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

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) and healthy control (n = 15) participants. We compared PCC functional connectivity between regulate (in which participants downregulated PCC activity) and view (in which participants did not exert regulatory control) conditions across the whole-brain as well as in a priori specified regions-of-interest. RESULTS: During regulate as compared to view conditions, only the PTSD group showed significant PCC connectivity with anterior DMN (dmPFC, vmPFC) and SN (posterior insula) regions, whereas both groups displayed PCC connectivity with other posterior DMN areas (precuneus/cuneus). Additionally, as compared with controls, the PTSD group showed significantly greater PCC connectivity with the SN (amygdala) during regulate as compared to view conditions. Moreover, linear regression analyses revealed that during regulate as compared to view conditions, PCC connectivity to DMN and SN regions was positively correlated to psychiatric symptoms across all participants. CONCLUSION: In summary, observations of PCC connectivity to the DMN and SN provide emerging evidence of neural mechanisms underlying PCC-targeted fMRI neurofeedback among individuals with PTSD. This supports the use of PCC-targeted neurofeedback as a means by which to recalibrate PTSD-associated alterations in neural connectivity within the DMN and SN, which together, may help to facilitate improved emotion regulation abilities in PTSD.

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

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.

Meditating in Virtual Reality 3: 360° Video of Perceptual Presence of Instructor.

OBJECTIVES: The need for remote delivery of mental health interventions including instruction in meditation has become paramount in the wake of the current global pandemic. However, the support one may usually feel within the physical presence of an instructor may be weakened when interventions are delivered remotely, potentially impacting one's meditative experiences. Use of head-mounted displays (HMD) to display video-recorded instruction may increase one's sense of psychological presence with the instructor as compared to presentation via regular flatscreen (e.g., laptop) monitor. This research therefore evaluated a didactic, trauma-informed care approach to instruction in mindfulness meditation by comparing meditative responses to an instructor-guided meditation when delivered face-to-face vs. by pre-recorded 360° videos viewed either on a standard flatscreen monitor (2D format) or via HMD (i.e., virtual reality [VR] headset; 3D format). METHODS: Young adults (n = 82) were recruited from a university introductory course and experienced a 360° video-guided meditation via HMD (VR condition, 3D format). They were also randomly assigned to practice the same meditation either via scripted face-to-face instruction (in vivo [IV] format) or when viewed on a standard laptop display (non-VR condition, 2D format). Positive and negative affect and meditative experience ratings were self-reported and participants' maintenance of focused attention to breathing (i.e., meditation breath attention scores [MBAS]) were recorded during each meditation. RESULTS: Meditating in VR (3D format) was associated with a heightened experience of awe overall. When compared to face-to-face instruction (IV format), VR meditation was rated as less embarrassing but also less enjoyable and more tiring. When compared to 2D format, VR meditations were associated with greater experiences of relaxation, less distractibility from the process of breathing, and less fatigue. No differences were found between VR and non-VR meditation in concentration (MBAS). Baseline posttraumatic stress symptoms were risk factors for experiencing distress while meditating in either (VR and non-VR) instructional format. Of those who reported a preference for one format, approximately half preferred the VR format and approximately half preferred the IV format. CONCLUSIONS: Recorded 360° video instruction in meditation viewed with a HMD (i.e., VR/3D format) appears to offer some experiential advantage over instructions given in 2D format and may offer a safe-and for some even preferred-alternative to teaching meditation face-to-face. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12671-021-01612-w.

Meditating in virtual reality: Proof-of-concept intervention for posttraumatic stress.

Objective: We investigate the potential therapeutic application of virtual reality (VR) technology as an aid to meditation practice among persons varying in posttraumatic stress disorder (PTSD) symptoms. Method: In this within-group mixed-methods study, 96 young adults practiced both VR- and non-VR-guided meditations and reported on their experience of positive affect (PA), negative affect (NA), other meditative experiences and perceived satisfaction-credibility of each meditation. Results: Participants reported more PA and greater perceived satisfaction-credibility following the VR as compared to non-VR-guided meditations primarily when the VR meditation was practiced first, before the non-VR meditation, as opposed to vice versa. The experience of NA during meditation practice was infrequent, although persons with increased PTSD symptoms reported increased distress during both VR and non-VR meditation. Conclusions: Further study of therapeutic applications of VR as an aid to meditation practice among people with PTSD symptoms is warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Proof of Concept of an Eclectic, Integrative Therapeutic Approach to Mental Health and Well-Being Through Virtual Reality Technology.

