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

Abstract

Background: Alterations within large-scale brain networks-namely, the default mode (DMN) and salience networks (SN)-are present among individuals with posttraumatic stress disorder (PTSD). Previous real-time functional magnetic resonance imaging (fMRI) and electroencephalography neurofeedback studies suggest that regulating posterior cingulate cortex (PCC; the primary hub of the posterior DMN) activity may reduce PTSD symptoms and recalibrate altered network dynamics. However, PCC connectivity to the DMN and SN during PCC-targeted fMRI neurofeedback remains unexamined and may help to elucidate neurophysiological mechanisms through which these symptom improvements may occur.Methods: Using a trauma/emotion provocation paradigm, we investigated psychophysiological interactions over a single session of neurofeedback among PTSD (n = 14) This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder

“…These findings emerge in the context of accruing evidence for exaggerated coupling between the intrinsically anti-correlated SN and DMN in PTSD. Exaggerated connectivity between the amygdala (SN) and the PCC/Precuneus (DMN) has been implicated in risk, severity, and maintenance of PTSD [27,31,58,59]. Such connectivity patterns are similarly implicated in transdiagnostic processes of aberrant stress response [29,33], threat reactivity [32], and trait anxiety [60,61].…”

A tale of two targets: examining the differential effects of posterior cingulate cortex- and amygdala-targeted fMRI-neurofeedback in a PTSD pilot study

“…rt-fMRI-NFB is a non-invasive brain-computer interface that enables individuals to self-regulate specific brain networks and functions, which can be particularly beneficial for treating various psychiatric conditions. Indeed, several studies have implemented rt-fMRI-NFB in a range of prevalent psychiatric conditions ( Linden et al, 2012 ; Li et al, 2013 ; Schoenberg and David, 2014 ; Hamilton et al, 2016 ; Young et al, 2017 ; Mehler et al, 2018 ), including post-traumatic stress disorder (PTSD) ( Gerin et al, 2016 ; Misaki et al, 2018 , 2019 , 2021 ; Nicholson et al, 2016a , 2018 , 2021 ; Zotev et al, 2018 ; Zweerings et al, 2018 , 2020 ; Chiba et al, 2019 ; Weaver et al, 2020 ; Lieberman et al, 2023 ; Zhao et al, 2023 ). In designing clinical rt-fMRI-NFB studies, multiple methodological factors require critical consideration; however, one of the most crucial decisions is the selection of the neurophysiological basis by which to generate the neurofeedback signal.…”

“…Taken together, these findings highlight the PCC’s clinical relevance in PTSD psychopathology and suggest that regulating activity within the region via rt-fMRI-NFB may generate positive clinical outcomes. Critically, however, very few studies have examined the neurobiological mechanisms associated with the regulation of the PCC with rt-fMRI-NFB ( Zhang et al, 2013 ; Garrison et al, 2013a , b ; Kirlic et al, 2022 ; Yu et al, 2022 ), with only one study examining the regulation of this region in PTSD ( Nicholson et al, 2021 ; Lieberman et al, 2023 ).…”

“…On the other hand, PCC downregulation was associated with simultaneous widespread decreases in neural activity within several brain regions implicated in PTSD psychopathology – namely, the dmPFC, postcentral gyrus, amygdala/hippocampus, cingulate cortex, and temporal pole/gyri ( Nicholson et al, 2021 ). Additionally, PCC downregulation was also associated with increased PCC connectivity with the dmPFC, vmPFC, posterior insula, and amygdala ( Lieberman et al, 2023 ). Hence, PCC downregulation may help to restore connectivity between functionally segregated posterior and anterior DMN structures and may also result in the concomitant regulation of brain regions involved in emotion generation/processing (i.e., amygdala) and embodiment (i.e., insula).…”

“…To do so, we compared whole-brain activation patterns between two groups of PTSD participants, who were trained to downregulate activity within either the amygdala or the PCC during an identical trauma provocation paradigm. Based on previous studies examining patterns of activation and connectivity associated with amygdala and PCC downregulation with rt-fMRI-NFB ( Gerin et al, 2016 ; Nicholson et al, 2016a , 2018 , 2021 ; Misaki et al, 2018 , 2019 ; Zotev et al, 2018 ; Lieberman et al, 2023 ; Zhao et al, 2023 ), we expected to observe unique neural mechanisms involved in the downregulation of these two target regions when comparing them directly. More specifically, we hypothesized that amygdala downregulation would be associated with increased neural activity in emotion regulation areas within the prefrontal cortex, as compared to the PCC group.…”