Carolyn Fleck-Prediger1, 2, Sujoy G. Hajra3,4, Bruce D. Dick1,5, D. Shaun Gray1,2,6 Careesa C. Liu
3,4, Lauren Petley7, and Ryan C.N. D’Arcy*3,4
1) Neuroscience and Mental Health Institute, University of Alberta, Alberta, Canada;
2) Halvar Jonson Centre for Brain Injury, Ponoka, Alberta, Canada;
3) Schools of Engineering and Computing Sciences, Simon Fraser University, British
4) Surrey Memorial Hospital, Fraser Health Authority, British Columbia, Canada;
5) Departments of Anesthesiology and Pain Medicine, Psychiatry & Pediatrics,
University of Alberta, Alberta, Canada;
6) Division of Physical Medicine and Rehabilitation, University of Alberta, and Glenrose
Rehabilitation Hospital, Edmonton, Alberta, Canada;
7) Biomedical Translational Imaging Centre, IWK Health Centre and QEII Health
Sciences Centre, Halifax, Nova Scotia, Canada
*Corresponding author: Simon Fraser University, Faculty of Applied Sciences School of Engineering Science, School of Computer Science, 250-13450 102nd Ave, Surrey, BC, Canada, V3T 0A3, 778-782-9190 (Telephone), 778-782-8116 (Fax)
Severe neurological damage can cause speech and movement limitations that mask preserved cognitive capacities and create challenges differentially diagnosing persistent vegetative, minimally conscious and “locked-in” states of consciousness. Significant practical challenges impede both the initial clinical evaluation of consciousness and ongoing appraisal of patient status over time. By necessity, clinical evaluation currently relies on observation of conscious awareness to estimate the functional repercussions of severe brain injury. This can lead to misdiagnosis when ‘mind-motor disconnection’ renders patients unable to demonstrate their capacities. The Halifax Consciousness Scanner (HCS) uses auditory event-related brain potentials (ERPs) to measure neural responses during information processing, without relying on overt behavioral responses. Here we describe this emerging neurotechnology using an illustrative case in an inpatient rehabilitation setting. In this case, the initial HCS profile demonstrated intact pre-linguistic capacities but impaired receptive language. Over time and with treatment, the patient’s HCS language response progressively improved and most importantly here, these progressive HCS changes coincided with clinical progress.
After severe brain injury, disorders of consciousness (DOC) such as persisting post-coma unawareness or unresponsive wakefulness syndrome (the so-called vegetative state), minimally conscious state, or even locked-in state, may persist well beyond the acute phases of injury. The clinical challenge is to accurately diagnose the correct DOC and monitor information processing as a reflection of functional status. Correct differential diagnosis is essential in order to identify the patients with the greatest potential for recovery as recent studies demonstrate substantial ongoing recovery in minimally responsive patients continuing up to two years post-injury with more modest potential for improvement following this period, up to five years post-injury . The problem can be separated into at least two inter-related challenges: 1) accurate initial level of awareness evaluation; and 2) ongoing monitoring of changes over time and with treatment.
There is a pressing need for enhanced objective evaluation and concrete diagnosis at the earliest stages of the critical care cascade. Up to 43% of patients with DOC were misdiagnosed as being in a vegetative state in one series . Severely injured patients often experience communication limitations and immobility that mask preserved cognitive capacities . It is becoming clear that conscious experience may well exist without overt behavioural signs of conscious awareness .
An injured brain is particularly plastic and this neuro-modulation can be adaptive or maladaptive, depending on the quantity and quality of experience . In stroke rehabilitation, enriched environments have been shown to improve social engagement in patients . Given the evidence supporting neuroplastic change and environmental enrichment, early responsiveness to intervention and probability of rehabilitation success needs to be assessed. While behavioral assessments will always be necessary, paralysis and apraxia can mask a patient’s true status and gains which hampers care planning and the provision of rehabilitation in this population. Further, these patients are not well followed over time which limits prognostication.
Advances in functional neuroimaging and related neurotechnologies are creating possible solutions to evaluation challenges outlined above . An emerging neurotechnology, the Halifax Consciousness Scanner (HCS) , uses auditory event-related brain potentials (ERPs) to measure neural responses during information processing using rapid and easily deployable electroencephalography (EEG) techniques. Foundational work for this technology has demonstrated the utility of ERPs in evaluating a range of functions (sensory to cognitive) in neurological patients who experience concomitant problems with communication [3, 9,10].
ERPs are frequently used to understand how the brain processes information in real time with temporal resolution at the level of milliseconds [7,11] and are particularly useful as brain responses related to information processing are captured without relying on overt behavioural responses. Furthermore, EEG-based techniques are non-invasive, easy to administer, and inexpensive making them practical, accessible, and easy to integrate into treatment.
