Insomnia is a frequent and heightened pathology in the general population of developed countries, and its condition generally leads to health discomfort and performance drop in daily and work-related tasks. As current pharmacological treatments for insomnia do not always seem sufficient to mitigate impairment, contemporary cognitive approaches might shed light on developing complementary therapies for this population. We propose a cognitive stimulation intervention program based on the importance of cognitive abilities as precipitating and maintenance variables of sleep disturbances. A full phase I-II-III clinical trial is proposed in which the first two studies will serve to assess the safety of the intervention and to identify the maximum tolerated time of the computerized cognitive training (phase I) and the minimum effective number of training sessions (phase II) in the absence of adverse events or side effects. Next, a phase-III double-blind randomized controlled trial design will be set. Sixty individuals with insomnia aged 25 to 55 years will enroll in a home-based personalized computerized cognitive stimulation program for a total time of 8 weeks, training 5 days per week. Sixty insomnia patients matched in a variety of factors will constitute the active control group, where the orthogonal activities will not be cognitively demanding. Sleep, cognitive, emotional, and quality of life variables will be measured before and immediately after training. A linear mixed model and hierarchical regression analysis will be used to investigate intervention effects. The results derived from this study will be precious for future research and treatment in cognitive performance and clinical pathologies.
Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT05050292].
Insomnia is a clinical condition characterized by a difficulty falling or staying asleep, or going back to sleep after morning awakenings, even when optimal environmental conditions are present. In addition, this situation must occur without apparent psychiatric or somatic causes (Thorpy, 2017). In recent decades, the prevalence of this disorder has increased in industrialized countries, estimating that around 12% of the general population suffers from insomnia (Grewal and Doghramji, 2017), reaching 60% when it occurs comorbidly (Morin et al., 2006). Insomnia or poor-quality sleep derived from insomnia negatively impacts cognitive performance, mainly affecting executive functions, attention, memory and concentration (Ilioudi et al., 2011). Although there is some controversy among the cognitive domains affected by insomnia, the main cognitive skills where there is consistent poor performance are those assessed by tasks that measure attentional control, working memory, and problem solving, which are part of the cognitive processes involved in executive functions (see Fortier-Brochu et al., 2012; Miyata et al., 2013; Ballesio et al., 2019; Wardle-Pinkston et al., 2019). Likewise, insomnia has also been associated with poor academic/work performance (Bolge et al., 2009), a greater propensity to suffer occupational accidents (Kessler et al., 2012), and a greater vulnerability to other medical or psychiatric disorders (Chien et al., 2010; Khurshid, 2018), all these factors clearly affecting the quality of life of the patients.
Since the 1980s, insomnia research has pinpointed negative intrusive thoughts and worries about sleep as the leading cause of difficulty initiating sleep (Borkovec, 1979, 1982). Subsequently, several studies have indicated that individuals with insomnia are prone to anxiety, worry, obsession, and hypervigilance during the day (Kales and Kales, 1987; Edinger et al., 1988; Morin, 1993). These discoveries gave way to cognitive models of insomnia, such as the one presented by Harvey (2002). According to this model, the presence of rumination and cognitive concern about not being able to fall asleep or not getting enough sleep to function the next day leads to a state of anxiety with the subsequent activation of the sympathetic nervous system. Consequently, attentional activity will focus on looking for potentially harmful stimuli, increasing brain activity, and feeding back concerns and worry about falling asleep. This fact of paying attention to internal and external stimuli and sensations has been contrasted using neuroimaging and neuronal activity recording techniques, supporting the central hypothesis of brain hyperactivation that underlies this model (Bastien et al., 2021).
Over the years, predisposing, precipitating, and maintaining factors of insomnia have been defined (Bastien et al., 2004b). Researchers and clinicians alike have relied on neurocognitive (Perlis et al., 1997), cognitive (Harvey, 2002), and psychobiological inhibition models (Espie, 2002) to try to understand insomnia better. Interestingly, one approach that is gaining increasing attention to discover specific details of the pathophysiology of this disorder is neurobiology.
Throughout the past decades, the presence of cortical and physiological excitation and difficulties in inhibitory processes in insomnia have been highlighted in several studies carried out using different neuroscientific techniques. At a morphological level, research on structural magnetic resonance imaging (MRI) shows a reduction in the volume of gray matter in the medial frontal lobes, the hippocampus, the parietal cortex, and the anterior cingulate cortex in patients with insomnia (see Riemann et al., 2015), implying plausible memory impairment and frontal lobe dysfunction. According to Killgore et al. (2013), the observed increased functional connectivity between motor and sensory areas may explain the increment of unwanted and uncontrolled sustained and sensory awareness and processing. In addition to the structural alteration, functional magnetic resonance imaging (fMRI) studies have revealed greater activation in the hippocampus and the medial frontal gyrus (Leerssen et al., 2018) and reduced blood flow of the default neural network (DMN), associated with the modulation of conscious processes (Santarnecchi et al., 2018). These findings are consistent with the hyperarousal theory of insomnia (see Riemann et al., 2010, for review), supporting the increased mental worry and rumination characterized in the sleep onset and sleep maintenance of individuals with insomnia.
Research in electroencephalography (EEG) is congruent with the dysfunctional worries and attentional focus that these individuals experience (Harvey and Tang, 2012). Different studies have reported higher beta wave activity (associated with alert states) and lower delta activity (related to drowsiness) at the onset of sleep (e.g., Freedman, 1986; Merica and Gaillard, 1992), and higher alpha, beta, and sigma activity together with lower delta activity during REM sleep (Krystal et al., 2002). In line with the fMRI studies on the DMN, Corsi-Cabrera et al. (2012) found impaired frontal deactivation of cortical regions involving cognitive functions related to attentional control, stimulus inhibition, and self-awareness. The state of wakefulness present on sleep onset has also been explored through positron emission tomography (PET), finding an increased alertness brain activation (Spiegelhalder et al., 2017). Furthermore, studies with event-related brain potentials (ERPs) show that patients with insomnia present greater amplitude of the P1 waveform (an ERP component associated with the cognitive cost of care) and the N1 component (related to the detection of stimuli) upon waking up (Loewy and Bootzin, 1998; Loewy et al., 1999; Bastien et al., 2008), and greater amplitude of the P300 component (an ERP component that reflects the update of active working memory) at the beginning of sleep (Hull, 1993). At the same time, a decrease in P2 waves has been observed upon awakening (Loewy and Bootzin, 1998; Loewy et al., 1999), and a lower N350 at the beginning of sleep (Bastien et al., 2008), both components being associated with inhibition of the processing of irrelevant potentially disturbing sleep stimuli. ERPs results are consistent with EEG and PET studies, observing cortical hyperactivation and hypervigilance and low cognitive inhibition performance. These cognitive deficits in both activation and inhibition functions interfere with the mechanisms to initiate and maintain sleep, thus hindering people’s chances of falling asleep, which translates into insomnia.
The first-line treatment for insomnia, stated by different clinical practice guidelines such as the American College of Physicians (ACP) and the European guide for the diagnosis and treatment of insomnia, is Cognitive Behavioral Therapy (CBT, or CBT-I for the insomnia variant) (Riemann et al., 2017). However, the most used treatment for people with insomnia remains medication (i.e., benzodiazepine, benzodiazepine receptor agonist, and non-benzodiazepine hypnotics), probably because of the lack of knowledge of alternatives by primary-care physicians and the generalized search for immediacy typically achieved with pharmacotherapy (see Koffel et al., 2018). Given the chronicity of insomnia and the well-known high addiction risk and long-term side effects of medication (Benca, 2005; Buscemi et al., 2007), non-pharmacological interventions should prevail in these patients.
美國醫師學會（ACP）和歐洲失眠診斷和治療指南等不同臨床實踐指南指出，失眠的第一線治療方法是認知行為療法（CBT，或 CBT-I）變體）（黎曼等人，2017 ）。然而，失眠患者最常用的治療方法仍然是藥物治療（即苯二氮平類藥物、苯二氮平受體激動劑和非苯二氮平類安眠藥），這可能是因為初級保健醫生缺乏對替代方案的了解，並且普遍尋求即時治療。鑑於失眠的慢性性以及眾所周知的高成癮風險和藥物的長期副作用（ Benca，2005 ； Buscemi 等，2007 ），非藥物幹預措施應在這些患者中占主導地位。
In a general sense, CBT-I therapy seeks to readjust maladaptive or misleading cognitive beliefs related to sleep through the following main components: (a) relaxation, focused on teaching patients to generate a relaxation response (i.e., slow breathing, reduced heart rate) contrary to the stress response that increases arousal levels; (b) sleep hygiene and stimulus control therapy, where psychoeducation is used to instill healthy behaviors related to sleep, such as avoiding large dinners, not using digital screens at night, or limiting excessive light or noise; and (c) sleep restriction, aimed to match sleeping periods with the adequate sleeping time by forbidding patients to sleep during daytime hence accumulated sleeplessness will force nighttime sleeping.
一般而言，CBT-I 療法旨在透過以下主要組成部分重新調整與睡眠相關的適應不良或誤導性認知信念：(a) 放鬆，重點在於教導患者產生放鬆反應（即緩慢呼吸、降低心率）與增加喚醒水平的壓力反應相反； (b) 睡眠衛生和刺激控制療法，利用心理教育灌輸與睡眠有關的健康行為，例如避免豐盛的晚餐、晚上不使用數位螢幕或限制過度的光線或噪音； (c) 睡眠限制，旨在透過禁止患者白天睡覺來使睡眠時間與充足的睡眠時間相匹配，因此累積的失眠將迫使患者夜間睡眠。
Despite the extensive literature that corroborates the effectiveness of CBT-I (Koffel et al., 2015; Trauer et al., 2015; Sato et al., 2019), this therapy presents significant setbacks, including the stigma or reluctance in receiving psychological treatments, the in-person appointments, and the need to be performed by a qualified therapist. Given the shortage of professionals trained in CBT-I, availability is limited, and in most cases, it requires the patient to travel long distances. To avoid these primary accessibility impediment, the standard face-to-face CBT-I intervention was adapted to be administered by telephone, while maintaining adequate effectiveness (Bastien et al., 2004a). Still, the need for a therapist continued limiting access because of the waiting lists, so in recent years CBT-I has been extended and computerized to be administered digitally and via online. In this sense, CBT-I has been developed as (1) a support tool for conventional therapy, where the patient has access to teaching material and exercises to be completed at home, (2) an autonomous intervention guide with sporadic support from trained healthcare personnel, and (3) an individualized, unguided, and fully automated intervention—namely self-help intervention. However, even though these digital applications have been shown to be effective in clinical trials (see Seyffert et al., 2016; Luik et al., 2017; for review), the complexity of some tasks in the absence of a therapist and the required self-commitment and self-discipline by the patient compromises treatment adherence, reporting in some clinical studies drop rates over 40% (Vincent and Hameed, 2003; Ong et al., 2008). Together with this, it is also worth noting that the normative rules and rigidity of the sleep restriction component of the CBT-I seems to be counterproductive in some patients, diminishing their motivation and leading to diurnal fatigue and sleepiness (Kyle et al., 2014).
儘管有大量文獻證實 CBT-I 的有效性（ Koffel 等人，2015 年； Trauer 等人，2015 年； Sato 等人，2019 年），但這種療法存在重大挫折，包括恥辱或不願接受心理治療、親自預約以及需要由合格的治療師進行。由於接受 CBT-I 培訓的專業人員短缺，可用性有限，而且在大多數情況下，需要患者長途跋涉。為了避免這些主要的無障礙障礙，標準的面對面 CBT-I 介入被調整為透過電話進行，同時保持足夠的有效性（ Bastien 等人，2004a ）。儘管如此，由於等待名單的原因，對治療師的需求仍然受到限制，因此近年來 CBT-I 已擴展和電腦化，以數位化和線上方式進行管理。從這個意義上說，CBT-I 已被開發為 (1) 常規治療的支持工具，患者可以在家中獲得教材和練習，(2) 自主幹預指南，並獲得訓練有素的醫療保健人員的零星支持人員，以及（3）個人化的、無指導的、完全自動化的介入－即自助幹預。然而，儘管這些數位應用程式已在臨床試驗中被證明是有效的（參見Seyffert 等人，2016 年； Luik 等人，2017 年；供審查），在沒有治療師的情況下某些任務的複雜性和所需的患者的自我承諾和自律會影響治療依從性，一些臨床研究報告下降率超過 40%（ Vincent 和 Hameed，2003 ； Ong 等，2008 ）。 除此之外，還值得注意的是，CBT-I 睡眠限制部分的規範性規則和僵化似乎對某些患者產生反作用，削弱他們的積極性並導致晝間疲勞和嗜睡（ Kyle 等，2014） ）。
Over the years, there have been other non-pharmacological approaches showing promising results. A recent review by Chan et al. (2021) on non-pharmacological interventions in insomnia mentions mindfulness or Tai Chi as possible alternatives or complementary practices to treat sleep disturbances. Nevertheless, the objective of these practices is comparable to the relaxation/meditation component of CBT-I, seeking better knowledge and perception of internal and external stimuli, a greater focus on attentional processes, and, therefore, an improvement in the inhibition of other stimuli considered irrelevant or potentially harmful. Currently, both mindfulness and Thai Chi interventions have functional digital support applications. However, as in the case of CBT-I, adherence and therapy commitment are compromised due to complexity, abstraction, patient reluctance, and low level of motivation (Li et al., 2004; Ong et al., 2014; Black et al., 2015).
