Matching Items (9)
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- All Subjects: Neural stimulation
- All Subjects: Brains
- Creators: Muthuswamy, Jitendran
- Creators: Rahman, Qasim
- Creators: Bimonte-Nelson, Heather
- Status: Published
Description
Neurostimulation methods currently include deep brain stimulation (DBS), optogenetic, transcranial direct-current stimulation (tDCS), and transcranial magnetic stimulation (TMS). TMS and tDCS are noninvasive techniques whereas DBS and optogenetic require surgical implantation of electrodes or light emitting devices. All approaches, except for optogenetic, have been implemented in clinical settings because they have demonstrated therapeutic utility and clinical efficacy for neurological and psychiatric disorders. When applied for therapeutic applications, these techniques suffer from limitations that hinder the progression of its intended use to treat compromised brain function. DBS requires an invasive surgical procedure that surfaces complications from infection, longevity of electrical components, and immune responses to foreign materials. Both TMS and tDCS circumvent the problems seen with DBS as they are noninvasive procedures, but they fail to produce the spatial resolution required to target specific brain structures. Realizing these restrictions, we sought out to use ultrasound as a neurostimulation modality. Ultrasound is capable of achieving greater resolution than TMS and tDCS, as we have demonstrated a ~2mm lateral resolution, which can be delivered noninvasively. These characteristics place ultrasound superior to current neurostimulation methods. For these reasons, this dissertation provides a developed protocol to use transcranial pulsed ultrasound (TPU) as a neurostimulation technique. These investigations implement electrophysiological, optophysiological, immunohistological, and behavioral methods to elucidate the effects of ultrasound on the central nervous system and raise questions about the functional consequences. Intriguingly, we showed that TPU was also capable of stimulating intact sub-cortical circuits in the anesthetized mouse. These data reveal that TPU can evoke synchronous oscillations in the hippocampus in addition to increasing expression of brain-derived neurotrophic factor (BDNF). Considering these observations, and the ability to noninvasively stimulate neuronal activity on a mesoscale resolution, reveals a potential avenue to be effective in clinical settings where current brain stimulation techniques have shown to be beneficial. Thus, the results explained by this dissertation help to pronounce the significance for these protocols to gain translational recognition.
ContributorsTufail, Yusuf Zahid (Author) / Tyler, William J (Thesis advisor) / Duch, Carsten (Committee member) / Muthuswamy, Jitendran (Committee member) / Santello, Marco (Committee member) / Tillery, Stephen H (Committee member) / Arizona State University (Publisher)
Created2011
Description
Motor behavior is prone to variable conditions and deviates further in disorders affecting the nervous system. A combination of environmental and neural factors impacts the amount of uncertainty. Although the influence of these factors on estimating endpoint positions have been examined, the role of limb configuration on endpoint variability has been mostly ignored. Characterizing the influence of arm configuration (i.e. intrinsic factors) would allow greater comprehension of sensorimotor integration and assist in interpreting exaggerated movement variability in patients. In this study, subjects were placed in a 3-D virtual reality environment and were asked to move from a starting position to one of three targets in the frontal plane with and without visual feedback of the moving limb. The alternating of visual feedback during trials increased uncertainty between the planning and execution phases. The starting limb configurations, adducted and abducted, were varied in separate blocks. Arm configurations were setup by rotating along the shoulder-hand axis to maintain endpoint position. The investigation hypothesized: 1) patterns of endpoint variability of movements would be dependent upon the starting arm configuration and 2) any differences observed would be more apparent in conditions that withheld visual feedback. The results indicated that there were differences in endpoint variability between arm configurations in both visual conditions, but differences in variability increased when visual feedback was withheld. Overall this suggests that in the presence of visual feedback, planning of movements in 3D space mostly uses coordinates that are arm configuration independent. On the other hand, without visual feedback, planning of movements in 3D space relies substantially on intrinsic coordinates.
ContributorsRahman, Qasim (Author) / Buneo, Christopher (Thesis director) / Helms Tillery, Stephen (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Motor behavior is prone to variable conditions and deviates further in disorders affecting the nervous system. A combination of environmental and neural factors impacts the amount of uncertainty. Although the influence of these factors on estimating endpoint positions have been examined, the role of limb configuration on endpoint variability has been mostly ignored. Characterizing the influence of arm configuration (i.e. intrinsic factors) would allow greater comprehension of sensorimotor integration and assist in interpreting exaggerated movement variability in patients. In this study, subjects were placed in a 3-D virtual reality environment and were asked to move from a starting position to one of three targets in the frontal plane with and without visual feedback of the moving limb. The alternating of visual feedback during trials increased uncertainty between the planning and execution phases. The starting limb configurations, adducted and abducted, were varied in separate blocks. Arm configurations were setup by rotating along the shoulder-hand axis to maintain endpoint position. The investigation hypothesized: 1) patterns of endpoint variability of movements would be dependent upon the starting arm configuration and 2) any differences observed would be more apparent in conditions that withheld visual feedback. The results indicated that there were differences in endpoint variability between arm configurations in both visual conditions, but differences in variability increased when visual feedback was withheld. Overall this suggests that in the presence of visual feedback, planning of movements in 3D space mostly uses coordinates that are arm configuration independent. On the other hand, without visual feedback, planning of movements in 3D space relies substantially on intrinsic coordinates.
