Evidence map›Paper›PMID 39096961›Full record

ArticleBrain stimulation

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

Abstract read
In one paragraph

Article in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Neuromodulation in Small Animal fMRI.Journal of magnetic resonance imaging : JMRI · 2025
    Review
  3. Pallidothalamic Circuit-Selective Manipulation Ameliorates Motor Symptoms in a Rat Model of Parkinsonian.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  4. Charting the path in rodent functional neuroimaging.Imaging neuroscience (Cambridge, Mass.) · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Yuhui LiDepartment of Biomedical Engineering, USA.
Sung-Ho LeeCenter 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 YuDepartment of Biomedical Engineering, USA.
Li-Ming HsuCenter 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 WangCenter for Animal MRI, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA.
Khoa DoDepartment of Biomedical Engineering, USA.
Hyeon-Joong KimCenter 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 ShihCenter 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. Electronic address: shihy@unc.edu.
Warren M GrillDepartment 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. Electronic address: warren.grill@duke.edu.

Funding

Circuit Mechanisms Governing the Default Mode NetworkR01MH126518 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Vinod Menon, Yen-Yu Ian Shih · 2021 to 2026
$4.3M
Temporal Patterns of Deep Brain StimulationR37NS040894 · NINDS · DUKE UNIVERSITY · PI GRILL, WARREN M. · 2015 to 2021
$4.2M
Chemogenetic Dissection of Neuronal and Astrocytic Compartment of the BOLD SignalR01MH111429 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHIH, YEN-YU IAN · 2016 to 2020
$2.7M
SORDINO-fMRI for mouse brain applicationsR01EB033790 · NIBIB · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Yen-Yu Ian Shih · 2023 to 2026
$2.5M
Functional dissection of therapeutic deep brain stimulation circuitryR01NS091236 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHIH, YEN-YU IAN · 2015 to 2019
$2.0M
9.4T Small Animal MRI scanner at UNCS10OD026796 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHIH, YEN-YU IAN · 2020 to 2020
$2.0M
AVANCE NEO upgrade for the BioSpec 9.4T/30cm MRI system at UNCS10MH124745 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHIH, YEN-YU IAN · 2020 to 2020
$600k
NIBIB NIH HHS R01 EB033790NIH HHS S10 OD026796NIMH NIH HHS R01 MH111429NIMH NIH HHS R01 MH126518NIMH NIH HHS S10 MH124745NINDS NIH HHS R01 NS091236NINDS NIH HHS R37 NS040894
6 · The paper itself

Abstract

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.

Indexed as

Deep Brain StimulationMagnetic Resonance ImagingOptogeneticsSubthalamic NucleusAnimalsFemaleGlobus PallidusParkinson DiseaseRatsRats, Sprague-DawleyDeep brain stimulationfMRIOptogeneticsParkinson's diseaseSubthalamic nucleus

Identifiers

PMID39096961
PMCPMC11364984

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.