Neuroimaging studies of psychological interventions for mood and anxiety disorders: empirical and methodological review.

This article reviews the methods and results of published neuroimaging studies of the effects of structured psychological interventions for mood and anxiety disorders. The results are consistent with neural models of improved affective- and self-regulation, as evidenced by psychotherapeutic modulation of brain metabolic activity within the dorsolateral, ventrolateral, and medial prefrontal cortices, the anterior cingulate, the posterior cingulate/precuneus, and the insular cortices. Specific recommendations for future studies are outlined, and the clinical and theoretical significance of this research is discussed

Mind over chatter: plastic up-regulation of the fMRI alertness network by EEG neurofeedback

EEG neurofeedback (NFB) is a brain-computer interface (BCI) approach used to shape brain oscillations by means of real-time feedback from the electroencephalogram (EEG), which is known to reflect neural activity across cortical networks. Although NFB is being evaluated as a novel tool for treating brain disorders, evidence is scarce on the mechanism of its impact on brain function. In this study with 34 healthy participants, we examined whether, during the performance of an attentional auditory oddball task, the functional connectivity strength of distinct fMRI networks would be plastically altered after a 30-min NFB session of alpha-band reduction (n=17) versus a sham-feedback condition (n=17). Our results reveal that compared to sham, NFB induced a specific increase of functional connectivity within the alertness/salience network (dorsal anterior and mid cingulate), which was detectable 30 minutes after termination of training. Crucially, these effects were significantly correlated with reduced mind-wandering 'on-task' and were coupled to NFB-mediated resting state reductions in the alpha-band (8-12 Hz). No such relationships were evident for the sham condition. Although group default-mode network (DMN) connectivity was not significantly altered following NFB, we observed a positive association between modulations of resting alpha amplitude and precuneal connectivity, both correlating positively with frequency of mind-wandering. Our findings demonstrate a temporally direct, plastic impact of NFB on large-scale brain functional networks, and provide promising neurobehavioral evidence supporting its use as a noninvasive tool to modulate brain function in health and disease

Trauma-Related Altered States of Consciousness: Exploring the 4-D Model

22 pagesFrewen and Lanius (in press) recently articulated a 4-D model as a framework for classifying symptoms of posttraumatic stress into those that potentially occur within normal waking consciousness (NWC) versus those that intrinsically represent dissociative experiences of trauma-related altered states of consciousness (TRASC). Four dimensions were specified: time-memory, thought, body, and emotion. The 4-D model further hypothesizes that in traumatized persons, symptoms of TRASC, compared with NWC forms of distress, will be (a) observed less frequently; (b) less intercorrelated, especially as measured as moment-to-moment states; (c) observed more frequently in people with high dissociative symptomatology as measured independently; and (d) observed more often in people who have experienced repeated traumatization, particularly early developmental trauma. The aim of the present research was to begin to evaluate these 4 predictions of the 4-D model. Within a sample of 74 women with posttraumatic stress disorder (PTSD) primarily due to histories of childhood trauma, as well as within a 2nd sample of 504 undergraduates (384 females), the 1st 2 hypotheses of the 4-D model were supported. In addition, within the PTSD sample, the 3rd hypothesis was supported. However, inconsistent with the 4th hypothesis, severity of childhood trauma history was not strongly associated with TRASC. We conclude that the hypotheses articulated by the 4-D model were generally supported, although further research in different trauma-related disorders is needed, and the role of childhood trauma history in the etiology of TRASC requires further research

A Review of the Relation Between Dissociation, Memory, Executive Functioning and Social Cognition in Military Members and Civilians with Neuropsychiatric Conditions

Dissociative experiences, involving altered states of consciousness, have long been understood as a consequence or response to traumatic experiences, where a reduced level of consciousness may aid in survival during and after a traumatic event. Indeed, the dissociative subtype of post-traumatic stress disorder (PTSD-DS) was added recently to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Dissociative symptoms are present across a host of neuropsychiatric conditions, including PTSD, psychotic spectrum illnesses, anxiety and mood disorders. Transdiagnostically, the presence of dissociative symptoms is associated with a greater illness burden and reduced treatment outcomes. Critically, dissociative symptoms are related to impaired performance on measures of attention, executive functioning, memory, and social cognition and may contribute to the widespread cognitive dysfunction observed across psychiatric illnesses. Despite this knowledge, the relation between dissociative symptoms and reduced cognitive function remains poorly understood. Here, we review the evidence linking dissociative symptoms to cognitive dysfunction across neuropsychiatric disorders. In addition, we explore two potential neurobiological mechanisms that may underlie the relation between dissociative symptoms and cognitive dysfunction in trauma-related neuropsychiatric conditions. Specifically, we hypothesize that: 1) functional sensory deafferentation at the level of the thalamus, as observed in the defence cascade model of dissociation, may underlie reduced attention and arousal leading to progressive cognitive dysfunction and; 2) altered functional connectivity between key brain networks implicated in cognitive functioning may represent a critical neurobiological mechanism linking dissociative symptoms and cognitive dysfunction in patients with PTSD-DS and transdiagnostically

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 neuroscientificallyinformed 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

Meta-analysis of alexithymia in posttraumatic stress disorder.