ContributorsRahman, Qasim (Author) / Buneo, Christopher (Thesis director) / Helms Tillery, Stephen (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
There is preclinical evidence that the detrimental cognitive effects of hormone loss can be ameliorated by estrogen therapy (Bimonte, Acosta, & Talboom, 2010), however, one of the primary concerns with current hormone therapies is that they are nonselective, leading to increased risk of breast and endometrial cancers as well as heart disease. Thus, in order to achieve a successful and clinically relevant long-term hormone therapy option, it is optimal to find an estrogen therapy regimen that is selective to its target tissue. Recently, phytoestrogens have been found to exert selective, beneficial effects on cognition and brain. For example, genistein and diadzein produce neuroprotective effects in cognitive brain regions (Zhao, Chen, & Diaz Brinton, 2002). The purpose of this study was threefold: 1) to examine the cognitive impact of phytoestrogens in young ovariectomized rats, 2) to replicate the dose effects found in the Luine study (Luine et al., 2006), while controlling for manufacturer differences, and 3) to assess if the rodent diet used in our laboratory has an estrogenic-like cognitive impact.The current findings suggest that, at least for object memory, diets containing varying amounts of phytoestrogens can alter cognition, with diets containing high amounts of phytoestrogens showing potential benefits to this type of memory.
ContributorsWhitton, Elizabeth Nicole (Author) / Bimonte-Nelson, Heather (Thesis director) / Presson, Clark (Committee member) / Baxter, Leslie (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2013-05
Description
It is unknown which regions of the brain are most or least active for golfers during a peak performance state (Flow State or "The Zone") on the putting green. To address this issue, electroencephalographic (EEG) recordings were taken on 10 elite golfers while they performed a putting drill consisting of hitting nine putts spaced uniformly around a hole each five feet away. Data was collected at three time periods, before, during and after the putt. Galvanic Skin Response (GSR) measurements were also recorded on each subject. Three of the subjects performed a visualization of the same putting drill and their brain waves and GSR were recorded and then compared with their actual performance of the drill. EEG data in the Theta (4 \u2014 7 Hz) bandwidth and Alpha (7 \u2014 13 Hz) bandwidth in 11 different locations across the head were analyzed. Relative power spectrum was used to quantify the data. From the results, it was found that there is a higher magnitude of power in both the theta and alpha bandwidths for a missed putt in comparison to a made putt (p<0.05). It was also found that there is a higher average power in the right hemisphere for made putts. There was not a higher power in the occipital region of the brain nor was there a lower power level in the frontal cortical region during made putts. The hypothesis that there would be a difference between the means of the power level in performance compared to visualization techniques was also supported.
ContributorsCarpenter, Andrea (Co-author) / Hool, Nicholas (Co-author) / Muthuswamy, Jitendran (Thesis director) / Crews, Debbie (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Vagal Nerve Stimulation (VNS) has been shown to be a promising therapeutic technique in treating many neurological diseases, including epilepsy, stroke, traumatic brain injury, and migraine headache. The mechanisms by which VNS acts, however, are not fully understood but may involve changes in cerebral blood flow. The vagus nerve plays a significant role in the regulation of heart rate and cerebral blood flow that are altered during VNS. Here, the effects of acute vagal nerve stimulation using varying stimulation parameters on both heart rate and cerebral blood flow were examined. Laser Speckle Contrast Analysis (LASCA) was used to analyze the cerebral blood flow of male Long–Evans rats. In the first experiment, results showed two distinct patterns of responses to 0.8mA of stimulation whereby animals either experienced a mild or severe decrease in heart rate. Further, animals that displayed mild heart rate decreases showed an increase in cerebral blood flow that persisted beyond VNS. Animals that displayed severe decreases showed a transient decrease in cerebral blood flow followed by an increase that was greater than that observed in mild animals but progressively decreased after VNS. The results suggest two distinct patterns of changes in both heart rate and blood flow that may be related to the intensity of VNS. To investigate the effects of lower levels of stimulation, an additional group of animals were stimulated at 0.4mA. The results showed moderate changes in heart rate but no significant changes in cerebral blood flow in these animals. The results demonstrate that VNS alters both heart rate and cerebral blood flow and that these effects are dependent on current intensity.