多年來，其他非藥物方法也顯示出有希望的結果。 Chan 等人最近的評論。 （2021）關於失眠的非藥物幹預措施提到正念或太極作為治療睡眠障礙的可能替代方案或補充做法。儘管如此，這些練習的目標與 CBT-I 的放鬆/冥想部分相當，尋求更好的知識和對內部和外部刺激的感知，更加關註註意力過程，從而改善對其他刺激的抑制被認為不相關或可能有害。目前，正念和太極幹預都有功能性的數位支援應用程式。然而，與 CBT-I 的情況一樣，由於複雜性、抽象性、患者不情願和低積極性，依從性和治療承諾受到損害（ Li 等人，2004 年； Ong 等人，2014 年； Black 等人， 2014 年）。
As the key component of insomnia seems to be hyperarousal and executive function deficit, interventions that enhance cognitive functioning (primarily inhibition mechanisms and attentional processes) might effectively reduce brain hyperactivation and distorted attentional stimulus focus. Even though the CBT-I might entail cognitive skills training, its main purpose is to restructure distorted cognitive beliefs and give the patient comprehensive safety behaviors, leaving aside the cognitive functioning alterations (i.e., attention, memory, and executive functions) present in patients with insomnia. In this sense, in recent years, computerized cognitive training (CCT) programs that reinforce the neural connections of the cognitive mechanisms underlying attentional control and inhibitory processes have been proposed as a successful method to directly focus on the dysfunctional cognitive mechanisms by stimulating the critical memory and attention cognitive domains, resulting in better ease of falling asleep.
由於失眠的關鍵組成部分似乎是過度覺醒和執行功能缺陷，因此增強認知功能（主要是抑制機制和注意力過程）的干預措施可能會有效減少大腦過度活躍和扭曲的注意力刺激焦點。儘管CBT-I 可能需要認知技能訓練，但其主要目的是重建扭曲的認知信念，並為患者提供全面的安全行為，不考慮患者存在的認知功能改變（即註意力、記憶和執行功能）。從這個意義上說，近年來，電腦化認知訓練（CCT）程序被提出來加強注意力控制和抑制過程背後的認知機制的神經連接，作為一種成功的方法，透過刺激關鍵記憶來直接專注於功能失調的認知機制。
The CCT approach is based on the concept of cognitive stimulation, aimed to strengthen neural connections through cognitive training by completing and repeating digital activities or exercises designed to improve cognitive skills with a mental workout (see Tapia and Duñabeitia, 2021). Numerous studies have demonstrated that cognitive training activities have remarkable positive results both in healthy population (Shatil, 2013; Bonnechère et al., 2020) and in different pathologies (e.g., Shatil et al., 2010; Preiss et al., 2013; Reijnders et al., 2013; Lawlor-Savage and Goghari, 2014; Spreij et al., 2014; Zhang et al., 2019) when assessing cognitive performance, even though the evidence showing far transfer effects is limited (e.g., Rebok et al., 2014; D’Antonio et al., 2019). However, an area of study in which CCT has been shown to be an effective method is that of sleep-related pathologies, evidencing improvements not only in the cognitive functioning but also in self-reported sleep quality when administered together with physical activity (Pa et al., 2014), and when compared to psychoeducation (Diamond et al., 2015; Almondes et al., 2017). To date, most studies that refer to cognitive training in the context of insomnia use the strategies and components of CBT-I but do not follow a proper CCT approach. For instance, Keramtinejad et al. (2019) proposed an 8-week cognitive training intervention to improve cognitive functioning and sleep quality of older adults with chronic insomnia. Although the intervention program included training of cognitive functions such as memory, attention, or executive functions, the proposed activities’ content was delivered in the form of group discussion or relied on cognitive therapy approaches. Therefore, due to the little coverage of pure cognitive rehabilitation in CBT-I interventions, it is worth considering CCT as an aid for patients with insomnia.
CCT 方法基於認知刺激的概念，旨在透過完成和重複旨在透過心理鍛鍊來提高認知技能的數位活動或練習，透過認知訓練來加強神經連結（參見Tapia 和 Duñabeitia，2021 ）。大量研究表明，認知訓練活動對健康人群（ Shatil，2013 ； Bonnechère 等，2020 ）和不同病理（例如， Shatil 等，2010 ； Preiss 等，2013 ； Reijnders）都具有顯著的正面效果。 2013 ； Lawlor-Savage 和 Goghari，2014 ； Spreij 等人，2014 ； Zhang 等人，2019 ），儘管顯示遠遷移效應的證據有限（例如， Rebok 等人，2014）。 2019 ）。然而，CCT 已被證明是一種有效方法的一個研究領域是與睡眠相關的病理學，證明當與身體活動一起進行時，不僅認知功能得到改善，而且自我報告的睡眠品質也得到改善（ Pa等）等人，2014 ），並與心理教育進行比較（ Diamond 等人，2015 ； Almondes 等人，2017 ）。迄今為止，大多數涉及失眠背景下認知訓練的研究都使用 CBT-I 的策略和組成部分，但沒有遵循正確的 CCT 方法。例如， Keramtinejad 等人。 (2019)提出了為期 8 週的認知訓練介入措施，以改善患有慢性失眠的老年人的認知功能和睡眠品質。 儘管幹預計畫包括記憶、注意力或執行功能等認知功能的訓練，但所提議的活動內容是以小組討論的形式進行的，或者依賴於認知治療方法。因此，由於CBT-I介入中純認知復健的通報很少，值得考慮CCT作為失眠患者的輔助手段。
In this line, Haimov and Shatil (2013) provided the first piece of evidence on the effectiveness of CCT in insomnia. The intervention of their study consisted of a home-based personalized and computerized cognitive training program using a commercial software and was carried out with seniors who suffered from insomnia. Participants were randomly assigned to either an experimental group that received personalized training, or to an active control group that was instructed to perform different tasks in typing and painting commercial software. To our knowledge, the study by Haimov and Shatil is the only existing one that uses CCT without applying cognitive therapy in individuals with insomnia.
在這方面， Haimov 和 Shatil (2013)首次提供了 CCT 對失眠有效性的證據。他們研究的干預措施包括使用商業軟體的家庭個人化和電腦化認知訓練計劃，並針對患有失眠症的老年人進行。參與者被隨機分配到接受個人化訓練的實驗組，或被指示在商業軟體中執行不同任務的主動對照組。據我們所知，Haimov 和 Shatil 的研究是現有的唯一一項在失眠患者中使用 CCT 而不進行認知治療的研究。
Given the disadvantages of pharmacological treatment for insomnia in the long term and the high costs of CBT-I, and considering the usefulness of computerized cognitive training (CCT) as an aid, the development of new lines of intervention in this perspective is deemed crucial. Based on the existing literature on the precipitating and maintenance factors of insomnia, we propose a research agenda with the proposal of a clinical trial aimed at demonstrating the safety and efficacy of an intervention based on a personalized CCT focused on the improvement of the cognitive components related to the processes of inhibition, attention, perception, and processing of stimuli, in order to partially compensate the problems related with cognitive states of concern and alert typically present in patients with insomnia disorder. To this end, a full phase I-II-III study protocol is presented. While the core of the intervention will be the phase-III randomized controlled trial, a safety and dose-limiting analysis protocol has also been designed as part of the phase-I/II trials to provide informed decisions. A phase-I trial will be conducted in order to assess the safety of the CCT and to determine the maximum tolerated training time per session (equivalent to the maximum tolerated dose of a medicine). Next, a phase-II trial will also be run to validate the safety of the CCT while determining the minimum necessary training sessions to observe significant effects (namely, to test the efficacy of the CCT). Finally, the critical phase-III trial will be carried out through an online platform of personalized CCT programs (CogniFit Inc., San Francisco, CA, United States), which will be administered to a group of patients with insomnia, while a different group of participants of similar characteristics will complete a control intervention lacking high cognitive demands and based on the completion of low-level computerized artistic tasks.
考慮到長期藥物治療失眠的缺點和 CBT-I 的高成本，並考慮到電腦認知訓練 (CCT) 作為輔助手段的有用性，從這個角度開發新的干預措施被認為至關重要。根據有關失眠誘發和維持因素的現有文獻，我們提出了一項研究議程，其中提出了一項臨床試驗，旨在證明基於個性化CCT 的干預措施的安全性和有效性，重點是改善與失眠相關的認知成分。為此，提出了完整的 I-II-III 期研究方案。雖然介入的核心將是 III 期隨機對照試驗，但安全性和劑量限制分析方案也被設計為 I/II 期試驗的一部分，以提供明智的決策。將進行一期試驗，以評估 CCT 的安全性並確定每次訓練的最大耐受訓練時間（相當於藥物的最大耐受劑量）。接下來，也將進行第二階段試驗來驗證 CCT 的安全性，同時確定觀察顯著效果（即測試 CCT 的功效）所需的最少訓練課程。最後，關鍵的 III 期試驗將透過個人化 CCT 計畫的線上平台（CogniFit Inc.）進行。，舊金山，加利福尼亞州，美國），這將被給予一組失眠患者，而另一組具有相似特徵的參與者將完成缺乏高認知要求並基於完成低水平計算機化的控制干預藝術任務。
This intervention could be of great help for patients with mild sleep problems or, if combined with CBT-I, for more severe cases. In addition, the proposed methodology allows access to the intervention to people with limited resources and those who reside in rural or isolated areas, given that it can be carried out from anywhere with an Internet connection and a smartphone, tablet, or computer. The main difference between our proposal and other treatments (and hence the reason for its value as a complementary approach) is that the intervention does not focus directly on the observable symptoms of insomnia but rather on the core underlying cognitive mechanisms that modulate them. Thus, the proposed CCT-based intervention aims to enhance executive functions and attentional processes, reduce monitoring of sleep-related threat signals, and improve inhibition processes of disruptive stimuli.
這種幹預措施對於患有輕度睡眠問題的患者可能有很大幫助，如果與 CBT-I 結合使用，對於更嚴重的病例可能會很有幫助。此外，所提出的方法允許資源有限的人和居住在農村或偏遠地區的人進行幹預，因為幹預可以在任何有網路連線和智慧型手機、平板電腦或電腦的地方進行。我們的建議與其他治療方法之間的主要區別（因此其作為補充方法的價值的原因）是，幹預措施並不直接關注可觀察到的失眠症狀，而是關注調節這些症狀的核心基礎認知機制。因此，所提出的基於 CCT 的干預旨在增強執行功能和注意力過程，減少對睡眠相關威脅訊號的監測，並改善破壞性刺激的抑制過程。
Given the findings that show that the excessive cognitive activity present in patients with insomnia is due to a deficit in the functioning of various cognitive functions related to attention and executive functions, we hypothesize that a systematized training in such functions will act as a catalyst on cortical hyperactivity, limiting rumination, intrusive thoughts and disturbing stimuli, thus improving the quality of sleep. We postulate that insomnia patients will also benefit from a general cognitive performance enhancement when CCT mainly targets cognitive functions.
鑑於研究結果表明，失眠患者存在的過度認知活動是由於與注意力和執行功能相關的各種認知功能的缺陷所致，我們假設對這些功能的系統化訓練將充當皮質功能的催化劑。活躍，限制沉思、侵入性想法和乾擾性刺激，從而提高睡眠品質。我們假設，當 CCT 主要針對認知功能時，失眠患者也將受益於一般認知能力的增強。
Therefore, the present study has three main objectives: (1) establish the acceptable sessions’ range to determine the maximum training time before fatigue or other adverse conditions appear; (2) determine the therapeutic efficacy of the intervention, establishing the range of needed training sessions, the tolerability to exercises, and the safety of the activity; and (3) verify that CCT can be a plausible non-pharmacological intervention to improve sleep quality in insomnia individuals.
因此，本研究有三個主要目標：（1）建立可接受的訓練時間範圍，以確定疲勞或其他不利情況出現之前的最長訓練時間； (2) 確定介入措施的治療效果，確定所需訓練的範圍、運動的耐受性、活動的安全性； (3) 驗證 CCT 可以作為合理的非藥物幹預措施來改善失眠個體的睡眠品質。
A standard 3 + 3 rule based up-and-down design without dose de-escalation will be followed (see Lin and Shih, 2001). This will be an open label prospective phase-I dose-escalation trial. Candidate participants will be recruited from the Sleep Unit of the Hospital Universitario de la Ribera (Spain). All participants will be individually interviewed in order to verify that they meet the inclusion criteria and to check their availability for the study. All participants will electronically sign an informed consent form prior to the beginning of the scientific actions. Together with the consent form, they will receive information about the approval of the protocol by the Ethics Committee in which the alignment with the criteria set by the declaration of Helsinki will be explicitly indicated. At all moments of the procedure, patients will be accompanied by trained medical doctors and psychologists from the research group.
