睡眠在人類生活中扮演重要角色，如同空氣、水和食物一樣不可或缺。良好睡眠對身心健康至關重要，而睡眠品質不佳可能導致疲勞、煩躁和注意力不集中等問題。然而，台灣患有慢性失眠的人口超過10%，長期面臨入睡困難、續睡困難或早醒等問題。更令人擔憂的是，在失眠患者中有高達40%同時出現精神狀態異常。這顯示失眠與焦慮、憂鬱密切相關。睡眠藥物是常見的治療方式，但長期使用可能導致藥物濫用和成癮等問題。此外，大多數睡眠藥物主要針對入睡困難而非續睡困難，而續睡困難同樣普遍甚至更為常見。入睡後醒來時間是衡量續睡困難的重要指標，過長的醒來時間對大腦而言是不正常的覺醒狀態，而α腦波通常與放鬆的清醒狀態相關，β波則與警覺的精神狀態相關，過多的α和β腦電波成分可能導致覺醒。因此，通過神經回饋訓練控制大腦腦波活動有機會改善失眠與覺醒。我們先前的研究發現，在接受α神經回饋訓練的患有焦慮或憂鬱的失眠患者中，主觀和客觀上都有減少入睡時間和提高睡眠效率的改善。然而，一些研究提出可能是安慰劑效應。為了回應臨床需求，相關研究應採用穩健的設計，如對照試驗和前後測試，以確保結果的可靠性，而受試者也應選擇具代表性的樣本，並選擇合適的客觀和主觀評估方法來評估睡眠質量。但目前有些研究並未充分提及受試者是否患有焦慮或憂鬱症，或者未清楚說明如何篩選失眠者。此外，一些研究缺乏對照組，僅依賴主觀問卷而未進行客觀量測，也有一些研究缺乏後續評估。因此，為了滿足臨床需求，本研究針對續睡困難的焦慮憂鬱患者提出一套完整的神經回饋訓練機制並用嚴格的評估方法來看是否改善。
本研究將受試者分為控制組與α組，兩組接受18次神經回饋訓練。控制組隨機回饋7~20Hz頻帶能量，α組則回饋α能量，訓練前後會兩組皆會進行主觀的睡眠問卷量表(ISI, PSQI, PSAS)以及客觀的睡眠評估(PSG)來衡量訓練前後睡眠品質。α組訓練後α振幅顯著增加，顯示有成功訓練出α波。此外，α組主觀問卷ISI平均減少5.5分(從13.8 ± 1.2分到8.3 ± 1.2分)，83%的受試者 ISI 下降；PSQI平均減少5.1分(從13.3 ± 0.8分到8.2 ± 1.4分)，75%的受試者 PSQI 下降；客觀睡眠指標方面，有 83%的受試者 WASO 下降，平均減少26分鐘，而覺醒指數則沒有顯著差異。因次，我們提出的神經回饋訓練機制確實有效改善了有續睡困難之焦慮憂鬱患者的睡眠品質。

Sleep plays a crucial role in human life, just like air, water, and food. Good sleep is essential for physical and mental well-being, while poor sleep quality can lead to fatigue, irritability, and lack of concentration. However, in Taiwan, the population suffering from chronic insomnia exceeds 10%, facing long-term difficulties in falling asleep, maintaining sleep or early awakening. What is even more concerning is that up to 40% of insomnia patients experience concurrent mental health abnormalities. This indicates a close association between insomnia and anxiety and depression. While sleep medication is a common treatment option, prolonged use can lead to issues such as drug abuse and addition. Furthermore, most sleep medications primarily target difficulties in falling asleep rather than maintaining sleep, which is equally prevalent, if not more common. The duration of wakefulness after sleep onset is an important indicator of sleep maintenance difficulties. Prolonged wakefulness is considered an abnormal state of arousal for the brain. Alpha brainwaves are typically associated with a relaxed wakeful state, while beta waves are related to alertness and mental states. An excess of alpha and beta brainwave components can lead to wakefulness. Therefore, controlling brainwave activity through neurofeedback training has the potential to improve both insomnia and wakefulness. Our previous research found improvements in subjective and objective measures of sleep onset time and sleep efficiency in insomnia patients with comorbid anxiety or depression who underwent alpha neurofeedback training. However, some studies have proposed that these improvements may be attributed to placebo effects. To address clinical needs, related studies should employ robust designs such as controlled trials and pre-post testing to ensure the reliability of results. Additionally, representative samples should be selected, and appropriate objective and subjective assessment methods should be used to evaluate sleep quality. Currently, some studies lack sufficient information about whether participants have anxiety or depression, or they do not clearly specify how they screened for individuals with insomnia. Additionally, certain studies lack control groups and rely solely on subjective questionnaires without objective measurements. Moreover, some studies lack follow-up assessments. Therefore, to meet clinical needs, this study proposes a comprehensive neurofeedback training mechanism for insomnia patients with sleep maintenance difficulties and comorbid anxiety or depression, using rigorous evaluation methods to determine if improvements occur.