Across three studies, we provide a proof-of-concept evaluation of an integrative psychotherapeutic application of virtual reality (VR) technology. Study 1 (n = 36) evaluated an unguided "safe-place" imagery task, where participants were instructed "to create a safe space… [such as] a scene, item, design, or any visual representation that makes you feel safe" using either the Google Tilt Brush application (VR condition), the standard Microsoft Paint application (2-D condition), or via eyes-closed mental imagery alone (IMG condition). Study 2 (n = 48) evaluated a narrative episodic recall task, where participants viewed their childhood and adult homes and places of schooling either using either the Google Earth VR application (VR condition) or the standard Google Earth application (2-D condition) or recalled these places with their eyes closed via mental imagery alone (IMG condition). Finally, Study 3 (n = 48) evaluated a guided wilderness imagery task, during which different scripts were narrated, specifically, a trail walk in autumn, a spring meadow, and a hillside walk in snowy winter, while either these same scenes were visually presented using the Nature Treks VR application (VR condition), the scenes were presented using the same software but shown on standard computer monitor (2-D condition), or participants' eyes were closed (IMG condition). Order of intervention format was randomized across participants. Across all three studies, quantitative survey ratings showed that the VR format of intervention delivery produced greater positive affect and satisfaction and perceived credibility ratings as an intervention for trauma- and stressor-related disorders and psychological well-being as rated by university students who varied in traumatic and stressful life event history and symptoms of posttraumatic stress disorder, whereas qualitative findings revealed additional themes of experiential response including increased experience of presence and vividness in the VR condition. Future research directions and clinical applications are discussed.

A randomized, controlled trial of alpha-rhythm EEG neurofeedback in posttraumatic stress disorder: A preliminary investigation showing evidence of decreased PTSD symptoms and restored default mode and salience network connectivity using fMRI.

OBJECTIVE: The default-mode network (DMN) and salience network (SN) have been shown to display altered connectivity in posttraumatic stress disorder (PTSD). Restoring aberrant connectivity within these networks with electroencephalogram neurofeedback (EEG-NFB) has been shown previously to be associated with acute decreases in symptoms. Here, we conducted a double-blind, sham-controlled randomized trial of alpha-rhythm EEG-NFB in participants with PTSD (n = 36) over 20-weeks. Our aim was to provide mechanistic evidence underlying clinical improvements by examining changes in network connectivity via fMRI. METHODS: We randomly assigned participants with a primary diagnosis of PTSD to either the experimental group (n = 18) or sham-control group (n = 18). We collected resting-state fMRI scans pre- and post-NFB intervention, for both the experimental and sham-control PTSD groups. We further compared baseline brain connectivity measures pre-NFB to age-matched healthy controls (n = 36). RESULTS: With regard to the primary outcome measure of PTSD severity, we found a significant main effect of time in the absence of a group × time interaction. Nevertheless, we found significantly decreased PTSD severity scores in the experimental NFB group only, when comparing post-NFB (dz = 0.71) and 3-month follow-up scores (dz = 0.77) to baseline measures. Interestingly, we found evidence to suggest a shift towards normalization of DMN and SN connectivity post-NFB in the experimental group only. Both decreases in PTSD severity and NFB performance were correlated to DMN and SN connectivity post-NFB in the experimental group. Critically, remission rates of PTSD were significant higher in the experimental group (61.1%) as compared to the sham-control group (33.3%). CONCLUSION: The current study shows mechanistic evidence for therapeutic changes in DMN and SN connectivity that are known to be associated with PTSD psychopathology with no patient dropouts. This preliminary investigation merits further research to demonstrate fully the clinical efficacy of EEG-NFB as an adjunctive therapy for PTSD.

Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis.

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

Restoring large-scale brain networks in PTSD and related disorders: a proposal for neuroscientifically-informed treatment interventions.

BACKGROUND: Three intrinsic connectivity networks in the brain, namely the central executive, salience, and default mode networks, have been identified as crucial to the understanding of higher cognitive functioning, and the functioning of these networks has been suggested to be impaired in psychopathology, including posttraumatic stress disorder (PTSD). OBJECTIVE: 1) To describe three main large-scale networks of the human brain; 2) to discuss the functioning of these neural networks in PTSD and related symptoms; and 3) to offer hypotheses for neuroscientifically-informed interventions based on treating the abnormalities observed in these neural networks in PTSD and related disorders. METHODS: Literature relevant to this commentary was reviewed. RESULTS: Increasing evidence for altered functioning of the central executive, salience, and default mode networks in PTSD has been demonstrated. We suggest that each network is associated with specific clinical symptoms observed in PTSD, including cognitive dysfunction (central executive network), increased and decreased arousal/interoception (salience network), and an altered sense of self (default mode network). Specific testable neuroscientifically-informed treatments aimed to restore each of these neural networks and related clinical dysfunction are proposed. CONCLUSIONS: Neuroscientifically-informed treatment interventions will be essential to future research agendas aimed at targeting specific PTSD and related symptoms.