將遵循基於標準 3+3 規則的上下設計，無需劑量遞減（參見Lin 和 Shih，2001 ）。這將是一項開放標籤前瞻性 I 期劑量遞增試驗。候選參與者將從拉里貝拉大學醫院（西班牙）睡眠部門招募。所有參與者都將接受單獨訪談，以驗證他們是否符合納入標準並檢查他們是否可以參加研究。所有參與者將在科學行動開始之前以電子方式簽署知情同意書。與同意書一起，他們將收到有關倫理委員會批准該方案的信息，其中將明確指出與赫爾辛基宣言規定的標準的一致性。在整個手術過程中，患者將由研究小組中訓練有素的醫生和心理學家陪同。
All participants will complete a first session in which they will respond to a general sociodemographic and medical questionnaire to ascertain that they meet the inclusion criteria. Together with this, they will also complete a general cognitive and psychological evaluation lasting for 60 min using either a laptop, PC or tablet. The instruments used for this assessment are described below (see Instruments and Outcome Measures section).
所有參與者將完成第一部分，其中他們將回答一般社會人口統計和醫學問卷，以確定他們符合納入標準。除此之外，他們還將使用筆記型電腦、PC 或平板電腦完成 60 分鐘的一般認知和心理評估。用於此評估的工具如下所述（請參閱工具和結果測量部分）。
The first cohort of participants (N = 3) will then start the phase I testing protocol. All participants will complete CogniFit Personalized Online Training, consisting of individual sessions in which three brain training games with a duration of around 5 min each need to be completed. The CCT will train six fundamental cognitive skills associated with the domains of memory, attention, perception and coordination: naming, working memory, non-verbal memory, visual perception, response time, divided attention and inhibition. The three participants from the first cohort will individually complete a 15-min training session under the supervision of a researcher from the team and a clinical psychologist. After finishing the session, they will complete a fatigue and safety evaluation questionnaire aimed at obtaining information about potential side effects and adverse events associated with the clinical process (see Instruments and Outcome Measures section). In case no side effects or adverse events are reported, a dose escalation will be implemented, and participants will then continue with a new training session of similar characteristics, structure and duration. The fatigue and safety questionnaire would be repeated right at the end of this new session, and the protocol would cyclically continue until the supervising researchers decide not to continue with an additional session because of having reached the dose-limiting toxicity level. If one participant from the cohort reports extreme fatigue levels (scores of 9 or 10 on the scale described below) or side effects or adverse events (see the questionnaire below) with a certain dose level (level i), a new cohort of three participants would start the protocol with the same dose level. If no other participant from the 3 + 3 cohort reports extreme fatigue, side effects or adverse events, the procedure would restart for a new cohort of three participants at the next dose level (level i + 1). However, if more than one participant from the 3 + 3 pool reports any of the outcomes, the maximum tolerated dose of the CCT would be set at level i-1. If two or more participants from the first cohort report extreme fatigue levels, or side effects, or adverse events with a certain dose level (level i), the maximum tolerated dose of the CCT would be set at level i-1.
然後，第一批參與者（ N = 3）將開始第一階段測試方案。所有參與者都將完成 CogniFit 個人化線上培訓，其中包括單獨的課程，其中需要完成三個大腦訓練遊戲，每個遊戲持續時間約為 5 分鐘。 CCT 將訓練與記憶、注意力、感知和協調領域相關的六種基本認知技能：命名、工作記憶、非語言記憶、視覺感知、反應時間、注意力分散和抑制。第一組的三位參與者將在團隊研究人員和臨床心理學家的監督下單獨完成 15 分鐘的訓練課程。會議結束後，他們將完成疲勞和安全評估問卷，旨在獲取與臨床過程相關的潛在副作用和不良事件的資訊（請參閱儀器和結果測量部分）。如果沒有副作用或不良事件的報告，將實施劑量遞增，然後參與者將繼續進行具有相似特徵、結構和持續時間的新訓練課程。疲勞和安全調查問卷將在新的會議結束時重複，並且該方案將循環繼續，直到監督研究人員因已達到劑量限制毒性水平而決定不再繼續進行額外的會議。如果隊列中的一名參與者報告在一定劑量水平（i 級）下出現極度疲勞程度（按照下述評分標準得分為9 或10）或副作用或不良事件（參見下面的問卷），則由三名參與者組成的新隊列將以相同的劑量水平開始該方案。 如果 3 + 3 隊列中沒有其他參與者報告極度疲勞、副作用或不良事件，則將為下一個劑量水平（水平 i + 1）的三名參與者組成的新隊列重新啟動該程序。然而，如果 3 + 3 池中超過一名參與者報告任何結果，則 CCT 的最大耐受劑量將設定為 i-1 級。如果第一組中的兩名或兩名以上參與者報告特定劑量等級（i 級）的極度疲勞程度、副作用或不良事件，則 CCT 的最大耐受劑量將設定為 i-1 級。
This trial will include a different group of 20 patients from the same hospital who meet the inclusion criteria described above, who will also sign the corresponding consent forms prior to initiation of collaboration. After having set the maximum tolerated training time per session in the phase I trial, a 15-day phase-II trial will be designed to ascertain the effectiveness of the CCT in the absence of adverse events or side effects.
該試驗將包括來自同一家醫院的符合上述納入標準的 20 名不同患者組，他們還將在開始合作之前簽署相應的同意書。在第一階段試驗中設定每次訓練的最大耐受時間後，將設計為期 15 天的第二階段試驗，以確定 CCT 在沒有不良事件或副作用的情況下的有效性。
To this end, 20 patients from the Sleep Unit of the Hospital Universitario de la Ribera (Spain) will be recruited and they will first complete an initial session (Day 1) that will serve to collect baseline data about their sleep problems and their cognitive skills, as well as about their sociodemographic information. As in the phase I trial, they will complete the general cognitive and psychological evaluation lasting for around 60 min (see Instruments and Outcome Measures section).
為此，將招募來自裡貝拉大學醫院睡眠科（西班牙）的 20 名患者，他們將首先完成初始會議（第一天），以收集有關他們的睡眠問題和認知技能的基線數據，以及他們的社會人口統計資料。與第一階段試驗一樣，他們將完成持續約 60 分鐘的一般認知和心理評估（請參閱儀器和結果測量部分）。
The day after the initial evaluation (Day 2), participants will be asked to visit the Sleep Unit again to complete the first training session with the CCT. The duration of the training session will be determined by the results of the phase I trial. Participants will complete this training session using either a tablet, a PC or a laptop, accompanied by the research and clinical team. Right at the end of the session, and in order to assess the safety of the intervention, participants will also complete the same safety questionnaire as in the phase I trial. In case any participant at any moment would report potential adverse events in any of the safety questions, the clinical psychologist would immediately interview them in order to classify the side effect or adverse event according to its seriousness following the criteria and elements adapted from the Patient-Reported Adverse Drug Event Questionnaire (de Vries et al., 2013).
初步評估後的第二天（第 2 天），參與者將被要求再次訪問睡眠單元，以完成 CCT 的第一次訓練課程。培訓課程的持續時間將根據第一階段試驗的結果來決定。參與者將在研究和臨床團隊的陪同下使用平板電腦、個人電腦或筆記型電腦完成本訓練課程。在會議結束時，為了評估介入的安全性，參與者也將完成與第一階段試驗相同的安全問卷。如果任何參與者在任何時候報告任何安全問題中的潛在不良事件，臨床心理學家將立即與他們面談，以便按照患者適應的標準和要素，根據其嚴重程度對副作用或不良事件進行分類。藥物不良事件問卷（ de Vries 等，2013 ）。
The protocol would then continue the next day (Day 3) with a full assessment identical to that of the first session. The day after (Day 4) would consist of the repetition of the training session of Day 2. This way, and alternating assessment and training sessions, participants will complete a 15-day cycle that will start and end with a full assessment (Day 1 and Day 15), and that will include eight different evaluation or test points (Day 1, Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, and Day 15) and seven training sessions (Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, and Day 14).
然後，該協議將在第二天（第 3 天）繼續進行，並進行與第一次會議相同的全面評估。第二天（第4 天）將包括重複第2 天的培訓課程。 （第1 天）和第15 天），其中包括八個不同的評估或測試點（第1 天、第3 天、第5 天、第7 天、第9 天、第11 天、第13 天和第15 天）和7 個訓練課程（第2 天、第1 天、第1 天） 4、第 6 天、第 8 天、第 10 天、第 12 天和第 14 天）。
The results of the effectiveness of the CCT will be evaluated using linear mixed models for repeated measures, analyzing differences in the primary and secondary outcomes described below. This will provide a first approach to and statistical validation of the usefulness of the CCT to alleviate the cognitive, psychological or medical symptoms of insomnia in the selected sample by determining the minimum number of training sessions needed to observe a significant change. Besides, quantitative and qualitative analysis of the results of the safety questionnaires will help us determine the safety of the intervention program.
CCT 效度的結果將使用重複測量的線性混合模型進行評估，分析下述主要和次要結果的差異。這將為 CCT 的有效性提供第一種方法和統計驗證，透過確定觀察顯著變化所需的最小訓練次數來減輕所選樣本中失眠的認知、心理或醫學症狀。此外，對安全性問卷結果進行定量和定性分析將有助於我們確定介入方案的安全性。
The final stage of the protocol will consist of a double-blind randomized controlled phase-III trial in which a large group of patients with insomnia recruited from the Sleep Unit of the Hospital Universitario de la Ribera, as well as from collaborating medical institutions will voluntarily enroll in an 8-weeks personalized and supervised cognitive training intervention. The medical team will inform those patients who meet the inclusion criteria of the possibility of voluntarily participating in the experiment. Those interested will be put in contact with the researchers, who will interview them individually. In this first contact, all the information regarding the study will be provided. Patients who agree to participate will complete the necessary legal documentation and informed consent and be included in the study.
該協議的最後階段將包括一項雙盲隨機對照 III 期試驗，其中從裡貝拉大學醫院睡眠科以及合作醫療機構招募的一大群失眠患者將自願參加為期8 週的個人化和監督認知訓練介入。醫療團隊將告知那些符合納入標準的患者自願參加實驗的可能性。有興趣的人將與研究人員聯繫，研究人員將對他們進行單獨訪談。在第一次聯繫中，將提供有關該研究的所有資訊。同意參與的患者將填寫必要的法律文件和知情同意書並參與研究。
A complete evaluation will be carried out at the beginning (pretest) and at the end of the intervention (post-test) using the materials and instruments also used in the phase-II study. The pretest will collect baseline data about sleep problems and cognitive skills, together with sociodemographic information. Standardized batteries and tests will be used to measure the general neurocognitive state and the emotional state, together with specific tests and measurements of the pattern and quality of sleep, and tests that measure health-related quality of life. All variables will be measured objectively (i.e., direct test scores) and subjectively (i.e., what the patient or her close associates express). The post-test will collect data on sleep problems and cognitive skills, but no additional sociodemographic data will be needed (see Instruments and Outcome Measures section for a description of the tools). Having already established the safety of the protocol in the phase-I and phase-II studies, no information will be collected in this regard in the phase-III trial.
將使用第二階段研究中使用的材料和儀器在幹預開始（預測試）和乾預結束（後測試）時進行完整的評估。預測試將收集有關睡眠問題和認知技能的基線數據以及社會人口統計資料。標準化電池和測試將用於測量一般神經認知狀態和情緒狀態，以及睡眠模式和品質的特定測試和測量，以及測量與健康相關的生活品質的測試。所有變數都將進行客觀（即直接測試分數）和主觀（即患者或其親密夥伴的表達）測量。後測將收集有關睡眠問題和認知技能的數據，但不需要額外的社會人口統計（有關工具的說明，請參閱儀器和結果測量部分）。由於已經在 I 期和 II 期研究中確定了該方案的安全性，因此在 III 期試驗中將不會收集這方面的資訊。
Next, the CCT intervention will be carried out. This will be done through the CogniFit online platform so that each participant will access it from home using a personal computer or smart device. The training will last for a total of 8 weeks, with five training days per week. This way, a total of 40 training sessions are expected. The duration of the sessions will be determined by the maximum tolerated training time resulting from the phase-I trial. Since this process will be autonomously managed by each participant, they will be contacted periodically (a minimum of two phone calls per week) to ensure adherence and check that they have not had any incidence. The platform will record participants’ performance, providing researchers with real-time feedback on the performance and adherence of each participant.
