Psychotherapy and Neuroscience

Applying Consolidation & Extinction Concepts to PTSD

When examining research findings comparing PTSD traumatic and fear conditioning research paradigms, differences can be found. Unlike healthy subjects who participate in fear conditioning studies, individuals with PTSD symptoms have functional memory disturbances and a constellation of symptoms. Fear conditioning memory in healthy individuals with an intact hippocampus is easily recallable and retrievable after the fear conditioning session. As noted earlier PTSD trauma memory lacks important personally meaningful and peripheral details and trauma narrative coherence.

On the other hand stimuli (US, CS, and conditioning contexts) associated with both fear conditioning during its initial phases and traumatic memory, before they have been sufficiently processed, are both perceived as aversive in nature and according to recent neuroscience research are both characterized by autonomic arousal. Like fear conditioning PTSD traumatic memory can be characterized as being a manifestation of emotional conditioning. Accordingly a certain time, place, objects and people become associated with an aversive, painful experience. As noted earlier often those predisposed to developing later PTSD symptoms seek avoidance to maintain a sense of well-being and equilibrium. But a traumatic experience’s enormity and overwhelming nature and avoidance may likely disrupt memory processing through disruptions in consolidation processes. This may inadvertently lock traumatic memory for an aversive experience into the brain and central nervous system. PTSD as illustrated below also shares fMRI (functional Magnetic Resonance Imaging) BOLD (blood oxygenated level dependent) signals and P.E.T. (positron emission tomography) rCBF (regional cerebral blood flow) activations with fear conditioning in its initial CS unpairing stage.

Fear conditioning according to Phelps and colleagues (2004) is characterized by three phases and regional activations as depicted in the chart below. The acquisition or pairing phase is characterized by physiological arousal and BOLD responses in the midcingulate, insula, anterior cingulate, and caudate nucleus (Buchel, Dolan, Armony, & Friston, 1999). The middle or unpairing phase is also characterized by autonomic arousal but with reductions in the anterior cingulate, insula, and caudate nucleus. The final or extinction phase is characterized by resumption of activity in the perigenual anterior cingulate, insula, caudate nucleus, etc. These findings can be summarized accordingly.

Fear Conditioning Temporal Sequencing

Neuroimaging studies of PTSD over the past decade have been elaborating on brain mechanisms underlying responses to experimentally-induced externally-generated traumatic scripts and films as well as presentation of (Stroop) words reminiscent of survivors’ earlier traumatic experiences. They have also been clarifying on the neural mechanisms underlying reactive responses to previously self-generated and tape recorded traumatic memory. Differences in methodologies among different research paradigms, neuroimaging system configurations, and data analyses probably underlie the variability in research findings. However the data suggest a few noteworthy regional activation patterns that may be linked with consolidation processes noted earlier.

Neuroimaging findings of PTSD suggest similarities with findings from fear conditioning and extinction (Phelps, Delgado, Nearing, & LeDoux, 2004). In response to traumatic reminders and cues reminiscent of personalized trauma narratives trauma survivors with PTSD symptoms, like subjects during the unpairing phase of fear conditioning and unlike asymptomatic survivors, experience significant physiological arousal evidenced in increases in diastolic blood pressure (Bremner, Staib, Kaloupek, Southwick, Soufer, & Charney, 1999a), heart rate (Shin, McNally, Kosslyn, Thompson, Rauch, et al., 1999; Shin, Orr, Carson, Rauch, Macklin, Lasko et al., 2004a), and skin conductance response (Liberzon, Taylor, Amdur, Jung, Chamberlain et al., 1999; Shin et al., 2004a). Symptomatic survivors’ autonomic arousal may emanate from amygdala-mediated engagement of subcortical structures (Liddell, Brown, Kemp, Barton, Das, Peduto, et al., 2005). Survivors with PTSD symptom expression also experience far greater rated fear, anxiety, depression, and guilt in response to traumatic reminders (Britton, Phan, Taylor, Fig, & Liberzon, 2005; Gilboa, Shalev, Laor, Lester, Louzoun, Chisin, & Bonne, 2004; Lanius, Williamson, Hopper, Densmore, Boksman, Gupta et al., 2003) when compared with the responses of asymptomatic trauma survivors.

