Integration of limbic self-neuromodulation with psychotherapy for complex post-traumatic stress disorder: treatment rationale and case study

ABSTRACT

Treatment Rationale: Exposure to repeated sexual trauma, particularly during childhood, often leads to protracted mental health problems. Childhood adversity is specifically associated with complex posttraumatic stress disorder (PTSD) presentation, which is particularly tenacious and treatment refractory, and features severe emotion dysregulation. Augmentation approaches have been suggested to enhance treatment efficacy in PTSD thus integrating first-line psychotherapy with mechanistically informed self-neuromodulation procedures (i.e. neurofeedback) may pave the way to enhanced clinical outcomes. A central neural mechanism of PTSD and emotion dysregulation involves amygdala hyperactivity that can be volitionally regulated by neurofeedback. We outline a treatment rationale that includes a detailed justification for the potential of combining psychotherapy and NF and delineate mechanisms of change. We illustrate key processes of reciprocal interactions between neurofeedback engagement and therapeutic goals.

Case Study: We describe a clinical case of a woman with complex PTSD due to early and repetitive childhood sexual abuse using adjunctive neurofeedback as an augmentation to an ongoing, stable, traditional treatment plan. The woman participated in (a) ten sessions of neurofeedback by the use of an fMRI-inspired EEG model of limbic related activity (Amygdala Electrical-Finger-Print; AmygEFP-NF), (b) traditional weekly individual psychotherapy, (c) skills group. Before and after NF training period patient was blindly assessed for PTSD symptoms, followed by a 1, 3- and 6-months self-report follow-up. We demonstrate mechanisms of change as well as the clinical effectiveness of adjunctive treatment as indicated by reduced PTSD symptoms and improved daily functioning within this single case.

Conclusions: We outline an integrative neuropsychological framework for understanding the unique mechanisms of change conferring value to conjoining NF applications with trauma-focused psychotherapy in complex PTSD.

HIGHLIGHTS

• Self-neuromodulation procedures that regulates limbic-related activity in adjunction to therapy show clinical effectivity in complex PTSD.

• We present an integrative perspective of neurofeedback embedded in psychotherapy, illustrated by a single case report.

• A single case provides an illustration of the potential utility of multifaced treatment including psychotherapy with adjunctive neurofeedback.

Justificación del tratamiento: La exposición a trauma sexual repetido, particularmente durante la infancia, con frecuencia conduce a problemas de salud mental prolongados. La adversidad en la infancia se asocia específicamente con la presentación del trastorno de estrés postraumático complejo, el cual es particularmente tenaz y refractario al tratamiento y presenta una desregulación emocional grave. Se han sugerido enfoques de potenciación para mejorar la eficacia del tratamiento en el trastorno de estrés postraumático, por lo que la integración de la psicoterapia de primera línea con procedimientos de autoneuromodulación mecanÍsticamente informados (es decir neurofeedback) puede allanar el camino para mejorar los resultados clínicos. Un mecanismo neuronal central del TEPT y la desregulación emocional implica la hiperactividad de la amígdala que puede regularse voluntariamente mediante neurofeedback. Describimos una justificación del tratamiento que incluye una justificación detallada del potencial de combinar psicoterapia y NF y delineamos los mecanismos de cambio. Ilustramos los procesos clave de interacciones recíprocas entre la participación del neurofeedback y los objetivos terapéuticos.

Estudio de caso: Describimos un caso clínico de una mujer con TEPT complejo debido a abuso sexual infantil temprano y repetitivo utilizando neurofeedback complementario como potenciación a un plan de tratamiento tradicional, estable y en continuación. La mujer participó en (a) diez sesiones de neurofeedback mediante el uso de un modelo de EEG de actividad límbica inspirado en fMRI (huella digital eléctrica de la amígdala; AmygEFP-NF por sus siglas en inglés), (b) psicoterapia individual semanal tradicional, (c) grupo de habilidades. Antes y después del entrenamiento de NF, se evaluó ciegamente al paciente por síntomas de TEPT, seguido de un seguimiento de auto-reporte al mes, 3 y 6 meses. Demostramos mecanismos de cambio, como también la efectividad clínica del tratamiento complementario, como lo indican la reducción de los síntomas de TEPT y la mejoría del funcionamiento diario en este único caso.

Conclusiones: Esbozamos un marco neuropsicológico integrador para la comprensión de los mecanismos únicos de cambio que confieren valor a la combinación de aplicaciones de NF con psicoterapia focalizada en TEPT complejo. El caso único ilustra la utilidad potencial del tratamiento multifacético que incluye psicoterapia con neurofeedback complementario.

治疗理由：反复遭受性创伤，特别是在童年期，往往会导致长期的心理健康问题。童年逆境尤其与复杂性创伤后应激障碍（PTSD）表现相关，这种症状特别顽固且难以治疗，以严重的情绪失调为特征。有人建议采用强化方法来提高 PTSD 的治疗效果，因此将一线心理治疗与机制相关自我神经调节过程（即神经反馈）相结合可能为改善临床结果铺平道路。 PTSD 和情绪失调的中枢神经机制涉及杏仁核过度活跃，可以通过神经反馈进行意志调节。我们概述了治疗的基本原理，其中包括对心理治疗和神经功能障碍可能结合的详细论证，并描述了改变的机制。我们说明了神经反馈参与和治疗目标之间相互作用的关键过程。

案例研究：我们描述了一名因早期和重复性童年期性虐待而患有复杂性PTSD女性的临床案例，使用辅助神经反馈作为持续、稳定、传统治疗计划的强化。该女性参加了 (a) 通过使用边缘相关活动的功能磁共振成像脑电图模型（杏仁核电指纹；AmygEFP-NF）进行的十次神经反馈，(b）传统的每周的个人心理治疗，(c）技能小组。 在 NF 训练期之前和之后，对患者的 PTSD 症状进行盲目评估，然后进行 1、3 和 6个月的自我报告随访。 我们证明了改变的机制以及辅助治疗对该病例PTSD 症状的减少和日常功能改善的临床有效性。

