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.

Increased top-down control of emotions during symptom provocation working memory tasks following a RCT of alpha-down neurofeedback in PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been found to be associated with emotion under-modulation from the prefrontal cortex and a breakdown of the top-down control of cognition and emotion. Novel adjunct therapies such as neurofeedback (NFB) have been shown to normalize aberrant neural circuits that underlie PTSD psychopathology at rest. However, little evidence exists for NFB-linked neural improvements under emotionally relevant cognitive load. The current study sought to address this gap by examining the effects of alpha-down NFB in the context of an emotional n-back task. METHODS: We conducted a 20-week double-blind randomized, sham-controlled trial of alpha-down NFB and collected neuroimaging data before and after the NFB protocol. Participants performed an emotional 1-back and 2-back working memory task, with interleaved trauma-neutral and trauma-relevant cues in the fMRI scanner. Data from 35 participants with a primary diagnosis of PTSD were analyzed in this study (n = 18 in the experimental group undergoing alpha-down NFB, n = 17 in the sham-control group). RESULTS: Firstly, within-group analyses showed clinically significant reductions in PTSD symptom severity scores at the post-intervention timepoint and 3-month follow-up for the experimental group, and not for the sham-control group. The neuroimaging analyses revealed that alpha-down NFB enhanced engagement of top-down cognitive and emotional control centers, such as the dorsolateral prefrontal cortex (dlPFC), and improved integration of the anterior and posterior parts of the default mode network (DMN). Finally, our results also indicate that increased alpha-down NFB performance correlated with increased activity in brain regions involved in top-down control and bodily consciousness/embodied processing of self (TPJ and posterior insula). CONCLUSION: This is the first study to provide mechanistic insights into how NFB may normalize dysfunctional brain activity and connectivity in PTSD under cognitive load with simultaneous symptom provocation, adding to a growing body of evidence supporting the therapeutic neuromodulatory effects of NFB. This preliminary study highlights the benefits of alpha-down NFB training as an adjunctive therapy for PTSD and warrants further investigation into its therapeutic effects on cognitive and emotion control in those with 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.

Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis.

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing.

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.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

The neural correlates of trauma-related autobiographical memory in posttraumatic stress disorder: A meta-analysis.

BACKGROUND: Autobiographical memory (AM) refers to memories of events that are personally relevant and are remembered from one's own past. The AM network is a distributed brain network comprised largely by prefrontal medial and posteromedial cortical brain regions, which together facilitate AM. Autobiographical memories with high arousal and negatively valenced emotional states are thought to be retrieved more readily and re-experienced more vividly. This is critical in the case of trauma-related AMs, which are related to altered phenomenological experiences as well as aberrations to the underlying neural systems in posttraumatic stress disorder (PTSD). Critically, these alterations to the AM network have not been explored recently and have never been analyzed with consideration to the different processes of AM, them being retrieval and re-experiencing. METHODS: We conducted a series of effect-size signed differential mapping meta-analyses across twenty-eight studies investigating the neural correlates of trauma-related AMs in participants with PTSD as compared with controls. Studies included either trauma-related scripts or trauma-related materials (i.e., sounds, images, pictures) implemented to evoke the recollection of a trauma-related memory. RESULTS: The meta-analyses revealed that control and PTSD participants displayed greater common brain activation of prefrontal medial and posteromedial cortices, respectively. Whereby the prefrontal medial cortices are suggested to facilitate retrieval monitoring, the posteromedial cortices are thought to enable the visual imagery processes of AM. CONCLUSIONS: Taken together, reduced common activation of prefrontal cortices may be interpreted as a bias toward greater re-experiencing, where the more salient elements of the traumatic memory are relived as opposed to retrieved in a controlled manner in PTSD.

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.

Overlapping frontoparietal networks in response to oculomotion and traumatic autobiographical memory retrieval: implications for eye movement desensitization and reprocessing.

