Comparative Functional Connectivity of Core Brain Regions between Implicit and Explicit Memory Tasks Underlying Negative Emotion in General Anxiety Disorder

Abstract

Objective To investigate not only differential patterns of functional connectivity of core brain regions between implicit and explicit verbal memory tasks underlying negatively evoked emotional condition, but also correlations of functional connectivity (FC) strength with clinical symptom severity in patients with generalized anxiety disorder (GAD). Methods Thirteen patients with GAD and 13 healthy controls underwent functional magnetic resonance imaging for memory tasks with negative emotion words. Results Clinical symptom and its severities of GAD were potentially associated with abnormalities of task-based FC with core brain regions and distinct FC patterns between implicit vs. explicit memory processing in GAD were potentially well discriminated. Outstanding FC in implicit memory task includes positive connections of precentral gyus (PrG) to inferior frontal gyrus and inferior parietal gyrus (IPG), respectively, in encoding period; a positive connection of amygdala (Amg) to globus pallidus as well as a negative connection of Amg to cerebellum in retrieval period. Meanwhile, distinct FC in explicit memory included a positive connection of PrG to inferior temporal gyrus (ITG) in encoding period; a positive connection of the anterior cingulate gyrus to superior frontal gyrus in retrieval period. Especially, there were positive correlation between GAD-7 scores and FC of PrG-IPG ( r 2 = 0.324, p = 0.042) in implicit memory encoding, and FC of PrG-ITG ( r 2 = 0.378, p = 0.025) in explicit memory encoding. Conclusion This study clarified differential patterns of brain activation and relevant FC between implicit and explicit verbal memory tasks underlying negative emotional feelings in GAD. These findings will be helpful for an understanding of distinct brain functional mechanisms associated with clinical symptom severities in GAD.

Imaging the cerebellum in post-traumatic stress and anxiety disorders: a mini-review

“…In line with this, another study using a similar task noted decreased activation of the left cerebellum in PD patients with comorbid agoraphobia, relative to controls ( Petrowski et al, 2014 ). A negative amygdala to cerebellum connectivity was found in GAD participants during implicit verbal memory tasks ( Park et al, 2022 ), and in SAD patients undergoing cognitive-behavioral treatment positive changes in amygdala-cerebellar connectivity predicted less improvement ( Sandman et al, 2020 ). Finally, fMRI studies on SP reported an increased bilateral activation of the cerebellum of participants with spider phobia and left cerebellum hyperactivation in blood-injection-injury phobia ( Caseras et al, 2010 ) during processing of phobia-related visual stimuli.…”

“…It has been increasingly recognized that the functions of cerebellum extend into emotions, including fear and anxiety. The cerebellum could work as a complementary region to the amygdala in emotional reactivity and modulation ( Strata, 2015 ), and the amygdala-cerebellum reciprocal link has been shown to be aberrantly functioning in post-traumatic stress and anxiety disorders ( Nicholson et al, 2015 ; Thome et al, 2017 ; Sandman et al, 2020 ; Du et al, 2021 ; Park et al, 2022 ). Hence, this mini-review evaluated functional (task activity, resting state connectivity) and structural (gray matter) findings on the cerebellum reported in MRI studies of patients with PTSD or anxiety disorders.…”

“…Across the anxiety disorders, results were mixed with regard to cerebellar hyper- or hypoactivation in task-based fMRI trials. Altered amygdala to cerebellum FC was noted in GAD ( Park et al, 2022 ) and also following psychological intervention in SAD ( Sandman et al, 2020 ). In SP, even when considering different types like blood and spider phobia, fMRI results seemed more homogeneous, showing increased activation of the left cerebellum and lobule VI.…”

The classification of brain network for major depressive disorder patients based on deep graph convolutional neural network

“… Cattarinussi et al (2022) collected the resting-state fMRI of Bipolar Disorder to study the alteration of the brain functional network between cortical-limbic structures. Park et al (2022) demonstrated that the severity of clinical symptoms in patients with Generalized Anxiety Disorder had a strong correlation with the strength of FC in brain regions under negative emotional conditions. Hirshfeld-Becker et al (2019) conducted a pilot study of MDD prediction in Adolescence by intrinsic brain FC.…”

Salivary Antioxidant Capacity and Magnesium in Generalized Anxiety Disorder

“…There are several studies on the morphology and biochemistry of GAD, but they are scattered and clearly not sufficient and have not yet been translated into clinical practice. To date, the main morphological biomarkers are obtained from neuroimaging studies, including various variants of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission computed tomography, and proton magnetic resonance spectroscopic imaging methods [ 3 , 4 , 5 ]. As for the biochemical analysis, plasma is mostly used as it contains certain brain metabolites that penetrate the blood–brain barrier and can be quantified for proteomic and metabolomic analyses.…”