Structural changes in the thalamus and its subregions in regulating different symptoms of posttraumatic stress disorder.

As a key center for sensory information processing and transmission, the thalamus plays a crucial role in the development of posttraumatic stress disorder (PTSD). However, the changes in the thalamus and its role in regulating different PTSD symptoms remain unclear. In this study, fourteen PTSD patients and eighteen healthy controls (HCs) were recruited. All subjects underwent whole-brain T1-weighted three-dimensional Magnetization Prepared Rapid Gradient Echo Imaging scans. Gray matter volume (GMV) in the thalamus and its subregions were estimated using voxel-based morphometry (VBM). Compared to HCs, PTSD patients exhibited significant GMV reduction in the left thalamus and its subregions, including anterior, mediodorsal, ventral-lateral-dorsal (VLD), ventral-anterior, and ventral-lateral-ventral (VLV). Among the significantly reduced thalamic subregions, we found positive correlations between the GMV values of the left VLD and VLV and the re-experiencing symptoms score, arousal symptoms score, and total CAPS score. When using the symptom-related GMV values of left VLV and VLD in combination as a predictor, receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) for binary classification reached 0.813. This study highlights the neurobiological mechanisms of PTSD related to thalamic changes and may provide potential imaging markers for diagnosis and therapy targets.

Hypothalamus volume mediates the association between adverse childhood experience and PTSD development after adulthood trauma.

The hypothalamus is critical for regulation of the hypothalamic-pituitary-adrenal (HPA) axis and response to stress. Adverse childhood experience (ACE) can affect brain structure, which may contribute to development of posttraumatic stress disorder (PTSD) after subsequent adult trauma. It is unclear, however, if ACE history is particularly associated with aspects of hypothalamic structure which contribute to development of PTSD. To address this issue, the present study longitudinally assessed hypothalamic volumes and their associations with ACE and early post-trauma stress symptoms in subjects who did or did not develop PTSD during 12 months after adult trauma. 109 subjects (18-60 years, F/M = 75/34) completed the PTSD Checklist (PCL) questionnaire for post-trauma stress symptoms, the Childhood Trauma Questionnaire (CTQ) for ACE assessment, and an initial MRI brain scan for hypothalamic volume measurement, within 2 weeks after adult trauma. At post-trauma 12 months, subjects underwent a subsequent PTSD diagnosis interview using the Clinician-Administered PTSD Scale (CAPS), and a follow-up MRI scan. Left and right hypothalamus volumes at 2 weeks after adult trauma negatively correlated with CTQ scores. Right hypothalamus volume at this early time mediated an association between ACE and PTSD symptoms 12 months later. Right hypothalamus volumes also remained persistently smaller from 2 weeks to 12 months after trauma in survivors who developed PTSD. These results suggest that smaller right hypothalamus volume may be related to ACE history in ways that contribute to PTSD development after trauma in adulthood.

Amygdala downregulation training using fMRI neurofeedback in post-traumatic stress disorder: a randomized, double-blind trial.

Hyperactivation of amygdala is a neural marker for post-traumatic stress disorder (PTSD) and improvement in control over amygdala activity has been associated with treatment success in PTSD. In this randomized, double-blind clinical trial we evaluated the efficacy of a real-time fMRI neurofeedback intervention designed to train control over amygdala activity following trauma recall. Twenty-five patients with PTSD completed three sessions of neurofeedback training in which they attempted to downregulate the feedback signal after exposure to personalized trauma scripts. For subjects in the active experimental group (N = 14), the feedback signal was from a functionally localized region of their amygdala associated with trauma recall. For subjects in the control group (N = 11), yoked-sham feedback was provided. Changes in control over the amygdala and PTSD symptoms served as the primary and secondary outcome measurements, respectively. We found significantly greater improvements in control over amygdala activity in the active group than in the control group 30-days following the intervention. Both groups showed improvements in symptom scores, however the symptom reduction in the active group was not significantly greater than in the control group. Our finding of greater improvement in amygdala control suggests potential clinical application of neurofeedback in PTSD treatment. Thus, further development of amygdala neurofeedback training in PTSD treatment, including evaluation in larger samples, is warranted.