Background: Oculomotor movements have been shown to aid in the retrieval of episodic memories, serving as sensory cues that engage frontoparietal brain regions to reconstruct visuospatial details of a memory. Frontoparietal brain regions not only are involved in oculomotion, but also mediate, in part, the retrieval of autobiographical episodic memories and assist in emotion regulation. Objective: We sought to investigate how oculomotion influences retrieval of traumatic memories by examining patterns of frontoparietal brain activation during autobiographical memory retrieval in post-traumatic stress disorder (PTSD) and in healthy controls. Method: Thirty-nine participants (controls, n = 19; PTSD, n = 20) recollected both neutral and traumatic/stressful autobiographical memories while cued simultaneously by horizontal and vertical oculomotor stimuli. The frontal (FEF) and supplementary (SEF) eye fields were used as seed regions for psychophysiological interaction analyses in SPM12. Results: As compared to controls, upon retrieval of a traumatic/stressful memory while also performing simultaneous horizontal eye movements, PTSD showed: i) increased SEF and FEF connectivity with the right dorsolateral prefrontal cortex, ii) increased SEF connectivity with the right dorsomedial prefrontal cortex, and iii) increased SEF connectivity with the right anterior insula. By contrast, as compared to PTSD, upon retrieval of a traumatic/stressful memory while also performing simultaneous horizontal eye movements, controls showed: i) increased FEF connectivity with the right posterior insula and ii) increased SEF connectivity with the precuneus. Conclusions: These findings provide a neurobiological account for how oculomotion may influence the frontoparietal cortical representation of traumatic memories. Implications for eye movement desensitization and reprocessing are discussed.

Antecedentes: Se ha visto que los movimientos óculomotores ayudan a la recuperación de memorias episódicas, sirviendo como señales sensoriales que envuelven las regiones cerebrales frontoparietales para reconstruir detalles visuoespaciales. Las regiones cerebrales frontoparietales no solo están involucradas críticamente en el movimiento ocular, pero ellos también median, en parte, la recuperación de la memoria episódica autobiográfica y ayudan en la regulación emocional.Objetivo: Buscamos investigar cómo el movimiento ocular influye en la recuperación de la memoria traumática al examinar patrones de activación cerebral frontoparietales durante la recuperación de la memoria autobiográfica en trastorno de estrés postraumático (TEPT) y controles sanos.Método: Se recolectaron en treinta y nueve participantes (controles, n= 19; TEPT, n=20): (i) neutral; y (ii) memorias autobiográficas traumáticas/estresantes mientras se señalaba simultáneamente por estímulos oculomotores horizontales y verticales. Se usaron los campos oculares frontal (FEF por sus siglas en inglés) y suplementario (SEF por sus siglas en inglés) como regiones bases para el análisis de interacción psico fisiológica en SPM12.Resultados: En comparación con los controles, al recuperar una memoria traumática/estresante mientras se realizan simultáneamente movimientos oculares horizontales, el TEPT mostró: (i) SEF aumentado y conectividad FEF con la corteza prefrontal dorsolateral derecha, (ii) conectividad SEF aumentada con la corteza prefrontal dorsomedial derecha y (iii) conectividad SEF aumentada con la ínsula anterior derecha. En contraste, al compararlo con TEPT, al recuperar una memoria traumática/estresante mientras se realizan simultáneamente movimientos oculares horizontales, los controles mostraron: (i) conectividad FEF aumentada con la región posterior derecha de la ínsula y (ii) conectividad SEF aumentada con el precuneoConclusiones: Estos hallazgos proveen un base neurobiológica de cómo los movimientos oculares pueden influir en la representación cortical frontoparietal de las memorias traumáticas. Se discuten las implicaciones del reprocesamiento y desensibilización por movimientos oculares.

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.

Mindfulness-based treatments for posttraumatic stress disorder: a review of the treatment literature and neurobiological evidence.

Mindfulness-based treatments for posttraumatic stress disorder (PTSD) have emerged as promising adjunctive or alternative intervention approaches. A scoping review of the literature on PTSD treatment studies, including approaches such as mindfulness-based stress reduction, mindfulness-based cognitive therapy and metta mindfulness, reveals low attrition with medium to large effect sizes. We review the convergence between neurobiological models of PTSD and neuroimaging findings in the mindfulness literature, where mindfulness interventions may target emotional under- and overmodulation, both of which are critical features of PTSD symptomatology. Recent emerging work indicates that mindfulness-based treatments may also be effective in restoring connectivity between large-scale brain networks among individuals with PTSD, including connectivity between the default mode network and the central executive and salience networks. Future directions, including further identification of the neurobiological mechanisms of mindfulness interventions in patients with PTSD and direct comparison of these interventions to first-line treatments for PTSD are discussed.

Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia.

BACKGROUND: Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS: We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS: In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS: Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma.

Mindfulness and Metta-based Trauma Therapy (MMTT): Initial Development and Proof-of-Concept of an Internet Resource.

