Memory and perception: Child maltreatment, inflammation and implications for psychotherapy

Abstract

In this article we focus on research that indicates that the adult brain, particularly the default mode network (DMN), exhibits significant plasticity in response to training of new skills, suggesting that language and creativity-based interventions are beneficial in long-term psychotherapy. The interface between neuroscience and psychotherapy reveals complex changes in brain connectivity, particularly in severe mental disorders (e.g., addiction, schizophrenia, and complex trauma related disorders). The understanding of brain function and perception informs therapeutic approaches, emphasizing the importance of memory reconsolidation and the need for studies in psychotherapy to focus on aspects such as DMN, memory retrieval, affect regulation, and memory modification. The important role of the DMN in internal mental processes, the clinical relevance and potential therapeutic implications for the treatment of complex conditions such as psychotic disorders are illustrated. In theory, memory contents that are not adequately symbolized and/or remain unconscious (for other reasons) are relived in the patient-therapist relationship rather than remembered as (past) memories. This perspective is intended to bridge the gap between psychotherapy and other sciences concerned with the study and processing of memory and its associated psychological, cognitive, and affective functions. The role of memory and related abilities and factors affecting psychological functioning are outlined. In addition, neuroinflammatory pathways are discussed. Research findings on memory vulnerability and insights that are relevant to future therapies are highlighted, concluding with open questions and further research directions, including the relevance of the study by Ge et al published in the recent issue of World Journal of Psychiatry.

Key Words: Memory; Vulnerability; Brain plasticity; Epigenetics; Neuroinflammation; Affect; Default mode network; Prediction error; Consolidation

Core Tip: The role of memory and related abilities and factors affecting psychic functioning, as well as neuroinflammatory pathways are relevant for future therapies. Research findings on memory vulnerability and affective insights are highlighted in their relevance for pathogenetic and therapeutic strategies. For further research directions predictive coding and inter-operationalization processes have to be focused in order to investigate the therapeutic processing of memory and its associated psychological, cognitive, and affective functions.

This editorial refers to “Effect of mindfulness stress reduction combined with cognitive behavioral therapy on perinatal anxiety disorder and maternal-infant bonding” by Ge et al, 2025; https://doi.org/10.5498/wjp.v15.i12.109408.

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INTRODUCTION

In the article by Ge et al[1] published in the World Journal of Psychiatry, mindfulness-based stress reduction combined with cognitive behavioral therapy is addressed. The goal of psychotherapy is conceptualized as emotional and behavioral change to the extent that individuals are constrained by their own (learning) history[2]. If behavioral and emotional change is started, then psychoanalysis aims to give individuals back the freedom to retell and reinterpret their own story in a less constrained way, particular with regard to internalized representations of parents and events with distinct meaning and lasting impact on the individual's life. Health means the ability to love and work, and these abilities can be recovered if basic, usually unconscious structures can be appropriately altered[3]. Werbart et al[3] identified in an inductive thematic analysis of patient interviews a third domain, the individual’s relationship to self (self-concept, self-acceptance, and self-care). However, changes in the domain of self could mediate changes in the other two domains (love and work). Emancipation from maladaptive ways of relating to oneself and one’s history is a process that involves shaping one’s memory in ways that seem to match one’s desires and talents and facilitating the management of desires and conflicts.

THE SELF AND THE OTHER

The strategies effective in learning and development processes are limited across cultures: Priming, predisposition, coherence of experience, approval/disapproval, and as important strategy: Operating with high affective arousal during learning, caring, parenting, mentoring, teaching. Socialization of emotion, emerging affectivity and affect tolerance consist in reciprocal pathways depending on the child’s affectivity/degree of arousal and the caregiver’s emotional awareness and (re)actions to the child’s emotional expressions. Within social learning theory, learning happens in social contexts and is motivated therein. Neurobiological research described the mirror neuron system, important for motor and observational learning, as specifically activated in the context of social learning.

