Innov Clin Neurosci. 2026;23(1–3):39–46.

by Steven Wickens, MPsych, and Trevor Brown, PhD

Both authors are with Neurocare Group, Melbourne, Australia.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors have no relevant conflicts of interest.

ABSTRACT: Objective: Recent decades have seen a surge in empirical support for the clinical application of noninvasive neuromodulation technology, such as repetitive transcranial magnetic stimulation (rTMS). The aim of this perspective is to review the emerging research exploring the literature on combined psychotherapy with rTMS. Methods: This article provides a narrative overview of studies combining psychotherapy and rTMS from the perspective of a practicing psychologist in the context of implicated neural networks and an evidenced-based contextual behavioral model of therapy. Results: It is advanced that the network flexibility and connectivity changes induced by rTMS may facilitate an effective neural context for psychotherapy processes to support meaningful change, providing a synergistic strengthening of psychological and brain network flexibility. More precisely, this clinical perspective considers existing studies that combine psychotherapy techniques with rTMS across diverse clinical populations, within an acceptance and commitment therapy (ACT) framework. Conclusion: It is argued that rTMS can be applied while concurrently fostering psychological flexibility pillars of openness, awareness, and engagement and applied as a transdiagnostic, process-based intervention in a psychosocial and biophysiological context. Keywords: ACT, rTMS, multimodal therapy, psychotherapy, neuromodulation

Introduction

Neurostimulation technology provides a direct means to noninvasively disrupt brain network function and there is robust and mounting empirical evidence that direct influence from electromagnetic brain stimulation (ie, repetitive transcranial magnetic stimulation [rTMS]) can result in meaningful change across a wide range of clinical expressions.1,2 rTMS involves the noninvasive and focal application of a pulsed magnetic field, repetitively stimulating underlying nerve cells through electromagnetic induction. Research has, however, demonstrated that the neuroplastic influence of stimulation extends beyond the cortical tissue underlying the stimulation. For example, a systematic review by Beynel et al3 investigated the effects of resting state functional connectivity from rTMS across a range of stimulation sites and associated networks and provided evidence that rTMS applied over superficial brain structures reliably induces distal effects on functional connectivity. Interestingly, it was also found that the interaction with the network changes were not necessarily in line with the assumed stimulation mechanisms, such that presumed inhibitory and excitatory stimulation parameters both demonstrated increased functional connectivity to distal networks.3 Despite the established and emerging clinical efficacy, the field requires further investigation to better understand and refine treatment protocols to personalize and enhance clinical response.

Beyond the direct impact of neurostimulation monotherapy, there is growing interest and literature supporting the combination of noninvasive brain stimulation and psychotherapy.4–6 From a behavioral perspective, the biological representation of behavior and the behavior itself are simply parts of the same event,7 although observed at different levels of measurement. However, targeting the same behavior from multiple perspectives simultaneously (eg, psychotherapeutically and electromagnetically) may prime brain plasticity through state-dependent effects, augment the response, and provide a more holistic experiential effect that could enhance sustained effects. In a systematic review and meta-analysis, Xu et al6 provided preliminary support for augmentation of clinical outcomes across a broad clinical context when combining rTMS with psychological intervention, including cognitive behavioral therapy (CBT), mindfulness-based stress reduction (MBSR), exposure therapy, and cognitive training, as compared to sham rTMS with psychotherapy. Considering qualitative research, interviews with participants completing a course of rTMS for anorexia nervosa revealed that 93% of participants acknowledged that the therapeutic relationship with the rTMS therapist was important to treatment, and 50% suggested that rTMS would be better if accompanied by psychotherapy because it would provide a useful means to discuss and cope better with any reported changes.8

As such, the specific therapeutic orientation may be less critical than an overarching model that focuses on relevant processes of change with targeted evidence-based treatment kernels.9 This is in line with the emerging paradigm shift in personalized medicine, and one such example of a flexible process-based therapy is acceptance and commitment therapy (ACT). The present perspective positions that delivering neurostimulation that directly encourages neural flexibility—within a context that promotes flexibility processes through pillars of openness, awareness, and engagement—may be synergistic for clinical outcomes with greater precision, depth, and scope for meaningful change. In addition, it is proposed that layering brain stimulation while modifying personalized contextual factors may work to sustain outcomes.

Methods

A literature search was conducted using PubMed, ProQuest, and Google Scholar databases to review the relevant literature on ACT/psychotherapy and rTMS, as well as implicated brain networks. Search terms included “transcranial magnetic stimulation” OR “brain networks” AND “acceptance and commitment therapy,” “psychological flexibility,” “mindfulness,” “psychotherapy,” or “behavior therapy.” Articles that discussed the use of psychotherapy practices and rTMS, OR “acceptance and commitment therapy,” OR psychological flexibility and neuroimaging or brain network connectivity were reviewed within a narrative framework. The search strategy was open, wide, and nonsystematic, as it is a novel domain of study within an emerging field, and it is expected that there would be a scarcity of literature directly examining the combination of ACT and rTMS.