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.

Reexperiencing and anxious arousal symptoms in relation to volumes of thalamus nuclei in posttraumatic stress spectrum adults.

INTRODUCTION: Trauma reexperiencing is dominated by recollection of sensory-perceptual elements of the trauma, pointing to involvement of the sensory thalamus. This study examined posttraumatic stress symptoms in relation to volumes of thalamic nuclei that were grouped based on their predominant functions. We hypothesized that reexperiencing, controlling for other symptom dimensions, would correlate with volumes of thalamic nuclei involved in primary and higher-order sensory processing. METHODS: Seventy-two trauma-exposed adults were interviewed with the Clinician Administered PTSD Scale for DSM-IV and underwent 3T magnetic resonance imaging. Scores were derived for reexperiencing, anxious arousal, dysphoric arousal, emotional numbing, and avoidance symptoms. These were entered as simultaneous predictors in five separate regression analyses, with age, sex, and total thalamus volume as covariates, predicting volumesf of five thalamus nuclear groupings corrected for intracranial volume: Specific sensory, associative-sensory, associative-cognitive, intralaminar, and motor groupings. RESULTS: Reexperiencing symptoms were significantly positively correlated with volumes of the motor thalamic grouping, which included the ventral anterior, ventral lateral, and ventromedial nuclei. Anxious arousal was significantly negatively correlated with volumes of all five thalamic groupings. CONCLUSIONS: Reexperiencing symptoms were correlated with volumes of the motor thalamus, while anxious arousal symptoms were related to all thalamic subregion volumes. Thalamic nuclei involved in motor functions, including oculomotor control and motor planning, may be implicated in posttraumatic reexperiencing symptoms.

Traumatic Autobiographical Memories: Preliminary fMRI Findings Among Men With Histories of Childhood Sexual Abuse.

Childhood sexual abuse (CSA) is associated with autobiographical memory (AM) disturbances. AM is important for future thinking, sense of self, and coping with negative emotions. CSA is under-researched among men, with research examining long-term neural correlates limited even further. This study explored the neural correlates of re-experiencing traumatic/negative memories to examine the influence of CSA on AM into adulthood. Fifteen males who experienced CSA, with and without posttraumatic stress disorder (PTSD; CSA+PTSD, n = 6; CSA-PTSD, n = 9) and control males without CSA histories nor PTSD (n = 11) completed a script-driven imagery paradigm during functional magnetic resonance imaging (fMRI). Males with CSA histories, with and without PTSD, processed their negative autobiographical memories with less activation compared to control males. The CSA+PTSD group of males had less activation in the left superior occipital, left superior parietal and left parahippocampal gyri compared to control participants. The CSA-PTSD group had reduced activation in the same regions to a lesser extent. This study provides preliminary empirical evidence to suggest CSA impacts AM for traumatic experiences, and the impact is notable even for men who experienced CSA but do not have PTSD. This study highlights the need for more research with men who have experienced CSA, so that, we can fully understand the neural correlates of emotional memories, and better support the mental health and continued wellness of men who experienced CSA.

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.

Amygdala electrical-finger-print (AmygEFP) NeuroFeedback guided by individually-tailored Trauma script for post-traumatic stress disorder: Proof-of-concept.

