Causally Probing the Role of the Hippocampus in Fear Discrimination: A Precision Functional Mapping–Guided, Transcranial Magnetic Stimulation Study in Participants With Posttraumatic Stress Symptoms

Ryan D. Webler, Cristian Morales Carrasco, Samuel E. Cooper, Mo Chen, Christopher O. Hunt, Sierra Hennessy, Lancy Cao, Carol Lam, Allen Chiu, Cash Differding, Erin Todd, Timothy J. Hendrickson, Desmond J. Oathes, Alik S. Widge, Robert J.M. Hermosillo, Steven M. Nelson, Damien A. Fair, Shmuel M. Lissek, Ziad Nahas

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Fear overgeneralization is a promising pathogenic mechanism of clinical anxiety. A dominant model posits that hippocampal pattern separation failures drive overgeneralization. Hippocampal network–targeted transcranial magnetic stimulation (HNT-TMS) has been shown to strengthen hippocampal-dependent learning/memory processes. However, no study has examined whether HNT-TMS can alter fear learning/memory. Methods: Continuous theta burst stimulation was delivered to individualized left posterior parietal stimulation sites derived via seed-based connectivity, precision functional mapping, and electric field modeling methods. A vertex control site was also stimulated in a within-participant, randomized controlled design. Continuous theta burst stimulation was delivered prior to 2 visual discrimination tasks (1 fear based, 1 neutral). Multilevel models were used to model and test data. Participants were undergraduates with posttraumatic stress symptoms (final n = 25). Results: Main analyses did not indicate that HNT-TMS strengthened discrimination. However, multilevel interaction analyses revealed that HNT-TMS strengthened fear discrimination in participants with lower fear sensitization (indexed by responses to a control stimulus with no similarity to the conditioned fear cue) across multiple indices (anxiety ratings: β = 0.10, 95% CI, 0.04 to 0.17, p = .001; risk ratings: β = 0.07, 95% CI, 0.00 to 0.13, p = .037). Conclusions: Overgeneralization is an associative process that reflects deficient discrimination of the fear cue from similar cues. In contrast, sensitization reflects nonassociative responding unrelated to fear cue similarity. Our results suggest that HNT-TMS may selectively sharpen fear discrimination when associative response patterns, which putatively implicate the hippocampus, are more strongly engaged.

Original languageEnglish (US)
Article number100309
JournalBiological Psychiatry Global Open Science
Volume4
Issue number3
DOIs
StatePublished - May 2024

Bibliographical note

Publisher Copyright:
© 2024

Keywords

  • Fear conditioning
  • Fear generalization
  • Hippocampal network–targeted TMS
  • Hippocampus
  • Precision functional mapping
  • TMS

Fingerprint

Dive into the research topics of 'Causally Probing the Role of the Hippocampus in Fear Discrimination: A Precision Functional Mapping–Guided, Transcranial Magnetic Stimulation Study in Participants With Posttraumatic Stress Symptoms'. Together they form a unique fingerprint.

Cite this