Stimulating flexibility with ACT combined with rTMS. ACT is a third-wave CBT approach founded in functional contextualism and behavior analysis, with theoretical and empirical grounding from relational frame theory (RFT).10 ACT is a transdiagnostic, process-based model that has widely demonstrated clinical efficacy over decades of research across a range of clinical psychiatric and physical health conditions as well as nonclinical settings,11 with over 1,000 published randomized controlled trials (RCTs) to date.12 ACT is a behavior therapy focused on building skills in psychological flexibility through the experiential use of acceptance and mindfulness as well as commitment and behavior change processes in the service of living a values-based life.10 Psychological flexibility is considered to be an interconnected and dynamic construct that is often distilled and organized into 6 processes (ie, acceptance, defusion, present moment awareness, self-as-context, values, and committed action) and/or 3 pillars of openness, awareness, and engagement.12 In contrast, the model of psychological inflexibility asserts that there are common underlying processes that are central to the development and maintenance of psychological suffering (ie, psychopathology), such as experiential avoidance and fusion, resulting in patterns of inflexible, rigid, and unworkable behavioral repertoires of varying topography that correspond to being closed, mindless, and disconnected.13

Although there are a plethora of different stimulation locations and parameters in the literature, consistently applied and clinically overlapping neurostimulation locations such as the dorsolateral prefrontal cortex (DLPFC) are also not diagnosis specific, but rather have revealed established clinical effects across symptoms of depression,14 post-traumatic stress disorder (PTSD),15 obsessive-compulsive disorder (OCD),16 addiction,17 chronic pain,18 and negative symptoms in schizophrenia.19 As such, perhaps there is a more direct link between transdiagnostic biophysiological intervention targets, such as the DLPFC, with underlying psychological and behavioral processes that may lend support toward combination with more process-based oriented intervention models.20 The evidence base and clinical application of rTMS is mostly applied in treatment-resistant clinical settings; in other words, patients receiving rTMS have typically failed to respond to previous pharmaceutical and/or psychotherapeutic intervention.21 Given the evidence base for ACT in complex transdiagnostic clinical settings and demonstrated sustained clinical efficacy in treatment-resistant populations,22,23 an ACT framework may be well suited to a flexible integration with rTMS.

To illustrate in a real-world setting, in a large naturalistic study of 196 patients with treatment-resistant depression, Donse et al4 found that rTMS delivered with concurrent psychotherapy (ie, “rTMS combined psychotherapy”), primarily in the form of CBT personalized with other psychotherapeutic models as required, resulted in high response and remission rates of 66% and 56%, respectively. Although the precise therapeutic tools and mechanisms were not described in detail, this well-powered observational study highlights the feasibility and real-world impact of a simultaneous multimodal and personalized therapy approach. Furthermore, quantitative synthesis of the small group of existing RCTs combining CBT with active rTMS revealed significant superiority in improvement of clinical symptoms compared to CBT with sham stimulation with studies including at least 10 sessions.6 Considering that ACT is organized as a third-wave CBT approach, it is reasonable to suggest that ACT-based processes may have been integrated in prior studies.

As a more direct and recent illustration, Bariani et al24 added a four-session, weekly group ACT intervention to a course of theta burst stimulation (TBS) in a small group of elderly adults with major depressive disorder. As compared to those receiving general support, the combined ACT+TBS program resulted in a faster treatment response and remission trajectory. The difference in response between groups trended towards, however, did not maintain significance by Week 12. Considering the small sample size and relatively brief number of psychotherapy sessions, this preliminary work is encouraging and invites further research.

 Brain Networks and Psychological Flexibility

Within an overarching model that appreciates context, process, and function over form, there is utility in considering flexibility from a biological, neuroscientific viewpoint in relation to brain network function. Psychological and behavioral influence with depth should mean that theory adheres across levels of analysis; that is, neuroscientific, psychological, and behavioral principals have cohesion.9 In turn, language from an exogenous biologically driven intervention (eg, rTMS) can synergistically integrate with psychological process–oriented language to find common ground. To briefly orient the reader, cognitive neuroscience research in recent decades has described several interconnected and overlapping large-scale brain networks that are thought to subserve various human functions. Uddin et al25 organized a taxonomy of major identified large-scale functional networks by neuroanatomical and cognitive domain into the occipital (ie, visual), pericentral (ie, somatomotor), dorsal frontoparietal (ie, attention), lateral frontoparietal (ie, cognitive control), midcingulo-insular (ie, salience), and medial frontoparietal (ie, default mode) networks. While useful, it is important to recognize that functional brain networks are superordinate approximations of dynamic states, and their function varies with the neural context.26 That is, brain networks are dynamic and flexible when operating in the service of complex behavior and their activation and communication respond dynamically to changing context.

There is extensive literature on network-based neurobiological models of psychopathology, and the triple network model (ie, cognitive control network [CCN], salience network [SN] and default mode network [DMN]), is well regarded to contain core implicated networks.27 The frontoparietal CCN holds core nodes in the DLPFC and posterior parietal cortex, and it has a major role in working memory, attention, and active goal-directed behavior. The medial frontoparietal DMN has critical structures such as the posterior cingulate and medial prefrontal cortices, and it plays an essential role in self-referential, autobiographical processing, activated during a resting state. The midcingulo-insular SN is critical for identifying salient external inputs and internal brain events, modulating the switch between the CCN and DMN, associating with structures such as the insula and dorsal anterior cingulate, and maintaining connectivity with subcortical and limbic structures involved in reward and motivation.