BACKGROUND: Amygdala activity dysregulation plays a central role in post-traumatic stress disorder (PTSD). Hence learning to self-regulate one's amygdala activity may facilitate recovery. PTSD is further characterized by abnormal contextual processing related to the traumatic memory. Therefore, provoking the personal traumatic narrative while training amygdala down-regulation could enhance clinical efficacy. We report the results of a randomized controlled trial (NCT02544971) of a novel self-neuromodulation procedure (i.e. NeuroFeedback) for PTSD, aimed at down-regulating limbic activity while receiving feedback from an auditory script of a personal traumatic narrative. To scale-up applicability, neural activity was probed by an fMRI-informed EEG model of amygdala activity, termed Amygdala Electrical Finger-Print (AmygEFP). METHODS: Fifty-nine adults meeting DSM-5 criteria for PTSD were randomized between three groups: Trauma-script feedback interface (Trauma-NF) or Neutral feedback interface (Neutral-NF), and a control group of No-NF (to control for spontaneous recovery). Before and immediately after 15 NF training sessions patients were blindly assessed for PTSD symptoms and underwent one session of amygdala fMRI-NF for transferability testing. Follow-up clinical assessment was performed at 3- and 6-months following NF treatment. RESULTS: Patients in both NF groups learned to volitionally down-regulate AmygEFP signal and demonstrated a greater reduction in PTSD symptoms and improved down-regulation of the amygdala during fMRI-NF, compared to the No-NF group. The Trauma-NF group presented the largest immediate clinical improvement. CONCLUSIONS: This proof-of-concept study indicates the feasibility of the AmygEFP-NF process-driven as a scalable intervention for PTSD and illustrates its clinical potential. Further investigation is warranted to elucidate the contribution of AmygEFP-NF beyond exposure and placebo effects.

Looking at the bigger picture: Cortical volume, thickness and surface area characteristics in borderline personality disorder with and without posttraumatic stress disorder.

Borderline personality disorder (BPD) is a severe psychiatric disorder accompanied by multiple comorbidities. Neuroimaging studies have identified structural abnormalities in BPD with most findings pointing to gray matter volume reductions in the fronto-limbic network, although results remain inconsistent. Similar alterations were found in posttraumatic stress disorder (PTSD), a common comorbidity of BPD. Only a small number of studies have investigated structural differences in BPD patients regarding comorbid PTSD specifically and studies conducting additional surface analyses are scarce. We investigated structural differences in women with BPD with and without PTSD and non-patient controls. Automated voxel-based and region-based volumetric analyses were applied. Additionally, four surface-based measures were analyzed: cortical thickness, gyrification index, fractal dimension, and sulcus depth. Analyses did not identify cortical volume alterations in the fronto-limbic network. Instead, hypergyrification was detected in the right superior parietal cortex in BPD patients compared to non-patient controls. No distinction was revealed between BPD patients with and without PTSD. These findings underline the importance of a holistic investigation examining volumetric and surface measures as these might enhance the understanding of structural alterations in BPD.

Neural changes following equine-assisted therapy for posttraumatic stress disorder: A longitudinal multimodal imaging study.

BACKGROUND: While effective treatments for posttraumatic stress disorder (PTSD) exist, many individuals, including military personnel and veterans fail to respond to them. Equine-assisted therapy (EAT), a novel PTSD treatment, may complement existing PTSD interventions. This study employs longitudinal neuro-imaging, including structural magnetic resonance imaging (sMRI), resting state-fMRI (rs-fMRI), and diffusion tensor imaging (DTI), to determine mechanisms and predictors of EAT outcomes for PTSD. METHOD: Nineteen veterans with PTSD completed eight weekly group sessions of EAT undergoing multimodal MRI assessments before and after treatment. Clinical assessments were conducted at baseline, post-treatment and at 3-month follow-up. RESULTS: At post-treatment patients showed a significant increase in caudate functional connectivity (FC) and reduction in the gray matter density of the thalamus and the caudate. The increase of caudate FC was positively associated with clinical improvement seen immediately at post-treatment and at 3-month follow-up. In addition, higher baseline caudate FC was associated with greater PTSD symptom reduction post-treatment. CONCLUSIONS: This exploratory study is the first to demonstrate that EAT can affect functional and structural changes in the brains of patients with PTSD. The findings suggest that EAT may target reward circuitry responsiveness and produce a caudate pruning effect from pre- to post-treatment.

Hippocampal volume recovery with real-time functional MRI amygdala neurofeedback emotional training for posttraumatic stress disorder.

