Judith Allanson

Spectral Signatures of Reorganised Brain Networks in Disorders of Consciousness

Theoretical advances in the science of consciousness have proposed that it is concomitant with balanced cortical integration and differentiation, enabled by efficient networks of information transfer across multiple scales. Here, we apply graph theory to compare key signatures of such networks in high-density electroencephalographic data from 32 patients with chronic disorders of consciousness, against normative data from healthy controls. Based on connectivity within canonical frequency bands, we found that patient networks had reduced local and global efficiency, and fewer hubs in the alpha band. We devised a novel topographical metric, termed modular span, which showed that the alpha network modules in patients were also spatially circumscribed, lacking the structured long-distance interactions commonly observed in the healthy controls. Importantly however, these differences between graph-theoretic metrics were partially reversed in delta and theta band networks, which were also significantly more similar to each other in patients than controls. Going further, we found that metrics of alpha network efficiency also correlated with the degree of behavioural awareness. Intriguingly, some patients in behaviourally unresponsive vegetative states who demonstrated evidence of covert awareness with functional neuroimaging stood out from this trend: they had alpha networks that were remarkably well preserved and similar to those observed in the controls. Taken together, our findings inform current understanding of disorders of consciousness by highlighting the distinctive brain networks that characterise them. In the significant minority of vegetative patients who follow commands in neuroimaging tests, they point to putative network mechanisms that could support cognitive function and consciousness despite profound behavioural impairment.

Dissociable endogenous and exogenous attention in disorders of consciousness

Recent research suggests that despite the seeming inability of patients in vegetative and minimally conscious states to generate consistent behaviour, some might possess covert awareness detectable with functional neuroimaging. These findings motivate further research into the cognitive mechanisms that might support the existence of consciousness in these states of profound neurological dysfunction. One of the key questions in this regard relates to the nature and capabilities of attention in patients, known to be related to but distinct from consciousness. Previous assays of the electroencephalographic P300 marker of attention have demonstrated its presence and potential clinical value. Here we analysed data from 21 patients and 8 healthy volunteers collected during an experimental task designed to engender exogenous or endogenous attention, indexed by the P3a and P3b components, respectively, in response to a pair of word stimuli presented amongst distractors. Remarkably, we found that the early, bottom-up P3a and the late, top-down P3b could in fact be dissociated in a patient who fitted the behavioural criteria for the vegetative state. In juxtaposition with healthy volunteers, the patients responses suggested the presence of a relatively high level of attentional abilities despite the absence of any behavioural indications thereof. Furthermore, we found independent evidence of covert command following in the patient, as measured by functional neuroimaging during tennis imagery. Three other minimally conscious patients evidenced non-discriminatory bottom-up orienting, but no top-down engagement of selective attentional control. Our findings present a persuasive case for dissociable attentional processing in behaviourally unresponsive patients, adding to our understanding of the possible levels and applications of consequent conscious awareness.

Traumatic brain injury in adults

Traumatic brain injury (TBI) remains a major public health problem. This review aims to present the principles upon which modern TBI management should be based. The early management phase aims to achieve haemodynamic stability, limit secondary insults (eg hypotension, hypoxia), obtain accurate neurological assessment and appropriately select patients for further investigation. Since 2003, the mainstay of risk stratification in the UK emergency departments has been a system of triage based on clinical assessment, which then dictates the need for a CT scan of the head. For patients with acute subdural or extradural haematomas, time from clinical deterioration to operation should be kept to a minimum, as it can affect their outcome. In addition, it is increasingly recognised that patients with severe and moderate TBI should be managed in neuroscience centres, regardless of the need for neurosurgical intervention. The monitoring and treatment of raised intracranial pressure is paramount for maintaining cerebral blood supply and oxygen delivery in patients with severe TBI. Decompressive craniectomy and therapeutic hypothermia are the subject of ongoing international multi-centre randomised trials. TBI is associated with a number of complications, some of which require specialist referral. Patients with post-concussion syndrome can be helped by supportive management in the context of a multi-disciplinary neurotrauma clinic and by patient support groups. Specialist neurorehabilitation after TBI is important for improving outcome.

