Browsing by Subject "Transcranial Magnetic Stimulation"
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Item Enhancement of learning: Does sleep benefit motor skill memory consolidation?(2010-12) Borich, Michael RobertPurpose: It remains unclear how the brain best recovers from neurologic injury and how to optimally focus rehabilitation approaches to maximize this recovery. Recent research has indicated that sleep may augment this recovery. Sleep has been shown to benefit memory consolidation for certain motor skills, but it remains unclear if this relationship exists for explicit, continuous, goal-directed motor skills with rehabilitation applications. We aimed to determine the neurobehavioral relationship between finger-tracking skill development and sleep following skill training in young, healthy subjects. Methods: Forty subjects were recruited to receive motor skill training in the morning (n=20) or the evening (n=20). Measures of skill and cortical excitability were collected before and after training. Following training, each group had a post-training interval consisting of waking activity or an interval containing sleep. After this twelve-hour interval, skill performance and cortical excitability were reassessed. Subjects underwent another twelve-hour interval containing either waking activity or a sleep episode and came back for a second assessment, twenty-four hours after training. A subset of subjects (n=10) underwent the same procedures except the training period involved simple, repeated movement of the finger. Results: Skill performance improved after training and then continued to improve offline during the first post-training interval. Improvement was not enhanced by sleep during this interval. Cortical excitability was not substantially altered by training but was related to level of skill performance at follow-up assessment. Sleep quality was also found to be related to level of skill at follow-up assessments. The skilled training period did not lead to significantly improved performance compared to simple movement activity. Discussion: These data suggest that sleep is not required for offline memory enhancement for a continuous, visuospatial finger-tracking skill. These findings are in agreement with recent literature indicating the type of motor skill trained may determine the beneficial effect of sleep on post-training information processing. These results, combined with related studies in patient populations, provide a foundation to evaluate the relationship between sleep, changes in neural activity, and the time course of continuous visuospatial motor skill learning in individuals following neurologic insult.Item Neuromodulation Using Primed Paired Associative Stimulation(2017-10) Frost, KatePurpose: Neuroplasticity governs mechanisms of cortical reorganization, adaptation and recovery following neural injury. Paired associative stimulation (PAS) alters neuroplasticity by pairing peripheral nerve and cortical stimuli which induces spike-timing-dependent-like plasticity. Preceding a principal bout of PAS that intends to weight plasticity in one direction (e.g. facilitatory) with a priming bout of PAS that intends to weight plasticity in the opposite direction (e.g. suppressive) may deploy homeostatic synaptic mechanisms resulting in a greater change from baseline corticospinal excitability. Exploring principles of homeostatic synaptic plasticity using all combinations of priming and principal suppressive PAS (PASLTD), facilitatory PAS (PASLTP) and sham PAS (PASSHAM), this study explores the efficacy of primed PAS as a method of neuromodulation and investigates a relationship between individual characteristics and response to PAS. Methods: Thirty-one healthy individuals were randomized into and completed one of two experiments. Experiment 1 (n=15, age 23.60 ± 2.33 years) investigated priming of PASLTD using a cross-over of the following four interventions separated by at least one-week washouts: 1. PASSHAM→PASLTD; 2. PASLTP→PASLTD; 3. PASLTD→PASLTD; 4. PASSHAM→PASSHAM. Experiment 2 (n=16, age 22.25 ± 2.28 years) investigated priming of PASLTP using a similar four-intervention cross-over of 1. PASSHAM→PASLTP; 2. PASLTD→PASLTP; 3. PASLTP→PASLTP; 4. PASSHAM→PASSHAM. The primary outcome for both experiments was the average peak-to-peak amplitude of 20 motor evoked potentials (MEPs) recorded at baseline and 0, 10, 20, 30, 40, 50 and 60 minutes following intervention. Secondary outcomes included presence of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and the latency of MEPs collected using an anterior-posterior current flow across the central sulcus. Results: In Experiment 1, the PASLTP→PASLTD intervention produced a significant increase from baseline corticospinal excitability. Nonresponders had a significantly higher presence of the BDNF Val66Met polymorphism. In Experiment 2, no intervention produced a significant change from baseline excitability. Priming did not convert individual nonresponders to responders for any PAS intervention. Discussion: Our results highlight the complexity of synaptic plasticity and the difficulty in harnessing mechanisms of plasticity to augment neuromodulation strategies. Individual characteristics may influence response to PASLTD and optimal protocols may need to be