Introduction
Patients with disorders of consciousness (DoC) have a condition characterised by severely impaired wakefulness and awareness, as a result of a broad range of pathologies such as acquired brain injury 1 and progressive brain degeneration 2. The clinical assessment of consciousness in this patient population, as well as in neurological conditions resulting in transiently altered conscious states, relies on an important distinction between the dimensions of arousal and awareness 3-8. Arousal (‘level of consciousness’) refers to the ability to demonstrate physical signs of wakefulness, whether that be opening the eyes or unprompted movements. On the other hand, awareness (‘content of consciousness’) is the ability to have subjective experiences. The bidimensional model of consciousness has proven particularly useful in the assessment of epilepsy-induced transient alterations of consciousness, often based on patients’ retrospective accounts 5,8-12. In the context of prolonged DoC, it is often difficult to confidently ascertain whether a patient is having a conscious experience because of the impairment in communication that defines this population 13-15.
Currently, the gold standard method for evaluating awareness in patients with DoC is a bedside behavioural assessment focusing on observable responses to external stimuli. The most commonly used behavioural assessment tools are the Glasgow Coma Scale (GCS) and the Coma Recovery Scale-Revised (CRS-R), with proven usefulness in this patient population 16. The GCS was developed in 1974 and quantifies the functioning of three behavioural domains related to the level of consciousness: eye opening, verbal and motor response 17. The CRS-R was developed in 1991 18 and revised in 2004 to align its behavioural criteria with the new definition of MCS 19,20. The CRS-R assesses auditory, visual and motor functioning, as well as verbal responsiveness, communication, and arousal 19. Since damage to motor systems frequently accompanies DoC, a significant percentage of patients with impaired consciousness might still retain some degree of awareness, but have insufficient voluntary control over their movements to demonstrate this through observable behaviours 21. Other confounders include sensory and cognitive impairment, as well as pain, potentially resulting in subtle or fluctuating behavioural signs that may be easily missed 13. Combined with observer bias, these factors account for a relatively high frequency of misdiagnosis of DoC based on behavioural assessments - as high as 40% 22.
The clinical spectrum of DoC ranges from coma and vegetative state (VS) to minimally conscious state (MCS) 23-25. Coma is the most severe DoC, as patients show no evidence of arousal; based on behavioural assessments, it is assumed that they have no awareness either 26. When patients with coma gradually regain consciousness, their diagnosis is often initially changed to VS, also referred to as unresponsive wakefulness syndrome (UWS) 27-29. Patients with UWS/VS retain sleep-wake cycles (arousal) and stimulus-induced movements (e.g. pupil dilation, apparently random movements of the limbs, chewing, teeth grinding). Despite the absence of clear and consistent behavioural evidence of awareness, inconsistent signs can be observed. Patients with MCS display inconsistent but reproducible behavioural responses, indicating awareness. In case of less obvious behavioural signs (e.g., a small hand or eye movement), assessments often need to be protracted over longer periods of time to achieve a confident diagnosis 30. It has been proposed to split the MCS diagnosis into MCS- and MCS+: patients with MCS- are thought to have the capacity for only a restricted range of rudimentary conscious contents (behaviourally expressed as visual pursuit, localization of noxious stimulation or appropriate smiling/crying to emotional stimuli), whereas patients with MCS+ are presumed to be able to enjoy a considerably wider range of conscious contents, involving a greater degree of cognitive sophistication, as shown by verbalised responses, command following, and intelligible verbalizations 16,31,32. Patients with locked-in syndrome lie outside the clinical spectrum of DoC, as both arousal and awareness are preserved, as shown by voluntary control of eye movements and blinking, despite inability to speak and complete paralysis of the limbs 4.
