A tale of two targets: examining the differential effects of posterior cingulate cortex- and amygdala-targeted fMRI-neurofeedback in a PTSD pilot study
Authors: Lieberman Jonathan M. , Rabellino Daniela , Densmore Maria , Frewen Paul A. , Steyrl David , Scharnowski Frank , Théberge Jean , Hosseini-Kamkar Niki , Neufeld Richard W. J. , Jetly Rakesh , Frey Benicio N. , Ros Tomas , Lanius Ruth A. , Nicholson Andrew A. 
Published: November 2023

IntroductionReal-time fMRI-based neurofeedback (rt-fMRI-NFB) is a non-invasive technology that enables individuals to self-regulate brain activity linked to neuropsychiatric symptoms, including those associated with post-traumatic stress disorder (PTSD). Selecting the target brain region for neurofeedback-mediated regulation is primarily informed by the neurobiological characteristics of the participant population. There is a strong link between PTSD symptoms and multiple functional disruptions in the brain, including hyperactivity within both the amygdala and posterior cingulate cortex (PCC) during trauma-related processing. As such, previous rt-fMRI-NFB studies have focused on these two target regions when training individuals with PTSD to regulate neural activity. However, the differential effects of neurofeedback target selection on PTSD-related neural activity and clinical outcomes have not previously been investigated.MethodsHere, we compared whole-brain activation and changes in PTSD symptoms between PTSD participants (n = 28) that trained to downregulate activity within either the amygdala (n = 14) or the PCC (n = 14) while viewing personalized trauma words.ResultsFor the PCC as compared to the amygdala group, we observed decreased neural activity in several regions implicated in PTSD psychopathology – namely, the bilateral cuneus/precuneus/primary visual cortex, the left superior parietal lobule, the left occipital pole, and the right superior temporal gyrus/temporoparietal junction (TPJ) – during target region downregulation using rt-fMRI-NFB. Conversely, for the amygdala as compared to the PCC group, there were no unique (i.e., over and above that of the PCC group) decreases in neural activity. Importantly, amygdala downregulation was not associated with significantly improved PTSD symptoms, whereas PCC downregulation was associated with reduced reliving and distress symptoms over the course of this single training session. In this pilot analysis, we did not detect significant between-group differences in state PTSD symptoms during neurofeedback. As a critical control, the PCC and amygdala groups did not differ in their ability to downregulate activity within their respective target brain regions. This indicates that subsequent whole-brain neural activation results can be attributed to the effects of the neurofeedback target region selection in terms of neurophysiological function, rather than as a result of group differences in regulatory success.ConclusionIn this study, neurofeedback-mediated downregulation of the PCC was differentially associated with reduced state PTSD symptoms and simultaneous decreases in PTSD-associated brain activity during a single training session. This novel analysis may guide researchers in choosing a neurofeedback target region in future rt-fMRI-NFB studies and help to establish the clinical efficacy of specific neurofeedback targets for PTSD. A future multi-session clinical trial of rt-fMRI-NFB that directly compares between PCC and amygdala target regions is warranted.