Trauma Responsive Recovery Routes for Alienated Children

THE DEFENSE CASCADE, TRAUMATIC DISSOCIATION AND THE SELF

A Neuroscientific Model

Frank M. Corrigan, Ulrich F. Lanius and Brenna Kaschor

The brain areas critical for the generation of affective and defensive responses are the midbrain periaqueductal gray (PAG) and the hypothalamus (Panksepp, 1998). The brain areas closely interacting with the PAG and hypothalamus for top-down regulation of their functioning are in the prefrontal cortex and anterior cingulate cortex (Price, 2006). Trauma responses involve a rapid interchange between the prefrontal cortex and the midbrain; the cortex exerts a dominant influence when the threat is distant and the midbrain assumes control when the threat is close and immediate (Mobbs et al., 2007). That is, it is much easier to engage in a logical risk/benefit analysis when not already in the clutches of a predator or perpetrator. The learning pertinent to the stimuli or situations relies on the amygdala and the hippocampus so behaviorist paradigms have focused on these structures and their prefrontal controls, ignoring the generation of the affect itself. The areas of medial prefrontal and cingulate cortices that have projections to the PAG and hypothalamus also have projections to these limbic areas to allow a rapid recruitment of learned experience in further responses, creating a network functioning to promote survival and connection.

Individuals with complex posttraumatic stress disorder (PTSD) often have learned that certain defense mechanisms do not work for them, so threat induces a rapid bypassing of active defense mechanisms that have failed them in the past and the associated affects are turned inwards. For example, an assault triggers active defensive responses, with their autonomic components manifest in changes in breathing, blood pressure, and heart rate, through the PAG and hypothalamus. Elements of the situation are learned through limbic system circuitry, especially through basolateral amygdala (McGaugh, 2004) for stimuli, and hippocampus for context. If active defensive responses are overwhelmed by a power imbalance and an inability to escape, passive defensive responses are activated and the prefrontal cortex may go further offline as dissociative neurochemicals intervene. The limbic learning then includes unresolved (i.e., incomplete) defensive responses and unresolved affects, which can be elicited by triggers activating the PAG and hypothalamus even decades after the initial assault.

The PAG has a columnar structure with a rostrocaudal differentiation of inputs that gives it the potential for a range of affective and defensive responses (Bandler & Shipley, 1994). The dorsal PAG involved in active defensive responding engages non-opioid (cannabinoid) analgesia while the ventrolateral PAG has a capacity for opioid-induced analgesia.

Thus, there is an intrinsic neurochemical capacity for both high arousal and low arousal dissociation as part of a peritraumatic response. However, for long-term clinical dissociative responses, especially in relation to structural dissociation, it may be necessary that there is some coactivation of columns, perhaps combined with neurochemical effects at higher levels of the brain. We argue for a critical role of the opioids of the ventrolateral PAG column in the long-term effects of trauma.

The Complexity of Dissociative Experiences

We seek here to offer testable hypotheses for different types of dissociative experience. Neurochemical dissociation is the peritraumatic response to overwhelming affect and is mediated by endogenous cannabinoids and endogenous opioids, amongst other mediators of stress-induced analgesia. Structural dissociation (Van der Hart, Nijenhuis & Steele, 2006) is the long-term consequence of the neurochemical dissociation from extremes of affect and obstructed defensive responding. This is hypothesized to engage “upper level” circuitry (cortex – basal ganglia – thalamus – cortex loop; Alexander, Crutcher, DeLong, 1990), although originally energized by traumatic experience overwhelming “lower level” circuitry (superior colliculi – periaqueductal gray – intralaminar thalamic nuclei – basal ganglia – superior colliculi loop; McHaffie, Stanford, Stein, Coizet, & Redgrave, 2005). Finally, we consider dissociative experiences such as derealization and depersonalization (Simeon & Abugel, 2006) which are harder to study in animal models as they rely on self-report, although some extrapolation from models of state-dependent learning (e.g., Jovasevic et al., 2015) may be justified.

We propose that these dissociative phenomena (i.e., derealization and depersonalization) represent a disturbance of the balance of activations in the cortex such that the integrity of conscious awareness is experienced as, in some way, subjectively abnormal. Derealization can include experiences of feeling alienated from one’s surroundings, from one’s friends and family, and various distortions of perception. Depersonalization can include feelings of not owning one’s body, of not being in charge of certain actions and functions of the body, and perceptual distortions related to the body. As the neuroimaging findings of these phenomena are diverse it is proposed that these groups of dissociative experiences are referred to as intracortical dissociation. It is postulated that these arise from highly charged arousal of systems ascending from the brainstem which disrupt the normally integrated functioning of widespread cortical systems.

Alexithymia may be another manifestation of intracortical dissociation even when it originates in subcortical responses to painful experiences (see below).

Emotions – Basic Affective Circuits

Darwin (1872) emphasized the continuity of emotional phenomena from non-human species to humans. Emotions are essential to survival. They allow successful coping with objects and situations that are potentially dangerous or advantageous. They promote attachment on one hand and defensive responses on the other. They are observable with scientific probes such as psychophysiological and neurophysiological measurements and endocrine assays. In mammals, these emotional responses are dependent on similar areas of the brain across species, leading Panksepp (1998) to study them in laboratory animals and thus define Basic Affective Circuits (Panksepp, 2011).

Panksepp (2011) suggests that at least seven hardwired basic affective circuits reside in the subcortical (including brainstem) regions of the mammalian brain. These are SEEKING (reflecting a generic drive, motivation and expectancy), FEAR (anxiety, dread, flight), RAGE (anger, attack, fight), LUST (sexual excitement), CARE (nurturance), PANIC/GRIEF (sadness, acute separation distress), as well as PLAY (social joy, opportunity to exercise and experiment with all emotional systems). Here the term “emotion” is used not only for an affective experience which has a clearlydefined subjective component, but also for those basic biological affective responses to environmental events regardless of whether the cortex brings it to full reportable experience or not. In keeping with Lanius, Paulsen, and Corrigan (2014), for clinical purposes we consider shame to be an eighth basic affect in humans as there is visceral pain, a defensive response (to hide), and a sympathetic nervous system activation (Corrigan & Elkin-Cleary, 2018).

