Prefrontal dysfunction and mismatch negativity in adolescent depression: A multimodal fNIRS-ERP study_Journal of Biomedical Engineering

Authors：

SUN Hongyi ¹ , ZHANG Lin ² , LI Jing ³ , LI Zhenhua ³ , HUANG Jiaxi ³ ,  ZHENG Zhong ^1,3 ,  ZOU Ke ¹

1. Neurobiological Laboratory, West China Hospital of Sichuan University, Chengdu 610041, P. R. China;
2. The Department of Rehabilitation Medicine, First People’s Hospital of Jintang County, Chengdu 610499, P. R. China;
3. Neurobiological Laboratory, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian 361000, P. R. China;

Corresponding author：

ZHENG Zhong, Email: zhengzhong1963@163.com; ZOU Ke, Email: keerdianer@163.com

Keywords：

Adolescents; Depression; Functional near-infrared spectroscopy; Mismatch negativity; Event-related potentials

DOI：

10.7507/1001-5515.202503053

Video：

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Early identification of adolescent depression requires objective biomarkers. This study investigated the functional near-infrared spectroscopy (fNIRS) activation patterns and mismatch negativity (MMN) characteristics in adolescents with first-episode mild-to-moderate depression. We enrolled 33 patients and 33 matched healthy controls, measuring oxyhemoglobin (Oxy–Hb) concentration in the frontal cortex during verbal fluency tasks via fNIRS, and recording MMN latency/amplitude at Fz/Cz electrodes using event-related potentials (ERP). Compared with healthy controls, the depression group showed significantly prolonged MMN latency [Fz: (227.88 ± 31.08) ms vs. (208.70 ± 25.35) ms, P < 0.01; Cz: (223.73 ± 29.03) ms vs. (204.18 ± 22.43) ms, P < 0.01], and obviously reduced Fz amplitude [(2.42 ± 2.18) μV vs. (5.65 ± 5.59) μV, P = 0.03]. A significant positive correlation was observed between MMN latencies at Fz and Cz electrodes (P < 0.01). Oxy-Hb in left frontopolar prefrontal channels (CH15/17) was significantly decreased in patient group (P < 0.05). Our findings suggest that adolescents with depression exhibit hypofunction in the left prefrontal cortex and impaired automatic sensory processing. The combined application of fNIRS and ERP techniques may provide an objective basis for early clinical identification.

