Functional neuroanatomy on the working memory under emotional distraction in patients with generalized anxiety disorder

Abstract

Aims: Patients with generalized anxiety disorder (GAD) suffer the symptoms of psychological distress, including excessive and uncontrollable anxiety. Until now, the functional neuroanatomy for working memory (WM) in conjunction with the major anxiety symptoms in GAD patients has not yet been clearly identified. This study investigated the neural activation patterns associated with the effect of neutral and anxiety-inducing distractors during the delayedresponse WM task in GAD patients.Methods: Eighteen patients with GAD and 18 agematched healthy controls participated in this study. The functional magnetic resonance images were obtained while the subjects performed a delayedresponse WM task with neutral and anxiety-inducing distractors.Results: During the neutral distractor, GAD patients compared to controls showed significantly lower activities in the fusiform gyrus, superior parietal gyrus, precuneus, superior occipital gyrus, lingual gyrus, cuneus, calcarine gyrus, parahippocampal gyrus and cerebellar cortex. During the anxietyinducing distractor, GAD patients showed significantly higher activity in the hippocampus, whereas they showed lower activities in the dorsolateral prefrontal cortex, fusiform gyrus, superior parietal gyrus, precuneus, superior occipital gyrus and cerebellar cortex. The blood-oxygen-level dependent signal changes in the dorsolateral prefrontal cortex in GAD patients during the anxiety-inducing distractor were negatively correlated with Anxiety Sensitivity IndexRevised scores.Conclusions: This study identified the specific brain areas associated with the interaction between emotional regulation and cognitive function associated with neutral and anxiety-inducing distractors during WM maintenance in GAD patients. These findings will be helpful for understanding the neural mechanism on the WM-related cognitive deficits and emotional dysfunction with typical anxiety symptoms in GAD.

Working memory dysfunction associated with brain functional deficits and cellular metabolic changes in patients with generalized anxiety disorder

“…Although GAD is a highly prevalent and incapacitating disorder, previous studies (Price et al, 2011;Ball et al, 2013;Moon et al, 2015a;Moon et al, 2015b) focusing on the cognitive dysfunctions in GAD have been performed and it is still unclear whether cerebral metabolic change is associated with the brain activation patterns during the WM tasks with emotional distraction. Therefore, it is assumed that a combined use of the fMRI and 1 H-MRS provides more valuable information on the neural mechanisms associated with GAD dysfunction.…”

“…The activation paradigm (Kim et al, 2015;Moon et al, 2015b) consisted of a string of cue and encoding (6 sec)-delay (4 sec)-distractor (6 sec)-button ready (2 sec)-retrieval (2 sec)-intertrial rest (12 sec) (Fig. 1).…”

“…Therefore, the DLPFC is considered as an important core region of interest on the neural mechanisms underlying the cognitive control and emotion regulation in GAD. Recently, a preliminary study (Moon et al, 2015b) reported the functional neuroanatomy on the WM with emotional dysfunction in GAD. In addition to fMRI, the use of proton magnetic resonance spectroscopy ( 1 H-MRS) would be useful to gain more valuable information on the neural mechanism associated with GAD symptoms, because 1 H-MRS is capable of providing the brain metabolic information related to the pathogenesis, status of axonal damage and neuronal loss prior to functional changes in brain tissue (Meyerhoff et al, 1994;Maddock et al, 2012).…”

“…The DLPFC plays an important role in cognitive functions including attention and working memory (WM), as well as in the regulation of emotional responses (Moon et al, 2015b). Therefore, the DLPFC is considered as an important core region of interest on the neural mechanisms underlying the cognitive control and emotion regulation in GAD.…”

Temporal profile of brain response to alprazolam in patients with generalized anxiety disorder

“…Surveying the broad cerebral effects of alprazolam in future research will require the use of an array of behavioral paradigms to probe brain activity more broadly. FMRI studies of emotion regulation in GAD, which combine emotionally laden stimuli with working memory or attentional control demands, have used paradigms that probe a wider variety of brain systems than investigated in this study (Klumpp, et al, 2014;Moon and Jeong, 2015).…”