EXPLORING BRAIN CHANGES IN SELF-REPORTED ANXIETY: CUTTING-EDGE EXPLORATORY DIFFUSION TENSOR IMAGING STUDY REVEALS DISTINCT ALTERATIONS IN WHITE MATTER TRACT STRUCTURE AMONG NON-CLINICAL INDIVIDUALS

Authors

  • Wan Adibah Nadiah Abd Razak Occupational Safety and Health Program, Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, 26300 Kuantan, Malaysia
  • Rajeev Shamsuddin Perisamy Department of Radiology, Sultan Ahmad Shah Medical Centre @IIUM, Jalan Sultan Ahmad Shah, 25200 Kuantan, Malaysia
  • Che Mohd Nasril Che Mohd Nassir Physiology Unit, School of Basic Medical Sciences, Faculty of Medicine, Universiti Sultan Zainal Abidin, 20400 Kuala Terengganu, Malaysia
  • Muzaimi Mustapha Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia. 16150 Kubang Kerian, Malaysia
  • Mohd Khairul Izamil Zolkefley Occupational Safety and Health Program, Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, 26300 Kuantan, Malaysia

DOI:

https://doi.org/10.37231/apj.2025.8.1.742

Abstract

Abstract: Previous research utilising diffusion tensor imaging (DTI) has reported disruptions in white matter pathways among individuals with anxiety-related disorders. However, there is limited research focusing on healthy or non-clinical groups with self-reported anxiety symptoms. This investigation aims to explore how self- reported anxiety relates to white matter microstructural differences in non-clinical adult brains. A total of twenty-nine participants took part in the study. Each participant completed the Depression Anxiety Stress Scale-21 (DASS-21) and underwent a detailed high-resolution 3T magnetic resonance imaging (MRI). Diffusion MRI connectometry was conducted to generate correlational tractography, identifying links between generalised fractional anisotropy (FA) values of white matter and anxiety scores derived from the DASS-21. The average anxiety score, as measured by the DASS-21, was 10.97 with a standard deviation of 7.002. Notably, a significant inverse association emerged between anxiety levels and FA values in several white matter regions, including the left and right inferior fronto-occipital fasciculi, the left inferior longitudinal fasciculus, the right superior longitudinal fasciculus, and the left parahippocampal cingulum bundle (p < 0.05). The local brain connectome associated with anxiety may serve as a biomarker for early diagnosis and prevention of anxiety disorders in non-clinical populations.

Keywords: Anxiety; Connectometry; Diffusion Tensor Imaging; White Matter; DASS-21

References

Abd Razak, W. A. N., Perisamy, R. S., Zulkifli, N. S. A., Abdul Basit, K. S., Mustapha, M., & Zolkefley, M. K. I. (2024). Role of Microstructural White Matter Changes of Somatosensory Cortex in Stress Among Non- Clinical Population: A Diffusion Tensor Imaging Study. IIUM Medical Journal Malaysia, 23(04), 78–85.

Ayling, E., Aghajani, M., Fouche, J.-P., & van der Wee, N. (2012). Diffusion Tensor Imaging in Anxiety Disorders. Current Psychiatry Reports, 14(3), 197–202.

Baron-Cohen, S., Ring, H., Moriarty, J., Schmitz, B., Costa, D., & Ell, P. (1994). Recognition of mental state terms. British Journal of Psychiatry, 165(5), 640–649.

Besteher, B., Gaser, C., & Nenadić, I. (2020). Brain Structure and Subclinical Symptoms: A Dimensional Perspective of Psychopathology in the Depression and Anxiety Spectrum. Neuropsychobiology, 79(4–5), 270–283.

Bishop, S. J. (2007). Neurocognitive mechanisms of anxiety: an integrative account. Trends in Cognitive Sciences, 11(7), 307–316.

Cannistraro, P. A., & Rauch, S. L. (2003). Neural circuitry of anxiety: evidence from structural and functional neuroimaging studies. Psychopharmacology Bulletin, 37(4), 8–25.

Claudino, R. G. e., de Lima, L. K. S., de Assis, E. D. B., & Torro, N. (2019). Facial expressions and eye tracking in individuals with social anxiety disorder: a systematic review. Psicologia: Reflexao e Critica, 32(1).

