Habenula-prefrontal resting-state connectivity in reactive aggressive men – A pilot study

G. Gan, A. Zilverstand, M. A. Parvaz, R. N. Preston-Campbell, F. d'Oleire Uquillas, S. J. Moeller, D. Tomasi, R. Z. Goldstein, N. Alia-Klein

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Disproportionate anger and reactive aggression in response to provocation are core symptoms of intermittent-explosive disorder (IED). Previous research shows a link between the propensity for aggression in healthy individuals and altered functioning of prefrontal-limbic and default-mode networks (DMN) at rest when no provocation is present. In a pilot study, we used resting-state functional magnetic resonance imaging to investigate the effects of pronounced reactive aggression in men, exemplified by IED, on the functional organization of resting-state brain networks including subcortical nodes such as the habenula previously implicated in aggression in preclinical models. Graph theory was applied to resting-state networks to determine alterations in global efficiency and clustering in high reactive aggressive men compared to low reactive aggressive men (controls). Further, we computed within-group correlations between trait aggression and graph measures, as well as within-group whole-brain seed-to-voxel regression analyses between trait aggression and habenula resting-state functional connectivity (rsFC). Reactive aggressive men compared to controls showed higher global efficiency in the left habenula, the left pulvinar in the thalamus, the left dorso-lateral prefrontal cortex, and the right temporal pole, as well as a trend for decreased clustering in DMN nodes. In the reactive aggressive group, high levels of trait aggression were linked to lower global efficiency of the left habenula, and to lower rsFC between the left habenula and the left ventro-lateral prefrontal cortex, a core region involved in inhibitory control. Together with preclinical evidence, our findings in men underline the relevance of aberrant habenula-prefrontal connectivity for the severity of aggressive behavior.

Original languageEnglish (US)
Article number107396
JournalNeuropharmacology
Volume156
DOIs
StatePublished - Sep 1 2019

Bibliographical note

Funding Information:
We thank Dr. Sam Golden (NIDA) for comments on the manuscript. This research was supported by the following funding agencies: National Institute of Mental health (NIMH; R01MH090134 to NAK), National Institute on Drug Abuse (NIDA; 1R01DA041528 to RZG; 1K01DA043615 to MAP; 1K01DA037452 to SJM), University of Heidelberg, Germany (the Olympia-Morata Program to GG), Nederlandse Organisatie voor Wetenschappelijk Onderzoek Netherlands (Rubicon 446-14-015 to AZ).

Funding Information:
We thank Dr. Sam Golden (NIDA) for comments on the manuscript. This research was supported by the following funding agencies: National Institute of Mental health (NIMH; R01MH090134 to NAK), National Institute on Drug Abuse (NIDA; 1R01DA041528 to RZG; 1K01DA043615 to MAP; 1K01DA037452 to SJM), University of Heidelberg, Germany (the Olympia-Morata Program to GG), Nederlandse Organisatie voor Wetenschappelijk Onderzoek Netherlands (Rubicon 446-14-015 to AZ).

Keywords

  • Graph theory
  • Habenula
  • Intermittent explosive disorder
  • Physical aggression
  • Reactive aggression
  • Resting-state fMRI

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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