结论：我们概述了一个综合神经心理学框架，用于理解独特的变化机制，为复杂性 PTSD 中 NF 应用与创伤聚焦心理治疗结合赋予了价值。 一个案例说明了包括心理治疗和辅助神经反馈的多方面治疗的潜在效用。

KEYWORDS:

• Childhood sexual abuse (CSA)
• neurofeedback
• emotion regulation (er)
• complex post-traumatic stress disorder (CPTSD)
• self-regulation

PALABRAS CLAVE:

• Abuso sexual infantil (ASI)
• neurofeedback
• regulación emocional (RE)
• trastorno de estrés postraumático complejo (TEPT-C)
• autorregulación

关键词:

• 童年期性虐待（CSA）
• 神经反馈
• 情绪调节（ER）
• 复杂性创伤后应激障碍（CPTSD）
• 自我调节

1. Introduction

Exposure to sustained trauma, particularly early-life sexual trauma has been proposed to result in complex post-traumatic stress disorder (CPTSD; Herman, 1992; ICD-11, World Health Organization, 2019). CPTSD is a diverse emotion-dysregulation presentation that, in addition to core PTSD symptoms of re-experiencing, avoidance and arousal, includes also emotion dysregulation, interpersonal disturbances and negative self-concept (Cloitre et al., 2009; Herman, 1992; Kessler, 2000; ICD-11). Critically, CPTSD responses to first-line interventions are limited in efficacy and a significant proportion of PTSD cases (33–60%) remain treatment refractory posing an immense disease burden (Berger et al., 2009; Bradley et al., 2005; Jaworska-Andryszewska & Rybakowski, 2019).

The goal of the presented clinical study is twofold; first, we aim to describe the treatment rationale for explicit neurofeedback treatment augmentation in complex post-traumatic stress disorder and outline the reciprocal gain of combining neurofeedback and trauma-focused therapy. Second, we aim to illustrate this adjunction in a single patient, demonstrating certain aspects of the proposed therapeutic mechanisms.

2. Aim 1: treatment rationale

CPTSD is considered a chronic dysregulated emotional reaction to traumatic reminders, reflected in the co-occurring of contradictory symptoms such as hyper and hypo-arousal (Frewen et al., 2006; Litz et al., 2000; Shipman et al., 2005). Disturbances in emotion regulation account for both heightened emotional states, such as explosive rage and self-destructive behaviour, as well as blunted emotional responses manifested in apathy, dissociation, and depression. Similarly, emotion dysregulation in interpersonal context often results in behaviours ranging from aggressive or dependent behaviours to self-isolation and avoidant behaviours (Molnar et al., 2001).

The development of emotion regulation skills is typically achieved through a process of Mutual Regulation, which includes the capacity for stress management, arousal regulation, reflective functioning and agency that develop through a meaningful, reliable and nurturing relational environment that fosters these functions (Fonagy, 1998). Since childhood perpetrators are often a family member or trusted familial acquaintances (Finkelhor, 2008) the primary development of emotion-regulation, in the context of a safe and reliable relationship is often compromised or unavailable (Davies & Frawley, 1994; Schwartz, 2000). During treatment patients re-learn to self-regulate emotions, behaviours and neurophysiological arousal (Gross & Thompson, 2007) through the external-environmentally-driven scaffold of therapy via the process of Mutual Regulation (Stringaris, 2015).

A current approach in PTSD interventions proposes utilizing adjunctive therapeutic options in order to enhance the therapeutic effects, especially in treatment refractory disorders such as CPTSD (Forbes et al., 2019; Metcalf et al., 2020). Adjunctive psychotherapy and medication is already considered standard of care among CPTSD, but even with this combination, effectiveness is limited (Lev-Wiesel, 2008). Additional add-on approaches that combined two guideline-recommended treatments also showed limited efficacy, possibly due to an excessive demand on participant's cognitive and emotional resources which are already taxed from most first-line psychological interventions (Bohus et al., 2013; Bongaerts et al., 2022; Bryant et al., 2003; Foa et al., 1999). Some promise has been shown in integrative treatment models such as dialectical behaviour therapy (DBT) for PTSD which is a prototypic phase-based, multicomponent treatment programme utilizing principles from several approaches (i.e. trauma-focused cognitive–behavioural, compassion-focused therapy and acceptance and commitment therapy, Bohus et al., 2020), and in models that investigate integrative means of delivery (Bongaerts et al., 2022). Positive results were also shown in utilization of adjunctive interventions that harness neuropsychological mechanisms and require different types of resources from the participant, which may partially account for their longer lasting effects and greater tolerability (Metcalf et al., 2020). Stronger additive effects have also been noted to be gained from interventions that target network plasticity in a similar way through different pathways (Metcalf et al., 2020). Congruent with these findings we henceforward suggest neurofeedback (NF) as a possible potent add-on in the treatment of complex PTSD.