It is not surprising that psychological interventions also exert an influence on measurable brain function and result in neuroplastic change, with evidence supporting neural involvement from a wide range of brain regions, including frontal and prefrontal regions, insula, and superior and inferior frontal gyri.28,29 Across psychotherapies targeting anxiety and depression, meta-analytic data supports the most robust changes related to decreased activity of the left anterior cingulate (ACC) and insula and bilateral inferior frontal gyrus.29 While there are likely many overlapping neural correlates of the different psychotherapeutic orientations, mindfulness-based interventions have implicated increased connectivity across networks of attention, salience, and limbic system (ie, CCN and DMN).30

The precise neural correlates of psychological flexibility have not been elucidated and perhaps are best represented in the dynamic flexibility and functional connectivity among the various functional brain networks of attention, salience, self, memory, language, and sensory experience. Mindfulness is contained within the 4 processes of acceptance, defusion, present moment awareness, and self-as-context, and the cognitive neuroscience literature on mindfulness therefore provides a window into the neurobiological representations of psychological flexibility.31 Fletcher et al32 provide a comprehensive account of proposed neural correlates of psychological flexibility mindfulness processes through a contextual behavioral lens. There is particular attention paid to the role of the medial prefrontal cortex and insula (ie, DMN and SN) due to the central role in self-referential processing, along with affective coupling and downregulation through salience and limbic structures, as well as attention and CCN nodes (eg, DLPFC).31 A recent study with healthy participants showed that higher psychological flexibility was associated with enhanced anticorrelation between the DMN and dorsal attention network, and suggested it related to a dynamic balance between internal and external cognitive states.33

Furthermore, there is evidence from pre- and post-ACT functional neuroimaging studies showing that therapeutic outcomes are associated with connectivity changes in the DMN (ie, posterior cingulate cortex and precuneus), SN (ie, insula) and CCN (ie, inferior frontal gyrus) in chronic pain34 and OCD,35 as well as SN activity as a predictor of ACT response in social anxiety disorder.36 Whelan and Schlund7 provide a summary of evidence from RFT-based functional magnetic resonance imaging studies which suggests that the DLPFC and inferior parietal lobule, core regions of the CCN, may be involved in the neural correlates of derived relational responding, that is, the uniquely human capacity to learn through deriving relations without any direct learning experience as expressed through ACT theoretical underpinnings (ie, RFT).37 It is interesting to postulate that direct activation and disruption of networks involved in derived relational responding may enhance the capacity for transformation of stimulus functions during rTMS sessions.

Psychological and Biophysiological Context: Psychological Flexibility Pillars and rTMS

Stimulating openness. The pillar of openness within ACT speaks to the fundamental human yearning to feel and construct coherence, that is, to make sense of lived experience and learning history to effectively plan, predict, and protect oneself in the future.38 It is argued from a functional contextual stance that when painful internal experience is unwanted, resisted, and avoided (ie, experiential avoidance), while content dominates awareness through rigid verbal rules, commands, and stories (ie, cognitive fusion), inflexible patterns of behavior emerge which narrow behavioral repertoires.39 Taken from a neuroscience perspective, flexible recruitment and functional connectivity between networks of affective regulation with executive attentional processes, such as the CCN, may facilitate openness to internal experience with acceptance as well as flexible acknowledgement of experiences as emotions, memories, thoughts and sensations in context (ie, defusion).32

Considering openness in rTMS invites the clinician to extend beyond symptom reduction as the therapeutic target, attending to processes of acceptance, willingness, and space to notice and hold experience for what it is in the service of new learning and growth, quality of life, and valued action. Deliberate and intentional contact with aversive stimuli through exposure-based methods is one of the most well-documented, evidence-based interventions available in behavioral psychology. Emotional acceptance is often made explicit in ACT-informed exposure, and exposure is reframed as a willingness to contact painful experiences to learn new ways of relating and responding in the service of valued living.40 As rTMS has well-established, state-dependent effects, it has been advanced that exposure in the form of symptom provocation may work to improve TMS response by activating the relevant brain-symptom circuitry.41,42 Exposure therapy conducted simultaneously during rTMS has been demonstrated as feasible in PTSD, although existing studies include small sample sizes.43,44 Exposure and response prevention (ERP) therapy is a strongly supported first-line therapy for OCD treatment,45 and there is established efficacy for ACT-informed ERP.46 Recent meta-analytic evidence has shown stronger effect sizes of rTMS with provocation compared to rTMS without provocation for nicotine use and OCD, although the effect failed to be statistically significant at the between-groups study level.42 Of note, there were very few studies that directly compared having or not having exposure/provocation within a study, and further well-powered RCTs are required.

For instance, a large landmark, multicenter, double-blind RCT treating 99 patients with medication and therapy–resistant OCD (ie, refractory OCD) showed a superiority in response rates for deep TMS vs sham (38% vs 11.1%, respectively).47 As mentioned above, both groups received brief personalized exposure to distressing thoughts prior to stimulation, thus activating relevant obsession circuitry, although response rates were clearly augmented in those receiving real stimulation. In other words, brief exposure without a stimulation context to modify response in this treatment-resistant group was far less effective than the combined approach. Viewed from a psychological flexibility perspective, there is willingness to contact emotionally distressing experience and widen a behavioral repertoire (eg, experience the thought without engaging in the compulsion in different context) while simultaneously exerting a biological source of modulatory influence that augments response prevention and new learning.

Huang et al48 followed 100 patients with refractory OCD assigned to either a pharmaceutical intervention only outpatient group or a multimodal intervention group, which combined medication, group and individual CBT (ie, ERP), and rTMS (ie, 10 sessions of 10 Hz; left DLPFC) over 2 weeks of inpatient admission. They showed a significant difference in response rates of the drug-only compared to the multimodal intervention (12.5% vs 52.3%, respectively), as defined by at least 30% reduction on the total Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Furthermore, it was revealed that the multimodal intervention led to more significant improvements of insight for several participants, and insight improvement was related to improved therapeutic outcomes. Moreover, insight in patients with OCD has been associated with emotional awareness,49 and mindfulness has been shown to predict higher insight in OCD.50 Though stemming from different therapeutic traditions, the functional overlap between the process of insight and cognitive defusion is to facilitate meta-awareness of internal experience that can weaken automatic responding and lead to more flexible behavior.

