Enhancing Balanced Time Perspective through Time App Mobile Intervention in Migraine: a Randomized Control Trial with MRI Outcomes

Abstract Objective: This study aims to assess the efficacy of a mobile-based intervention (Time App) enhancing a balanced time perspective in individuals with episodic and chronic migraine. Methods: A randomized, assessor-blinded trial with neuroimaging outcomes will be conducted with 120 adult participants diagnosed with episodic and chronic migraine, recruited from four neurological clinics. Participants will be randomly assigned to one of three groups: the intervention group (Time App group; n = 40), the active control group (Mindfulness App group; n = 40), and the passive control group (wait-list controls; n = 40). Both interventions involve performing exercises from mobile apps for 8 weeks every day for approximately 10 minutes. The primary clinical outcome will be the reduction in the number of headache days from baseline to 16 weeks. The primary neuroimaging outcome measures will capture both structural and functional aspects of the brain. Secondary outcomes will be pain intensity and headache-related disability. The number of migraine days, migraine pain intensity and migraine relate-disability will be assessed using mobile migraine diarie and Migraine Disability Assessment (MIDAS) questionnaire. Magnetic resonance imaging (MRI) outcomes will include cortical thickness, grey matter volume, and resting state intrinsic functional connectivity. Introduction Migraine constitutes a significant neurological disorder and represents the second leading cause of disability globally (James et al., 2018). Migraine headaches are characterized by acute disruptions within the trigeminovascular system, accompanied by dynamic alterations in cerebral perfusion and widespread fluctuations in neural activity (Buse et al., 2020). Structural brain differences have been identified in migraineurs compared to healthy controls (Bashir et al., 2013; Jia et al., 2017). These neuroanatomical alterations frequently involve regions associated with cognitive and emotional processing, including the insular cortex (Borsook et al., 2016). Despite its considerable impact, approximately two-thirds of individuals affected by migraine discontinue pharmacological therapies, primarily due to inadequate efficacy or intolerable side effects (Lipton et al., 2019). This is further augmented by migraine being an underdiagnosed disorder with many not even treating their headaches with medications that may be more effective and specific for treating migraine headaches (Katsarava et al., 2018; Lipton et al., 2019; Ryvlin et al., 2021). This situation underscores an urgent need to identify and develop effective non-pharmacological interventions for the management of migraine. Empirical evidence indicates that psychological interventions—particularly those involving structured training and exercises—are effective in mitigating migraine symptoms (Cronin et al., 2018; Minen et al., 2020). For example, previous research (Seminowicz et al., 2020) showed that mindfulness based stress reduction intervention contributed to greater reduction in headache days and headache-related disability from baseline to 20 weeks compared to stress management for headache intervention. Additionally, Wells et al. (2020) reported that mindfulness-based stress reduction intervention contributed to reduction migraine days per month. In addition to observed reductions in migraine severity and frequency, such interventions have been associated with structural and functional neural changes, notably within the insular cortex (Seminowicz et al., 2020). These findings underscore the significant role of psychological factors in the etiology and management of migraine (Huang et al., 2020). Given the complexity and heterogeneity of migraine, as well as the individualized psychological profiles associated with the condition, it is imperative to develop a broad spectrum of psychological interventions to alleviate migraine. The efficacy of psychological interventions is significantly shaped by a range of initial factors, including individual personality traits, levels of experienced stress, and preferred types of activities (Shalom & Aderka, 2020; Spielmans i Flückiger, 2018). Consequently, it is essential to develop a diverse array of therapeutic approaches for individuals with migraines, varying in both content and delivery format. Such diversity enables patients to select the therapeutic approach that aligns most closely with their personal preferences and individual capacities. In the present study, balanced time perspective is proposed as a factor in reducing migraine frequency, migraine pain severity, and migraine-related disability. The theoretical underpinnings of this framework draw from two key perspectives: the conception of migraine as a manifestation of allostatic load (Maleki et al., 2012) and the time perspective theory (Zimbardo & Boyd, 2008). Furthermore, we based on a growing body