Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Moral wounds run deep: exaggerated midbrain functional network connectivity across the default mode network in posttraumatic stress disorder.

BACKGROUND: A moral injury occurs when a deeply held moral code has been violated, and it can lead to the development of symptoms of posttraumatic stress disorder (PTSD). However, the neural correlates that differentiate moral injury and PTSD remain largely unknown. Intrinsic connectivity networks such as the default mode network (DMN) appear to be altered in people with PTSD who have experienced moral injury. However, brainstem, midbrain and cerebellar systems are rarely integrated into the intrinsic connectivity networks; this is a critical oversight, because these systems display marked differences in people with PTSD and are thought to underlie strong moral emotions such as shame, guilt and betrayal. METHODS: We conducted an independent component analysis on data generated during script-driven memory recall of moral injury in participants with military- or law enforcement-related PTSD (n = 28), participants with civilian-related PTSD (n = 28) and healthy controls exposed to a potentially morally injurious event (n = 18). We conducted group-wise comparisons of functional network connectivity differences across a DMN-correlated independent component, with a particular focus on brainstem, midbrain and cerebellar systems. RESULTS: We found stronger functional network connectivity in the midbrain periaqueductal grey (t 71 = 4.95, p FDR = 0.028, k = 39) and cerebellar lobule IX (t 71 = 4.44, p FDR = 0.046, k = 49) in participants with civilian-related PTSD as compared to healthy controls. We also found a trend toward stronger functional network connectivity in the midbrain periaqueductal grey (t 71 = 4.22, p FDR = 0.076, k = 60) in participants with military- or law enforcement-related PTSD as compared to healthy controls. LIMITATIONS: The significant clusters were large, but resolution is generally lower for subcortical structures. CONCLUSION: In PTSD, the DMN appears to be biased toward lower-level, midbrain systems, which may drive toxic shame and related moral emotions that are common in PTSD, highlighting the depth at which moral injuries are represented neurobiologically.

Shame on the brain: Neural correlates of moral injury event recall in posttraumatic stress disorder.

BACKGROUND: Moral injury (MI) is consistently associated with adverse mental health outcomes, including the development of posttraumatic stress disorder (PTSD) and suicidality. METHODS: We investigated neural activation patterns associated with MI event recall using functional magnetic resonance imaging in participants with military and public safety-related PTSD, relative to civilian MI-exposed controls. RESULTS: MI recall in the PTSD as compared to control group was associated with increased neural activation among salience network nodes involved in viscerosensory processing and hyperarousal (right posterior insula, dorsal anterior cingulate cortex; dACC), regions involved in defensive responding (left postcentral gyrus), and areas responsible for top-down cognitive control of emotions (left dorsolateral prefrontal cortex; dlPFC). Within the PTSD group, measures of state and trait shame correlated negatively with activity among default mode network regions associated with self-related processing and moral cognition (dorsomedial prefrontal cortex; dmPFC) and salience network regions associated with viscerosensory processing (left posterior insula), respectively. CONCLUSIONS: These findings suggest that MI event processing is altered in military and public safety-related PTSD, relative to MI-exposed controls. Here, it appears probable that as individuals with PTSD recall their MI event, they experience a surge of blame-related processing of bodily sensations within salience network regions, including the right posterior insula and the dACC, which in turn, prompt regulatory strategies at the level of the left dlPFC aimed at increasing cognitive control and inhibiting emotional affect. These results are consistent with previous findings showing enhanced sensory processing and altered top-down control in PTSD samples during autobiographical memory recall.

Machine learning multivariate pattern analysis predicts classification of posttraumatic stress disorder and its dissociative subtype: a multimodal neuroimaging approach.