2.1. Neurofeedback for complex PTSD

In this framework, we outline the utility of explicit neurofeedback (NF), a self-neuromodulation adjunctive technique aimed at regulating disruption in specific neural circuits via a closed-loop brain-computer-interface guided procedure of reinforcement learning (Lubianiker et al., 2022; Sitaram et al., 2017). We describe the ways in which explicit protocols of NF have the potential of augmenting traditional CPTSD treatment outcomes; First, understanding the multiple, diffuse, and contradictory symptoms of complex PTSD as reflecting a disturbed process of emotion regulation can lead to identifying underlying neural mechanisms that can be then modified by NF. This notion has been recently conceptualized in framework named ‘process-based NF’ (Lubianiker et al., 2019) that outlines the premise of psychiatric treatments by targeting dysfunctional processes (e.g. s emotion-regulation) with defined neural substrates rather than clusters of symptoms. Relevant to the current investigation, amygdala hyperactivation has systematically reported to be involved in emotion dysregulation and PTSD (Etkin et al., 2015; Hayes et al., 2012) and its attenuation has been previously shown to be feasible and to associate with PTSD and borderline personality symptom reduction following various forms of NF such as real-time functional magnetic resonance (fMRI)-NF (Paret et al., 2016; Zaehringer et al., 2019), limbic-inspired EEG-NF (Fruchtman-Steinbok et al., 2021) and alpha oscillation EEG-NF (Nicholson et al., 2016, 2017). A single randomized control trial investigated the clinical efficacy of EEG-NF training among patients with PTSD following childhood adversities (Gapen et al., 2016). These investigations show clinical promise but they do not describe sufficiently the mutual relationship between NF and other treatment modules. Second, NF does not heavily rely on cognitive and emotional resources, which are already taxed in psychotherapy. This supports adherence and compliance as the traumatic event is not explicitly evoked and emotional resources are not exhausted (Lev-Wiesel, 2008). Third, compared to psychotropic treatment, explicit NF is a self-volitional tool and such recruits many processes that are targeted in psychotherapy such as arousal regulation, reflective functions, sense of agency, self-management and emotion regulation skills (Burde & Blankertz, 2006). Targeting similar goals by diverse pathways has been proposed to lead to stronger additive effects (Metcalf et al., 2020).

2.2. Principal considerations for neurofeedback augmentation

Several principles should be considered in NF add-on; (a) Timing – of NF augmentation may be crucial (Metcalf et al., 2020) as NF might be particularly beneficial at treatment onset, during the intensive stage of skill-building or, alternatively, during a more advanced trauma-processing phase in order to negotiate refractory difficulties. (b) NF Target of Modulation – should be matched to the specific clinical manifestation (Lubianiker et al., 2019). For example the mesolimbic reward system could be targeted for mood and motivational dysfunctions (i.e. anhedonia) and the inferior frontal gyrus could be targeted for inhibitory control difficulties (associated with dysregulation such as substance abuse). Relevant to childhood abuse-PTSD the most consistent abnormality related to emotion dysregulation involves amygdala hyperactivation (Eder-Moreau et al., 2022; Teicher et al., 2016) (c) Treatment baseline – certain initial capacities are crucial for treatment initiation such as basic emotion regulation abilities such as dissociation and frustration management that may hinder NF.

In the treatment augmentation programme described herein, several modules were integrated, following these guidelines: we integrated Amyg-EFP neurofeedback, trauma-focused psychotherapy, and skills group in order to capitalize on the potential synergistic effects. In the following sections, we will detail each module followed by an integrative rational for their combination and interactions.

2.3. Description of distinct treatment modules

Amyg-EFP-Neurofeedback includes an innovative fMRI-inspired electroencephalogram (EEG) model that is designed to target deeply located limbic-related activity (Meir-Hasson et al., 2014a). This model was developed applying machine learning algorithms on EEG data acquired simultaneously with fMRI, resulting in a Time-Delay X Frequency X weight coefficient matrix. EEG data recorded from the electrode Pz at every time point are multiplied by the coefficient matrix of the model to produce the predicted amygdala fMRI-BOLD activity (c.f., Meir-Hasson et al., 2014b). This model has previously demonstrated its validity (Keynan et al., 2016) and clinical utility (e.g. Fruchtman-Steinbok et al., 2021; Keynan et al., 2018). Amyg-EFP amplitude (See supplementary materials for EEG Data Recording details) was assessed by calculating a personal NF success index in each session (i.e. average of 5 NF blocks minus average of baseline blocks, divided by average baseline standard deviation) using the following formula: $\mathrm{NF}\mathrm{success}\mathrm{index}={\displaystyle \frac{\mathrm{mean}\mathrm{regulate}-\mathrm{mean}\mathrm{baseline}}{\mathrm{SD}\mathrm{baseline}}}$

The NF protocol included ten sessions, each lasting approximately 50 min and began with a 3-minute ‘global baseline’ recording (see Figure 1). Every NF block consisted of two consecutive conditions repeated 5 times: active baseline, passively watching the interface (Watch; 1 min) and downregulating Amyg-EFP (Regulate; 3 min) followed by a debriefing graph that presented success during conditions and a set of questions that documented the mental strategies employed (i.e. ‘what strategy did you employ during the current NF cycle?’). During ‘Watch’, participants were guided not to consider any mental strategies or previous successes or failures stressing the importance of creating a significant mental difference between conditions. During ‘Regulate’ a free and uninstructed exploration of mental strategies during regulation was encouraged in order to allow participants to adopt individual strategies that are most effective.

Figure 1. NF Procedure. NF Training Block; Each session consisted of 5 repetitions of consecutive conditions: watch (1 min), regulate (3 min) and a strategy debriefing with a graphic feedback on the signal modulation time-course in addition to a 3 min ‘Global Baseline’ that appeared once in the beginning. During regulate participants were instructed to down-regulate the feedback stimuli by practicing self-generated mental strategies.

Global baseline includes a bland screen with fixation with a 180 sec duration. Then five blocks include: watching the scenario for 60 s, regulating for 180 s, and debriefing.

The feedback interface consisted of an audio-visual scenario including avatars and sound of chatter and commotion in a busy emergency room. During both conditions, 75% of the characters congregate at the front desk, expressing agitation through body movements and verbal sounds. While during ‘Watch’ condition this arousal level remained constant, during the ‘Regulate’ condition it changes according to the Amyg-EFP signal. Lower Amyg-EFP (relative to baseline, measured every 3 sec) is represented by incrementally changes in the avatars’ position from standing to sitting with a matching soundtrack of a noisy emergency room complementing the system output (c.f. Keynan et al., 2016, 2018). The system was implemented using the Unreal Development Kit game engine, which controls relevant animations (walking, sitting, standing, and protesting), as well as their transitions for individual characters.