Over the last few decades, other assessment strategies have been developed to provide additional or more reliable information about awareness in patients with DoC. The most promising tools to complement behavioural assessments are neuroimaging and neurophysiology, either in isolation or in combination 33-35. Neuroimaging proved useful in reliably detecting differences in resting state brain activity and metabolism between patients with impaired consciousness and healthy controls, as well as in discriminating between patients with different levels of consciousness 36-39. In neuroimaging-based mental imagery paradigms, patients with DoC are instructed to engage in an imagination task and responses are recorded using fMRI or EEG 31,40. Patients can be asked to perform either complex motor imagery tasks, such as imagining playing tennis, or more simple motor tasks, such as imagining moving the right hand. They can also be asked to engage in spatial imagery - for example, imagining walking around each room in their house. A differential increase in activity in specific brain regions demonstrates that the patient successfully engaged with the task at hand. This also provides evidence for significant levels of consciousness (arousal) coupled with relevant contents of consciousness (awareness), as imagery tasks require understanding of and compliance to specific instructions. This promising research avenue is attracting an increasing amount of interest because of its clinical and theoretical implications. We therefore set out to conduct a systematic literature review to assess whether the available evidence indicates that fMRI and EEG based mental imagery paradigms are viable tools for assessing awareness in patients with DoC.
Methods
The present systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 41. On 25/05/2024, we performed a search on the PubMed, Embase, and PsycInfo databases for original studies in which fMRI or EEG imagery paradigms were used to assess awareness in patients with DoC. For our search, we combined the terms ‘minimally conscious’ OR ‘vegetative’ OR ‘disorders of consciousness’ AND ‘awareness’ OR ‘consciousness’ AND ‘imag*’ OR ‘magnetic resonance’ OR ‘electroencephalograph*’ (the search strategies for the three databases are detailed in the Supplementary Material). The reference lists of eligible articles were manually screened to identify any further relevant articles.
We included studies on patients diagnosed with any form of DoC following behavioural assessments according to the GCS, the CRS-R, or equivalent diagnostic measures. We restricted our search to studies that used fMRI or EEG approaches to mental imagery-based paradigms for assessing awareness in patients with DoC. Neuroimaging studies focusing on neural resting states instead of mental imagery were excluded, as they did not directly address our research question. Both case series and controlled studies were included in this review. Case studies of single patients were excluded. We excluded from our review studies published in languages other than English and studies published before 2004, the year in which the CRS-R was made available. By excluding the studies that used outdated instruments, we have focused our review on current gold standard methodology for the behavioural assessment of DoC.
Two independent reviewers (T.L.C., A.E.C.) collected data from each report without using automation tools. The reviewed studies contained all the relevant information and therefore there was no need to implement any processes for obtaining or confirming data from study investigators. The Crowe Critical Appraisal Tool (CCAT) was used to perform quality assessment on the reviewed studies 42. The CCAT has eight sections: preliminaries, introduction, design, sampling, data collection, ethical matters, results, discussion. Each section is awarded a minimum of 0 points and a maximum of 5 points, with higher points indicating higher methodological quality. In the present review, scores were awarded as follows: 0-1 points indicated a section with a degree of flawed methodological quality that resulted in exclusion of the study from the review; 2 points indicated at least two methodological flaws leading to bias in the relevant section; 3 points indicated one methodological flaw likely leading to bias; 4 points indicated one methodological flaw unlikely to lead to bias; and 5 points indicated that any possible methodological flaws did not lead to bias. The sum of the scores of the eight sections yielded a combined CCAT score (0-40), with higher scores indicating higher methodological quality.
Results
In total, eleven fMRI studies and six EEG studies were selected for inclusion in this review, with research being conducted across nine different countries. The article selection process is summarised in the PRISMA flow diagram (Fig. 1).
Five out of the 17 studies took place in the United States 43-47, two each in Austria 48,49, Israel 50,51, and Italy 52,53, and one each in Australia, Belgium, China, and Germany 54-57. Two further studies 58,59 were conducted across two countries, Belgium and the United Kingdom. All studies took place in specialist centres for the clinical management of patients with DoC resulting from acquired brain injury. The CRS-R was used as a behavioural measure in all studies except for the one by Liang et al. 54, who used the GCS and equivalent scales. The GCS was also used alongside the CRS-R in three studies 46,47,59. Twelve out of the 17 studies recruited age-matched healthy controls to validate the mental imagery tasks by verifying the feasibility of detecting specific neural activity in response to a command as a standard indicator of awareness 43,45,46-48,51,52,54-56,58,59.
