Hippocampal GABA enables inhibitory control over unwanted thoughts

• Published in: Nature communications Vol. 8; no. 1; pp. 1311 - 12
• Main Authors: Schmitz, Taylor W., Correia, Marta M., Ferreira, Catarina S., Prescot, Andrew P., Anderson, Michael C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.11.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1595/1554; 631/378/2649/2150; Adult; Blood; Female; Functional magnetic resonance imaging; Functional Neuroimaging; gamma-Aminobutyric Acid - physiology; Hallucinations; Hippocampus; Hippocampus - physiology; Humanities and Social Sciences; Humans; Hyperactivity; Hypotheses; Interneurons; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Medical imaging; Memory; Memory - physiology; Mental disorders; Models, Neurological; Models, Psychological; multidisciplinary; Neuroimaging; Post traumatic stress disorder; Predictive control; Prefrontal cortex; Prefrontal Cortex - physiology; Repression, Psychology; Retrieval; Schizophrenia; Science; Science (multidisciplinary); Spectroscopy; Spectrum analysis; Temporal Lobe - physiology; Young Adult; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-00956-z

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. 1 H 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. It is not fully understood how intrusive or unwanted memories are regulated. Here the authors show that hippocampal GABA concentrations, and coupling between the dorsolateral prefrontal cortex and hippocampus, predict how well subjects can suppress unwanted memories when presented with a reminder.