Trauma-focused Psychotherapy treatment protocol relies on common and well-established principles of relational trauma treatment (Davies & Frawley, 1994; Schwartz, 2000) and is built upon the three-phase modal (Cloitre et al., 2012; Herman, 1992). In this model the first stage includes education, stabilization and safety and is comprised of founding a therapeutic alliance, working on basic health needs (e.g. regulation of sleep and dissociation) and basic environmental needs. Transferring to stage two requires the capacity to build a safe alliance as it includes deep intra-personal work that includes processing, remembering, and mourning the trauma. The final stage includes meaning and reconnection leading to authority over traumatic memories and a coherent sense of meaning. Each of these stages can last months to years, depending on trauma characteristics (i.e. duration, severity and age of trauma) and can relapse due to the need to re-institute safety and stabilization. Therapeutic techniques and processes include psychoeducation, regulation of physiological arousal, expanding reflective functioning, increasing sense of agency, and improving emotion regulation capacities including dissociation management with tools and skills from DBT (Linehan, 2015) and trauma processing (Van der Kolk, 2014). Details of psychopharmacological treatment are described in the supplementary materials since it is not central to the augmentation approach.

Skills Group is a structured didactic group therapy for patients who have a trauma-related dissociative disorder and emotion dysregulation difficulties (Boon et al., 2011; Linehan, 2014). It includes short educational scripts, homework sheets, exercises that practice coping with dissociation/emotion dysregulation in daily life, and provides support and guidance for communication with self-dissociated parts. Topics include understanding dissociation and PTSD, practicing inner reflection, emotion regulation, coping with dissociative problems related to triggers and traumatic memories, resolving sleep problems related to dissociation, coping with relational difficulties, alongside promoting adaptive management of daily life challenges. In addition it provides an opportunity to practice and engage in inter-personal regulatory skills in a guided context.‏

2.4. Augmentative rationale; integration and synergy of treatment modules

Following the description of the treatment modules we propose a central therapeutic mechanism through which NF can augment therapeutic processes in trauma-focused psychotherapy. Specifically, we suggest that Mutual Regulation is a key mechanism in each treatment module (individual therapy, skills group), as well as in NF, but expressed in different levels of experiences (experiential, didactic and cognitive), and may be mapped on intra- to interpersonal regulatory continuum. We further suggest this formulation aligns with several well-established emotion regulation models (i.e. dual process model, information-processing framework, perception-valuation-action (PVA) process model).

Mutual regulation can be detected in each therapeutic module as follows: In individual therapy, the role of the therapist is of a co-regulator, attuning to the moment-by-moment regulatory needs of their own as well as the patients’, supporting both external and internal-driven processes. Collective mutual regulation was instituted through an external environment by practicing emotion regulatory capacities in-vivo during skills group sessions. NF induces reciprocal self-neural representations via a brain–computer interface, perceived as a reliable mirroring function of the inner state promoting internal emotion regulation supported by an external device. Acquiring self-driven emotion regulation could then be translated to an expanded ability to participate in mutual regulation.

Regulatory processes manifest in a multi-leveled experience; the therapeutic dyad provides an experiential environment through which co-regulation is experienced in a shared habitat (e.g. warm, calming presence, or during mutual exposure to pain or interpersonal friction). The patient practices emotion regulation, but simultaneously relies on the security, sensitivity, and responsiveness of the therapist particularly in moments of high and dysregulated arousal such as fear or distress, that can then be regulated together (Lyons-Ruth, Bronfman & Atwood, 1999). Group sessions are a didactic experience, employing cognitive and executive function resources utilized in a socially shared mutual-regulation environment. NF is an mental process within the individual, diverging from inter-personal regulation, relying on co-regulation between different aspects of the self through diverging mental processes. Specifically, it involves regulation of an internal signal by practicing a range of mental configurations such as control, reward, and reinforcement learning mechanisms (Lubianiker et al., 2022).

NF augmentation can be mapped on the regulatory space from inter-to intra-personal domains (Zaki & Craig Williams, 2013), both targeted in adjunctive therapy. This continuum ranges from intra-personal attempts to regulate one’s own experiences (NF procedures) on the one hand and regulating through the company of others (skills group) on the other hand, bridged by a deep, live, continuous and intimate inter-personal interaction (individual therapy) (Figure 2).

Figure 2. Multi-Level Regulatory Model. Figure 2 depicts the association between emotion regulation process in different treatment modules (Neurofeedback, individual psychotherapy and group skills ranging from intra-to-interpersonal domains, or from self to mutual-regulation, correspondingly) and experience mode (experiential, mental effort including control, reward, and reinforcement learning and didactic learning). Grey shade depicts the degree of involvement in each module (e.g. NF involves a high degree of mental effort, medium degree of experiential learning and low degree of didactic, explicit learning). Moreover, top and bottom bars allude the correspondence of central emotion regulation treatment models illustrating the association between the level of experience and continuum of each emotion regulation model (i.e. experiential, mental effort and didactic learning mapped on range from implicit to explicit and bottom-up to top-down, respectively). Top-down/Bottom-up and explicit/implicit axes refer to the experience level nodes (experiential, mental effort, and didactic learning).

Rows include therapeutic modules, from intra-personal to inter-personal: Neurofeedback, individual therapy, and group skills. Columns include experience level, from implicit to explicit and from bottom-up to top-down: experiential, mental effort, didactic. Colouring depicts degree of experience involvement in specific modules, so that darkest depicts highest involvement (experiential in individual therapy, mental effort in neurofeedback, and didactic in group skills), medium depicts middling involvement (experiential in neurofeedback, mental effort in individual therapy and in group skills), and lightest depicts lowest involvement (didactic in neurofeedback and in individual therapy, experiential in group skills).