AFFECT AND MEMORY

Affects with their somatic sensations and ideas are unconscious and become feelings, when subjective experiences are added. The symbolic history of a subject is, in a psychoanalytic understanding, memory. However, the term memory is also used differently within neurobiological contexts and fusion of the concepts (organic models and psychoanalytical ones) remains inconclusive, but the ongoing discourse might enhance innovation in both fields. According to psychoanalytic conceptualization up to 80% of psychic phenomena are being processed unconsciously. Symptoms and repressed content in the creation of meaning are thus fruitful hints for the psychoanalytic professional in treating patients suffering from psychic illness. Breuer and Freud focused on the important function of memories, especially unconscious (that had lost connection with consciousness) and false ones[4]. Freud suggested that suppressed memory contents cause symptoms, with memory traces being symbolized experiences. Concerning traumatic experiences, a differentiated view on (the) repression (of trauma) is necessary. Traumatic incidents can lack the actual experience of the incident in past time, in the actual moment happening, and often miss symbolized formations[5].

From experiencing and perceiving, humans gather memories of feelings and form representations in their psyche (of self and objects together with recalled relationships), constructing an internal world. The latter repeatedly is complemented with newer experiences (with current affect-cognitive moments), and can additionally be supplemented with (iterative) perceptions of past states, and is revised by reconsidering, dreaming or fantasizing future options[6]. These processes rely on affective regulation and affective experiencing capacities. In this context, Winnicott pointed at the importance of the mother-baby/caregiver-child relationship and the ongoing affective exchange processes in this dyad/relationship. For the adult other, it is indispensable to recognize the intentional self as an emerging separate human being with its own wishes, desires, anxieties and boundaries to help and support prosperous development[7]. The child’s search for identity and the confirming or regulating mirroring processes of the caregiver are essential research questions and theoretical achievements, as are the function of language in identity development and the role of intersubjective embedment.

Identity formation based on conscious as well as unconscious intrapsychic and interpersonal experiences provides a field for establishing meaning[8]. Due to language acquisition, symbolization processes emerge and unfold the exchange with the environment. For all these processes, memory functions are essential for integration and constructive development of a core self.

Affect regulation plays an important role, as mental health depends on styles of affect regulation, and preferred styles may differ between affectivity groups[9]. A recent meta-analysis showed that patients diagnosed with borderline personality disorders less often use affect regulation strategies effective at calming negative affect (cognitive reappraisal, problem solving, and acceptance), instead they use rumination and avoidance strategies[10]. For depression, connections between negative cognitive classification and affective processing of negative emotional experiences are described conceptually and shown in a meta-analytic review (medium to large effect size)[11]. For psychotic disorders, associations of maladaptive affect regulation and positive symptoms are known. Questionnaire-based cross-sectional studies have shown more frequent rumination, self-blaming and distraction strategies as dysfunctional affect regulation styles in psychotic patients[12]. Moderate to large associations were shown for dissociation and other similar maladaptive affect regulatory functions, i.e., detachment from inner and outer reality, and repetitive rejecting cognitions. Overmodulation of affective states can also be associated with dissociation. The basis seems to be the attachment style. A meta-analysis pointed at the caregiver-child attachment (i.e., disorganized, ambivalent, avoidant, and secure) and the influence on the child’s developing affect competence. Various affect perception (global negative and positive affect) and different affect regulation (e.g., reality focused response, avoidant or externalizing defenses, and social subsidy or different cognitive strategies) styles yield diverse attachment patterns in children[13].

Affects interfere and influence memory, as bias and adherence to emphasized positive self-images are known to establish self-esteem in healthy humans. Accordingly, the same bias applies to autobiographical memory processing, storing and retrieval processes. Described as the fading affect bias, humans generally keep emotions associated with positive memories more sustainably; a resilience factor connected to well-being. Positive valenced memories usually are more detailed, sensory and vivid, compared to negative ones.

Coping with distressing memories is challenging, and affect regulation has to include managing the recalled affects connected to negatively perceived life events. Adaptive coping, while reconsidering autobiographical incidents or even intrusive memory contents, includes the acceptance of particular stressful events as psychic events and distinguishes the self from them. In depressive disorder, often self-focused rumination (mainly on actually feeling negative valenced feelings) is connected with a network activation of certain regions in the brain (e.g., the medial prefrontal cortex and subgenual anterior cingulate cortex). This is similar to the process of constant self-referential ruminating combined with actually feeling all negative emotions, instead of accepting them in an adaptive way[14]. Under experimental training conditions for excessive rumination prevention, patients aimed to contain negative affect without increasing it: A “why” focusing insight-oriented approach helped to distance themselves, instead of a “what” focusing and self-indulged strategy.

