The sensorimotor network receives a rich variety of somesthetic afferents and outputs considerable motor efferents, both of which drive experience-dependent plasticity in the system. It remains unclear to what extent subtle changes in somaesthesis and motor function extrinsic to the brain drive plasticity in the functional organisation and anatomy of the sensorimotor network. This thesis contains a series of multimodal MRI experiments to investigate how altered-use and disuse can induce plastic changes in the sensorimotor network of the human brain. In Chapter 3, a method of mapping digit somatotopy in primary somatosensory cortex at the single-subject level using 7.0 tesla fMRI was developed and applied for a study of healthy participants. Using a phase-encoding paradigm, digit representations were accurately mapped in under 10 minutes. These maps were reproducible over time and comparable to a standard block design. In Chapter 4, a further fMRI study assessed the potential for short-term reorganisation of digit representations in primary somatosensory cortex following a manipulation whereby the right index and right middle fingers were glued together for 24 hours. There was a marked shift in the cortical overlap of adjacent digits after the glued manipulation, not seen across an equivalent control period, providing strong evidence for short-term remapping of primary somatosensory cortex. In Chapter 5, a patient study investigated plasticity associated with chronic unilateral disuse of the upper limb. A cross-sectional comparison with control participants showed reduced grey matter density in the posterior right temporoparietal junction, and increased radial diffusivity in the white matter of the right superior longitudinal fasciculus, consistent with change in the right ventral attention network. A complementary longitudinal study in Chapter 6 investigated structural plasticity associated with rehabilitation of the disused limb. There were localised increases in grey matter density, notably in the right temporoparietal junction, further implicating a potential role for regions responsible for egocentric attention in regaining upper limb use. In Chapter 7, a further patient study investigated candidate predictive biomarkers at the sub-acute stage of stroke recovery, identifying CST-lesion cross-section and sensorimotor network strength as correlates of motor function, which warrant further study. The results of the studies presented in this thesis provide a novel insight into the nature and time frame of functional and structural plasticity associated with altered use and disuse. Further study of how subtle changes in our sensory and motor use shape the sensorimotor network is warranted, particularly in the context of disuse in non-neurological clinical populations.

The spatiotemporal dynamics of ongoing beta band (15-30 Hz) cortical oscillations and the modulation of this neural activity by tactile input and movement provide insight into how the brain achieves proper sensorimotor processing. Earlier studies have shown that the synchrony of the cortical beta rhythms within and between central and peripheral neuronal populations is modulated during and following somatosensation or movement, and correlated with effective motor control. In addition, abnormal levels of beta oscillations in the basal ganglia are correlated with motor dysfunction in Parkinson’s disease. Numerous functional roles for the beta rhythm have been proposed – ranging from inhibition to the facilitation of long-range communication. However, the neural network that generates the sensorimotor beta rhythm and the functional significance of this activity have not been fully specified. Thus, I used magnetoencephalography to complete three studies of the beta rhythm in healthy right-handed adults. In the first study, I hypothesized that finger vibration at beta frequencies would generate stimulus-coherent neuronal firing in the neural network that generates the beta rhythm – thus revealing the nodes of this network. Data were analyzed for nineteen subjects (10 females). The coherent activity was revealed using a novel analysis technique that generated whole-brain maps of inter-trial synchrony during passive repetitive finger vibration at 23 Hz. These maps identified contralateral primary somatosensory cortex (SI), posterior parietal cortex, supplementary motor area and primary motor cortex (MI), and ipsilateral brainstem as nodes in the network. In the second study, I correlated changes in focused attention with modulations in beta band cortical responses to specify the functional significance of this activity. Data were analyzed for twelve subjects (7 females). With increased focused attention to the stimulus, I hypothesized that the beta band responses to finger vibration would be enhanced in areas involved in somatosensory processing. A transient increase in the magnitude of beta oscillations in MI (event-related synchronization) following vibration offset was significantly enhanced by attention, as compared to passive stimulation. In addition, attention caused the suppression of beta oscillations (event-related desynchronization, ERD) in ipsilateral SI beginning 1 second prior to vibration offset. Strong attention-modulation of the beta rhythm outside of contralateral SI implies that these changes are indicative of higher-order processing of afferent information. In the third study, I tested the hypothesis that synchrony between beta rhythms in contralateral MI and the relevant muscle supports effective neuronal communication. I correlated changes in task performance with corticomuscular coherence (CMC) during the sustained application of force to match a visually-presented target. Data were analyzed for eighteen subjects (9 females). As predicted, CMC in MI was significantly increased during improved performance in this task. This suggests that central-peripheral synchrony plays an important functional role in sustaining isometric muscle control. Concurrent beta ERD in bilateral SI and primary visual cortices during the contraction indicates the importance of afferent feedback in this task. Gender-related effects were not investigated in these studies. Beta band neuromagnetic responses to movement and somatosensation identify a pervasive neural network that is involved in processing the relevant properties of somatic input and regulating sustained motor output.