From a broader perspective, extrinsic and intrinsic mutual regulatory processes relate to several well-established conceptual frameworks. First, contemporary research on emotion regulation focuses on explicit (effortful) and implicit (automatic) attempts to alter the course and intensity of emotional responses (Etkin et al., 2015; Gyurak et al., 2011) claiming that both forms of regulation are necessary for well-being. Correspondingly, the proposed treatment reinforces explicit initiation of conscious effort and regulatory monitoring (e.g. skills in group and individual therapy, conscious and proactive mental exertion in neuro-modulation) as well as evoking implicit regulation by automatic processes with a low degree of awareness (e.g. relational co-regulation in group and individual therapy, neurofeedback reinforcement learning).

Secondly, the adjunctive intervention regulatory components could be understood with the bottom-up/top-down information processing framework (McRae et al., 2012). In particular, emotions can be generated and regulated primarily from the ‘bottom up’ (in response to inherently emotional perceptual properties of a situation) or ‘top down’ (in response to cognitive appraisals of an event). Congruent with previous research that relies upon this formulation to explain therapy mechanisms (Chiesa et al., 2013), we suggest that skill training is associated with ‘top–down’ regulation (e.g. psychoeducation, cognitive restructuring) and is of unique advantage in the short-term, while ‘bottom–up’ regulation is often achieved experientially, within relationships (e.g. psychotherapy) has long-term regulatory benefits (Chiesa et al., 2013). Intriguingly, NF may be situated between these two processes since it involves active mental effort and processing but also targets automatic, implicit processing (i.e. top-down and bottom-up, respectively; Collura, 2014).

Finally, a recent framework has in fact integrated these concepts into a coherent emotion regulation model (Paret & Hendler, 2020). Specifically, neural regulation via NF can be understood as a form of mental state regulation following the perception-valuation-action (PVA) schema such that neural feedback is perceived (P) by the person who valuates (V) the feedback, lending to reflective functioning, and performs a mental action (A) to achieve the desired brain state which, importantly, is then incorporated as a being perceived as part of the individual’s emotion – and arousal-regulation capabilities, lending to a sense of agency. This additive effect has been confirmed by NF studies that showed that reinforcement of the mental action by the received feedback strengthened corresponding regulatory skills (e.g. Lawrence et al., 2014) thus highlighting the reciprocal gain of emotion regulation skills from NF interventions. This model has recently been theoretically and computationally developed within the prism of reinforcement learning, proving an algorithmic description of this proposal (Lubianiker et al., 2022). Following these understandings, we extend this notion to provide a possible map of the complementary interactions between NF and psychotherapy on several key processes.

2.5. Interactions between psychotherapy and adjunctive NF in therapeutic processes

Reciprocal regulatory gain can be a result of several therapeutic processes that are targeted both in trauma-focused psychotherapy and NF, we henceforward suggest a few of these processes and describe how they adjunct and correspond to the aforementioned multi-level regulatory model (Figure 3).

Figure 3. Multi-Level Regulatory Model integrating Therapeutic Processes. Figure 3 depicits the therapeutic processes that correspond to the different treatment modules (neurofeedback, individual therapy, and group skills(demonstrating the additive as well as specific gain in each process. Grey shade depicts the magnitude of gain (i.e. arousal regulation is extensively targeted and improved in neurofeedback, vs. medium and low levels targeted in individual and group therapy, correspondingly).

Rows include therapeutic modules, from intra-personal to inter-personal: Neurofeedback, individual therapy, and group skills. Columns include therapeutic processes: arousal regulation, reflective functioning, agency and dissociation management. Colouring depicts magnitude of process gains in each module, so that darkest depicts highest gains (arousal regulation, agency, and dissociation management in neurofeedback, reflective functioning in individual therapy, and dissociation management in group skills), medium depicts middling gains (reflective functioning in neurofeedback, arousal regulation and agency in individual therapy), and lightest depicts lowest gains (arousal regulation, reflective functioning and agency in group skills).

Arousal Regulation – Hyperarousal is one of the most prominent disturbances in PTSD and poses a challenge in psychotherapy. Traumatic content in therapy can induce heightened affective and physical arousal that may lead to avoidance and hinder reflective functioning. Hyperarousal is most commonly linked to amygdala hyper-activation (Hayes et al., 2012) and thus directly targeted via process-based NF (Lubianiker et al., 2019). However, NF interface degree of arousal may also serve as a surrogate of the individuals’ subjective feeling of arousal. Specifically, the degree of interface agitation (manifested by the level of unrest in a scenario) may intuitively correspond to the individuals’ subjective self-representation of arousal. As opposed to real-life, in which this experience might be overwhelming, the NF interface enables participants to modulate their perceived vigilance from a distance, reinforcing internally driven locus-of-control over their sympathetic arousal. Gaining a sense of control over hyperarousal (Stein et al., 2012), as well as decreasing disrupted neural activity is considered a necessary phase in order to progress in therapy. Once a certain decrease of arousal is obtained it allows mental and sensory resources to be allocated to higher-order processes in psychotherapy.

Reflective Functioning – Survivors of childhood sexual abuse (CSA) often experience emotional chaos including the difficulty to distinguish, identify and describe emotions, as well as failure to differentiate between feelings and the bodily sensations of emotional arousal (McLean et al., 2008). Exercising reflective functioning through a multifaceted interface, may be perceived by patients as a visual mirror of their ‘inner state’, might aid in the ability to differentiate emotions, affective and physical states. This notion was articulated clearly by a patient who related to the animated individuals in the interface as different ‘emotions in her head’, gradually shifting from experiencing them as noisy, vague and fused, and therefore threatening and overwhelming, into an assorted experience that can be mentalized. This reflective functioning holds the potential for conducting an inner dialog between the multi-voiced self, which is an important capacity in psychotherapy work since it prompts a more complex, self-aware, and flexible organization of the self (Aron, 1998).