Remembering is described to emerge maladaptively in stress-related, trauma, anxiety, and mood disorders. Although several diverse memory systems are incorporated, (mal)adaptive autobiographical memory converting is disequilibrated and leads to symptom persistence, which thus influences relapse. Depressed patients have lower affect suppression for both negative and positive memories[15]. Depressive syndrome was connected to reduced affect repression for negative memories compared to positive ones, being acquainted to the trend to indulge in negative experiences/memories more frequently (retrieved in congruent mood).

CLINICAL IMPLICATIONS

In the case of mental disorders accompanied by functional memory dysfunction, it could be assumed that a maladaptive pattern was established as a strategy for coping with (intense) negative affects. However, this is not the best strategy. The affected person gets detached from their motives, desires and aspirations, and therefore loses the capacity to really relate to themselves and the world; a situation that might lead to a feeling of internal emptiness or meaninglessness.

Remodulation of different various memory traces rather than eradicating and superseding consisting memories might be a more prosperous way to go today. Additionally, the pattern and process leading the person to affectively color and recall their memories might be amended, if necessary. Investigations of memory plasticity showed progress especially in the area of basic science over the past decade. Nevertheless, questions concerning clinical utilizations remain unanswered. Personal inner and circumstantial outer stimuli and experiences build up subjectively colored memories with specific personal meaning and valence. By influencing other further affect-cognitive processes, forming self-perception, and influencing our way of thinking affectively, memories contribute in a dynamic way to the core of human existence. Thus, for a sustainable longer run it is necessary to focus such processes in subjectively suffering patients with mental disorders and also focus on their real-world implications[16]. The challenge is to do this as subtly as possible and only to the extent necessary. In doing so, we must consider the needs of the individual and the subjective conscious and unconscious goals, which must first be determined together with the patient. Care should be taken to ensure that these interventions targeting memory patterns are used only for mental disorders in which memory patterns have been shown to be impaired [e.g., depression, substance abuse, anxiety disorders, and posttraumatic stress disorder (PTSD)] and not in mainly somatically caused memory impairments (e.g., dementia). The manner in which memory processing is impaired should be further investigated on a disorder-by-disorder and real-world basis, as much of the research conducted lacks such an understanding of the nature of the disorder in clinical practice. However, long-term effects of interventions are difficult to study, especially in real-world scenarios. Outcome parameters in studies examining such effects must be defined with caution. To ensure relevance to the individual, outcomes must match the individual's goals, but this makes it difficult to compare studies.

Hence, it is proposed that research should focus on the question, under which conditions memories become labile and influenceable. One hypothesis is that prediction error might be a necessary condition for inducing reconsolidation of human associative memory upon retrieval[17]. However, many other influences on memory processes have already been outlined in this paper, and questions arise about the precise effects that these conditions have on different memory domains, about their timing, and about their sensitive phases (e.g., in utero, in childhood, or in adolescence). The next step is to define the contextual conditions and interventions needed to achieve a lasting effect on memory, as well as the dosage, duration, and frequency of these interventions. The development of the psyche and mental cognitive functions are intertwined with memory function. Therefore, interventions targeting memory always impact multiple systems and modalities. It is expected that therapies that focus on memory will need to use a multimodal approach.

PREDICTION ERROR

Exposure-based cognitive therapies based on fear acquisition and extinction learning have been used to treat PTSD. Accelerated extinction learning and enhanced extinction retrieval have been shown to depend on a genetic variation in the fatty acid amide hydrolase (FAAH) gene[18]. For example, fear learning in women with PTSD depends on whether they have FAAH polymorphism C385A, making inhibition of FAAH a potential treatment target for PTSD. While these findings illustrate how specific genetic and neurobiological mechanisms shape fear learning and its modulation, more recent theoretical frameworks aim to situate such processes within a broader computational account of brain function. In this context, the free-energy formulation proposes that biological systems seek to minimize differences between predictions and the actual encounters[19]. Storing knowledge and past experiences might be conceptualized as an “attempt to reduce surprise”, as adaption towards the environment[19]. Nevertheless, surprising, even shocking situations appear all the time. For this reason, regulatory strategies have to be developed and continuously transformed to create new approaches. In this line memory functions in a dynamic way and recalled contents depend on personal anticipatory versions of their future in the state of remembering. Experiencing consists of inter-relations a person gained about and from their context and internal world, and thus relies on memory and available affect regulatory pattern. Consequently, reconsolidation through reactivation of memories and integrative inclusion of current new perceptions is proposed as a promising therapeutic approach[20]. Prediction error (i.e., the incongruence between experience-based expectation and the actual experiencing), was suggested as required (pre)condition to influence retrieval-induced alteration of existing memory[17].