Magnetoencephalography was used to investigate the effect of directed attention on changes in sensorimotor mu (8-12Hz) response (mu reactivity) to non-painful electrical stimulation of the median nerve in healthy adults. Results indicated attention-related sex differences in mu reactivity, with females showing i) prolonged mu suppression when attending to somatosensory stimuli indicating active processing of the sensory stimuli; ii) task-dependent attentional modulation of the mu response, which was absent in males, and iii) a trend for greater neuronal excitability of the primary somatosensory region suggesting greater physiological responsiveness to stimulation overall. Sex-related differences in attentional modulation of sensorimotor rhythms suggest that females and males use different top-down control strategies when processing somatosensory information. These sex differences in attention may underlie well-documented sex-related biases in pain processing wherein females typically report greater sensitivity to experimental and clinical pain.

Magnetoencephalography was used to investigate the effect of directed attention on changes in sensorimotor mu (8-12Hz) response (mu reactivity) to non-painful electrical stimulation of the median nerve in healthy adults. Results indicated attention-related sex differences in mu reactivity, with females showing i) prolonged mu suppression when attending to somatosensory stimuli indicating active processing of the sensory stimuli; ii) task-dependent attentional modulation of the mu response, which was absent in males, and iii) a trend for greater neuronal excitability of the primary somatosensory region suggesting greater physiological responsiveness to stimulation overall. Sex-related differences in attentional modulation of sensorimotor rhythms suggest that females and males use different top-down control strategies when processing somatosensory information. These sex differences in attention may underlie well-documented sex-related biases in pain processing wherein females typically report greater sensitivity to experimental and clinical pain.