Assessing residual reasoning ability in overtly non-communicative patients using fMRI☆

It is now well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are also capable of logical thought. Here, we validate an fMRI paradigm that can detect the neural fingerprint of reasoning processes and moreover, can confirm whether a participant derives logical answers. We demonstrate the efficacy of this approach in a physically non-communicative patient who had been shown to engage in mental imagery in response to simple auditory instructions. Our results demonstrate that this individual retains a remarkable capacity for higher cognition, engaging in the reasoning task and deducing logical answers. We suggest that this approach is suitable for detecting residual reasoning ability using neural responses and could readily be adapted to assess other aspects of cognition.

A hierarchy of event-related potential markers of auditory processing in disorders of consciousness

Functional neuroimaging of covert perceptual and cognitive processes can inform the diagnoses and prognoses of patients with disorders of consciousness, such as the vegetative and minimally conscious states (VS;MCS). Here we report an event-related potential (ERP) paradigm for detecting a hierarchy of auditory processes in a group of healthy individuals and patients with disorders of consciousness. Simple cortical responses to sounds were observed in all 16 patients; 7/16 (44%) patients exhibited markers of the differential processing of speech and noise; and 1 patient produced evidence of the semantic processing of speech (i.e. the N400 effect). In several patients, the level of auditory processing that was evident from ERPs was higher than the abilities that were evident from behavioural assessment, indicating a greater sensitivity of ERPs in some cases. However, there were no differences in auditory processing between VS and MCS patient groups, indicating a lack of diagnostic specificity for this paradigm. Reliably detecting semantic processing by means of the N400 effect in passively listening single-subjects is a challenge. Multiple assessment methods are needed in order to fully characterise the abilities of patients with disorders of consciousness.

fMRI for vegetative and minimally conscious states

A more balanced perspective

The epidemiology of a specialist neurorehabilitation clinic: Implications for clinical practice and regional service development

Abstract Objective: To examine the epidemiology of referrals to a specialist neurotrauma clinic and explore and highlight implications for clinical practice and service development for persons with head injury/traumatic brain injury (HI/TBI). Design and methods: A retrospective population-based cohort study of all referrals to a specialist neurotrauma clinic over a 9-year period. Data from a specialist head injury database (which included all persons presenting to hospital with traumatic brain injury) were analysed. Results: In total, 1235 new patients of all ages, severities of injury, both admitted and non-admitted were referred. Referrals have increased due to successful integration with new service developments and resulting optimization of resources. Conclusions: Data gathered from the cohort gives increased understanding of the characteristics and numbers of patients requiring rehabilitation and adds to the evidence-base. Integration with new and complementary service developments has optimized the function/aims of the clinic and enhanced its role in terms of patient service and outcome and as a research resource. The model provides principles which may be applied to planning, organizing and providing follow-up/rehabilitation services for HI/TBI.

Efficiency of hospital reporting systems in detecting head injury admissions

Abstract Objectives. To examine the completeness of data on admission with head injury at a Regional Neuroscience Centre. Design. A comparative study using retrospective and prospective data sources. Subjects. All adults admitted to all specialties with all severities of head injury. Methods. Adult admissions with ‘head injury’ in a single month were identified from two sources: (a) prospective ED reports using ED codes for head injury + site ‘Head/Face’ and ‘Reason for attendance’, (b) retrospective ICD-10 coding reports of codes S00-09. Data from both sources were compared and reasons for non-capture analysed. Admissions from both reports were combined to obtain a more complete number of admissions with head injury. Results. A total of 112 admissions with head injury were identified from both sources. Completeness from ED reports was 70% (n = 78) and 83% (n = 93) from ICD-10 reports. In total, 53% (n = 59) of admissions were captured in both reports. The main reasons for non-capture in the ED reports were non-coding of head injury (56%, n = 19), and admission via another routes, for example, transfers (44%, n = 15). The main reasons for non-capture in the ICD-10 reports were non-coding of head injury or not the primary diagnosis (74%, n = 14). Conclusions. Reliable epidemiological data is required for planning and commissioning services, however, identification of head injury admissions is difficult due to ambiguity in terminology and patient population. More than one source is necessary for completeness of data, however, data issues such as comprehensiveness, reliability and inclusion criteria/possible bias need to be considered.