BACKGROUND: Small hippocampal volume is a prevalent neurostructural abnormality in posttraumatic stress disorder (PTSD). However, whether the hippocampal atrophy is the cause of disease symptoms or a pre-existing risk factor and whether it is a reversible alteration or a permanent trait are unclear. The trait- or state-dependent alteration could also differ among the hippocampal subfields. METHODS: The study examined the longitudinal hippocampal volume changes due to positive emotional training with left amygdala (LA) real-time fMRI neurofeedback (rtfMRI-nf) in combat veterans with PTSD. The participants were trained to increase the neurofeedback signal from LA (experimental group, N = 20) or brain region not involved in emotion processing (control group, N = 9) by recalling a positive autobiographical memory. The pre- and post-training structural MRI brain images were processed with FreeSurfer to evaluate the hippocampal subfield volumes. Hippocampal volumes for healthy controls (N = 43) were also examined to evaluate the baseline abnormality in PTSD. RESULTS: A significant group difference in volume change was found in the left CA1 head region. This region had the most significant volume reduction at the baseline in PTSD. The experimental group showed a significant volume increase, while the control group showed a significant volume decrease in this region. The volume change in the control group negatively correlated with interval days between the scans. LIMITATIONS: A cognitive improvement due to the hippocampal volume increase could not be found with symptom scales. CONCLUSIONS: RtfMRI-nf positive emotional training increased the hippocampus volume among people with PTSD, suggesting that hippocampal atrophy in PTSD is modifiable.

Neural correlates of script-driven imagery in adolescents with interpersonal traumatic experiences: A pilot study.

In adults, trauma imagery has proven to be a useful tool to assess the neural mechanisms of psychological trauma processing. In adolescents, heterogeneous results could be found for other tasks, however, a trauma imagery paradigm has not been evaluated. For this purpose, we investigated a trauma imagery paradigm with control scripts to assess neural correlates of traumatic experiences in youth. 15 adolescents, who had experienced a traumatic interpersonal event in the past and have developed clinically relevant symptoms, underwent an fMRI scan while listening to their individual trauma- versus two control scripts (positive/negative). We analysed a parametric contrast of the imagery phases (trauma > negative > positive) which revealed activity in the thalamus, dorsal anterior cingulate cortex, cuneus, dorsomedial prefrontal cortex and amygdala. Additionally, amygdala-activity correlated positively with depression-symptom-severity. Our data provide evidence for the feasibility of fMRI during a trauma imagery task in adolescents to investigate networks previously related to hyperarousal in adults with PTSD. Further, we demonstrate the specificity of the activated networks for trauma imagery as compared to imagery of other emotional situations. The task might be particularly useful to evaluate neural correlates of treatment in adolescents when hyperarousal is a target symptom.

Trauma, treatment and Tetris: video gaming increases hippocampal volume in male patients with combat-related posttraumatic stress disorder.

Background: Tetris has been proposed as a preventative intervention to reduce intrusive memories of a traumatic event. However, no neuroimaging study has assessed Tetris in patients with existing posttraumatic stress disorder (PTSD) or explored how playing Tetris may affect brain structure. Methods: We recruited patients with combat-related PTSD before psychotherapy and randomly assigned them to an experimental Tetris and therapy group (n = 20) or to a therapy-only control group (n = 20). In the control group, participants completed therapy as usual: eye movement desensitization and reprocessing (EMDR) psychotherapy. In the Tetris group, in addition to EMDR, participants also played 60 minutes of Tetris every day from onset to completion of therapy, approximately 6 weeks later. Participants completed structural MRI and psychological questionnaires before and after therapy, and we collected psychological questionnaire data at follow-up, approximately 6 months later. We hypothesized that the Tetris group would show increases in hippocampal volume and reductions in symptoms, both directly after completion of therapy and at follow-up. Results: Following therapy, hippocampal volume increased in the Tetris group, but not the control group. As well, hippocampal increases were correlated with reductions in symptoms of PTSD, depression and anxiety between completion of therapy and follow-up in the Tetris group, but not the control group. Limitations: Playing Tetris may act as a cognitive interference task and as a brain-training intervention, but it was not possible to distinguish between these 2 potential mechanisms. Conclusion: Tetris may be useful as an adjunct therapeutic intervention for PTSD. Tetris-related increases in hippocampal volume may ensure that therapeutic gains are maintained after completion of therapy.

