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<p> Clinical diagnosis, classification of injury and the reliable and detailed description of a patient's neurological status are key factors in determining intervention, rehabilitation programs and predicting recovery. The American Spinal Injury Association (ASIA) impairment scale (AIS) is a standardized method for spinal cord injury (SCI) classification and neurologic status examination. Studies have revealed the AIS classification to be a general assessment tool that fails to explain the varying degrees and patterns of neurological damage, especially in individuals with incomplete injuries. In addition, intragroup variability can be attributed to inaccuracies in examinations and improper assessment tools that have limited research findings. Transcranial Magnetic Stimulation (TMS) has been used as a non-invasive method of evaluating the integrity of the motor nervous system. The primary purpose of this study was to evaluate TMS as an assessment tool to describe motor impairment of SCI individuals. A second purpose of this study was to assess AIS accuracy and sensitivity to muscle activation by using surface electromyographic (sEMG) techniques during clinical examinations. Six incomplete SCI participants were clinically assessed to obtain their individual motor scores from key muscles following AIS assessment criteria. TMS was then used to stimulate the motor cortex to elicit motor evoked potentials (MEPs) in 4 key muscles. MEPs correlated with motor scores, where significantly higher and lower MEPs corresponded to the highest and lowest motor scores, respectively. Of the 48 muscles analyzed, 18 received a motor score of zero; however MEPs were obtained in 7 of these 18 muscles. In general, MEPs paralleled motor function as assessed by the AIS. Results suggest that TMS may provide information on the relationship between corticospinal integrity and the quality of motor function. In addition, TMS demonstrated adequate validity and sensitivity to SCI individual differences. MEPs provided additional information regarding the existence of spared neuronal pathways not identified by standard clinical evaluations. The therapeutic potential of these motor pathways has yet to be explored. EMG activity was significantly correlated to motor scores and MEPs however; EMG analysis revealed some inaccuracies in muscle examinations and supported MEP data. Results suggest that the implementation of electrophysiological assessment tools may be more sensitive to detect motor damage, adaptive movement patterns and overall muscle activation that may be misinterpreted during clinical examinations.</p> / Thesis / Master of Science (MSc)

Transcranial magnetic stimulation (TMS) is commonly used to measure corticospinal and intracortical excitability in basic and clinical neuroscience. However, the effect of glucose on TMS-based measures is not well defined, despite a potentially impactful influence on precision and reliability. Here, a double-blinded placebo-controlled study was used to test the effects of glucose on two commonly used TMS measures: short-interval intracortical inhibition (SICI), and the area under the motor evoked potential recruitment curves (AURC). SICI and AURC are thought to reflect inhibitory (GABAergic) and excitatory (glutamatergic) neurotransmission respectively. Healthy males (N=18) each participated in four sessions. Session 1 involved TMS familiarization and acquisition of an individualized blood glucose response curve. During sessions 2, 3 and 4, dependent measures were taken before (T0) and twice after (T1 & T2) drinking 300 mL of solution containing glucose (75 g), sucralose-sweetened placebo (control for sweetness) or plain water (control for time). The T1 and T2 measurements were started 5 minutes prior to the blood glucose peak observed during Session 1. Blood glucose and mean arterial pressure (MAP) were also monitored. Sucralose, but not water or glucose increased AURC and none of the treatments altered SICI. There was no association between blood glucose level and TMS measures, but in all three conditions MAP rose after consumption of the drink. There was a positive correlation between the rise in blood pressure and the relative increase in AURC at the higher stimulus intensities. Eleven participants returned for a fifth session to quantify the smallest detectible change in the AURC measurements and it was confirmed that significant changes were real while non-significant differences in measurement means fell within the range of expected measurement error. This study also suggests a relationship between corticospinal excitability and autonomic tone. Additional investigation is required to understand the mediating factors of this association. / Thesis / Master of Science (MSc)

Previous research has established that observing another in pain activates both affective and sensorimotor cortical activity that is also present during the first-hand experience of pain. Some researchers have taken this “mirroring” response as indicative of empathic processing. However, very little work has explored the downstream behavioral effects of empathic pain observation. The aim of this dissertation is to begin to fill this gap in the literature by exploring the relationship between empathic pain observation, overt motor behaviours, and sensorimotor activity. In chapters 2-4, I provide robust evidence that observing pain inflicted on another person leads to faster reaction time responses. This effect is shown to be temporally extended (by at least 500ms after pain observation), effector-general (affecting both finger and foot responses), influenced by top-down (i.e., instructions to explicitly empathize) but not bottom-up (i.e., the perceived level of pain) factors, and is not influenced by adaptive (approach/withdraw) behaviours. In chapter 5, I show that sensorimotor activity, measured via TMS-induced Motor Evoked Potentials, increases while observing another in pain regardless whether the observer is preparing to make an action vs. passively observing the stimuli. These results run counter to the literature, and I provide several explanations for why these results were found. Lastly, in chapter 6, I show that sensorimotor activity, measured via Mu and Beta suppression, also increases while observing another in pain regardless whether the observer is preparing to make an action vs. passively observing the stimuli. Interestingly, I do not find significant correlations between sensorimotor activity during pain observation and faster reaction times after pain observation. I embed these findings in relation to the wider social neuroscience of empathy literature and discuss several limitations and challenges in empirically measuring “empathy” as a psychological construct. Overall, this dissertation furthers our understanding of empathy for pain by highlighting the behavioural consequences of pain observation and its connection (or rather, lack thereof) to sensorimotor activity during pain observation. / Thesis / Doctor of Philosophy (PhD) / Past research suggests that overlapping brain activity during the first-hand experience of pain and pain observation may be indicative of empathy. However, very little work has been done to explore how pain observation influences overt behaviours. This thesis investigates this issue by having participants complete a reaction time task while watching videos of needles stabbing a person’s hand. The findings reported in this thesis suggests that observing another in pain facilitates motor behaviours (i.e., faster reaction times); this facilitation extends 500ms after pain observation, affects both the hand and feet, is accentuated by instructing participants to explicitly empathize, and is not influenced by approach vs. withdraw movements. Brain activity in the motor system was also found to increase during pain observation. Overall, this thesis begins the discussion of how empathic pain observation influences explicit motor behaviours, and how such behaviours may be related to brain activity.

