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Cited by 156Memory and Neural MechanismsTranscranial Magnetic Stimulation StudiesNeural and Behavioral Psychology Studies

Prefrontal Cortex Stimulation Enhances Fear Extinction Memory in Humans

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Raij, Tommi, Nummenmaa, Aapo, Marin, Marie-France, Porter, Daria, Furtak, Sharon, Setsompop, Kawin, Milad, Mohammed R.·2018·Biological Psychiatry
DOI 10.1016/j.biopsych.2017.10.022PMC PMC5936658
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Abstract

Background Animal fear conditioning studies have illuminated neuronal mechanisms of learned associations between sensory stimuli and fear responses. In rats, brief electrical stimulation of the infralimbic cortex has been shown to reduce conditioned freezing during recall of extinction memory. Here, we translated this finding to humans with magnetic resonance imaging-navigated transcranial magnetic stimulation (TMS). Methods Subjects (N = 28) were aversively conditioned to two different cues (day 1). During extinction learning (day 2), TMS was paired with one of the conditioned cues but not the other. TMS parameters were similar to those used in rat infralimbic cortex: brief pulse trains (300 ms at 20 Hz) starting 100 ms after cue onset, total of four trains (28 TMS pulses). TMS was applied to one of two targets in the left frontal cortex, one functionally connected (target 1) and the other unconnected (target 2, control) with a human homologue of infralimbic cortex in the ventromedial prefrontal cortex. Skin conductance responses were used as an index of conditioned fear. Results During extinction recall (day 3), the cue paired with TMS to target 1 showed significantly reduced skin conductance responses, whereas TMS to target 2 had no effect. Further, we built group-level maps that weighted TMS-induced electric fields and diffusion magnetic resonance imaging connectivity estimates with fear level. These maps revealed distinct cortical regions and large-scale networks associated with reduced versus increased fear. Conclusions The results showed that spatiotemporally focused TMS may enhance extinction learning and/or consolidation of extinction memory and suggested novel cortical areas and large-scale networks for targeting in future studies.

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  • TMS during extinction learning to an area of the frontal cortex functionally connected to the vmPFC (left lateral PFC), but not to an area thought to be unconnected to the vmPFC, led to enhanced extinction recall.

    “Similarly, Raij et al. [102] found that TMS, during extinction learning, to an area of the frontal cortex functionally connected to the vmPFC (i.e., the left lateral PFC), but not to an area of the frontal cortex thought to be unconnected to the vmPFC, led to enhanced extinction recall.”

    From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [102]

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Cited by

Sorted by citations

Authors
Raij, T., Nummenmaa, A., Marin, M.-F., Porter, D., Furtak, S., Setsompop, K., & Milad, M. R.
Affiliations
  • Harvard University (US)
  • Massachusetts General Hospital (US)
Corresponding author
  • Raij, Tommi
  • Milad, Mohammed R.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2018-07
Volume
84
Issue
2
Pages
129-137
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2017.10.022
PMC
PMC5936658
OpenAlex
W2767738832
Cited by
156
References
8
Citations by year
2026: 15 · 2025: 11 · 2024: 16 · 2023: 20 · 2022: 20 · 2021: 22 · 2020: 32 · 2019: 11 · 2018: 8 · 2017: 1
FWCI
8.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Defense (DM 102304)
  • National Institutes of Health
  • National Institute of Biomedical Imaging and Bioengineering (P41EB015896)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
fear extinction memory, transcranial magnetic stimulation, prefrontal cortex, infralimbic cortex, ventromedial prefrontal cortex, fear conditioning, skin conductance response, extinction consolidation, functional connectivity, large-scale brain networks, electric field mapping
MeSH terms
Animals, Conditioning, Classical, Extinction, Psychological, Fear, Humans, Magnetic Resonance Imaging, Mental Recall, Regression Analysis, Prefrontal Cortex, Transcranial Magnetic Stimulation, Rats

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