A reciprocal inhibition model of alternations between under-/overemotional modulatory states in patients with PTSD

Abstract

Patients with posttraumatic stress disorder (PTSD) appear to manifest two opposing tendencies in their attentional biases and symptoms. However, whether common neural mechanisms account for their opposing attentional biases and symptoms remains unknown. We here propose a model in which reciprocal inhibition between the amygdala and ventromedial prefrontal cortex (vmPFC) predicts synchronized alternations between emotional under-and overmodulatory states at the neural, behavioral, and symptom levels within the same patients. This reciprocal inhibition model predicts that when the amygdala is dominant, patients enter an emotional undermodulatory state where they show attentional bias toward threat and manifest re-experiencing symptoms. In contrast, when the vmPFC is dominant, patients are predicted to enter an emotional overmodulatory state where they show attentional bias away from threat and avoidance symptoms. To test the model, we performed a behavioral meta-analysis (total N = 491), analyses of own behavioral study (N = 20), and a neuroimaging metaanalysis (total N = 316). Supporting the model, we found the distributions of behavioral attentional measurements to be bimodal, suggesting alternations between the states within patients. Moreover, attentional bias toward threat was related to re-experiencing symptoms, whereas attentional bias away from threat was related with avoidance symptoms. We also found that the increase and decrease of activity in the left amygdala activity was related with re-experiencing and avoidance symptoms, respectively. Our model may help elucidate the neural mechanisms differentiating nondissociative and dissociative subtypes of PTSD, which usually show differential emotional modulatory levels. It may thus provide a new venue for therapies targeting each subtype.

Neural responses to emotional stimuli across the dissociative spectrum: Common and specific mechanisms

“…These advantages might address limitations previously discussed concerning the clarification of key patterns of neural activity underlying the whole DS 56 . Moreover, this methodological approach might sustain extensions of existing neurobiological models of dissociative‐related disorders 28,29 above and beyond the PTSD.…”

“…Furthermore, provisional considerations suggested that compartmentalization should be viewed as the key mechanism underlying somatoform dissociative symptoms among individuals with CD and SDs 12 . PTSD shows a constellation of dissociative phenomena, including positive dissociative symptoms (e.g., reexperiencing) and negative dissociative symptoms (e.g., emotional numbing) 28,29 . Referring to PTSD linked to repeated interpersonal traumatic experiences (PTSD‐IT) and DDs (e.g., dissociative identity disorder [DID]), clinical literature posits at the base of these conditions a key role of a “structural dissociation.” 30,31 This kind of structural dissociation is sustained by a complex system of dissociative symptoms including negative psychoform dissociative symptoms (e.g., amnesia and numbing), negative somatoform dissociative symptoms (e.g., anesthesia and sensory loss), positive psychoform dissociative symptoms (e.g., traumatic memories and nightmares), and positive somatoform dissociative symptoms (intrusions of sensorimotor aspects of traumatic reexperiences and pain) 31,32 …”

Brain network dynamics fingerprints are resilient to data heterogeneity

“…While the aforementioned studies on functional connectivity have significantly increased our understanding of the brain as a system that obeys network-wide principles, they are mainly agnostic to temporal dynamics within the scanning sessions. This may prevent the level of precision that could at times be the most clinically relevant [45]. Differently from [16,20], where time seemed to play a negligible effect, we found that different scanning days greatly affected our estimation of brain network dynamics.…”

“…In other words, a one-size-fitsall approach could be employed to build the model in its general terms, consequently allowing us to move to a personalized course of action by evaluating the model at the individual level. For instance, closed-loop fMRI neurofeedback [50,51] could significantly benefit from these models, which will allow for a more holistic approach to the dynamical properties of mental and cognitive processes, particularly from a clinical perspective [37,45,52,53].…”

Towards Assessing Subcortical “Deep Brain” Biomarkers of PTSD with Functional Near-Infrared Spectroscopy

“…The negative weights within the left dlPFC highlight the reciprocal relation between this region and activity in the limbic system (i.e., amygdala and hippocampus). In this context, it is worth noting that there is debate about whether aberrant functional connectivity in PTSD reflects alterations in top-down regulation of the limbic system (e.g., amygdala) via the prefrontal cortex [34][35][36][37][38][39] or altered reciprocal regulation between these regions [108,109]. It is unclear whether the temporal resolution of fMRI (e.g., 1-2 seconds) is suitable for studying these dynamic and directional connections.…”