Panksepp (2011) emphasizes the role of ancient, in brain evolution terms, subcortical structures like the hypothalamus and midbrain in the expression of emotion. The midbrain, or mesencephalon, is at the topmost part of the brainstem which forms the connection between brain and spinal cord and includes the PAG. That is, while frontal and limbic structures (e.g., the amygdala and the ventromedial prefrontal cortices) may trigger emotions, they are not at the core of emotion generation. Given that emotions can be expressed by decorticate animals, as well as by humans born without a cerebral cortex (Merker, 2007), it appears that the relevant subcortical structures for the expression of emotion (e.g., PAG, hypothalamus) directly signal, chemically and neurally, to other brain regions and to the body.

Thus, the midbrain or mesencephalon can respond to environmental input in a reflexive manner, expressing the entire repertoire of basic emotions. It is instinctual and fast to respond. However, this way of expressing emotion does not necessarily produce complex feelings. The response is largely hardwired – though some basic associative learning is also likely involved –and occurs quickly with sudden state changes, as required by the situation.

In evolutionary terms, the human brain has developed systems for integrating information about “where” one is in relation to “what” is in the environment (Fricchione, 2011), a distinction perhaps most usually seen in relation to the dorsal and ventral visual systems (Goodale & Milner, 2006). Basic affects can be the first response to “what” the organism is oriented towards, an interaction that has its anatomical basis in the midbrain superior colliculi, reticular formation, and PAG, with cortical structures notably absent. When the “what” is so unbelievable, so impossible to countenance, or so incongruent with the expected experience that the capacity of these structures to process the input is overwhelmed, integration with “where” systems cannot readily occur. In this way, memories of unrelated or unexpected “what” stimuli can trigger these untethered basic affects. Grounding in the “where” self, in the body-centered space, becomes more difficult when there are these highly charged intrusions.

The Midbrain Structures

The tegmentum forms the ventral, or lower, part of the midbrain that is involved in many subconscious and reflexive pathways, including the relaying of inhibitory signals to the thalamus for the prevention of unwanted body movement. It includes the rostral part of the reticular formation, several nuclei coordinating eye movements, the red nucleus (involved in motor coordination), substantia nigra (involved in reward and movement), the ventral tegmental area (VTA) (involved in motivational salience, associative learning and positively-valenced emotions, including orgasm; Holstege et al., 2003), as well as the PAG (involved in analgesia, defensive responses, reproductive behavior, maternal behavior, play and joy) (see Figure 37.1).

The colliculi, superior and inferior, two of each, also referred to as the tectum or corpora quadrigemina, form the dorsal or upper part of the midbrain. While the inferior colliculi are active in the processing of auditory input, the superficial layers of the superior colliculi receive projections from the retina and are interconnected with the intermediate and deep layers for integration of visual information with somatosensory, auditory, and even olfactory signals. The general function of the superior colliculi is to coordinate behavioral responses toward specific points in ‘ego-centric’ or body-centered space. The collicular integration of sensory input with other information from the body, in conjunction with basic affective responses mediated by the PAG, immediately ventral to the colliculi, can be the most basic sensorimotor transformation to a stimulus for promotion of the survival of the organism.

The midbrain is in a crucial position for the integration of a single response to widespread activation of the cerebral cortex, what Merker (2013) refers to as the efference cascade. The massive processing power of the cortex cascades from layer five through subcortical centers to an integrative hub in the superior colliculi where a decision can be made about gaze and attention direction. Under normal conditions, there may be more control through pathways from cortex to colliculi but, as with the prefrontal cortex – periaqueductal gray (PFC-PAG) axis, threat conditions will bias the organism towards collicular dominance for rapid and effective responding. The midbrain is also closely connected with the cerebellum and has output tracts to the spinal cord, giving it the circuitry and connectivity for the regulation of the body’s postural orienting to the space around it. Panksepp (2003) suggests that the basis of the self is in the somatic motor map between the superior colliculi and the PAG, an idea explored by Solms (2021), and interestingly the PAG is the last structure to evidence activity in the face of imminent death (Panksepp, personal communication, April 19, 2009).

Integration of Information at the Subcortical (including the Brainstem) Level

Animal defense responses that occur at the level of the PAG (Carrive, 1993) are likely elicited naturally through stimulation of the superior colliculus (e.g., Evans et al., 2018) and the inferior colliculus (e.g., Brandão, Anseloni, Pandóssio, De Araújo, & Castilho, 1999) as electrical and chemical stimulation of the PAG elicits these responses in laboratory animals.
Essentially, the superior and inferior colliculi mediate orienting and goal-directed behavior through the integration of sensory input from the environment and their proximity to the PAG allows generation of affective and defensive responses without the delay of complex cortical processing.
That is, the capacity for integration of information in the lower brain structures depends on the colliculi. It is where sensory integration still occurs under extreme threat. The midbrain is an integrative hub which receives input from the neocortex and limbic system and directs outputs to the basal ganglia, also known as the reptilian brain in the triune brain model (MacLean, 1985), resulting in organized behaviors. Therefore organisms can engage in complex, species-specific, behaviors, and have affective responses in the body, without first thinking them through.

Higher Brain Stem Structures – Alexithymia and Feelings

Alexithymia, the inability to feel, or to experience feelings in a way which can be described in words, may be attributable to a negatively valenced state of the mesolimbic and mesocortical dopamine systems (e.g., Markovic et al., 2021).

However, alexithymia is commonly associated with dissociation (e.g., Reyno, Simmons, & Kinley, 2020) so may also be a manifestation of intracortical disequilibrium. Both states then arise from a disconnection between conscious aspects of experiences and perceptions, and an alteration in the subjective awareness of both the observing self and the body.

Feelings rely on transmission of sensory information to the neocortex, especially the somatosensory cortices, anterior cingulate and insula. It is those cortical structures that mediate body awareness and different patterns of body activation represent neural correlates of feelings, thereby allowing sensory awareness to inform our awareness of feelings.