ContributorsHillebrand, Peter (M.S.) (Author) / Kleim, Jeffrey A (Thesis advisor) / Helms Tillery, Stephen I (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2019
Description
Long-term monitoring of deep brain structures using microelectrode implants is critical for the success of emerging clinical applications including cortical neural prostheses, deep brain stimulation and other neurobiology studies such as progression of disease states, learning and memory, brain mapping etc. However, current microelectrode technologies are not capable enough of reaching those clinical milestones given their inconsistency in performance and reliability in long-term studies. In all the aforementioned applications, it is important to understand the limitations & demands posed by technology as well as biological processes. Recent advances in implantable Micro Electro Mechanical Systems (MEMS) technology have tremendous potential and opens a plethora of opportunities for long term studies which were not possible before. The overall goal of the project is to develop large scale autonomous, movable, micro-scale interfaces which can seek and monitor/stimulate large ensembles of precisely targeted neurons and neuronal networks that can be applied for brain mapping in behaving animals. However, there are serious technical (fabrication) challenges related to packaging and interconnects, examples of which include: lack of current industry standards in chip-scale packaging techniques for silicon chips with movable microstructures, incompatible micro-bonding techniques to elongate current micro-electrode length to reach deep brain structures, inability to achieve hermetic isolation of implantable devices from biological tissue and fluids (i.e. cerebrospinal fluid (CSF), blood, etc.). The specific aims are to: 1) optimize & automate chip scale packaging of MEMS devices with unique requirements not amenable to conventional industry standards with respect to bonding, process temperature and pressure in order to achieve scalability 2) develop a novel micro-bonding technique to extend the length of current polysilicon micro-electrodes to reach and monitor deep brain structures 3) design & develop high throughput packaging mechanism for constructing a dense array of movable microelectrodes. Using a combination of unique micro-bonding technique which involves conductive thermosetting epoxy’s with hermetically sealed support structures and a highly optimized, semi-automated, 90-minute flip-chip packaging process, I have now extended the repertoire of previously reported movable microelectrode arrays to bond conventional stainless steel and Pt/Ir microelectrode arrays of desired lengths to steerable polysilicon shafts. I tested scalable prototypes in rigorous bench top tests including Impedance measurements, accelerated aging and non-destructive testing to assess electrical and mechanical stability of micro-bonds under long-term implantation. I propose a 3D printed packaging method allows a wide variety of electrode configurations to be realized such as a rectangular or circular array configuration or other arbitrary geometries optimal for specific regions of the brain with inter-electrode distance as low as 25 um with an unprecedented capability of seeking and recording/stimulating targeted single neurons in deep brain structures up to 10 mm deep (with 6 μm displacement resolution). The advantage of this computer controlled moveable deep brain electrodes facilitates potential capabilities of moving past glial sheath surrounding microelectrodes to restore neural connection, counter the variabilities in signal amplitudes, and enable simultaneous recording/stimulation at precisely targeted layers of brain.
ContributorsPalaniswamy, Sivakumar (Author) / Muthuswamy, Jitendran (Thesis advisor) / Buneo, Christopher (Committee member) / Abbas, James (Committee member) / Arizona State University (Publisher)
Created2016
Description
There is a strong medical need and important therapeutic applications for improved wireless bioelectric interfaces to the nervous system. Multichannel devices are desired for neural control of robotic prosthetics that interface to remaining nerves in limb stumps of amputees and as alternatives to traditional wired arrays used in for some types of brain stimulation. This present work investigates a new approach to ultrasound-powering of implantable microelectronic devices within the tissue that may better support such applications. These devices are of ultra-miniature size that is enabled by a wireless technique. This study investigates two types of ultrasound-powered neural interfaces for multichannel sensory feedback in neurostimulation. The piezoceramics lead zirconate titanate (PZT) ceramic and polyvinylidene fluoride (PVDF) polymer were the primary materials used to build the devices. They convert ultrasound to electricity that when rectified by a diode produce a current output that is neuro stimulatory to peripheral nerve or the neurons in the brain. Multichannel devices employ a form of spatial multiplexing that directs focused ultrasound towards localized and segmented regions of PVDF or PZT that allows independent channels of nerve actuation. Different frequencies of ultrasound were evaluated for best results. Firstly, a 2.25 MHz frequency signal that is reasonably penetrating through body tissue to an implant several centimeters deep and also a 5 MHz frequency more suited to application for actuation of devices within a less than a centimeter of nerve. Results show multichannel device performance to have a complex inter-relationship with frequency, size and thickness, angular incidence, channel separations, and number of folds (layers connected in series and parallel). The output electrical port impedances of PVDF devices were examined in relationship to that of stimulating electrodes and tissue interfaces. Miniature multichannel devices were constructed using an unreported method of employing state of the art laser cutting systems. The results show that PVDF based devices have advantages over PZT, because of better acoustic coupling with tissue, known better biocompatibility, and better separation between multiple channels. However, the PZT devices proved to be better overall in terms of compactness and higher outputs for a given ultrasound power level.