1.	Huang J, Shan J. Application of near-infrared spectroscopy in early detection of antidepressant treatment efficacy in major depressive disorder: a longitudinal study. Actas Esp Psiquiatr, 2025, 53: 275-283.
2.	滕云, 王宾. 氯胺酮治疗抑郁症的机制研究进展. 大连医科大学学报, 2024, 46(6): 481-487.
3.	Shin J E, Lee Y S, Park S Y, et al. The relationship between depression severity and prefrontal hemodynamic changes in adolescents with major depression disorder: a functional near-infrared spectroscopy study. Clin Psychopharmacol Neurosci, 2024, 22: 118-128.
4.	Chang C H, Liu W C, Chou P H. Near-infrared spectroscopy-guided personalized repetitive transcranial magnetic stimulation for bipolar depression: a case report. Front Psychiatry, 2024, 15: 1514153.
5.	Shen Y, Wu B, Yu J, et al. Functional near-infrared spectroscopy (fNIRS) in patients with major depressive disorder, generalized anxiety disorder and their comorbidity: comparison with healthy controls. Asian J Psychiatr, 2025, 105: 104382.
6.	孙叶菁, 冯珍. 事件相关电位成分失匹配负波和P300在神经精神系统疾病中的临床应用研究进展. 中国康复医学杂志, 2024, 39(7): 1054-1059.
7.	Cao P, Tan J, Liao X, et al. Standardized treatment and shortened depression course can reduce cognitive impairment in adolescents with depression. J Korean Acad Child Adolesc Psychiatry, 2024, 35: 90-97.
8.	Quan W, Wu T, Li Z, et al. Reduced prefrontal activation during a verbal fluency task in Chinese-speaking patients with schizophrenia as measured by near-infrared spectroscopy. Prog Neuropsychopharmacol Biol Psychiatry, 2015, 58: 51-58.
9.	Hare B D, Duman R S. Prefrontal cortex circuits in depression and anxiety: contribution of discrete neuronal populations and target regions. Mol Psychiatry, 2020, 25: 2742-2758.
10.	Krystal S, Gracia L, Piguet C, et al. Functional connectivity of the amygdala subnuclei in various mood states of bipolar disorder. Mol Psychiatry, 2024, 29: 3344-3355.
11.	Korgaonkar M S, Grieve S M, Koslow S H, et al. Loss of white matter integrity in major depressive disorder: evidence using tract-based spatial statistical analysis of diffusion tensor imaging. Hum Brain Mapp, 2011, 32: 2161-2171.
12.	Saleh A, Potter G G, McQuoid D R, et al. Effects of early life stress on depression, cognitive performance and brain morphology. Psychol Med, 2017, 47(1): 171-181.
13.	Pang X, Xu J, Chang Y, et al. Mismatch negativity of sad syllables is absent in patients with major depressive disorder. PLoS One, 2014, 9: e91995.
14.	Murphy N, Lijffijt M, Ramakrishnan N, et al. Does mismatch negativity have utility for NMDA receptor drug development in depression?. Braz J Psychiatry, 2022, 44: 61-73.
15.	Toyomaki, Kusumi I, Matsuyama T, et al. Tone duration mismatch negativity deficits predict impairment of executive function in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32: 95-99.
16.	Wen Q H, Liu Y, Chen H D, et al. Relationship between depression after hemorrhagic stroke and auditory event-related potentials in a Chinese patient group. Neuropsychiatr Dis Treat, 2022, 18: 1917-1925.
17.	Heller A S, Johnstone T, Shackman A J, et al. Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation. Proc Natl Acad Sci U S A, 2009, 106: 22445-22450.
18.	Morey R A, Mitchell T V, Inan S, et al. Neural correlates of automatic and controlled auditory processing in schizophrenia. J Neuropsychiatry Clin Neurosci, 2008, 20: 419-430.
19.	Light G A, Swerdlow N R, Braff D L. Preattentive sensory processing as indexed by the MMN and P3a brain responses is associated with cognitive and psychosocial functioning in healthy adults. J Cogn Neurosci, 2007, 19: 1624-1632.
20.	Zweerings J, Zvyagintsev M, Turetsky B I, et al. Fronto-parietal and temporal brain dysfunction in depression: a fMRI investigation of auditory mismatch processing. Hum Brain Mapp, 2019, 40: 3657-3668.
21.	Jialin A, Zhang H G, Wang X H, et al. Cortical activation patterns in generalized anxiety and major depressive disorders measured by multi-channel near-infrared spectroscopy. J Affect Disord, 2025, 379: 549-558.
22.	Comai S, De Martin S, Mattarei A, et al. N-methyl-D-aspartate receptors and depression: linking psychopharmacology, pathology and physiology in a unifying hypothesis for the epigenetic code of neural plasticity. Pharmaceuticals (Basel), 2024, 17(12): 1618.
23.	Zhao Y, Qiu C, Lin P, et al. Decreased prefrontal activation during verbal fluency task after repetitive transcranial magnetic stimulation treatment for depression in Alzheimer’s disease: a functional near-infrared spectroscopy study. Front Aging Neurosci, 2024, 16: 1460853.
24.	范亚丹, 陈晶, 余小定, 等. 问题解决疗法对首发中重度抑郁症患者抑郁症状和认知灵活性的影响. 中华全科医学, 2025, 23(1): 103-106,161.
25.	Han S, Li X X, Wei S, et al. Orbitofrontal cortex-hippocampus potentiation mediates relief for depression: a randomized double-blind trial and TMS-EEG study. Cell Rep Med, 2023, 4: 101060.