BACKGROUND: The field of psychiatry would benefit significantly from developing objective biomarkers that could facilitate the early identification of heterogeneous subtypes of illness. Critically, although machine learning pattern recognition methods have been applied recently to predict many psychiatric disorders, these techniques have not been utilized to predict subtypes of posttraumatic stress disorder (PTSD), including the dissociative subtype of PTSD (PTSD + DS). METHODS: Using Multiclass Gaussian Process Classification within PRoNTo, we examined the classification accuracy of: (i) the mean amplitude of low-frequency fluctuations (mALFF; reflecting spontaneous neural activity during rest); and (ii) seed-based amygdala complex functional connectivity within 181 participants [PTSD (n = 81); PTSD + DS (n = 49); and age-matched healthy trauma-unexposed controls (n = 51)]. We also computed mass-univariate analyses in order to observe regional group differences [false-discovery-rate (FDR)-cluster corrected p < 0.05, k = 20]. RESULTS: We found that extracted features could predict accurately the classification of PTSD, PTSD + DS, and healthy controls, using both resting-state mALFF (91.63% balanced accuracy, p < 0.001) and amygdala complex connectivity maps (85.00% balanced accuracy, p < 0.001). These results were replicated using independent machine learning algorithms/cross-validation procedures. Moreover, areas weighted as being most important for group classification also displayed significant group differences at the univariate level. Here, whereas the PTSD + DS group displayed increased activation within emotion regulation regions, the PTSD group showed increased activation within the amygdala, globus pallidus, and motor/somatosensory regions. CONCLUSION: The current study has significant implications for advancing machine learning applications within the field of psychiatry, as well as for developing objective biomarkers indicative of diagnostic heterogeneity.

Predicting patterns of service utilization within children's mental health agencies.

BACKGROUND: Some children with mental health (MH) problems have been found to receive ongoing care, either continuously or episodically. We sought to replicate patterns of MH service use over extended time periods, and test predictors of these patterns. METHODS: Latent class analyses were applied to 4 years of visit data from five MH agencies and nearly 6000 children, 4- to 13-years-old at their first visit. RESULTS: Five patterns of service use were identified, replicating previous findings. Overall, 14% of cases had two or more episodes of care and 23% were involved for more than 2 years. Most children (53%) were seen for just a few visits within a few months. Two patterns represented cases with two or more episodes of care spanning multiple years. In the two remaining patterns, children tended to have just one episode of care, but the number of sessions and length of involvement varied. Using discriminant function analyses, we were able to predict with just over 50% accuracy children's pattern of service use. Severe externalizing behaviors, high impairment, and high family burden predicted service use patterns with long durations of involvement and frequent visits. CONCLUSIONS: Optimal treatment approaches for children seen for repeated episodes of care or for care lasting multiple years need to be developed. Children with the highest level of need (severe pathology, impairment, and burden) are probably best served by providing high intensity services at the start of care.

Nonlinear Indices with Applications to Schizophrenia and Bipolar Disorder.

In this article we study the application of nonlinear indices (sometimes called complexity indices) to univariate time series data arising from studies of schizophrenia and bipolar disorder. Specifically, we consider time series arising from EEG studies, ECG studies, and self-report mood data. As part of our analysis, we empirically examine the claim in the literature that complexity tends to be higher in the EEG of schizophrenia patients than controls and that this tendency is dampened or even inverted by medication, increasing age, and reduced symptomatology. Our conclusion is that this claim is only partially supported and propose that symptomatology, specifically the presence or absence of schizophrenia 'deficit syndrome,' may be the most important factor. Results are more consistent in ECG studies in which reduced heart rate complexity is observed in both schizophrenia and bipolar disorder. The applications of nonlinear indices to the effects of antipsychotic medication and the discrimination of mood states are also examined. It is concluded that the monitoring of nonlinear indices may be useful in predicting response to medication and predicting onset of specific mood states.

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.

Dynamic causal modeling in PTSD and its dissociative subtype: Bottom-up versus top-down processing within fear and emotion regulation circuitry.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with decreased top-down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top-down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls. METHODS: To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting-state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [n = 62]; PTSD + DS [n = 41]; age-matched healthy trauma-unexposed controls [n = 52]). RESULTS: PTSD was characterized by a pattern of predominant bottom-up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top-down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC. CONCLUSIONS: These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper- vs. hypo-emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom-up defensive fear processing versus enhanced top-down regulation. Hum Brain Mapp 38:5551-5561, 2017. © 2017 Wiley Periodicals, Inc.

The neurobiology of emotion regulation in posttraumatic stress disorder: Amygdala downregulation via real-time fMRI neurofeedback.