In a more direct comparison of approaches, Zou et al51 investigated rTMS (20 sessions of 1 Hz supplementary motor area daily over 4 weeks) compared to ACT (twice weekly for 4 weeks) in drug and medication–naïve inpatients with OCD. The findings showed significant improvements in anxiety, depression, and obsessive-compulsive symptoms in both groups. Interestingly, both TMS and ACT groups also revealed improvements in psychological flexibility and cognitive fusion, as per the Acceptance and Action Questionnaire and Cognitive Fusion Questionnaire. This provides evidence that rTMS without concurrent psychological therapy can still lead to improvements in psychological flexibility, in this instance, through inhibitory disruption of regions with hyperactive motor and/cognitive rigidity. Unsurprisingly, the ACT group showed further improvement in psychological flexibility in the follow-up, likely suggesting that explicit skills-building promoted ongoing progression postintervention.51 However, all clients were also prescribed sertraline at admission, and therefore, specific treatment effects are unclear and confounded. Future RCTs can explore the possible augmentation of combined ACT and rTMS in treatment-resistant OCD over those only receiving rTMS or ACT alone in promoting and sustaining psychological flexibility and clinical outcomes.

Following rTMS of the DLPFC in a cohort of patients with depression, Leong et al52 explored mindfulness-related outcomes and found that there was significant improvement in nonreactivity to inner experience subscale on the Five Facet Mindfulness Questionnaire and decentering subscale of the Experiences Questionnaire. Although preliminary, these findings indicate that repeated stimulation of the DLPFC can facilitate processes of nonjudgment, emotional allowance, and stepping back to observe internal experiences. Interestingly, this effect was demonstrated even for the group of individuals not showing significant reduction in depression symptoms. From a therapeutic process–oriented perspective, the clinician may consider whether processes (eg, nonjudgmental acceptance, defusion, etc.) were related to outcomes (eg, depression) in the latter nonresponse group or perhaps mediated by a different process. Moreover, if there were attempts to link processes and outcomes in important ways for the individual during active stimulation, that in turn may facilitate a meaningful change in outcome. This suggestion, however, cannot be drawn from nomothetic data and may require a more idionomic approach.9

Stimulating awareness. The ongoing capacity to observe and attend to what is internally and externally available to contact in the “here-and-now,” from the perspective of self, serves a fundamental human yearning to be oriented and connected.38 Within an ACT framework, mindfulness is captured through flexibility processes of openness (ie, acceptance and defusion) and awareness (ie, present moment awareness and self-as-context);32 however, for the purposes of stimulating awareness in rTMS, we can highlight flexible attentional awareness (ie, here-and-now component) with openness of experience. The benefits of purposeful, nonjudgmental observation and attention through the varied mindfulness practices have well-documented empirical support.53 Mindfulness processes from a neuroscientific view have received the attention of several comprehensive reviews,30,32,54,55 and there is central involvement of the DMN in mindfulness practice. Inflexibility of the DMN, as overactivation and failure to deactivate the DMN and engage the CCN, has been related to rumination, worry, negative self-talk, distraction, disengagement, and detachment from goal-directed behaviors.56

Considering neuromodulation and mindfulness practice, there is preliminary empirical support for augmenting clinical outcomes with concurrent mindfulness in rTMS and transcranial direct current stimulation (tDCS) for depression and anxiety.57,58 Duan et al59 showed that mindfulness intervention (ie, MBSR) combined with rTMS to the DLPFC in poststroke depression had superiority over both sham rTMS with mindfulness and sham rTMS with general psychological care. Similar positive effects of combined mindfulness and rTMS was seen in patients with generalized anxiety disorder.60 Alternatively, another study found that using audio-guided mindfulness meditation practices during rTMS for depression was not feasible and resulted in a very high drop-out rate,61 which highlights the importance of considering the method of delivery of mindfulness interventions during stimulation. Despite the high attrition, for those who completed the treatment course, there were significant improvements across mindfulness facets of observation, description, awareness, nonjudgmental inner experience, and nonreactivity, alongside significant reduction in clinical symptoms of depression and stress.61 Taken together, there is evidence to support the use of mindfulness practices, a central component of psychological flexibility, during simultaneous stimulation of brain networks involved in attentional control, self-awareness, and emotion regulation. These findings coincide with recent meta-analytic evidence from the present authors showing that active anodal tDCS can more directly augment self-reported mindfulness compared to sham stimulation when integrated with concurrent mindfulness practices.62

In a small sample of 9 individuals undergoing rTMS in the context of depression, thematic analysis of patient interviews reported an important mindfulness theme such that there were perceived changes in the way people observed thought content and self while imagining new ways of performing and engaging interpersonally, suggesting that the experience of neurostimulation may promote self-awareness and flexible perspective taking (ie, self-as-context).63 In a case report of a 68-year-old woman with chronic and severe treatment-resistant depression, high frequency left DLPFC rTMS combined with mindfulness-based cognitive therapy resulted in sustained remission following a course of 30 sessions, whereby the patient engaged in meditation practice briefly prior to and during each stimulation.64 Focused attention practices with concurrent DLPFC stimulation were argued to enhance awareness and lessen reactivity to stressful life events and following more than 30 years of chronic treatment-resistant depression; the patient remained in remission at 8-month follow-up with reduction in medication use. This case exemplifies the potential of a combined multimodal approach targeting flexibility processes on sustained outcomes.