Trauma and stressor-related disorders, including post-traumatic stress disorder (PTSD) and related comorbid disorders such as anxiety, depression, and dissociative disorders, are difficult to treat. Mindfulness-based clinical interventions have proven efficacy for mental health treatment in face-to-face individual and group modalities, although the feasibility and efficacy of delivering these interventions via the internet has not been evaluated. The present research developed mindfulness and metta-based trauma therapy (MMTT) as an internet resource to support the practice of mindfulness and metta (lovingkindness) meditations for self-regulation and healing from trauma and stressor-related disorders. In the present "proof-of-concept" study, research participants (n = 177) recruited online practiced mindfulness and metta meditations and related therapeutic exercises available via the website and rated their perceived credibility as interventions for improving self-regulation and well-being and reducing PTSD symptoms, anxiety, depressive, and dissociative experiences, as well as their experienced ease, helpfulness, and informational value. Results suggest that, independent of level of self-reported current and past psychiatric history and PTSD symptoms, participants considered the MMTT website as a credible and helpful therapeutic intervention for improving self-regulation and well-being and reducing PTSD, anxiety, depression, and dissociation. Overall, participants considered guided and non-guided meditation practices more helpful than a journaling exercise, and participants with increased PTSD symptoms preferred metta (lovingkindness) meditations less than other participants. We conclude that MMTT should be piloted in clinical trials as an adjunctive intervention to evidence-based treatments for persons with mood, anxiety, and trauma and stressor-related disorders, as well as more generally as an online resource to support self-regulation and well-being practices.

Dissociation in borderline personality disorder: Disturbed cognitive and emotional inhibition and its neural correlates.

Evidence is heterogeneous regarding whether patients with borderline personality disorder (BPD) display disturbed emotional inhibition in the emotional Stroop task. Previous findings suggest that state dissociation may influence cognitive inhibition of task-irrelevant material, particularly with negative content. Our aim was to examine performance in an emotional Stroop task including negative, neutral, and positive words in BPD patients and healthy controls during functional magnetic resonance imaging. In advance, half of the BPD patients underwent a dissociation induction using script-driven imagery. BPD patients without dissociation induction showed behavioural performance comparable to that of healthy controls but displayed stronger neural responses, especially to positive stimuli, in the superior temporal gyrus, dorsomedial prefrontal cortex, and anterior cingulate cortex. BPD patients with dissociation induction showed overall slower and less accurate responses as well as increased reaction times for negative versus neutral words compared with BPD patients without dissociation induction. Moreover, they showed comparatively decreased neuronal activity in the fusiform gyrus and parietal cortices independent of valence, but elevated activity in the left inferior frontal gyrus in response to negative versus neutral words. In conclusion, experimentally induced dissociation in BPD was associated with inefficient cognitive inhibition, particularly of negative stimuli, in the emotional Stroop task.

Effect of direct eye contact in women with PTSD related to interpersonal trauma: Psychophysiological interaction analysis of connectivity of an innate alarm system.

In healthy individuals, direct eye contact is thought to modulate a cortical route eliciting social cognitive processes via activation of a fast subcortical pathway. This study aimed to examine functional brain connectivity during direct eye contact in women with posttraumatic stress disorder (PTSD) related to childhood abuse as compared with healthy controls. We conducted psychophysiological interaction (PPI) analyses in Statistical Parametric Mapping-8 (SPM8) using the superior colliculus (SC) and locus coeruleus (LC) as seed regions while 16 healthy subjects and 16 patients with a primary diagnosis of PTSD related to childhood maltreatment viewed a functional magnetic resonance imaging (fMRI) paradigm involving direct (D) versus averted (A) gaze (happy, sad, neutral). The PTSD group showed a significantly enhanced connectivity between the SC and the anterior cingulate, and between the LC and the thalamus, caudate, putamen, insula, cingulate gyrus, and amygdala, as compared with healthy individuals. Symptom severity scores on the Clinician-Administered PTSD Scale (CAPS) showed significant positive correlations with superior colliculus connectivity with the perigenual and posterior cingulate, insula, and sublenticular extended amygdala. Functional connectivity data suggest increased recruitment of brain regions involved in emotion processing during direct gaze in PTSD in association with the fast subcortical pathway. The interpretation of eye contact as a signal of threat may require more emotion regulatory capacities in patients with PTSD.

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.

Mind over chatter: plastic up-regulation of the fMRI salience network directly after EEG neurofeedback.

