This thesis describes studies assessing the ability of somatosensory evoked potentials (SEPs) to predict outcome following severe brain injury by examining outcome and determining the predictive value of SEPs directly and in comparison to alternative tests in both patients and systematic reviews of the literature. Outcome was assessed using a functional and quality of life measure. It changed over time and was influenced by age, mechanism, timing and the type of outcome measure. When 5 year functional outcome was used, sensitivity and specificity for the initial SEPs were 63.2% and 93.3% with a positive predictive value of 92.3% for favourable outcome and 66.7%, 94.7% and 90.9% for unfavourable outcome prediction. SEPs predictive performance varied and was better in patients with 1 year outcomes, when outcome was measured with the quality of life tool and in patients suffering hypoxicischaemic encephalopathy. Importantly, only twelve false positives were identified in the systematic review of 55 studies from 903 patients with bilaterally absent SEPs. Eight of these false positives suffered focal lesions of the brain stem, large cerebral fluid collections or recent decompressive craniectomy which cause SEPs to be absent because of a mechanical disruption to the electrical signal. Comparisons between SEPs and other tests in the patient cohort and wider literature showed that SEPs were the best overall predictors of outcome but were outperformed by some clinical tests in specific areas. Specificity for unfavourable outcome prediction was better for ICP, CPP and the last pupillary response. In patients with any cause of brain injury, the combination of SEPs and Motor responses provided the best predictions for unfavourable outcome while for favourable outcome the best overall prediction and specificity were achieved with a combination of either SEPs or Motor responses and the best sensitivity with pupillary responses alone or a combination of either SEPs or Pupillary responses. The studies in this thesis provide a detailed evaluation of SEPs and showed that SEPs have a place in the prediction of outcome, alone or in combination with existing tests. Overall, they are superior to clinical tests and can be easily obtained at the bedside and in the presence of pharmacological paralysis and analgesia/sedation.

Neck pain has the potential to result in altered afferent input to the central nervous system which may thereby result in altered sensorimotor integration and eventually further disability. One “at risk” population for neck pain may be university students, particularly given the growing use of laptop computers in the university setting. This thesis presents two pilot studies which aim to develop and assess instruments to use as screening tools for risk factors associated with neck pain. The first study explores the environment in which university students utilize their laptop computers and the relationship to known risk factors for neck pain. A new questionnaire, The Student Laptop Use and Neck Pain Risk Questionnaire (SLUNPRQ) was created to measure the presence of risk factors known to increase the risk of developing neck pain. This questionnaire was piloted for reliability using test- retest measures. Results indicated that the SLUNPRQ had good reliability based on Cohen’s Kappa scores. A modified questionnaire was developed based on questions with either low reliability or ambiguous answers and is ready for further testing. The second study sought to determine if dual somatosensory evoked potential (SEP) ratios changed with long term chiropractic care. This was part of the overall goal of finding neural markers that could identify those who are at risk for developing neck pain. This study sought to determine the feasibility of using dual SEPs to evaluate changes in neural markers of sensorimotor integration after 12 weeks of chiropractic care and demonstrated that dual SEPs shows potential as a marker to screen individuals at risk of neck pain as the SEP markers showed improvement after long term chiropractic care. / UOIT

Altered afferent input resulting from neck joint dysfunction has become a growing area of study. Cervical spine manipulation, specifically in individuals with subclinical neck pain (SNCP); induces neurological changes, suggesting it has a positive neuromodulatory effect on brain processing. The effects of manipulation on motor learning in individuals with SCNP have not been investigated until now. Studies in this thesis sought to develop and investigate a novel motor training task to be coupled with cervical spine manipulation to investigate its effects on individual’s ability to process new task information. The studies revealed significant changes in neural activity specific to the cerebellum and sensorimotor integration following a complex motor training task as compared to a simple repetitive task, suggesting that those specific regions are involved in processing of more complex motor skill learning tasks. This novel task was then coupled with manipulation which revealed significant activation increases in cortical and decreases in subcortical brain regions following manipulation. Regions specific to sensorimotor integration (SMI) showed increased activation in both the manipulation and passive head movement control groups, corroborating with the results from the first study. The use of a complex motor training task is a useful tool for determining intervention effects on neural processing in individuals with SCNP. / UOIT

Thesis (PhD) - Swinburne University of Technology, 2006. / Submitted for the degree of Doctor of Philosophy, Swinburne University of Technology - 2006. Typescript. Bibliography: p. 191-223.

Thesis (Ph. D.)--Hong Kong Polytechnic University, 2003. / Includes bibliographical references (leaves 199-216). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (Ph. D.)--Hong Kong Polytechnic University, 2003. / Includes bibliographical references (leaves 199-216).

