Evidence map›Paper›PMID 35247646›Full record

ArticleBrain stimulation

Local and distant cortical responses to single pulse intracranial stimulation in the human brain are differentially modulated by specific stimulation parameters.

Angelique C Paulk, Rina Zelmann, Britni Crocker, Alik S Widge, Darin D Dougherty, Emad N Eskandar, Daniel S Weisholtz, R Mark Richardson, G Rees Cosgrove, Ziv M Williams and 1 more

Open access · goldAbstract 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 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% 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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

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  20. Exploring individual differences in amygdala-mediated memory modulation.Cognitive, affective & behavioral neuroscience · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Angelique C PaulkDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: apaulk@mgh.harvard.edu.
Rina ZelmannDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Britni CrockerDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Harvard-MIT Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Alik S WidgeDepartment of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
Darin D DoughertyCenter for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
Emad N EskandarDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Daniel S WeisholtzDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, 02114, USA.
R Mark RichardsonCenter for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
G Rees CosgroveDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, 02114, USA.
Ziv M WilliamsCenter for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Sydney S CashDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Harvard University · USBrigham and Women's Hospital · US

Funding

Using microstimulation to map prefrontal fear modules in the ratP50MH086400 · NIMH · UNIVERSITY OF ROCHESTER · PI HABER, SUZANNE N · 2009 to 2013
$10.3M
Integrated Biophysical and Neural Model of Electrical Stimulation EffectsR01NS109553 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BAZHENOV, MAKSIM V, HALGREN, ERIC · 2019 to 2023
$4.4M
Multi-Site Non-Invasive Magnetothermal Excitation and Inhibition of Deep Brain StructuresR01MH111872 · NIMH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ANIKEEVA, POLINA O, PRALLE, ARND · 2016 to 2019
$3.6M
Combined Cortical and Subcortical Recording and Stimulation as a Circuit-Oriented Treatment for Obsessive-Compulsive DisorderUH3NS100548 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI DOUGHERTY, DARIN D, WIDGE, ALIK S. · 2016 to 2024
$3.2M
Neostriatum in Learning and MemoryR01EY017658 · NEI · MASSACHUSETTS GENERAL HOSPITAL · PI ESKANDAR, EMAD N · 2007 to 2013
$2.7M
Striatal Deep Brain Stimulation for Learning EnhancementR01DA026297 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI ESKANDAR, EMAD N · 2008 to 2011
$1.5M
Seizure focus delineation using spontaneous and stimulus evoked EEG featuresK24NS088568 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI CASH, SYDNEY S · 2015 to 2019
$923k
Synchronizing a Fear Regulation Circuit By Temporally Patterned Closed-LoopNeurostimulationR21MH109722 · NIMH · UNIVERSITY OF MINNESOTA · PI WIDGE, ALIK S. · 2016 to 2017
$444k
NEI NIH HHS R01 EY017658NIDA NIH HHS R01 DA026297NIMH NIH HHS P50 MH086400NIMH NIH HHS R01 MH111872NIMH NIH HHS R21 MH109722NINDS NIH HHS K24 NS088568NINDS NIH HHS R01 NS109553NINDS NIH HHS UH3 NS100548
6 · The paper itself

Abstract

backgroundElectrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses.

objectiveTo better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated.

methodsWe measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites).

resultsIncreasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation.

conclusionThese results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.

Indexed as

Cerebral CortexWhite MatterBrainElectric StimulationEvoked PotentialsHumansCortexHumanIntracranialNonlinearSingle pulse electrical stimulationWhite matter

Identifiers

PMID35247646
PMCPMC8985164
OpenAlexW4214900398

What OpenQuestion holds

Textmetadata
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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.