Amygdala dysregulation has been shown to be central to the pathophysiology of posttraumatic stress disorder (PTSD) representing a critical treatment target. Here, amygdala downregulation was targeted using real-time fMRI neurofeedback (rt-fMRI-nf) in patients with PTSD, allowing us to examine further the regulation of emotional states during symptom provocation. Patients (n = 10) completed three sessions of rt-fMRI-nf with the instruction to downregulate activation in the amygdala, while viewing personalized trauma words. Amygdala downregulation was assessed by contrasting (a) regulate trials, with (b) viewing trauma words and not attempting to regulate. Training was followed by one transfer run not involving neurofeedback. Generalized psychophysiological interaction (gPPI) and dynamic causal modeling (DCM) analyses were also computed to explore task-based functional connectivity and causal structure, respectively. It was found that PTSD patients were able to successfully downregulate both right and left amygdala activation, showing sustained effects within the transfer run. Increased activation in the dorsolateral and ventrolateral prefrontal cortex (PFC), regions related to emotion regulation, was observed during regulate as compared with view conditions. Importantly, activation in the PFC, rostral anterior cingulate cortex, and the insula, were negatively correlated to PTSD dissociative symptoms in the transfer run. Increased functional connectivity between the amygdala- and both the dorsolateral and dorsomedial PFC was found during regulate, as compared with view conditions during neurofeedback training. Finally, our DCM analysis exploring directional structure suggested that amygdala downregulation involves both top-down and bottom-up information flow with regard to observed PFC-amygdala connectivity. This is the first demonstration of successful downregulation of the amygdala using rt-fMRI-nf in PTSD, which was critically sustained in a subsequent transfer run without neurofeedback, and corresponded to increased connectivity with prefrontal regions involved in emotion regulation during the intervention. Hum Brain Mapp 38:541-560, 2017. © 2016 Wiley Periodicals, Inc.

Trauma-Related Altered States of Consciousness (TRASC) and Functional Impairment I: Prospective Study in Acutely Traumatized Persons.

A theoretical framework referred to as a 4-D model has been described for classifying posttraumatic stress symptoms into those potentially occurring within normal waking consciousness (NWC) versus those thought to intrinsically exemplify dissociative experiences, specifically, trauma-related altered states of consciousness (TRASC). As a further test of this theoretical distinction, this prospective study evaluated whether TRASC and NWC forms of distress incrementally and prospectively predicted functional impairment at 6 and 12 weeks following presentation at hospital emergency departments in the acute aftermath of traumatic events in 180 persons. Establishing the clinical significance of both TRASC and NWC-distress symptoms, we found that 6-week markers of TRASC and NWC-distress independently predicted 12-week self-reported levels of social and occupational impairment. We also observed broad support for various predictions of the 4-D model except that, in contrast with hypotheses, childhood trauma history was generally more strongly correlated with symptoms of NWC-distress than with TRASC. Future research directions are discussed.

Defining Episodes of Care in Children's Mental Health Using Administrative Data.

Criteria to define an episode of care in children's mental health services are needed. Various criteria were applied to 5 years of visit data from children 4-11 years (N = 5,206) at their first visit to 1 of 3 children's mental health agencies. A minimum of 3 visits with 180 days between episodes optimized agreement with other dates (e.g., telephone intake assessment) marking the start and end of an episode, and clinician-rated number of episodes. Grouping visits into episodes provides a clearer representation of how services are distributed over extended periods of time, facilitating research and enhancing accuracy in service planning.

The impact of acute violent videogame exposure on neurocognitive markers of emotional empathic state.

Research examining the purported association between violent gaming and aggression remains controversial due to concerns related to methodology, unclear neurocognitive mechanisms, and the failure to adequately consider the role of individual differences in susceptibility. To help address these concerns, we used fMRI and an emotional empathy task to examine whether acute and cumulative violent gaming exposure were associated with abnormalities in emotional empathy as a function of trait-empathy. Emotional empathy was targeted given its involvement in regulating not only aggression, but also other important social functions such as compassion and prosocial behaviour. We hypothesized that violent media exposure increases the risk of aberrant social behaviour by altering the aversive value of distress cues. Contrary to expectations, neither behavioural ratings nor empathy-related brain activity varied as a function of violent gaming exposure. Notably, however, activation patterns in somatosensory and motor cortices reflected an interaction between violent media exposure and trait empathy. Thus, our results are inconsistent with a straightforward relationship between violent media exposure and reduced empathy. Furthermore, they highlight the importance of considering both individual differences in susceptibility, and other aspects of cognition related to social functioning to best inform public concern regarding safe gaming practices.

