Design, Characterization, and In Vivo Applications of a Novel, Concentric, Hybrid micro-ECoG Array

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Description
Neurological disorders are the leading cause of physical and cognitive declineglobally and affect nearly 15% of the current worldwide population. These disorders include, but are not limited to, epilepsy, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. With the aging population, an increase

Neurological disorders are the leading cause of physical and cognitive declineglobally and affect nearly 15% of the current worldwide population. These disorders include, but are not limited to, epilepsy, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. With the aging population, an increase in the prevalence of neurodegenerative disorders is expected. Electrophysiological monitoring of neural signals has been the gold standard for clinicians in diagnosing and treating neurological disorders. However, advances in detection and stimulation techniques have paved the way for relevant information not seen by standard procedures to be captured and used in patient treatment. Amongst these advances have been improved analysis of higher frequency activity and the increased concentration of alternative biomarkers, specifically pH change, during states of increased neural activity. The design and fabrication of devices with the ability to reliably interface with the brain on multiple scales and modalities has been a significant challenge. This dissertation introduces a novel, concentric, multi-scale micro-ECoG array for neural applications specifically designed for seizure detection in epileptic patients. This work investigates simultaneous detection and recording of adjacent neural tissue using electrodes of different sizes during neural events. Signal fidelity from electrodes of different sizes during in vivo experimentation are explored and analyzed to highlight the advantages and disadvantages of using varying electrode sizes. Furthermore, the novel multi-scale array was modified to perform multi-analyte detection experiments of pH change and electrophysiological activity on the cortical surface during epileptic events. This device highlights the ability to accurately monitor relevant information from multiple electrode sizes and concurrently monitor multiple biomarkers during clinical periods in one procedure that typically requires multiple surgeries.
Date Created
2024
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Physiological Changes during Non-Invasive Supraorbital Trigeminal Nerve Stimulation

Description

Neuromodulation is an emerging field of research that has a proven therapeutic benefit on a number of neurological disorders, including epilepsy and stroke. It is characterized by using exogenous stimulation to modify neural activity. Prior studies have shown the positive

Neuromodulation is an emerging field of research that has a proven therapeutic benefit on a number of neurological disorders, including epilepsy and stroke. It is characterized by using exogenous stimulation to modify neural activity. Prior studies have shown the positive effect of non-invasive trigeminal nerve stimulation (TNS) on motor learning. However, few studies have explored the effect of this specific neuromodulatory method on the underlying physiological processes, including heart rate variability (HRV), facial skin temperatures, skin conductance level, and respiratory rate. Here we present preliminary results of the effects of 3kHz supraorbital TNS on HRV using non-linear (Poincaré plot descriptors) and time-domain (SDNN) measures of analysis. Twenty-one (21) healthy adult subjects were randomly assigned to 2 groups: 3kHz Active stimulation (n=11) and Sham (n=10). Participants’ physiological markers were monitored continuously across three blocks: one ten-minute baseline block, one twenty-minute treatment block, and one ten-minute recovery block. TNS targeting the ophthalmic branches of the trigeminal nerve was delivered during the treatment block for twenty minutes in 30 sec. ON/OFF cycles. The active stimulation group exhibited larger values of all Poincaré descriptors and SDNN during blocks two and three, signifying increased HRV and autonomic nervous system activity.

Date Created
2023-05
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Visuomotor Rotation Task to Assess Sensorimotor Adaptation

Description

Sensorimotor adaptation is a type of learning that allows sustaining accurate movements by adjusting motor output. This allows the brain to adapt to temporary changes when engaged in a certain task. Within sensorimotor adaptation, visuomotor adaptation (VMA) is one’s ability

Sensorimotor adaptation is a type of learning that allows sustaining accurate movements by adjusting motor output. This allows the brain to adapt to temporary changes when engaged in a certain task. Within sensorimotor adaptation, visuomotor adaptation (VMA) is one’s ability to correct a visual perturbation. In this study, we present preliminary results on the effects of VMA with the control group, compared to groups undergoing trigeminal nerve stimulation (TNS) or SHAM (placebo) effects. Twenty-two healthy subjects with no past medical history participated in this study. Subjects performed a visuomotor rotation task, which required gradually adapting to a perturbation between hand motion and corresponding visual feedback. Five total blocks were completed: two familiarization blocks, one baseline block, one rotation block with a 30◦ counterclockwise rotation, and one washout block with no rotation. The control group performed better than the 120 Hz (TNS) and SHAM groups due to less directional error (DE) on the respective learning curves. Additionally, the control group adapted faster (less DE) than the SHAM groups that either felt stimulation, or did not feel the stimulation. The results yield new information regarding VMA which can be used in the future when comparing sensorimotor adaptation and its many applications.