Mental imagery was assessed by asking participants to imagine carrying out specific tasks that required them to use either their motor or spatial imagery. Seven out of the 17 studies used both motor and spatial imagery tasks 43,49,50,54,55,57,59. One very typical way to assess motor imagery was to ask patients to imagine playing a simple game that requires the same repetitive action, preferably with the same arm. Specifically, participants were instructed to “imagine playing tennis” in seven studies 43,45,49,54,55,57,59, and to “imagine swimming” in three studies 43,44,49. Alternative commands to determine the presence of motor imagery included “imagine opening and closing your hand” and “imagine squeezing your hand”, which were utilised in six studies 45-48,53,58. In two further studies, patients were instructed to raise their hand 56 and to hold their hand firm 48, respectively. Spatial imagery was most commonly assessed by asking patients to imagine navigating through their house (five studies 49, 54, 55, 57, 59). Personally familiar face imagery was used in two studies 51,54, whereas in one instance patients were asked to imagine objects from their kitchen 50. Finally, two studies utilised instructions that were different from these simple commands. Along with a simple hand squeezing test, Naro and Calabrò 53 also asked subjects to imagine dancing, either while being shown simultaneous footage of people dancing in a video, or independent of external visual stimuli. Claassen et al. 47 took a slightly different approach: instead of asking patients with no behavioural response to motor commands to imagine moving their hand, they asked their participants to actually try carrying out that motor task.
A summary of the eleven studies using a fMRI mental imagery paradigm to investigate awareness in patients with DoC is provided in Table I. Data were collected for a total of 252 patients with DoC: 79 patients diagnosed with MCS, 74 patients with UWS/VS, 3 patients in a coma, and 96 patients with unspecified DoC. The aetiological processes leading to DoC were documented as follows: 95 patients had a traumatic brain injury, 39 an anoxic brain damage, 16 a cerebrovascular accident, and 4 other conditions, including infectious diseases. Two patients in the study by Monti et al. 59 had two pathologies each (traumatic brain injury and anoxia, traumatic brain injury and infection). The aetiology of 96 patients who underwent fMRI in the studies by Forgacs et al. 44 and Stender et al. 55 was not specified. A total of 121 healthy controls were recruited across eight studies 43,45,46,51,54-56,59. The mean age of patients ranged from 27 years 45 to 46 years 57. The youngest patient across all studies was 8 years old 56 and the oldest was 75 years old 44.
Each fMRI study that was eligible for inclusion in this review demonstrated successful evidence of engagement in mental imagery tasks upon command by at least some of the patients. Between one third and one fourth of the combined sample (76/252 or 30%) demonstrated brain activation in response to mental imagery tasks. The proportion of patients able to engage in these tasks with evidence of mental imagery ranged from 5/54 (9%) 59 to 4/4 (100%) 51. Monti et al. 59 also found that fMRI based mental imagery paradigms could be used successfully as a communication tool to answer simple yes/no questions, although this was only investigated in one patient.
A summary of the six studies using an EEG mental imagery paradigm to investigate awareness in patients with DoC is provided in Table II. A total of 165 patients were included for analysis, along with over 42 healthy controls. Höller et al 48 did not specify the number of controls used to validate the imagery tasks. Only Horki et al 49 did not include a control group. The most common diagnosis was UWS/VS (64 patients), followed by MCS (54 patients) and coma (47 patients). All patients who were in a coma were recruited by Claassen et al. 47. With regard to aetiology, 55 patients had an anoxic brain damage, 52 a cerebrovascular accident, and 39 a traumatic brain injury. Two patients had two pathologies each: one patient with traumatic brain injury and cerebrovascular accident in the study by Horki et al. 49 and one patient with traumatic brain injury and anoxia in the study by Mangia et al. 52. The remaining 17 patients in the study by Claassen et al. 47 had other, non-specified conditions. The mean age of patients ranged from 41 years 58 to 51 years 48, with the youngest patient being 14 years old 58 and the oldest being 78 years old 53.
