1. Introduction
Depressive disorders are progressive clinical mental disorders that affects 151.2 million people worldwide. It is the fourth leading disease causing health problems [1]. It is diagnosed when a person has feelings of guilt or worthlessness, lack of energy, poor concentration, changes in appetite, slowness or psychomotor restlessness, sleep disorders or suicidal thoughts, or decreased interest in pleasurable activities [2]. The results of a systematic study on the prevalence of major depressive disorder in Iran reported a prevalence of 1.4% which was 1.95 times higher in women than in men [3].
Nowadays, one of the modern and most non-invasive methods affecting executive functions that has attracted the attention of psychologists and psychiatrists is neurofeedback method. Given the current debate about the effectiveness of neurofeedback on working memory and cognitive flexibility and depressive disorders, not only attention should be paid to the affected area of executive functions in treatment, but also the techniques and methods that can affect defective executive dysfunctions should be used. In this regard, the present study aims to evaluate the effects of neurofeedback on working memory and cognitive flexibility in patients with mild depression.
2. Methods
This is a quasi-experimental study (clinical trial; ID= IRCT20210611051540N1) with a pretest/posttest design using a control group, which has an ethical approval (code: IR.IAU.LIAU.REC.1400.017). The study population consisted of all patients with mild depression referred to six counseling and psychological clinics in Rasht, Iran in 2022 (n= 100). OF these, 40 patients were selected using a purposive sampling method and randomly divided into intervention (n=20) and control (n=20) groups. Participants in the intervention group individually underwent neurofeedback therapy for 3 months at 20 sessions each for 30 min using a 2-channel neurofeedback device (Parto Danesh Company, Iran), which can be implemented using a PC and related software.
Prior to intervention, the Goldberg Depression Inventory, Cognitive Flexibility Questionnaire, Working Memory Questionnaire, counseling, history recording and clinical interview were completed and performed by a psychiatrist and clinical psychologist. Then, the patient was referred to a neurotherapist for neurofeedback therapy and to determine the treatment protocol. Patients had no concurrent psychiatric disorders and were not affected by medication. Most of the patients with depression were at a young age. Inclusion criteria were: being depressed, age 20-40 years, resident of Rasht city, and willingness to participate in the study. 
The Goldberg Depression Inventory was developed by Goldberg and has 18 items rated on a 5-point Likert scale as  5=Very high, 4=high, 3= medium, 2=low, and 1=very low. The total score ranges from 0 to 90, with a cut-off point of 45. The Cognitive Flexibility Questionnaire was developed by Dennis and Vander Wal and has 20 questions rated on a 7-point scale from strongly agree to strongly disagree. The total score ranges from 20 to 140 with a cut-off point of 80. The Working Memory Questionnaire was developed by Danman & Carpenter and has 27 items (statements) divided into six sets of  2-, 3-, 4-, 5-, 6-, and 7-sentence statements.
3. Results 
Of 20 patients, the data of 15 people were finally analyzed. In the intervention group, 8 patients (53.3%) were male and 7 (46.7%) were female. in the control group, 7 (46.7%) were male and 8 (53.3%) female. Most of patients at both groups were at the age range of 31-40 years (66.7% in intervention group and 60% in the control group). Moreover, most of patients in the intervention group had high school diploma (33.3%) while in the control group, most of them had a bachelor’s degree (40%). The results of analyses showed that neurofeedback therapy increased working memory and improved cognitive flexibility and symptoms in patients with depression in the intervention group compared to the control group. 
4. Conclusion
The purpose of this study was to determine the effect of neurofeedback on working memory and cognitive flexibility in patients with mild depression. The results showed that neurofeedback training increased working memory and improved cognitive flexibility and symptoms in patients. According to the findings, it can be said that neurofeedback helps people with mild depression achieve better adaptive psychological response and mood control skills by conditioning their brain waves, and reduces mood disorders such as depression.

Ethical Considerations
Compliance with ethical guidelines
This study was extracted from a master thesis. It has an ethical approval from Islamic Azad University of Lahijan Branch (Code: IR.IAU.LIAU.REC.1400.017) and registered by Iranian Registry of Clinical Trials (ID=IRCT20210611051540N1).