Resting State Functional Connectivity of the Thalamus in North Korean Refugees with and without Posttraumatic Stress Disorder.

In posttraumatic stress disorder (PTSD), functional connectivity (FC) between the thalamus and other brain areas has yet to be comprehensively investigated. The present study explored resting state FC (rsFC) of thalamus and its associations with trauma-related features. The included subjects were North Korean refugees with PTSD (n = 23), trauma-exposed North Korean refugees without PTSD (trauma-exposed control [TEC] group, n = 22), and South Korean healthy controls (HCs) without traumatic experiences (HC group, n = 40). All participants underwent psychiatric evaluation and functional magnetic resonance imaging (fMRI) procedures using the bilateral thalamus as seeds. In the TEC group, the negative rsFC between each thalamus and its contralateral postcentral cortex was stronger relative to the PTSD and HC groups, while positive rsFC between the left thalamus and left precentral cortex was stronger in the HC group compared to the PTSD and TEC groups. Thalamo-postcentral rsFC was positively correlated with the CAPS total score in the TEC group, and with the number of traumatic experiences in the PTSD group. The present study identified the difference of thalamic rsFC alterations among traumatized refugees and HCs. Negative rsFC between the thalamus and somatosensory cortices might be compensatory changes after multiple traumatic events in refugees.

Rt-fMRI neurofeedback-guided cognitive reappraisal training modulates amygdala responsivity in posttraumatic stress disorder.

BACKGROUND: Traumatic experiences are associated with neurofunctional dysregulations in key regions of the emotion regulation circuits. In particular, amygdala responsivity to negative stimuli is exaggerated while engagement of prefrontal regulatory control regions is attenuated. Successful application of emotion regulation (ER) strategies may counteract this disbalance, however, application of learned strategies in daily life is hampered in individuals afflicted by posttraumatic stress disorder (PTSD). We hypothesized that a single session of real-time fMRI (rtfMRI) guided upregulation of prefrontal regions during an emotion regulation task enhances self-control during exposure to negative stimuli and facilitates transfer of the learned ER skills to daily life. METHODS: In a cross-over design, individuals with a PTSD diagnosis after a single traumatic event (n = 20) according to DSM-IV-TR criteria and individuals without a formal psychiatric diagnosis (n = 21) underwent a cognitive reappraisal training. In randomized order, all participants completed two rtfMRI neurofeedback (NF) runs targeting the left lateral prefrontal cortex (lPFC) and two control runs without NF (NoNF) while using cognitive reappraisal to reduce their emotional response to negative scenes. During the NoNF runs, two %%-signs were displayed instead of the two-digit feedback (FB) to achieve a comparable visual stimulation. The project aimed at defining the clinical potential of the training according to three success markers: (1) NF induced changes in left lateral prefrontal cortex and bilateral amygdala activity during the regulation of aversive scenes compared to cognitive reappraisal alone (primary registered outcome), (2) associated changes on the symptomatic and behavioral level such as indicated by PTSD symptom severity and affect ratings, (3) clinical utility such as indicated by perceived efficacy, acceptance, and transfer to daily life measured four weeks after the training. RESULTS: In comparison to the reappraisal without feedback, a neurofeedback-specific decrease in the left lateral PFC (d = 0.54) alongside an attenuation of amygdala responses (d = 0.33) emerged. Reduced amygdala responses during NF were associated with symptom improvement (r = -0.42) and less negative affect (r = -0.63) at follow-up. The difference in symptom scores exceeds requirements for a minimal clinically important difference and corresponds to a medium effect size (d = 0.64). Importantly, 75% of individuals with PTSD used the strategies in daily life during a one-month follow-up period and perceived the training as efficient. CONCLUSION: Our findings suggest beneficial effects of the NF training indicated by reduced amygdala responses that were associated with improved symptom severity and affective state four weeks after the NF training as well as patient-centered perceived control during the training, helpfulness and application of strategies in daily life. However, reduced prefrontal involvement was unexpected. The study suggests good tolerability of the training protocol and potential for clinical use in the treatment of 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.