Dalgleish, T. (2004). The emotional brain. Nature Reviews Neuroscience, 5(7), 583–589.

Dupont, W. D., & Plummer, W. D. (1990). Power and sample size calculations. A review and computer program. Controlled Clinical Trials, 11(2), 116–128.

Etkin, A., & Mathalon, D. H. (2024). Bringing Imaging Biomarkers Into Clinical Reality in Psychiatry. JAMA Psychiatry, 81(11), 1142–1147.

Fan, Y. S., Li, Z., Duan, X., Xiao, J., Guo, X., Han, S., Guo, J., Yang, S., Li, J., Cui, Q., Liao, W., & Chen, H. (2020). Impaired interactions among white-matter functional networks in antipsychotic-naive first-episode schizophrenia. Human Brain Mapping, 41(1), 230–240.

Fan, Y. T., Lin, K. C., Liu, H. L., Chen, Y. L., & Wu, C. Y. (2015). Changes in structural integrity are correlated with motor and functional recovery after post-stroke rehabilitation. Restorative Neurology and Neuroscience, 33(6), 835–844.

Gawryluk, J. R., Mazerolle, E. L., & D’Arcy, R. C. N. (2014). Does functional MRI detect activation in white matter? A review of emerging evidence, issues, and future directions. Frontiers in Neuroscience, 8(239).

Gore, J. C., Li, Muwei., Gao, Yurui., Wu, T. L., Schilling, K. G., Huang, Y., Mishra, A., Newton, A. T., Rogers, B. P., Chen, L. M., Anderson, A. W., & Ding, Z. (2019). Functional MRI and resting state connectivity in white matter - a mini-review. Magnetic Resonance Imaging, 63, 1–11.

Hahn, A., Stein, P., Windischberger, C., Weissenbacher, A., Spindelegger, C., Moser, E., Kasper, S., & Lanzenberger, R. (2011). Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. NeuroImage, 56(3), 881–889.

Hasan, K. M., & Narayana, P. A. (2006). Retrospective measurement of the diffusion tensor eigenvalues from diffusion anisotropy and mean diffusivity in DTI. Magnetic Resonance in Medicine, 56(1), 130–137.

Hein, T. C., Mattson, W. I., Dotterer, H. L., Mitchell, C., Lopez-Duran, N., Thomason, M. E., Peltier, S. J., Welsh, R. C., Hyde, L. W., & Monk, C. S. (2018). Amygdala habituation and uncinate fasciculus connectivity in adolescence: A multi-modal approach. NeuroImage, 183, 617–626.

Henry, J. D., & Crawford, J. R. (2005). The short-form version of the Depression Anxiety Stress Scales (DASS- 21): Construct validity and normative data in a large non-clinical sample. British Journal of Clinical Psychology, 44(2), 227–239.

Huang, Y., Yang, Y., Hao, L., Hu, X., Wang, P., Ding, Z., Gao, J. H., & Gore, J. C. (2020). Detection of functional networks within white matter using independent component analysis. Neuroimage, 222(117278).

Iidaka, T., Okada, T., Murata, T., Omori, M., Kosaka, H., Sadato, N., & Yonekura, Y. (2002). Age-related differences in the medial temporal lobe responses to emotional faces as revealed by fMRI. Hippocampus, 12(3), 352–362.

Jeurissen, B., Descoteaux, M., Mori, S., & Leemans, A. (2019). Diffusion MRI fiber tractography of the brain. NMR in Biomedicine, 32(4), e3785.

Jung, Y. H., Shin, J. E., Lee, Y. I., Jang, J. H., Jo, H. J., & Choi, S. H. (2018). Altered amygdala resting-state functional connectivity and hemispheric asymmetry in patients with social anxiety disorder. Frontiers in Psychiatry, 9(164).

Kartashov, S., Mitiureva, D., & Martynova, O. (2022). Reproduced correlations between integrity of white matter tracts and self-reported anxiety. Procedia Computer Science, 213, 546–555.

Kim, S. H., Cornwell, B., & Kim, S. E. (2012). Individual differences in emotion regulation and hemispheric metabolic asymmetry. Biological Psychology, 89(2), 382–386.

Kim, Y. K., & Yoon, H. K. (2018). Common and distinct brain networks underlying panic and social anxiety disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 80, 115–122.

