Altered Task-Evoked Corticolimbic Responsivity in Generalized Anxiety Disorder

Abstract

Generalized anxiety disorder (GAD) is marked by uncontrollable, persistent worry and exaggerated response to uncertainty. Here, we review and summarize the findings from the GAD literature that employs functional neuroimaging methods. In particular, the present review focuses on task-based blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We find that select brain regions often regarded as a part of a corticolimbic circuit (e.g., amygdala, anterior cingulate cortex, prefrontal cortex) are consistently targeted for a priori hypothesis-driven analyses, which, in turn, shows varying degrees of abnormal BOLD responsivity in GAD. Data-driven whole-brain analyses show the insula and the hippocampus, among other regions, to be affected by GAD, depending on the task used in each individual study. Overall, while the heterogeneity of the tasks and sample size limits the generalizability of the findings thus far, some promising convergence can be observed in the form of the altered BOLD responsivity of the corticolimbic circuitry in GAD.

Editorial of the Special Issue “Neurobiological Mechanisms Implicated in Stress-Related Psychiatric Disorders”

“…Kim et al reviewed neuroimaging reports on generalized anxiety disorder (GAD). Their findings confirmed various degrees of abnormal blood oxygenation level-dependent (BOLD) responsivity in the corticolimbic circuitry of patients with GAD, including the amygdala, prefrontal and anterior cingulate cortex, hippocampus, and insula [13].…”

Topographical similarity of cortical thickness represents generalized anxiety symptoms in adolescence

“…Adolescents with heightened generalized anxiety symptoms shared similar cortical thickness topography in the left caudal ACC with each other, more so than those with lower anxiety. The ACC, one of the most frequently targeted brain regions in GAD research (Kim & Kim, 2021), is generally understood to be important for generating worry – a defining characteristic of GAD (Comer et al, 2004). In particular, the caudal ACC is known to be associated with fear expression, especially in regulating heart rate and skin conductance response (Heilbronner & Hayden, 2016; Milad et al, 2007).…”

Sex differences in anxiety and threat avoidance in GAD65 knock-out mice

“…One of those variants results in increased GABA levels especially in the ACC, as revealed by fMRI-SPECT, and was associated to increased harm avoidance behavior in females but not males as an anxietyrelated trait (Colic, 2018). While functional imaging studies indeed pinpoint to the ACC as an important region for emotion regulation (Mochkovotich et al, 2014;Goossen et al, 2019;Kim & Kim, 2021), sex-specific regulation differences are not well studied. Interestingly in female, but not male healthy volunteers ACC volume and positive coping style predicted lower anxiety-or depression-related psychopathologies (Holz et al, 2016).…”

“…Differential activation of frontal cortical areas such as the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) is evident between men and women depending on the emotional valence of presented stimuli, induced stress levels or prior adverse childhood experiences (Thomas et al, 2019; Javanbakht et al, 2016; Seo et al, 2017; Stevens & Hamann 2012). Accordingly, a dysfunctional activation of those cortical regions and their interaction with the amygdala and the hippocampal formation are observed during emotion regulation in anxiety patients (Mochkovotich et al, 2014; Goossen et al, 2019; Kim & Kim, 2021). This matches the basic function of these areas and their homologous structures in rodents regulating fear and anxiety as well as emotional affect, attention and decision making (Admon et al, 2013; Tovote et al, 2015; van Heukelum et al, 2020; Chen et al, 2022).…”