Evidence map›Paper›PMID 39096960›Full record

ArticleBrain stimulation

Neuromodulation modifies α-synuclein spreading dynamics in vivo and the pattern is predicted by changes in whole-brain function.

Ehsan Dadgar-Kiani, Gregor Bieri, Ronald Melki, Aronee Hossain, Aaron D Gitler, Jin Hyung Lee

Abstract read
PubMed Full text at PMC Publisher
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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Ehsan Dadgar-KianiDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Gregor BieriDepartment of Genetics, Stanford University, CA, 94305, USA.
Ronald MelkiInstitut François Jacob, MIRCen, CEA and Laboratory of Neurodegenerative Diseases, CNRS, Fontenay-aux-Roses, France.
Aronee HossainDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
Aaron D GitlerDepartment of Genetics, Stanford University, CA, 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA, 94158, USA.
Jin Hyung LeeDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA; Department of Electrical Engineering, Stanford University, CA, 94305, USA; Department of Neurosurgery, Stanford University, Stanford, CA, 94305, USA. Electronic address: ljinhy@stanford.edu.

Funding

Innovating Yeast and Human Genetics Approaches to Define Mechanisms of Neurodegenerative DiseaseR35NS097263 · NINDS · STANFORD UNIVERSITY · PI GITLER, AARON D. · 2017 to 2024
$8.6M
VECTOR COREP30NS069375 · NINDS · STANFORD UNIVERSITY · PI SHAMLOO, MEHRDAD · 2011 to 2019
$6.3M
Defining Cell Type Specific Contributions to fMRI SignalsRF1MH114227 · NIMH · STANFORD UNIVERSITY · PI LEE, JIN HYUNG · 2017 to 2017
$3.7M
Dynamic regulation of whole brain circuit function by basal ganglia pathwaysR01NS091461 · NINDS · STANFORD UNIVERSITY · PI LEE, JIN HYUNG · 2015 to 2019
$2.4M
Deconstructing Arousal Regulation Circuits for Optimal DBS Therapy DesignR01NS087159 · NINDS · STANFORD UNIVERSITY · PI LEE, JIN HYUNG · 2014 to 2018
$1.9M
Direct Visualization of Cell-Type Specific AD Networks for Drug DevelopmentRF1AG047666 · NIA · STANFORD UNIVERSITY · PI LEE, JIN HYUNG · 2014 to 2014
$1.8M
NIA NIH HHS RF1 AG047666NIMH NIH HHS RF1 MH114227NINDS NIH HHS P30 NS069375NINDS NIH HHS R01 NS087159NINDS NIH HHS R01 NS091461NINDS NIH HHS R35 NS097263
6 · The paper itself

Abstract

backgroundMany neurodegenerative disease treatments, such as deep brain stimulation for Parkinson's Disease, can alleviate symptoms by primarily compensating for circuit dysfunctions. However, the stimulation's effect on the underlying disease progression remains relatively unknown. Here, we report that neuromodulation can not only modulate circuit function but also modulate the in vivo spreading dynamics of α-synuclein pathology, the primary pathological hallmark observed in Parkinson's Disease.

methodsIn a mouse model, pre-formed fibrils were injected into the striatum to induce widespread α-synuclein pathology. Two days after fibril injection, mice were treated for two weeks with daily optogenetic stimulation of the Secondary Motor Area, Layer V. Whole brains were then extracted, immunolabeled, cleared, and imaged with light-sheet fluorescent microscopy.

resultsRepeated optogenetic stimulation led to a decrease in pathology at the site of stimulation and at various cortical and subcortical regions, while the contralateral cortex saw a consistent increase. Aligning the pathology changes with optogenetic-fMRI measured brain activity, we found that the changes in pathology and brain function had similar spatial locations but opposite polarity.

conclusionThese results demonstrate the ability to modulate and predict whole brain pathology changes using neuromodulation, opening a new horizon for investigating optimized neuromodulation therapies.

Indexed as

alpha-SynucleinOptogeneticsAnimalsBrainDeep Brain StimulationDisease Models, AnimalMagnetic Resonance ImagingMaleMiceParkinson Diseasealpha-SynucleinSnca protein, mouseCircuit functionNeuromodulationOptogeneticsParkinson's diseaseα-Synuclein

Identifiers

PMID39096960
PMCPMC11416857

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.