In addition PTSD symptomatic trauma survivors responses to trauma-related cues, such as combat slides, words representing personalized trauma narratives given earlier, and fearful faces (Bremner, Narayan, Staib, Southwick, McGlashan, & Charney, 1999b; Driessen, Beblo, Mertens, Piefke, Rullkoetter, Silva-Saavedra, et al., 2004; Shin, Whalen, Pitman, Bush, Macklin, Lasko et al., 2001; Shin, Wright, Cannistraro, Wedig, McMullin et al., 2005), or listening to prerecorded personalized trauma scripts (Bremner et al., 1999b; Lanius, Williamson, Densmore, Boksman, Neufeld, Gati, & Menon, 2004) are characterized by significant increases in the posterior cingulate cortex when compared with asymptomatic trauma survivors. In response to traumatic unsafe words (Protopopescu, Pan, Tuescher, Cloitre, Goldstein et al., 2005), fearful faces (Shin et al., 2001), and listening to prerecorded personalized trauma scripts (Rauch, van der Kolk, Fisler, Alpert, Orr et al., 1996; Shin et al., 2004) subjects with PTSD symptom expression demonstrate regional activations in the amygdala, a limbic structure associated with facilitating fear expression and modulating brainstem autonomic arousal. Their neuroimaging findings also reflect concurrent decreases in the anterior medial prefrontal cortex (Talairach & Tournoux, 1988, coronal coordinate of over +55mm, horizontal coordinate from +10 to -10) (Bremner et al., 1999ab; Shin et al., 2004), more rostral and ventral regions of the perigenual anterior cingulate cortex (coronal coordinate of +35 to +50mm, horizontal coordinate of 0 to -10mm) (Britton, Phan, Taylor, Fig, & Liberzon, 2005), and anterior insula (Bremner et al., 1999a) in response to listening to prerecorded personalized trauma narratives or to viewing fearful faces reminiscent of traumatic emotion.

On the other hand in response to trauma related scripts and cues, asymptomatic trauma survivors produce neuroimaging activations in the anterior/rostral midcingulate fear region (Vogt, Berger, & Derbyshire, 2003) and dorsal perigenual anterior cingulate cortex (Bremner et al., 1999b; Lanius et al., 2004; Shin, McNally, Kosslyn, Thompson, Rauch, et al., 1999), mPFC (Bremner et al., 1999a; Driessen et al., 2004; Lanius et al., 2004), rostral ventral portions of the perigenual anterior cingulate cortex (Lanius et al., 2003, 2004; Shin et al., 1999) with concurrent decreases in the posterior cingulate cortex (Bremner et al., 1999b). Furthermore asymptomatic survivors, as cited above, experience significantly less autonomic arousal when compared with PTSD symptomatic survivors. Regional activations in the midcingulate cortex and dorsal pACC, ventral pACC, mPFC, and anterior insula coupled with lower autonomic arousal suggest successful unpairing of the internal representation of the traumatic memory (CS) with its original physiological arousal (US), suggesting engagement of extinction processes (Phelps et al., 2004). Neuroimaging activations in the rostral midcingulate cortex region also suggest the experience of the emotion of fear (Vogt, Berger, & Derbyshire, 2003).

Recent neuroscience findings (Eisengerger, Taylor, Gable, Hilmert, & Lieberman, 2007) have provided an explanation for the differential responses between symptomatic and asymptomatic populations. Elevations in salivary cortisol and neuroimaging activations in the anterior hippocampus (18,-18,12) and posterior cingulate (-2,-24,34) were associated with task-dependent acute stress responses when social support was not available or scarce. When social support was available, salivary cortisol levels significantly lower and neuroimaging activations were cited in the anterior cingulate cortex, namely the fear region of the rostral midcingulate cingulate cortex (14,30,38) (Vogt, Berger, & Derbyshire, 2003). These authors concluded that social support offered participants resiliency that supported well-being. Therefore lack of social support under duress seems to be associated with stress hormone secretion and neuroimaging activations in the anterior hippocampus and PCC. Social support seems to mitigate acute stress’s impact.

