Browsing by Subject "neuromodulation"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Brain Circuitry, Neuromodulation, and Rehabilitation in Unilateral Cerebral Palsy
    (2017-12) Rich, Tonya
    Background We investigated the safety and preliminary efficacy of transcranial direct current stimulation (tDCS) combined with occupation-centered, bimanual training in children and young adults with unilateral cerebral palsy (UCP). This study utilized cathodal tDCS to the non-lesioned hemisphere, an intervention hypothesized to inhibit excitation of the non-lesioned hemisphere. Methods Eight participants with contralateral or bilateral corticospinal tract (CST) circuitry participated in an open-label study with multiple-baseline design and combined intervention. The combined intervention consisted of 10 sessions of tDCS applied to the non-lesioned hemisphere (20 minutes) concurrently with bimanual motor training tailored to the child’s goals (120 minutes). We measured safety by monitoring the frequency of adverse events and measured intervention efficacy with the Assisting Hand Assessment. Other measurements included subjective (Canadian Occupational Performance Measure - COPM) and neurophysiologic (single pulse amplitude, cortical silent period - CSP, and motor mapping) data. Results All 8 participants were evaluated with all safety, behavioral, and neurophysiologic measures. No serious adverse events occurred. All children demonstrated improvement on at least one measure of hand function. We noted achievements of clinically significant improvements on hand function measures however no significant differences with group-level pre/post comparisons were found. Significant group-level increases were observed with subjective measures such as performance (p=.01, mean change: 2.76, 95% CI 1.77 to 3.74) and satisfaction (p=.02, mean change: 2.54, 95% CI: 1.34 to 3.74) on the COPM and the ABILHAND (p=0.04, mean change 0.19, 95% CI: 0.02 to 0.37). Neurophysiologic data suggest a decrease in amplitude of single-pulse transcranial magnetic stimulation (TMS) responses in the non-lesioned hemisphere as hypothesized, although group-level pre/post-test comparisons were non-significant. However, a decrease in the CSP duration (p<.03) and increases in the motor mapping sites suggest an excitatory influence of cathodal tDCS on the non-lesioned hemisphere. Conclusions The neurophysiologic effect of cathodal tDCS to the non-lesioned hemisphere confirmed the hypothesized inhibitory effect on amplitude of responses but also documented an excitatory effect on CSP duration and mapping sites. Future studies combining additional assessment measures and computational modeling will contribute to our understanding of the neurophysiologic influence of tDCS in children with UCP. Clinical Trials Registration: Clinicaltrials.gov NCT 02250092.
  • Thumbnail Image
    Item
    Combining TMS and EEG for Characterizing Motor Network Interactions and Improving Motor Recovery after Stroke
    (2016-12) Johnson, Nessa
    Imaging of electrophysiological activity within the brain is crucial to understanding function in both healthy and disease conditions. The overall goal of this dissertation is to use both non-invasive neuromodulation and non-invasive neuroimaging to characterize and manipulate underlying neurological network dynamics in both healthy and stroke affected subjects. The two main applications of work are for the evaluation of peripheral motor activity on motor network dynamics in healthy subjects, and as a brain-based treatment for motor recovery after stroke. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) imaging can be used to analyze cortical reactivity and connectivity of underlying brain networks. However, the effect of corticospinal and peripheral muscle activity on TMS-evoked potentials (TEPs), particularly in motor areas, is not well understood. One aim of the present dissertation is to evaluate the relationship between cortico-spinal activity, in the form of peripheral motor-evoked potentials (MEPs), and the TEPs from motor areas, along with the connectivity among activated brain areas. This research demonstrates that TMS-EEG, along with adaptive connectivity estimators, can be used to evaluate the cortical dynamics associated with sensorimotor integration and proprioceptive manipulation. Stroke is a devastating neurological disorder which can result in lasting impairment affecting quality-of-life. Combining contralesional repetitive TMS (rTMS) with EEG-based brain-computer interface (BCI) training can address motor impairment after stroke by down-regulating exaggerated inhibition from the contralesional hemisphere and encouraging ipsilesional activation. Another aim of this dissertation was to evaluate the efficacy of combined rTMS+BCI, compared to sham rTMS+BCI, and BCI alone, on motor recovery after stroke in subjects with lasting motor paresis. As evaluated in a series of stroke patients, such a brain-based neuromodulatory and imaging approach for rehabilitation could potentially lead to greater understanding of the influence of brain network dynamics in recovery and design of optimal treatment strategies for individual patients. Our findings demonstrate the feasibility and efficacy of not only combined rTMS+BCI but also BCI alone, as demonstrated by significant improvements over time in behavioral and electrophysiological measures. In summary, the present dissertation research developed and evaluated the combination of neuromodulation and neuroimaging for the non-invasive mapping of motor network activities in the diseased and normal brain. Evaluations were conducted in healthy controls to evaluate the influence of peripheral muscle activity on resulting neural network activity, as well as in stroke patients to provide a brain-based treatment for motor rehabilitation. The results obtained suggest the importance of non-invasive spatiotemporal neuroimaging, along with non-invasive neuromodulation, for providing insight into neuroscience questions and providing novel treatments for clinical problems in a brain-based manner.
