CLINICAL NEUROSCIENCE OF
ADDICTION: NEUROBIOLOGICAL
DISRUPTIONS AND TRANSLATIONAL
MODELS OF SOCIAL DYSFUNCTION
NEUROCIENCIA CLÍNICA DE LA ADICCIÓN: DISRUPCIONES
NEUROBIOLÓGICAS Y MODELOS TRASLACIONALES DE
DISFUNCIÓN SOCIAL
Fabiano de Abreu Agrela Rodrigues
Department of Neurosciences and Genomics
Ricardo Santos Ferreira
Department of Neurobusiness, Brazil & Portugal
Lincol Nunes Cruz
Department of Philosophy, Brazil & Portugal
Cássio Jandir Pagnoncelli
Department of Tecnology, Brazil & Portugal

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DOI: https://doi.org/10.37811/cl_rcm.v9i3.18443
Clinical Neuroscience of Addiction: Neurobiological Disruptions and
Translational Models of Social Dysfunction
Fabiano de Abreu Agrela Rodrigues 1
contato@cpah.com.br
https://orcid.org/0000-0002-5487-5852
Department of Neurosciences and Genomics
Ricardo Santos Ferreira
contato@cpah.com.br
https://orcid.org/0009-0001-6575-8520
Bachelor in Law, Master in Administration
Heraclitus Research and Analysis Center
(CPAH), Department of Neurobusiness
Brazil & Portugal
Lincol Nunes Cruz
contato@cpah.com.br
https://orcid.org/0009-0008-7916-4062
Bachelor in Philosophy and Psychoanalyst
Heraclitus Research and Analysis Center
(CPAH), Department of Philosophy
Brazil & Portugal
Cássio Jandir Pagnoncelli
cassiopagnoncelli@gmail.com
https://orcid.org/0009-0000-7114-7008
Heraclitus Research and Analysis Center
(CPAH), Department of Tecnology, Brazil &
Portugal
ABSTRACT
Background: A comprehensive understanding of the neurobiological substrates that modulate social
behavior is essential for identifying etiologies and proposing effective approaches to social dysfunction
and addiction. Rather than relying on speculative or metaphysical premises, this framework is based on
measurable neurological alterations resulting from chronic environmental stress and early relational
deficits. These conditions may lead to maladaptive engrammatic patterns and dysregulated
neurocircuitry, with direct implications for the emergence of compulsive behaviors. Aims: This study
aims to propose a conceptual refinement in the field of clinical neuroscience, with emphasis on the
integration of addiction medicine within a neuroevolutionary and precision-based model. Methods: The
methodological approach combines descriptive observational analysis with a neuroethological
perspective, incorporating data from peer-reviewed literature in behavioral neuroscience and
neuroimaging studies (fMRI), focused on the identification of patterns consistent with dysregulation in
dopaminergic and prefrontal-limbic pathways. Conclusion: Based on consistent neuroscientific
parameters, we delineate a structured framework to interpret addiction-related phenomena, introducing
a neurobiologically grounded model that contributes to clinical and theoretical advancement in the
understanding of addictive behaviors.
Keywords: addiction, neurocircuitry, social behavior, dopaminergic pathways, neuroevolutionary
model
1 Autor Principal
Correspondencia: contato@cpah.com.br

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Neurociencia Clínica de la Adicción: Disrupciones Neurobiológicas y
Modelos Traslacionales de Disfunción Social
RESUMEN
Antecedentes: Una comprensión integral de los sustratos neurobiológicos que modulan el
comportamiento social es esencial para identificar las etiologías y proponer enfoques efectivos frente a
la disfunción social y la adicción. En lugar de basarse en premisas especulativas o metafísicas, este
marco se fundamenta en alteraciones neurológicas medibles, producto del estrés ambiental crónico y de
déficits relacionales tempranos. Estas condiciones pueden conducir a patrones engramáticos
desadaptativos y a una neurocircuitería disfuncional, con implicaciones directas en la aparición de
conductas compulsivas. Objetivos: Este estudio busca proponer un refinamiento conceptual en el campo
de la neurociencia clínica, con énfasis en la integración de la medicina de la adicción dentro de un
modelo neuroevolutivo y basado en la precisión. Métodos: El enfoque metodológico combina un análisis
observacional descriptivo con una perspectiva neuroetológica, incorporando datos de literatura científica
revisada por pares en neurociencia del comportamiento y estudios de neuroimagen (fMRI), centrados
en la identificación de patrones consistentes con la desregulación de las vías dopaminérgicas y prefronto-
límbicas.Conclusión: Basándonos en parámetros neurocientíficos consistentes, delineamos un marco
estructurado para interpretar fenómenos relacionados con la adicción, introduciendo un modelo con base
neurobiológica que contribuye al avance clínico y teórico en la comprensión de las conductas adictivas.
Palabras clave: adicción, neurocircuitería, comportamiento social, vías dopaminérgicas, modelo
neuroevolutivo
Artículo recibido 14 abril 2025
Aceptado para publicación: 20 mayo 2025