of empirical research indicating that psychological rigidity constitutes a central characteristic commonly observed in individuals with migraine (e.g., Grazzi et al., 2021; Latka et al., 2004; Peng & May, 2019; Sánchez-Román et al., 2007; Van Oosterhout et al., 2018). Maleki et al. (2012) propose that migraine can be conceptualized within the framework of allostatic load, which refers to the cumulative physiological burden on the body and brain resulting from repeated or chronic exposure to stressors (McEwen & Stellar, 1993). Within this framework, the recurrent nature of migraine attacks, alongside associated psychosocial and physiological stressors, is believed to contribute to both functional and structural changes within neural networks. These alterations may result in dysregulated and maladaptive responses to environmental stimuli. Supporting this view, research has demonstrated that perimenopausal individuals with migraines exhibit higher levels of allostatic load compared to non-migraine controls (Alebna & Maleki, 2021), indicating a heightened biological susceptibility to stress-related dysregulation. Time perspective refers to an individual’s habitual focus on the past, present, or future, combined with a positive or negative evaluation of each temporal frame. Balanced time perspective represents an adaptive temporal orientation, characterized by the capacity to flexibly shift attention among positively appraised views of the past, present, and future, depending on situational demands and available personal resources (Zimbardo & Boyd, 2008; Stolarski et al., 2020). Individuals with a well-developed balanced time perspective exhibit cognitive and behavioral flexibility. For example, they are capable of planning and goal setting when required, while also being able to fully engage in present-moment enjoyment during leisure. Moreover, they are able to reflect on a positively evaluated past, drawing strength, self-assurance, and meaning from their memories (Zimbardo & Boyd, 1999, 2008). This capacity to focus on the positive aspects of various time frames is associated with enhanced emotional regulation, increased well-being, and reduced stress—factors known to alleviate pain perception (Koechlin et al., 2018). Previous research has identified a negative correlation between a balanced time perspective and perceived stress (Papastamatelou et al., 2015; Rönnlund & Carelli, 2018), as well as physiological outcomes such as allostatic load (Bourdon et al., 2020). Furthermore, Olivera-Figueroa et al. (2015) reported that an unbalanced time perspective is associated with dysregulation of cortisol secretion, suggesting a potential link between temporal orientation and broader health-related dysfunctions. Recent studies have also emphasized a significant relationship between time perspective and pain perception. Specifically, a past negative time perspective has been linked to heightened pain sensitivity, increased susceptibility to pain catastrophizing, and elevated pain-related fear (Gács et al., 2020; Simon et al., 2022). Oyanadel and Buela-Casal (2014) found that individuals with a predominant negative past orientation reported higher levels of pain intensity. Similarly, Dany et al. (2016) observed that patients with chronic pain who evaluated their past negatively exhibited greater psychological distress. Moreover, findings by Sobol-Kwapińska et al. (2017) demonstrated that even in the context of objectively verifiable somatic pain—such as postoperative pain resulting from surgical tissue damage—a past negative time perspective significantly contributed to the subjective intensity of pain and the tendency to catastrophize it. When it comes to research on rigidity as one of the most characteristic features of migraine patients, Van Oosterhout et al. (2018) identified heightened rigidity in chronotypes and a reduced capacity to adapt to circadian rhythm fluctuations among migraine sufferers. Such findings align with broader evidence linking migraine episodes to disruptions in established daily routines, including altered sleep patterns, irregular eating schedules, and increased sensitivity to sensory stimuli such as light, sound, and odors. In this context, Peng and May (2019) proposed a conceptualization of migraine as a "sensory threshold disease," suggesting that its onset may be associated with impaired adaptability to environmental change. Importantly, indications of rigidity in individuals with migraine are not limited to psychological domains but extend to neurophysiological processes as well. Latka et al. (2004) described a form of “fractal rigidity” in migraine patients, characterized by decreased short-term adaptability and hyperactivity in cerebral blood flow regulation systems. While psychological and neurological rigidity represent distinct constructs, emerging evidence points to their potential interrelation. Cognitive inflexibility, often defined as difficulty in shifting attention or mental sets, has been associated with reduced activ