The authors present a meta-analysis investigating the prevalence of alexithymia in 12 studies encompassing 1,095 individuals with posttraumatic stress disorder (PTSD). A large effect size was found associating PTSD with alexithymia. Effect sizes were higher in studies of male combat PTSD samples in comparison with studies of other PTSD samples. Clinical and research directions are discussed

Contrasting Associations Between Heart Rate Variability and Brainstem-Limbic Connectivity in Posttraumatic Stress Disorder and Its Dissociative Subtype: A Pilot Study

Background: Increasing evidence points toward the need to extend the neurobiological conceptualization of posttraumatic stress disorder (PTSD) to include evolutionarily conserved neurocircuitries centered on the brainstem and the midbrain. The reticular activating system (RAS) helps to shape the arousal state of the brain, acting as a bridge between brain and body. To modulate arousal, the RAS is closely tied to the autonomic nervous system (ANS). Individuals with PTSD often reveal altered arousal patterns, ranging from hyper- to blunted arousal states, as well as altered functional connectivity profiles of key arousal-related brain structures that receive direct projections from the RAS. Accordingly, the present study aims to explore resting state functional connectivity of the RAS and its interaction with the ANS in participants with PTSD and its dissociative subtype. Methods: Individuals with PTSD (n = 57), its dissociative subtype (PTSD + DS, n = 32) and healthy controls (n = 40) underwent a 6-min resting functional magnetic resonance imaging and pulse data recording. Resting state functional connectivity (rsFC) of a central node of the RAS – the pedunculopontine nuclei (PPN) – was investigated along with its relation to ANS functioning as indexed by heart rate variability (HRV). HRV is a prominent marker indexing the flexibility of an organism to react adaptively to environmental needs, with higher HRV representing greater effective adaptation. Results: Both PTSD and PTSD + DS demonstrated reduced HRV as compared to controls. HRV measures were then correlated with rsFC of the PPN. Critically, participants with PTSD and participants with PTSD + DS displayed inverse correlations between HRV and rsFC between the PPN and key limbic structures, including the amygdala. Whereas participants with PTSD displayed a positive relationship between HRV and PPN rsFC with the amygdala, participants with PTSD + DS demonstrated a negative relationship between HRV and PPN rsFC with the amygdala. Conclusion: The present exploratory investigation reveals contrasting patterns of arousal-related circuitry among participants with PTSD and PTSD + DS, providing a neurobiological lens to interpret hyper- and more blunted arousal states in PTSD and PTSD + DS, respectively

The Vestibulocerebellum and the Shattered Self: a Resting-State Functional Connectivity Study in Posttraumatic Stress Disorder and Its Dissociative Subtype

The flocculus is a region of the vestibulocerebellum dedicated to the coordination of neck, head, and eye movements for optimal posture, balance, and orienting responses. Despite growing evidence of vestibular and oculomotor impairments in the aftermath of traumatic stress, little is known about the effects of chronic psychological trauma on vestibulocerebellar functioning. Here, we investigated alterations in functional connectivity of the flocculus at rest among individuals with post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS) as compared to healthy controls. Forty-four healthy controls, 57 PTSD, and 32 PTSD + DS underwent 6-min resting-state MRI scans. Seed-based functional connectivity analyses using the right and left flocculi as seeds were performed. These analyses revealed that, as compared to controls, PTSD and PTSD + DS showed decreased resting-state functional connectivity of the left flocculus with cortical regions involved in bodily self-consciousness, including the temporo-parietal junction, the supramarginal and angular gyri, and the superior parietal lobule. Moreover, as compared to controls, the PTSD + DS group showed decreased functional connectivity of the left flocculus with the medial prefrontal cortex, the precuneus, and the mid/posterior cingulum, key regions of the default mode network. Critically, when comparing PTSD + DS to PTSD, we observed increased functional connectivity of the right flocculus with the right anterior hippocampus, a region affected frequently by early life trauma. Taken together, our findings point toward the crucial role of the flocculus in the neurocircuitry underlying a coherent and embodied self, which can be compromised in PTSD and PTSD + DS

