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Review
. 2023 Feb 15:224:109355.
doi: 10.1016/j.neuropharm.2022.109355. Epub 2022 Nov 26.

The role of dlPFC laterality in the expression and regulation of anxiety

Lauren K White  1 , Walid Makhoul  2 , Marta Teferi  2 , Yvette I Sheline  2 , Nicholas L Balderston  3
Affiliations
Review

The role of dlPFC laterality in the expression and regulation of anxiety

Lauren K White et al. Neuropharmacology. .

Abstract

Anxiety disorders are the most common mental health disorder. Therefore, elucidating brain mechanisms implicated in anxiety disorders is important avenue for developing novel treatments and improving care. The dorsolateral prefrontal cortex (dlPFC) is thought to be critically involved in working memory processes (i.e. maintenance, manipulation, suppression, etc.). In addition, there is evidence that this region is involved in anxiety regulation. However, it is unclear how working memory related dlPFC processes contribute to anxiety regulation. Furthermore, we know that laterality plays an important role in working memory related dlPFC processing, however there is no current model of dlPFC mediated anxiety regulation that accounts for potential laterality effects. To address this gap, we propose a potential framework where the dlPFC contributes to emotion regulation via working memory processing. According to this framework, working memory is a fundamental process executed by the dlPFC. However, the domain of content differs across the left and right dlPFC, with the left dlPFC sensitive to primarily verbal content, and the right dlPFC sensitive to primarily non-verbal (affective content). Critically, working memory processes allow for both the retention and suppression of affective information in working memory and the overall net effect of processing on mood will depend on the balance of retention and suppression, the valence of the information being processed (positive vs. negative), and the domain of the information (verbal vs. non-verbal). If accurate, the proposed framework predicts that effects of neuromodulation targeting the dlPFC may be dependent upon the context during which the stimulation is presented. This article is part of the Special Issue on 'Fear, Anxiety and PTSD'.

Keywords: Anxiety; Neuromodulation; Threat; Working memory; dlPFC.

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Conflict of interest statement

Declaration of competing interest The authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1.
Figure 1.. Content domain framework.
According to the content domain framework, the dlPFC is primarily engaged in working memory related processes. However, the domain of information being processed differs across hemispheres. We posit that the primary domain of information processed by the left dlPFC is verbal, while the primary domain of information processed by the right dlPFC is non-verbal, with affect-related content making up a key sub-domain. Accordingly, both the left and right dlPFC can contribute to emotion regulation, depending on which working memory process is engaged, but their contributions will differ based on the domain of information being processed.
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