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INTRODUCTION
According to the American Society of Addiction Medicine (ASAM), addiction is defined as “a chronic,
treatable medical disease that involves complex interactions among brain circuits, genetics,
environment, and an individual’s life experiences. People with substance use addiction engage in
compulsive behaviors and often continue despite harmful consequences”1. This classification aligns
with the neurobiological frameworks that currently inform evidence-based approaches to addiction
treatment.
Recent neurobiological advances, supported by molecular tracing techniques such as Arc-driven
mGRASP, in conjunction with behavioral neuroscience and functional neuroimaging methods, have
contributed to a broader understanding of synaptic connectivity and memory-related processes in
addiction. These findings allow for the refinement of clinical constructs in addiction medicine, with a
focus on measurable maladaptive neural configurations rather than speculative multidimensional
models2.
Empirical data continue to demonstrate that exposure to early life stressors and emotionally adverse
conditions increases the risk for multiple psychopathologies, including substance use disorders (SUDs).
Computational models of memory engrams reveal that overlapping neural circuits may sustain
pathological associations in response to such experiences. These patterns can persist into adulthood and
influence the development of comorbid conditions such as post-traumatic stress disorder and affective
dysregulation3.
In the context of clinical research and decision-making, the investigation of addiction-related
phenomena requires precision in interpretation and methodological restraint. The presence of
interpretative errors due to attentional network dysfunctions has been documented in studies examining
the relationship between structural damage and functional outcomes, suggesting the need for a cautious
and evidence-based analysis of neurocognitive data4.
The accurate identification of etiologies and therapeutic targets for social behavior dysfunctions depends
on the recognition of specific neurological correlates. These include dysfunctional network patterns and
altered connectivity signatures that typically emerge under sustained environmental stress or lack of
affective stimulation. These neurological anomalies have been observed in clinical presentations

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involving visual-spatial processing impairments and attention deficits, reinforcing the argument that
social deficits in addiction may be rooted in identifiable cerebral alterations5.
Clinical neuroscience provides a valid pathway for integrating these observations into a structured model
of precision medicine. Evidence from white matter disconnection studies supports the premise that
disruptions in connectivity, rather than isolated gray matter lesions, play a central role in syndromes
affecting awareness and executive function. This conceptual shift informs the understanding of addiction
not as a singular behavioral manifestation but as a complex, network-level dysfunction6.
Primary Neuro Determinism
The interaction between familial psychosocial dynamics and genetic-epigenetic influences contributes
to the development of identifiable personality traits rooted in specific neurobiological dysfunctions. This
configuration, involving eight commonly observed clinical neurodysfunctions (CNDs), appears to
precede socioeconomic and educational variables in its impact on the early formation of emotional and
behavioral regulation patterns6.
These dysfunctions, when acting in interpersonal contexts, particularly within early relational
environments, may give rise to maladaptive behavioral responses characterized as neurodysfunctional
interpersonal relationships (RINs). The observed microstructural personality elements are primarily
oriented toward affective survival in both internal and social domains, particularly under emotionally
inconsistent conditions7.
Such dysfunctional interpersonal patterns within family systems have been associated with increased
resistance to treatment and a higher risk of relapse in individuals with substance use disorders and other
behavioral addictions. These phenomena are understood to arise from neurobiological triggers,
involuntary emotional unavailability, and impairments in volitional control and agency across members
of the relational group (8).
Within this framework, it becomes necessary to consider clinical approaches that target family-level
dynamics. Specifically, strategies incorporating the understanding of Family Coping processes and
Family Schema configurations—both of which are grounded in neurobiological and psychological
structures—may enhance intervention outcomes by addressing the emotional survival systems that
sustain maladaptive cycles (8).