No / The right temporoparietal cortex plays a critical role in body representation. Here, we applied repetitive transcranial magnetic stimulation (rTMS) over right extrastriate body area (EBA) and temporoparietal junction (TPJ) to investigate their causative roles in perceptual representations of one's own and others' body. Healthy women adjusted size-distorted pictures of their own body or of the body of another person according to how they perceived the body (subjective task) or how others perceived it (intersubjective task). In keeping with previous reports, at baseline, we found an overall underestimation of body size. Crucially, EBA-rTMS increased the underestimation bias when participants adjusted the images according to how others perceived their own or the other woman's body, suggesting a specific role of EBA in allocentric body representations. Conversely, TPJ-rTMS increased the underestimation bias when participants adjusted the body of another person, either a familiar other or a close friend, in both subjective and intersubjective tasks, suggesting an involvement of TPJ in representing others' bodies. These effects were body-specific, since no TMS-induced modulation was observed when participants judged a familiar object. The results suggest that right EBA and TPJ play active and complementary roles in the complex interaction between the perceptions of one's own and other people's body.

Ultrasound waves are mechanical undulations above the threshold for human hearing, and have been used widely in both the human body and brain for diagnostic and therapeutic purposes. Ultrasound can be controlled using specially designed transducers into a focus of a few millimeters in diameter. Low intensity ultrasound, such as used in imaging applications, appears to be safe in adults. It is also known that ultrasound waves can penetrate through the skull and be focused within the brain for ablation purposes, employing the heat generation properties of high intensity focused ultrasound. High intensity focused ultrasound is thus used to irreversibly ablate brain tissue in localized areas without observable damage to intermediate tissue and vasculature. Ablation with high intensity focused ultrasound guided by magnetic resonance imaging is used for abolishing brain tumors, and experimentally for pain. Low intensity ultrasound can be utilized beyond imaging in neuroscience and neurology by focusing the ultrasound beam to investigate the structure and function of discrete brain circuits. In contrast to high intensity focused ultrasound, the effects of low intensity focused ultrasound on neurons are reversible. Considering the volume of work on high intensity focused ultrasound, low intensity focused ultrasound remains decidedly underdeveloped. Given the great potential for impact of low intensity focused ultrasound in both clinical and scientific neuromodulation applications, we sought to advance the use of low intensity focused ultrasound for noninvasive, transcranial neuromodulation of human cortex. This dissertation contains novel research on the use of low intensity transcranial focused ultrasound for noninvasive neuromodulation of human cortex. The importance of mechanical forces in the nervous system is highlighted throughout to expand beyond the stigma that nervous function is governed chiefly by electrical and chemical means. Methods of transcranial focused ultrasound are applied to significantly modulate human cortical function, shown using electroencephalographic recordings and behavioral investigations of sensory discrimination performance. This dissertation also describes computational models used to investigate the insertion behavior of ultrasound across various tissues in the context of transcranial neuromodulation, as ultrasound's application for neuromodulation is relatively new and crudely understood. These investigations are critical for the refinement of device design and the overall advancement of ultrasound methods for noninvasive neuromodulation. / Ph. D.

No / In this report, we evaluate the role of visual areas responsive to motion in the human brain in the perception of stimulus speed. We first identified and localized V1, V3A, and V5/MT+ in individual participants on the basis of blood oxygenation level-dependent responses obtained in retinotopic mapping experiments and responses to moving gratings. Repetitive transcranial magnetic stimulation (rTMS) was then used to disrupt the normal functioning of the previously localized visual areas in each participant. During the rTMS application, participants were required to perform delayed discrimination of the speed of drifting or spatial frequency of static gratings. The application of rTMS to areas V5/MT and V3A induced a subjective slowing of visual stimuli and ( often) caused increases in speed discrimination thresholds. Deficits in spatial frequency discrimination were not observed for applications of rTMS to V3A or V5/MT+. The induced deficits in speed perception were also specific to the cortical site of TMS delivery. The application of TMS to regions of the cortex adjacent to V5/MT and V3A, as well as to area V1, produced no deficits in speed perception. These results suggest that, in addition to area V5/MT+, V3A plays an important role in a cortical network that underpins the perception of stimulus speed in the human brain. / BBSRC

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