Date Created
2023-05
Agent

An Experimental Evaluation of the Influence of Transcranial Direct Current Stimulation to the Trigeminal Nerve on Attention and Arousal

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Description
Sustained attention, the ability to concentrate on a stimulus or task over a prolonged period, is essential for goal pursuit and fulfillment. Sustained attention failures can have catastrophic consequences, underscoring the importance of understanding the mechanisms that underlie variability in

Sustained attention, the ability to concentrate on a stimulus or task over a prolonged period, is essential for goal pursuit and fulfillment. Sustained attention failures can have catastrophic consequences, underscoring the importance of understanding the mechanisms that underlie variability in sustained attention, and developing interventions targeting these mechanisms to reduce such failures. A growing body of research implicates the brainstem locus coeruleus (LC) as a core modulator of attention and arousal. Activation of LC afferents, such as the trigeminal nerve, may indirectly modulate the LC. The altered LC activity could theoretically be tracked via well-established psychological and physiological indicators of attention and arousal, such as performance, self-reports of attention state, and pupillary activity during attention tasks. The present study tests the hypothesis that continuous transcranial direct current stimulation (tDCS) over the trigeminal nerve of the face improves attentional state, attentional performance, and pupillary reactivity via indirect modulation of the LC. Participants received 2 mA of anodal or cathodal stimulation or sham stimulation over the dorsolateral prefrontal cortex while completing the Psychomotor Vigilance Task. Participants occasionally reported on their attentional state. Pupillary activity was recorded continuously throughout the task. To compare patterns of attention task performance, frequency of task-unrelated thoughts, and pupillary activity across time by stimulation condition, linear mixed-effects models were implemented. The results replicate the complex interplay between attentional state, attentional performance, and pupillary activity reported in the literature. Specifically, a ubiquitous pattern of performance deterioration was observed, which coincided with an increase in task-unrelated thoughts and reduced pretrial and task-evoked pupil responses. However, tDCS over the face did not produce significant effects compared to the sham condition in attention task performance, proportion of task-unrelated thoughts, and pupillary activity that would indicate LC modulation. This study addresses the causal relations between LC activity, attentional state, attentional performance, and pupillary reactivity that are still poorly understood in human subjects. The findings reported here support the dominant theory of the role of the LC in attentional processes but fail to support hypotheses suggesting that tDCS of the trigeminal nerve influences activity of the LC and indicators of LC activity.
Date Created
2022
Agent

Micro-Scale In Vivo Human Electrophysiological Functional Connectivity During Simple Language Production and Parkinson’s Disease

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Description
Information processing in the brain is mediated by network interactions between anatomically distant (centimeters apart) regions of cortex and network action is fundamental to human behavior. Disruptive activity of these networks may allow a variety of diseases to develop. Degradation

Information processing in the brain is mediated by network interactions between anatomically distant (centimeters apart) regions of cortex and network action is fundamental to human behavior. Disruptive activity of these networks may allow a variety of diseases to develop. Degradation or loss of network function in the brain can affect many aspects of the human experience; motor disorder, language difficulties, memory loss, mood swings, and more. The cortico-basal ganglia loop is a system of networks in the brain between the cortex, basal ganglia, the thalamus, and back to the cortex. It is not one singular circuit, but rather a series of parallel circuits that are relevant towards motor output, motor planning, and motivation and reward. Studying the relationship between basal ganglia neurons and cortical local field potentials may lead to insights about neurodegenerative diseases and how these diseases change the cortico-basal ganglia circuit. Speech and language are uniquely human and require the coactivation of several brain regions. The various aspects of language are spread over the temporal lobe and parts of the occipital, parietal, and frontal lobe. However, the core network for speech production involves collaboration between phonologic retrieval (encoding ideas into syllabic representations) from Wernicke’s area, and phonemic encoding (translating syllables into motor articulations) from Broca’s area. Studying the coactivation of these brain regions during a repetitive speech production task may lead to a greater understanding of their electrophysiological functional connectivity. The primary purpose of the work presented in this document is to validate the use of subdural microelectrodes in electrophysiological functional connectivity research as these devices best match the spatial and temporal scales of brain activity. Neuron populations in the cortex are organized into functional units called cortical columns. These cortical columns operate on the sub-millisecond temporal and millimeter spatial scale. The study of brain networks, both in healthy and unwell individuals, may reveal new methodologies of treatment or management for disease and injury, as well as contribute to our scientific understanding of how the brain works.
Date Created
2021
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The effects of square breathing as a vagal nerve stimulant on learning new motor strategies in unreliable proprioceptive conditions