A Pilot Randomized Controlled Trial of Goal Management Training in Canadian Military Members, Veterans, and Public Safety Personnel Experiencing Post-Traumatic Stress Symptoms

Post-traumatic stress disorder (PTSD) is a severe psychiatric illness that disproportionately affects military personnel, veterans, and public safety personnel (PSP). Evidence demonstrates that PTSD is significantly associated with difficulties with emotion regulation (ER) and difficulties with cognitive functioning, including difficulties with attention, working memory, and executive functioning. A wide body of evidence suggests a dynamic interplay among cognitive dysfunction, difficulties with ER, and symptoms of PTSD, where numerous studies have identified overlapping patterns of alterations in activation among neuroanatomical regions and neural circuitry. Little work has examined interventions that may target these symptoms collectively. The primary objective of this pilot randomized controlled trial (RCT) with a parallel experimental design was to assess the effectiveness of goal management training (GMT), a cognitive remediation intervention, in reducing difficulties with cognitive functioning, and to determine its effects on PTSD symptoms and symptoms associated with PTSD, including difficulties with ER, dissociation, and functioning among military personnel, veterans, and PSP. Forty-two military personnel, veterans, and PSP between the ages of 18 and 70 with symptoms of PTSD were recruited across Ontario, Canada between October 2017 and August 2019. Participants were randomized to either the waitlist (WL) (n = 18) or the GMT (n = 22) condition. Participants in both conditions received self-report measures and a comprehensive neuropsychological assessment at baseline, post-intervention, and 3-month follow-up. Following their completion of the 3-month follow-up, participants in the WL condition were given the opportunity to participate in GMT. Assessors and participants were blind to intervention allocation during the initial assessment. A series of 2 (time) × 2 (group) ANOVAs were conducted to assess the differences between the WL and GMT conditions from pre-to post-intervention for the self-report and neuropsychological measures. The results demonstrated significant improvements in measures of executive functioning (e.g., verbal fluency, planning, impulsivity, cognitive shifting, and discrimination of targets) and trending improvements in short-term declarative memory for participants in the GMT condition. Participants in the GMT condition also demonstrated significant improvements from pre-to post-testing in measures of subjective cognition, functioning, PTSD symptom severity, difficulties with ER, dissociative symptom severity, and depression and anxiety symptoms. No adverse effects were reported as a result of participating in GMT. The results of this pilot RCT show promise that GMT may be a useful intervention to improve symptoms of cognitive dysfunction, symptoms of PTSD, and symptoms associated with PTSD within military personnel, veterans, and PSP. Future work is needed to address the small sample size and the durability of these findings

The hijacked self: Disrupted functional connectivity between the periaqueductal gray and the default mode network in posttraumatic stress disorder using dynamic causal modeling.

Self-related processes define assorted self-relevant or social-cognitive functions that allow us to gather insight and to draw inferences related to our own mental conditions. Self-related processes are mediated by the default mode network (DMN), which, critically, shows altered functionality in individuals with posttraumatic stress disorder (PTSD). In PTSD, the midbrain periaqueductal gray (PAG) demonstrates stronger functional connectivity with the DMN [i.e., precuneus (PCN), medial prefrontal cortex (mPFC)] as compared to healthy individuals during subliminal, trauma-related stimulus processing. Here, we analyzed the directed functional connectivity between the PAG and the PCN, as well as between the PAG and the mPFC to more explicitly characterize the functional connectivity we have observed previously on the corresponding sample and paradigm. We evaluated three models varying with regard to context-dependent modulatory directions (i.e., bi-directional, bottom-up, top-down) among individuals with PTSD (n = 26) and healthy participants (n = 20), where Bayesian model selection was used to identify the most optimal model for each group. We then compared the effective connectivity strength for each parameter across the models and between our groups using Bayesian model averaging. Bi-directional models were found to be favoured across both groups. In PTSD, we revealed the PAG to show stronger excitatory effective connectivity to the PCN, as well as to the mPFC as compared to controls. In PTSD, we further demonstrated that PAG-mediated effective connectivity to the PCN, as well as to the mPFC were modulated more strongly during subliminal, trauma-related stimulus conditions as compared to controls. Clinical disturbances towards self-related processes are reported widely by participants with PTSD during trauma-related stimulus processing, where altered functional connectivity directed by the PAG to the DMN may elucidate experiential links between self- and trauma-related processing in traumatized individuals