The ability to control thoughts is fundamental to our wellbeing. When this capacity breaks down, it causes some of the most debilitating symptoms of psychiatric diseases: intrusive memories, images, hallucinations, ruminations, and pathological worry. These debilitating symptoms are widely believed to reflect, in part, the diminished engagement of the prefrontal cortex to stop unwanted mental processes, a process known as inhibitory control. However, these disorders share another feature that is not usually considered relevant to controlling thoughts: hippocampal hyperactivity.
In this article, published in Nature Communications journal, MRC Cognition and Brain Sciences Unit’s Mike Anderson and Taylor Schmitz worked with colleagues to examine why this recurring feature, rarely considered by researchers interested in cognitive control, is often strongly related to the occurrence and frequency of intrusive symptomatology.
In a group of healthy participants, the relationship between cognitive control and hippocampal GABA were examined by combining a cognitive manipulation that indexes the ability to suppress unwanted thoughts, with fMRI and in vivo measures of GABA obtained with 1H MR spectroscopy. This multimodal neuroimaging strategy allowed us to detect, within the same individuals, co-localized measures of cortical GABA concentrations and cortical activity when people were suppressing the retrieval process to exclude an unwanted thought from awareness.
Hippocampal GABA predicted suppression-induced hippocampal BOLD reductions and how well people forgot the thoughts they tried to suppress. These relationships were both functionally and anatomically specific. The observed relationships were not accounted for by other inhibitory control tasks that involved inhibiting actions rather than thoughts (Stop-Signal task). Nor was either relationship accounted for by GABA concentrations in other brain regions such as prefrontal and visual cortex. Importantly, hippocampal GABA concentration predicts the functional connectivity within a broader network involving lateral prefrontal cortex.
Their work establishes that hippocampal GABA constrains the ability to the prefrontal cortex to exert long-range control over the hippocampus, specifically in the context of suppressing unwanted thoughts. These findings motivate further research on the hippocampal GABAergic system in humans. Ultimately, such work advanced the mechanistic basis cognitive control and its dysregulation across multiple psychiatric disorders.
Schmitz, TW et al. Hippocampal GABA enables inhibitory control over unwanted thoughts. Nature Communications; 3 Nov 2017; DOI: 10.1038/s41467-017-00956-z