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Description

Lack of proprioceptive feedback is one cause for the high upper-limb prosthesis abandonment rate. The lack of environmental interaction normalcy from unreliable proprioception creates dissatisfaction among prosthesis users. The purpose of this experiment is to investigate the effects of square

Lack of proprioceptive feedback is one cause for the high upper-limb prosthesis abandonment rate. The lack of environmental interaction normalcy from unreliable proprioception creates dissatisfaction among prosthesis users. The purpose of this experiment is to investigate the effects of square breathing on learning to navigate without reliable proprioception. Square breathing is thought to influence the vagus nerve which is linked to increased learning rates. In this experiment, participants were instructed to reach toward targets in a semi-immersive virtual reality environment. Directional error, peak velocity, and peak acceleration of the reaching hand were investigated before and after participants underwent square breathing training. As the results of<br/>this experiment are inconclusive, further investigation needs to be done with larger sample sizes and examining unperturbed data to fully understand the effects of square breathing on learning new motor strategies in unreliable proprioceptive conditions.

Date Created
2021-05
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Transcranial Focused Ultrasound for Modulation of Attention Networks in Humans

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Description
Transcranial focused ultrasound (tFUS) is a unique neurostimulation modality with potential to develop into a highly sophisticated and effective tool. Unlike any other noninvasive neurostimulation technique, tFUS has a high spatial resolution (on the order of millimeters) and can penetrate

Transcranial focused ultrasound (tFUS) is a unique neurostimulation modality with potential to develop into a highly sophisticated and effective tool. Unlike any other noninvasive neurostimulation technique, tFUS has a high spatial resolution (on the order of millimeters) and can penetrate across the skull, deep into the brain. Sub-thermal tFUS has been shown to induce changes in EEG and fMRI, as well as perception and mood. This study investigates the possibility of using tFUS to modulate brain networks involved in attention and cognitive control.Three different brain areas linked to saliency, cognitive control, and emotion within the cingulo-opercular network were stimulated with tFUS while subjects performed behavioral paradigms. The first study targeted the dorsal anterior cingulate cortex (dACC), which is associated with performance on cognitive attention tasks, conflict, error, and, emotion. Subjects performed a variant of the Erikson Flanker task in which emotional faces (fear, neutral or scrambled) were displayed in the background as distractors. tFUS significantly reduced the reaction time (RT) delay induced by faces; there were significant differences between tFUS and Sham groups in event related potentials (ERP), event related spectral perturbation (ERSP), conflict and error processing, and heart rate variability (HRV).
The second study used the same behavioral paradigm, but targeted tFUS to the right anterior insula/frontal operculum (aIns/fO). The aIns/fO is implicated in saliency, cognitive control, interoceptive awareness, autonomic function, and emotion. tFUS was found to significantly alter ERP, ERSP, conflict and error processing, and HRV responses.
The third study targeted tFUS to the right inferior frontal gyrus (rIFG), employing the Stop Signal task to study inhibition. tFUS affected ERPs and improved stopping speed. Using network modeling, causal evidence is presented for rIFG influence on subcortical nodes in stopping.
This work provides preliminarily evidence that tFUS can be used to modulate broader network function through a single node, affecting neurophysiological processing, physiologic responses, and behavioral performance. Additionally it can be used as a tool to elucidate network function. These studies suggest tFUS has the potential to affect cognitive function as a clinical tool, and perhaps even enhance wellbeing and expand conscious awareness.
Date Created
2020
Agent

The Safety, Tolerability, and Efficacy of Electrical Nerve Stimulation on Physiological Activity and Golf Performance

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Description
Electrical nerve stimulation is a promising drug-free technology that could treat a variety of ailments and disorders. Methods like Vagus Nerve Stimulation have been used for decades to treat disorders like epilepsy, and research with non-invasive vagus nerve stimulation has

Electrical nerve stimulation is a promising drug-free technology that could treat a variety of ailments and disorders. Methods like Vagus Nerve Stimulation have been used for decades to treat disorders like epilepsy, and research with non-invasive vagus nerve stimulation has shown similar effects as its invasive counterpart. Non-invasive nerve stimulation methods like vagus nerve stimulation could help millions of people treat and manage various disorders.