Kolesar, T. A., Bilevicius, E., Wilson, A. D., & Kornelsen, J. (2019). Systematic review and meta-analyses of neural structural and functional differences in generalized anxiety disorder and healthy controls using magnetic resonance imaging. NeuroImage: Clinical, 24, 102016.

Kotov, R., Krueger, R. F., Watson, D., Achenbach, T. M., Althoff, R. R., Bagby, R. M., Brown, T. A., Carpenter, W. T., Caspi, A., Clark, L. A., Eaton, N. R., Forbes, M. K., Forbush, K. T., Goldberg, D., Hasin, D., Hyman, S. E., Ivanova, M. Y., Lynam, D. R., Markon, K., … Zimmerman, M. (2017). The Hierarchical Taxonomy of Psychopathology (HiTOP): A dimensional alternative to traditional nosologies. Journal of Abnormal Psychology, 126(4), 454–477.

Latini, F. (2015). New insights in the limbic modulation of visual inputs: The role of the inferior longitudinal fasciculus and the Li-Am bundle. Neurosurgical Review, 38(1), 179–190.

Lee, K. S., & Lee, S. H. (2020). White matter-based structural brain network of anxiety. In Advances in Experimental Medicine and Biology, 1191, 61–70.

Li, F., Sun, H., Biswal, B. B., Sweeney, J. A., & Gong, Q. (2021). Artificial intelligence applications in psychoradiology. Psychoradiology, 1(2), 94–107.

Li, P., Legault, J., & Litcofsky, K. A. (2014). Neuroplasticity as a function of second language learning: Anatomical changes in the human brain. Cortex, 58, 301–324.

Linke, J. O. (2019). The Uncinate Fasciculus in Anxiety Disorders: A Potential Treatment Target? Biological Psychiatry, 86(12), e47–e48.

Liu, Z., Hu, Y., Zhang, Y., Liu, W., Zhang, L., Wang, Y., Yang, H., Wu, J., Cheng, W., & Yang, Z. (2021). Altered gray matter volume and structural co-variance in adolescents with social anxiety disorder: evidence for a delayed and unsynchronized development of the fronto-limbic system. Psychological Medicine, 51(10), 1742–1751.

Lochner, C., Fouché, J. P., du Plessis, S., Spottiswoode, B., Seedat, S., Fineberg, N., Chamberlain, S. R., & Stein, D. J. (2012). Evidence for fractional anisotropy and mean diffusivity white matter abnormalities in the internal capsule and cingulum in patients with obsessive-compulsive disorder. Journal of Psychiatry and Neuroscience, 37(3), 193–199.

Lu, M., Yang, C., Chu, T., & Wu, S. (2018). Cerebral White Matter Changes in Young Healthy Individuals With High Trait Anxiety: A Tract-Based Spatial Statistics Study. Frontiers in Neurology, 9(704).

Lui, S., Zhou, X. J., Sweeney, J. A., & Gong, Q. (2016). Psychoradiology: The frontier of neuroimaging in psychiatry. Radiology, 281(2), 357–372.

Martinez-Heras, E., Grussu, F., Prados, F., Solana, E., & Llufriu, S. (2021). Diffusion-Weighted Imaging: Recent Advances and Applications. Seminars in Ultrasound, CT and MRI, 42(5), 490–506.

Martynova, O., Tetereva, A., Balaev, V., Portnova, G., Ushakov, V., & Ivanitsky, A. (2020). Longitudinal changes of resting-state functional connectivity of amygdala following fear learning and extinction. International Journal of Psychophysiology, 149, 15–24.

Marussich, L., Lu, K. H., Wen, H., & Liu, Z. (2017). Mapping white-matter functional organization at rest and during naturalistic visual perception. Neuroimage, 146, 1128–1141.

Mellings, T. M. B., & Alden, L. E. (2000). Cognitive processes in social anxiety: the effects of self-focus, rumination and anticipatory processing. Behaviour Research and Therapy, 38(3), 243–257.

Mišić, B., & Sporns, O. (2016). From regions to connections and networks: New bridges between brain and behavior. Current Opinion in Neurobiology, 40, 1–7.

Mizzi, S., Pedersen, M., Lorenzetti, V., Heinrichs, M., & Labuschagne, I. (2022). Resting-state neuroimaging in social anxiety disorder: a systematic review. Molecular Psychiatry, 27(1), 164–179.