Under normal circumstances, when an organism is not under threat, sensory information gets relayed by the thalamus to the cerebral cortex, allowing different mnemonic traces to be integrated at the cortical level. Selective thalamic deafferentation of the cortex in dissociative disorders may result in difficulties in integrating thoughts, feelings and experiences into consciousness and memory, negatively impacting emotion awareness/regulation and reflective functioning.

When there is a disruption of body awareness in dissociative disorders there is an alteration of the balance of activation of the medial prefrontal and insular cortices, with altered connectivity of the posterior insula (Harricharan et al., 2019) and altered medial prefrontal inhibition of limbic and brainstem regions (Frewen & Lanius, 2015). As the insular cortex is central to the processing of interoceptive sensations and the subjective awareness of feelings (Craig, 2015), one interpretation of such findings is that in PTSD without dissociation there is increased connectivity between the insula and cortical areas involved in sensorimotor processing and environmental monitoring resulting in a hypersensitivity and hyperarousal state. With dissociative disorders, on the other hand, the insula shows increased connectivity with more posterior cortical areas involved in implicit neural processing, leading to an overdependence on past experiences as compared to conscious awareness of the present when considering responses to the environment.

Under Threat – Decreased Cortical Function

Under threat the brain can shift from dominance of cortical functioning to subcortical functioning with a hierarchical mobilization of defense responses (e.g., Mobbs et al., 2007). Associated brain areas are the extended amygdala, hypothalamus, PAG, the tectum – superior and inferior colliculi, the ventral pontine tegmentum, ventral and dorsal medulla, and spinal cord. Many of these areas are in the brainstem rather than in the limbic system. The brain decreases information processing at the cortical level that is energy-intensive, and relatively slow, in favor of subcortical, mainly brainstem, information processing that is relatively fast and energetically more efficient. It is hypothesized that sensitization to traumatic experience occurs neurochemically in these brainstem and subcortical areas and creates the capacity for triggering by stimuli and contexts. Resilience to adversity may also have its base at this deep level but be dependent on how much of the stress experienced is controllable and escapable versus uncontrollable and inescapable (Horovitz, Richter-Levin, Xu, Jing, & Richter-Levin, 2017).

BASIC Affective Circuits – Defensive Emotions

For this chapter the focus is on those basic affective circuits that are commonly activated under threat. These include SEEKING, FEAR, RAGE, and GRIEF/PANIC. In any perilous situation the dominant defense response evoked will depend on the nature of the threat and the context within which it occurs, the species-specific defense repertoire, as well as on genetic predisposition and individual differences derived from the organism’s attachment and trauma history.

SEEKING safety with a parent or with other conspecifics (animals belonging to the same species) is usually the initial response to a threat. If there is nobody available who provides rescue, perhaps through protection from the threat, FEAR or RAGE are then mobilized. Herd species, as well as anxious individuals, are more likely to initially respond with FEAR and a flight response, whereas predatory species and combative individuals are more likely to engage in RAGE or fight before fleeing. If neither fight nor flight are successful, or are not expected to be successful, the energy expenditure is wasteful, another strategy is required, and ultimately immobility ensues. The more severe and inescapable the threat, the more likely some form of immobilization will occur. This may be initially with rigidity of the body, as in tonic immobility, but as the situation becomes more dire a hypotonic or collapsed immobility will follow. Panksepp and Biven (2012) consider panic attacks to be functions of the activated GRIEF/separation distress, rather than the FEAR, system, and this explains their response to tricyclic antidepressants rather than to benzodiazepines. When the threat to life has been accompanied by an intense feeling of aloneness and abandonment, trauma survivors may have activation of both FEAR and GRIEF systems, a combination of terror and panic which can be utterly confusing.

Defense Responses are Hierarchical

Defense responses occur in a hierarchical manner and the dominance of fight or flight may reflect the position and size of the threat, whether it is physical or social, and whether there is previous sensitization through adverse experiences.

Fight and flight responses are dependent on the dorsal PAG, that is, on the lateral and dorsolateral columns (l/dlPAG).

Initially, active defense responses dominate in the defense cascade. In an infant, the initial defense response to a potential threat is an orienting response, looking away from the threat and towards a place of safety or a person who may provide safety. This may be followed by a more organized SEEKING of a primary attachment figure for protection. If a caregiver – usually a parent – is available and the caregiver’s CARE circuits can be activated, the infant’s sense of safety can be reinstated. In some cases that may involve the caregiver engaging in a fight response or RAGE directed toward the potential threat to protect the infant.

If such support is unavailable in the face of threat, a RAGE and fight response may be mobilized to ward off danger. If the threat is more than the organism may reasonably be able to overcome, or if the fight response has previously proven unsuccessful in similar situations (as in child neglect or abuse), the RAGE response is unlikely to be fully expressed.

That is, it becomes obstructed and/or internalized. The next defense response, flight, may also be unavailable to a small child if the caregiver is additionally the perpetrator and the source of the threat: there is nowhere to escape to. Again, the defensive response is obstructed while the associated affect, FEAR, is experienced and turned inwards, especially if a display of emotion increases the risk to the child. That is, the terror has no outlet in action, and the situation of threat is experienced as inescapable or uncontrollable. Despair, immobilization, and collapse may ensue. The inhibition of fight-and-flight responses because they will be ineffective, or even make the situation more dangerous, can have long-term consequences. It appears that the internal inhibition is not simply a prefrontal cortex block on defensive action which can easily be thrown off when the event has passed but rather is a deep paralysis of responding, rooted in brainstem systems, that confers increased vulnerability in later years when the required defenses are found, in moments of sudden threat, to be unavailable. This involuntary failure to defend, because of the early learning that obstructs the necessary actions, then adds to the burden of shame and guilt carried by the unfortunate victim who will not be easily convinced that it was early programming rather than a personality characteristic that was contributing to further traumatic experiences.

The enabling of the individual to clear the rapid and involuntary bypass of active defense responses, so that these are again available when required, may reduce the risk of re-traumatization.