Agency – The ability to self-regulate one’s neural state involves a sense of agency, as it requires the patient to perform efficient means-ends actions in order to achieve an intended goal. Additionally, the sense of agency aids in restoring the survivors’ belief regarding their ability to control and own their actions and anticipate the associated outcomes (Bandura, 2006). Agency can be efficiently and deliberately utilized after accomplishing distinction between self/others and between different elements of the self (as described above). However, preserving self-agency is an ongoing task in CSA survivors as the sense of self as an agent that can influence the environment was largely violated in the act of abuse (Cook et al., 2005). Therefore, NF may serve as another method to reinforce agency as the individual gains a sense of control over the interface. NF can also be instrumental in recruiting motivation, derived from the sense of subjective competence reinforced by the continuous feedback the individual receives (Brenninkmeijer, 2013). The ability to practice goal oriented mental operations may be a preceding condition to promote agency in more conflictual representations of the trauma. Lastly, the capability to internalize and implement techniques in face of corrective feedback is easier to gain in a non-interpersonal NF environment, and therefore may expedite this ability in the interpersonal trauma work (i.e. corresponding to the rational of exposure hierarchy in prolonged exposure therapy, Rothbaum, Foa & Hembree, 2007).

Dissociation Management – Dissociation is considered a tenacious symptom of complex PTSD and is fundamentally understood as a maladaptive form of emotion and arousal regulation, utilizing emotional disengagement in order to avoid overwhelming experiences. In the aftermath of trauma, dissociation may appear as a disruption and/or discontinuity in the integration of consciousness, memory, identity, emotion, perception, body representation, motor control, or behaviour (American Psychiatric Association, D. S. M. T. F., & American Psychiatric Association, 2013). Dissociation perpetuates emotion dysregulation since the overwhelming affect is experienced as external to the individuals’ self or is not consciously experienced at all, and as such, it hinders the ability to regain self-regulation processes (Van Der Hart et al., 2005). To address this matter, dissociation could be monitored intermittently between NF cycles ensuring that participants do not use maladaptive regulatory strategies, and that awareness was not detached. This also facilitates close monitoring of dissociation during which the patient specifically focused on their degree of disengagement (e.g. temporary loss of time and de-realization). During this process the individual learnt how to identify and detect when dissociation patterns appear, and possibly why they occur. This insight, together with the valuable pre-knowledge individuals gain in skills group regarding dissociation and its causal relationship to traumatic triggers, can then be recruited more easily to understand how dissociation influences real-life situations. The ability to acknowledge (i.e. recognize, monitor, and detect causality) dissociative tendencies brings clarity that provides relief and, via this form of reflective functioning, further encourages a sense of control and agency.

To sum, the general and specific aforementioned rationale aspires to tease apart neural and psychotherapeutic mechanisms of change, while providing a broad justification for integrative therapeutic augmentation in these adjunctive therapies. To demonstrate this, we hereby describe a case study exemplifying the application of process-based NF in the treatment of an individual suffering from complex PTSD due to early and long-lasting sexual abuse.

3. Aim 2: single case illustration

This case study was conducted as part of a large, pre-registered randomized control trial (RCT, ClinicalTrials.gov ID; NCT03416764) investigating the effectiveness of EEG limbic-related NF augmentation to psychotherapy. We will henceforward describe part of the RCT procedures and illustrate several of the aforementioned therapeutic processes in a single case study.

3.1. Participants and recruitment

Women who were treated in an outpatient clinic dedicated to CSA survivors and participated in ongoing trauma-focused psychotherapy for a minimum of one year with insufficient responses (Fonzo et al., 2020; Hinton et al., 2011) were offered participation in NF add-on. Treatment included weekly individual psychotherapy, skills group and psychotropic medication which was maintained throughout the NF training period (see full description of treatment modules in aim 1; medication management was not central to the augmentation approach and is described in the supplementary materials). Certified psychologist screening included PTSD evaluation (Clinician-Administered PTSD Scale, CAPS-5) and a Structured Clinical Interview for DSM-IV axis I disorders. Exclusion criteria included comorbidities associated with significant neural damage that may hinder ability to benefit from treatment.

3.1.1 General procedure

Participants were assessed for eligibility, patients meeting DSM-5 criteria for PTSD (ages 21-65) were enrolled and randomized in a blinded fashion to 10 Amyg-EFP-NF sessions and psychotherapy or psychotherapy alone. Primary outcome was based on CAPS-5 administered before and immediately after NF sessions by clinicians who were blinded to treatment attendance and adherence. Follow-up self-report PTSD (Post Traumatic Checklist for DSM-5, PCL-5) measures were collected at 1-, 3- and 6 months post completion of NF. All procedures were approved by the Medical Center Ethics Committee (No. 0696-17). Lily was chosen for this case report since she was one of the first participants to enrol.

3.2. Clinical measures

Clinician-Administered PTSD Scale (CAPS): We used the gold standard structured clinician interview for assessing PTSD diagnosis and symptom severity. We administered a version of the CAPS that combines DSM-IV and DSM-5 criteria in order to maintain continuity between classifications (Friedman et al., 2016; Hoge et al., 2014, 2016). The CAPS contains explicit, behaviourally anchored probes for each of the 17 PTSD symptom criteria of the DSM-IV (on severity and frequency scale of 0–4), and 20 symptoms of the DSM-5 (on a scale of 0–4). Post Traumatic Checklist for DSM-5 (PCL-5) – A 20-item self-administered inventory that indexes PTSD symptoms in the past month (Weathers et al., 2013). Responses are rated on a scale of 0–4 and are summed to a total score.