接下來，將進行CCT幹預。這將透過 CogniFit 線上平台完成，以便每位參與者都可以使用個人電腦或智慧型裝置在家中存取平台。培訓為期總計8週，每週培訓5天。這樣一來，預計總共有 40 場訓練課程。課程的持續時間將由第一階段試驗產生的最大耐受訓練時間決定。由於此過程將由每個參與者自主管理，因此我們將定期聯繫他們（每周至少兩次電話），以確保遵守並檢查他們是否沒有發生任何事件。該平台將記錄參與者的表現，為研究人員提供每個參與者的表現和依從性的即時回饋。
Participants will be randomly assigned to one out of two groups (control/experimental). The experimental group will complete a personalized CCT intervention based on CogniFit’s Personalized Online Training, including a series of games and activities targeting attention, memory and executive functions. The difficulty level of each of the activities will dynamically change to match the cognitive profile of each participant on each training day. By automatically adjusting the activities’ difficulty and requirements according to each participant’s performance, cognitive taxing is adapted and a maximum cognitive effort is always required. Similar to Haimov and Shatil (2013), the active control group will complete a series of painting activities specifically designed not to result cognitively demanding and to maintain a low complexity level and constant difficulty throughout the intervention. These activities will not target the intended cognitive processes (namely, they will target orthogonal unrelated aspects). Participants will be randomly assigned to either the experimental or control group, with the experimenters and the patients being fully blind to the group classification.
參與者將被隨機分配到兩組（對照組/實驗組）中的一組。實驗組將基於CogniFit的個人化線上訓練完成個人化的CCT幹預，包括一系列針對注意力、記憶力和執行功能的遊戲和活動。每項活動的難度等級都會動態變化，以配合每個訓練日每個參與者的認知概況。透過根據每個參與者的表現自動調整活動的難度和要求，認知負荷得到調整，並且始終需要最大的認知努力。與Haimov 和 Shatil (2013)類似，主動對照組將完成一系列專門設計的繪畫活動，這些活動不會產生認知要求，並在整個幹預過程中保持較低的複雜性水平和恆定的難度。這些活動不會針對預期的認知過程（即，它們將針對正交的不相關方面）。參與者將被隨機分配到實驗組或對照組，實驗者和患者對組分類完全不知情。
After post-test data collection, and prior to statistical analyses, all variables will be checked for normality of distribution, and plots will be visually inspected for asymmetry and kurtosis. Then, descriptive statistics will be obtained to provide an overview of the sociodemographic and clinical characteristics of the participants. To examine intervention effectiveness, the changes in all outcome measures from baseline (pretest) to post-intervention (post-test) will be analyzed. Differences in primary outcomes and secondary outcomes will be analyzed through linear mixed models for repeated measures. Models will assess within and between-group differences before and after the intervention. The Group factor (experimental, control) will be included as an independent variable, together with Time (pre-test at baseline, post-test after the intervention). Sociodemographic factors such as gender and age will be used as moderators. Dependent variables will be sleep quality, insomnia severity, quality of life, cognitive abilities, executive function, depressive symptoms, anxiety symptoms, and worrying. To isolate the variable that better explains the model, a hierarchical regression analysis will be conducted with the sleep quality improvements as the dependent variable and the cognitive improvements as the independent ones. This hierarchical regression analysis will be also useful to evaluate the impact of the adherence to the training in the whole sample of participants, regardless of whether they have effectively completed the intervention or not (i.e., cases of attrition or incomplete sessions). The hierarchical regression analysis with the sleep quality improvement as the dependent variable will follow a stepwise approach in which sociodemographic factors will be added in a first step, the data corresponding to the adherence to the treatment (namely, number and length of the completed sessions) in a second step, and the cognitive data from the BRIEF-A and the Cognitive Assessment Battery CAB™ as a third and final step.
在測試後資料收集之後和統計分析之前，將檢查所有變數的分佈常態性，並目視檢查圖的不對稱性和峰度。然後，將獲得描述性統計數據，以概述參與者的社會人口統計和臨床特徵。為了檢查幹預效果，將分析從基線（預測試）到干預後（後測試）的所有結果測量的變化。主要結果和次要結果的差異將透過重複測量的線性混合模型進行分析。模型將評估介入前後組內和組間的差異。組因素（實驗、對照）將與時間（基線前測試、幹預後測試後）一起作為自變量包含在內。性別和年齡等社會人口因素將用作調節因素。因變數包括睡眠品質、失眠嚴重程度、生活品質、認知能力、執行功能、憂鬱症狀、焦慮症狀和擔憂。為了分離出更好地解釋模型的變量，將以睡眠品質改善作為因變量、認知改善作為自變量進行分層回歸分析。這種層次迴歸分析也可用於評估整個參與者樣本中堅持訓練的影響，無論他們是否有效地完成了介入（即，減員或不完整課程的情況）。 以睡眠品質改善作為因變量的分層回歸分析將遵循逐步方法，其中第一步將添加社會人口因素，即與治療依從性相對應的數據（即完成療程的數量和長度）第二步是來自Brief-A 和認知評估電池CAB™ 的認知數據，第三步也是最後一步。
Participants will be recruited from the Sleep Unit of the Hospital Universitario de la Ribera (Spain) for the phase-I and phase-II trials, and from the same Unit and associated medical centers for the phase-III trial. According to the a priori established eligibility criteria, participants will be adults between 25 and 55 years old who have been diagnosed by Insomnia Disorder according to DSM-5, fully matching the diagnostic criteria (e.g., showing a predominant complaint of dissatisfaction with sleep quantity or quality occurring at least three nights per week and having been present for a minimum of 3 months, despite them having adequate opportunity for sleep and in the absence of sleep-wake disorders or the use of substances, which causes clinically relevant impairment). We selected this age range in an attempt to improve sample homogeneity in executive function development (see Ferguson et al., 2021), and to ensure that participants would have access to new technologies. Participants will be excluded from the study if they meet any of the following a priori established criteria: (1) they present another sleep-wake disorder (e.g., narcolepsy, restless leg syndrome, a breathing-related sleep disorder, a circadian sleep-wake rhythm disorder, a parasomnia); (2) they present a relevant medical, psychiatric or neurological disorder; (3) they show significant visual or motor impairments; (4) they present history of alcohol or drug abuse or dependence; (5) they show a caffeine consumption higher than 150 mg per day or an alcohol consumption higher that 250 ml per day; (6) they use medication with stimulant action, except the sedatives or hypnotics specifically prescribed for sleep.
參與者將從拉里貝拉大學醫院睡眠科（西班牙）招募進行 I 期和 II 期試驗，並從同一科室和相關醫療中心招募受試者進行 III 期試驗。根據先驗確定的資格標準，參與者將是根據 DSM-5 診斷為失眠障礙的 25 至 55 歲成年人，完全符合診斷標準（例如，主要抱怨睡眠品質不滿意或儘管他們有足夠的睡眠機會並且沒有睡眠-覺醒障礙或使用導致臨床相關損害的物質，但每周至少三個晚上出現這種質量，並且已經存在至少3 個月。我們選擇這個年齡範圍是為了提高執行功能開發中的樣本同質性（參見Ferguson 等人，2021 ），並確保參與者能夠接觸到新技術。如果參與者符合以下任何先驗既定標準，則將被排除在研究之外：（1）他們出現另一種睡眠-覺醒障礙（例如發作性睡病、不寧腿症候群、與呼吸相關的睡眠障礙、晝夜節律睡眠-覺醒障礙）節律紊亂，異態睡眠）； (2) 存在相關的醫學、精神或神經系統疾病； (3) 有明顯的視覺或運動障礙； (4) 有酗酒或吸毒或依賴的歷史； (5) 每日咖啡因攝取量超過 150 毫克，或每日酒精攝取量超過 250 毫升； （六）使用具有興奮作用的藥物，但專門用於睡眠的鎮靜劑或安眠藥除外。
The phase-I trial will follow a standard 3 + 3 protocol. Consequently, the minimum number of participants will be three, and the maximum number of participants will depend on the results of each of the 3-patient cohorts. The phase-II trial will include 20 insomnia patients. Finally, the phase-III trial will consist of a minimum sample size set at 60 participants per group, given that the purpose of this research is to make a first approach to the positive impact of a cognitive training of executive functions on insomnia and to be able to generalize the results obtained with a 95% confidence interval and sufficient statistical power to test hypotheses (sig. bilateral). While a larger number of participants would be desirable for a phase-III trial, it should be considered that the specific selection criteria of the sample and the restricted number of patients that are available at the hospital and the associated centers make it difficult to increase the sample size to account for potential attrition rates and lack of adherence.
I 期試驗將遵循標準的 3 + 3 方案。因此，最小參與者人數為三人，最大參與者人數將取決於 3 名患者群組中每組的結果。 II期試驗將包括20名失眠患者。最後，III 期試驗的最小樣本量將設定為每組 60 名參與者，因為這項研究的目的是首先探討執行功能認知訓練對失眠的正面影響，並能夠概括以95% 置信區間和足夠的統計能力所獲得的結果來檢驗假設（sig.雙邊）。雖然 III 期試驗需要更多的參與者，但應該考慮到樣本的具體選擇標準以及醫院和相關中心的患者數量有限，使得增加樣本量變得困難。
We will carry out a specific evaluation of sleep quality and insomnia, together with a general evaluation of the participant’s neurocognitive and emotional state. Likewise, these evaluations will be complemented with an assessment of the quality of life.
我們將對睡眠品質和失眠進行具體評估，同時對參與者的神經認知和情緒狀態進行整體評估。同樣，這些評估將輔以生活品質評估。
The Pittsburgh Sleep Quality Index (PSQI) will be used. The PSQI is a self-report questionnaire that assesses sleep quality and consists of 19 individual items, creating seven components that produce one global score. It takes 5–10 min to complete. The PSQI includes a scoring key for calculating a patient’s seven sub-scores, each of which can range from 0 to 3. The sub-scores are tallied, yielding a global score that can range from 0 to 21. A global score of five or more indicates poor sleep quality, and the higher the score is, the worse the sleep quality can be considered.
將使用匹茲堡睡眠品質指數 (PSQI)。 PSQI 是一種評估睡眠品質的自我報告問卷，由 19 個單獨項目組成，創建七個組成部分，產生一個總體分數。需要 5-10 分鐘才能完成。 PSQI 包括一個評分鍵，用於計算患者的七個子分數，每個子分數的範圍為 0 到 3。品質越差，分數越高可以認為睡眠品質越差。
The Insomnia Severity Index (ISI) will be used. The ISI is a brief instrument designed to assess the severity of both nighttime and daytime components of insomnia. It comprises seven items assessing the perceived severity of difficulties initiating sleep, staying asleep, early morning awakenings, satisfaction with current sleep pattern, interference with daily functioning, noticeability of impairment attributed to the sleep problem, and degree of distress or concern caused by the sleep problem. Possible scores range from 0 (no clinically significant insomnia) to 28 (clinical severe insomnia).
將使用失眠嚴重程度指數（ISI）。 ISI 是一種簡短的工具，旨在評估夜間和白天失眠的嚴重程度。它包括七個項目，評估入睡困難、保持睡眠困難、清晨醒來的感知嚴重程度、對當前睡眠模式的滿意度、對日常功能的干擾、睡眠問題造成的損害的明顯程度以及睡眠引起的痛苦或擔憂的程度問題。可能的評分範圍為 0（無臨床顯著失眠）至 28（臨床嚴重失眠）。
The Measuring Quality of Life | The World Health Organization–abridged version (WHOQOL-BREF) will be used. The WHOQOL-BREF is a generic questionnaire to measure the quality of life created by the Study Group on Quality of Life of the World Health Organization. It has two general questions on the quality of life and satisfaction with the state health, and 24 questions grouped into four areas or domains: Physical Health, Psychological Health, Social Relations, and Environment. The measure is calculated by summing the scores in the questions corresponding to each domain and then transforming them to a 0–100 point interval. Possible scores for each domain range from 0 (poor perceived quality of life) to 100 (greater perceived quality of life).
衡量生活品質|將使用世界衛生組織的刪節版 (WHOQOL-BREF)。 WHOQOL-BREF 是世界衛生組織生活品質研究小組創建的衡量生活品質的通用問卷。它有兩個關於生活品質和對國家健康滿意度的一般問題，以及分為四個領域或領域的 24 個問題：身體健康、心理健康、社會關係和環境。此衡量標準的計算方法是將每個領域對應的問題的分數相加，然後將其轉換為 0-100 分區間。每個領域的可能分數範圍為 0（感知生活品質較差）到 100（感知生活品質較高）。
Additionally, the short version of the self-perceived global physical and mental health scale from the Patient-Reported Outcomes Measurement Information System (PROMIS v.1.2; see (Hays et al., 2015, 2017), will be also used. Participants will respond to the following questions: In general, how would you rate your health? (Options: Excellent, Very Good, Good, Fair, Poor); In general, how would you rate your physical health? (Options: Excellent, Very Good, Good, Fair, Poor); To what extent are you able to carry out your everyday physical activities such as walking, climbing stairs, carrying groceries, or moving a chair? (Options: Completely, Mostly, Moderately, A little, Not at all); In general, how would you rate your mental health, including your mood and your ability to think? (Options: Excellent, Very Good, Good, Fair, Poor); In general, how would you rate your satisfaction with your social activities and relationships? (Options: Excellent, Very Good, Good, Fair, Poor).