The reviewed EEG studies reported how accurately EEG data could signal mental imagery engagement compared to rest conditions. Five out of the six EEG studies found that EEG based paradigms could detect awareness 47,49,52,53,58, with degrees of accuracy ranging from 19% 58 to 86% 52. Naro and Calabrò 53 found distinctions between the neural response to commands in different subgroups of patients with DoC. Classification accuracy between resting and task-related electrical activity was validated in controls and although the difference in response was weaker in MCS patients than in controls, classification accuracy was still statistically significant for all mental imagery tasks in this patient subgroup. On the other hand, patients with UWS/VS did not consistently demonstrate responses to mental imagery. Naro and Calabrò 53 also found that motor imagery tasks outperformed spatial imagery tasks in terms of classification accuracy in patients with MCS. Visuo-motor assisted imagery had the greatest classification accuracy in patients with MCS, but did not perform significantly better than simple motor imagery tasks. In the study by Cruse et al. 58, 19% of patients could repeatedly and reliably generate appropriate EEG responses to two distinct commands, despite being behaviourally entirely unresponsive (mean accuracy 70%). Mangia et al. 52 found that EEG based mental imagery paradigms were able to classify responses into ‘yes’ or ‘no’ during communication trials with 97% accuracy. Claassen et al. 47 found that 15% of patients in a coma had significant neural responses to the command to move their hand, even without the presence of physical movement: like mental imagery, this cognitive-motor dissociation establishes some level of awareness, with a degree of preserved cognitive ability. The study by Höller et al. 48 was the only outlier. These authors found that their EEG based paradigm could accurately distinguish between times when an unspecified number of controls were engaging in mental imagery, and times when they were not (79% accuracy). However, these findings were not replicated in their series of 14 patients with DoC after correction for false discovery.
Discussion
The ability to assess DoC using fMRI or EEG based mental imagery paradigms is a relatively novel approach that has significant advantages over behavioural testing alone. Our literature search identified 17 original studies presenting high-quality data on the use of fMRI and EEG based mental imagery paradigms for detecting awareness in patients with DoC. The combined results of the reviewed studies indicate that mental imagery paradigms developed within experimental settings have the potential to become reliable tools for the assessment of covert consciousness in this patient population.
The strongest levels of evidence were provided by neuroimaging findings, documenting successful mental imagery in at least some of the patients in each clinical sample. Four out of the five fMRI studies that included data about DoC subgroups found that patients diagnosed with less severe forms of DoC, such as MCS or emerging MCS, were more likely to demonstrate engagement in mental imagery tasks than patients with more severe impairments in consciousness, such as UWS/VS or coma 43,44,56,57. In the study by Vogel et al. 57, all the patients with UWS/VS who demonstrated mental imagery responses had their diagnosis changed to MCS or emerging MCS by their follow-up assessment, suggesting that fMRI may be able to predict recovery of awareness more accurately than behavioural assessments. In 2016, a systematic review and meta-analysis of studies using active, passive, and resting state fMRI or EEG paradigms 60 found that patients with MCS show signs of preserved consciousness more frequently than patients with UWS/VS across both active and passive paradigms. A more recent meta-analysis of neuroimaging studies published between 2005 and 2017 found that active and passive cognitive tasks rely on well-segregated patterns of fMRI activations 61.
The results of five out of the six reviewed EEG studies were broadly in agreement: EEG based paradigms were found to be reliable tools for assessing awareness in patients with DoC, as they could accurately differentiate cortical activity when engaging in mental imagery tasks from resting state activity 47,49,52,53,58. Moreover, the study by Claassen et al. 47 showed that alongside mental imagery, cognitive-motor dissociation (evidence of covert consciousness) was predictive of better recovery of consciousness at 12-month follow-up, highlighting its sensitivity for detecting awareness in the early stages of recovery. The study by Naro and Calabrò 53 included data about DoC subgroups, showing that changes in EEG activity in response to mental imagery were detectable in less severe forms of DoC, such as MCS, but not in patients with a diagnosis of UWS/VS. The same authors also found that visuomotor-guided imagery paradigms had a 16% higher classification accuracy than standard motor imagery paradigms in patients with MCS. In turn, Horki et al. 49 found motor imagery to be significantly more sensitive at detecting awareness than spatial imagery paradigms, raising the possibility of clinically relevant differences across imagery paradigms in their sensitivity to detect signals of awareness.