The spatiotemporal dynamics of ongoing beta band (15-30 Hz) cortical oscillations and the modulation of this neural activity by tactile input and movement provide insight into how the brain achieves proper sensorimotor processing. Earlier studies have shown that the synchrony of the cortical beta rhythms within and between central and peripheral neuronal populations is modulated during and following somatosensation or movement, and correlated with effective motor control. In addition, abnormal levels of beta oscillations in the basal ganglia are correlated with motor dysfunction in Parkinson’s disease. Numerous functional roles for the beta rhythm have been proposed – ranging from inhibition to the facilitation of long-range communication. However, the neural network that generates the sensorimotor beta rhythm and the functional significance of this activity have not been fully specified. Thus, I used magnetoencephalography to complete three studies of the beta rhythm in healthy right-handed adults. In the first study, I hypothesized that finger vibration at beta frequencies would generate stimulus-coherent neuronal firing in the neural network that generates the beta rhythm – thus revealing the nodes of this network. Data were analyzed for nineteen subjects (10 females). The coherent activity was revealed using a novel analysis technique that generated whole-brain maps of inter-trial synchrony during passive repetitive finger vibration at 23 Hz. These maps identified contralateral primary somatosensory cortex (SI), posterior parietal cortex, supplementary motor area and primary motor cortex (MI), and ipsilateral brainstem as nodes in the network. In the second study, I correlated changes in focused attention with modulations in beta band cortical responses to specify the functional significance of this activity. Data were analyzed for twelve subjects (7 females). With increased focused attention to the stimulus, I hypothesized that the beta band responses to finger vibration would be enhanced in areas involved in somatosensory processing. A transient increase in the magnitude of beta oscillations in MI (event-related synchronization) following vibration offset was significantly enhanced by attention, as compared to passive stimulation. In addition, attention caused the suppression of beta oscillations (event-related desynchronization, ERD) in ipsilateral SI beginning 1 second prior to vibration offset. Strong attention-modulation of the beta rhythm outside of contralateral SI implies that these changes are indicative of higher-order processing of afferent information. In the third study, I tested the hypothesis that synchrony between beta rhythms in contralateral MI and the relevant muscle supports effective neuronal communication. I correlated changes in task performance with corticomuscular coherence (CMC) during the sustained application of force to match a visually-presented target. Data were analyzed for eighteen subjects (9 females). As predicted, CMC in MI was significantly increased during improved performance in this task. This suggests that central-peripheral synchrony plays an important functional role in sustaining isometric muscle control. Concurrent beta ERD in bilateral SI and primary visual cortices during the contraction indicates the importance of afferent feedback in this task. Gender-related effects were not investigated in these studies. Beta band neuromagnetic responses to movement and somatosensation identify a pervasive neural network that is involved in processing the relevant properties of somatic input and regulating sustained motor output.

Advancements in movement restoration have accelerated in recent years while the restoration of somatosensation has progressed relatively slowly. This dissertation attempts to partially correct this oversight by developing an electrotactile feedback system that might be used to restore the sense of touch.Initially, the perceptual parameters of the skin regions likely to be used as a source of tactile information (the fingertip) and as a destination for electrotactile feedback (the back of the neck) were evaluated. The perceptual parameters of tactile threshold sensitivity, spatial acuity, and gain scaling were collected from subjects for both regions of skin. These same parameters were also gathered in response to electrotactile stimulation of the neck. The threshold sensitivity and spatial acuity of the fingertip was found to be far superior to that on the back of the neck, yet the mechanical perceptual gain scaling parameters of the neck were similar to that of the finger tip. Yet, the psychometric functions for electrical stimulation on the neck differed markedly in gain sensitivity from that of mechanical stimulation. A mapping function between the two modalities was then calculated based upon the tactile and electrotacile characterization data that was collected.An electrotactile feedback system was then developed based upon the calculated mapping function, allowing conversion of force applied to an artificial sensor on the fingertip to a perceptually equivalent electrical stimulus on the neck. The system proved to be quite effective: Subjects were able to effectively evaluate electrical stimulus that was derived from application of force to the sensor on the fingertip. The perceptual gain scaling for the feedback system matched that of natural mechanical stimulation.A grip force matching task was evaluated in test subjects under three conditions: a) normal tactile sensation, b) anesthesia of the fingers, and c) anesthesia of the fingers with restored tactile information via the electrotactile feedback system. The relative loss in grip-force matching ability when tactile feedback was abolished by local anesthetic was mild, indicating a strong ability for individuals to generate target force levels using other forms of feedback. Electrotactile feedback, therefore, offered only modest improvement when deployed in the anesthetized hand.