ContributorsNanda Kumar, Yashwanth (Author) / Towe, Bruce (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Nikkhah, Mehdi (Committee member) / Arizona State University (Publisher)
Created2015
Description
Noninvasive neuromodulation could help treat many neurological disorders, but existing techniques have low resolution and weak penetration. Ultrasound (US) shows promise for stimulation of smaller areas and subcortical structures. However, the mechanism and parameter design are not understood. US can stimulate tail and hindlimb movements in rats, but not forelimb, for unknown reasons. Potentially, US could also stimulate peripheral or enteric neurons for control of blood glucose.
To better understand the inconsistent effects across rat motor cortex, US modulation of electrically-evoked movements was tested. A stimulation array was implanted on the cortical surface and US (200 kHz, 30-60 W/cm2 peak) was applied while measuring changes in the evoked forelimb and hindlimb movements. Direct US stimulation of the hindlimb was also studied. To test peripheral effects, rat blood glucose levels were measured while applying US near the liver.
No short-term motor modulation was visible (95% confidence interval: -3.5% to +5.1% forelimb, -3.8% to +5.5% hindlimb). There was significant long-term (minutes-order) suppression (95% confidence interval: -3.7% to -10.8% forelimb, -3.8% to -11.9% hindlimb). This suppression may be due to the considerable heating (+1.8°C between US
on-US conditions); effects of heat and US were not separable in this experiment. US directly evoked hindlimb and scrotum movements in some sessions. This required a long interval, at least 3 seconds between US bursts. Movement could be evoked with much shorter pulses than used in literature (3 ms). The EMG latency (10 ms) was compatible with activation of corticospinal neurons. The glucose modulation test showed a strong increase in a few trials, but across all trials found no significant effect.
The single motor response and the long refractory period together suggest that only the beginning of the US burst had a stimulatory effect. This would explain the lack of short-term modulation, and suggests future work with shorter pulses could better explore the missing forelimb response. During the refractory period there was no change in the electrically-evoked response, which suggests the US stimulation mechanism is independent of normal brain activity. These results challenge the literature-standard protocols and provide new insights on the unknown mechanism.
To better understand the inconsistent effects across rat motor cortex, US modulation of electrically-evoked movements was tested. A stimulation array was implanted on the cortical surface and US (200 kHz, 30-60 W/cm2 peak) was applied while measuring changes in the evoked forelimb and hindlimb movements. Direct US stimulation of the hindlimb was also studied. To test peripheral effects, rat blood glucose levels were measured while applying US near the liver.
No short-term motor modulation was visible (95% confidence interval: -3.5% to +5.1% forelimb, -3.8% to +5.5% hindlimb). There was significant long-term (minutes-order) suppression (95% confidence interval: -3.7% to -10.8% forelimb, -3.8% to -11.9% hindlimb). This suppression may be due to the considerable heating (+1.8°C between US
on-US conditions); effects of heat and US were not separable in this experiment. US directly evoked hindlimb and scrotum movements in some sessions. This required a long interval, at least 3 seconds between US bursts. Movement could be evoked with much shorter pulses than used in literature (3 ms). The EMG latency (10 ms) was compatible with activation of corticospinal neurons. The glucose modulation test showed a strong increase in a few trials, but across all trials found no significant effect.
The single motor response and the long refractory period together suggest that only the beginning of the US burst had a stimulatory effect. This would explain the lack of short-term modulation, and suggests future work with shorter pulses could better explore the missing forelimb response. During the refractory period there was no change in the electrically-evoked response, which suggests the US stimulation mechanism is independent of normal brain activity. These results challenge the literature-standard protocols and provide new insights on the unknown mechanism.
ContributorsGulick, Daniel Withers (Author) / Kleim, Jeffrey (Thesis advisor) / Towe, Bruce (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Herman, Richard (Committee member) / Helms Tillery, Steven (Committee member) / Arizona State University (Publisher)
Created2015