Last Resort – Collapse, Despair, Immobilization, Death

The last defensive responses are passive rather than active and are mediated by the ventrolateral column of the PAG. The autonomic components of these responses, which give rise to low blood pressure, bradycardia, and slow breathing, are likely the result of the withdrawal of sympathetic nervous system activation (Keay & Bandler, 2001), and activation of vagal motoneurons by projections from the ventrolateral column of the PAG (vlPAG) (Bandler & Shipley, 1994). Other important changes with this state, such as opioid-induced analgesia and decreased level of arousal, are also mediated by the ventrolateral PAG through opiate receptors. For example, direct injection of ß-endorphin into the PAG produces profound catatonia and immobilization (Sakurada, Sokoloff & Jacquet, 1978), a state antithetical to interpersonal or relational connection. Generally, significant opioid-mediated vlPAG activation under threat is associated with separation, withdrawal, and immobilization, perhaps preparing the organism for impending death. This results in a decrease of cortical functioning, with affective information no longer being relayed to the cerebral cortex, resulting in truncated affective circuits.

These truncated affective circuits can occur with active (fight, flight, hide), as well as with passive (low arousal, collapsed immobility) responses. (Freeze, it was argued in Lanius et al. (2014) could be a high arousal or a low arousal state depending on the activated area of the PAG). The likely reason that affective circuits associated with active defense responses become truncated is the incomplete expression of those l/dlPAG-mediated active defense responses due to immobilization or obstructed expression that results from simultaneous vlPAG-mediated parasympathetic activation or organ-specific sympathetic withdrawal (also see below). That is, while the parasympathetic response predominates, this may be masking concurrent strong sympathetic activation. Thus, active defensive responses will not in themselves necessarily lead to structurally-dissociated states, as these can be fully expressed and recovered from with little emotional impact. Even when they are accompanied by stress-induced analgesia through endogenous cannabinoids (Riebe, Pamplona, Kamprath, & Wotja, 2012), for example, they can clear without long-term impact. People can shrug off even intensely vitriolic exchanges and terrifying flight events and move on in their lives without apparent hurt or continuing fear.

What is different with traumatic experiences, we suggest, is that there is concomitant involvement of passive defense response areas and associated endogenous opioids. Then there may be a subjective experience of being unable to fully express feelings, of numbing out, of not being fully present, of some kind of dysphoric discontinuity with the situation.

The terror, rage, panic or shame, or some combination of the affects associated with the active defense responses, have peaked at a level which necessitates neurochemical capping for physiological safety; then there is not only the high arousal dissociation but the simultaneous emergence of the passive defense responses. To put it another way, when the active defense responses are not expressed freely and effectively, but are instead truncated or obstructed, then the vlPAG with its opioid-mediated potential for dissociation is simultaneously engaged. This, we suggest, forms the basis of structural dissociation and separate ego-states. That is, ego states that hold traumatic material associated with mammalian active defensive responses driven by the l/dlPAG are conditioned to also elicit a vlPAG response, every time they are accessed, thus interfering with therapeutic efforts to integrate them at the cortical level. When the structurally dissociated self-states are sufficiently cortical that they can take executive control it may be that they have then left behind their neurochemical origins in the PAG and are working through relatively independent cortico-striato-thalamo-cortical loops.

Dorsal and Ventral PAG – Active vs Passive Defensive Responses

Lateral/Dorsolateral PAG (l/dlPAG) Activation

The active and passive coping mechanisms mediated by the PAG have characteristic autonomic nervous system (ANS) responses, but they also have skeletomotor and antinociceptive components and it is misleading to see the ANS changes as paramount and somehow independent of the controls in the prefrontal cortex and PAG. For example, l/dlPAG responses include non-opioid (likely cannabinoid) analgesia, increased blood flow to specific muscle groups, depending on whether the preparedness is for fight or flight, as well as hypertension and tachycardia. The vlPAG has projections to the rostroventrolateral medulla (RVLM) for inhibition of sympathoexcitatory neurons, which can block an increase in blood pressure and pulse rate (Longhurst, 2011). Hypothalamic regions, such as the paraventricular nucleus, interact with the prefrontal cortex and the PAG in the control of ANS changes (Dampney, 2011) but the hypothalamus may be functioning independently of the PAG in some pressor responses (catecholamine-induced increases in blood pressure) when the stress is psychological rather than physical (Carrive, 2011). For this chapter we consider the lateral and dorsolateral PAG columns as functionally together although the dorsolateral column receives inputs from highly evolved areas of the medial prefrontal cortex in humans and may have a specific role in emotional responses to cognitive processes (Dampney, 2018).

While common notions of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activation suggest that autonomic balance is reciprocal in nature, they ignore the case of psychological stressors that, if sufficiently large, can result in coactivation of the sympathetic and parasympathetic systems (Berntson, Norman, Hawkley, & Cacioppo, 2008). Parasympathetic dominance is generally considered desirable for health outcomes but this may not be the case when high levels of sympathetic coactivation occur. Indeed, massive and simultaneous activation of both sympathetic and parasympathetic activation that can become antagonistic, a so-called “autonomic conflict,” is a potentially lethal phenomenon. Simultaneous signals for tachycardia and bradycardia can result in lethal arrhythmias (e.g., Shattock & Tipton, 2012).

The co-activation of sympathetic and parasympathetic systems may in part reflect the activation and readying of both active defense responses, like fight and flight, and the passive defense response of immobilization, where immobilization interferes with the discharge and completion of the active defense response. Further, it is likely that stress-related opioid release not only truncates the active defensive responses but also triggers high levels of sympathetic and parasympathetic coactivation by simultaneously stimulating both noradrenaline/norepinephrine and acetylcholine (Bouaziz, Tong, Yoon, Hood, & Eisenach, 1996). Tonic immobility is the defensive response state most clearly demonstrated to involve dorsal and ventral PAG coactivation: in this state activation of both SNS and PNS is likely. A combination of entrapment and FEAR sufficient to elicit tonic immobility in animals has been demonstrated to involve the superior colliculus and a coactivation of lateral and ventrolateral PAG columns (Vieira, Menescal-de-Oliveira, & Leite-Panissi, 2011).

Kreibig (2010) emphasized that each organ is innervated by distinct sympathetic and parasympathetic pathways such that individual circuits can be engaged. The direct SNS innervation can activate organs precisely and selectively, separate from the adrenomedullary hormonal system which makes metabolic adjustments, although the two parts may work together when there is an emergency.