Whether ongoing electroencephalogram (EEG) signal contributes to event related potential (ERP) generation is currently a matter of discussion for all sensory modalities. Resolving the controversy between additive and the oscillatory models has become crucial because evoked potentials are increasingly used in clinical practice as a physiological and neuropsychological index of brain areas or as a link with other functional approaches such as fMRI and the underlying network. The key issue is the search for a function underlying these mechanisms. <p><p>Somatosensory evoked potentials are robust indicators of the afferent information at cortical level. In particular, the frontal N30 component of SEP can serve as a reliable physiological index of the dopaminergic motor pathway (Insola et al. 1999, Pierantozzi et al. 1999). Its properties in sensory-motor gating and cognitive processes make its fine analysis particularly interesting. The physiological interpretation and the origin of the frontal N30 are still debated (Allison et al. 1991, Cheron et al. 1994, Karnovsky et al. 1997, Balzamo et al. 2004, Barba et al. 2005).<p><p>In this thesis we have investigated the mechanisms generating the N30 SEP component produced by electrical stimulation at median nerve at wrist, with reference to the current questioning of the additive and oscillatory models of the ERP (Sayers et al. 1974; Basar et al. 1980).<p><p>We have applied analysis of the spectral content of neuronal oscillatory activity recorded in electroencephalographic (EEG) in order to study of dynamic brain processing underlying the N30 component. Concretely for studying whether the occurrence of the N30 related input induce amplitude modulation and/or reorganization of EEG rhythms we have analyzed separately power perturbation and phase synchrony of single EEG oscillations trials by means of event-related spectral perturbation (ERSP) and intertrial coherence (ITC) measurements. In addition, in order to model brain localizations of phase synchrony and power enhancement and to compare them to model localization of the N30 SEP we used swLORETA, a distributive method of source analysis.<p><p>We have demonstrated that:<p>(1) Ongoing EEG signals contribute to the generation of the N30 component (Cheron et al. 2007).<p>(2) Dynamics of ongoing EEG signals underlie the specific behavior of the N30 during gating produced by movement execution (Cebolla et al. 2009).<p>(3) Localization of brain sources generating the N30 SEP component overlaps those generating beta-gamma ongoing oscillations at the same short latency (Cebolla et al. 2010).<p><p>Additionally the work developed during this thesis has served to develop a comprehensive, pragmatic paradigm to identify, evaluate and understand the somatosensory alterations in defined contexts, as illustrated by our recent work on perturbations and adaptations in astronauts over long term microgravity stay. We think that addressing this topic is essential in order to optimize and objectively evaluate adaptation to microgravity. We therefore proposed a detailed project to European Space Agency entitled “The frontal N30 somatosensory evoked potential for the study of sensory-motor and cognitive adaptations in weightlessness: NeuroSEP” (ILSRA 2009) in which we also proposed direct applications for quality of life aboard International Space Station, for the medical field and industry. / Doctorat en Sciences de la motricité / info:eu-repo/semantics/nonPublished

