Towards simultaneous electroencephalography and functional near-infrared spectroscopy for improving diagnostic accuracy in prolonged disorders of consciousness: a healthy cohort study

Qualitative clinical assessments of the recovery of awareness after severe brain injury require an assessor to differentiate purposeful behaviour from spontaneous behaviour. As many such behaviours are minimal and inconsistent, behavioural assessments are susceptible to diagnostic errors. Advanced neuroimaging tools such as functional magnetic resonance imaging and electroencephalography (EEG) can bypass behavioural responsiveness and reveal evidence of covert awareness and cognition within the brains of some patients, thus providing a means for more accurate diagnoses, more accurate prognoses, and, in some instances, facilitated communication. As each individual neuroimaging method has its own advantages and disadvantages (e.g., signal resolution, accessibility, etc.), this thesis studies on healthy individuals a burgeoning technique of non-invasive electrical and optical neuroimaging—simultaneous EEG and functional near-infrared spectroscopy (fNIRS)—that can be applied at the bedside. Measuring reliable covert behaviours is correlated with participant engagement, instrumental sensitivity and the accurate localisation of responses, aspects which are further addressed over three studies. Experiment 1 quantifies the typical EEG changes in response to covert commands in the absence and presence of an object. This is investigated to determine whether a goal-directed task can yield greater EEG control accuracy over simple monotonous imagined single-joint actions. Experiment 2 characterises frequency domain NIRS changes in response to overt and covert hand movements. A method for reconstructing haemodynamics using the less frequently investigated phase parameter is outlined and the impact of noise contaminated NIRS measurements are discussed. Furthermore, classification performances between frequency-domain and continuous-wave-like signals are compared. Experiment 3 lastly applies these techniques to determine the potential of simultaneous EEG-fNIRS classification. Here a sparse channel montage that would ultimately favour clinical utility is used to demonstrate whether such a hybrid method containing rich spatial and temporal information can improve the classification of covert responses in comparison to unimodal classification of signals. The findings and discussions presented within this thesis identify a direction for future research in order to more accurately translate the brain state of patients with a prolonged disorder of consciousness

A developmental shift in habituation to pain in human neonates

Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain. Neonates, especially if preterm, are exposed to repeated noxious procedures during their clinical care. They can mount strong behavioral, autonomic, spinal, and cortical responses to a single noxious stimulus; however, it is not known whether the developing nervous system can adapt to the recurrence of these inputs. Here, we used electroencephalography to investigate changes in cortical microstates (representing the complex sequential processing of noxious inputs) following two consecutive clinically required heel lances in term and preterm infants. We show that stimulus repetition dampens the engagement of initial microstates and associated behavioral and autonomic responses in term infants, while preterm infants do not show signs of habituation. Nevertheless, both groups engage different longer-latency cortical microstates to each lance, which is likely to reflect changes in higher-level stimulus processing with repeated stimulation. These data suggest that while both age groups are capable of encoding contextual differences in pain, the preterm brain does not regulate the initial cortical, behavioral, and autonomic responses to repeated noxious stimuli. Habituation mechanisms to pain are already in place at term age but mature over the equivalent of the last trimester of gestation and are not fully functional in preterm neonates

Widespread nociceptive maps in the human neonatal somatosensory cortex

Topographic cortical maps are essential for spatial localisation of sensory stimulation and generation of appropriate task-related motor responses. Somatosensation and nociception are finely mapped and aligned in the adult somatosensory (S1) cortex, but in infancy, when pain behaviour is disorganised and poorly directed, nociceptive maps may be less refined. We compared the topographic pattern of S1 activation following noxious (clinically required heel lance) and innocuous (touch) mechanical stimulation of the same skin region in newborn infants (n=32) using multi-optode functional near-infrared spectroscopy (fNIRS). Within S1 cortex, touch and lance of the heel elicit localised, partially overlapping increases in oxygenated haemoglobin concentration (D[HbO]), but while touch activation was restricted to the heel area, lance activation extended into cortical hand regions. The data reveals a widespread cortical nociceptive map in infant S1, consistent with their poorly directed pain behaviour

Clinical thresholds in pain-related facial activity linked to differences in cortical network activation in neonates

In neonates, a noxious stimulus elicits pain-related facial expression changes and distinct brain activity as measured by electroencephalography, but past research has revealed an inconsistent relationship between these responses. Facial activity is the most commonly used index of neonatal pain in clinical settings, with clinical thresholds determining if analgesia should be provided; however, we do not know if these thresholds are associated with differences in how the neonatal brain processes a noxious stimulus. The objective of this study was to examine whether subclinical vs clinically significant levels of pain-related facial activity are related to differences in the pattern of nociceptive brain activity in preterm and term neonates. We recorded whole-head electroencephalography and video in 78 neonates (0-14 days postnatal age) after a clinically required heel lance. Using an optimal constellation of Neonatal Facial Coding System actions (brow bulge, eye squeeze, and nasolabial furrow), we compared the serial network engagement (microstates) between neonates with and without clinically significant pain behaviour. Results revealed a sequence of nociceptive cortical network activation that was independent of pain-related behavior; however, a separate but interleaved sequence of early activity was related to the magnitude of the immediate behavioural response. Importantly, the degree of pain-related behavior is related to how the brain processes a stimulus and not simply the degree of cortical activation. This suggests that neonates who exhibit clinically significant pain behaviours process the stimulus differently and that neonatal pain-related behaviours reflect just a portion of the overall cortical pain response

Shining a Light on Awareness::A Review of Functional Near-Infrared Spectroscopy for Prolonged Disorders of Consciousness

Qualitative clinical assessments of the recovery of awareness after severe brain injury require an assessor to differentiate purposeful behavior from spontaneous behavior. As many such behaviors are minimal and inconsistent, behavioral assessments are susceptible to diagnostic errors. Advanced neuroimaging tools can bypass behavioral responsiveness and reveal evidence of covert awareness and cognition within the brains of some patients, thus providing a means for more accurate diagnoses, more accurate prognoses, and, in some instances, facilitated communication. The majority of reports to date have employed the neuroimaging methods of functional magnetic resonance imaging, positron emission tomography, and electroencephalography (EEG). However, each neuroimaging method has its own advantages and disadvantages (e.g., signal resolution, accessibility, etc.). Here, we describe a burgeoning technique of non-invasive optical neuroimaging—functional near-infrared spectroscopy (fNIRS)—and review its potential to address the clinical challenges of prolonged disorders of consciousness. We also outline the potential for simultaneous EEG to complement the fNIRS signal and suggest the future directions of research that are required in order to realize its clinical potential