There are conflicting neuroimaging findings though. Either the asymptomatic (Lanius et al., 2003; Shin et al., 1999, 2005) or PTSD symptomatic survivors of traumatic experience (Bremner et al., 1999ab; Britton et al., 2005) can activate the midcingulate pain region (Vogt, Berger, & Derbyshire, 2003) depending upon the study. In fact both subject populations can activate the midcingulate pain region (Lanius, Williamson, Boksman, Densmore, Gupta, et al., 2002; Lanius et al., 2004; Shin et al., 2001; Vogt et al., 2003), the anterior insula (Britton et al., 2005; Lanius et al., 2004; Shin et al., 2001), and posterior cingulate-midcingulate cortices regions (Lanius et al., 2004; Shin et al., 2001) in the same study. However these discrepancies can best be reconciled by reexamining and reinterpreting coordinate citations given in these respective studies. Survivors with PTSD symptom expression tend to activate more caudal (posterior) medial and prefrontal areas; asymptomatic trauma survivors tend to engage more rostral (anterior) medial and prefrontal regions. Accordingly survivors with PTSD activate the posterior cingulate or midcingulate cortices compared with asymptomatic survivors, who tend to engage the ventral perigenual anterior cingulate cortex (Bremner et al., 1999ab, Driessen et al., 2004). In addition (Lanius et al., 2004; Shin et al., 2001) survivors with PTSD symptoms tend to activate more posterior regions of the posterior cingulate-midcingulate cortices and medial insula regions, whereas asymptomatic survivors tend to activate more anterior portions of the posterior cingulate and midcingulate as well as the ventral pACC, medial prefrontal, and anterior insular cortices regions, respectively. Apparent regional similarities of activation sites in both types of trauma survivors can be explained by examining and comparing the nature of their rostral-caudal extent.

Interestingly Shin and colleagues (2004a) found an inverse relationship between increased P.E.T. regional cerebral blood flow (rCBF) in the amygdala and activity in the perigenual anterior cingulate or medial prefrontal cortex and vice versa in response to prerecorded personalized traumatic scripts. PTSD symptom severity (evidenced in high CAPS scores-Clinician Administered Posttraumatic Stress Disorder Scale) was positively associated with amygdala activity and amygdalo-hippocampal interaction, but negatively associated with rostral perigenual anterior cingulate and medial prefrontal cortices activity. Therefore they found the severity of PTSD symptom expression (as measured by CAPS) to be inversely correlated with dorsal and ventral medial prefrontal cortex activity (Shin et al., 2005).

According to the neuroimaging findings of Lanius and colleagues (2004) there seems to be a difference in the activation sites between both symptomatic and asymptomatic trauma survivors, suggesting that both populations may process their trauma narratives differently. For instance PTSD symptomatic survivors engage the thalamus, insula, a more caudal region of the caudate nucleus, posterior cingulate and increased number of sensory regions with physiological arousal. Asymptomatic survivors engage more rostral regions of the insula, caudate, and midcingulate/perigenual anterior cingulate cortex with far less autonomic arousal. These findings suggest differences in memory processing, i.e. PTSD symptomatic survivors may be reactively processing raw sensory data that is more physiologically arousing than asymptomatic survivors, who may more intentionally retrieve and recall traumatic memory with associated emotion.