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 

Authors' contributions
All authors have equal contribution in the research running and manuscript writing.

Conflicts of interest
The authors declared no conflict of interest.
Acknowledgements
The authors would like to thank the research's participants for their valuable cooperation.


References

1. Institute of Health Metrics and Evaluation. Global Health Data Exchange (GHDx) [Internet]. 2019 [Updated 2019]. Available from: http://ghdx.healthdata.org/gbd-results-tool?params=gbd-api-2019permalink/d780dffbe8a381b25e1416884959e88b
2. World Health Organization. Depression [Internet]. 2021 [Updated 2021 September 13]. Available from: https://www.who.int/news-room/fact-sheets/detail/depression
3. Liu J, Fan Y, Zeng LL, Liu B, Ju Y, Wang M, et al. The neuroprogressive nature of major depressive disorder: Evidence from an intrinsic connectome analysis. Translational Psychiatry. 2021; 11:102. [DOI:10.1038/s41398-021-01227-8] [PMID] [PMCID]
4. Gharraee B, Zahedi Tajrishi K, Sheybani F, Tahmasbi N, Mirzaee M, Farahani H, et al. Prevalence of major depressive disorder in the general population of Iran: A systematic review and meta-analysis. Medical Journal of the Islamic Republic of Iran. 2019; 33(1):926-34. [DOI:10.47176/mjiri.33.151] [PMID] [PMCID]
5. Yu SH, Tseng CY, Lin WL. A neurofeedback protocol for executive function to reduce depression and rumination: A controlled study. Clinical Psychopharmacology and Neuroscience. 2020; 18(3):375-85. [DOI:10.9758/cpn.2020.18.3.375] [PMID] [PMCID]
6. Noreen S, Cooke R, Ridout N. Investigating the mediating effect of working memory on intentional forgetting in dysphoria. Psychological Research. 2020; 84(8):2273-86. [DOI:10.1007/s00426-019-01225-y] [PMID] [PMCID]
7. MacQueen GM, Memedovich KA. Cognitive dysfunction in major depression and bipolar disorder: Assessment and treatment options. Psychiatry and Clinical Neurosciences. 2017; 71(1):18-27. [DOI:10.1111/pcn.12463] [PMID]
8. Halappa NG, Thirthalli J, Varambally Sh, Rao M, Christopher R, Nanjundaiah GB. Improvement in neurocognitive functions and serum brain-derived neurotrophic factor levels in patients with depression treated with antidepressants and yoga. Indian Journal of Psychiatry. 2018; 60(1):32-7. [DOI:10.4103/psychiatry.IndianJPsychiatry_154_17] [PMID] [PMCID]
9. Pellegrino LD, Peters ME, Lyketsos CG, Marano CM. Depression in cognitive impairment. Current Psychiatry Reports. 2013; 15(9):384. [DOI:10.1007/s11920-013-0384-1] [PMID] [PMCID]
10. Lee HH, Chang CH, Wang LJ, Wu CC, Chen HL, Lu T, et al. The correlation between longitudinal changes in Hypothalamic-Pituitary-Adrenal (HPA)-axis activity and changes in neurocognitive function in mixed-state bipolar II disorder. Neuropsychiatric Disease and Treatment. 2018; 14:2703-13. [DOI:10.2147/NDT.S173616] [PMID] [PMCID]
11. Nazer M, Mirzaei H, Mokhtaree MR. Effectiveness of neurofeedback training on verbal memory, visual memory and self-efficacy in students. Electronic Physician. 2018; 10(9):7259-65. [DOI:10.19082/7259] [PMID] [PMCID]
12. Yu JC, Chang TY, Yang CT. Individual differences in working memory capacity and workload capacity. Frontiers in Psychology. 2014; 5:1465. [DOI:10.3389/fpsyg.2014.01465] [PMID] [PMCID]
13. Spencer JP. The development of working memory. Current Directions in Psychological Science. 2020; 29(6):545-53. [DOI:10.1177/0963721420959835] [PMID] [PMCID]
