Effects of virtual reality-based cognitive training on working memory and frontotemporal lobe in patients with major depressive disorder: A randomized controlled study

Xiaodan Lu; Shuya Yan; Yiliang Zhang; Shunkai Lai; Dong Huang; Huiyun Zhu; Jianzhao Zhang; Xiaodong Song; Qilin Zhong; Rongxu Zhang; Yangyu Wu; Yitong Liu; Jingyan Sun; Yilkun Liang; Meiqi Zhang; Dongxue Wei; Shuming Zhong; Yanbin Jia

doi:10.1016/j.jad.2025.119770

Effects of virtual reality-based cognitive training on working memory and frontotemporal lobe in patients with major depressive disorder: A randomized controlled study

J Affect Disord. 2025 Jun 24:119770. doi: 10.1016/j.jad.2025.119770. Online ahead of print.

Authors

Xiaodan Lu¹, Shuya Yan¹, Yiliang Zhang¹, Shunkai Lai², Dong Huang¹, Huiyun Zhu³, Jianzhao Zhang¹, Xiaodong Song¹, Qilin Zhong¹, Rongxu Zhang¹, Yangyu Wu¹, Yitong Liu⁴, Jingyan Sun⁴, Yilkun Liang⁴, Meiqi Zhang⁴, Dongxue Wei⁴, Shuming Zhong⁵, Yanbin Jia⁶

Affiliations

¹ Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
² Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China; Department of Psychiatry, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital), Heyuan 517000, China.
³ Department of Psychiatry, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital), Heyuan 517000, China.
⁴ School of Management, Jinan University, Guangzhou 510316, China.
⁵ Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China. Electronic address: Shuming19882006@126.com.
⁶ Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou 510630, China; Department of Psychiatry, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital), Heyuan 517000, China. Electronic address: yanbinjia2006@163.com.

PMID: 40570936
DOI: 10.1016/j.jad.2025.119770

Abstract

Background: Most patients with major depressive disorder (MDD) have working memory (WM) impairment, which can be improved by virtual reality-based working memory (VR-WM) training; however, the specific neural mechanisms remain unclear. This study aimed to clarify how VR-WM training improves WM in patients with MDD and further explore the role of the frontotemporal lobe in related neural mechanisms.

Methods: A total of 57 patients with MDD were included in a randomized controlled study to clarify the effects of 20 sessions of VR-WM training on WM in patients with MDD and to explore the role of the frontotemporal lobe in associated neural mechanisms. The Stroop color word test, 2-back task, digit task switching, and digit span test were used to measure the inhibition, updating and switching functions of WM and WM span. The functional features of the frontotemporal lobe in patients with MDD at rest were detected using functional near-infrared spectroscopy before and after training.

Results: After VR-WM training, patients with MDD exhibited significant improvements in the accuracy of the Stroop color word test (p = 0.013) and 2-back task (p = 0.002), the scores of digit span test (p = 0.030) and Hamilton Depression Rating Scale (HDRS) score (p = 0.006). Significant group-by-time interactions of local efficiency (p = 0.005) and clustering coefficient (p = 0.004) of the frontotemporal lobe were observed between groups. The degree of improvement in the total score of the digit span test was positively correlated with the change in the clustering coefficient (p = 0.034).

Conclusions: VR-WM training effectively improved inhibition, updating and memory span in the WM of patients with MDD. Furthermore, VR-WM training was observed to enhance functional connectivity in the frontotemporal lobe, thereby improving WM performance in patients with MDD.

Keywords: Frontotemporal lobe; Functional near-infrared spectroscopy; Major depressive disorder; Virtual reality-based; Working memory.