As we have seen above, active defensive responses initiated by the l/dlPAG and hypothalamus are generally mobilizing and require energy expenditure mediated by the SNS. The l/dlPAG initiates a RAGE/Fight or FEAR/Flight response that is commonly characterized by a release of adrenaline and noradrenaline associated with increased heart rate, increased blood pressure and cardiac output. Simultaneously, there is skeletal muscle vasodilation with concomitant cutaneous and gastrointestinal vasoconstriction, but this is region-specific depending on the defensive needs of the situation. In addition, pupillary dilation and bronchial dilation may occur, as well as hairs standing on end (piloerection).

The overall effect is to prepare the organism for response to imminent danger. Sympathetic activation essentially has a mobilizing and accelerative function.

Ventrolateral PAG (vlPAG) Activation

In contrast to sympathetic activation, parasympathetic activation has a decelerative or braking impact on the body’s functioning. The parasympathetic response is associated with decreased heart rate and blood pressure, bronchial constriction, and decreased respiration. In addition, constriction of pupils, increased production of saliva and mucus, promotion of digestion, and increased urine secretion may occur. A sense of safety allows the relatively risky – due to heightened immobility and a concomitant inability for the organism to mobilize active defense responses – engagement in excretory functions. During massive stress-related parasympathetic activation, a loss of cortical control over excretory functions can also occur, a phenomenon that may confer a survival advantage in that it may induce disgust in the predator and thus decreased interest in the food value of the victim. The pontine micturition center is largely under the control of the PAG, which mediates the influence of the anterior cingulate and insular cortices (Drake et al., 2010).

Parasympathetic activation is generally considered a positive goal state, being responsible for stimulation of “rest-and-digest” or “feed and breed” responses (e.g., McCorry, 2007). However, parasympathetic activation is likely more complex. In the vlPAG it may depend on whether the hormonal environment is suffused with oxytocin or stress hormones such as corticotropin-releasing factor (CRF). That is, in both instances the organism may exhibit a withdrawal of sympathetic activation. Yet, in one case, the organism may be calm while, in the other, it may have disconnected and be detached from its outer world. The hormonal environment of the vlPAG is likely to be the determining factor, along with the nature of the input from the prefrontal cortex.

Activation of vlPAG in an extreme threat condition acts to decrease metabolic activity and heart rate during hiding and death feigning. When the animal can’t fight or flee, when the terror is intense, and the end of life is imminent, vlPAG activation typically ensues. The sudden withdrawal of SNS activation via the rostroventrolateral medulla is accompanied by activation of dorsal vagal motoneurons via the same pathway. This hard brake ultimately results in immobilization and freezing and a shutdown of the nervous system, in part through an endogenous opioid-mediated dissociative or numbing response, perhaps surrendering and preparing for death. We hypothesize that it is this type of vlPAG activation that accounts for the extensive duration of the “void” states of detachment. The vlPAG has a high density of opioid receptors and its analgesia is opioid-mediated. It is activated by physical restraint, as well as by electric, opioidergic and cholinergic stimulation. It is likely the involvement of the opioid systems of the vlPAG that ensures that obstructed l/dlPAG active defense can be transmuted into differentiated self-states.

The vlPAG-mediated collapsed immobility must be distinguished from the state of tonic immobility commonly encountered in survivors of interpersonal trauma. Tonic immobility is a state of speechless rigidity and terror, which can be seen in animals who are subjected to helpless entrapment. The animal studies show concomitant activation of lPAG and vlPAG (Vieira et al., 2011); that is, concurrent involvement of areas for active and passive defensive responses and their motor and ANS accompaniments. Tonic immobility is sometimes considered to be a passive response, because of the immobility, and sometimes an active response, because of the rigidity of the muscles and the fluctuations in the ANS.

Opioidergic simulation of the vlPAG increases immobilization, an effect that can be reversed with the opioid antagonist naloxone (Monassi, Leite-Panissi, & Menescal-de-Oliveira, 1999). That is, activation of the vlPAG results in immobility, loss of tension of the muscles, bradycardia and reduced respirations. It is no surprise that altered PAG function and connectivity has been reported to be associated with prolonged stress (Della Valle, Mohammadmirzaei, & Knox, 2019), as well as PTSD (Brandão & Lovick, 2019) and its dissociative subtype (Harricharan et al., 2016). Also, immobilization may be at the juncture between traumatic stress and altered immune system functioning as immobilization resulting from acute restraint induces opioid-mediated immune system effects, particularly in the ventromedial hypothalamus and the PAG (Farabollini et al., 1993).

Adjacent to the vlPAG in the midbrain is the dorsal raphe nucleus (DRN), which is the source of ascending serotoninergic responses to stressors such as inescapable tail shock in laboratory animals. If the animals are then subjected to another stress, a cold swim stress, cytokine changes indicative of a pro-inflammatory response are seen (Donner et al., 2018). A difference between the relative weighting of ascending projections from the DRN to the cortex and to the amygdala may account for some of the impact of stress and trauma on mood, in addition to inflammatory responses, and it has been proposed that therapeutic interventions in this circuitry may be beneficial for PTSD (Alexander & Vasefi, 2021). In dissociative disorders there are frequently impairments of physical health that appear to be the result of an accumulation of stresses. Given that disorganized attachment predisposes to the development of dissociative disorders (see Schimmenti, Chapter 10, this volume) it is of interest that maternal separation of a rat pup is used in animal models of irritable bowel syndrome (Larauche, Mulak, & Tache, 2012). The critical brain areas for the effects of trauma mediated by CRF and pro-inflammatory cytokines will be in PAG (Borelli et al., 2013) and hypothalamus (Jiang, Rajamanickam & Justice, 2019) in addition to DRN (e.g. Donner et al., 2018) and limbic structures.