Shin and colleagues (2004b) found that increased activation of the amygdala and symptom severity was positively associated with increased hippocampal activity in PTSD survivors of trauma (Shin, Shin, Heckers, Krangel, Macklin, Orr et al., 2004b). Though some studies have found hippocampal decreases in symptomatic populations (Bremner et al., 1999b; Britton et al., 2005), other studies have referenced hippocampal decreases in asymptomatic survivors (Britton et al., 2005) and hippocampal increases in PTSD patient populations (Shin et al., 2001). Shin and colleagues (2004b) helped to clarify on these differences by focusing on methodological variability. PTSD symptom survivors tend to activate the hippocampus and amygdala during Low Recall conditions. During High Recall conditions they tend to engage sensorimotor areas of the lingual and post central gyri areas. Intensity of effort and response to temporarily reliving traumatic material was associated with involvement of the medial prefrontal cortex (e.g. -8, +54,-10). The mPFC’s involvement at this stage of processing suggests its increased role in traumatic processing. Intensely reliving fear-filled emotion, distress, and physiological arousal associated with the traumatic event may help to transfer trauma memory from the amygdala to mPFC. This process may help the memory to become part of the trauma survivor’s personally meaningful autobiographical memory. It may also help the trauma survivor to own the memory and its event sequencing. Interestingly in this study (Shin et al., 2004b) asymptomatic survivors activated the hippocampus during High Recall conditions with supportive involvement of the sensory fusiform gyrus and orbitofrontal cortex. PTSD symptomatic survivors activated the hippocampus and amygdala during the Low Recall condition; asymptomatic survivors involved the hippocampus during the High Recall condition, the nature of hippocampal activity probably determined by procured progress along the consolidation process.

Confusion in interpreting the data can also be clarified by reexamining Phelps and colleagues’ (2004) neuroimaging research of fear conditioning processes. According to their study’s findings autonomic arousal, when linked with midcingulate activity, is associated with the US-CS pairing phase. Posterior cingulate and insular cortices activity when paired with arousal is associated with the both pairing and unpairing phases. Midcingulate, insular, and posterior cingulate cortices activity coupled with a lack of autonomic arousal is associated with the extinction phase. The nature of respective regional activations with or without physiological arousal may also help to clarify on the nature and meaning of consolidation phases for traumatic memory processing. This is important for our understanding of PTSD and its associated compilation of symptoms. If PTSD is understood as being a condition that is a manifestation of a disruption in consolidation processes, i.e. getting stuck in the unpairing phase of traumatic consolidation processes, then this can help to focus therapeutic efforts. For instance neuropsychotherapeutic efforts can be directed to help in the development of methods that release traumatic memory to facilitate its concluding during consolidation processes, with the end result of physiological arousal extinction in response to traumatic reminders.

Trapping trauma memory in the unpairing phase of traumatic conditioning may result in persistent and enduring physiological arousal, neurohormone secretion, and a persistent enduring perceived sense of the trauma (van der Kolk, 1996). Containing trauma and isolating it from awareness also inhibits further processing of traumatic memory and its extinction. Developing a declared trauma narrative during the course of cognitive therapy which is imputed with personal meaning may transform implicit trauma memory to declarative memory, thus reducing abnormal amygdala-mediated brainstem arousal. This process may allow emotional and medial prefrontal cortical expression (Gilboa, Shalev, Laor, Lester, Louzoun, Chisin, & Bonne, 2004) and not vice versa, i.e. traumatic processing may force the mPFC’s functional integrity by modulating, reducing, and eventually ceasing amygdaloid involvement. These interpretations, those of Vogt and colleagues (2003), and Destrebecqz and researchers (2003, 2005) suggest that healthy “declared” emotion and explicit sequencing learning involves activity of the medial prefrontal cortex (Destrebecqz, Peigneux, Laureys, Degueldre, Del Fiore, Aerts, et al., 2003, 2005). These interpretations are also supported by Levin and colleagues (1999). These authors found that after an information processing therapy, like eye movement desensitization and repressing (EMDR) therapy, a patient diagnosed with PTSD experienced significant symptom reduction and reduced arousal in response to post-treatment traumatic imagery. This was also accompanied by post-treatment neuroimaging activations in the medial prefrontal cortex (Levin, Lazrove, & van der Kolk, 1999).


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