Osma, J., Martínez-Loredo, V., Quilez-Orden, A., Peris-Baquero, Ó., & Suso-Ribera, C. (2021). Validity Evidence of the Multidimensional Emotional Disorders Inventory among Non-Clinical Spanish University Students. International Journal of Environmental Research and Public Health, 18(16), 8251.

Parsaei, M., Hasehmi, S. M., Seyedmirzaei, H., Cattarinussi, G., Sambataro, F., Brambilla, P., & Delvecchio, G. (2024). Microstructural white matter alterations associated with social anxiety disorders: A systematic review. Journal of Affective Disorders, 350, 78–88.

Porta-Casteràs, D., Fullana, M., Tinoco, D., Martínez-Zalacaín, I., Pujol, J., Palao, D., Soriano-Mas, C., Harrison, B., Via, E., & Cardoner, N. (2020). Prefrontal-amygdala connectivity in trait anxiety and generalized anxiety disorder: Testing the boundaries between healthy and pathological worries. Journal of Affective Disorders, 267, 211–219.

Pourtois, G., Sander, D., Andres, M., Grandjean, D., Reveret, L., Olivier, E., & Vuilleumier, P. (2004). Dissociable roles of the human somatosensory and superior temporal cortices for processing social face signals. European Journal of Neuroscience, 20(12), 3507–3515.

Ramos-Fresnedo, A., Segura-Duran, I., Chaichana, K. L., & Pillai, J. J. (2019). Supratentorial white matter tracts. In Comprehensive Overview of Modern Surgical Approaches to Intrinsic Brain Tumors (pp. 23–35). Academic Press.

Rolls, E. T. (2000). Functions of the Primate Temporal Review Lobe Cortical Visual Areas in Invariant Visual Object and Face Recognition. Neuron, 27(2), 205–218.

Sandman, C. F., Young, K. S., Burklund, L. J., Saxbe, D. E., Lieberman, M. D., & Craske, M. G. (2020). Changes in functional connectivity with cognitive behavioral therapy for social anxiety disorder predict outcomes at follow-up. Behaviour Research and Therapy, 129, 103612.

Saviola, F., Pappaianni, E., Monti, A., Grecucci, A., Jovicich, J., & De Pisapia, N. (2020). Trait and state anxiety are mapped differently in the human brain. Scientific Reports, 10(1), 11112.

Shan, X., Yan, H., Li, H., Liu, F., Xie, G., Li, P., Zhao, J., & Guo, W. (2023). Abnormal causal connectivity of prefrontal-limbic circuit by structural deficits in drug-naive anxiety disorders. Journal of Psychiatric Research, 163, 14–23.

Šimić, G., Tkalčić, M., Vukić, V., Mulc, D., Španić, E., Šagud, M., Olucha-Bordonau, F. E., Vukšić, M., & R. Hof, P. (2021). Understanding Emotions: Origins and Roles of the Amygdala. Biomolecules, 11(6), 823.

Stein, M. B., & Stein, D. J. (2008). Social anxiety disorder. The Lancet, 371(9618), 1115–1125.

Thorn, E. L., Ostrowski, L. M., Chinappen, D. M., Jing, J., Westover, M. B., Stufflebeam, S. M., Kramer, M. A., & Chu, C. J. (2020). Persistent abnormalities in Rolandic thalamocortical white matter circuits in childhood epilepsy with centrotemporal spikes. Epilepsia, 61(11), 2500–2508.

Tomczyk, S., Schlick, S., Gansler, T., McLaren, T., Muehlan, H., Peter, L.-J., Schomerus, G., & Schmidt, S. (2023). Continuum beliefs of mental illness: a systematic review of measures. Social Psychiatry and Psychiatric Epidemiology, 58(1), 1–16.

Tükel, R., Ulasoglu Yildiz, C., Ertekin, E., Kurt, E., Koyuncu, A., & Aydın, K. (2017). Evidence for alterations of the right inferior and superior longitudinal fasciculi in patients with social anxiety disorder. Brain Research, 1662, 16–22.

Tulving, E., Kapurt, S., Craik, F. I. M., Moscovitch, M., & Houlet, S. (1994). Hemispheric encoding/retrieval asymmetry in episodic memory: Positron emission tomography findings. Proceedings of the National Academy of Sciences USA, 91(6), 2016–2020.