D’Arcy et al  provide an overview of HCS ERP methods. In brief, the system uses variants of well-established ERP’s that cover the spectrum of information processing. Target ERPs are extracted by presenting a series of stimuli and averaging the associated EEG activity to isolate the signal resulting from the brain’s response to the stimuli from the overall background EEG ‘noise’. The two components of interest here are the P300, a measure of attention , and the N400, a measure of semantic processing and comprehension . Recording electrodes cover the midline anterior-posterior axis (Fz, Cz, Pz). ERP components are obtained using a 5-minute auditory stimulus sequence that combines tones (2.5 minutes) and speech (2.5 minutes). Through earphones, tones of varying intensity and pattern are presented. The 600 tone sequence is comprised of two spectrally rich tones (A and B). Standard tones are presented in an alternating pattern (ABABAB...) with an intensity of 75 dB SPL. The stimuli contain occasional deviant stimuli consisting of repetition deviants (repetitions of either the A or the B tone, e.g., ABABBBA) and intensity deviants which follow the standard alternating pattern of the sequence, but have an intensity of 100 dB SPL. Occasional deviant stimuli, particularly intensity deviants, evoke the P300.
After the tone stimuli, subjects hear 30 phrases that build sentences with ‘semantic expectation.’ Each phrase is presented twice – once with a congruent ending and once with an incongruent ending. The N400 is elicited maximally by the incongruent endings. For example, the phrase “The pizza is too hot to ____” builds an expectation for the congruent terminal word “eat” in comparison to the incongruent terminal word “sing”. The phrases begin with either the subject’s own name or a control name with no personal relevance. These two names are distributed randomly among the phrases. Signal-averaged responses for each indicator are calculated to generate a final “consciousness score”. By comparing patient results to norms, basic cognitive status is revealed. The condensed nature of the screening is critical for easily fatigued, severely injured patients. The HCS protocol also enables rapid bedside testing to minimize interruptions to patient care.
Case Study: HCS Clinical Application Examined
FM, a 45-year-old male, sustained an assault resulting in severe traumatic brain injury with an initial Glascow Coma Scale of 3T. Imaging revealed intracerebral hemorrhage involving the left frontobasal portions of the brain from the upper basal ganglia to coronal radiata. He required a craniotomy and ventricular drain. FM was admitted to rehabilitation 7-months post-injury with an altered but undetermined level of conscious awareness. Initial HCS screening was completed 20 days post-admission. At this time, FM’s GCS was 9/15 (4 Eyes, 1 Verbal, 4 Motor). He was dependent on a gastrostomy feeding tube and required suction oral care. He was unable to maintain an upright posture without support and was entirely dependent for bed/wheelchair mobility. FM demonstrated little awareness of his environment and his gaze was fixed to the upper left quadrant. He did not follow instructions, speak or communicate his needs. In view of this, great debate ensued amongst his caregivers regarding his capacity to process information. This debate was further fuelled by the fact that he was able to spontaneously move his left arm but could not follow any motor commands with this limb.
Prior to HCS testing, Otoacoustic Emission (OEA) and Auditory Brainstem Response (ABR) tests were conducted. FM’s OEA results were normal, but ABR was highly confounded by tone and muscle twitches. Unlike the HCS, the ABR instrumentation could not effectively eliminate noise artifact. FM clearly demonstrated auditory capacity, as he startled to unexpected, out of sight noise. Over the treatment period, FM underwent three HCS testing sessions to evaluate brain function and monitor electrophysiological changes. Figure 1 shows ERPs responses for FM and a typical healthy control for comparison.
Pre-treatment: Level of comprehension was unknown. In pre-treatment testing, basic sensation and perception indicators were present (N100 and mismatch negativity, respectively). Consistent P300 responses to deviant tones were observed, reflecting ‘automatic’ attention responses. However, in pre-treatment tests, the N400 response was equivocal, suggesting impaired semantic processing and comprehension.
Given that FM possessed basic sensory and attention capacities but impaired auditory comprehension, he received intensive speech-language intervention focusing on receptive language. Messages were relayed to him in simplified language and verbal messages were augmented with printed words, drawings, pictures, hand gestures and demonstrations. As treatment progressed, FM’s engagement improved slowly. HCS testing at 7-months post-admission verified that, despite persistent communication limitations, his receptive language had improved. Specifically, HCS testing revealed the emergence of the N400 response.
Post Treatment: On post-treatment tests (11 months post-admission), FM’s semantic processing and comprehension performance was within normal limits as measured by a clear N400 response on the HCS. Figure 2 shows no change in FM’s P300 across three test sessions, while there is a statistically significant (p < 0.05 ) re-emergence of the N400 response (Figure 3).