established for stratified groups.Item Neurophysiology and Neuromodulation: Incorporating Task Training to Harness Cerebellar Neuroplasticity in Rehabilitation(2018-12) Summers, RebekahDystonia is a neurologic movement disorder characterized by involuntary muscular contractions that may be sustained or intermittent, resulting in abnormal movement and postures. The burden associated with dystonia is considerable as there is no cure or known pathophysiology. Despite the immediate need for innovative treatments, alternative interventions are barred by a lack of understanding of the pathology and mechanism of dystonia. To develop and refine effective rehabilitative interventions for patients with focal dystonia, the pathology must be better understood and methods to assess corticospinal excitability refined. There are emerging lines of evidence that suggest there is an altered balance of inhibition and excitation contributing to the cause of dystonia. This may be due to dysfunctional interplays between the cerebellum, basal ganglia and motor cortex that generate network dysfunction. One strategy to study the affected brain regions in people with dystonia is via the use of non-invasive brain stimulation to measure and modulate motor cortical excitability. The overall goal of this dissertation is to evaluate the use of non-invasive brain stimulation, using both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), to assess and modulate aspects of neurophysiology and neuroplasticity in people with cervical dystonia (CD) and healthy controls. Four studies were designed to achieve this research goal. 1) The first study evaluated the validity of using fine-wire electrodes to record motor evoked responses. Fine-wire electrodes were found to be a valid means to record muscle responses, allowing the investigation of motor cortical excitability in small or intrinsic muscles that can be affected by dystonia. 2) The second study evaluated the use of cerebellar neuromodulation with simultaneous task training in healthy adults. This investigation revealed that cerebellar neuromodulation interfered with practice-related changes in corticospinal excitability. 3) The third study evaluated ipsilateral and contralateral motor evoked responses in the upper trapezius between people with CD and controls and provided evidence that inhibitory responses are asymmetrically regulated in people with CD. 4) The fourth study explored the use of cerebellar tDCS to modulate eye-blink classical conditioning and measures of motor cortical excitability. The results suggest poor conditioning responses in all participants, limiting the interpretation of the study; however, no differences between groups were detected in outcomes of motor cortical excitability. These studies add to our understanding of how non-invasive brain stimulation may be used to assess measures of excitation and inhibition in-vivo to probe aspects of neuroplasticity and the effects of neuromodulation.Item Tools for Improving and Understanding Transcranial Magnetic Stimulation(2020-10) Shirinpour, SeyedsinaTranscranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that can modulate brain activity through a time-varying magnetic field which induces an electric field in the brain. TMS has been used extensively in research and clinical applications because of its ability to non-surgically deliver suprathreshold stimulation to the brain in a safe manner. Despite the popularity of TMS, there are still major gaps in our understanding of how TMS modulates brain activity on a fundamental neuroscience level. Therefore, the TMS mechanism of action is still under investigation. Improved stimulation technology and computational tools have promise for bridging this gap in our understanding. In my dissertation, I developed new methodologies and computational models that advance the current state-of-the-art in TMS and can assist researchers in their future investigations. First, I describe a closed-loop TMS system that can deliver the stimulation based on the instantaneous brain state. This allows researchers to investigate the role of the intrinsic neural activity on the brain’s responsiveness to TMS. To further provide insights into how TMS modulates brain activity at a large brain-scale and the neuronal level, I developed a multi-scale modeling paradigm. Computational simulations have been used extensively to estimate electric fields induced in the brain by TMS, however, their results still need to be validated. To this end, in the second study here, I utilize analytical solutions to evaluate these numerical simulations. After confirming the accuracy of the electric field models, I incorporated multi-scale modeling to further investigate how the externally induced electric fields alter the behavior of neurons and their subcellular activity. The subcellular modeling of neurons allows researchers to study the lasting effects of TMS in neurons in a sophisticated multi-scale model for the first time. In summary, the tools developed in my PhD can facilitate answering long-lasting questions about the TMS mechanism of action. This, in turn, will enable developing more effective TMS protocols/equipment which can lead to improved clinical outcomes in the treatment of psychiatric and neurological disorders with TMS.