14. Maramis MM, Mahajudin MS, Khotib J. Impaired cognitive flexibility and working memory precedes depression: A rat model to study depression. Neuropsychobiology. 2021; 80(3):225-33. [DOI:10.1159/000508682] [PMID] [PMCID]
15. Bernardo ABI, Presbitero A. Cognitive flexibility and cultural intelligence: Exploring the cognitive aspects of effective functioning in culturally diverse contexts. International Journal of Intercultural Relations. 2018; 66:12-21. [DOI:10.1016/j.ijintrel.2018.06.001]
16. Esmaeeli Sh. The effectiveness of neuro feedback training on the working-memory of people with obsessive-compulsive disorder symptoms. European Journal of Molecular & Clinical Medicine. 2021; 8(1):1795-803. https://ejmcm.com/article_8092.html
17. Vásquez-Rosati A, Montefusco-Siegmund R, López V, Cosmelli D. Emotional influences on cognitive flexibility depend on individual differences: A combined micro-phenomenological and psychophysiological study. Frontiers in Psychology. 2019; 10:1138. [DOI:10.3389/fpsyg.2019.01138] [PMID] [PMCID]
18. Uddin LQ. Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations. Nature Reviews Neuroscience. 2021; 22(3):167-79. [DOI:10.1038/s41583-021-00428-w] [PMID] [PMCID]
19. Ionescu T. Exploring the nature of cognitive flexibility. New Ideas in Psychology. 2012; 30(2):190-200. [DOI:10.1016/j.newideapsych.2011.11.001]
20. Gabrys RL, Tabri N, Anisman H, Matheson K. Cognitive control and flexibility in the context of stress and depressive symptoms: The cognitive control and flexibility questionnaire. Frontiers in Psychology. 2018; 9:2219. [DOI:10.3389/fpsyg.2018.02219] [PMID] [PMCID]
21. Compton RJ, Hofheimer J, Kazinka R. Stress regulation and cognitive control: Evidence relating cortisol reactivity and neural responses to errors. Cognitive, Affective, & Behavioral Neuroscience. 2013; 13(1):152-63. [DOI:10.3758/s13415-012-0126-6] [PMID] [PMCID]
22. Shields GS, Sazma MA, Yonelinas AP. The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol. Neuroscience & Biobehavioral Reviews. 2016; 68:651-68. [DOI:10.1016/j.neubiorev.2016.06.038] [PMID] [PMCID]
23. Goldfarb EV, Froböse MI, Cools R, Phelps EA. Stress and cognitive flexibility: Cortisol increases are associated with enhanced updating but impaired switching. Journal of Cognitive Neuroscience. 2017; 29(1):14-24. [DOI:10.1162/jocn_a_01029] [PMID]
24. Jensen PS, Martin D, Cantwell DP. Comorbidity in ADHD: Implications for research, practice, and DSM-V. Journal of the American Academy of Child and Adolescent Psychiatry. 1997; 36(8):1065-79. [DOI:10.1097/00004583-199708000-00014] [PMID]
25. Ensafi E, Rostami R, Dolatshahi B, Poursharifi H, Nouri M. The effectiveness of neurofeedback on the working memory in children with ADHD. Practice in Clinical Psychology. 2014; 2(2):101-8. http://jpcp.uswr.ac.ir/article-1-144-en.html
26. Wang JR, Hsieh Sh. Neurofeedback training improves attention and working memory performance. Clinical Neurophysiology. 2013; 124(12):2406-20. [DOI:10.1016/j.clinph.2013.05.020] [PMID]
27. Trambaiolli LR, Cassani R, Mehler DMA, Falk TH. Neurofeedback and the aging brain: A systematic review of training protocols for dementia and mild cognitive impairment. Frontiers in Aging Neuroscience. 2021; 13:682683. [DOI:10.3389/fnagi.2021.682683] [PMID] [PMCID]
28. Orndorff-Plunkett F, Singh F, Aragón OR, Pineda JA. Assessing the effectiveness of neurofeedback training in the context of clinical and social neuroscience. Brain Sciences. 2017; 7(8):95. [DOI:10.3390/brainsci7080095] [PMID] [PMCID]