Homeostatic normalization of alpha brain rhythms within the default-mode network and reduced symptoms in post-traumatic stress disorder following a randomized controlled trial of electroencephalogram neurofeedback.

Collective research has identified a key electroencephalogram signature in patients with post-traumatic stress disorder, consisting of abnormally reduced alpha (8-12 Hz) rhythms. We conducted a 20-session, double-blind, randomized controlled trial of alpha desynchronizing neurofeedback in patients with post-traumatic stress disorder over 20 weeks. Our objective was to provide mechanistic evidence underlying potential clinical improvements by examining changes in aberrant post-traumatic stress disorder brain rhythms (namely, alpha oscillations) as a function of neurofeedback treatment. We randomly assigned participants with a primary diagnosis of post-traumatic stress disorder (n = 38) to either an experimental group (n = 20) or a sham-control group (n = 18). A multichannel electroencephalogram cap was used to record whole-scalp resting-state activity pre- and post-neurofeedback treatment, for both the experimental and sham-control post-traumatic stress disorder groups. We first observed significantly reduced relative alpha source power at baseline in patients with post-traumatic stress disorder as compared to an age/sex-matched group of neurotypical healthy controls (n = 32), primarily within regions of the anterior default mode network. Post-treatment, we found that only post-traumatic stress disorder patients in the experimental neurofeedback group demonstrated significant alpha resynchronization within areas that displayed abnormally low alpha power at baseline. In parallel, we observed significantly decreased post-traumatic stress disorder severity scores in the experimental neurofeedback group only, when comparing baseline to post-treatment (Cohen's d = 0.77) and three-month follow-up scores (Cohen's d = 0.75), with a remission rate of 60.0% at the three-month follow-up. Overall, our results indicate that neurofeedback training can rescue pathologically reduced alpha rhythmicity, a functional biomarker that has repeatedly been linked to symptoms of hyperarousal and cortical disinhibition in post-traumatic stress disorder. This randomized controlled trial provides long-term evidence suggesting that the 'alpha rebound effect' (i.e. homeostatic alpha resynchronization) occurs within key regions of the default mode network previously implicated in post-traumatic stress disorder.

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.

The vicious cycle of psychopathology and stressful life events: A meta-analytic review testing the stress generation model.

Stress generation theory initially posited that depression elevates risk for some stressful events (i.e., dependent events) but not others (i.e., independent events). This preregistered meta-analytic review examined whether stress generation occurs transdiagnostically by examining 95 longitudinal studies with 38,228 participants (537 total effect sizes) from over 30 years of research. Our multilevel meta-analyses found evidence of stress generation across a broad range of psychopathology, as evidenced by significantly larger prospective effects for dependent (overall psychopathology: r = .23) than independent (overall psychopathology: r = .10) stress. We also identified unique patterns of effects across specific types of psychopathology. For example, effects were larger for depression than anxiety. Furthermore, effects were sometimes larger in studies with younger participants, shorter time lags between assessments, checklist measures of stress, and for interpersonal stressors. Finally, a multilevel meta-analytic structural equation model suggested that dependent stress exacerbates psychopathology symptoms over time (ß = .04), possibly contributing to chronicity. Interventions targeting the prevention of stress generation may mitigate chronic psychopathology. Conclusions of this study are limited by the predominance of depression effect sizes in the literature and our review of only English language articles. On the other hand, the findings are strengthened by rigorous inclusion criteria, lack of publication bias, and absence of moderating effects by publication year. The latter underscores the replicability of the stress generation effect over the last 30 years. Taken together, the review provides robust evidence that stress generation is a cross-diagnostic phenomenon that contributes to a vicious cycle of increasing stress and psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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

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

Progressive membrane phospholipid changes in first episode schizophrenia with high field magnetic resonance spectroscopy.