Stimulating engagement. Engagement relates to behaving with a sense of competency, intention and purpose that is driven by values.38 From a brain network perspective, it is offered that engagement processes employ goal-directed attentional resources toward salient features of internal and external stimuli operating on fronto-limbic and striatal dopaminergic reward circuitry of intrinsic motivation leading to organized motor planning, sequencing, and execution. Facilitating change through rTMS and neurostimulation technology requires short-term, intensive, often daily sessions, demanding the physical presence of the individual. Committed action through adhering to the intensive treatment schedule is a critical starting point for behavioral activation, especially in populations whereby withdrawal and avoidance are pronounced clinical features; indeed, sham TMS studies have shown large placebo effects.65 However, there is added time-efficiency and treatment value for the individual to promote engagement in sessions when rTMS sessions are delivered and facilitated by the mental health clinician administering psychotherapy, further allowing more fine-grained clinical monitoring.

Deliberate contact with sources of positive reinforcement through individualized behavioral monitoring and activity scheduling is a well-established intervention for patterns of avoidance, withdrawal, and inactivity.66 Modern forms of behavioral activation typically integrate values identification when establishing target goals for activation.67 In a small sample of 9 patients with treatment-resistant major depressive disorder, Russo et al68 demonstrated feasibility of integrating behavioral activation with rTMS, showing a response rate of 55% in the sample. Larger scale RCTs are required to determine if adding behavioral activation augments clinical outcomes in rTMS, but the integration certainly makes clinician sense. In terms of psychological flexibility, promoting meaningful behavior that focuses on life enrichment and engagement provides the TMS clinician the opportunity to widen and operationalize therapy outcomes from emotional- to behavioral-based goals.

Extending beyond psychiatry, engagement in concurrent rehabilitation behaviors combined with rTMS stimulation have demonstrated benefit in neurological conditions such as stroke, traumatic brain injury, and Alzheimer’s disease.6,69,70 These examples of combined multimodal and multidisciplinary applications lend support to the notion that committed action of specific, relevant behaviors, such as physical movement/motor exercises and/or cognitive training, concurrent to stimulation may activate relevant neural circuity and work to synergistically enhance outcomes.

Limitations

A notable limitation of the present narrative review is that it has a clinical integrative focus, and it lacks systematic methodology. Therefore, it is subject to selection bias informed by a particular clinical perspective without formal and explicit evaluation of study quality. This article describes one of many possible therapeutic integrations of evidence-based psychological interventions with rTMS, and it is not the intention, nor is there evidence, to support a superiority or augmentation of this integration compared to other integrations and/or monotherapy options at this time. As stated in the aim, ACT provides an example of a process-oriented therapy. To date, there is presently an ongoing trial of ACT combined rTMS for depression and chronic pain by Tynan et al71 that may help to more directly elucidate the efficacy of this integration of therapies.

In clinical practice, it is unlikely that there is a one-size-fits-all approach, and while multimodal integrations may prove effective for some, monotherapy-based approaches may be more suitable for others, depending on their individual complex and unique context. In a randomized pilot trial intervention for borderline personality disorder (BPD), Kujovic et al72 failed to show any significant add-on benefit of rTMS (ie, intermittent theta burst stimulation [iTBS]) to dialectical behavior therapy on BPD symptoms, despite a tendency for greater effect sizes in the active vs sham TMS groups. These findings may suggest that a multimodal combined therapy was not indicated at the group level in this context over the monotherapy course; alternatively, further post-hoc analyses from this sample also showed that there were significant improvements in impulsivity only seen in the active iTBS group.73 These findings also possibly suggest that the augmentation effects of combining a neurostimulation technique with a psychological intervention may be symptom-specific in some contexts.

Implications and Conclusion

Research combining psychotherapy with rTMS is still emerging and limited to exploring specific therapeutic techniques and orientations across diverse clinical populations. It is argued that the existing studies of combined rTMS and psychotherapy can be interpreted more broadly within the context of a model of psychological flexibility processes, and, in doing so, may personalize therapy to add greater precision, scope, and depth of the clinical applicability. Patient-therapist interactions surrounding brain stimulation are not only feasible but hold the potential to make the most of the state-dependent neuroplastic effects in a time-efficient capacity through psychologist-led sessions. This can create space to consider the broader life context that interact with relevant modifiable contextual factors. In other words, disruption to brain network function via neurostimulation may be symptom-nonspecific and result in changes to cognitive, emotional, and attentional biological processes. However, when stimulation is overlayed with evidence-based therapy kernels that are personalized to the individual, such as through provocation/exposure, acceptance, cognitive insight, defusion, mindful presence and awareness, or values engagement, a context for meaningful change that is more targeted and flexible to changing circumstances is created.

There is great clinical care and trepidation when the perceived mechanism of behavioral change is fundamentally exogenous, especially from a short-term intensive intervention. As Fletcher et al31 express, the view that brain causes behavior without consideration of important contextual cues from the individual, learning history, and their complex interaction with the environment may be reductive to the individual. To combine psychotherapy with neurostimulation invites both directions of causality integrated into a whole; that is, brain causes behavior changes and behavior causes brain changes. With the latter, however, it invites change and growth to continue long after stimulation has ended, responding to the ever-changing context.