In patients with right-hemisphere stroke, and anosognosia for hemiplegia after stroke, motor unawareness and lack of negative emotions about acquired disabilities is observed. Negative emotion induction resulted in significant improvement of motor awareness and better integration of new sensorimotor information[21]. Hence, controlled induction of negative emotion may enhance the prediction error between the patient’s prior belief of being physically intact and the actual motor deficit, thereby promoting updating of motor awareness.

Along these lines, optimizing the patient’s environment after stroke has been shown to be important. Music as an approach in neurorehabilitation, especially in stroke, has been used as a form of environmental enrichment with the goal of inducing activity-dependent neuroplasticity. This approach draws on knowledge of the diversity of brain networks involved in processing music and studies confirming effects on these networks from musical training[22]. Recovery of verbal memory and attention, as well as improvement in mood, have been shown to be associated with gray matter changes in patients with left hemisphere lesions. Vocal components of music affect verbal memory and support language recovery in aphasia, especially in the early recovery phase (stimulation of the bilateral frontotemporal network). Studies examining the effects of music on patients after traumatic brain injury showed that intra- and inter-network connectivity alterations in cognitive networks increased the connectivity between frontal and parietal regions involved in music processing. After traumatic brain injury, a randomized controlled trial also showed that music therapy improves executive function and structural neuroplasticity in the prefrontal area (effects persisted after 6 months)[23]. Virtual-reality-based motor control training retrieved promising results on neuroplasticity in patients with chronic stroke[24].

Neuronal recovery and plasticity are given, as neurotrophins are signaling molecules that coordinate neuroplasticity following neuronal damage and disease. For example, brain-derived neurotrophic factor (BDNF) is a neurotrophin that has been shown to be decreased in Alzheimer’s disease, Parkinson’s disease, autism spectrum disorders, depression, and post-traumatic stress disorder. Therefore, its role as a potential biomarker was further investigated. After stroke, BDNF blood levels were lower in patients with depression and positively correlated with poststroke recovery (cognition, affect, and motor function), and positive short-term effects of exercise or rehabilitation were demonstrated.

BIOMARKERS

Inflammatory pathways are related to disintegration of neuronal plasticity and the development of neurodegenerative diseases and mood disorders (Figure 1). Complex inflammatory networks promote systemic alterations in vascular homeostasis and may ultimately also enable the breakdown of the blood-brain barrier, facilitating neuroinflammatory diseases[25,26]. Here, the highly conserved signaling pathways through pattern recognition receptors like the NOD-like and Toll-like receptors (TLRs) play a major role[27,28] The latter are also crucial during viral sensing and induced proinflammatory and prothrombotic pathways. Inflammasome activation seems to be fundamental in depression. Here, NOD-like receptor pyrin containing protein 3 (NLRP3) activation, which can also occur by TLR-induced pathways, is a link to endothelial dysfunction and thus subsequently atherosclerotic processes and cardiovascular diseases[29]. Neuroinflammation can be driven by TLR- induced signaling and involves microglial activation, the breakdown of the blood-brain barrier, tissue oedema, caspase-induced pyroptosis and also apoptosis of neurons[30].