29. Thibault RT, Lifshitz M, Raz A. Neurofeedback or neuroplacebo? Brain. 2017; 140(4):862-4. [DOI:10.1093/brain/awx033] [PMID]
30. Cicerone KD, Langenbahn DM, Braden C, Malec JF, Kalmar K, Fraas M, et al. Evidence-based cognitive rehabilitation: Updated review of the literature from 2003 through 2008. Archives of Physical Medicine and Rehabilitation. 2011; 92(4):519-30. [DOI:10.1016/j.apmr.2010.11.015] [PMID]
31. Gazzaley A, Nobre AC. Top-down modulation: Bridging selective attention and working memory. Trends in Cognitive Sciences. 2012; 16(2):129-35. [DOI:10.1016/j.tics.2011.11.014] [PMID] [PMCID]
32. Karbach J, Verhaeghen P. Making working memory work: A meta-analysis of executive-control and working memory training in older adults. Psychological Science. 2014; 25(11):2027-37. [DOI:10.1177/0956797614548725] [PMID] [PMCID]
33. Cheon EJ, Koo BH, Choi JH. The efficacy of neurofeedback in patients with major depressive disorder: An open labeled prospective study. Applied Psychophysiology and Biofeedback. 2016; 41(1):103-10. [DOI:10.1007/s10484-015-9315-8] [PMID]
34. Kupfer DJ, Frank E, Phillips ML. Major depressive disorder: New clinical, neurobiological, and treatment perspectives. The Lancet. 2012; 379(9820):1045-55. [DOI:10.1016/S0140-6736(11)60602-8]
35. Otte Ch, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. Major depressive disorder. Nature Reviews Disease Primers. 2016; 2:16065. [DOI:10.1038/nrdp.2016.65] [PMID]
36. Fodor LA, Georgescu R, Cuijpers P, Szamoskozi Ş, David D, Furukawa TA, et al. Efficacy of cognitive bias modification interventions in anxiety and depressive disorders: A systematic review and network meta-analysis. The Lancet Psychiatry. 2020; 7(6):506-14. [DOI:10.1016/S2215-0366(20)30130-9]
37. Sharp T. Molecular and cellular mechanisms of antidepressant action. In: Cowen P, Sharp T, Lau J, editors. Behavioral Neurobiology of Depression and Its Treatment. Current Topics in Behavioral Neurosciences. Vol. 14. Berlin/Heidelberg: Springer; 2012. pp. 309-325. [DOI:10.1007/7854_2012_216] [PMID]
38. Trambaiolli LR, Kohl SH, Linden DEJ, Mehler DMA. Neurofeedback training in major depressive disorder: A systematic review of clinical efficacy, study quality and reporting practices. Neuroscience & Biobehavioral Reviews. 2021; 125:33-56. [DOI:10.1016/j.neubiorev.2021.02.015] [PMID]
39. Mutz J, Vipulananthan V, Carter B, Hurlemann R, Fu CHY, Young AH. Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: Systematic review and network meta-analysis. BMJ. 2019; 364:l1079. [DOI:10.1136/bmj.l1079] [PMID] [PMCID]
40. Sitaram R, Ros T, Stoeckel L, Haller S, Scharnowski F, Lewis-Peacock J, et al. Closed-loop brain training: The science of neurofeedback. Nature Reviews Neuroscience. 2017; 18(2):86-100. [DOI:10.1038/nrn.2016.164] [PMID]
41. Aarts E, Dolan CV, Verhage M, van der Sluis S. Multilevel analysis quantifies variation in the experimental effect while optimizing power and preventing false positives. BMC Neuroscience. 2015; 16:94. [DOI:10.1186/s12868-015-0228-5] [PMID] [PMCID]
42. Heydarinasab L, Madani AS, Yaghoubi H, Rostami R, Kazemi R. [The effectiveness of neurofeedback with computrized training in improving working memory in adults with attention deficit disorder/ hyperactivity (Persian)]. Yafteh. 2016; 18(1):101-12. http://yafte.lums.ac.ir/article-1-2220-fa.html