Neuromodulation technology such as rTMS can be applied as an evidence-based biophysiological treatment to enhance brain network and psychological flexibility within the context of an empirically grounded, process-based model of psychotherapy. However, further direct empirical research that explores the efficacy of the combined approach in addition to the psychological and neurophysiological mediating processes of change is required moving forward. Whether or not neuromodulation is integrated within more formal ACT-based intervention, it is positioned that there is an intuitive advantage for rTMS facilitators to gently encourage approaching rTMS flexibly with openness, awareness, and engagement.

References

  1. Lefaucheur JP, André-Obadia N, Antal A, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014;125(11):2150–2206.
  2. Lefaucheur JP, Aleman A, Baeken C, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014–2018). Clin Neurophysiol. 2020;131(2):474–528.
  3. Beynel L, Powers JP, Appelbaum LG. Effects of repetitive transcranial magnetic stimulation on resting-state connectivity: a systematic review. Neuroimage. 2020;211:116596.
  4. Donse L, Padberg F, Sack AT, et al. Simultaneous rTMS and psychotherapy in major depressive disorder: clinical outcomes and predictors from a large naturalistic study. Brain Stimul. 2018;11(2):337–345.
  5. Tatti E, Phillips AL, Paciorek R, et al. Boosting psychological change: combining noninvasive brain stimulation with psychotherapy. Neurosci Biobehav Rev. 2022;142,104867.
  6. Xu X, Xu M, Su Y, et al. Efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with psychological interventions: a systematic review and meta-analysis of randomized controlled trials. Brain Sci. 2023;13(12):1665.
  7. Whelan R, Schlund MW. Reframing relational frame theory research: gaining a new perspective through the application of novel behavioral and neurophysiological methods. In: Dymond S, Roche B, eds. Advances in Relational Frame Theory and Contextual Behavioral Science. New Harbinger Publications; 2013:151–177.
  8. Dalton B, Austin A, Ching BC, et al. ‘My dad was like “it’s your brain, what are you doing?”’: participant experiences of repetitive transcranial magnetic stimulation treatment in severe enduring anorexia nervosa. Eur Eat Disord Rev. 2022;30(3):237–249.
  9. Hayes SC, Ciarrochi J, Hofmann SG, et al. Evolving an idionomic approach to processes of change: towards a unified personalized science of human improvement. Behav Res Ther. 2022;156:104155.
  10. Hayes SC, Strosahl K, Wilson KG. Acceptance and Commitment Therapy: The Process and Practice of Mindful Change. 2nd ed. The Guilford Press; 2012.
  11. Gloster AT, Walder N, Levin ME, et al. The empirical status of acceptance and commitment therapy: a review of meta-analyses. J Contextual Behav Sci. 2020;18:
    181–192.
  12. Hayes SC, King GA. Acceptance and commitment therapy: what the history of ACT and the first 1,000 randomized controlled trials reveal. J Contextual Behav Sci. 2024;33:100809.
  13. Luoma JB, Hayes SC, Walser RD. Learning ACT: An Acceptance and Commitment Therapy Skills Training Manual for Therapists. New Harbinger Publications; 2017.
  14. Sehatzadeh S, Daskalakis ZJ, Yap B, et al. Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment resistant depression: a meta-analysis of randomized controlled trials over 2 decades. J Psychiatry Neurosci. 2019; 44(3):151–163.
  15. Kan RLD, Zhang BB, Zhang JJ, et al. Noninvasive brain stimulation for posttraumatic stress disorder: a systematic review and meta-analysis. Transl Psychiatry. 2020;10(1):168.
  16. Fitzsimmons SM, van der Werf YD, van Campen AD, et al. Repetitive transcranial magnetic stimulation for obsessive-compulsive disorder: a systematic review and pairwise/network meta-analysis. J Affect Disord. 2022;302:
    302–312.
  17. Johnstone S, Sorkhou M, Al-Saghir N, et al. Neuromodulation to treat substance use disorders in people with schizophrenia and other psychoses: a systematic review. Front Psychiatry. 2022;13:793938.
  18. Che X, Cash RFH, Luo X, et al. High-frequency rTMS over the dorsolateral prefrontal cortex on chronic and provoked pain: a systematic review and meta-analysis. Brain Stimul. 2021;14(5):1135–1146.
  19. Lorentzen R, Nguyen TD, McGirr A, et al. The efficacy of transcranial magnetic stimulation (TMS) for negative symptoms in schizophrenia: a systematic review and meta-analysis. Schizophrenia (Heidelb). 2022;8(1):35.
  20. Hayes SC, Hofmann SG. “Third‐wave” cognitive and behavioral therapies and the emergence of a process‐based approach to intervention in psychiatry. World Psychiatry. 2021;20(3):
    363–375.
  21. Hussain S, Chamoli S, Fitzgerald P, et al. Royal Australian and New Zealand College of Psychiatrists professional practice guidelines for the administration of repetitive transcranial magnetic stimulation. Aust N Z J Psychiatry. 2024;58(8):641–655.
  22. Clarke S, Kingston J, James K, et al. Acceptance and Commitment Therapy group for treatment-resistant participants: a randomized controlled trial. J Contextual Behav Sci. 2014; 3(3):179–188.
