<mods:mods xmlns:mods="http://www.loc.gov/mods/v3" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-7.xsd"><mods:titleInfo><mods:title>Optogenetics-based Neuromodulation of the Cortico-Basal-Ganglia Circuitry in a hemi-Parkinsonian Rat Model</mods:title></mods:titleInfo><mods:name type="personal"><mods:namePart>Yu, Zeyang</mods:namePart><mods:role><mods:roleTerm type="text">creator</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Nurmikko, Arto</mods:namePart><mods:role><mods:roleTerm type="text">Advisor</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Asaad, Wael</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Borton, David</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Hoffman-Kim, Diane</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Ozden, Ilker</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="corporate"><mods:namePart>Brown University. Biology and Medicine: Biomedical Engineering</mods:namePart><mods:role><mods:roleTerm type="text">sponsor</mods:roleTerm></mods:role></mods:name><mods:originInfo><mods:copyrightDate>2019</mods:copyrightDate></mods:originInfo><mods:physicalDescription><mods:extent>xx, 220 p.</mods:extent><mods:digitalOrigin>born digital</mods:digitalOrigin></mods:physicalDescription><mods:note type="thesis">Thesis (Ph. D.)--Brown University, 2019</mods:note><mods:genre authority="aat">theses</mods:genre><mods:abstract>Deep brain stimulation (DBS) is an effective treatment for the mid/late stage Parkinson’s disease (PD), which significantly reduces the dopamine medication and improves motor symptoms. However, it does not offer a complete relief and some symptoms typically persist. A better understanding of its mechanism of action, further improvement in efficacy, and the identification of new therapeutic targets could benefit from pathway- and cell-type specific modulation methods. This dissertation focuses on utilizing optogenetic neuromodulation to interrogate the therapeutic effects of modulating multiple brain nuclei and fiber pathways within the cortico-basal-ganglia circuitry. In this thesis, I first developed methodological approaches for the functional opsin expression in the subthalamic nucleus (STN), globus pallidus externus (GPe), and motor cortex of non-transgenic rats. I then systematically evaluated the efficacies of various modulation paradigms on the alleviation of the characteristic symptom of rotational bias in a 6-OHDA hemi-Parkinsonian rat model, based on three main hypothesis: the inhibition of STN, the excitation of GPe, and the excitation of motor cortex. I found therapeutic improvements in rotational behavior, with individual differences, yielded from all of these optogenetic modulations. I also performed microelectrode array recording from the motor cortices of hemi-Parkinsonian rats to characterize the features of motor cortical beta-band oscillatory activities as biomarkers for the underlying Parkinsonism. I found the pathologically elevated beta band oscillations contained variations in spatial distribution, fluctuations in temporal dynamics, and instability in the frequencies. Additionally, I also showed that the phase synchrony of beta oscillations was enhanced across different motor cortical sites, which may serve as a complementary biomarker to the power-based measures. Overall, my work provided new considerations towards a closed-loop, adaptive neuromodulation paradigm for the treatment of Parkinson’s disease, utilizing optogenetics for pathway specific modulations and motor cortical pathophysiological biomarkers for feedback.</mods:abstract><mods:subject authority="fast" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/01027584"><mods:topic>Motor cortex</mods:topic></mods:subject><mods:subject authority="fast" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/01909981"><mods:topic>Optogenetics</mods:topic></mods:subject><mods:subject authority="fast" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/01053693"><mods:topic>Parkinson's disease</mods:topic></mods:subject><mods:subject><mods:topic>Deep Brain Stimulation</mods:topic></mods:subject><mods:subject><mods:topic>Globus pallidus externus</mods:topic></mods:subject><mods:subject><mods:topic>Subthalamic nucleus</mods:topic></mods:subject><mods:subject><mods:topic>6-OHDA Rat Model</mods:topic></mods:subject><mods:subject><mods:topic>Beta oscillations</mods:topic></mods:subject><mods:language><mods:languageTerm authority="iso639-2b">English</mods:languageTerm></mods:language><mods:recordInfo><mods:recordContentSource authority="marcorg">RPB</mods:recordContentSource><mods:recordCreationDate encoding="iso8601">20190603</mods:recordCreationDate></mods:recordInfo><mods:identifier type="doi">10.26300/yt0j-sf75</mods:identifier><mods:accessCondition type="rights statement" xlink:href="http://rightsstatements.org/vocab/InC/1.0/">In Copyright</mods:accessCondition><mods:accessCondition type="restriction on access">Collection is open for research.</mods:accessCondition><mods:typeOfResource authority="primo">dissertations</mods:typeOfResource></mods:mods>