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The set of ONCs (Observed Neuroclinical Conditions) refers to a cluster of behavioral tendencies
formed through early affective interaction. These configurations are partially dependent on
neurobiological substrates and are linked to a spectrum of psychological phenomena, including
internalizing and externalizing temperaments, personality traits, affective dysregulation, and
mechanisms of stress response (9).
According to current literature, the ONCs involve the following clinical and neurobiological features
(10):
1. Neurological Deficit of Family Synchrony (DNSF),
2. Maladaptive amygdalar-limbic modulation related to family schemas,
3. Hormonal and immune-inflammatory dysregulation,
4. Dysfunctions in neuropsychodynamic feedback and mirror systems within family interactions,
5. Dysregulation of the dopaminergic reward system and dopamine homeostasis,
6. Neural network impairments involving emotional engrams and deficits in both primary and
higher-order cognitive processing (associated with the conceptual framework of
Neuroschematic Survival Syndrome),
7. Secondary simultanagnosia and executive cognitive limitations (1),
8. Dissociative neuroadaptive disorders of consciousness.
Specific manifestations within this framework include:
• Secondary Simultanagnosia: a visual-perceptual limitation preventing the simultaneous
recognition of multiple elements within the visual field (1);
• Secondary Alexithymia: reduced access to internal affective states, impairing emotional self-
awareness;
• Secondary Anosognosia: inability to accurately infer or recognize others’ affective states;
• Anosodiaphoria: attenuated concern or awareness regarding one's health status, often
accompanied by affective indifference.
These dysfunctions, collectively representing a survival-based emotional personality architecture,
reflect a form of maladaptive habituation embedded in disrupted neurocognitive circuits. The resulting

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engrammatic structures function as stable, but dysfunctional, neural patterns—also referred to as
emotional engrams, neural signatures, or maladaptive cognitive schemas (11).
Neurobiopsychosocial Conditioning
Biopsychosocial conditioning within family environments involves the simultaneous activation of
multiple cognitive-affective schemas over extended periods. These schemas are frequently reactivated
by specific environmental or interpersonal cues originating within the family context (12). This process
is associated with adaptive mechanisms for coping with chronic stressors, often involving abrupt
amygdala hyperactivation. This hyperactivation leads to a restricted attentional field and decreased
affective modulation, which in turn may contribute—implicitly and without deliberate intention—to
patterns of emotional neglect (12).
Vygotsky's theoretical model distinguishes between elementary and higher psychological functions,
offering a developmental framework for understanding cognitive complexity (13). Higher psychological
functions encompass operations such as voluntary attention, intentional memorization, conceptual
abstraction, symbolic thought, reasoning, imagination, goal-directed behavior, and language-mediated
cognition. These functions are considered “higher” because they emerge through cultural mediation and
are not reducible to reflexive or instinctual responses, which are more characteristic of elementary
biological mechanisms shared with non-human species (13,14).
When biopsychosocial conditioning becomes neurofunctionally dysregulated, it reflects impairments in
neurocognitive systems responsible for attentional anchoring, intersubjective perception, and emotional-
cognitive integration. This includes deficits in neural connectivity associated with value-directed
attentional capture (VDAC), reduced attention during interpersonal exchanges across verbal, nonverbal,
and symbolic domains, and disruptions in the recognition of agency and intentionality (14–16).
Further dysfunctions encompass disturbances in motivation processes regulated by valence attribution,
involuntary emotional responses such as alexithymia, deficits in visuospatial awareness like
simultanagnosia, and limitations in recognizing internal or external states consistent with anosognosia.
Memory systems—both episodic and schematic—are also implicated, contributing to the consolidation
of maladaptive emotional engrams within these disrupted circuits (17–20).