In this study, subjects are divided into a control group and an alpha group, both of which undergo 18 sessions of neurofeedback training. The control group receives random feedback on the 7-20Hz frequency band energy, while the alpha group receives on alpha energy. Both groups undergo subjective sleep questionnaires (ISI, PSQI, PSAS) and objective sleep assessments (PSG) before and after the training to measure changes in sleep quality. The alpha group shows a significant increase in alpha amplitude after training, indicating successful training of alpha waves. In addition, in the alpha group, the subjective questionnaire ISI showed an average decrease of 5.5 points (from 13.8 ± 1.2 to 8.3 ± 1.2), with 83% of participants experiencing a decrease in ISI scores. The PSQI scores also exhibited an average reduction of 5.1 points (from 13.3 ± 0.8 to 8.2 ± 1.4), with 75% of participants demonstrating a decrease in PSQI scores. Regarding objective sleep indicators, 83% of participants experienced a reduction in Wake After Sleep Onset (WASO) by an average of 26 minutes, while the arousal index did not show significant differences. Therefore, our proposed neurofeedback training mechanism indeed effectively improves sleep quality in insomnia patients with comorbid anxiety or depression and sleep maintenance difficulties.

Akyar, I., & Akdemir, N. (2013). The effect of light therapy on the sleep quality of the elderly: an intervention study. Australian Journal of Advanced Nursing, 31(2), 31-38.
Arns, M., Feddema, I., & Kenemans, J. (2014). Differential effects of theta/beta and SMR neurofeedback in ADHD on sleep onset latency. Frontiers in Human Neuroscience, 8, 1019.
Ashtaputre-Sisode, A. (2016). Emotions and brain waves. The International Journal of Indian Psychology, 3(2), 14-18.
Backhaus, J., Junghanns, K., Broocks, A., Riemann, D., & Hohagen, F. (2002). Test–retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia. Journal of Psychosomatic Research, 53(3), 737-740.
Baglioni, C., Battagliese, G., Feige, B., Spiegelhalder, K., Nissen, C., Voderholzer, U., Lombardo, C., & Riemann, D. (2011). Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. Journal of Affective Disorders, 135(1-3), 10-19.
Benatti, B., Girone, N., Conti, D., Celebre, L., Macellaro, M., Molteni, L., Vismara, M., Bosi, M., Colombo, A., & Dell’Osso, B. (2023). Intensive Neurofeedback Protocol: An Alpha Training To Improve Sleep Quality and Stress Modulation In Health Care Professionals During The COVID-19 Pandemic. A Pilot Study. Clinical Neuropsychiatry, 20(1), 61.
Berry, R. B., Brooks, R., Gamaldo, C. E., Harding, S. M., Marcus, C., & Vaughn, B. V. (2012). The AASM manual for the scoring of sleep and associated events. Rules, Terminology and Technical Specifications, Darien, Illinois, American Academy of Sleep Medicine, 176, 2012.