FM made significant cognitive and physical gains during treatment. While an inpatient, FM learned to use his left hand to communicate a limited set of functional gestures. ‘Motor-mind disconnectedness’ continued to be a significant barrier to intentional movement and speech. Occasionally, FM sang and spoke in short phrases, which were intelligible in context. He intermittently responded to humor. He became able to safely consume food and fluid orally. He learned to feed himself with close supervision. He recognized familiar people. FM was able to reposition himself in bed, sit unsupported at bedside for short periods, and mobilize short distances in a manual wheelchair (single left arm and bilateral leg propulsion). Despite mobility gains, he continued to require encouragement to move due to residual initiation deficits. He became attentive to the right visual field and was no longer locked in an upward left gaze. FM was discharged to a community residential setting. Shortly after discharge, his gastrostomy tube was removed. At 6 months post-discharge follow-up, his family reported that he had maintained his gains and continued to demonstrate slow, steady physical and cognitive improvements.
HCS Impact on Practice:
The HCS testing results provided critical information for both initial evaluation and monitoring of treatment progress. Initial evaluation demonstrated that FM had intact attention (P300) but impaired comprehension (N400). Appreciating comprehension limitations helped to define speech-language treatment goals and enabled appropriate inter-disciplinary therapists/family member interactions. During intensive treatment, serial HCS monitoring revealed receptive language gains, as indexed by the emergence of the N400 response. These results helped justify continued specialized rehabilitation over an eleven month period. The HCS results provided critical information about FM’s functional information processing status to his family, treatment team, and healthcare funders.
Enriched (versus standard) living environments trigger structural changes in the brain and enhance functional outcomes . As demonstrated here, significant functional gains are possible when strategic rehabilitation is provided, even in very severe TBI. The HCS eliminates “motor-mind disconnection” confounds by using electrophysiology to evaluate and monitor the functional progress of patients. In this case, treatment time was not wasted in debating FM’s cognitive status (i.e., initial evaluation). Advanced service and care was delivered with treatment focused on comprehension and measured in terms of the recovery of the HCS N400 response (i.e., treatment monitoring).
Given the challenges in objective evaluation and monitoring of conscious awareness, there are understandable difficulties in accurately discriminating the relevant DOC (vegetative versus minimally conscious versus locked-in states) and therefore planning for appropriate rehabilitation and ongoing care. This difficulty in accurately diagnosing disorders of consciousness has confounded not only clinical care but even attempts to understand the prevalence of vegetative and minimally conscious states . ERP techniques such as the Halifax Consciousness Scanner may provide an inexpensive, non-invasive, valid, and reliable bedside method of assessing cognitive processing in patients with disorders of consciousness. We would agree with Duncan et al  that “It is likely that the use of ERPs in evaluating and planning the treatment of TBI survivors will become standard clinical practice”. We believe that our case study not only offers proof of this general concept but also aided significantly in improving the rehabilitation outcome for our patient. Given the ability of ERPs to signal learning even before overt signs of task improvement are seen in healthy individuals [18-19], it is possible that frequent ERP testing in brain injured patients could provide evidence of neuroplastic changes to help optimize rehabilitation even before gains are clinically observed. Further studies evaluating ERP-based neurotechnologies in larger patient samples with significant motor and/or communication impairments after moderate to severe acquired brain injury are underway.
The authors would like to acknowledge the administration, medical and rehabilitation personnel at the Halvar Jonson Centre for Brain Injury (Ponoka, Alberta, Canada). The authors also acknowledge the patient and his family for agreeing to participate.
Primary development of the Halifax Consciousness Scanner was funded by the National Research Council of Canada (NRC), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Province of Nova Scotia (Innovacorp). While employees of the Government of Canada, several of the authors were inventors on the initial patent describing the intellectual property for the Halifax Consciousness Scanner, which is wholly owned by the Crown (international PCT application number CA2011050367). Their inventorship may qualify them to receive a small percentage of royalties from the Crown. The Halifax Consciousness Scanner is under exclusive license to Mindful Scientific, Inc., for which Dr. D’Arcy has served as Chief Scientific Advisor.
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Figure 1: HCS ERP responses – the P300 (left) to intensity deviant and the N400 (right) to incongruent word in FM (top) and a healthy control (bottom). Time is on the horizontal axis (seconds) and response size and polarity is on the vertical axis (microvolts).
Figure 2: P300 (intensity deviant) and N400 (incongruent word) components measured at 3 time points for FM. The P300 responses to are consistent across the 3 time points. In contrast, the N400 responses increase across the 3 time points. All other details as in Fig. 1.
Figure 3: P300 (intensity deviant) and N400 (incongruent word) differences between T1 and T3. Mean ± SE. *p<0.05.