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These conditions are often subtle and difficult to detect in standard clinical assessments. However, their
impact is significant, manifesting as micro-level distortions in awareness (micro-dissociations),
cognitive-affective biases, and decision-making errors anchored in survival-oriented emotional
frameworks. These processes undermine neurosemantic integration and contribute to persistent patterns
of social dysfunction (21).
Engrams
An engram refers to a persistent and detectable physical or molecular alteration within a neural network,
resulting from activity-dependent processes in specific neuronal populations. These changes occur in
response to episodic stimuli and can be reactivated by partial or complete re-exposure to the original
conditions, thereby enabling memory retrieval (22). Experimental evidence shows that repeated
exposure to the same contextual stimulus leads to consistent activation of the same cell ensembles,
commonly tracked through the expression of immediate early genes (IEGs) such as c-Fos, Arc, and the
activity-regulated cytoskeleton-associated protein (22).
In the hippocampus, engram cells have been identified as forming synaptic connections with other
neurons participating in the encoding of the same memory episode (22). These engram networks operate
as coordinated assemblies of memory-encoding cells, and their reactivation is both necessary and
sufficient for the conscious retrieval of stored experiences (22–27).
Furthermore, experimental models have demonstrated that artificial activation of engram circuits can
produce memory distortions, including the generalization of fear to unrelated contexts or the induction
of context-specific memories never actually experienced (22–27). Evidence from optogenetic studies,
such as those conducted by Kitamura et al., indicates that engrams form simultaneously in the
hippocampus and the medial prefrontal cortex (mPFC) during the initial phase of memory encoding,
although mPFC engram cells remain inactive during recent memory retrieval and are classified as “silent
engrams” (22–27).
The relatively low degree of overlap between neuronal populations activated during memory acquisition
and later recall—typically between 10 and 40 percent—suggests a dynamic restructuring of engrams
throughout the memory consolidation process. This reorganization reflects the capacity of neural

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networks to adapt their composition to optimize selectivity and behavioral relevance of stored
information (22–27).
Competition among neurons within a brain region for inclusion in an engram is modulated by neuronal
excitability. Cells with higher excitability levels have an increased probability of being recruited into
the memory trace, influencing the spatial and functional configuration of the engram ensemble (28–30).
Structural plasticity in engram cells includes increased synaptic strength and dendritic spine density,
along with preferential downstream connectivity to other engram-encoded neurons, even during resting
or offline states (28–30).
Advances in molecular neuroscience have enabled selective manipulation of these cell populations using
promoter-specific gene expression strategies, allowing for precise targeting of engram-related processes
at the cellular and circuit levels. These methodologies incorporate constitutively active proteins or
activity-inducible genetic markers to isolate and characterize engram cell subtypes (28–30).
Conceptual Memory
The encoding and retrieval of memory are mediated by specific subpopulations of neurons, referred to
as cellular engrams. In the human brain, memory formation frequently involves the association of
semantically or perceptually related concepts, a process supported by distributed yet selective neural
assemblies (31–33).
According to the Hebbian learning principle, synaptic connections between neurons exhibiting
temporally correlated activity are progressively strengthened, whereas those between neurons with
weakly correlated activity tend to undergo synaptic depression or elimination. This process enhances
the probability that the neural activation pattern present during encoding will be reactivated during
subsequent retrieval, establishing a synaptic engram as a memory substrate within coactive neuronal
ensembles (31–33).
In the human medial temporal lobe (MTL), individual neurons referred to as “concept cells” exhibit
invariant responses to representations of specific persons, places, or abstract elements. These neurons
selectively increase their firing rates upon exposure to stimuli associated with a particular conceptual
domain (34–37). The activity of a concept cell reflects the encoding of a discrete representational unit,
suggesting that each concept is represented by a distinct and distributed subset of neurons. When a

