Optogenetic fMRI reveals therapeutic circuits of subthalamic nucleus deep brain stimulation

Yuhui Li; Sung-Ho Lee; Chunxiu Yu; Li-Ming Hsu; Tzu-Wen W. Wang; Khoa Do; Hyeon-Joong Kim; Yen-Yu Ian Shih; Warren M. Grill

Brain Stimulation (Jul 2024)

Optogenetic fMRI reveals therapeutic circuits of subthalamic nucleus deep brain stimulation

Yuhui Li,
Sung-Ho Lee,
Chunxiu Yu,
Li-Ming Hsu,
Tzu-Wen W. Wang,
Khoa Do,
Hyeon-Joong Kim,
Yen-Yu Ian Shih,
Warren M. Grill

Affiliations

Yuhui Li: Department of Biomedical Engineering, USA
Sung-Ho Lee: Center for Animal MRI, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA; Department of Neurology, University of North Carolina, Chapel Hill, NC, USA
Chunxiu Yu: Department of Biomedical Engineering, USA
Li-Ming Hsu: Center for Animal MRI, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA; Department of Neurology, University of North Carolina, Chapel Hill, NC, USA
Tzu-Wen W. Wang: Center for Animal MRI, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA
Khoa Do: Department of Biomedical Engineering, USA
Hyeon-Joong Kim: Center for Animal MRI, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA; Department of Neurology, University of North Carolina, Chapel Hill, NC, USA
Yen-Yu Ian Shih: Center for Animal MRI, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA; Department of Neurology, University of North Carolina, Chapel Hill, NC, USA; Corresponding author. Department of Neurology, University of North Carolina at Chapel Hill, Marsico Hall SB212, 125 Mason Farm Road, Chapel Hill, NC, 27519, USA.
Warren M. Grill: Department of Biomedical Engineering, USA; Department of Electrical and Computer Engineering, USA; Department of Neurobiology, Duke University, Durham, NC, USA; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA; Corresponding author. Department of Biomedical Engineering, Duke University. CIEMAS, Room 1139, 101 Science Drive, Durham, NC, 27708, USA.

Journal volume & issue: Vol. 17, no. 4
pp. 947 – 957

Abstract

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While deep brain stimulation (DBS) is widely employed for managing motor symptoms in Parkinson's disease (PD), its exact circuit mechanisms remain controversial. To identify the neural targets affected by therapeutic DBS in PD, we analyzed DBS-evoked whole brain activity in female hemi-parkinsonian rats using functional magnetic resonance imaging (fMRI). We delivered subthalamic nucleus (STN) DBS at various stimulation pulse repetition rates using optogenetics, allowing unbiased examination of cell-type specific STN feedforward neural activity. Unilateral optogenetic STN DBS elicited pulse repetition rate-dependent alterations of blood-oxygenation-level-dependent (BOLD) signals in SNr (substantia nigra pars reticulata), GP (globus pallidus), and CPu (caudate putamen). Notably, this modulation effectively ameliorated pathological circling behavior in animals expressing the kinetically faster Chronos opsin, but not in animals expressing ChR2. Furthermore, mediation analysis revealed that the pulse repetition rate-dependent behavioral rescue was significantly mediated by optogenetic DBS induced activity changes in GP and CPu, but not in SNr. This suggests that the activation of GP and CPu are critically involved in the therapeutic mechanisms of STN DBS.

Published in Brain Stimulation

ISSN: 1935-861X (Print); 1876-4754 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/brain-stimulation

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