Bonnet, M., & Arand, D. (1997). Hyperarousal and insomnia. Sleep Medicine Reviews, 1(2), 97-108.
Buscemi, N., Vandermeer, B., Friesen, C., Bialy, L., Tubman, M., Ospina, M., Klassen, T. P., & Witmans, M. (2007). The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. Journal of General Internal Medicine, 22, 1335-1350.
Buysse, D. J., Reynolds III, C. F., Monk, T. H., Berman, S. R., & Kupfer, D. J. (1989). The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Research, 28(2), 193-213.
Cortoos, A., De Valck, E., Arns, M., Breteler, M. H., & Cluydts, R. (2010). An exploratory study on the effects of tele-neurofeedback and tele-biofeedback on objective and subjective sleep in patients with primary insomnia. Applied Psychophysiology and Biofeedback, 35, 125-134.
de Mendonça, F. M., de Mendonça, G. P. R. R., Souza, L. C., Galvao, L. P., Paiva, H. S., de Azevedo Marques Périco, C., Torales, J., Ventriglio, A., Maurício Castaldelli-Maia, J., & Sousa Martins Silva, A. (2023). Benzodiazepines and sleep architecture: a systematic review. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 22(2), 172-179.
Dew, M. A., Hoch, C. C., Buysse, D. J., Monk, T. H., Begley, A. E., Houck, P. R., Hall, M., Kupfer, D. J., & Reynolds III, C. F. (2003). Healthy older adults’ sleep predicts all-cause mortality at 4 to 19 years of follow-up. Psychosomatic Medicine, 65(1), 63-73.
Espie, C. A., MacMahon, K. M., Kelly, H.-L., Broomfield, N. M., Douglas, N. J., Engleman, H. M., McKinstry, B., Morin, C. M., Walker, A., & Wilson, P. (2007). Randomized clinical effectiveness trial of nurse-administered small-group cognitive behavior therapy for persistent insomnia in general practice. Sleep, 30(5), 574-584.
Feige, B., Baglioni, C., Spiegelhalder, K., Hirscher, V., Nissen, C., & Riemann, D. (2013). The microstructure of sleep in primary insomnia: an overview and extension. International Journal of Psychophysiology, 89(2), 171-180.
Harris, C. D. (2005). Neurophysiology of sleep and wakefulness. Respiratory Care Clinics of North America, 11(4), 567-586.
Hehr, A., Huntley, E. D., & Marusak, H. A. (2023). Getting a Good Night's Sleep: Associations Between Sleep Duration and Parent-Reported Sleep Quality on Default Mode Network Connectivity in Youth. Journal of Adolescent Health, 72(6), 933-942.
Hsueh, J. J., Chen, T. S., Chen, J. J., & Shaw, F. Z. (2016). Neurofeedback training of EEG alpha rhythm enhances episodic and working memory. Human Brain Mapping, 37(7), 2662-2675.
Imperatori, C., Della Marca, G., Amoroso, N., Maestoso, G., Valenti, E. M., Massullo, C., Carbone, G. A., Contardi, A., & Farina, B. (2017). Alpha/theta neurofeedback increases mentalization and default mode network connectivity in a non-clinical sample. Brain Topography, 30, 822-831.
Jobert, M., Poiseau, E., Jähnig, P., Schulz, H., & Kubicki, S. (1992). Pattern recognition by matched filtering: an analysis of sleep spindle and K-complex density under the influence of lormetazepam and zopiclone. Neuropsychobiology, 26(1-2), 100-107.
Kao, C.-C., Huang, C.-J., Wang, M.-Y., & Tsai, P.-S. (2008). Insomnia: prevalence and its impact on excessive daytime sleepiness and psychological well-being in the adult Taiwanese population. Quality of Life Research, 17, 1073-1080.
