG-based brain-computer interfaces for rehabilitation of patients with disorders of consciousness
DOC are neurological conditions in which awareness and responsivity to environmental stimuli are compromised.
The DOCs include the Coma, characterised by closed eyes and no volitional responses to commands or sensory stimulation. When eye-opening appears, without other changes in responsivity, the Unresponsive Wakefulness Syndrome (UWS) is recognised. Consistent voluntary reactions to external stimuli characterise the Minimal Conscious State (MCS). The Complete Locked-in Syndrome (CLIS) is contiguous to the DOC. The affected patients present anarthria and quadriplegia, with impossible verbal language and voluntary movements. Consequently, they can’t communicate by any means with the external environment, despite preserving intact cognitive functioning, according to the evidence of preservation of cortical circuits (Fig. 1).
The bedside diagnosis of the DOCs and CLIS represents a challenge even for expert physicians. It has been estimated that up to 43 % of clinically diagnosed UWS preserve a minimal consciousness, which can’t be recognised because of motor impairment, attention fluctuations, severe hypertonus and other clinical characteristics.
The diagnostic precision of the DOC has relevant ethical implications. UWS patients don’t have access to life-prolonging treatments and rehabilitation programs in most countries due to a reduced possibility of recovery.
From these premises arises the need for instrumental support to the clinical diagnosis to detect covert awareness in patients unresponsive at the bedside. For this purpose, we applied EEG-based brain-computer interface (BCI) paradigms to record non-invasively the cortical activity and directly measure the execution of mental tasks. Besides the diagnostic application, we explored the potential use of these devices to establish communication with these vulnerable patients, possibly directed to collecting their needs and wishes. Finally, we studied the potential role of EEG-based BCIs on the rehabilitation of DOC.
Key scientific objectives of Comalive included:
I. Use of EEG-based brain-computer interfaces for diagnosis, prediction and communication with patients with disorders of consciousness
II. Use of EEG-based brain-computer interfaces for rehabilitation of patients with disorders of consciousness
As part of the Comalive project, we compared simultaneously the repetitive assessment of consciousness performed with a behavioural scale (CRS-R) and a vibrotactile-based BCI to detect command following on a group of sixteen DOC (Fig. 2, 3). We could observe that the first CRS-R lead to a considerable rate of misdiagnosis. Moreover, over a comparative assessment that lasted at least two months, the BCI detected covert command following before the behavioural scale in several cases.
Moreover, we implemented a BCI training protocol on a cohort of DOC patients and analysed the effects on the behavioural responsivity assessed by the CRS-R. This research showed that BCI training protocols could be safely applied to DOC patients. Moreover, at the end of the two-week study period, we observed an improvement in the CRS-R score in 5 out of 10 DOC patients.
Still, as preparatory studies on communication with CLIS and DOC patients, we analysed the capacity to give consent to treatment (CCT) of severely disabled patients. This study showed that most Amyotrophic Lateral Sclerosis (ALS) patients preserve CCT, which is affected by frontal dysfunction and educational level.
We also tested a prototype vibrotactile-based BCI system with 7 stimuli on healthy subjects and patients.
Moreover, we reviewed the literature on the BCI applications on the DOC and developed a “clinical friendly guide” for not healthcare experts. Finally, we have undertaken a meta-analysis of the published data on the BCI paradigms used for detecting command following in the UWS patients.
Dissemination activities included five papers, three international conferences, including the Federation of European Neuroscience Societies (FENS) Forum, three workshops, including the BCI & Neurotechnology Spring School 2021, and several internal meetings.
Moreover, we implemented a BCI training protocol on a cohort of DOC patients and analysed the effects on the behavioural responsivity assessed by the CRS-R. This research showed that BCI training protocols could be safely applied to DOC patients. Moreover, at the end of the two-week study period, we observed an improvement in the CRS-R score in 5 out of 10 DOC patients.
Still, as preparatory studies on communication with CLIS and DOC patients, we analysed the capacity to give consent to treatment (CCT) of severely disabled patients. This study showed that most Amyotrophic Lateral Sclerosis (ALS) patients preserve CCT, which is affected by frontal dysfunction and educational level.
We also tested a prototype vibrotactile-based BCI system with 7 stimuli on healthy subjects and patients.
Moreover, we reviewed the literature on the BCI applications on the DOC and developed a “clinical friendly guide” for not healthcare experts. Finally, we have undertaken a meta-analysis of the published data on the BCI paradigms used for detecting command following in the UWS patients.
Dissemination activities included five papers, three international conferences, including the Federation of European Neuroscience Societies (FENS) Forum, three workshops, including the BCI & Neurotechnology Spring School 2021, and several internal meetings.
This research shows that BCI paradigms can be integrated into the diagnosis pathway of the DOCs to increase the diagnostic precision and provide reproducible proof of command following earlier than the behavioural examination. The advanced detection of minimal responsivity might be crucial in clinical contexts in which several repetitions of the CRS-R are hard to perform or when the patient’s ability to respond might influence decisions on life-prolonging interventions or end-of-life decisions. We also observed that BCI training protocols might be applied safely to DOC patients for therapeutic purposes. This is the basis for future randomised controlled trials on BCI for rehabilitation of the DOC. Finally, we paved the way for new communication tools for DOC and CLIS patients, with potential benefit on quality of life and autonomy of these severely disabled patients.
In conclusion, our study suggests that somatosensory BCI paradigms might improve the diagnosis and management of DOC on a large scale, including small or non-specialised clinical centres and in the middle or low-income countries in the world.
In conclusion, our study suggests that somatosensory BCI paradigms might improve the diagnosis and management of DOC on a large scale, including small or non-specialised clinical centres and in the middle or low-income countries in the world.