  • Thumbnail Image
    Item
    Delineating the Neural Correlates of Visual Awareness through the Integration of Multimodal Neuroimaging and Noninvasive Electrical Neuromodulation
    (2016-12) Roy, Abhrajeet
    In recent years, there has been a push to develop a fundamental theory of consciousness in the neuroscience community. However, to date, the physical mechanisms underlying conscious awareness remain unclear. The major aim of this dissertation was to delineate neural correlates of consciousness through the integration of multimodal functional neuroimaging and noninvasive electrical neuromodulation. To this extent, we utilized simultaneous EEG-fMRI imaging to investigate both the electrophysiological and hemodynamic correlates of visual awareness during binocular rivalry. Binocular rivalry is a classic visual phenomenon in which one’s perception spontaneously fluctuates between two different images that are presented simultaneously to the viewer, one to each eye. These random alternations in visual awareness occur despite the static dichoptic input, making binocular rivalry a promising framework for the study of brain networks involved in consciousness. In addition, we evaluated the feasibility of using transcranial direct/alternating current stimulation to modulate behavioral and electrophysiological correlates of rivalry and visual perception in general. Our findings point to the existence of multiple neural networks operating independently during rivalry for its resolution. Differential patterns of activation in fronto-parietal networks and across the default mode network were associated with both subjective changes in visual awareness and maintaining perceptual stability during rivalry. Collectively, our findings suggest that suppression of eye-specific neural activity during rivalry is mainly due to bottom-up processing in early visual cortex, while fronto-parietal activity appears more generalized and predominantly related to attentional processes and conscious awareness of changes in sensory information.
  • Thumbnail Image
    Item
    A High-Precision Bioelectric Neural Interface Toward Human-Machine Symbiosis
    (2021-01) Nguyen, Anh Tuan
    Objective. A symbiosis of human intelligence and artificial intelligence (AI) cannot be achieved without establishing an intuitive, bidirectional, and high-bandwidth information conduit between the minds and machines. Approach. Here we focus on developing high-precision bioelectronics underlying a new class of bioelectric neural interfaces that could bring us one step closer to this feat. We pioneer new circuit techniques, including frequency shaping (FS), redundant sensing (RS), RS-based super-resolution, and redundant crossfire (RXF), to enhance the effective resolution of neural recording and stimulation. These fundamentals allow the implementation of a series of fully-integrated microchips called Neuronix capable of acquiring low-noise neural signals and delivering high-precision electrical microstimulation. The Neuronix chips are incorporated to create miniaturized neuromodulation devices, including the Scorpius system, to enable bidirectional communications with neural circuits. Results. In a clinical study with human amputees, the Scorpius system helps establish a peripheral nerve interface that allows deep learning-based AI models to read and decode the patients' intents of moving individual fingers. Our analysis of acquired electroneurography (ENG) signals demonstrates this robust nerve interface has a sufficient information capacity to enable real-time control of a multi-degree-of-freedom (DOF) neuroprosthetic hand with near-natural dexterity and intuitiveness while simultaneously delivering somatosensory feedback. Significance. Our study layouts the principled foundation toward not only a dexterous control strategy for advanced neuroprostheses but also an intuitive conduit for connecting the human minds and machines. This opens up possibilities for many biomedical applications and manifests the basis of the future human-machine symbiosis.