Longitudinal Bedside Assessments of Brain Networks in Disorders of Consciousness: Case Reports From the Field

Clinicians are regularly faced with the difficult challenge of diagnosing consciousness after severe brain injury. As such, as many as 40% of minimally conscious patients who demonstrate fluctuations in arousal and awareness are known to be misdiagnosed as unresponsive/vegetative based on clinical consensus. Further, a significant minority of patients show evidence of hidden awareness not evident in their behavior. Despite this, clinical assessments of behavior are commonly used as bedside indicators of consciousness. Recent advances in functional high-density electroencephalography (hdEEG) have indicated that specific patterns of resting brain connectivity measured at the bedside are strongly correlated with the re-emergence of consciousness after brain injury. We report case studies of four patients with traumatic brain injury who underwent regular assessments of hdEEG connectivity and Coma Recovery Scale-Revised (CRS-R) at the bedside, as part of an ongoing longitudinal study. The first, a patient in an unresponsive wakefulness state (UWS), progressed to a minimally-conscious state several years after injury. HdEEG measures of alpha network centrality in this patient tracked this behavioral improvement. The second patient, contrasted with patient 1, presented with a persistent UWS diagnosis that paralleled with stability on the same alpha network centrality measure. Patient 3, diagnosed as minimally conscious minus (MCS–), demonstrated a significant late increase in behavioral awareness to minimally conscious plus (MCS+). This patients hdEEG connectivity across the previous 18 months showed a trajectory consistent with this increase alongside a decrease in delta power. Patient 4 contrasted with patient 3, with a persistent MCS- diagnosis that was similarly tracked by consistently high delta power over time. Across these contrasting cases, hdEEG connectivity captures both stability and recovery of behavioral trajectories both within and between patients. Our preliminary findings highlight the feasibility of bedside hdEEG assessments in the rehabilitation context and suggest that they can complement clinical evaluation with portable, accurate and timely generation of brain-based patient profiles. Further, such hdEEG assessments could be used to estimate the potential utility of complementary neuroimaging assessments, and to evaluate the efficacy of interventions.

Methylphenidate-mediated motor control network enhancement in patients with traumatic brain injury

ABSTRACT Primary Objective: To investigate functional improvement late (>6 months) after traumatic brain injury (TBI). To this end, we conducted a double-blind, placebo-controlled experimental medicine study to test the hypothesis that a widely used cognitive enhancer would benefit patients with TBI. Research Design: We focused on motor control function using a sequential finger opposition fMRI paradigm in both patients and age-matched controls. Methods and Procedures: Patients’ fMRI and DTI scans were obtained after randomised administration of methylphenidate or placebo. Controls were scanned without intervention. To assess differences in motor speed, we compared reaction times from the baseline condition of a sustained attention task. Main Outcomes and Results: Patients’ reaction times correlated with wide-spread motor-related white matter abnormalities. Administration of methylphenidate resulted in faster reaction times in patients, which were not significantly different from those achieved by controls. This was also reflected in the fMRI findings in that patients on methylphenidate activated the left inferior frontal gyrus significantly more than when on placebo. Furthermore, stronger functional connections between pre-/post-central cortices and cerebellum were noted for patients on methylphenidate. Conclusions: Our findings suggest that residual functionality in patients with TBI may be enhanced by a single dose of methylphenidate.