The implementation of mental imagery paradigms as a communication tool in patients with DoC was explored in two of the reviewed studies, using different techniques. In the fMRI study by Monti et al. 59, a single patient with a diagnosis of UWS/VS who demonstrated evidence of awareness was able to answer five out of six questions with 100% accuracy using mental imagery to communicate ‘yes’ or ‘no’. The authors noted that it remained impossible to establish any form of communication with this patient at the bedside assessment. Similar findings were obtained in the EEG study by Mangia et al. 52, where classification accuracy between ‘yes’ and ‘no’ answers provided using motor imagery was 92% in patients with a diagnosis of MCS. In addition to allowing meaningful communication, these approaches open up new avenues for a more fine-grained assessment of the broader spectrum of cognitive functions affected by DoC 62. Mental imagery-based studies attempting to obtain volitional responses from patients with DoC could detect their command-following capability and therefore may provide an effective means to communicate with selected patients 63.
Despite the general trend of agreement between studies, their estimations of the proportion of patients with DoC who retain awareness and the accuracy of mental imagery paradigms in detecting awareness were characterised by high variability. One of the possible reasons for the discrepancy in findings is the intrinsic difficulty in establishing validity. For example, across both fMRI and EEG studies, it is unclear whether studies with lower classification accuracy included a higher number of patients who failed to produce a detectable response to an imagery task or used mental imagery paradigms with lower sensitivity. Differences in sampling/analysis techniques and sample sizes could also account for a few discrepancies between the findings of the reviewed studies. For example, the fMRI study by Bick et al. 50 reported a high proportion (5/7 or 71%) of patients demonstrating evidence of mental imagery, however the authors recruited patients whose families believed they were showing signs of consciousness, raising the possibility that their clinical sample was biased towards patients with more intact consciousness. Most of the reviewed studies had relatively small sample sizes, often due to the large number of patients who did not meet the eligibility criteria 43,45,46,48-52,54,58. In 2018, a systematic review and meta-analysis focusing on the relationship between brain data and clinical outcomes of patients with DoC 64 found that insufficient power and lack of an appropriate description of patient selection characterized about half of the reviewed neuroimaging and neurophysiology studies. Small sample sizes with participant selection bias could be at least partly responsible for variability of findings across studies and poor generalisability to the wider DoC population.
In the reviewed studies, measures of awareness provided by mental imagery paradigms were compared with structured behavioural assessments as the existing gold standard methodology. All studies used the CRS-R as the behavioural measure of choice, with the exception of the study by Liang et al. 54, who used the GCS and equivalent scales. It has been highlighted that the limitations of the GCS as a measure of consciousness include its suboptimal inter-rater reliability 65 and over-reliance on eye response to stimuli 66. The CRS-R has been proposed as a more accurate and reliable tool for assessing awareness based on behavioural evidence 67. However, its implementation can be problematic because of the need for multiple assessments over time and its reliance on the patients’ ability to convey physical manifestations of awareness which, depending on injuries to their motor systems, might not be consistently possible. As for the non-behavioural protocols, a significant advantage of the fMRI technique is its higher accuracy at localising responses to specific brain regions (e.g. supplementary motor areas for motor imagery tasks and parahippocampal gyrus for spatial imagery tasks). This increases confidence that the detected neural activity is a direct effect of intended execution of the required mental imagery task, rather than simply a response to auditory feedback or other environmental stimuli. An obvious disadvantage is its impractical use, which is prevented in the case of patients with surgical implants that make them unsuitable for this neuroimaging approach 33. Despite lower spatial localisation power, the practicality of using EEG equipment makes neurophysiology investigations better suited for the patient’s bedside assessment.
