Evidence map›Paper›PMID 25129402›Full record

ArticleBrain stimulation

Endogenous cortical oscillations constrain neuromodulation by weak electric fields.

Stephen L Schmidt, Apoorva K Iyengar, A Alban Foulser, Michael R Boyle, Flavio Fröhlich

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 68 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 2 pooled it
–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

68 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  6. Randomized trial of transcranial alternating current stimulation for treatment of auditory hallucinations in schizophrenia.European psychiatry : the journal of the Association of European Psychiatrists · 2018
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  9. Functional role of frontal alpha oscillations in creativity.Cortex; a journal devoted to the study of the nervous system and behavior · 2015
    Trial
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  15. Interactions Between Active Matters and Endogenous Fields.Advanced materials (Deerfield Beach, Fla.) · 2025
    Review
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8 more citing papers are in PubMed but not listed here.

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

5 authors.

Stephen L SchmidtDepartment of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Apoorva K IyengarDepartment of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
A Alban FoulserDepartment of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Michael R BoyleDepartment of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Flavio FröhlichDepartment of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: flavio_frohlich@med.unc.edu.

Funding

Targeting Cortical Dynamics: Rational Design of Individualized Brain StimulationR01MH101547 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FROHLICH, FLAVIO · 2013 to 2017
$2.2M
NIMH NIH HHS R01 MH101547NIMH NIH HHS R01MH101547
6 · The paper itself

Abstract

backgroundTranscranial alternating current stimulation (tACS) is a non-invasive brain stimulation modality that may modulate cognition by enhancing endogenous neocortical oscillations by application of sine-wave electric fields. Yet, the role of endogenous network activity in enabling and shaping the effects of tACS has remained unclear.

objectiveWe combined optogenetic stimulation and multichannel slice electrophysiology to elucidate how the effect of a weak sine-wave electric field depends on the ongoing cortical oscillatory activity. We hypothesized that endogenous cortical oscillations constrain neuromodulation by tACS.

methodsWe studied the effect of weak sine-wave electric fields on oscillatory activity in mouse neocortical slices. Optogenetic control of the network activity enabled the generation of in vivo-like cortical oscillations for studying the temporal relationship between network activity and sine-wave electric field stimulation.

resultsWeak electric fields enhanced endogenous oscillations but failed to induce a frequency shift of the ongoing oscillation for stimulation frequencies that were not matched to the endogenous oscillation. This constraint on the effect of electric field stimulation imposed by endogenous network dynamics was limited to the case of weak electric fields targeting in vivo-like network dynamics. Together, these results suggest that the key mechanism of tACS may be enhancing, but not overriding, intrinsic network dynamics.

conclusionOur results contribute to understanding the inconsistent tACS results from human studies and propose that stimulation precisely adjusted in frequency to the endogenous oscillations is key to rational design of non-invasive brain stimulation paradigms.

Indexed as

Transcranial Direct Current StimulationAnimalsBiological ClocksBrain WavesMiceNeocortexNerve NetOptogeneticsPyramidal CellsElectric fieldMultielectrode arrayOptogeneticsResonancetACSTranscranial alternating current stimulation

Identifiers

PMID25129402
PMCPMC4259839

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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.