此外，還將使用患者報告結果測量資訊系統（PROMIS v.1.2；參見（ Hays 等人，2015 年、 2017 年）中的自我感知全球身心健康量表的簡短版本。參與者將回答以下問題：一般而言，您如何評估您的健康狀況？ （選項：優秀、非常好、良好、一般、差）；一般而言，您如何評價您的身體健康狀況？程度上進行日常體力活動，例如步行、爬樓梯、搬運雜貨或移動椅子？您的情緒和思考能力？一般、差）。
The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) will be used. The BRIEF-A is a standardized measure that captures views of an adult’s executive functions or self-regulation in his or her everyday environment. Only the self-report format will be used. The BRIEF-A comprises 75 items within nine theoretically and empirically derived clinical scales that measure various aspects of executive functioning; Inhibit, Self-Monitor, Plan/Organize, Shift, Initiate, Task Monitor, Emotional Control, Working Memory, Organization of Materials. The clinical scales form two broader indexes: Behavioral Regulation (BRI) and Metacognition (MI), and these indexes form the overall summary score, the Global Executive Composite (GEC). It also includes three validity scales (Negativity, Inconsistency, and Infrequency). It takes approximately 10–15 min to administer. All 75 items are rated in terms of frequency on a 3-point scale: 0 (never), 1 (sometimes), 2 (often). Raw scores for each scale are summed for the total score.
將使用執行功能行為評定量表-成人版（BRIEF-A）。 Brief-A 是一種標準化測量方法，旨在了解成年人在日常環境中的執行功能或自我調節能力。僅使用自我報告格式。 Brief-A 包含 9 個從理論和經驗得出的臨床量表中的 75 個項目，用於衡量執行功能的各個方面；抑制、自我監控、計畫/組織、輪班、啟動、任務監控、情緒控制、工作記憶、材料組織。臨床量表形成兩個更廣泛的指數：行為調節（BRI）和後設認知（MI），這些指數形成總體總結分數，即全球執行綜合指數（GEC）。它還包括三個有效性量表（消極性、不一致性和不頻繁性）。給藥大約需要 10-15 分鐘。所有 75 個項目均以 3 分制的頻率進行評級：0（從不）、1（有時）、2（經常）。每個量表的原始分數相加即為總分。
The Cognitive Assessment Battery CAB™ test provides a general cognitive score as well as specific scores in each of the measured cognitive skills. The Cognitive Assessment Battery CAB™ includes a series of 17 short tests (∼2–3 min each) that measure a variety of different cognitive abilities, putting a heavy focus on executive functions. These are then used to obtain a general score, as well as five different sub-scores based on perception, attention, memory, coordination and reasoning. The resulting scores per participant in each of the 23 cognitive skills measured by the CAB™ are contrasted with the normative database of the test and each converted into z-scores and percentiles. It takes about 40 min to administer when done for the first time prior to any form of computerized training, and then it automatically updates the information and scores by recalculating the output as a function of participants’ performance in the tasks included in CogniFit’s Personalized Online Training.
認知評估電池 CAB™ 測試提供一般認知分數以及每項測量的認知技能的具體分數。認知評估電池 CAB™ 包括一系列 17 個簡短測試（每個測試約 2-3 分鐘），用於測量各種不同的認知能力，並專注於執行功能。然後使用這些分數來獲得總分，以及基於感知、注意力、記憶、協調和推理的五個不同的子分數。 CAB™ 測量的 23 種認知技能中每位參與者的得分與測試的規範資料庫進行對比，並將每項得分轉換為 z 得分和百分位數。在任何形式的電腦化訓練之前首次完成時，需要大約 40 分鐘進行管理，然後根據參與者在 CogniFit 個人化線上訓練中包含的任務中的表現重新計算輸出，自動更新資訊和分數。
The Beck Depression Inventory-II (BDI-II) will be used. The BDI-II is a 21-item, self-report inventory designed to measure the frequency and severity of depressive symptoms. Items include somatic-affective symptoms as well as cognitive symptoms. Possible scores range from 0 (no depressive symptoms) to 63 (severe depression).
將使用貝克憂鬱量表-II (BDI-II)。 BDI-II 是一份包含 21 項的自我報告清單，旨在衡量憂鬱症狀的頻率和嚴重程度。項目包括軀體情緒症狀以及認知症狀。可能的分數範圍為 0（無憂鬱症狀）到 63（重度憂鬱）。
The State-Trait Anxiety Inventory (STAI) will be used. The STAI is a self-report that assesses two types of anxiety: state anxiety, or anxiety about an event, and trait anxiety, or anxiety level as a personal characteristic. Only the 20 items referred to state anxiety will be administered. Possible scores range from 0 (no anxiety) to 60 (severe anxiety).
將使用狀態特質焦慮量表（STAI）。 STAI 是一份自我報告，評估兩種類型的焦慮：狀態焦慮，或對某一事件的焦慮，以及特質焦慮，或作為個人特徵的焦慮程度。僅管理 20 個涉及狀態焦慮的項目。可能的分數範圍從 0（無焦慮）到 60（嚴重焦慮）。
The Penn State Worry Questionnaire (PSWQ) will be used. The PSWQ is a 16-item questionnaire that aims to measure the trait of worry. The items on the scale assess the occurrence, intrusiveness, pervasiveness, and other characterizing features of an individual’s experience with worry. The scale has been shown to identify worry, over and above anxiety and depression. Items are rated on a five-point scale: 1-Not at all typical of me to 5-Very typical of me. Possible scores range from 16 (low worry) to 80 (high worry).
將使用賓州州立大學憂慮問卷 (PSWQ)。 PSWQ 是一份包含 16 項的問卷，旨在衡量擔憂的特徵。量表上的項目評估個人擔憂經歷的發生率、侵入性、普遍性和其他特徵。該量表已被證明可以識別焦慮和憂鬱以外的擔憂。項目以五分制評分：1-對我來說完全不典型，5-對我來說非常典型。可能的分數範圍為 16（低擔憂）到 80（高擔憂）。
Participants will respond to a first question targeting the fatigue level felt at the time of finishing the session, adapted from the Brief Fatigue Inventory (Mendoza et al., 1999): Please rate your fatigue (weariness, tiredness) by selecting the number that best describes your fatigue right now [Options: Scale from 0 (no fatigue) to 10 (as bad as you can imagine)].
參與者將回答第一個問題，針對結束課程時感受到的疲勞程度，該問題改編自《簡要疲勞量表》（ Mendoza 等人，1999 年）：請透過選擇最適合的數字來評估您的疲勞程度（疲倦、疲倦）描述您現在的疲勞程度[選項：從 0（無疲勞）到 10（如您想像的那樣嚴重）]。
The safety questionnaire will include a definition of side effects as any effect that was not the intended clinical effect of the CCT, regardless of it being harmful or adverse. Participants will respond to a binary question (yes/no) to indicate whether they feel any side effect right after the session. Similarly, all participants will be also asked a binary (yes/no) question about possible adverse events they may feel. Adverse events will be defined as any undesirable experience associated with the use of the CCT platform: Please indicate if you feel any side effect of the Computerized Cognitive Training session you have just finished, regardless of it being harmful or adverse (Options: Yes, No); Please indicate if you feel any undesirable experience associated with the Computerized Cognitive Training (Options: Yes, No).
安全問卷將包括副作用的定義，即任何非 CCT 預期臨床效果的效果，無論其是否有害或不利。參與者將回答一個二元問題（是/否），以顯示他們在療程結束後是否感到任何副作用。同樣，所有參與者也會被問到一個關於他們可能感受到的不良事件的二元（是/否）問題。不良事件將被定義為與使用 CCT 平台相關的任何不良體驗：請說明您是否感覺到剛完成的電腦認知訓練課程有任何副作用，無論它是有害的還是不利的（選項：是、否）；請指出您是否感到與電腦認知訓練相關的任何不良體驗（選項：是、否）。
In case any participant at any moment would respond “yes” to any of the two safety questions, a member of the research team would immediately interview them in order to classify the side effect or adverse event according to its seriousness following the criteria and elements adapted from the Patient-Reported Adverse Drug Event Questionnaire (de Vries et al., 2013).
如果任何參與者在任何時候對兩個安全問題中的任何一個回答“是”，研究團隊的成員將立即採訪他們，以便根據其嚴重程度按照適應的標準和要素對副作用或不良事件進行分類摘自患者報告的藥物不良事件問卷（ de Vries 等，2013 ）。
We expect results to show between-group significant improvements for the cognitive stimulation training group (namely, the experimental group completing the CCT intervention) on sleep quality, quality of life, and cognitive performance. Moreover, due to the relationship between cognitive performance—mainly of cognitive functions—and cognitive awareness and distraction avoidance, we also anticipate a reduction in depressive and anxiety symptoms, and cognitive worrying, all of these linked to a reduced insomnia severity. The fact of receiving the treatment could cause minor improvement in the active control group. Being immersed in the intervention program and carrying out the proposed activities daily—even if they are not designed for it—could lead to an improvement in cognitive functioning. However, if it were to occur, it would not be expected that this improvement would be significant, or if it were, it would be expected to occur in cognitive functions not related to the pathology under study (i.e., verbal fluency).
我們預期結果將顯示認知刺激訓練組（即完成 CCT 介入的實驗組）在睡眠品質、生活品質和認知表現方面的組間顯著改善。此外，由於認知表現（主要是認知功能）與認知意識和避免分心之間的關係，我們也預期憂鬱和焦慮症狀以及認知擔憂會減少，所有這些都與失眠嚴重程度的減輕有關。接受治療的事實可能會導致積極對照組的輕微改善。沉浸在幹預計畫中並每天進行建議的活動——即使它們不是為此而設計的——可能會導致認知功能的改善。然而，如果發生的話，這種改善不會是顯著的，或者如果是的話，預計會發生在與所研究的病理學無關的認知功能中（即語言流暢性）。
This project represents an advance in cognitive and health science research and presents a transfer potential of great relevance. The results hope to offer a viable and accessible intervention that aims to enhance the cognitive performance and the quality of life of those who suffer from sleep disturbances. If the results are as expected, this study may encourage the implementation of home-based personalized cognitive stimulation interventions for patients with insomnia and sleep disturbances. This intervention could decongest the health system, improve patients’ care and quality of life, reduce the side effects of pharmacological treatment, and save on medical care. In order to overcome clinician barriers briefly mentioned above (i.e., lack of knowledge of non-pharmacological interventions by clinicians), planned dissemination of the results would be necessary.
該計畫代表了認知和健康科學研究的進步，並呈現出具有重大意義的轉移潛力。研究結果希望提供一種可行且易於使用的干預措施，旨在提高睡眠障礙患者的認知表現和生活品質。如果結果符合預期，這項研究可能會鼓勵對失眠和睡眠障礙患者實施家庭為基礎的個人化認知刺激幹預措施。這種幹預措施可以緩解衛生系統的擁堵，改善患者的護理和生活質量，減少藥物治療的副作用，並節省醫療費用。為了克服上面簡要提到的臨床醫生障礙（即臨床醫生缺乏非藥物幹預知識），有必要有計劃地傳播結果。
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.
研究中提出的原始貢獻包含在文章/補充資料中，進一步的詢問可以直接聯繫相應的作者。
This study was reviewed and approved by the Comité de Ética en Investigación—CEI (UNNE-2021-006) and the Comité de Ética de la Investigación of the Generalitat Valenciana, Consellería de Sanitat Universal i Salut Pública. The patients/participants provided their written informed consent to participate in this study.
這項研究得到了 CEI (UNNE-2021-006) 和巴倫西亞自治區衛生調查委員會、Universal i Salut Pública 衛生委員會的審查和批准。患者/參與者提供了參與本研究的書面知情同意書。
All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.
列出的所有作者都對這項工作做出了實質、直接的智力貢獻，並批准其出版。
This project was partially funded by the Ministry of Science, Innovation, and Universities, Spanish Government (FPU19/02239; 2020-2024; and PGC2018-097145-B-I00; RED2018-102615-T) and by the Comunidad de Madrid (H2019/HUM-5705).
