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Nat Commun. 2017 Nov 3;8(1):1311. doi: 10.1038/s41467-017-00956-z.

Hippocampal GABA enables inhibitory control over unwanted thoughts.

Author information

1
MRC Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, UK. tws35@cam.ac.uk.
2
Wolfson College, University of Cambridge, Cambridge, CB3 9BB, UK. tws35@cam.ac.uk.
3
MRC Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, UK.
4
Downing College, University of Cambridge, Cambridge, CB2 1DQ, UK.
5
Research Center for Mind, Brain and Behavior, University of Granada, Granada, 18011, Spain.
6
School of Medicine, University of Utah, Salt Lake City, Utah, 84132, USA.
7
MRC Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, UK. Michael.Anderson@mrc-cbu.cam.ac.uk.
8
Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, CB2 3EB, UK. Michael.Anderson@mrc-cbu.cam.ac.uk.

Abstract

Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory for suppressed content. 1H magnetic resonance spectroscopy revealed that greater resting concentrations of hippocampal GABA predicted better mnemonic control. Higher hippocampal, but not prefrontal GABA, predicted stronger fronto-hippocampal coupling during suppression, suggesting that interneurons local to the hippocampus implement control over intrusive thoughts. Stopping actions did not engage this pathway. These findings specify a multi-level mechanistic model of how the content of awareness is voluntarily controlled.

PMID:
29101315
PMCID:
PMC5670182
DOI:
10.1038/s41467-017-00956-z
[Indexed for MEDLINE]
Free PMC Article

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