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stimulus is presented, the coactivation of γN neurons defines the engram of a single concept, while the
overlap between two unrelated concepts is estimated as γ²N, where N denotes the total number of
neurons in the relevant cortical region (34–37).
Experimental data confirm that individual neurons can become responsive to newly learned associations,
particularly when two concepts are presented in paired configurations. In such cases, the proportion of
shared neurons increases from less than one percent for unrelated concepts to approximately four to five
percent for concept pairs that have undergone associative learning, supporting the hypothesis that neuron
sharing facilitates cognitive integration and memory binding (38–39).
Theoretical models such as those proposed by Romani and Tsodyks demonstrate that memory engrams
maintain structural independence from network size constraints. Nonetheless, they allow for statistically
significant overlap between certain engram pairs, enabling sequential activation under conditions of
oscillatory or periodic background input. This mechanism may underlie the neurobiological basis for
concept sequencing and inferential reasoning (40–43).
Persistent structural connectivity has also been observed in animal models. Long-term potentiation of
Arc-expressing neurons between hippocampal subfields such as dCA3 and CA1 has been demonstrated
following continuous learning, confirming the stability and traceability of functional engrams in vivo.
These findings contribute to the clinical characterization and potential targeting of memory circuits (40–
43).
Neurodysfunctional Family Interpersonal Relationships
The quality of early family interactions plays a central role in child development, attachment formation,
and mental health outcomes. Several studies have established the correlation between caregiver
responsiveness and neuropsychological maturation in the child (45–47). Exposure to childhood
adversity, including chronic stress and parental depression, has been shown to affect the dynamics of
the mother-father-child triad, disrupting interactional quality and emotional attunement within the
family system (45–47).
Triadic synchrony—defined as temporally coordinated behaviors involving physical proximity,
affectionate contact, and mutual gaze between both parents and their infant—has been associated with

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parental oxytocin levels. These synchronous interactions contribute to the formation of secure relational
patterns during early development (45–47).
Oxytocin has emerged as a key modulator of social behavior, implicated in mechanisms underlying
trust, empathy, affiliation, and the regulation of interpersonal interactions, particularly in parent–child
bonding. Behavioral studies suggest that parental sensitivity correlates positively with endogenous
oxytocin production, reinforcing its role in shaping attachment-specific behaviors (48,49).
Evidence also supports the intergenerational transmission of stress-related vulnerabilities. Parents with
histories of adverse childhood experiences (ACEs) often display increased levels of depressive
symptoms, which in turn compromise their responsiveness to their children. This reduced sensitivity
affects both dyadic and triadic interactions within the family, contributing to less effective emotional
regulation and behavioral involvement in children (48,49).
Maternal and paternal sensitivity appear to be mutually reinforcing. Higher sensitivity in parent–child
dyads is associated with more adaptive triadic coordination, enhancing the child's capacity for emotional
regulation and relational engagement. Conversely, reduced synchrony correlates with the emergence of
internalizing symptoms in children, particularly in contexts where parental mental health is
compromised (48,49).
Notably, improvement in children's psychological outcomes has been observed when maternal
depressive symptoms are alleviated. However, this effect is not uniform across cases. In families where
mothers report histories of early trauma—such as emotional abuse, sexual abuse, or physical neglect—
traditional interventions may have limited efficacy. In these contexts, maladaptive parenting strategies,
including lower acceptance and increased psychological control, tend to persist independently of
perinatal factors (48,49).
These findings underscore the necessity of early, targeted interventions that address both the
psychological health of the parent and the relational mechanisms that mediate parent–child interaction.
Enhancing positive parenting behaviors through structured, neurobehavioral frameworks may contribute
to improved developmental trajectories in at-risk offspring (48,49).

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Intrusive Neurodysfunctional Interpersonal Relationships
The concept of alienation encompasses multiple dimensions in interpersonal dynamics and is frequently
observed in family systems. Functionally, it is characterized by bidirectional influence. One individual
may encroach upon the rights or autonomy of another through overt or covert behaviors, often driven
by affective control mechanisms, behavioral regulation, volitional imposition, and financial self-interest.
These behavioral patterns, commonly associated with parental affective neglect and authoritarianism,
manifest within a relational context where the alienator exhibits dominance and the alienated assumes a
submissive role (50).
Such intrusive interactions are often subtle and normalized within dysfunctional environments. They are
maintained by maladaptive conditioning mechanisms that serve momentary relief functions, frequently
co-occurring with other interpersonal strategies that obscure their pathological nature (50). These
behaviors typically originate during early developmental stages and reflect alterations in familial role
expectations. These may involve role inversion, hyper-authoritarianism, or deficits in caregiving due to
emotional absence or neglect (51–52).
Violations of relational boundaries and personal autonomy are consistent with maladaptive expressions
of selfishness. These are hypothesized to emerge from involuntary neuroadaptive patterns linked to
neurodevelopmental emotional dysfunctions (NDE) or ONCs. In this context, the punitive or aversive
nature of the behavior is tied to a diminished perception of relational responsibility (51–52).
Individuals exhibiting these traits may present selective deficits in affective processing, despite retaining
functional cognitive capacity in survival-oriented domains. This dissociation is reflected in reduced
flexibility of thought, impaired conceptual reasoning, and compromised social-affective functioning.
Symptomatically, such profiles may resemble traits observed in pervasive developmental conditions,
including restricted empathy, underdeveloped communication, diminished resilience, and a narrow
range of social interests (51–52).
Neurobiological evidence suggests that affiliative bonds—mediated by systems such as oxytocin—can
rapidly shift from attraction to aversion. Feldman and colleagues have demonstrated that the same neural
substrates implicated in attachment and empathy also contribute to antagonistic emotional responses.