Figure 1 Inter-relation between cardiovascular diseases, infections and neuropsychological disorders. Inflammatory processes as they occur for, e.g., during infections have an impact on cardiovascular and neuropsychological diseases driving their development and progression[25,34]. Activation of conserved immunological pathways by the pathogen-recognition receptors including Toll- and NOD-like receptors initiates proinflammatory pathways, leading to inflammasome activation and pyroptosis[27,35]. Moreover, infections lead to a disbalance in the Virchow’s triad, driving endothelial dysfunction, altered hemodynamics and stasis. These mechanisms enable, on the one hand, cardiovascular diseases including disturbed microcirculation, (micro-) thrombosis, atherosclerosis, and tissue edema of different end organs, and on the other hand, drive neuropsychological disorders[36-38]. The latter include not only mood disorders and attention deficit syndromes, or neuropathic pain, but can manifest years later as dementia or multiple sclerosis[28,39,40]. On the molecular level, linking elements are among others the activation of leukocytes, platelets, complement and the inflammasome, as well as the release of proinflammatory cytokines, vasoactive amines and peptides, proteolytic enzymes, extracellular traps and reactive oxygen species[29,35,39,41]. A hyperactive hypothalamus-pituitary-adrenal axis drives changes in neuroplasticity with negative impact on mood disorders[42]. These complex networks can be modulated by a variety of factors including lipid mediators like resolvins, lipoxins or those mediators derived from docosahexaenoic acid, and eicosapentaenoic acid[43-45]. Future research should emphasize more strongly on inflammatory pathways to shift gears on the therapeutic potentials of chronic neurodegenerative and neuropsychological diseases. HPA axis: Hypothalamus-pituitary-adrenal axis; ETosis: Extracellular trap formation; ROS: Reactive oxygen species; PRR: Pattern recognition receptor; ADHD: Attention deficit hyperactivity disorder.

Repair of neural tissue requires several processes that are only partially understood to date (angiogenesis, neurogenesis, synaptic remodeling), so research into additional biomarkers of neuroplasticity will continue in this area of research. In neuronal recovery after stroke, inflammatory cells play multiple roles in these mechanisms; for example, by releasing proinflammatory cytokines that promote angiogenesis[31]. Angiogenesis is triggered by the hypoxic environment. Newly formed blood vessels create a suitable microenvironment for cell migration and neuronal remodeling. They support neural stem cell proliferation and provide guidance for migration and axonal growth; and they provide growth factors such as fibroblast growth factor, epidermal growth factor, and brain neurotrophic factor[31]. For a review of biomarkers relevant to angiogenesis and neuroplasticity in poststroke recovery see reference[32]. Plasticity prevails even in the aging brain, white matter plasticity was induced by aerobic exercise in a clinical study[32].

Taking the concepts together clinical work may be further investigated and evaluated via blood level control of inflammatory biomarkers/neurotrophins or functional connectivity of brain networks for therapy effectiveness in combination with psychodynamic parameters. For bridging the gap between brain and mind, considerations around the physical principle of free energy have become a mating element, thus linking psychoanalysis with the neurosciences[33]. The free energy principle might serve as a strong theoretical framework for this future work. For further research purposes simulation models of the human mind might also provide effective chances for finding the best way to treat a specific patient.

CONCLUSION

Early maltreatment reshapes how affects and memories are formed, retrieved and linked. This is often tied to a measurable imbalance in the default mode network and its connections to other brain networks, leading to difficulties in the regulation of inter- and intrapersonal processes. With reference to the free energy principle, patients cling to rigid priors that narrow perception and learning. Psychoanalytic psychotherapy can widen that channel. By naming unrepresented affect, cultivating autobiographical specificity, and allowing safe, tolerable prediction errors, the analytic relationship enables reconsolidation of maladaptive memory traces/priors.

Biological parameters influence these processes. Neuroinflammatory signaling, including TLR and NLRP3 pathways, undermines plasticity and vascular integrity, while neurotrophins such as BDNF mark capacity for change. Sleep and dreaming recalibrate emotional memory. Multimodal approaches, from music-based methods to virtual environments, can drive network reorganization and support learning.

Based on the current state of literature, it is proposed that memory is not a static archive but a dynamic, affectively charged system. By situating psychoanalytic treatment within a neurobiological framework of network plasticity, the editorial proposes an integrative model, which should be evaluated in further research. Specifically, this might be empirically tested in: (1) multimodal longitudinal studies linking changes in autobiographical memory, affect regulation, and therapeutic processes to alterations in large-scale brain networks and plasticity-related biomarkers (e.g., BDNF, inflammatory markers); and (2) experimental paradigms that systematically manipulate prediction error during autobiographical recall to determine conditions for reconsolidation effects.