The implementation of mental imagery paradigms in a multimodal approach to assess awareness in patients with DoC could significantly increase diagnostic accuracy, leading to better informed decisions regarding care and rehabilitation programmes. Moreover, it has been argued that patients with DoC demonstrating neuroimaging evidence of covert consciousness may benefit from early adapted rehabilitation 68. One of the developments of artificial intelligence is in the integration of mental imagery paradigms with brain computer interfaces 69. As part of neurofeedback protocols, both fMRI and EEG signals can be converted into meaningful responses to facilitate communication 70. Importantly, the available evidence suggests that imagery-based fMRI and EEG paradigms have the potential to outperform behavioural assessments in generating prognostic data to predict recovery trajectories in patients with DoC 71,72. Coupled with the findings of resting state activity studies, functional neuroimaging studies implementing mental imagery paradigms allow for increasingly more reliable network mapping of connectivity alterations in DoC, which in turn paves the way for targeted neuromodulation 73.
Our systematic literature review has limitations. First, we deliberately focused on research published in English language during the last 20 years, possibly leaving out relevant studies. Second, although the reviewed studies were rated as having satisfactory methodological quality, they were mostly conducted in specialist centres across Europe 48,49,52,53,55,57-59 and North America 43-47, resulting in a geographical bias of the patient population. Third, the process of combining and comparing findings from heterogeneous studies was hindered by inter-individual variability in the behavioural assessment of consciousness and differences in the mental imagery paradigms. Finally, few studies presented data on the longitudinal trajectories of patients with DoC 47,51,55,57, thus limiting generalisations about the stability of findings over time.
Despite these limitations, the present review provides evidence that both fMRI and EEG mental imagery paradigms could become viable tools for assessing awareness in patients with DoC. A review published in 2022 covering studies that were conducted within the previous ten years showed that about 40% of patients with DoC can be misdiagnosed because specifically designed behavioural scales are not employed or improperly administered 74. To improve diagnostic accuracy for these patients, the authors suggested that neuroimaging and electrophysiological techniques can play an important role in the differentiation between VS/UWS and MCS patients. Based on the available literature, mental imagery paradigms might prove more sensitive than behavioural assessments at detecting awareness, and could successfully be used as communication tools, especially in patients with compromised motor responses. These findings have important clinical and theoretical implications, paving the way to improved management of DoC and shedding light on the neural correlates of consciousness 75.
In order to overcome the limitations of relatively underpowered studies, further research should be conducted on larger sample sizes to establish the feasibility of mental imagery paradigms as a reliable method of assessing awareness in patients with DoC and to establish the consistency and specificity of findings across different patient subgroups. It would be especially important to incorporate healthy controls in the study design to confirm the generalisability of previously validated paradigms and to assess the validity of novel mental imagery paradigms, such as the visuomotor guided imagery task 49. Overall, future research should focus on the further development of more sensitive imagery paradigms that can generate stronger neural responses in a reproducible manner and in a wide range of DoC, thus facilitating the implementation of these paradigms in a clinical setting. Longitudinal studies with follow-up assessments at 3, 6, and 12 months would provide useful indications about the predictive power of mental imagery paradigms about the long-term outcomes of patients with DoC. Finally, it would be essential to conduct further research combining both fMRI and EEG mental imagery paradigms within the same clinical samples, in order to allow direct comparisons between non-behavioural methods of assessing awareness in DoC. Advances in this field would play a crucial role in promoting the incorporation of mental imagery paradigms in improved diagnostic protocols for patients with DoC, alongside validated behavioural assessments.
Conflict of interest statement
The authors declare no conflict of interest.
Funding
None.
Authors contribution
Planning: A.E.C., T.L.J.; supervision: A.E.C.; data extraction: A.E.C., T.L.C.; text drafting: T.L.J.; text reviewing: A.E.C., A.P.B.
Ethical consideration
Not applicable.
Figures and tables
FIGURE 1. PRISMA flow diagram outlining the identification, screening, assessment for eligibility, and inclusion of studies in the present review.
