Differential White Matter Tracts in Generalized Anxiety Disorder using 7T Diffusion Tensor Imaging
Poster No:
429
Submission Type:
Abstract Submission
Authors:
Chang-Le Chen1, Yueyang Chi1, Minjie Wu1, Max Rose1, Jessica Weber1, Shannon Lamb1, Cecile Ladouceur1, Yue-Fang Chang1, Kuei Tseng2, Howard Aizenstein1, Shaolin Yang1
Institutions:
1University of Pittsburgh, Pittsburgh, PA, 2University of Illinois at Chicago, Chicago, IL
First Author:
Co-Author(s):
Introduction:
Generalized anxiety disorder (GAD) is a prevalent psychiatric condition that is frequently underdiagnosed primarily due to the limited understanding of its neurobiological mechanisms [1,2]. The emotion dysregulation model has been proposed to explain the neural basis of GAD by presenting two competing hypotheses: one suggests hyper-activation of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) during emotion regulation due to overactive top-down control, while the other proposes attenuated PFC and ACC responses, reflecting insufficient top-down control during this process [2]. Both hypotheses denote that GAD is associated with altered neurocircuitry underlying the emotional deregulation process [1,3]; however, literature using diffusion MRI techniques has reported inconsistent findings of altered neuronal pathways. To address the hypotheses, we utilized 7T diffusion tensor imaging (DTI) with correlational tractography to investigate altered neuronal circuits involved in GAD.
Methods:
Twenty-seven young adults with GAD (age: 21.9 [2.5], female: 20) and their demographic-matched controls (n = 61, age: 21.7 [2.4], female: 43) were enrolled in this study. To identify the altered neural pathway in GAD, all participants went through brain MRI examination with a 7T scanner (Siemens MAGNETOM, Erlangen, Germany) to acquire DTI data (46 diffusion encoding direction plus 4 b0 images, TR=6500ms, TE=81.6ms, b-value=1010 s/mm², in-plane resolution=1.5mm, slice thickness=1.5mm). The DTI data were preprocessed using TOPUP/EDDY from FSL to correct susceptibility artifact and eddy current distortion. The DTI data were then reconstructed in the MNI space using q-space diffeomorphic reconstruction to obtain spin orientations for tractography [4]. Tensor metrics including fractional anisotropy (FA) and mean diffusivity (MD) were calculated to represent white matter (WM) properties. Connectometry analysis was performed to derive whole brain correlational tractography that traces the neuronal pathway correlated with the difference in tensor metrics between GAD and controls while adjusting the effects of age, sex, education, handedness, and the lateral ventricle volume [5]. A false discovery rate threshold of 0.05 was used to select tracks. The identified differential WM tracts were automatically recognized and clustered according to the fiber system [6]. The tensor metrics were further sampled to confirm the group difference based on the tract streamlines and correlated with emotional measures such as Penn State Worry Questionnaire (PSWQ) score and Hamilton Anxiety Rating Scale (HAM-A) score to test neuropsychological relevance.
Results:
Two differential WM fiber bundles were identified in the FA metric between GAD and controls; the fiber bundles in the right PFC showed significantly decreased FA values in GAD (0.303 [0.096]) compared to the controls (0.352 [0.100]) (pFDR = 0.0394) (Figure 1). The fiber bundles mainly cover the corpus callosum forceps minor and corticostriatal tract anterior. In contrast, the fiber bundles in the right cingulum showed significantly increased FA values in GAD (0.502 [0.093]) compared to the controls (0.435 [0.095]) (pFDR = 0.0078) (Figure 1). The fiber bundles mainly include the cingulum frontoparietal connection. However, no significant finding was found in the MD metric. The FA value of the identified fiber bundles in the right cingulum revealed significantly positive correlation with PSWQ (pFDR = 0.0196) and HAM-A (pFDR = 0.0486) after adjusting covariates, while that in the right PFC only showed marginally negative correlation with HAM-A (pFDR = 0.0803) (Figure 2).
Conclusions:
The results indicate that reduced WM integrity in the right PFC may support the hypothesis of hypoactive PFC top-down control, while increased WM integrity in the right cingulum aligns with the hypothesis of hyperactive ACC regulation. These identified fiber bundles may serve as potential differential markers for the neural basis of GAD.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Diffusion MRI Modeling and Analysis
Keywords:
Anxiety
Emotions
MRI
Psychiatric Disorders
Tractography
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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[2] Mochcovitch, M. D., da Rocha Freire, R. C., Garcia, R. F., & Nardi, A. E. (2014). A systematic review of fMRI studies in generalized anxiety disorder: evaluating its neural and cognitive basis. Journal of affective disorders, 167, 336-342.
[3] Qiao, J., Li, A., Cao, C., Wang, Z., Sun, J., & Xu, G. (2017). Aberrant functional network connectivity as a biomarker of generalized anxiety disorder. Frontiers in human neuroscience, 11, 626.
[4] Yeh, F. C., & Tseng, W. Y. I. (2011). NTU-90: a high angular resolution brain atlas constructed by q-space diffeomorphic reconstruction. Neuroimage, 58(1), 91-99.
[5] Yeh, F. C., Badre, D., & Verstynen, T. (2016). Connectometry: A statistical approach harnessing the analytical potential of the local connectome. Neuroimage, 125, 162-171.
[6] Yeh, F. C. (2022). Population-based tract-to-region connectome of the human brain and its hierarchical topology. Nature communications, 13(1), 4933.