本計畫部分由西班牙政府科學、創新和大學部 (FPU19/02239; 2020-2024; 和 PGC2018-097145-B-I00; RED2018-102615-T) 和馬德里自治區 (H2019) 資助/HUM-5705）。
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
作者聲明，該研究是在不存在任何可能被視為潛在利益衝突的商業或財務關係的情況下進行的。
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
本文所表達的所有主張僅代表作者的主張，不一定代表其附屬組織的主張，也不代表出版商、編輯和審稿人的主張。本文中可能評估的任何產品或其製造商可能提出的聲明均未得到出版商的保證或認可。
Almondes, K. M. D., Leonardo, M. E. M., and Moreira, A. M. S. (2017). Effects of a cognitive training program and sleep hygiene for executive functions and sleep quality in healthy elderly. Dement. Neuropsychol. 11, 69–78. doi: 10.1590/1980-57642016dn11-010011
阿爾蒙德斯 (KMD)、萊昂納多 (MEM) 和莫雷拉 (AMS) (2017)。認知訓練計畫和睡眠衛生對健康老年人執行功能和睡眠品質的影響。德門特。神經心理學。 11、69-78。號碼：10.1590/1980-57642016dn11-010011
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Ballesio, A., Aquino, M. R. J. V., Kyle, S. D., Ferlazzo, F., and Lombardo, C. (2019). Executive functions in insomnia disorder: a systematic review and exploratory meta-analysis. Front. Psychol. 10:101. doi: 10.3389/fpsyg.2019.00101
Ballesio, A.、Aquino, MRJV、Kyle, SD、Ferlazzo, F. 和 Lombardo, C. (2019)。失眠症的執行功能：系統性回顧與探索性統合分析。正面。心理。 10:101。 doi: 10.3389/fpsyg.2019.00101
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Bastien, C. H., Vallières, A., and Morin, C. M. (2004b). Precipitating factors of insomnia. Behav. Sleep Med. 2, 50–62. doi: 10.1207/s15402010bsm0201_5
Bastien, CH、Vallières, A. 與 Morin, CM (2004b)。失眠的誘發因素。行為。睡眠醫學。 2、50-62。編號：10.1207/s15402010bsm0201_5
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Bastien, C. H., Morin, C. M., Ouellet, M. C., Blais, F. C., and Bouchard, S. (2004a). Cognitive-behavioral therapy for insomnia: comparison of individual therapy, group therapy, and telephone consultations. J. Consult. Clin. Psychol. 72, 653–659. doi: 10.1037/0022-006X.72.4.653
Bastien, CH、Morin, CM、Ouellet, MC、Blais, FC 和 Bouchard, S. (2004a)。失眠的認知行為治療：個別治療、團體治療和電話諮詢的比較。 J. 諮詢。臨床。心理。 72、653–659。號碼：10.1037/0022-006X.72.4.653
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Bastien, C. H., Provencher, T., Lebel, J., and Bolduc-Landry, R. (2021). “Neurobiology of insomnia,” in Sleep Neurology, eds L. M. Attarian and R. Ferri (Cham: Springer), 91–109.
Bastien, CH、Provencher, T.、Lebel, J. 與 Bolduc-Landry, R. (2021)。 “失眠的神經生物學”， 《睡眠神經學》，LM Attarian 和 R. Ferri 編輯（Cham：Springer），91-109。
Bastien, C. H., St-Jean, G., Morin, C. M., Turcotte, I., and Carrier, J. (2008). Chronic psychophysiological insomnia: Hyperarousal and/or inhibition deficits? An ERPs investigation. Sleep 31, 887–898. doi: 10.1093/sleep/31.6.887
Bastien, CH、St-Jean, G.、Morin, CM、Turcotte, I. 與 Carrier, J. (2008)。慢性心理生理性失眠：過度覺醒和/或抑制缺陷？ ERP 調查。睡眠31, 887–898。 doi：10.1093/睡眠/31.6.887
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Benca, R. M. (2005). Diagnosis and treatment of chronic insomnia: a review. Psychiatr. Serv. 56, 332–343. doi: 10.1176/appi.ps.56.3.332
本卡，RM (2005)。慢性失眠的診斷和治療：綜述。精神病學。服務。 56、332–343。 doi：10.1176/appi.ps.56.3.332
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Black, D. S., O’Reilly, G. A., Olmstead, R., Breen, E. C., and Irwin, M. R. (2015). Mindfulness meditation and improvement in sleep quality and daytime impairment among older adults with sleep disturbances: a randomized clinical trial. JAMA Intern. Med. 175, 494–501. doi: 10.1001/jamainternmed.2014.8081
Black, DS、O'Reilly, GA、Olmstead, R.、Breen, EC 與 Irwin, MR (2015)。正念冥想以及改善睡眠品質和睡眠障礙老年人的日間障礙：一項隨機臨床試驗。 JAMA 實習生。醫學。 175, 494–501。 doi: 10.1001/jamainternmed.2014.8081
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Bolge, S. C., Doan, J. F., Kannan, H., and Baran, R. W. (2009). Association of insomnia with quality of life, work productivity, and activity impairment. Q. Life Res. 18, 415–422. doi: 10.1007/s11136-009-9462-6
Bolge, SC、Doan, JF、Kannan, H. 與 Baran, RW (2009)。失眠與生活品質、工作效率和活動障礙的關聯。問：生命研究。 18, 415–422。 DOI：10.1007/s11136-009-9462-6
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Bonnechère, B., Langley, C., and Sahakian, B. J. (2020). The use of commercial computerised cognitive games in older adults: a meta-analysis. Sci. Rep. 10:15276. doi: 10.1038/s41598-020-72281-3
Bonnechère, B.、Langley, C. 與 Sahakian, BJ (2020)。商業電腦化認知遊戲在老年人中的使用：薈萃分析。科學。報告10：15276。編號：10.1038/s41598-020-72281-3
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Borkovec, T. D. (1979). Pseudo (experiental)-insomnia and idiopathic (objective) insomnia: theoretical and therapeutic issues. Adv. Behav. Res. Ther. 2, 27–55. doi: 10.1016/0146-6402(79)90004-3
博爾科維克，TD (1979)。偽（經驗）失眠和特發性（客觀）失眠：理論和治療問題。副詞。行為。資源。瑟爾。 2、27-55。號碼：10.1016/0146-6402(79)90004-3
Borkovec, T. D. (1982). Insomnia. J. Consult. Clin. Psychol. 50, 880–895.
博爾科維克，TD (1982)。失眠J. 諮詢。臨床。心理。 50、880–895。
Buscemi, N., Vandermeer, B., Friesen, C., Bialy, L., Tubman, M., Ospina, M., et al. (2007). The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. J. Gen. Intern. Med. 22, 1335–1350. doi: 10.1007/s11606-007-0251-z
Buscemi, N.、Vandermeer, B.、Friesen, C.、Bialy, L.、Tubman, M.、Ospina, M. 等人。 （2007）。成人慢性失眠藥物治療的有效性和安全性：隨機對照試驗的統合分析。 J. Gen. 實習生。醫學。 22, 1335–1350。 DOI：10.1007/s11606-007-0251-z
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Chan, N. Y., Chan, J. W. Y., Li, S. X., and Wing, Y. K. (2021). Non-pharmacological approaches for management of insomnia. Neurotherapeutics 9, 717–727. doi: 10.1007/s13311-021-01029-2
Chan, NY、Chan, JWY、Li, SX 與 Wing, YK (2021)。治療失眠的非藥物方法。神經治療學9, 717–727。 DOI：10.1007/s13311-021-01029-2
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Chien, K. L., Chen, P. C., Hsu, H. C., Su, T. C., Sung, F. C., Chen, M. F., et al. (2010). Habitual sleep duration and insomnia and the risk of cardiovascular events and all-cause death: report from a community-based cohort. Sleep 33, 177–184. doi: 10.1093/sleep/33.2.177
Chien, KL, Chen, PC, Hsu, HC, Su, TC, Sung, FC, Chen, MF 等。 （2010）。習慣性睡眠持續時間和失眠以及心血管事件和全因死亡的風險：來自社區隊列的報告。睡眠33, 177–184。 doi：10.1093/睡眠/33.2.177
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Corsi-Cabrera, M., Figueredo-Rodríguez, P., del Río-Portilla, Y., Sánchez-Romero, J., Galán, L., and Bosch-Bayard, J. (2012). Enhanced frontoparietal synchronized activation during the wake-sleep transition in patients with primary insomnia. Sleep 35, 501–511. doi: 10.5665/sleep.1734
Corsi-Cabrera, M.、Figueredo-Rodríguez, P.、del Río-Portilla, Y.、Sánchez-Romero, J.、Galán, L. 和 Bosch-Bayard, J. (2012)。原發性失眠患者在清醒-睡眠轉變過程中額頂葉同步活化增強。睡眠35, 501–511。 doi：10.5665/sleep.1734
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
D’Antonio, J., Simon-Pearson, L., Goldberg, T., Sneed, J. R., Rushia, S., Kerner, N., et al. (2019). Cognitive training and neuroplasticity in mild cognitive impairment (COG-IT): protocol for a two-site, blinded, randomised, controlled treatment trial. BMJ Open 9:e028536. doi: 10.1136/bmjopen-2018-028536corr1
D'Antonio, J.、Simon-Pearson, L.、Goldberg, T.、Sneed, JR、Rushia, S.、Kerner, N. 等。 （2019）。輕度認知障礙（COG-IT）中的認知訓練與神經可塑性：兩中心、盲法、隨機、對照治療試驗方案。 BMJ 公開賽9：e028536。 doi: 10.1136/bmjopen-2018-028536corr1
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
de Vries, S. T., Mol, P. G., de Zeeuw, D., Haaijer-Ruskamp, F. M., and Denig, P. (2013). Development and initial validation of a patient-reported adverse drug event questionnaire. Drug Saf. 36, 765–777. doi: 10.1007/s40264-013-0036-8
de Vries, ST、Mol, PG、de Zeeuw, D.、Haaijer-Ruskamp, FM 與 Denig, P. (2013)。患者報告的藥物不良事件問卷的開發和初步驗證。毒品安全。 36、765–777。 DOI：10.1007/s40264-013-0036-8
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Diamond, K., Mowszowski, L., Cockayne, N., Norrie, L., Paradise, M., Hermens, D. F., et al. (2015). Randomized controlled trial of a healthy brain ageing cognitive training program: effects on memory, mood, and sleep. J. Alzheimers Dis. 44, 1181–1191. doi: 10.3233/JAD-142061
Diamond, K.、Mowszowski, L.、Cockayne, N.、Norrie, L.、Paradise, M.、Hermens, DF 等人。 （2015）。健康大腦老化認知訓練計畫的隨機對照試驗：對記憶、情緒和睡眠的影響。 J.阿茲海默症。 44, 1181–1191。號碼：10.3233/JAD-142061
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Edinger, J. D., Stout, A. L., and Hoelscher, T. J. (1988). Cluster analysis of insomniacs’ MMPI profiles: relation of subtypes to sleep history and treatment outcome. Psychosom. Med. 50, 77–87. doi: 10.1097/00006842-198801000-00010
Edinger, JD、Stout, AL 與 Hoelscher, TJ (1988)。失眠症患者 MMPI 概況的聚類分析：亞型與睡眠史和治療結果的關係。心智體。醫學。 50、77–87。編號：10.1097/00006842-198801000-00010
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Espie, C. A. (2002). Insomnia: conceptual issues in the development, persistence, and treatment of sleep disorder in adults. Annu. Rev. Psychol. 53, 215–243. doi: 10.1146/annurev.psych.53.100901.135243
加州埃斯皮 (2002)。失眠：成人睡眠障礙的發展、持續與治療的概念問題。安努。心理學牧師。 53、215–243。 doi：10.1146/annurev.psych.53.100901.135243
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Ferguson, H. J., Brunsdon, V. E., and Bradford, E. E. (2021). The developmental trajectories of executive function from adolescence to old age. Sci. Rep. 11:1382. doi: 10.1038/s41598-020-80866-1
Ferguson, HJ、Brunsdon, VE 與 Bradford, EE (2021)。從青春期到老年執行功能的發展軌跡。科學。報告11:1382。編號：10.1038/s41598-020-80866-1
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Fortier-Brochu, É, Beaulieu-Bonneau, S., Ivers, H., and Morin, C. M. (2012). Insomnia and daytime cognitive performance: a meta-analysis. Sleep Med. Rev. 16, 83–94. doi: 10.1016/j.smrv.2011.03.008
Fortier-Brochu, É、Beaulieu-Bonneau, S.、Ivers, H. 與 Morin, CM (2012)。失眠與白天認知表現：統合分析。睡眠醫學。啟示錄16，83-94。 doi：10.1016/j.smrv.2011.03.008
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Freedman, R. R. (1986). EEG power spectra in sleep-onset insomnia. Electroencephalogr. Clin. Neurophysiol. 63, 408–413. doi: 10.1016/0013-4694(86)90122-7
弗里德曼，RR (1986)。入睡失眠的腦電圖功率譜。腦電圖學家。臨床。神經生理學。 63、408–413。編號：10.1016/0013-4694(86)90122-7
Grewal, R. G., and Doghramji, K. (2017). “Epidemiology of insomnia,” in Clinical Handbook of Insomnia, 3rd edn, ed. H. P. Attarian (Totowa, NJ: Humana Press), 13–25
Grewal, RG 與 Doghramji, K. (2017)。 “失眠的流行病學”， 《失眠臨床手冊》 ，第 3 版，編輯。 HP Attarian（新澤西州托托瓦：Humana Press），13–25
Haimov, I., and Shatil, E. (2013). Cognitive training improves sleep quality and cognitive function among older adults with insomnia. PLoS One 8:e61390. doi: 10.1371/journal.pone.0061390
Haimov, I. 與 Shatil, E. (2013)。認知訓練可改善失眠老年人的睡眠品質和認知功能。 《公共科學圖書館一號》 8：e61390。 doi：10.1371/journal.pone.0061390
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Harvey, A. G. (2002). A cognitive model of insomnia. Behav. Res. Ther. 40, 869–893. doi: 10.1016/S0005-7967(01)00061-4
哈維，AG（2002）。失眠的認知模型。行為。資源。瑟爾。 40、869–893。編號：10.1016/S0005-7967(01)00061-4
Harvey, A. G., and Tang, N. K. (2012). (Mis) perception of sleep in insomnia: a puzzle and a resolution. Psychol. Bull. 138, 77–101. doi: 10.1037/a0025730
Harvey, AG 與 Tang, NK (2012)。失眠症中對睡眠的（錯誤）認知：一個謎題和一個解決方案。心理。公牛。 138、77-101。編號：10.1037/a0025730
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Hays, R. D., Schalet, B. D., Spritzer, K. L., and Cella, D. (2017). Two-item PROMIS global physical and mental health scales. J. Patient Rep. Outcomes 1:2. doi: 10.1186/s41687-017-0003-8
Hays, RD、Schalet, BD、Spritzer, KL 與 Cella, D. (2017)。兩項 PROMIS 全球身心健康量表。 J. 患者代表結果1:2。號碼：10.1186/s41687-017-0003-8
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Hays, R. D., Spritzer, K. L., Thompson, W. W., and Cella, D. (2015). US general population estimate for “excellent” to “poor” self-rated health item. J. Gen. Intern. Med. 30, 1511–1516. doi: 10.1007/s11606-015-3290-x
Hays, RD、Spritzer, KL、Thompson, WW 和 Cella, D. (2015)。美國一般人口對自評健康項目「優」到「差」的估計。 J. Gen. 實習生。醫學。 30, 1511–1516。 DOI：10.1007/s11606-015-3290-x
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Hull, J. S. (1993). Event-Related Potentials During the Wake/Sleep Transition in Adults With and Without Primary Insomnia. Ph.D. dissertation. Hattiesburg, MS: University of Southern Mississippi.