| Study | Country | N. (aetiology) | DoC | Behavioural measure | Imagery paradigm | Main findings | CCAT score |
|---|---|---|---|---|---|---|---|
| Monti et al., 2010 59 | Belgium, United Kingdom | 54 ABI (31 TBI, 1 TBI + ABD, 1 TBI + infection, 15 ABD, 3 CVA, 3 infection) 16 HC | 23 UWS/VS 31 MCS | CRS-R, GCS | Motor imagery: playing tennis; spatial imagery: mental navigation in own house | 5/54 patients showed fMRI activation in imagery tasks (4/5 with UWS/VS); communication tested in 1 imagery responsive patient with UWS/VS (classified 5/6 answers with 100% accuracy) | 37/40 |
| Bardin et al., 2011 43 | United States | 5 ABI (3 TBI, 1 ABD, 1 CVA) 14 HC | 5 MCS | CRS-R | Motor imagery: playing tennis or swimming; choice task: responding yes/no through imagery to matching/unmatching cards | 2/5 patients showed fMRI activation in motor imagery task; 1 patient showed fMRI activation in choice task | 36/40 |
| Bick et al., 2013 50 | Israel | 11 ABI (7 TBI, 4 ABD) | 6 UWS/VS 5 MCS | CRS-R | Preliminary auditory task; imagery: playing ball game, humming song, walking home, visualizing objects from kitchen | 7/11 patients showed fMRI activation in preliminary auditory task; 5/7 showed fMRI activation in at least one imagery task (1/7 in all four tasks) | 33/40 |
| Sharon et al., 2013 51 | Israel | 4 ABI (2 ABD, 2 TBI) 13 HC | 4 UWS/VS | CRS-R | Personally familiar face imagery: visualization of parent’s face | All patients and HC showed fMRI activation in familiar face imagery task; strongest brain connectivity in the 2 patients who later recovered | 35/40 |
| Vogel et al., 2013 57 | Germany | 22 ABI (10 ABD, 6 CVA, 6 TBI) | 10 UWS/VS 12 MCS | CRS-R | Motor imagery: playing tennis; spatial imagery: mental navigation in own house | 14/22 patients showed fMRI activation in imagery tasks (5/14 with UWS/VS, transitioned to MCS at follow-up); 8/22 patients did not show fMRI activation (5/8 with UWS/VS, did not transition to MCS at follow-up) | 37/40 |
| Forgacs et al., 2014 44 | United States | 26 ABI (NS) | NS | CRS-R | Motor imagery: swimming | 4/26 patients showed fMRI activation in motor imagery task (3/4 with MCS, 1/4 with emerging MCS) | 35/40 |
| Liang et al., 2014 54 | Australia | 5 ABI (4 TBI, 1 other) 11 HC | 3 UWS/VS 2 MCS | GCS, GOS, WHIM | Motor imagery: playing tennis; spatial imagery: mental navigation in own house; personally familiar face imagery; counting up from 10 by 7s | 2/5 patients (1 UWS/VS, 1 MCS) showed fMRI responses to imagery tasks, producing activations in similar areas to HC | 35/40 |
| Stender et al., 2014 55 | Belgium | 70 ABI (NS) 16 HC | NS | CRS-R | Motor imagery: playing tennis; spatial imagery: mental navigation in own house | Agreement between CRS-R and mental imagery fMRI was recorded in 44/70 patients; mental imagery fMRI predicted 56% of all known outcomes | 36/40 |
| Bodien et al., 2017 45 | United States | 10 ABI (10 TBI) 10 HC | 1 coma 4 UWS/VS 2 MCS- 3 MCS+ | CRS-R | Motor imagery: playing tennis, squeezing hand | 2/10 patients showed fMRI activation in tennis playing motor imagery task (0/2 with behavioural evidence); 3/10 patients showed fMRI activation in hand squeezing motor imagery task (2/3 with behavioural evidence) | 35/40 |
| Edlow et al., 2017 46 | United States | 16 ABI (16 TBI) 16 HC | 2 coma 3 UWS/VS 3 MCS- 8 MCS+ | CRS-R, GCS | Motor imagery: squeezing hand | 11/16 HS and 7/16 patients showed fMRI activation in hand squeezing motor imagery task (3/7 with behavioural evidence) | 35/40 |
| Wang et al., 2019 56 | China | 29 ABI (16 TBI, 7 ABD, 6 CVA) 15 HC | 21 UWS/VS 8 MCS | CRS-R | Motor imagery: raising hand | 4/29 patients (2 MCS, 2 UWS/VS) showed fMRI activation in hand raising motor imagery task | 35/40 |