3.3. The case of Lily – patient background

Lily is a 28-year-old female survivor of early onset and recurrent sexual and relational trauma. She enrolled in weekly sessions of individual psychotherapy in addition to participation in regulatory DBT skill management group and psychiatric treatment (See Supplementary Material for details of psychiatric treatment).

Lily comes from a religious, strict, and chaotic family. Her mother was raised by holocaust survivors and her father suffered from combat PTSD. Her parents’ emotional burden hindered their availability to nurture and protect their six boys and middle daughter Lily. At the onset of therapy, Lily described disturbed familial relational patterns as well as difficulties in regulating emotions and behaviour. Her mother was portrayed as unpredictable and explosive as she used to respond in immense rage or profound pain to any disobedience. For example, she would disappear into her bedroom for days as a response to her children’s behaviour or force Lily to randomly leave the house for the night as a penalty for what she perceived as ‘bad’ behaviour with little explanation. Alternatively, on other occasions, her mother would grab and hug her intensely without any apparent reason. Lily’s father was described as passive, detached, and unprotective even in times of extreme violence between her siblings.

When Lily was seven, her older brother formed a close relationship with her. This relationship felt occasionally reassuring as it was the only expression of warmth she received, but gradually became uncomfortable as it became invasive and sexual. While her brother was ‘examining her anatomy’ Lily would dissociate and physically and mentally detach from the situation. Lily acknowledged the abuse but did not relate to it emotionally ‘I guess it hurt me, what he did, look at how broken I am. but I don't feel it was hurtful. I don't know if I ever felt it’. The relationship with her brother became more demanding and sexualized as Lily matured. At the age of 14 Lily began to display misconduct at school, dramatic weight loss, and substance abuse. She also conducted non-suicidal self-injury behaviours such as cutting, a strategy which served both for regulation and to draw attention to her emotional pain. This extreme acting-out ended the sexual abuse but for the next several years she was admitted to psychiatric facilities numerous times and for periods that ranged from days to months due to self-injuries. In her twenties, her substance abuse intensified and concurrently she formed relationships with abusive partners as a familiar way of receiving comfort. At the age of twenty, she took an accidental overdose of opiates, following which she enrolled in a drug rehabilitation centre. During this period, she participated for the first time in individual psychotherapy that stabilized her substance-use and enabled her to regain partial occupational functioning.

Lily was referred to the Lotem Center at Tel Aviv Medical Center, a specialized clinic for the treatment of adult survivors of CSA. Treatment was within a community care standard but not manualized and measured. At the onset of therapy, she managed an ascetic steady work routine as a gardener but reported rapid mood fluctuations and was easily overwhelmed. Her disturbances in emotion regulation included both hyperarousal and re-experiencing such as nightmares and flashbacks and intrusive thoughts, as well as depression and dissociation. Her dissociative symptoms included time loss, distorted body image and uncontrollable shifts between different self-states (Bromberg, 2009).¹ In order to sustain functioning she suppressed urges for harmful behaviours, yet this included an overall reservation and preventive self-isolation, as Lily did not acquire sufficient alternative regulatory capacities. Lilly was then left with little social support.

In the first two years of psychotherapy, Lily struggled to create a safe environment in which she could expose her painful and traumatic experiences. Although she consistently attended therapeutic sessions, her interpersonal behaviour was dysregulated and unpredictable; aggressive and rejecting at times, yet clingy and demanding during other occasions. She would also enter dissociative states during sessions, during which she would lose the ability to sense or move her limbs. She could fall asleep curled up in fetal position on the floor or experience her voice or words as foreign to her. In the therapeutic relationship, she experienced her female therapist as her father, ineffective and passive, or as her brother, examining and poking at her for his own satisfaction.

Lily gradually devoted herself to routine psychotherapy which slowly became a consistent and predictable environment for her. She developed a sound therapeutic alliance that led to a sense of stability and protectiveness. Her attachment patterns in therapy transformed over time from disorganized to more secure. Mutual regulation in therapy included both verbal and nonverbal communication that led to a sense of being recognized and protected, providing a calm and soothing feeling. However, as her emotional state stabilized and she developed more reflective functioning, she was also more attuned to her distress, and experienced an exacerbation of arousal and irritability. In therapy sessions, Lily would dissociate when emotions overwhelmed her, which hindered the ability to identify and understand the subtleties of her emotions and thoughts. To overcome this emotional blurriness, Lily learned about her tendency to detach, and recognized that disengagement regulatory strategies were harmful and maladaptive. Moreover, she ascertained the capacity to identify dissociative symptoms and their causal attribution to specific stressful triggers. At this point, after approximately four years of therapy, Lily was referred to Amyg-EFP NF intervention.

Lily was chosen as a candidate as she entered the trauma-processing phase. She remained highly symptomatic, suffering from hypervigilance, intrusions, and avoidance of trauma-related cues thus down-regulation of amygdala was congruent with the clinical manifestation (Lubianiker et al., 2019). Additionally, she acquired certain basic emotion regulation such as dissociation monitoring skills, stress and frustration management that are crucial for treatment.

3.4. Treatment outcome

During the NF intervention period and thereafter the outpatient treatment staff reported that Lily was calmer, with higher capacity to actively regulate her arousal and therefore was more engaged in her psychotherapeutic work. Lily herself reported a decrease in daily tension and dissociation together with an expanded ability to reflect and observe her mental state. According to her psychotherapist and psychiatrist, her reflective functioning increased and she gained a higher sense of agency. Consequently, these changes set the ground for the ability to distinguish, identify and describe emotions and mental experiences. She shifted from a confused and fearful experience she described as ‘commotion inside her head’ to a reflective, mentalizing stance (Bateman & Fonagy, 2006) that assisted her in dealing with internal and external conflicts. She became more aware of her mental and bodily states and hence could detect more clearly triggers of hyperarousal and dissociation. She felt less overwhelmed by inner chaos and could exercise reflective functioning apparent in her ability to identify her and other’s needs. These capacities increased her sense of control and agency and improved her capacity to monitor the environment, select and perform efficient means-ends actions, and to achieve an intended goal. Using improved reflective functioning she noticed and expressed her needs more clearly, and this expression of emotion regulation translated into the ability to set boundaries in her internal world as well as in relationships.