赫爾，JS (1993)。有或沒有原發性失眠的成年人在清醒/睡眠轉變期間的事件相關電位。博士論文。哈蒂斯堡，MS：南密西西比大學。
Ilioudi, C., Martín-Plasencia, P., Fernández-Mendoza, J., Olavarrieta-Bernardino, S., and Vela-Bueno, A. (2011). Deficiency of executive functions in chronic primary insomnia. Neurosci. Lett. 500, e36–e37. doi: 10.1016/j.neulet.2011.05.174
Ilioudi, C.、Martín-Plasencia, P.、Fernández-Mendoza, J.、Olavarrieta-Bernardino, S. 與 Vela-Bueno, A. (2011)。慢性原發性失眠的執行功能缺陷。神經科學。萊特。 500，e36–e37。 doi：10.1016/j.neulet.2011.05.174
Kales, J. D., and Kales, A. (1987). Evaluation and treatment of insomnia. Psychiatr. Ann. 17, 459–464. doi: 10.3928/0048-5713-19870701-08
Kales, JD 與 Kales, A. (1987)。失眠的評估和治療。精神病學。安. 17, 459–464。編號：10.3928/0048-5713-19870701-08
Keramtinejad, M., Azadi, A., Taghinejad, H., and Khorshidi, A. (2019). The effectiveness of cognitive training on improving cognitive function and sleep quality in community-dwelling elderly in Iran. Sleep Sci. 12, 88–93. doi: 10.5935/1984-0063.20190065
Keramtinejad, M.、Azadi, A.、Taghinejad, H. 與 Khorshidi, A. (2019)。認知訓練對改善伊朗社區老年人認知功能和睡眠品質的有效性。睡眠科學。 12、88-93。編號：10.5935/1984-0063.20190065
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Kessler, R. C., Berglund, P. A., Coulouvrat, C., Fitzgerald, T., Hajak, G., Roth, T., et al. (2012). Insomnia, comorbidity, and risk of injury among insured Americans: results from the America insomnia survey. Sleep 35, 825–834. doi: 10.5665/sleep.1884
Kessler, RC、Berglund, PA、Coulouvrat, C.、Fitzgerald, T.、Hajak, G.、Roth, T. 等人。 （2012）。受保美國人的失眠、共病和受傷風險：美國失眠調查的結果。睡眠35, 825–834。 doi: 10.5665/sleep.1884
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Khurshid, K. A. (2018). Comorbid insomnia and psychiatric disorders: an update. Innov. Clin. Neurosci. 15, 28–32.
堪薩斯州庫希德（2018）。共病失眠和精神疾病：更新。創新。臨床。神經科學。 15、28-32。
Killgore, W. D., Schwab, Z. J., Kipman, M., DelDonno, S. R., and Weber, M. (2013). Insomnia-related complaints correlate with functional connectivity between sensory–motor regions. Neuroreport 24, 233–240. doi: 10.1097/WNR.0b013e32835edbdd
Killgore, WD、Schwab, ZJ、Kipman, M.、DelDonno, SR 與 Weber, M. (2013)。失眠相關的投訴與感覺運動區域之間的功能連結有關。神經報告24, 233–240。 doi: 10.1097/WNR.0b013e32835edbdd
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Koffel, E., Bramoweth, A. D., and Ulmer, C. S. (2018). Increasing access to and utilization of cognitive behavioral therapy for insomnia (CBT-I): a narrative review. J. Gen. Intern. Med. 33, 955–962. doi: 10.1007/s11606-018-4390-1
Koffel, E.、Bramoweth, AD 與 Ulmer, CS (2018)。增加失眠認知行為療法（CBT-I）的獲取和利用：敘述性回顧。 J. Gen. 實習生。醫學。 33、955–962。號碼：10.1007/s11606-018-4390-1
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Koffel, E. A., Koffel, J. B., and Gehrman, P. R. (2015). A meta-analysis of group cognitive behavioral therapy for insomnia. Sleep Med. Rev. 19, 6–16. doi: 10.1016/j.smrv.2014.05.001
Koffel, EA、Koffel, JB 與 Gehrman, PR (2015)。失眠團體認知行為治療的統合分析。睡眠醫學。修訂版19，6-16。 doi：10.1016/j.smrv.2014.05.001
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Krystal, A. D., Edinger, J. D., Wohlgemuth, W. K., and Marsh, G. R. (2002). NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes. Sleep 25, 626–636. doi: 10.1093/sleep/25.6.626
Krystal, AD、Edinger, JD、Wohlgemuth, WK 和 Marsh, GR (2002)。 NREM 睡眠腦電圖光譜與原發性失眠亞型的睡眠抱怨有關。睡眠25, 626–636。 doi：10.1093/睡眠/25.6.626
Kyle, S. D., Miller, C. B., Rogers, Z., Siriwardena, A. N., MacMahon, K. M., and 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, 229–237. doi: 10.5665/sleep.3386
Kyle, SD、Miller, CB、Rogers, Z.、Siriwardena, AN、MacMahon, KM 與 Espie, CA (2014)。失眠的睡眠限制療法與客觀總睡眠時間減少、白天嗜睡增加和客觀警覺性受損有關：對失眠臨床治療的影響。睡眠37, 229–237。 doi: 10.5665/sleep.3386
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Lawlor-Savage, L., and Goghari, V. M. (2014). Working memory training in schizophrenia and healthy populations. Behav. Sci. 4, 301–319. doi: 10.3390/bs4030301
Leerssen, J., Wassing, R., Ramautar, J. R., Stoffers, D., Lakbila-Kamal, O., Perrier, J., et al. (2018). Increased hippocampal-prefrontal functional connectivity in insomnia. Neurobiol. Learn. Mem. 160, 144–150. doi: 10.1016/j.nlm.2018.02.006
Leerssen, J.、Wassing, R.、Ramautar, JR、Stoffers, D.、Lakbila-Kamal, O.、Perrier, J. 等。 （2018）。失眠時海馬-前額葉功能連結增加。神經生物學。學習。內存。 160、144–150。 doi：10.1016/j.nlm.2018.02.006
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Li, F., Fisher, K. J., Harmer, P., Irbe, D., Tearse, R. G., and Weimer, C. (2004). Tai Chi and self-rated quality of sleep and daytime sleepiness in older adults: a randomized controlled trial. J. Am. Geriatr. Soc. 52, 892–900. doi: 10.1111/j.1532-5415.2004.52255.x
Li, F.、Fisher, KJ、Harmer, P.、Irbe, D.、Tearse, RG 與 Weimer, C. (2004)。太極拳與老年人自評睡眠品質和白天嗜睡：一項隨機對照試驗。 J. Am.老年病。蘇克。 52、892–900。 doi：10.1111/j.1532-5415.2004.52255.x
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Lin, Y., and Shih, W. J. (2001). Statistical properties of the traditional algorithm-based designs for phase I cancer clinical trials. Biostatistics 2, 203–215. doi: 10.1093/biostatistics/2.2.203
Lin, Y. 與 Shih, WJ (2001)。 I 期癌症臨床試驗是基於傳統演算法的設計的統計特性。生物統計學2，203-215。 doi：10.1093/生物統計/2.2.203
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Loewy, D. H., and Bootzin, R. R. (1998). Event-related potential measures of information processing in insomniacs at bedtime and during sleep. Sleep 21, (Suppl. 1):98.
Loewy, DH 與 Bootzin, RR (1998)。失眠症患者在就寢時間和睡眠期間訊息處理的與事件相關的潛在測量。睡眠21，（增刊 1）：98。
Loewy, D. H., Burdik, R. S., Al-Shajlawi, A., Franzen, P., and Bootzin, R. (1999). Enhanced information processing at the peri-sleep onset period in insomniacs as measured by event-related potentials. Sleep 22, (Suppl. 1):S152.
Loewy, DH、Burdik, RS、Al-Shajlawi, A.、Franzen, P. 與 Bootzin, R. (1999)。透過事件相關電位測量失眠症患者圍睡眠開始期的訊息處理能力增強。睡眠22，（補充 1）：S152。
Luik, A. I., Kyle, S. D., and Espie, C. A. (2017). Digital cognitive behavioral therapy (dCBT) for insomnia: a state-of-the-science review. Curr. Sleep Med. Rep. 3, 48–56. doi: 10.1007/s40675-017-0065-4
Mendoza, T. R., Wang, X. S., Cleeland, C. S., Morrissey, M., Johnson, B. A., Wendt, J. K., et al. (1999). The rapid assessment of fatigue severity in cancer patients: use of the brief fatigue inventory. Cancer 85, 1186–1196. doi: 10.1002/(sici)1097-0142(19990301)85:5<1186::aid-cncr24>3.0.co;2-n
Mendoza, TR、Wang, XS、Cleeland, CS、Morrissey, M.、Johnson, BA、Wendt, JK 等。 （1999）。癌症患者疲勞嚴重程度的快速評估：使用簡短的疲勞清單。巨蟹座85, 1186–1196。 doi: 10.1002/(sici)1097-0142(19990301)85:5<1186 id=1>3.0.co;2-n
Merica, H., and Gaillard, J. M. (1992). The EEG of the sleep onset period in insomnia: a discriminant analysis. Physiol. Behav. 52, 199–204. doi: 10.1016/0031-9384(92)90258-4
Merica, H. 與 Gaillard, JM (1992)。失眠入睡期的腦電圖：判別分析。生理學。行為。 52、199-204。編號：10.1016/0031-9384(92)90258-4
Miyata, S., Noda, A., Iwamoto, K., Kawano, N., Okuda, M., and Ozaki, N. (2013). Poor sleep quality impairs cognitive performance in older adults. J. Sleep Res. 22, 535–541. doi: 10.1111/jsr.12054
Miyata, S.、Noda, A.、Iwamoto, K.、Kawano, N.、Okuda, M. 與 Ozaki, N. (2013)。睡眠品質差會損害老年人的認知能力。 J.睡眠研究。 22、535-541。 DOI：10.1111/jsr.12054
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Morin, C. M. (1993). Insomnia: Psychological Assessment and Management. New York, NY: Guilford Press.