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These systems, initially structured within the maternal-infant bond, are later adapted for broader social
functioning and group cohesion among mammals (51–52).
The concept of the affiliative brain, as defined in these studies, has been associated with vulnerabilities
to specific psychopathologies, including dissocial personality disorder, borderline personality disorder,
and subtypes with sociopathic or psychopathic features (53–54). Trajectories leading to antisocial
behavior include disorganized attachment, early life maltreatment, parental rejection, negative
attribution of others’ mental states (low mentalization), verbal deficits, impulsivity, and increased peer
affiliation with antisocial individuals (53–54).
A key factor in the emergence of these dysfunctions is the absence of sensitive parental responsiveness,
also known as mentalism. This refers to the caregiver’s inability to detect and appropriately respond to
the child’s affective and developmental cues. Intrusive parenting behaviors, which involve disregarding
the child's autonomy and imposing adult-centric priorities, reflect a disruption in the neural substrates
responsible for family synchrony (53–54).
Intrusive parental conduct is characterized by a pattern of adult-centered interactions, in which parents
assert control over tasks that the child is developmentally capable of handling independently. This
behavior suppresses autonomy, disregards the child’s emotional feedback, and often reflects an
immaturity in caregiving capacity (55). Consequences of such patterns include restricted emotional
exploration, inhibition of independent coping skills, and heightened physiological arousal in the child.
These responses interfere with emotional regulation, particularly the ability to manage fear and
perceptions of safety (55).
As a result, parental intrusiveness is considered a significant risk factor for altered neurodevelopment in
socioemotional domains. It may result in persistent neurobiological alterations and sequelae that
compromise healthy psychological maturation (56).
Secondary Neuro Determinism
Secondary Neuro Determinism (SND) refers to unconscious and involuntary stress-response
mechanisms primarily oriented toward emotional survival, often manifesting as adaptive strategies
within physical, economic, or relational contexts. These responses are frequently observed in both

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family systems and occupational environments, where behavioral patterns emerge as coping
mechanisms under chronic stress exposure (57).
In this state of neuroactivation, individuals often remain unaware of the presence of secondary emotional
gains, particularly those mediated by dysfunctional relational dynamics within neurodysfunctional
interpersonal relationships (RINs). Behaviors such as compulsive routines or dopaminergic
reinforcement cycles may arise as attempts to manage psychosocial stress. However, these behaviors
also paradoxically induce instability and reinforce maladaptive affect regulation strategies (57).
Both primary and secondary survival-based neurodeterminisms may operate concurrently, giving rise
to observable behavioral deviations such as exaggerated self-importance or maladaptive conduct in
professional contexts (58).
Coping and Addiction
Behaviors initiated as stress-coping strategies may, under certain conditions, evolve into habitual
patterns. When these behaviors serve dual functions—both alleviating aversive emotional states and
activating reward circuitry—the risk of transition into addiction increases, particularly in the presence
of genetic predispositions or highly pleasurable reinforcement cycles (59).
Addiction is clinically characterized by a neuropsychological dependency on the coping behavior,
evidenced by the inability to cease the behavior despite genuine attempts and preserved motivation to
change (59). Across different forms of addiction, individuals commonly experience deficits in judgment,
reduced predictive awareness, and impaired self-referential processing (59).
Functional neuroimaging studies have shown evidence of abrupt, automatic activations within the
amygdala, which operate as neurobiological triggers for mesolimbic reward pathways. These findings
support the hypothesis that maladaptive coping behaviors are reinforced through dysregulated
connectivity between affective and dopaminergic systems (59). Despite this evidence, no comprehensive
synthesis of mediating or moderating factors has been established to inform structured prevention or
treatment programs for substance use disorders (SUDs) (59).
Most existing studies focus on isolated moderators or mediators within individual levels of the
socioecological framework, which limits the understanding of multifactorial contributors to behavioral
pathology. A broader, integrative model could guide more conscious and effective clinical interventions