The l/dlPAG are involved with positive affect systems such as CARE/Nurturing and it is often unrecognized that positive affects engage the SNS through l/dlPAG. The vlPAG is engaged for states of calmness and connection when its environment is imbued with oxytocin and opioids in a safe and secure, rather than life-threatening, situation. Essentially, the quiescence of the vlPAG activation appears to have been modified in a way that immobilization can occur in the absence of fear to serve the intimate needs of mammals that involve parturition, nursing, and the establishment of social bonds (Carter, 1998; Insel & Young, 2001). The PAG is at the core of the affective connection and attachment that involves the SEEKING and CARE circuits. These require the capacity to switch readily between the SNS activation of dorsal PAG and the soothing and calming emotional regulation of the vlPAG which is, at least in part, oxytocin-mediated.

Peritraumatic Dissociation, Structural Dissociation, Intracortical Dissociation

From the foundations and mechanisms outlined above, which are derived from clinical observation combined with animal and human neuroscience findings, we argue that peritraumatic dissociation reflects an acute neurochemical capping of the physiological components of an affective and defensive response. The neurochemical modulation is acutely necessary not only for analgesia but for the prevention of fatal states of activation. However, that essential regulation can establish circuitry that is a substrate for relatively independent activation of physiological responses to threat stimuli. “Triggers” become detached from the context in which they first occurred and stimulate emotional responses disproportionate to the environmental event. This circuitry is initially at the lower level of midbrain – thalamus –basal ganglia – midbrain looping (as described by McHaffie et al., 2005) but acquires a different form of agency, and autobiographical details, when it additionally engages upper-level circuitry (as described in Alexander et al., 1990). The varieties of presentations of structural dissociation then depend on the relative degree of connection or disconnection between upper and lower levels.

Derealization and depersonalization are hypothesized to be forms of intracortical dissociation in which a disturbance of integrated functioning of the cortex leads to subjective states in which the coherent sense of self in relation to the body and the environment is disrupted. Traumatic activation of ascending noradrenergic systems from the locus coeruleus is hypothesized to be one such mechanism but cholinergic, dopaminergic, and serotoninergic projections may similarly be involved.

We have considered the PAG to be the core structure in affective and defensive responding and therefore key to the development of post-traumatic and dissociative disorders, in their various clinical manifestations. We have highlighted the theory that the long-term effects are not mediated entirely by whether neurochemical dissociation occurs at the time of the traumatic experience but also by whether the combination of active and passive defense responses has specific long-term neurochemical and structural consequences. These consequences include the truncation of resolution of the affective and defensive aspects of traumatic experiences and this leads to the detachment of upper-level circuits through the basal ganglia, thalamus, and cortex for the expression of the different parts of the self. We also offer for testing the hypothesis that intracortical dissociation of the type which presents as the subjective experience of derealization or depersonalization can be the result of overwhelming activation of ascending neurotransmitter systems from the brainstem which initially bypass the affective and defensive aspects of the traumatic experience. The alarm circuitry involving the noradrenergic locus coeruleus, rather than the PAG, is critical in this arousal (Corrigan & Christie-Sands, 2020), but cholinergic, serotoninergic, and dopaminergic systems are also involved in response to adversity (see below).

An animal model of dissociation (Vesuna et al., 2020) which focused on the retrosplenial cortex observed an enhancement of thalamic connectivity with posterior cortical areas and a reduction of connectivity with frontal cortical areas.

It is, we expect, that kind of intracortical disturbance or altered connectivity that would be experienced by the patient as derealization or depersonalization. Shocking disconnection and horrifying misattunements experienced by an infant in a disorganized attachment may activate this pathway momentarily before there is any affective or defensive response (Corrigan & Christie-Sands, 2020).

Attachment – Setting the Stage

Severe dissociative disorders arise from disorganized attachment in infancy (Lyons-Ruth, Dutra, Schuder, & Bianchi, 2006) being followed, or accompanied, by neglect and abuse (Ross, 1997). This means that theories on the neurobiological origins of dissociative disorders require a focus not only on neurochemical responses to threat but also on disorganized attachment. It will be readily seen how erratic responses from the caregiver lead to the activation of basic affects such as fear, rage, grief, and shame – and we have seen how PAG activation can engage neurochemical mediators of dissociation – but what of the urge to attach itself? Are there subcortical systems for connection underlying the advanced attachment capabilities of the prefrontal cortices?

The first point of response to a sensory stimulus is in the superior colliculi. The infant’s midbrain will be activated by mother’s face, voice, and touch. Through the midbrain reticular formation, an area of the tegmentum which contains various nuclei, this connection will have an impact on ascending systems from the brainstem. For example, an unsatisfactory interaction will activate the mesolimbic cholinergic system and manifest as an anxious state with distress vocalizations (Brudzynski, 2021). In contrast, an engaging interaction will result in a motivated movement through dopamine systems ascending from the midbrain. Watt and Panksepp (2009), in a model of depression, have emphasized the importance of oxytocin and opioids in blocking the effects of stress in the context of secure attachments and much of their impact on emotional state may be mediated by the dopamine pathways from the midbrain to the limbic system (mesolimbic) and from the midbrain to the cortex (mesocortical). The basic affective response to a stimulus in the mother-infant interaction comes from an activation of the PAG via the superior colliculi.

Attachment and Endogenous Opiates

Human attachment is at least in part mediated by the endogenous opiate system. Brain circuits involved in the maintenance of affiliative behavior are those most richly endowed with opioid receptors (Kling & Steklis, 1976) and, in general, the endogenous opioid system is activated by positive social interactions. Opioids result in feelings of comfort and alleviate emotional distress arising from loss and social isolation, as well as attenuating the reaction to social separation by powerfully inhibiting separation distress (Panksepp, 1998; Panksepp & Biven, 2012). Bonding to the mother and mother preference particularly appears to be mediated by endogenous opioids (Shayit, Nowak, Keller, & Weller, 2003).

It is important clinically to appreciate that the response to opioids is non-linear: a low basal level of opioids increases, whereas a high level of opioids decreases, motivation to seek out social contact.

