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Association of explicit memory dysfunction with regional brain volume alterations in patients with generalized anxiety disorder

Chung Man Moon^1,2 and Gwang Woo Jeong²

¹National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, United States, ²Radiology, Chonnam National University Medical School, Gwangju, Korea, Republic of

Synopsis

Generalized anxiety disorder (GAD) causes emotional dysregulations and/or cognitive deficits, including excessive anger, impairments of explicit and implicit memories and poor attention. A DARTEL-based voxel-based morphometry (VBM) study for assessing the relationship between morphometric abnormalities and explicit memory dysfunction in patients with GAD has not yet been reported. Therefore, the purpose of this study is to investigate the regional gray matter (GM) and white matter (WM) volume alterations over the whole brain in patients with GAD, as well as the correlation between the brain structural abnormality and explicit memory dysfunction. Our findings would be helpful to understand the association between the brain structure abnormality and the functional deficit in the explicit memory in GAD.

Purpose

Subjects and Methods

Twenty patients with GAD and 20 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted MRI at a 3 T Magnetom Verio MR scanner (Siemens Medical Solutions, Erlangen, Germany). The subjects performed the explicit memory tasks with the neutral and anxiety-inducing words.

The explicit memory tasks were performed using neutral and anxiety-inducing words for the evaluation of the effect of the emotional regulation on memory function in GAD. The words of each type were selected from a lexical database of the Korean language, in which neutral words consist of a kind of words inducing a comfortable feeling, while anxiety-inducing words include threatening words.

The MRI data were post-processed using the statistical parametric mapping (SPM) 12 program (Wellcome Department of Imaging Neuroscience Group, London, UK) with DARTEL analysis. To clarify the association between the GM and WM volumes and explicit memory impairments, the multiple regressions for the volumetric change and the accuracy and reaction time were analyzed using the SPM statistical package, in which the correlation coefficients were assessed by Pearson’s correlation test with a 95% confidence interval.

Results and Discussion

Patients with GAD showed significantly reduced GM volumes in the midbrain (MB), thalamus (Th), hippocampus (Hip), insula (Ins) and superior temporal gyrus (STG) (Fig. 1); and reduced WM volumes in the MB, anterior limb of the internal capsule (ALIC), dorsolateral prefrontal cortex (DLPFC) and precentral gyrus (PrG) (Fig. 2).

It is important to note that the GM volume of the Hip and the WM volume of the DLPFC were positively correlated with the recognition accuracy (%) in the explicit memory tasks with neutral and anxiety-inducing words, respectively (Fig. 3). On the other hand, the WM volume of the PrG was negatively correlated with the reaction time in the same memory tasks (Fig. 3).

One of most interesting findings in this study is the reduced volumes of the Hip and DLPFC in patients with GAD. It is well-known that the Hip plays critical roles in memory storage and retrieval in connection with cognitive functions, as well as the integration of emotion and cognition. Also, the DLPFC is a key center involved in cognitive functions including attention and working memory, as well as regulation of emotional responses.

These findings suggest that the morphological alterations in the Hip and DLPFC disrupt the cognitive and emotional functions, resulting in the psychopathological symptoms of GAD.

Conclusion

This study demonstrated the regional volume changes of the GM and WM across the whole-brain and the correlation between the brain structural alteration and explicit memory dysfunction was also evaluated. These findings would be helpful to understand the association between the brain structure abnormality and the functional deficit in the explicit memory in GAD.

Acknowledgements

This work was supported by the funds from the National Research Foundation of Korea (2017R1A6A3A11030092; 2018R1A2B2006260) and JNU Research Distinguished Emeritus Professor (2017-2022).

References

Strawn JR, Wehry AM, Chu WJ et al. Neuroanatomic abnormalities in adolescents with generalized anxiety disorder: a voxel-based morphometry study. Depress Anxiety 2013;30:842-848.

Figures

Figure 1. Brain areas showing significantly reduced gray matter (GM) volumes in patients with GAD relative to healthy controls, which were resulted from two-sample t-test.

Figure 2. Brain areas showing significantly reduced white matter (WM) volumes in patients with GAD relative to healthy controls, which were resulted from two-sample t-test.

Figure 3. The correlations between the GM or WM volume changes and the accuracy (%) and reaction times (ms) for the recognition test in the explicit memory tasks with neutral and anxiety-inducing words: GM volume in the Hip vs. accuracy with neutral word (a) (γ = 0.672, p = 0.001) and anxiety-inducing word (b) (γ = 0.556, p = 0.011), WM volume in the DLPFC vs. accuracy with neutral word (c) (γ = 0.547, p = 0.013) and anxiety-inducing word (d) (γ = 0.601, p = 0.005), and WM volume in the PrG vs. reaction time with neutral word (e) (γ = -0.497, p = 0.026) and anxiety-inducing word (f) (γ = -0.541, p = 0.014) in patients with GAD, in which the band with dotted lines shows 95% confidence interval.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)

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