  • Thumbnail Image
    Item
    Inducing Neural Plasticity and Modulation Using Multisensory Stimulation: Techniques for Sensory Disorder Treatment
    (2017-06) Gloeckner, Cory Dale
    In this dissertation, we characterized the modulatory and plasticity effects of paired multisensory stimulation on neural firing in sensory systems across the brain. In the auditory system, we discovered that electrical somatosensory stimulation can either suppress or facilitate neural firing in the inferior colliculus (IC) and primary auditory cortex (A1) depending stimulation location. We also tested plasticity effects in A1 in response to paired somatosensory and acoustic stimulation with different inter-stimulus delays in anesthetized guinea pigs, and found that plasticity induced by paired acoustic and right mastoid stimulation was consistently suppressive regardless of delay, but paired acoustic and pinna stimulation was timing-dependent, where one inter-stimulus delay was consistently suppressive while other delays induced random changes. These experiments were repeated in awake animals with paired acoustic and pinna stimulation, and two animal groups of different stress levels were used to assess stress effects on plasticity. We found that in low-stress animals, the same inter-stimulus delay was consistently suppressive and a neighboring delay was consistently facilitative across all animals, which matches previous invasive spike-timing dependent plasticity studies (anesthesia may have affected these trends). Meanwhile, high-stress animal results were not consistent with expected time dependence and exhibited no trends across inter-stimulus delays, indicating that stress can have adverse effects on neuromodulation plasticity outcomes. In all other primary sensory cortices, we found that differential effects can be induced with paired sensory stimulation such that the location, amount, type, and timing of plasticity can be controlled by strategically choosing sensory stimulation parameters for modulation of each sensory cortex. We also investigated the ability to target subpopulations of neurons within a brain region and found that by stimulating at levels near activation thresholds, specific subpopulations of IC neurons can be targeted by varying somatosensory stimulation location. Furthermore, acoustic stimulation can excite or modulate specific areas of somatosensory cortex, and we mapped the guinea pig homunculus to characterize this. Overall, these findings illustrate the immense interconnectivity between sensory systems, and multisensory stimulation may provide a noninvasive neuromodulation approach for inducing controlled plasticity to disrupt pathogenic neural activity in neural sensory disorders, such as tinnitus and pain.
  • Thumbnail Image
    Item
    Invasive and Noninvasive Brain Stimulation Strategies for the Treatment of Tinnitus
    (2014-06) Markovitz, Craig
    The central auditory system consists of a series of relay stations at which auditory information is processed in stages before reaching the auditory cortex for sound perception. However, descending projections and non-auditory inputs into the central auditory system also play a vital role in shaping neural coding along the auditory pathway. The work in this thesis seeks to investigate the organization and role of these modulatory pathways of the central auditory system, particularly to devise and improve upon existing neuromodulation strategies for treating neurological disorders related to the auditory system, including tinnitus and hyperacusis. Through animal studies, we have shown that the descending projections from primary auditory cortex to subcortical centers, particularly the central nucleus of the inferior colliculus, exhibit a precise spatial organization based on frequency coding, supporting the role of the corticofugal system for modulating specific and relevant coding features within the ascending auditory system. Further, by combining stimulation of auditory cortex with an irrelevant acoustic stimulus, we were able to suppress neural firing throughout the inferior colliculus, revealing at least one potential mechanism for gating relevant versus irrelevant sound inputs. Targeting this gating mechanism could provide a neuromodulation treatment for tinnitus and/or hyperacusis which are associated with hyperactivity across auditory centers. Finally, we introduce a new neuromodulation approach using simultaneous noninvasive stimulation of multimodal pathways, focusing initially on somatosensory and auditory inputs. We present our proof-of-concept studies showing the ability to modulate neural coding in the inferior colliculus up to auditory cortex in a systematic way depending on the stimulation parameters (e.g., interstimulus interval and body stimulation location). These invasive and noninvasive techniques for modulating the brain provide potential options for the treatment of hearing disorders as well as other neurological and neuropsychiatric conditions.