Differential mechanisms of posterior cingulate cortex downregulation and symptom decreases in posttraumatic stress disorder and healthy individuals using real‐time fMRI neurofeedback

Abstract

Background Intrinsic connectivity networks, including the default mode network (DMN), are frequently disrupted in individuals with posttraumatic stress disorder (PTSD). The posterior cingulate cortex (PCC) is the main hub of the posterior DMN, where the therapeutic regulation of this region with real‐time fMRI neurofeedback (NFB) has yet to be explored. Methods We investigated PCC downregulation while processing trauma/stressful words over 3 NFB training runs and a transfer run without NFB (total n = 29, PTSD n = 14, healthy controls n = 15). We also examined the predictive accuracy of machine learning models in classifying PTSD versus healthy controls during NFB training. Results Both the PTSD and healthy control groups demonstrated reduced reliving symptoms in response to trauma/stressful stimuli, where the PTSD group additionally showed reduced symptoms of distress. We found that both groups were able to downregulate the PCC with similar success over NFB training and in the transfer run, although downregulation was associated with unique within‐group decreases in activation within the bilateral dmPFC, bilateral postcentral gyrus, right amygdala/hippocampus, cingulate cortex, and bilateral temporal pole/gyri. By contrast, downregulation was associated with increased activation in the right dlPFC among healthy controls as compared to PTSD. During PCC downregulation, right dlPFC activation was negatively correlated to PTSD symptom severity scores and difficulties in emotion regulation. Finally, machine learning algorithms were able to classify PTSD versus healthy participants based on brain activation during NFB training with 80% accuracy. Conclusions This is the first study to investigate PCC downregulation with real‐time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG‐NFB targeting brain networks linked to the PCC.

Posterior cingulate cortex targeted real‐time fMRI neurofeedback recalibrates functional connectivity with the amygdala, posterior insula, and default‐mode network in PTSD

“…In a previously published analysis, we reported that individuals in the PTSD group showed reduced symptoms of reliving and distress in response to trauma-related stimuli over neurofeedback training (Nicholson et al, 2021), an effect not observed during the single-session rt-fMRI-NFB study targeting the amygdala (Nicholson et al, 2018;. While both groups were able to downregulate their PCC activity with similar success over neurofeedback training, downregulation was associated with unique within-PTSD group decreases in neural activity in several brain regions including those of the DMN (i.e., bilateral dmPFC, hippocampus) and SN (i.e., amygdala, mid-cingulate cortex) (Nicholson et al, 2021). Interestingly, these findings add to a growing body of research that highlight the critical involvement of the PCC in emotion regulation, including associations between normalized PCC activity and positive clinical outcomes following psychotherapy (Fresco et al, 2017;Garrett et al, 2019;Scult et al, 2019), as well as positive correlations between PCC-amygdala connectivity and PTSD symptom severity following trauma exposure Zhou et al, 2012).…”

“…In the present analysis, our goal was to further examine how PCC-targeted fMRI neurofeedback may recalibrate connectivity within large-scale brain networks. In doing so, we were able to characterize neural mechanisms that might underlie improvements in emotion regulation among PTSD participants that were previously reported by our group (Nicholson et al, 2021) and also evaluate whether findings are convergent with that of previous EEG-based neurofeedback studies (Kluetsch et al, 2014;Nicholson et al, 2018). Given the accumulation of functional neuroimaging findings of altered DMN and SN activity in PTSD, as well as studies which have demonstrated a recalibration of DMN and SN connectivity as a function of successful neurofeedback treatment for PTSD, examination of functional connectivity between the PCC and key hubs of both networks was of particular interest in this study.…”

“…In PTSD, it is well documented that there are strong associations between symptom presentations and multiple functional disruptions in the brain (Fenster et al, 2018;Lanius et al, 2015;Tursich et al, 2015). As such, emerging research supports the notion that recalibrating PTSD-associated functional disruptions within neural circuits constitutes a promising treatment approach that may complement existing psycho-and pharmacotherapies (Chiba et al, 2019;Koek et al, 2019;Nicholson et al, 2021;Panisch & Hai, 2020;Rogel et al, 2020).…”

“…Most recently, our group utilized rt-fMRI-NFB to train individuals with PTSD and healthy controls to downregulate PCC activity during the same trauma/emotion provocation paradigm in which participants viewed personalized trauma/distressing words (Nicholson et al, 2021).…”

“…The PCC was targeted for neurofeedback as it shows hyperactivity during the reliving and reexperiencing of trauma memories among individuals with PTSD (Awasthi et al, 2020;Fenster et al, 2018;Frewen et al, 2011;Hopper et al, 2007;Liberzon & Abelson, 2016;Mickleborough et al, 2011;Ramage et al, 2013;Thome et al, 2020). In a previously published analysis, we reported that individuals in the PTSD group showed reduced symptoms of reliving and distress in response to trauma-related stimuli over neurofeedback training (Nicholson et al, 2021), an effect not observed during the single-session rt-fMRI-NFB study targeting the amygdala (Nicholson et al, 2018;. While both groups were able to downregulate their PCC activity with similar success over neurofeedback training, downregulation was associated with unique within-PTSD group decreases in neural activity in several brain regions including those of the DMN (i.e., bilateral dmPFC, hippocampus) and SN (i.e., amygdala, mid-cingulate cortex) (Nicholson et al, 2021).…”