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(59). Furthermore, variations in exposure, individual response patterns, and access to services
significantly influence clinical outcomes and should be included in evaluative frameworks (59).
Although some meta-analyses have attempted to address contextual factors in relational environments,
results have not demonstrated sufficient robustness. This suggests the need for evaluators to adopt a
critical and motivated stance, regardless of clinical specialization, to facilitate meaningful behavioral
change (60).
In several cases, behaviors such as problem gambling may not conform strictly to addiction models but
instead reflect maladaptive coping strategies developed to manage unmet emotional needs. Dysregulated
coping and internet addiction are not mutually exclusive; rather, dysfunctional coping can act as a
predictor of addictive behaviors. This positions certain maladaptive behaviors as forms of psychological
self-medication (60).
The dopaminergic midbrain, particularly the substantia nigra and ventral tegmental area (SN/VTA),
plays a central role in processing reward stimuli (60). This region is also sensitive to novelty, indicating
shared mechanisms between novelty detection and reward processing. The hippocampus, which is
implicated in encoding novel experiences, exhibits anticipatory responses distinct from those of the
SN/VTA when processing expected versus unexpected novelty (61).
Memory recall is significantly enhanced for anticipated novel stimuli when compared to those that are
unexpected, suggesting differential encoding and consolidation pathways (62). These differences are
reflected in functional connectivity profiles of SN/VTA regions during reward prediction tasks (63).
Specifically, stimuli predictive of reward that are novel enhance the functional connectivity between
medial SN/VTA and mesolimbic targets, including the nucleus accumbens, hippocampus, and primary
visual cortex (64).
This connectivity likely enables the integration of novelty and reward signals, contributing to the
modulation of memory processes associated with emotionally salient or motivationally relevant events.
The medial SN/VTA may act either as a convergence point for novelty-reward interactions or as a
modulatory hub for memory encoding related to reward-predictive novelty (65).

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METHODS
The methodological design adopted in this study was descriptive and observational, with field-based
ethnographic components. This was integrated with an extensive literature review focused on behavioral
neurobiology in both human and animal models. The selected studies were primarily based on analyses
using functional magnetic resonance imaging (fMRI) and were retrieved from indexed databases such
as PubMed and Web of Science. Article inclusion followed a contextual analysis protocol to ensure
relevance and alignment with the neurobiological framework under investigation.
DISCUSSION
The application of a pragmatic research paradigm reflects a methodological alignment with the need to
address complex, real-world phenomena through empirical inquiry. This approach prioritizes functional
solutions to social and clinical problems, emphasizing translational potential. In the context of addiction
medicine, the integration of experiential data with structured observational protocols aligns with
pragmatic epistemology, which posits that meaning is derived from lived experience and is essential for
constructing applicable knowledge.
This study presents a comprehensive model within the domain of precision medicine that offers a
structured, evidence-informed framework for clinical decision-making in addiction. The methodology
enabled the identification of functional patterns and clinical categories relevant to complex, uncontrolled
behavioral disorders.
Mixed methods research continues to be adopted in healthcare sciences, where pragmatism serves not
only as a philosophical foundation but also as a practical strategy for integrating patient-oriented
perspectives and empirical rigor. The synergy between methodological pluralism and stakeholder
engagement enhances both the depth and applicability of health-related research outcomes (66–67).
CONCLUSION
Based on descriptive observational field research, a novel conceptual and clinical model was identified.
This model contributes to the understanding of addiction as a multifactorial condition and opens new
investigative pathways by offering a resolution-oriented framework for intervention.
Declaration of Conflicts of Interest
The authors declare no conflicts of interest relevant to the content or execution of this study.

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