This study observed the effects of three different non-invasive nerve stimulation paradigms in human participants. The first study analyzed the safety and efficacy of transcutaneous auricular vagal nerve stimulation in healthy humans using a bilateral stimulation protocol with uniquely designed dry-hydrogel electrodes. Results demonstrate bilateral auricular vagal nerve stimulation has significant effects on specific parameters of autonomic activity and is safe and well tolerated. The second study analyzed the effects of non-invasive electrical stimulation of a region on the side of the neck that contains the Great Auricular Nerve and the Auricular Branch of the Vagus Nerve called the tympanomastoid fissure on golf hitting performance in healthy golfers. Results did not show significant effects on hitting performance or physiological activity, but the nerve stimulation had significant effects on reducing state-anxiety and improving the quality of feel of each shot. The third study analyzed the effects of non-invasive nerve stimulation of cervical nerves on the back of the neck on putting performance of yips-affected golfers. Results demonstrated that cervical nerve stimulation had significant effects on improving putting performance but did not have significant effects on physiological activity. Data from these studies show there are potential applications for non-invasive electrical nerve stimulation for healthy and athletic populations. Future research should also examine the effects of these stimulation methods in clinical populations.
Date Created
2020
Agent

Using Graphene as a Flex Resistor to Detect Biodynamics

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Description
Over the past 30 years the use of graphene has been increasing at a rapid rate. The reason why graphene has become more popular is because it is starting to be understood better, and researchers are starting to recognize graphene’s

Over the past 30 years the use of graphene has been increasing at a rapid rate. The reason why graphene has become more popular is because it is starting to be understood better, and researchers are starting to recognize graphene’s unique properties. Graphene is a single atomic layer of graphite, and graphite is a three-dimensional cube base structure of carbon. Graphite has a high conductivity rate, and graphene has an even higher conductivity, meaning that graphene makes for an excellent resistor in any hardware system. Graphene is flexible, has high durability, and can vary in resistance based on its shape (Sharon 2015). With graphene being able to change its resistivity, it can act as different types of sensors. These sensors include measuring pressure, resistance, force, strain, and angle. One problem across the globe is that patients have arthritis, decaying bone density, and injuries which can easily go mistreated or not treated at all. It can be hard to determine the severity of injuries in joints by observation of the patient. There are tools and equipment that will allow a doctor to track the force and degrees of motion of certain joints, but they are mostly limited to hospitals. With graphene acting as a sensor it can be embedded into casts, braces, and even clothing. With a mobile sensor that relays accurate and continuous data to a doctor they can more precisely determine a therapy or recovery time that will better suit the patients’ needs. In this project the graphene was used to measure the angle of a patient’s wrist while they were wearing a wrist brace. From the data collected, the graphene was able to track the user’s movement of their wrist as they moved it in a single direction. The data showed the angle of the wrist ranging from zero degrees to 90 degrees. This proves that graphene can shape the way biosensing is accomplished. Biodynamics is a growing field, and with more injuries everyday it is important to study graphene and how it can be used to diagnose and prevent injuries related to joints. Graphene can be used as a biosensor which can then be implemented into a brace to allow for accurate biodynamic tracking.
Date Created
2020-05
Agent

Acute Vagus Nerve Stimulation Spares Motor Map Topography and Reduces Infarct Size After Cortical Ischemia

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Description
Stroke remains a leading cause of adult disability in the United States. In recent studies, chronic vagus nerve stimulation (VNS) has been proven to enhance functional recovery when paired with motor rehabilitation training after stroke. Other studies have

Stroke remains a leading cause of adult disability in the United States. In recent studies, chronic vagus nerve stimulation (VNS) has been proven to enhance functional recovery when paired with motor rehabilitation training after stroke. Other studies have also demonstrated that delivering VNS during the onset of a stroke may elicit some neuroprotective effects as observed in remaining neural tissue and motor function. While these studies have demonstrated the benefits of VNS as a treatment or therapy in combatting stroke damage, the mechanisms responsible for these effects are still not well understood or known. The aim of this research was to further investigate the mechanisms underlying the efficacy of acute VNS treatment of stroke by observing the effect of VNS when applied after the onset of stroke. Animals were randomly assigned to three groups: Stroke animals received cortical ischemia (ET-1 injection), VNS+Stroke animals received acute VNS starting within 48 hours after cortical ischemia and continuing once per day for three days, or Control animals which received neither the injury nor stimulation. Results showed that stroke animals receiving acute VNS had smaller lesion volumes and larger motor cortical maps than those in the Stroke group. The results suggest VNS may confer neuroprotective effects when delivered within the first 96 hours of stroke.
Date Created
2019
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