Real-life occupational and interpersonal functions improved as well, though Lily still suffered from labile affect that influenced her relationships with others. She transitioned from her position in gardening, which included little interaction with others and was perceived by Lily and her therapist as a protective, avoidant measure of self-isolation, to pursuing a genuine interest she had in sports coaching. This job facilitated flexibility and spontaneity and provided a more rewarding and interpersonal work environment. It also represented her transformative potential, as she utilized her improved emotion regulation capability to creatively manage daily challenges. She experienced prolonged periods of contentment and formed a significant long-term romantic and intimate relationship.

Clinical measures demonstrated a symptomatic improvement following intervention. Specifically, Clinician-Administered PTSD scale for DSM-5 and DSM-4 (CAPS-5, 4) was reduced pre- to post-intervention (CAPS-5, 64 to 34, CAPS-4, 101 to 61), with a reduction on all subscales, surpassing the 30% typically required to ascertain clinical response to treatment (Marx et al., 2021). Moreover, according to expectations as in previous NF studies (Fruchtman-Steinbok et al., 2021; Goldway et al., 2019; Rance et al., 2018), PTSD symptom improvement enhanced as exhibited in self-report PCL-5 scores in months following treatment (PCL-5; Pre NF: 77, Post NF: 71, 1 month: 73, 3 months: 70, 6 months: 56).

4. General discussion

In this work, we outlined a mechanistic rationale for the adjunction between brain-guided neuromodulation procedures with trauma-focused therapy in CPTSD, a treatment-resistant disorder with significant difficulties in emotion regulation, which have impact on functioning, relationships, and subjective experience. We have illustrated its clinical potential in self-referential healing processes through a single case-study. We described potential changes in arousal regulation, reflective functioning, sense of agency, and dissociation management via emotion regulation processes across treatment modules, demonstrating several of them in Lily’s case. These therapeutic operations are achieved via mutual regulation in both top-down (e.g. acquiring specific strategies for self-soothing during NF, for instance Lily reinterpreted the noisy interface scenario as being a waiting room in a labour ward thus making the meaning less negative) and bottom-up processes (e.g. responding to feedback received during and following each NF cycle, reinforcing the sense of self-control and agency) processes, as well as both implicit (e.g. evident in sessions in which Lily’s cognitive resources were limited and therefore more automatic attempts to alter the course of feedback were prominent) and explicit (e.g. Lily voluntarily used regulation strategies taught in therapy such as body focus and grounding techniques) processes (see full details of Lily’s NF strategies in Supplementary Materials).

Together with the novelty of the present investigation, it is important to mention several limitations and future directions. First, we relied on the ‘process-based NF’ theoretical framework that suggests that NF interventions should target dysfunctional processes with defined neural substrates (Lubianiker et al., 2019). To that end, each unique symptom presentation could be delineated separately, as they might reflect different neural substrates and processes. However, the present case study did not assess specific CPTSD symptoms as treatment was held in a community care standard, and this should be incorporated in future studies. Furthermore, monitoring should be carried out in a more quantifiable matter both on daily regulation (e.g. DBT cards or self-report measures) and on identified maladaptive emotion dysregulation tendencies (e.g. self-reports measures such as Dissociative Experiences Scale). Personal clinical characterization could also promote an individual tailoring the different aspects of the intervention (e.g. feedback interface) leading to even more personalized and effective procedures (Lubianiker et al., 2019). Finally, CPTSD is usually a chronic illness raising a question regarding the need to maintain NF intervention gains over time, perhaps using booster sessions. Recent reports have pointed to enhanced symptom reduction weeks after completing neurofeedback (Rance et al., 2018), that could provide a clue as to a delayed clinical enhancement that should therefore be reinforced. This matter may be clarified in future research, as current protocols are mostly powered to check intensive dosage of NF sessions and their short-term effects.

To conclude, the current case capitalizes on the human ability to volitionally modulate brain functions in order to regulate underlying neural dysfunctions of complex post-traumatic stress disorder and conceptualizes the unique contribution of embedding NF procedures in standard care. Cases like Lily’ suggest a new and promising horizon for integrative effective treatments, that should be urgently investigated in methodologically strong, double-blinded randomized controlled trials.

Ethical approval

Participant was enrolled to a larger randomized control trial investigating the effectiveness of a Amg-EFP intervention (ClinicalTrials.gov ID; NCT03416764). All procedures performed in the study were in accordance with the ethical standards of the institutional and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by Tel-Aviv Sourasky Medical Center Ethics Committee (No. 0696-17).

Patient consent

The patient gave a written informed consent for publication of the manuscript on her treatment.

Disclosure statement

T.H. is a chief medical scientist of Graymatters Health. No potential conflict of interest was reported by other authors.

Data availability statement

Data are not available for privacy reasons. We report the results of one case (not of a set of data). The scores on the administered questionnaires and interview are reported in the manuscript. The paper describes the protocol and a first treatment.

Additional information

Funding

This work was supported by Israel Science Foundation [grant number 2107/17]; Israel Science Foundation [grant number 2923/20]; National Institute of Psychobiology for Israel Young Investigator; Brain and Behavior Foundation, NARSAD [grant number 26302]; European Union’s Horizon 2020 Framework Programme for Research and Innovation [grant number 945539].

Notes

1 Self-State refers to the self as composed of many different self-states with different affective, perceptual, and cognitive features. As result of trauma, the self-states are thought to become defensively dissociated from each other.