Transcutaneous electrical nerve stimulation (TENS) is a simple, non-invasive technique used in the control of chronic pain. Despite the success of TENS and its continued use for over twenty years, some patients either fail to respond or show only a partial response. Furthermore some patients respond initially to TENS but then become tolerant to its analgesic effects. The reasons for poor response to TENS are unknown; different clinics report widely differing success rates, and information on long-term efficacy is sparse. Furthermore, TENS is still administered on an empirical basis in which the patient determines by trial and error the most appropriate stimulator settings (i. e. electrical characteristics of TENS) to treat his or her particular pain. It is impossible to predict whether an individual patient will respond to TENS or which stimulator settings will be optimal. In an attempt to elucidate these problems, the clinical, electrophysiological, neuropharmacological, psychological and sociological factors that influence the analgesic effects and clinical efficacy of TENS have been examined in this thesis. Three clinical studies were performed. The first (Study 2.1) reviewed the use of TENS since its introduction to Newcastle Pain Relief Clinic in 1979. It was found that 1582 patients have been given a trial of TENS of which 927 (58.6%) continue to use a stimulator on a long-term basis (Study 2.1). The clinical use of TENS by 179 of these patients was examined in-depth (Study 2.2). Although previous literature suggests that TENS is most efficacious for pains of neurogenic (neuropathic) origin, it was found that any type of pain may respond. No relationships were found to exist between the electrical characteristics of TENS (i. e. stimulator settings) used by patients during TENS treatment and the cause and site of pain. However, patients utilised specific pulse frequencies and patterns and consistently used these settings on subsequent treatment sessions (Study 2.3). These clinical studies showed that in this population, 41.4% of patients failed to respond to TENS and half using TENS on a long-term basis achieved less than 50% relief of pain. Thus, a systematic investigation to determine optimal electrical characteristics of TENS was performed. Three experiments were undertaken to examine separately the analgesic effects of different electrical characteristics of TENS (pulse frequency, pulse pattern and stimulation mode) on cold-pressor pain in healthy subjects. The effects of a range of Long Abstract pulse frequencies (10Hz to 160Hz) applied to produce a 'strong but comfortable' electrical paraesthesia within the painful site were measured (Exp. 3.1). It was found that frequencies between 20-80Hz were most effective. However, no differential effects were observed between a range of pulse patterns (continuous, burst, modulation, random; Exp. 3.2). When TENS was applied in burst mode at an intensity sufficient to produce phasic muscle twitches at a site distant yet myotomally related to the site of pain (acupuncture-like TENS) a powerful analgesic effect was observed during and post-stimulation (Exp. 3.3). It is suggested that continuous mode stimulation at 80Hz, producing a 'strong but comfortable' electrical paraesthesia within the painful site, should be the primary TENS treatment choice in the clinic but that in selected cases AL-TENS may be more effective. A number of improvements in stimulator design are suggested. Further experiments were aimed at elucidating the mechanism of TENS effects by investigating the influence of TENS on electrophysiological and neuropharmacological variables. It was found that TENS reduced peak-to-peak amplitudes of the late waveform components (N1P2) of somatosensory evoked potentials (Exp. 4.1) and increased alpha, beta and theta activity of spontaneous EEG in healthy subjects (Exp. 4.2) and/or pain patients (Exp. 4.3). As TENS produced changes in SEPs elicited from non-painful stimuli, and also changes in spontaneous EEG in pain-free subjects, it is suggested that the effects of TENS may be due in part to changes in sensory processing at several levels in the nervous system which may not specific for the perception of pain. The surprising finding that TENS increased peripheral circulating met-enkephalin in chronic pain patients was attributed to a stress-like release although this observation remains to be confirmed using a larger population sample (Exp. 5.1). The results of these experiments suggest that baseline electrophysiological and neuropharmacological variables may be important determinants of individual response to TENS. Thus, a prospective investigation was undertaken on 29 patients who were undergoing a trial of TENS to control chronic pain, in an attempt to identify predictors of patient response. Patient response to TENS was related to baseline SEP amplitudes and spontaneous EEG but was not related to biochemical, psycho-social, personality or pain related factors (Exp. 6.1). Thus, patients with small peak-to-peak amplitudes of the SEP, and low power spectrum of spontaneous EEG showed poor response to TENS (Exp. 6.1). It is suggested that an individual's intrinsic central response pattern to external stimuli may influence response to TENS.

Thesis (Ph.D.) -- McMaster University, 2002. / Includes bibliographical references (leaves 90-105). Also available via World Wide Web.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Toledo, 2008. / "In partial fulfillment of the requirements for the degree of Master of Science in Biomedical Sciences." Title from title page of PDF document. Bibliography: p. 44-53, p. 77-90.