As animals explore and interact with their surroundings, information about their environment is constantly processed from sensory stimuli into perception. This information informs their behavior, decision-making, and understanding of their world. Information processing and perception have long been thought to be modulated by the behavior state of the animal (Cano et al. 2006; Niell and Stryker 2010; Polack et al. 2013; Poulet & Petersen, 2008; Briggs 2013, Schölvinck et al. 2015). Previous research has shown that behavior state strongly correlates with perceptual performance in a sensory discrimination task in rodents (McGinley et al. 2015, Schriver et al., 2018). However, the neural correlates behind this modulation of perception, information processing, and behavioral performance are not yet fully understood. The first part of this work investigates the relationship between cell-type specific spontaneous cortical activity and behavior state as defined by pupil-linked arousal. Spontaneous activity is essential in understanding the link between behavior state and information processing as it serves as the baseline state of activity prior to processing any stimuli information. Within the sensory cortices, excitatory and inhibitory neurons work in unison to dictate network activity. Three main classes of cortical inhibitory neurons are somatostatin-expressing neurons (SST), vasointestinal peptide-expressing neurons (VIP), and parvalbumin-expressing neurons (PV). These four cell types comprise the VIP disinhibitory circuit, in which VIP neurons disinhibit excitatory neurons by inhibiting PV and SST neurons. PV and SST neurons directly inhibit excitatory cells, so by suppressing their activity VIP neurons indirectly disinhibit excitatory cells. This circuit is a vitally important system used to modify excitatory activity in all cortical regions. The spontaneous activity of excitatory neurons and three classes of inhibitory neurons (somatostatin-expressing neurons (SST), vasointestinal peptide-expressing neurons (VIP), and parvalbumin-expressing neurons (PV)) was individually examined in this study. To visualize in-vivo spontaneous cortical activity, a genetically encoded calcium indicator (GCaMP) was expressed in the somatosensory cortex, and the population-level neural activity was imaged using fiber photometry. Despite the relationship between these neurons as defined by the VIP disinhibitory circuit, the spontaneous activity of excitatory, VIP, PV, and SST neurons was found to positively correlate with pupil size for all of these neuron types. This supports the theory that VIP and other interneuron types may be active in various functions, not just the disinhibition of excitatory cells. Pupil-evoked activity, or spontaneous activity during highly aroused states, was also found to positively correlate with pupil size for all cell types and had the strongest correlation for all correlation types. Therefore, pupil-linked arousal level relates to the increased activity of both excitatory and inhibitory cortical cells. While the first chapter focuses on spontaneous activity, the second focuses on stimulus-evoked activity. Stimulus-evoked activity in the somatosensory pathway can be caused by both internally generated stimuli and external stimuli. In the first step of sensory processing, the sensory receptors cannot distinguish between these two types of stimuli. However, the differentiation between the two is necessary in order to distinguish self from non-self. The motor-related timing signals that influence sensory processing and enable distinction between internally generated and external stimuli is termed corollary discharge. Where and how the mechanism of corollary discharge occurs in the somatosensory system is not well understood. To investigate corollary discharge in the somatosensory system, the neural activity in the somatosensory cortex was analyzed during internally generated stimuli and during delivery of external stimuli. More specifically, the activity in the vibrissa somatosensory cortex of rodents during self-induced whisking and during delivery of an air puff to the whiskers was examined. In the primary and secondary somatosensory cortex, excitatory activity was inhibited just prior to whisking and suppressed to a lower level during whisking in comparison to the activity level during air puff delivery. The three main classes of inhibitory neurons were studied to explore the possibility of local inhibition causing this suppression of the excitatory signal during whisking. VIP, PV and SST neurons all exhibited a similar pre-whisking inhibition and suppression of activity during whisking, eliminating the possibility of their role in pre-whisking inhibition and whisking activity suppression. Other regions involved in the somatosensory pathway and sensorimotor processing, such as the thalamus and motor cortex, were also found to not contribute to pre-whisking inhibition or whisking activity suppression as they were also found to exhibit the same phenomenon. After ruling out cortical inhibitory neurons and somatosensory regions in the involvement of corollary discharge, external higher-order regions were investigated. Previous studies on the sources of corollary discharge in the cerebellum have shown corollary discharge signals originate from coordination of several different higher-order brain regions (Person A., 2019). To determine these potential regions for somatosensory corollary discharge, viral tracing vectors were used to locate regions with long-range inhibitory projections to the somatosensory cortex. The globus pallidus (GP) was first investigated due to its role in voluntary movement and projections to the frontal cortex (Saunders et al. 2015). However, no inhibitory projections from the GP to the somatosensory cortex were found. The striatum, which is mainly GABAergic (and therefore inhibitory), also seemed to be a likely candidate. Preliminary tracing results suggest the striatum does have inhibitory projections to the somatosensory cortex. Further studies of both retrograde and anterograde tracing must be performed to confirm this finding. Nonetheless, the evidence of corollary discharge as seen through pre-whisking inhibition and the suppression of activity during whisking in S1, S2, thalamus, and motor cortex is a novel finding and opens up many avenues for further research.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23774号 / 医博第4820号 / 新制||医||1057(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊佐 正, 教授 高橋 淳, 教授 井上 治久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p>This dissertation examined perturbation effects during complex tactile information transmission. The four experiments provide evidence regarding sensory and information processing demands in early stages of complex tactile learning.</p> <p>Experiment 1 established complex tactile learning behavioural performance. Vibrotactile stimuli representing Morse code letters were communicated to participants with or without induced perturbation to the finger of letter reception. Response performance was measured and augmented feedback was provided retroactively. Perturbation conditions lead to poor performance during tactile acquisition, but improved performance during application of knowledge.</p> <p>Experiment 2 determined if the experiment 1 results demonstrated masking or response competition paradigms. Target “masking” is the reduced ability to detect or interpret a stimuli pattern by presentation of other information (Craig, 1985; Verrillo, 1985). Response competition is the competition or distraction from target response generation by secondary stimuli (Craig, 2000; Bolanowski et al., 2000). Experiment 2 tested response competition by spatially separating the perturbation and tactile information delivery sites.</p> <p>Experiments 3 and 4 served to replicate behavioural acquisition data from experiments 1 and 2. They also extended the findings of the first two experiments by introducing neurophysiological measurement to reflect the changes associated with the two perturbation conditions. The study discerned whether the masking and response competition paradigms from experiments 1 and 2 were predominantly impacting the peripheral or central information processing.</p> <p>Results from the four studies collectively demonstrate that increased demands are placed on the sensory system during early stages of complex tactile learning when perturbation is spatially congruent with tactile information delivery. Experiments 1 and 2 revealed that attention does not supersede spatial location of perturbation, and perturbation location is paramount to yield sufficient interference to impede acquisition yet lead to enhanced knowledge retention and transfer. Experiments 3 and 4 determined that cortical information processing associated with complex tactile information acquisition are neurophysiologically differentiated when relative locations of meaningful and perturbation stimuli are congruent or spatially separated. The findings from this dissertation serve as an advancement of our understanding of masking and response competition phenomenon as they pertain to complex tactile learning.</p> / Doctor of Philosophy (PhD)