| Abbreviations. ABD, anoxic brain damage; ABI, acquired brain injury; CCAT, Crowe Critical Appraisal Tool; CRS-R, Coma Recovery Scale-Revised; CVA, cerebrovascular accident; DoC, disorders of consciousness; fMRI, functional magnetic resonance imaging; GCS, Glasgow Coma Scale; GOS, Glasgow Outcome Scale; MCS, minimally conscious state (+/-, with/without verbalised responses to environmental stimuli); NS, not specified; TBI, traumatic brain injury; UWS, unresponsive wakefulness syndrome; VS, vegetative state; WHIM, Wessex Head Injury Matrix. | |||||||
| Study | Country | N. (aetiology) | DoC | Behavioural measure | Imagery paradigm | Main findings | CCAT score |
|---|---|---|---|---|---|---|---|
| Cruse et al., 2011 58 | Belgium, United Kingdom | 16 ABI (9 ABD, 5 TBI, 2 CVA) 12 HC | 16 UWS/VS | CRS-R | Motor imagery: squeezing hand, wiggling toe | 3/16 patients and 9/12 HC showed significant differences in EEG activity in motor imagery task; mean (range) imagery classification accuracy with EEG activity: ABI 70% (61-78%), HC 68% (60-91%) | 37/40 |
| Höller et al., 2013 48 | Austria | 14 ABI (6 CVA, 4 ABD, 4 TBI) 22 HC | 9 UWS/VS 5 MCS | CRS-R | Motor imagery: opening/closing hand, holding hand firm | No significant differences in EEG activity after correcting for false positives | 36/40 |
| Horki et al., 2014 49 | Austria | 6 ABI (3 TBI, 1 TBI + CVA, 2 ABD) | 6 MCS | CRS-R | Motor imagery: playing sport, moving foot; spatial imagery: mental navigation in own house | Significant differences in EEG activity for all imagery paradigms (higher accuracy for motor imagery than for spatial imagery) | 35/40 |
| Mangia et al., 2014 52 | Italy | 5 ABI (4 TBI, 1 TBI + ABD) 5 HC | 1 UWS/VS 4 MCS | CRS-R | Motor imagery: moving hand/foot; communication task: responding yes/no through hand/foot movement imagery | Mean imagery classification accuracy with EEG activity: ABI 85%, HC 82%; mean communication classification accuracy with EEG activity: ABI 92%, HC 81% | 36/40 |
| Claassen et al., 2019 47 | United States | 104 ABI (39 CVA, 33 ABD, 15 TBI, 17 other) 10 HC | 47 coma 27 UWS/VS 30 MCS | CRS-R, GCS | Motor imagery: opening and closing right/left hand | 16/104 patients showed significant differences in EEG activity in motor imagery task (8/16 with coma, 3/16 with UWS/VS, 5/16 with MCS); 44% of patients who showed cognitive-motor dissociation (covert consciousness) reported improvement at 12-month follow-up behavioural assessment | 38/40 |
| Naro and Calabrò, 2020 53 | Italy | 20 ABI (8 TBI, 7 ABD, 5 CVA) | 11 UWS/VS 9 MCS | CRS-R | Visuomotor-guided imagery: dancing while watching group dance video; simple motor imagery: squeezing hand; advanced motor imagery: dancing without visual guidance | 7/20 patients showed significant differences in EEG activity in visuomotor-guided imagery task (1/11 with UWS, 6/9 with MCS); 4/20 patients showed significant differences in EEG activity in simple motor imagery task (0/11 with UWS/VS, 4/9 with MCS); 4/13 patients showed significant differences in EEG activity in simple motor imagery task (1/7 with UWS/VS, 3/6 with MCS) | 38/40 |
| Abbreviations. ABD, anoxic brain damage; ABI, acquired brain injury; CCAT, Crowe Critical Appraisal Tool; CRS-R, Coma Recovery Scale-Revised; CVA, cerebrovascular accident; DoC, disorders of consciousness; EEG, electroencephalography; GCS, Glasgow Coma Scale; MCS, minimally conscious state; NS, not specified; TBI, traumatic brain injury; UWS, unresponsive wakefulness syndrome; VS, vegetative state. | |||||||
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