  23. Gloster AT, Haller E, Villanueva J, et al. Psychotherapy for chronic in- and outpatients with common mental disorders: the “Choose Change” effectiveness trial. Psychother Psychosom. 2023;92(2):124–132.
  24. Bariani B, Pinto BS, Santos LA, et al. Effect of a brief, focal acceptance and commitment therapy (ACT) protocol to accelerate repetitive transcranial magnetic stimulation treatment with theta-burst stimulation (TBS) for elderly patients with depression: a randomized, blinded, controlled clinical trial. J Affect Disord. 2026;393(Pt A):120182.
  25. Uddin LQ, Yeo BT, Spreng RN. Towards a universal taxonomy of macro-scale functional human brain networks. Brain Topog. 2019;32(6):926–942.
  26. Ciric R, Nomi JS, Uddin LQ, Satpute AB. Contextual connectivity: a framework for understanding the intrinsic dynamic architecture of large-scale functional brain networks. Sci Rep. 2017;7(1):6537.
  27. Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011;15(10):483–506.
  28. Cera N, Monteiro J, Esposito R, et al. Neural correlates of psychodynamic and non-psychodynamic therapies in different clinical populations through fMRI: a meta-analysis and systematic review. Front Neurosci. 2022;16:1029256.
  29. Marwood L, Wise T, Perkins AM, Cleare AJ. Meta-analyses of the neural mechanisms and predictors of response to psychotherapy in depression and anxiety. Neurosci Biobehav Rev. 2018;95:61–72.
  30. Melis M, Schroyen G, Pollefeyt J, et al. The impact of mindfulness-based interventions on brain functional connectivity: a systematic review. Mindfulness. 2022;13(8):1857–1875.
  31. Hayes SC, Law S, Malady M, et al. The centrality of sense of self in psychological flexibility processes: what the neurobiological and psychological correlates of psychedelics suggest. J Contextual Behav Sci. 2020;15(2):
    30–38.
  32. Fletcher LB, Schoendorff B, Hayes SC. Searching for mindfulness in the brain: a process-oriented approach to examining the neural correlates of mindfulness. Mindfulness. 2010;1:41–63.
  33. Cho SE, Jung JY, Kang CK, Na KS. Functional connectivity correlates of psychological flexibility: a resting-state fMRI study of the default mode and dorsal attention networks. J Contextual Behav Sci. 2025;100900.
  34. Aytur SA, Ray KL, Meier S, et al. Neural mechanisms of acceptance and commitment therapy for chronic pain: a network-based fMRI approach. Front Hum Neurosci. 2021;15:587018.
  35. Lee SW, Kim SH, Lee SY. Neural mechanisms of acceptance-commitment therapy for obsessive-compulsive disorder: a resting-state and task-based fMRI study. Psychol Med. 2024;54(2):374–384.
  36. Burklund LJ, Torre JB, Lieberman MD, et al. Neural responses to social threat and predictors of cognitive behavioral therapy and acceptance and commitment therapy in social anxiety disorder. Psychiatry Res Neuroimaging. 2017;261:52–64.
  37. Torneke N. Learning RFT: An Introduction to Relational Frame Theory and Its Clinical Application. New Harbinger Publications; 2010.
  38. Hayes SC. Constructing a liberated and modern mind: six pathways from pathology to euthymia. World Psychiatry. 2020;19(1):51–52.
  39. Villatte M, Villatte JL, Hayes SC. Mastering the Clinical Conversation: Language as Intervention. The Guilford Press; 2015.
  40. Thompson BL, Pilecki BC, Chan JC. ACT-Informed Exposure for Anxiety: Creating Effective, Innovative, and Values-Based Exposures Using Acceptance and Commitment Therapy. New Harbinger Publications; 2023.
  41. Silvanto J, Muggleton N, Walsh V. State-dependency in brain stimulation studies of perception and cognition. Trends Cogn Sci. 2008;12(12):447–454.
  42. Bello D, Jones M, Gadiyar I, et al. Symptom provocation and clinical response to transcranial magnetic stimulation: a systematic review and meta-analysis. JAMA Psychiatry. 2025;82(8):768–777.
  43. Fryml LD, Pelic CG, Acierno R, et al. Exposure therapy and simultaneous repetitive transcranial magnetic stimulation: a controlled pilot trial for the treatment of posttraumatic stress disorder. J ECT. 2017;35(1):53–60.
  44. Osuch EA, Benson BE, Luckenbaugh DA, et al. Repetitive TMS combined with exposure therapy for PTSD: a preliminary study. J Anxiety Disord. 2009;23(1):54–59.
  45. Stein DJ, Costa DL, Lochner C, et al. Obsessive–compulsive disorder. Nat Rev Dis Primers. 2019;5(1):52.
  46. Twohig MP, Abramowitz JS, Smith BM, et al. Adding acceptance and commitment therapy to exposure and response prevention for obsessive-compulsive disorder: a randomized controlled trial. Behav Res Ther. 2018;108:1–9.
  47. Carmi L, Tendler A, Bystritsky A, et al. Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: a prospective multicenter randomized double-blind placebo-controlled trial. Am J Psychiatry. 2019;176(11):931–938.
  48. Huang Y, Yang H, Zhu C, et al. An exploratory study of a novel combined therapeutic modality for obsessive-compulsive disorder. Brain Sci. 2022;12(10):1309.
  49. Manarte L, Andrade AR, do Rosario L, et al. Poor insight in obsessive compulsive disorder (OCD): associations with empathic concern and emotion recognition. Psychiatry Res. 2021;304:114129.
