Evidence map›Paper›PMID 34481095›Full record

Trial reportBrain stimulation

Individual differences in neuroanatomy and neurophysiology predict effects of transcranial alternating current stimulation.

Theodore P Zanto, Kevin T Jones, Avery E Ostrand, Wan-Yu Hsu, Richard Campusano, Adam Gazzaley

Open access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 4 pooled it
3.5field-weighted citation impact, top 6% of its field
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

33 citing papers in PubMed, 4 syntheses or guidelines pooled it, 62 citations in OpenAlex.

  1. Effects of transcranial alternating current stimulation on cognitive function in older adults: a systematic review and meta-analysis of randomized controlled trials.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
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  14. Advances in electrical stimulation for wound healing.Frontiers in bioengineering and biotechnology · 2025
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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 at 1 institution in 1 country.

Theodore P ZantoDepartment of Neurology, University of California-San Francisco, San Francisco, CA, USA; Neuroscape, University of California-San Francisco, San Francisco, CA, USA. Electronic address: theodore.zanto@ucsf.edu.
Kevin T JonesDepartment of Neurology, University of California-San Francisco, San Francisco, CA, USA; Neuroscape, University of California-San Francisco, San Francisco, CA, USA.
Avery E OstrandDepartment of Neurology, University of California-San Francisco, San Francisco, CA, USA; Neuroscape, University of California-San Francisco, San Francisco, CA, USA.
Wan-Yu HsuDepartment of Neurology, University of California-San Francisco, San Francisco, CA, USA.
Richard CampusanoDepartment of Neurology, University of California-San Francisco, San Francisco, CA, USA; Neuroscape, University of California-San Francisco, San Francisco, CA, USA.
Adam GazzaleyDepartment of Neurology, University of California-San Francisco, San Francisco, CA, USA; Neuroscape, University of California-San Francisco, San Francisco, CA, USA; Departments of Physiology and Psychiatry, University of California-San Francisco, San Francisco, CA, USA.
University of California, San Francisco · US

Funding

Clinical and Translational Science InstituteUL1TR001872 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLARD, HAROLD R, JACOBY, VANESSA · 2016 to 2025
$112.1M
Enhancing cognitive control in amnestic mild cognitive impairment via non-invasive brain stimulationR21AG062395 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GAZZALEY, ADAM H, ZANTO, THEODORE P · 2018 to 2019
$377k
NCATS NIH HHS UL1 TR001872NIA NIH HHS R21 AG062395
6 · The paper itself

Abstract

backgroundNoninvasive transcranial electrical stimulation (tES) research has been plagued with inconsistent effects. Recent work has suggested neuroanatomical and neurophysiological variability may alter tES efficacy. However, direct evidence is limited.

objectiveWe have previously replicated effects of transcranial alternating current stimulation (tACS) on improving multitasking ability in young adults. Here, we attempt to assess whether these stimulation parameters have comparable effects in older adults (aged 60-80 years), which is a population known to have greater variability in neuroanatomy and neurophysiology. It is hypothesized that this variability in neuroanatomy and neurophysiology will be predictive of tACS efficacy.

methodsWe conducted a pre-registered study where tACS was applied above the prefrontal cortex (between electrodes F3-F4) while participants were engaged in multitasking. Participants were randomized to receive either 6-Hz (theta) tACS for 26.67 min daily for three days (80 min total; Long Exposure Theta group), 6-Hz tACS for 5.33 min daily (16-min total; Short Exposure Theta group), or 1-Hz tACS for 26.67 min (80 min total; Control group). To account for neuroanatomy, magnetic resonance imaging data was used to form individualized models of the tACS-induced electric field (EF) within the brain. To account for neurophysiology, electroencephalography data was used to identify individual peak theta frequency.

resultsResults indicated that only in the Long Theta group, performance change was correlated with modeled EF and peak theta frequency. Together, modeled EF and peak theta frequency accounted for 54%-65% of the variance in tACS-related performance improvements, which sustained for a month.

conclusionThese results demonstrate the importance of individual differences in neuroanatomy and neurophysiology in tACS research and help account for inconsistent effects across studies.

Indexed as

Transcranial Direct Current StimulationAgedElectroencephalographyHumansIndividualityNeuroanatomyPrefrontal CortexYoung AdultComputational modelingMultitaskingTheta bandTranscranial alternating current stimulation

Identifiers

PMID34481095
PMCPMC9492518
OpenAlexW3197283795

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.