43. Alizadeh G, Kordnoghabi R, Rashid Kh, Gholizadeh Z. [The impact of upper alpha neurofeedback training on executive functions of the female students of Kurdistan University with academic burnout syndrome and depression symptoms (Persian)]. Clinical Psychology Studies. 2018; 8(30):163-88. [DOI:10.22054/JCPS.2018.8613]
44. Peeters F, Oehlen M, Ronner J, van Os J, Lousberg R. Neurofeedback as a treatment for major depressive disorder -- A pilot study. PLoS One. 2014; 9(3):e91837. [DOI:10.1371/journal.pone.0091837] [PMID] [PMCID]
45. Choobforoushzadeh A, Neshat-Doost HT, Molavi H, Abedi MR. Effect of neurofeedback training on depression and fatigue in patients with multiple sclerosis. Applied Psychophysiology and Biofeedback. 2015; 40(1):1-8. [DOI:10.1007/s10484-014-9267-4] [PMID]
46. Abdian H, Rezaei M, Eskandari Z, Ramezani Sh, Pirzeh R, Dadashi M. The effect of quantitative electroencephalography-based neurofeedback therapy on anxiety, depression, and emotion regulation in people with generalized anxiety disorder. Basic and Clinical Neuroscience. 2021; 12(2):281-90. [DOI:10.32598/bcn.12.2.2378.1] [PMID] [PMCID]
47. Eskandari Z, Taremian F, Nazari MA, Bakhtiari M, Momtazi S, Rezaei M. [Effectiveness of neurofeedback treatment to decrease severity symptoms in major depression disorder (Persian)]. Journal of Advances in Medical and Biomedical Research. 2014; 22(92):86-95. http://zums.ac.ir/journal/article-1-2681-fa.html
48. Lee YJ, Lee GW, Seo WS, Koo BH, Kim HG, Cheon EJ. Neurofeedback treatment on depressive symptoms and functional recovery in treatment-resistant patients with major depressive disorder: An open-label pilot study. Journal of Korean Medical Science. 2019; 34(42):e287. [DOI:10.3346/jkms.2019.34.e287] [PMID] [PMCID]
49. Martínez-Briones BJ, Bosch-Bayard J, Biscay-Lirio RJ, Silva-Pereyra J, Albarrán-Cárdenas L, Fernández T. Effects of neurofeedback on the working memory of children with learning disorders - An EEG power-spectrum analysis. Brain Sciences. 2021; 11(7):957. [DOI:10.3390/brainsci11070957] [PMID] [PMCID]
50. Segrave RA, Thomson RH, Cooper NR, Croft RJ, Sheppard DM, Fitzgerald PB. Upper alpha activity during working memory processing reflects abnormal inhibition in major depression. Journal of Affective Disorders. 2010; 127(1-3):191-8. [DOI:10.1016/j.jad.2010.05.022] [PMID]
51. Ansarhossein S, Abdolghasemi A, Mikaeili N, Hajloo N. [Effectiveness of behavioral activation treatment on asymmetry of alpha EEG in frontal lobe, cognitive flexibility and selective attention in patients suffering from depressive disorder (Persian)]. Thoughts and Behavior in Clinical Psychology. 2018; 13(48):67-76. https://jtbcp.riau.ac.ir/article_1459.html
52. Li K, Jiang Y, Gong Y, Zhao W, Zhao Zh, Liu X, et al. Functional near-infrared spectroscopy-informed neurofeedback: Regional-specific modulation of lateral orbitofrontal activation and cognitive flexibility. Neurophotonics. 2019; 6(2):025011. [DOI:10.1117/1.NPh.6.2.025011] [PMID] [PMCID]
53. Menon V. Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences. 2011; 15(10):483-506. [DOI:10.1016/j.tics.2011.08.003] [PMID]
54. Ioannides AA. Neurofeedback and the neural representation of self: Lessons from awake state and sleep. Frontiers in Human Neuroscience. 2018; 12:142. [DOI:10.3389/fnhum.2018.00142] [PMID] [PMCID]
55. Barreiros AR, Almeida I, Baía BC, Castelo-Branco M. Amygdala modulation during emotion regulation training with fMRI-based neurofeedback. Frontiers in Human Neuroscience. 2019; 13:89. [DOI:10.3389/fnhum.2019.00089] [PMID] [PMCID]