Brain activity mediators of PTSD symptom reduction during real-time fMRI amygdala neurofeedback emotional training.

Self-regulation of brain activation with real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) is emerging as a promising treatment for psychiatric disorders. The association between the regulation and symptom reduction, however, has not been consistent, and the mechanisms underlying the symptom reduction remain poorly understood. The present study investigated brain activity mediators of the amygdala rtfMRI-nf training effect on combat veterans' PTSD symptom reduction. The training was designed to increase a neurofeedback signal either from the left amygdala (experimental group; EG) or from a control region not implicated in emotion regulation (control group; CG) during positive autobiographical memory recall. We employed a structural equation model mapping analysis to identify brain regions that mediated the effects of the rtfMRI-nf training on PTSD symptoms. Symptom reduction was mediated by low activation in the dorsomedial prefrontal cortex (DMPFC) and the middle cingulate cortex. There was a trend toward less activation in these regions for the EG compared to the CG. Low activation in the precuneus, the right superior parietal, the right insula, and the right cerebellum also mediated symptom reduction while their effects were moderated by the neurofeedback signal; a higher signal was linked to less effect on symptom reduction. This moderation was not specific to the EG. MDD comorbidity was associated with high DMPFC activation, which resulted in less effective regulation of the feedback signal. These results indicated that symptom reduction due to the neurofeedback training was not specifically mediated by the neurofeedback target activity, but broad regions were involved in the process.

Allocentric spatial memory performance predicts intrusive memory severity in posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is characterized by distressing trauma-related memories. According to the dual representation theory, intrusive memories arise from strengthened egocentric encoding and a poor contextual encoding, with spatial context requiring allocentric processing. Contextualization of mental imagery is proposed to be formed hierarchically through the ventral visual stream (VVS) to the hippocampal formation. Here, we tested this notion by investigating whether neuronal aberrations in structures of the VVS or in the hippocampus, as well as allocentric memory performance are associated with intrusive memory severity. METHODS: The sample comprised 33 women with PTSD due to childhood trauma. Allocentric memory performance was measured with the virtual Town Square Task and T1-weighted images acquired on a 3T Siemens Scanner. Intrusive memories were evoked by presenting an audio script describing parts of their trauma (script-driven imagery). RESULTS: Using hierarchical linear regression analysis, we found a significant association between lower intrusive memory severity and higher allocentric spatial memory, controlling for age, working memory, and general visuospatial ability. No significant association was found between cortical thickness of VVS structures, hippocampal volume and intrusive memory severity. Post hoc exploratory analyses revealed a negative correlation between years since index trauma and left hippocampal volume. LIMITATIONS: Our results are based on correlational analyses, causality cannot be inferred. CONCLUSION: This study supports the dual representation theory, which emphasizes the role of allocentric spatial memory for the contextualization of mental imagery in PTSD. Clinical implications are discussed.

Eye movement desensitization and reprocessing for post-traumatic stress disorder from the perspective of three-dimensional model of the experiential selfhood.

Eye Movement Desensitization and Reprocessing (EMDR) therapy is included in many international trauma treatment guidelines and is also shortlisted as an evidence-based practice for the treatment of psychological trauma and Post-Traumatic Stress Disorder (PTSD). However, its neurobiological mechanisms have not yet been fully understood. In this brief article we propose a hypothesis that a recently introduced neurophysiologically based three-dimensional construct model for experiential selfhood may help to fill this gap by providing the necessary neurobiological rationale of EMDR. In support of this proposal we briefly overview the neurophysiology of eye movements and the triad selfhood components, as well as EMDR therapy neuroimaging studies.