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Peer-reviewedCC BY 4.0PeerJ

Neural substrates of knowledge integration: differential effects of high-definition transcranial direct current stimulation (HD-tDCS) on angular gyrus and ventrolateral prefrontal cortex

5 affiliations
  1. 1Rotman Research Institute, Baycrest Hospital, Toronto, ON, Canada
  2. 2Department of Psychology, University of Toronto, Toronto, ON, Canada
  3. 3Department of Psychology, York University, Toronto, ON, Canada
  4. 4Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada
  5. 5University Health Network, Toronto, ON, Canada

Abstract

Background: Humans develop extensive knowledge systems throughout their lives, which are continuously updated in response to new information. One way in which prior knowledge is updated is through semantic integration, where related semantic facts are integrated to support derivation of new information.

Methods: This study investigates how anodal high-definition transcranial direct current stimulation (HD-tDCS) applied to the left angular gyrus (AG; Experiment 1) or to the left ventrolateral prefrontal cortex (vlPFC; Experiment 2) influences semantic integration and the derivation of novel information. In both studies, participants were first randomly assigned to a stimulation or sham group. Following the stimulation protocol, they were presented with a series of intermixed pairs of related facts and asked to rate their familiarity with each. Participants then completed a semantic integration test following a brief delay, answering questions about novel information that could be derived by integrating the related facts. Participants’ integration scores (primary outcome) and their correlations with general intelligence (IQ) (secondary outcome) were measured. Building on exploratory findings from Experiment 1, Experiment 2 was pre-registered to test the impact of stimulation on the correlation between IQ and integration.

Results: There was no overall mean difference in integration scores between stimulation groups and their sham stimulation counterparts (all p s > 0.10). Stimulation to the left AG resulted in significantly lower variance in integration scores compared to sham stimulation ( p < 0.05), reflecting fewer stimulation participants scoring very low on integration. Conversely, stimulation to the left vlPFC reduced the correlation between participants’ IQ and their integration scores ( p < 0.05).

Conclusion: Self-derivation of new knowledge is a complex, multifactorial process that was not uniquely enhanced by stimulation of the left AG or vlPFC. However, these regions appear to differentially modulate performance by reducing variability for lower-performing individuals (AG) or decoupling the dependence of performance on baseline cognitive capacity (vlPFC).

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BibTeX
@article{zhang2026neural,
  title = {{Neural substrates of knowledge integration: differential effects of high-definition transcranial direct current stimulation (HD-tDCS) on angular gyrus and ventrolateral prefrontal cortex}},
  author = {Xuan Zhang and Michael Lochner and Karen Joseph and Asaf Gilboa},
  journal = {PeerJ},
  year = {2026},
  month = oct,
  doi = {10.7717/peerj.21761},
  url = {https://peerj.com/articles/21761},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Neural substrates of knowledge integration: differential effects of high-definition transcranial direct current stimulation (HD-tDCS) on angular gyrus and ventrolateral prefrontal cortex
AU  - Xuan Zhang
AU  - Michael Lochner
AU  - Karen Joseph
AU  - Asaf Gilboa
PY  - 2026
DA  - 2026/10/06
JO  - PeerJ
DO  - 10.7717/peerj.21761
UR  - https://peerj.com/articles/21761
AB  - Background: Humans develop extensive knowledge systems throughout their lives, which are continuously updated in response to new information. One way in which prior knowledge is updated is through semantic integration, where related semantic facts are integrated to support derivation of new information.  Methods: This study investigates how anodal high-definition transcranial direct current stimulation (HD-tDCS) applied to the left angular gyrus (AG; Experiment 1) or to the left ventrolateral prefrontal cortex (vlPFC; Experiment 2) influences semantic integration and the derivation of novel information. In both studies, participants were first randomly assigned to a stimulation or sham group. Following the stimulation protocol, they were presented with a series of intermixed pairs of related facts and asked to rate their familiarity with each. Participants then completed a semantic integration test following a brief delay, answering questions about novel information that could be derived by integrating the related facts. Participants’ integration scores (primary outcome) and their correlations with general intelligence (IQ) (secondary outcome) were measured. Building on exploratory findings from Experiment 1, Experiment 2 was pre-registered to test the impact of stimulation on the correlation between IQ and integration.  Results: There was no overall mean difference in integration scores between stimulation groups and their sham stimulation counterparts (all p s > 0.10). Stimulation to the left AG resulted in significantly lower variance in integration scores compared to sham stimulation ( p < 0.05), reflecting fewer stimulation participants scoring very low on integration. Conversely, stimulation to the left vlPFC reduced the correlation between participants’ IQ and their integration scores ( p < 0.05).  Conclusion: Self-derivation of new knowledge is a complex, multifactorial process that was not uniquely enhanced by stimulation of the left AG or vlPFC. However, these regions appear to differentially modulate performance by reducing variability for lower-performing individuals (AG) or decoupling the dependence of performance on baseline cognitive capacity (vlPFC).
SN  - 2167-8359
ER  -