Intrusive Experiences In Post-Traumatic Stress Disorder: Treatment Response Induces Changes In The Effective Connectivity of The Anterior Insula

Abstract

Introduction: One of the core features of posttraumatic stress disorder (PTSD) is reexperiencing the trauma. Th anterior insula (AI) was proposed to play a crucial role in these intrusive experiences. However, the dynamic function of the AI in reexperiencing trauma, as well as its putative modulation by effective therapy, still need to be specified. Methods: Thirty PTSD patients were enrolled and exposed to chemo-facilitated traumatic memory reactivation therapy. Resting-state fMRI scans were acquired before and after treatment. To explore AI directed influences over the rest of the brain, we referred to a mixed-model using pre/post Granger causality analysis seeded on the AI as a within-subject factor and treatment response as a between-subject factor. To further identify correlates of reexperiencing trauma, we investigated how intrusive severity affected : (i) causality maps and (ii) the spatial stability of other intrinsic brain networks. Results: We observed dynamic changes in AI effective connectivity in PTSD patients. Many within- and between-network causal paths were found to be less influenced by the AI after effective therapy. Insular influences were found positively correlated with flashback severity, while reexperiencing was linked with a stronger default mode network (DMN) and more unstable central executive network (CEN) connectivity. Discussion: We showed that directed changes in AI signalling to the DMN and CEN at rest may underlie the degree of intrusive symptoms in PTSD. A positive response to treatment further induced changes in network-to-network anticorrelated patterns. Such findings may guide targeted neuromodulation strategies in PTSD patients not suitably improved by conventional treatment.

Neuroimaging Evidence for Clinical Hypnosis and its Relationship with the Triple Network Model of Psychopathology: An fMRI Perspective

“…DMN dysfunction marked by altered withinnetwork connectivity is consistently found in schizophrenia (Krishnadas et al, 2014), major depressive disorder (Manoliu et al, in review), and dissociative identity disorder (Lebois et al, 2022). In particular, hyperconnectivity of the posterior DMN relates to re-experiencing symptoms in PTSD (Leroy et al, 2021) and dissociative symptoms in dissociative identity disorder involving perceptual and memory disturbances (Lebois et al, 2022). This matches the DMN's functions in episodic memory and visual imagery.…”

“…Across disorders, a consistent finding is insular dysfunction marked by reduced connectivity within the SN. This is evident in schizophrenia during acute psychosis and remission (Manoliu et al, 2013b), major depressive disorder (Manoliu et al, in review), and post-traumatic stress disorder (PTSD) (Leroy et al, 2021). Aberrant SN connectivity also correlates dimensionally with symptom severity, linking to positive symptoms in schizophrenia (Krishnadas et al, 2014) and depressive symptoms in major depressive disorder (Manoliu et al, in review).…”

“…Prior neuroimaging studies have associated hypnotizability with activation patterns in regions within the SN, DMN, CEN (Hoeft et al, 2012;Jiang et al, 2017;Cojan et al, 2015). Abnormalities within these same triple networks have also been independently linked to symptoms across a range of psychiatric disorders (Krishnadas et al, 2014;Leroy et al, 2021;Lebois et al, 2022). However, few studies have linked the results of fMRI studies of hypnosis and modulation of connectivity throught the lens of the triple network model despite their supposed mutual relevance.…”

“…Understanding dynamic connectivity within and between the SN, DMN and CEN during hypnosis could provide key insights into the neural mechanisms underlying this unique state of consciousness, extending theories on the neural bases of cognitive control, internal awareness, and self-processing (Hoeft et al, 2012;Jiang et al, 2017;Terhune et al, 2017). By mapping functional alterations in the triple networks onto connectivity disruptions observed in conditions like depression and PTSD may elucidate novel brain-based targets for hypnotherapeutic interventions in treating psychiatric symptoms (Lebois et al, 2022;Leroy et al, 2021).…”

A longitudinal mediation study of peer victimization and resting-state functional connectivity as predictors of development of adolescent psychopathology

“…Some studies have shown that activity in posterior insula also enhances in response to intense experiences of social pain and exclusion, such as romantic rejection ( 43 , 44 ). Posterior insula has also been implicated in intrusive or “re-experiencing” symptoms of post-traumatic stress disorders (PTSD) (e.g., flashbacks, nightmares, recurrent and unwanted distressing memories) ( 45 , 46 ). Exposure to PV during adolescence is also an intense and traumatic experience for many youth which impacts their self-esteem and threatens their feelings of social connection ( 47 , 48 ).…”