Neurofeedback (NFB) involves a brain-computer interface that allows users to learn to voluntarily control their cortical oscillations, reflected in the electroencephalogram (EEG). Although NFB is being pioneered as a noninvasive tool for treating brain disorders, there is insufficient evidence on the mechanism of its impact on brain function. Furthermore, the dominant rhythm of the human brain is the alpha oscillation (8-12 Hz), yet its behavioral significance remains multifaceted and largely correlative. In this study with 34 healthy participants, we examined whether during the performance of an attentional task, the functional connectivity of distinct fMRI networks would be plastically altered after a 30-min session of voluntary reduction of alpha rhythm (n=17) versus a sham-feedback condition (n=17). We reveal that compared to sham-feedback, NFB induced an increase of connectivity within regions of the salience network involved in intrinsic alertness (dorsal anterior cingulate), which was detectable 30 min after termination of training. The increase in salience network (default-mode network) connectivity was negatively (positively) correlated with changes in 'on task' mind-wandering as well as resting state alpha rhythm. Crucially, we observed a causal dependence between alpha rhythm synchronization during NFB and its subsequent change at resting state, not exhibited by the SHAM group. Our findings provide neurobehavioral evidence for the brain's exquisite functional plasticity, and for a temporally direct impact of NFB on a key cognitive control network, suggesting a promising basis for its use to treat cognitive disorders under physiological conditions.

Emotional numbing in posttraumatic stress disorder: a functional magnetic resonance imaging study.

OBJECTIVE: To explore the functional neural correlates of emotional numbing symptoms in individuals with posttraumatic stress disorder (PTSD). METHOD: The study was conducted between September 2006 and June 2008 at the University of Western Ontario. Women with (n = 14) and without (n = 16) PTSD (based on DSM-IV criteria) completed a standardized emotional imagery task while undergoing functional magnetic resonance imaging, in addition to an assessment for emotional numbing symptoms. The study design was correlational, with primary outcome measures being blood oxygenation level-dependent (BOLD) response to emotional imagery task and self-reported severity of emotional numbing symptoms. Women without PTSD were not trauma exposed. RESULTS: In women with PTSD, emotional numbing symptoms predicted less positive affect in response to positive-valence scripts (P < .05) and less BOLD response within the dorsomedial prefrontal cortex during imagery of positive and negative scripts that were explicitly socially relevant (P < .001). In contrast, in women without PTSD, emotional numbing symptoms, while unrelated to subjective emotional responses, predicted greater response within the ventromedial prefrontal cortex during positive and negative scripts, in addition to scripts that elicited fear anxiety by nonsocial means (all P values < .001). The findings could not be attributed to dysphoria. CONCLUSIONS: These findings are consistent with previous research regarding emotional numbing and emotional awareness. Less response within the medial prefrontal cortex during emotional imagery in individuals with high emotional numbing may indicate deficient conscious and reflective emotional processing. Further study is required to elucidate associations between state and trait emotional numbing and the neural correlates of psychological treatments specific to emotional numbing.

Neural correlates and predictive power of trait resilience in an acutely traumatized sample: a pilot investigation.

OBJECTIVE: Resilience refers to the ability to thrive despite adversity and is defined as a multidimensional phenomenon, spanning internal locus of control, sense of meaning, social problem-solving skills, and self-esteem. We aimed to investigate the predictive value of resilience for the development of posttraumatic stress disorder (PTSD) and to examine the neural correlates mediating the relationship between resilience and recovery from a traumatic event in acutely traumatized subjects. We hypothesized that resilience would mediate the relationship between childhood trauma and posttraumatic recovery. METHOD: We conducted a prospective study with 70 acutely traumatized subjects with DSM-IV PTSD recruited at the emergency department, assessing PTSD symptom severity at 3 time points within the first 3 months posttrauma. Scores for childhood trauma as assessed with the Childhood Trauma Questionnaire and trait resilience as assessed with the Connor-Davidson Resilience Scale were used as predictors of symptom severity. A subsample of 12 subjects additionally underwent a functional 4 Tesla magnetic resonance imaging scan 2 to 4 months posttrauma. We employed the traumatic script-driven imagery paradigm to assess the correlations between trait resilience and blood oxygen level-dependent (BOLD) response. The study was conducted from 2003 to 2007. RESULTS: Resilience predicted PTSD symptom severity at 5 to 6 weeks (ß = -0.326, P = .01) as well as at 3 months (ß = -0.423, P = .003) posttrauma better than childhood trauma. Resilience essentially mediated the relationship between childhood trauma and posttraumatic adjustment. Resilience scores were positively correlated with BOLD signal strength in the right thalamus as well as the inferior and middle frontal gyri (Brodmann area 47). CONCLUSIONS: This pilot investigation revealed a significant relationship between resilience and emotion regulation areas during trauma recall in an acutely traumatized sample. Resilience was established as a significant predictor of PTSD symptom severity and mediated the influence of childhood trauma on posttraumatic adjustment.