  50. Landmann S, Cludius B, Tuschen-Caffier B, et al. Mindfulness predicts insight in obsessive-compulsive disorder over and above OC symptoms: an experience-sampling study. Behav Res Ther. 2019;121:103449.
  51. Zou J, Wu S, Yuan X, et al. Effects of acceptance and commitment therapy and repetitive transcranial magnetic stimulation on obsessive–compulsive disorder. Front Psychiatry. 2022;12:720518.
  52. Leong KW, Chan P, Grabovac A, et al. Changes in mindfulness following repetitive transcranial magnetic stimulation for mood disorders. Can J Psychiatry. 2013;58(12):687–691.
  53. Goldberg SB, Riordan KM, Sun S, Davidson RJ. The empirical status of mindfulness-based interventions: a systematic review of 44 meta-analyses of randomized controlled trials. Perspect Psychol Sci. 2022;17(1):108–130.
  54. Tang YY, Hölzel BK, Posner MI. The neuroscience of mindfulness meditation. Nat Rev Neurosci. 2015;16(4):213–225.
  55. Sezer I, Pizzagalli DA, Sacchet MD. Resting-state fMRI functional connectivity and mindfulness in clinical and non-clinical contexts: a review and synthesis. Neurosci Biobehav Rev. 2022;135:104583.
  56. Rayner G, Jackson G, Wilson S. Cognition-related brain networks underpin the symptoms of unipolar depression: evidence from a systematic review. Neurosci Biobehav Rev. 2016;61:53–65.
  57. Demina A, Petit B, Meille V, et al. Combination of noninvasive brain stimulation with mindfulness-based interventions for anxiety and depression symptoms: systematic review and meta-analysis of randomized controlled trials. Eur Arch Psychiatry Clin Neurosci. 2025;275(6):1739–1785.
  58. Kochanowski B, Kageki-Bonnert K, Pinkerton EA, et al. A review of transcranial magnetic stimulation and transcranial direct current stimulation combined with medication and psychotherapy for depression. Harv Rev Psychiatry. 2024;32(3):77–95.
  59. Duan H, Yan X, Meng S, et al. Effectiveness evaluation of repetitive transcranial magnetic stimulation therapy combined with mindfulness-based stress reduction for people with post-stroke depression: a randomized controlled trial. Int J Environ Res Public Health. 2023;20(2):930.
  60. Gao L, Xie J, Huang T, et al. Effects of mindfulness decompression therapy combined with transcranial magnetic stimulation in generalized anxiety disorder. Am J Transl Res. 2021;13(6):6827–6836.
  61. Cavallero F, Gold MC, Tirrell E, et al. Audio-guided mindfulness meditation during transcranial magnetic stimulation sessions for the treatment of major depressive disorder: a pilot feasibility study. Front Psychol. 2021;12:678911.
  62. Wickens S, Gummersall T, Brown T. Mindfulness practices and transcranial direct current stimulation: a systematic review and meta-analysis of self-reported mindfulness. Brain Cogn. 2025;188:106307.
  63. Rosedale M, Lisanby SH, Malaspina D. The structure of the lived experience for persons having undergone rTMS for depression treatment. J Am Psychiatr Nurses Assoc. 2009;15(5):333–337.
  64. Pradhan B, Makani R, Chatterjee MB. Combining mindfulness based cognitive therapy (MBCT) with brain stimulation using concurrent repetitive transcranial magnetic stimulation (rTMS) and focused attention meditation during the rTMS session for refractory depression: a case report. EC Neurology. 2018;10(4):241–251.
  65. Brunoni AR, Lopes M, Kaptchuk TJ, Fregni F. Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis. PloS One. 2009;4(3):e4824.
  66. Jacobson NS, Martell CR, Dimidjian S. Behavioral activation treatment for depression: returning to contextual roots. Clin Psychol Sci Pract. 2001;8(3):255–270.
  67. Kanter JW, Manos RC, Bowe WM, et al. What is behavioral activation? A review of the empirical literature. Clin Psychol Rev. 2010;30(6):
    608–620.
  68. Russo GB, Tirrell E, Busch A, Carpenter LL. Behavioral activation therapy during transcranial magnetic stimulation for major depressive disorder. J Affect Disord. 2018;236:101–104.
  69. Chen J, Dong Y, Guo H, et al. Efficacy of rTMS combined with cognitive training in TBI with cognition disorder: a systematic review and meta-analysis. Neurol Sci. 2024;45(8):
    3683–3697.
  70. Galvão SCB, Dos Santos RBC, Dos Santos PB, et al. Efficacy of coupling repetitive transcranial magnetic stimulation and physical therapy to reduce upper-limb spasticity in patients with stroke: a randomized controlled trial. Arch Phys Med Rehabil. 2014;95(2):222–229.
  71. Tynan M, Martinez E, Chu G, et al. Neuromodulation-assisted psychotherapy: can transcranial magnetic stimulation increase the efficacy of acceptance and commitment therapy for comorbid chronic pain and depression? J Pain. 2023;24(4):63.
  72. Kujovic M, Bahr C, Riesbeck M, et al. Effects of intermittent theta burst stimulation add-on to dialectical behavioral therapy in borderline personality disorder: results of a randomized, sham-controlled pilot trial. Eur Arch Psychiatry Clin Neurosci. 2025;275(8):2301–2314.
  73. Kujovic M, Bahr C, Riesbeck M, et al. Effects on impulsivity and delay discounting of intermittent theta burst stimulation add-on to dialectical behavioral therapy in borderline personality disorder: a randomized, sham-controlled pilot trial. Borderline Personal Disord Emot Dysregul. 2025;12(1):2.