Vandekerckhove, M. (2020). Neural networks in bottom up ‘experiential emotion regulation.’ Behavioural Brain Research, 383, 111242.

Vidaurre, C., Nikulin, V. V., & Herrojo Ruiz, M. (2023). Identification of spatial patterns with maximum association between power of resting state neural oscillations and trait anxiety. Neural Computing and Applications, 35(8), 5737–5749.

Wang, W., Qian, S., Liu, K., Li, B., Li, M., Xin, K., & Sun, G. (2016). Reduced white matter integrity and its correlation with clinical symptom in first-episode, treatment-naive generalized anxiety disorder. Behavioural Brain Research, 314, 159–164.

Westlye, L. T., Bjørnebekk, A., Grydeland, H. K., Fjell, A. M., & Walhovd, K. B. (2011). Linking an anxiety- related personality trait to brain white matter microstructure: Diffusion tensor imaging and harm avoidance. Archives of General Psychiatry, 68(4).

Xu, E. P., Nguyen, L., Leibenluft, E., Stange, J. P., & Linke, J. O. (2023). A meta-analysis on the uncinate fasciculus in depression. Psychological Medicine, 53(7), 2721–2731.

Yang, C., Zhang, Y., Lu, M., Ren, J., & Li, Z. (2020). White Matter Structural Brain Connectivity of Young Healthy Individuals With High Trait Anxiety. Frontiers in Neurology, 10, 1421.

Yeh, F. C., Badre, D., & Verstynen, T. (2016). Connectometry: A statistical approach harnessing the analytical potential of the local connectome. Neuroimage, 125, 162–171.

Yeh, F. C., Panesar, S., Barrios, J., Fernandes, D., Abhinav, K., Meola, A., & Fernandez-Miranda, J. C. (2019). Automatic removal of false connections in diffusion MRI tractography using Topology-Informed Pruning (TIP). Neurotherapeutics, 16(1), 52–58.

Yeh, F. C., Verstynen, T. D., Wang, Y., Fernández-Miranda, J. C., & Tseng, W. Y. I. (2013). Deterministic diffusion fiber tracking improved by quantitative anisotropy. PLoS ONE, 8(11), e80713.

Zhang, N., Chen, S., Jiang, K., Ge, W., Im, H., Guan, S., Li, Z., Wei, C., Wang, P., Zhu, Y., Zhao, G., Liu, L., Chen, C., Chang, H., & Wang, Q. (2024). Individualized prediction of anxiety and depressive symptoms using gray matter volume in a non-clinical population. Cerebral Cortex, 34(4).

Zhang, X., Suo, X., Yang, X., Lai, H., Pan, N., He, M., Li, Q., Kuang, W., Wang, S., & Gong, Q. (2022). Structural and functional deficits and couplings in the cortico-striato-thalamo-cerebellar circuitry in social anxiety disorder. Translational Psychiatry, 12(1), 26.

Zhao, Y., Niu, R., Lei, D., Shah, C., Xiao, Y., Zhang, W., Chen, Z., Lui, S., & Gong, Q. (2020). Aberrant gray matter networks in non-comorbid medication-naive patients with major depressive disorder and those with social anxiety disorder. Frontiers in Human Neuroscience, 14(172).

Zolkefley, M. K. I., Abdull, N., Shamsuddin Perisamy, R., Mustapha, M., Adam, D., & Muhamad Noordin, M. A. (2024). Investigating white matter changes in auditory cortex and association fibres related to speech processing in noise-induced hearing loss: a diffusion tensor imaging study. Egyptian Journal of Radiology and Nuclear Medicine, 55(1), 93.

Downloads

Published

2025-04-29

How to Cite

EXPLORING BRAIN CHANGES IN SELF-REPORTED ANXIETY: CUTTING-EDGE EXPLORATORY DIFFUSION TENSOR IMAGING STUDY REVEALS DISTINCT ALTERATIONS IN WHITE MATTER TRACT STRUCTURE AMONG NON-CLINICAL INDIVIDUALS. (2025). Asian People Journal (APJ), 8(1), 181-195. https://doi.org/10.37231/apj.2025.8.1.742