Kripke, D. F., Langer, R. D., & Kline, L. E. (2012). Hypnotics' association with mortality or cancer: a matched cohort study. BMJ Open, 2(1), e000850.
Kyle, S. D., Miller, C. B., Rogers, Z., Siriwardena, A. N., MacMahon, K. M., & Espie, C. A. (2014). Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder. Sleep, 37(2), 229-237.
Li, S.-H. (2021). The clinical application of neurofeedback training on symptom improvement in insomnia (Master’s thesis). National Cheng-Kung University, Tainan. https://hdl.handle.net/11296/h9spvu
Lin, I.-M., Fan, S.-Y., Yen, C.-F., Yeh, Y.-C., Tang, T.-C., Huang, M.-F., Liu, T.-L., Wang, P.-W., Lin, H.-C., & Tsai, H.-Y. (2019). Heart rate variability biofeedback increased autonomic activation and improved symptoms of depression and insomnia among patients with major depression disorder. Clinical Psychopharmacology and Neuroscience, 17(2), 222.
McCall, W. V. (2001). A psychiatric perspective on insomnia. Journal of Clinical Psychiatry, 62, 27-32.
Nano, M., Fonseca, P., Overeem, S., Vullings, R., & Aarts, R. M. (2020). Lying awake at night: cardiac autonomic activity in relation to sleep onset and maintenance. Frontiers in Neuroscience, 13, 1405.
Nofzinger, E. A., Nissen, C., Germain, A., Moul, D., Hall, M., Price, J. C., Miewald, J. M., & Buysse, D. J. (2006). Regional cerebral metabolic correlates of WASO during NREM sleep in insomnia. Journal of Clinical Sleep Medicine, 2(03), 316-322.
Oxley, B. C. (2017). International 10-20 system for EEG-MCN. https://commons.wikimedia.org/wiki/File:International_10-20_system_for_EEG-MCN.svg?uselang=zh-tw
Schabus, M., Griessenberger, H., Gnjezda, M.-T., Heib, D. P., Wislowska, M., & Hoedlmoser, K. (2017). Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia. Brain, 140(4), 1041-1052.
Schabus, M., Heib, D. P., Lechinger, J., Griessenberger, H., Klimesch, W., Pawlizki, A., Kunz, A. B., Sterman, B. M., & Hoedlmoser, K. (2014). Enhancing sleep quality and memory in insomnia using instrumental sensorimotor rhythm conditioning. Biological Psychology, 95, 126-134.
Spiegelhalder, K., Regen, W., Feige, B., Holz, J., Piosczyk, H., Baglioni, C., Riemann, D., & Nissen, C. (2012). Increased EEG sigma and beta power during NREM sleep in primary insomnia. Biological Psychology, 91(3), 329-333.
Taylor, D. J., & Pruiksma, K. E. (2014). Cognitive and behavioural therapy for insomnia (CBT-I) in psychiatric populations: a systematic review. International Review of Psychiatry, 26(2), 205-213.
Tsai, P.-S., Wang, S.-Y., Wang, M.-Y., Su, C.-T., Yang, T.-T., Huang, C.-J., & Fang, S.-C. (2005). Psychometric evaluation of the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in primary insomnia and control subjects. Quality of Life Research, 14, 1943-1952.
Walsh, J. K. (2004). Clinical and socioeconomic correlates of insomnia. Journal of Clinical Psychiatry, 65(8), 13-19.
Xuan, Y.-B., Guo, J., Wang, L.-P., & Wu, X. (2007). Randomized and controlled study on effect of acupuncture on sleep quality in the patient of primary insomnia. Zhongguo zhen jiu= Chinese acupuncture & moxibustion, 27(12), 886-888.
Yang, M., Morin, C. M., Schaefer, K., & Wallenstein, G. V. (2009). Interpreting score differences in the Insomnia Severity Index: using health-related outcomes to define the minimally important difference. Current Medical Research and Opinion, 25(10), 2487-2494.