1. Huang J, Shan J. Application of near-infrared spectroscopy in early detection of antidepressant treatment efficacy in major depressive disorder: a longitudinal study. Actas Esp Psiquiatr, 2025, 53: 275-283.
2. 滕云, 王宾. 氯胺酮治疗抑郁症的机制研究进展. 大连医科大学学报, 2024, 46(6): 481-487.
3. Shin J E, Lee Y S, Park S Y, et al. The relationship between depression severity and prefrontal hemodynamic changes in adolescents with major depression disorder: a functional near-infrared spectroscopy study. Clin Psychopharmacol Neurosci, 2024, 22: 118-128.
4. Chang C H, Liu W C, Chou P H. Near-infrared spectroscopy-guided personalized repetitive transcranial magnetic stimulation for bipolar depression: a case report. Front Psychiatry, 2024, 15: 1514153.
5. Shen Y, Wu B, Yu J, et al. Functional near-infrared spectroscopy (fNIRS) in patients with major depressive disorder, generalized anxiety disorder and their comorbidity: comparison with healthy controls. Asian J Psychiatr, 2025, 105: 104382.
6. 孙叶菁, 冯珍. 事件相关电位成分失匹配负波和P300在神经精神系统疾病中的临床应用研究进展. 中国康复医学杂志, 2024, 39(7): 1054-1059.
7. Cao P, Tan J, Liao X, et al. Standardized treatment and shortened depression course can reduce cognitive impairment in adolescents with depression. J Korean Acad Child Adolesc Psychiatry, 2024, 35: 90-97.
8. Quan W, Wu T, Li Z, et al. Reduced prefrontal activation during a verbal fluency task in Chinese-speaking patients with schizophrenia as measured by near-infrared spectroscopy. Prog Neuropsychopharmacol Biol Psychiatry, 2015, 58: 51-58.
9. Hare B D, Duman R S. Prefrontal cortex circuits in depression and anxiety: contribution of discrete neuronal populations and target regions. Mol Psychiatry, 2020, 25: 2742-2758.
10. Krystal S, Gracia L, Piguet C, et al. Functional connectivity of the amygdala subnuclei in various mood states of bipolar disorder. Mol Psychiatry, 2024, 29: 3344-3355.
11. Korgaonkar M S, Grieve S M, Koslow S H, et al. Loss of white matter integrity in major depressive disorder: evidence using tract-based spatial statistical analysis of diffusion tensor imaging. Hum Brain Mapp, 2011, 32: 2161-2171.
12. Saleh A, Potter G G, McQuoid D R, et al. Effects of early life stress on depression, cognitive performance and brain morphology. Psychol Med, 2017, 47(1): 171-181.
13. Pang X, Xu J, Chang Y, et al. Mismatch negativity of sad syllables is absent in patients with major depressive disorder. PLoS One, 2014, 9: e91995.
14. Murphy N, Lijffijt M, Ramakrishnan N, et al. Does mismatch negativity have utility for NMDA receptor drug development in depression?. Braz J Psychiatry, 2022, 44: 61-73.
15. Toyomaki, Kusumi I, Matsuyama T, et al. Tone duration mismatch negativity deficits predict impairment of executive function in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32: 95-99.
16. Wen Q H, Liu Y, Chen H D, et al. Relationship between depression after hemorrhagic stroke and auditory event-related potentials in a Chinese patient group. Neuropsychiatr Dis Treat, 2022, 18: 1917-1925.
17. Heller A S, Johnstone T, Shackman A J, et al. Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation. Proc Natl Acad Sci U S A, 2009, 106: 22445-22450.
18. Morey R A, Mitchell T V, Inan S, et al. Neural correlates of automatic and controlled auditory processing in schizophrenia. J Neuropsychiatry Clin Neurosci, 2008, 20: 419-430.
19. Light G A, Swerdlow N R, Braff D L. Preattentive sensory processing as indexed by the MMN and P3a brain responses is associated with cognitive and psychosocial functioning in healthy adults. J Cogn Neurosci, 2007, 19: 1624-1632.
20. Zweerings J, Zvyagintsev M, Turetsky B I, et al. Fronto-parietal and temporal brain dysfunction in depression: a fMRI investigation of auditory mismatch processing. Hum Brain Mapp, 2019, 40: 3657-3668.
21. Jialin A, Zhang H G, Wang X H, et al. Cortical activation patterns in generalized anxiety and major depressive disorders measured by multi-channel near-infrared spectroscopy. J Affect Disord, 2025, 379: 549-558.
22. Comai S, De Martin S, Mattarei A, et al. N-methyl-D-aspartate receptors and depression: linking psychopharmacology, pathology and physiology in a unifying hypothesis for the epigenetic code of neural plasticity. Pharmaceuticals (Basel), 2024, 17(12): 1618.
23. Zhao Y, Qiu C, Lin P, et al. Decreased prefrontal activation during verbal fluency task after repetitive transcranial magnetic stimulation treatment for depression in Alzheimer’s disease: a functional near-infrared spectroscopy study. Front Aging Neurosci, 2024, 16: 1460853.
24. 范亚丹, 陈晶, 余小定, 等. 问题解决疗法对首发中重度抑郁症患者抑郁症状和认知灵活性的影响. 中华全科医学, 2025, 23(1): 103-106,161.
25. Han S, Li X X, Wei S, et al. Orbitofrontal cortex-hippocampus potentiation mediates relief for depression: a randomized double-blind trial and TMS-EEG study. Cell Rep Med, 2023, 4: 101060.

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