莫蘭，CM (1993)。失眠：心理評估與管理。紐約州紐約：吉爾福德出版社。
Morin, C. M., LeBlanc, M., Daley, M., Gregoire, J. P., and Merette, C. (2006). Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med. 7, 123–130. doi: 10.1016/j.sleep.2005.08.008
Morin, CM、LeBlanc, M.、Daley, M.、Gregoire, JP 和 Merette, C. (2006)。失眠的流行病學：盛行率、自助治療、諮商和尋求幫助行為的決定因素。睡眠醫學。 7、123-130。 doi：10.1016/j.sleep.2005.08.008
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Ong, J. C., Kuo, T. F., and Manber, R. (2008). Who is at risk for dropout from group cognitive-behavior therapy for insomnia? J. Psychosom. Res. 64, 419–425. doi: 10.1016/j.jpsychores.2007.10.009
Ong, JC、Kuo, TF 與 Manber, R. (2008)。誰有退出失眠團體認知行為治療的風險？ J.Psychosom。資源。 64、419–425。 doi：10.1016/j.jpsychores.2007.10.009
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Ong, J. C., Manber, R., Segal, Z., Xia, Y., Shapiro, S., and Wyatt, J. K. (2014). A randomized controlled trial of mindfulness meditation for chronic insomnia. Sleep 37, 1553–1563. doi: 10.5665/sleep.4010
Ong, JC、Manber, R.、Segal, Z.、Xia, Y.、Shapiro, S. 與 Wyatt, JK (2014)。正念冥想治療慢性失眠的隨機對照試驗。睡眠37，1553–1563。 doi: 10.5665/sleep.4010
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Pa, J., Goodson, W., Bloch, A., King, A. C., Yaffe, K., and Barnes, D. E. (2014). Effect of exercise and cognitive activity on self-reported sleep quality in community-dwelling older adults with cognitive complaints: a randomized controlled trial. J. Am. Geriatr. Soc. 62, 2319–2326. doi: 10.1111/jgs.13158
Pa, J.、Goodson, W.、Bloch, A.、King, AC、Yaffe, K. 與 Barnes, DE (2014)。運動和認知活動對有認知問題的社區老年人自我報告的睡眠品質的影響：一項隨機對照試驗。 J. Am.老年病。蘇克。 62、2319–2326。 doi：10.1111/jgs.13158
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Perlis, M. L., Giles, D. E., Mendelson, W. B., Bootzin, R. R., and Wyatt, J. K. (1997). Psychophysiological insomnia: the behavioural model and a neurocognitive perspective. J. Sleep Res. 6, 179–188. doi: 10.1046/j.1365-2869.1997.00045.x
Perlis, ML、Giles, DE、Mendelson, WB、Bootzin, RR 和 Wyatt, JK (1997)。心理生理學失眠：行為模型與神經認知觀點。 J.睡眠研究。 6、179-188。 doi：10.1046/j.1365-2869.1997.00045.x
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Preiss, M., Shatil, E., Cermakova, R., Cimermannova, D., and Flesher, I. (2013). Personalized cognitive training in unipolar and bipolar disorder: a study of cognitive functioning. Front. Hum. Neurosci. 7:108. doi: 10.3389/fnhum.2013.00108
Preiss, M.、Shatil, E.、Cermakova, R.、Cimermannova, D. 與 Flesher, I. (2013)。單相和雙相情感障礙的個人化認知訓練：認知功能的研究。正面。哼。神經科學。 7:108。 doi: 10.3389/fnhum.2013.00108
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Rebok, G. W., Ball, K., Guey, L. T., Jones, R. N., Kim, H. Y., King, J. W., et al. (2014). Ten-year effects of the advanced cognitive training for independent and vital elderly cognitive training trial on cognition and everyday functioning in older adults. J. Am. Geriatr. Soc. 62, 16–24. doi: 10.1111/jgs.12607
Reijnders, J., van Heugten, C., and van Boxtel, M. (2013). Cognitive interventions in healthy older adults and people with mild cognitive impairment: a systematic review. Ageing Res. Rev. 12, 263–275. doi: 10.1016/j.arr.2012.07.003
Riemann, D., Baglioni, C., Bassetti, C., Bjorvatn, B., Dolenc Groselj, L., Ellis, J. G., et al. (2017). European guideline for the diagnosis and treatment of insomnia. J. Sleep Res. 26, 675–700. doi: 10.1111/jsr.12594
Riemann, D., Nissen, C., Palagini, L., Otte, A., Perlis, M. L., and Spiegelhalder, K. (2015). The neurobiology, investigation, and treatment of chronic insomnia. Lancet Neurol. 14, 547–558. doi: 10.1016/S1474-4422(15)00021-6
Riemann, D., Spiegelhalder, K., Feige, B., Voderholzer, U., Berger, M., Perlis, M., et al. (2010). The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med. Rev. 14, 19–31. doi: 10.1016/j.smrv.2009.04.002
Santarnecchi, E., Del Bianco, C., Sicilia, I., Momi, D., Di Lorenzo, G., Ferrone, S., et al. (2018). Age of insomnia onset correlates with a reversal of default mode network and supplementary motor cortex connectivity. Neural Plast. 2018:3678534. doi: 10.1155/2018/3678534
Sato, D., Yoshinaga, N., Nagai, E., Nagai, K., and Shimizu, E. (2019). Effectiveness of internet-delivered computerized cognitive behavioral therapy for patients with insomnia who remain symptomatic following pharmacotherapy: randomized controlled exploratory trial. J. Med. Internet Res. 21:e12686. doi: 10.2196/12686
Seyffert, M., Lagisetty, P., Landgraf, J., Chopra, V., Pfeiffer, P. N., Conte, M. L., et al. (2016). Internet-delivered cognitive behavioral therapy to treat insomnia: a systematic review and meta-analysis. PLoS One 11:e0149139. doi: 10.1371/journal.pone.0149139
Seyffert, M.、Lagisetty, P.、Landgraf, J.、Chopra, V.、Pfeiffer, PN、Conte, ML 等。 （2016）。網路提供的認知行為療法治療失眠：系統性回顧與統合分析。 《公共科學圖書館一號》 11：e0149139。 doi：10.1371/journal.pone.0149139
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Shatil, E. (2013). Does combined cognitive training and physical activity training enhance cognitive abilities more than either alone? A four-condition randomized controlled trial among healthy older adults. Front. Aging Neurosci. 5:8. doi: 10.3389/fnagi.2013.00008
Shatil, E., Metzer, A., Horvitz, O., and Miller, A. (2010). Home-based personalized cognitive training in MS patients: a study of adherence and cognitive performance. Neurorehabilitation 26, 143–153. doi: 10.3233/NRE-2010-0546
Shatil, E.、Metzer, A.、Horvitz, O. 與 Miller, A. (2010)。多發性硬化症患者的家庭個人化認知訓練：依從性與認知表現的研究。神經復健26, 143–153。 doi：10.3233/NRE-2010-0546
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Spiegelhalder, K., Nissen, C., and Riemann, D. (2017). “Clinical sleep–wake disorders II: focus on insomnia and circadian rhythm sleep disorders,” in Sleep-Wake Neurobiology and Pharmacology, Vol. 253, eds H. P. Landolt and D. J. Dijk (Cham: Springer), 261–276. doi: 10.1007/164_2017_40
Spiegelhalder, K.、Nissen, C. 與 Riemann, D. (2017)。 “臨床睡眠 - 覺醒障礙 II：關注失眠和晝夜節律睡眠障礙”，《睡眠 - 覺醒神經生物學和藥理學》 ，卷。 253，HP Landolt 和 DJ Dijk 編輯（Cham：Springer），261-276。編號：10.1007/164_2017_40
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Spreij, L. A., Visser-Meily, J., van Heugten, C. M., and Nijboer, T. C. (2014). Novel insights into the rehabilitation of memory post acquired brain injury: a systematic review. Front. Hum. Neurosci. 8:993. doi: 10.3389/fnhum.2014.00993
Spreij, LA、Visser-Meily, J.、van Heugten, CM 與 Nijboer, TC (2014)。獲得性腦損傷後記憶復健的新見解：系統性回顧。正面。哼。神經科學。 8:993。 doi: 10.3389/fnhum.2014.00993
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Tapia, J. L., and Duñabeitia, J. A. (2021). Improving language acquisition and processing with cognitive stimulation. Front. Psychol. 12:663773. doi: 10.3389/fpsyg.2021.663773
Tapia, JL 與 Duñabeitia, JA (2021)。透過認知刺激改善語言習得和處理。正面。心理。 12:663773。 doi: 10.3389/fpsyg.2021.663773
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Thorpy, M. (2017). “International classification of sleep disorders,” in Sleep Disorders Medicine, 4th Edn, ed. S. Chokroverty (New York, NY: Springer), 475–484.
索皮，M.（2017）。 “睡眠障礙的國際分類”， 《睡眠障礙醫學》 ，第四版，編輯。 S. Chokroverty（紐約，紐約：施普林格），475–484。
Trauer, J. M., Qian, M. Y., Doyle, J. S., Rajaratnam, S. M., and Cunnington, D. (2015). Cognitive behavioral therapy for chronic insomnia: a systematic review and meta-analysis. Ann. Intern. Med. 163, 191–204. doi: 10.7326/M14-2841
Trauer, JM、Qian, MY、Doyle, JS、Rajaratnam, SM 與 Cunnington, D. (2015)。慢性失眠的認知行為療法：系統性回顧與統合分析。安.實習生。醫學。 163、191-204。號碼：10.7326/M14-2841
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Vincent, N. K., and Hameed, H. (2003). Relation between adherence and outcome in the group treatment of insomnia. Behav. Sleep Med. 1, 125–139. doi: 10.1207/S15402010BSM0103_1
文森特，NK 和哈米德，H. (2003)。失眠團體治療的依從性與結果之間的關係。行為。睡眠醫學。 1、125-139。編號：10.1207/S15402010BSM0103_1
Wardle-Pinkston, S., Slavish, D. C., and Taylor, D. J. (2019). Insomnia and cognitive performance: a systematic review and meta-analysis. Sleep Med. Rev. 48:101205. doi: 10.1016/j.smrv.2019.07.008
Wardle-Pinkston, S.、Slavish, DC 與 Taylor, DJ (2019)。失眠和認知表現：系統性評價和薈萃分析。睡眠醫學。啟示錄48：101205。 DOI：10.1016/j.smrv.2019.07.008
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Zhang, H., Wang, Z., Wang, J., Lyu, X., Wang, X., Liu, Y., et al. (2019). Computerized multi-domain cognitive training reduces brain atrophy in patients with amnestic mild cognitive impairment. Transl. Psychiatry 9:48. doi: 10.1038/s41398-019-0385-x
張紅、王Z.、王J.、呂X.、王X.、劉Y.等。 （2019）。電腦化多領域認知訓練可減少遺忘性輕度認知障礙患者的腦萎縮。譯。精神病學9:48。編號：10.1038/s41398-019-0385-x
PubMed Abstract | CrossRef Full Text | Google Scholar
考研摘要|全文交叉引用|谷歌學術
Keywords: insomnia, cognitive stimulation, cognitive intervention, sleep disorder, sleep quality, cognitive performance, quality of life
關鍵字：失眠，認知刺激，認知幹預，睡眠障礙，睡眠質量，認知表現，生活質量
Citation: Tapia JL, Puertas FJ and Duñabeitia JA (2022) Study Protocol for a Randomized Controlled Trial Assessing the Effectiveness of Personalized Computerized Cognitive Training for Individuals With Insomnia. Front. Behav. Neurosci. 16:779990. doi: 10.3389/fnbeh.2022.779990
引用： Tapia JL、Puertas FJ 和 Duñabeitia JA (2022) 評估失眠個體個人化電腦認知訓練有效性的隨機對照試驗研究方案。正面。行為。神經科學。 16:779990。 DOI：10.3389/fnbeh.2022.779990
Received: 20 September 2021; Accepted: 07 February 2022;
收稿日期： 2021 年 9 月 20 日；接受日期： 2022 年 2 月 7 日；
Published: 28 February 2022.
發佈日期： 2022 年 2 月 28 日。
Reviewed by: 審閱者：
Andrea Botturi, IRCCS Carlo Besta Neurological Institute Foundation, ItalyCopyright © 2022 Tapia, Puertas and Duñabeitia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
版權所有© 2022 Tapia、Puertas 和 Duñabeitia。這是一篇根據知識共享署名授權 (CC BY)條款分發的開放取用文章。允許在其他論壇使用、分發或複製，但須註明原作者和版權所有者，並根據公認的學術慣例引用本期刊的原始出版物。不允許不遵守這些條款的使用、散佈或複製。
*Correspondence: Jon Andoni Duñabeitia, jdunabeitia@nebrija.es
*通訊作者：喬恩‧安多尼‧杜納貝蒂亞 (Jon Andoni Duñabeitia)， jdunabeitia@nebrija.es
Disclaimer:
All claims expressed in this article are solely those of the authors and
do not necessarily represent those of their affiliated organizations, or
those of the publisher, the editors and the reviewers. Any product that
may be evaluated in this article or claim that may be made by its
manufacturer is not guaranteed or endorsed by the publisher.
免責聲明：本文所表達的所有主張僅代表作者的主張，不一定代表其附屬組織的主張，也不代表出版商、編輯和審查者的主張。本文中可能評估的任何產品或製造商可能提出的聲明均不得到出版商的保證或認可。
Clinical Trial
Published on 08 Jun 2016
Clinical Trial
Published on 22 Mar 2022
Jose Luis Tapia
Francisco Javier Puertas
Jon Andoni Duñabeitia