Attachment, Stress, and Opioidergic Activation

Stresses like helplessness and terror cause massive opioid activation that coincides with immobilization. Further, the stress associated with immobilization ‘per se’ is a stressor that induces endogenous opioid activation. We have seen that the vlPAG is particularly important in mediating this. Further, such immobilization does not necessarily need to be physical: it can be social. Bandura, Cioffi, Taylor, and Brouillard (1988) gave an unsolvable math task to student probands and found decreased pain perception that could be reversed by an opioid antagonist (naltrexone), consistent with significant opioid activation. In contrast to physical injury, which activates the lateral PAG column, social or psychological stressors tend to activate the dorsolateral column, in addition to the ventrolateral column (Keay & Bandler, 2001).

Oxytocin and opioids combine in the vlPAG to modulate the pain (Yang et al., 2011).

Opioid Effects – Sensory and Affective

Opioids have both sensory and affective effects. Opioids decrease affective aspects of pain not only through release in the PAG but also in the parahippocampal gyrus, amygdala, and anterior insula. Sensory aspects of pain are less affected – with a linear dose relationship evident in primary and secondary somatosensory cortices and the posterior insular cortex (Oertel et al., 2008). Given the regions involved it is likely that opioid activation accounts at least in part for the decreased experience of emotion encountered in alexithymia, as well as having an impact on a person’s sense of self in relation to their body. Disturbances of insular cortex functioning may be involved in some of the dissociation states described collectively as intracortical; altered functional connectivity of the insula has been reported in PTSD (Harricharan et al., 2019).

Interoceptive awareness arising from the anterior insular cortex (Craig, 2015) may be enhanced, at least in certain respects, in some patients with dissociative disorders whereas others have an impairment of this function and have difficulty observing visceral responses. We do not know of any work linking the degree of interoceptive awareness, enhanced, normal or blunted, with behavioral manifestations indicative of emotional dysregulation in dissociative, and other, disorders. For example, there is an association between the withdrawing behavior of mothers towards their infants and self-harm behavior when those infants had grown to be 19 years old (Lyons-Ruth, Bureau, Holmes, Easterbrook, & Brooks, 2013), but correlations with interoceptive awareness and insular connectivity in this group have not been studied. Will there be times in which the emotional pain is so great that some form of self-harm is used as a regulator of it? Will there be other pain conditions manifesting in later life which have their origins in such adversity?

Emotion Dysregulation in PTSD and Dissociative Disorders

The early traumatic experiences encountered in disorganized attachments engender dissociative responses and defenses. The enhanced medial prefrontal cortex activity seen in the dissociative subtype of PTSD, relative to the re-experiencing subtype (Frewen & Lanius, 2015; See Schiavone & R. Lanius, Chapter 39, this volume), may be an adaptive strategy that suppresses the distress in such a way that the child can continue to function apparently normally. That is, the short-term neurochemical defense is replaced by a longer-term functional adaptation with the same goal of reducing the experience of distress. This has the side-effect of a continuing inability to feel and, perhaps, an inability to read emotion, which impairs relationships and inhibits the development of other pathways to emotion regulation. There are then intrusions of affects that are not understood because they are appearing out of context, without clear precipitants, and for which there are no learned methods of coping that are not dissociative. As the person with the dissociative disorder gets older, there is often a breakthrough of memory and associated affect which can be experienced as overwhelming. There is then a rapid switching between the over-control and under-control of the prefrontal cortex with a sense of loss of control of the unpleasant affects. In dissociative PTSD it is found that even at rest there can be intrusions from the PAG (Harricharan et al., 2016), which have an impact on self-agency and self-worth. It is not clear why some patients with complex trauma histories have greater problems with emotional dysregulation while others are more likely to have dissociative disorders. It may be linked to a propensity for hypnotizability (Dell, 2019; See Dell, Chapter 14, this volume), but the biological underpinnings of this are not clear.

Attachment – Seeking for Food

We have seen that the mesolimbic dopamine system is essential for the motivation to attach. Another ascending dopamine system, the nigrostriatal system, is necessary for movement behaviors that work in synchrony with the drive for attachment behaviors (Feldman, 2017) but also for seeking food that is essential for survival. Until this motor system is fully functioning to allow exploratory behavior such as foraging, the nutritional needs of the infant must be met by the parents and primary caregivers. Separation from this primary source of nutrition would be life-threatening so this readily stimulates distress states and the associated vocalizations, for which the mesolimbic cholinergic system is important (Brudzynski, 2021). If the distress vocalizations of this protest state are unmet by a caregiver and an adequate food supply is not forthcoming, despair, in the sense of loss of drive and loss of hope, will develop and the balance of oxytocin and opioids in the vlPAG will shift towards analgesia. With continued absence of adequate caregiving, the vlPAG more fully converts to negative valence – as does the mesolimbic dopamine system (Watt & Panksepp, 2009).

These changes promote energy conservation to facilitate survival for as long as possible while the young child becomes increasingly helpless and hopeless. The changes in endogenous opioids are now serving to prepare for a painless death. If the caregiver returns and meets the need through feeding with milk, nutrients such as caseomorphine activate opioid receptors and infant calling rates are much reduced. The profoundly relational attention of the caregiver stimulates the release of oxytocin which modulates not only the potentially addictive nature of caseomorphin but also other endogenous opioids.

Neglect in infancy must have many and profound effects on the systems ascending from the brainstem and on their neurochemical environments. Some of these effects are mediated by endogenous opioids. For example, studies with rodents suggest that lack of caregiving during the first few weeks of life decreases the number of opioid receptors in the cingulate gyrus and thalamus (Bonnet, Hiller & Simon, 1976). With fewer receptors to bind available opioids, the capacity of the opioid system to modulate neural functioning likely becomes severely compromised. That is, fewer receptors exist to bind released opioids secondary to stress, and they are likely to become saturated more quickly, thus resulting in more pronounced vlPAG activation, including dissociation, in response to even a relatively minor release of endogenous opioids. The ensuing decreased modulation will increase the likelihood of a sudden or abrupt shutting down of the nervous system. The subgenual anterior cingulate cortex (BA25) is one of the medial prefrontal network areas that has projections to the ventrolateral PAG (Price, 2006) so is likely to be the key prefrontal area for this effect.