Patients with a first episode of schizophrenia generally have increased phospholipid membrane breakdown products within the brain, while findings in chronic patients have been inconsistent. In this study we examine progressive changes in phosphorus membrane metabolites in the same patient group through the early years of schizophrenia in brain regions associated with the disease. Sixteen never-treated and medicated first episode schizophrenic patients were assessed at 10 months and 52 months after diagnosis. Sixteen matched volunteers were assessed at baseline and after 35 months. Phospholipid membrane metabolism was assessed with phosphorous magnetic resonance spectroscopy in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex, parieto-occipital cortex, superior temporal gyrus and temporal pole. At 10 months, glycerophosphocholine was increased in the anterior cingulate in patients as compared to controls. Glycerophosphocholine was decreased in the anterior cingulate and increased in the posterior cingulate and left superior temporal gyrus; glycerophosphoethanolamine was decreased in the left thalamus and increased in the left hippocampus within patients over time. At 52 months, compared to controls phosphocholine was increased in the left thalamus and glycerophosphoethanolamine was increased in the left hippocampus. These results imply a gradual inclusion of brain regions in schizophrenia where an initial increase, followed by a decrease in phospholipid membrane metabolites was observed. This pattern, observed in the early years of schizophrenia, is consistent with excitotoxic neural membrane breakdown in these regions.

Nonlinear bifurcations of psychological stress negotiation: new properties of a formal dynamical model.

Dynamical systems analysis is applied to a nonlinear model of stress and coping (Neufeld, 1999). The model is composed of 6 order parameters and 11 control parameters, and integrates core constructs of the topic domain, including variants of cognitive appraisal, differential stress susceptibility, stress activation, and coping propensity. In part owing to recent advances in Competitive Modes Theory (Yao, Yu & Essex, 2002), previously intractable but substantively significant dynamical properties of the 6-dimensional model are identified. They include stable and unstable fixed-point equilibria (higher-dimensional saddle-node bifurcation), oscillatory patterns attending fixed-point de-stabilization, and chaotic behaviors. Examination of the nature of system fixed-point de-stabilization, in relation to its control parameters, unveils mechanisms of re-stabilization, and dynamic stability control. All identified dynamics emerge naturally from a system whose construction guideposts are lodged in the addressed content domain. Dynamical complexities therefore may be intrinsic to the present content domain, possibly no less so than in other disciplines where the presence of such attributes has been established.

Predicting youth aggression with empathy and callous unemotional traits: A Meta-analytic review.

Historically, empathy has been thought to motivate prosocial behaviour and inhibit aggressive behaviour. Contrary to current assumptions and theoretical support, a meta-analysis revealed a small effect of empathy on aggression among adults (Vachon, Lynam, & Johnson, 2014). The current study sought to determine whether broadening the focus from empathy to include other socially relevant affective characteristics (i.e., callous-unemotional traits) was advantageous in predicting aggressive behaviour. As little is known about the strength of this association among youth, the current study meta-analytically examined 192 unique effect sizes drawn from published and unpublished studies reporting on samples of children and adolescents. Analyses were conducted across general, cognitive, and emotional empathy, as well as callous-unemotional traits, and general, direct, indirect, proactive, and reactive aggression. Significant variability was noted across effect sizes. Consistent with a prior meta-analysis involving adults (Vachon et al., 2014), small to moderate associations were identified between aggression and traditional measures of empathy (i.e., general, emotional, cognitive); these effects ranged from r = -0.06 to -0.26. Among broader measures of emotional style (i.e., callous-unemotional traits), moderate to large effects were found; ranging from r = 0.30 to 0.37. Results suggested that broader affective measures may be more strongly associated with aggression than empathy alone. The results raise questions about the nature of empathy assessment and indicate the utility of targeting multiple emotion-related factors during treatment to effectively reduce aggressive behaviour. In particular, the results underscore of the importance of considering the limited prosocial emotions specifier (perhaps trans-diagnostically given the varied nature of the sample) when considering implications for prognosis and treatment targets.

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.