In short, with a decreased number of receptors available to bind released opioids, the brain is more sensitive to the release of opioids with the effect of decreased modulation. Not only may the limited number of receptors account for a decreased capacity to experience pleasure, it likely accounts for the increased likelihood of dissociative shutdown in the face of stress in individuals that have adverse attachment histories.

Child Rearing – Pain, Isolation, Social Defeat

We argue that peritraumatic dissociation reflects the consequences of the brain’s inability to integrate information from the outside world, filtered through the colliculi, with the internal concepts of the self and its relationship to the world. The resulting fragmentation requires compartmentalization for continued adaptive functioning in the world.

The caring and reassuring presence of an attuned parent or support figure in the peritraumatic period will help to regulate the distress such that the traumatic event can be processed and integrated into the episodic narrative of the person’s life. The abnormal neurochemical environment that has potentiated the experience of dissociation can be normalized, and the dimensions of time, thought, body and emotion can return to the present (Frewen & Lanius, 2015; See Frewen, Wong & R. Lanius, Chapter 19, this volume).

Child rearing is crucial in determining the likelihood of dissociating under stress as it provides a template for which defense response is dominant in a person’s repertoire. Relational disruption, and the attendant pain, may be followed by fear, rage, grief or shame, all affects dependent on the dorsal PAG. However, stressors such as threat of abandonment, withdrawal of love, lack of connection, and being overpowered physically or emotionally, will also trigger excessive opioid activation in the vlPAG. This in turn makes immobilization more likely, acting as a biological leash that decreases the need for supervision/engagement on the part of a parent and contributes to dissociative responses. Interfering with exploratory behavior – as is frequently the case in overly anxious or excessively disciplinarian parents –has similar effects to neglect, presumably because the impaired opportunities for positive affect are compounded by negative affects in response to feelings of entrapment or threat. Decreased PLAY, CARE, LUST, SEEKING and a lack of exercise of basic affective circuits likely results in a lack of positive emotions and decreased opioid receptors.

Dissociative Disorders – Implications for Therapeutic Interventions

Endogenous opioids are dominant in the passive defense response, whereas endogenous cannabinoids are more involved in the active defense responses. When one starts blocking the opioid system with an opioid antagonist like naltrexone or naloxone, one starts biasing the nervous system away from a passive defense response towards an active defense response.

The attendant opioid withdrawal can have different effects depending on the social context, precipitating either vasopressin release when threat is detected or oxytocin release when there is a sense of safety. Vasopressin is associated with either FEAR, flight, and avoidance or alternatively RAGE, fight and attack. Oxytocin, on the other hand, is associated with an activation of SEEKING and CARE circuitry. Opioid blockade facilitates cognitive processing and cortico-thalamocortical processing of visual stimuli (Lensing et al., 1995) and naltrexone has been found to result in alpha-blocking that is associated with increased exteroceptive awareness (i.e., grounding). We have seen that the administration of opioid antagonists to the vlPAG decreases immobilization and this explains the effects of naltrexone clinically.

For example, beneficial treatment effects have been reported with low-dose naltrexone in patients with dissociative disorders (Pape & Woller, 2015; Pape, 2020) and Complex PTSD (Lanius & Forster, 2020). Among the reported positive effects were a clearer perception of both the environment and the person’s awareness of their inner life; an increased ability to assess and cope with reality; an increased body awareness; better affect tolerance; and improved self-regulation.

While opioid antagonists are potentially problematic, especially when used as a stand-alone treatment for dissociative disorders, their reported benefits have theoretical implications for the pathophysiology of these conditions (Lanius & Corrigan, 2014). Indeed, animal studies suggest that chronic naltrexone administration produces receptor upregulation and increased opioid receptor density (Lesscher, Bailey, Burbach, Van Ree, Kitchen, & Gerrits, 2003), thus potentially reversing some of the neurobiological effects of neglect described by Bonnet et al. (1976). Understanding how the nonlinear effects of opioids interact with an individual’s genetic and epigenetic make-up will be key to unlocking the therapeutic potential of the opioid system in trauma and dissociation. Clinical observations suggest that the administration of opioid antagonists may sensitize the cannabinoid system. That is, cannabis users commonly report requiring lower doses of cannabinoids to achieve the same effect, whether it is therapeutic or recreational, an effect that is, at least in part, mediated by the ventrolateral PAG (Wilson-Poe, Pocius, Herschbach, & Morgan, 2013).

Other implications are that our understanding supports the notion of proceeding in a hierarchical fashion by addressing SEEKING and CARE emotions first. That is, the therapist will focus the initial interventions on relational safety. Then therapy can proceed to the regulation of active defense responses like FEAR and RAGE. Only once the active defense responses are processed with mindfulness does the sympathetic loading disappear, but with this processing then comes a reduction of the sympathetic withdrawal of the shutdown states, at which time lower arousal responses make therapeutic work more successful. Further the role of the lower brain structures in sensory and motor functions supports interventions that focus on basic orienting responses and sensorimotor processing, as well as approaches that are guided by the neuroanatomy of the brainstem such as Deep Brain Reorienting (DBR) (Corrigan & Christie-Sands, 2020).

Summary

We argue that the neuroscientific exploration of complex trauma disorders and dissociative disorders will be most effective when based in an understanding of the brain mechanisms for attachment seeking and threat responding. No brain area works in isolation – all are parts of wider systems – but attention to brainstem areas for responding to threat and seeking the connection that precedes attachment offers hypotheses on the origins of disrupted systems. For attachment, we focus on sensorimotor transformation of stimuli related to interpersonal connection in the midbrain superior colliculi and PAG and on the altered drive and motivation to seek attachment that arises in the mesolimbic dopamine system. For threat, we focus on the sensorimotor transformations that occur in the midbrain superior colliculi and PAG and on the resulting affects, positive and negative, and defensive responses. We differentiate active and passive defensive responses according to the activation of the PAG columns and consider the neurochemicals involved in the associated analgesia. Stress-induced analgesia involving endogenous opioids is not just a component of peritraumatic dissociation, but a likely contributor to longer-term structural dissociation. Finally, we propose that trauma-evoked activations of ascending brainstem systems disrupt the continuity of the integrated functions of the neocortex and can lead to the subjective experiences of dereal.

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