Rakesh Jetly

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

Background Three intrinsic connectivity networks in the brain, namely the central executive, salience, and default mode networks, have been identified as crucial to the understanding of higher cognitive functioning, and the functioning of these networks has been suggested to be impaired in psychopathology, including posttraumatic stress disorder (PTSD). Objective 1) To describe three main large-scale networks of the human brain; 2) to discuss the functioning of these neural networks in PTSD and related symptoms; and 3) to offer hypotheses for neuroscientifically-informed interventions based on treating the abnormalities observed in these neural networks in PTSD and related disorders. Method 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.

Plastic modulation of PTSD resting‐state networks and subjective wellbeing by EEG neurofeedback

Electroencephalographic (EEG) neurofeedback training has been shown to produce plastic modulations in salience network and default mode network functional connectivity in healthy individuals. In this study, we investigated whether a single session of neurofeedback training aimed at the voluntary reduction of alpha rhythm (8–12 Hz) amplitude would be related to differences in EEG network oscillations, functional MRI (fMRI) connectivity, and subjective measures of state anxiety and arousal in a group of individuals with post‐traumatic stress disorder (PTSD).

Unintended Consequences of Changing the Definition of Posttraumatic Stress Disorder in DSM-5: Critique and Call for Action

T he 2013 DSM-5, the first major revision of US psychiatric nomenclature since 1994’s DSM-IV, was coordinated by the American Psychiatric Association in a manner to ensure revisions were empirically supported and maintained continuity with previous editions.1,2 Although many important evidence-based changes resulted, core criteria and diagnostic language for most common conditions affecting adults remained unchanged, safeguarding continued use of treatments validated over decades.1,3 A notable exception was posttraumatic stress disorder (PTSD). Criteria were added and major wording changes were made to symptoms that have been foundational clinical descriptors even before DSM-IV— revisions that workgroup members themselves acknowledged were controversial.4-6 Their rationale4-6 appeared to reflect selective interpretations of evidence (eg, based on nonsystematic literature review and overlooking complex neuroscience domains); cognitive theory influenced key changes, potentially lessening the emphasis of other wellestablished neurobiological models underlying evidence-based treatments.7,8 Emerging research has demonstrated that the revised definition offers no improvement in clinical utility, identifies different individuals,andexcludesmanyindividualsmeetingpreviouscriteria.9-11 This article details problematic changes, implications, and rationale for immediate action.

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 (nu2009=u200910) 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.

Deployment-related mental health support: comparative analysis of NATO and allied ISAF partners

Background For years there has been a tremendous gap in our understanding of the mental health effects of deployment and the efforts by military forces at trying to minimize or mitigate these. Many military forces have recently systematized the mental support that is provided to support operational deployments. However, the rationale for doing so and the consequential allocation of resources are felt to vary considerably across North Atlantic Treaty Organisation (NATO) International Security Assistance (ISAF) partners. This review aims to compare the organization and practice of mental support by five partnering countries in the recent deployment in Afghanistan in order to identify and compare the key methods and structures for delivering mental health support, describe bottlenecks and illustrate new developments. Method Information was collected through document analysis and semi-structured interviews with key military mental healthcare stakeholders. The review resulted from close collaboration between key military mental healthcare professionals within the Australian Defense Forces (ADF), Canadian Armed Forces (CAF), United Kingdom Armed Forces (UK), Netherlands Armed Forces (NLD), and the United States Army (US). Key stakeholders were interviewed about the mental health support provided during a servicepersons military career. The main items discussed were training, prevention, early identification, intervention, and aftercare in the field of mental health. Results All forces reported that much attention was paid to mental health during the individuals military career, including deployment. In doing so there was much overlap between the rationale and applied methods. The main method of providing support was through training and education. The educative focus was to strengthen the mental resilience of individual soldiers while providing a range of mental healthcare services. All forces had abandoned standard psychological debriefing after critical incidents. Instead, by default, mental healthcare professionals acted to support the leader and peer led “after action” reviews. All countries provided professional mental support close to the front line, aimed at early detection and early return to normal activities within the unit. All countries deployed a mental health support team that consisted of a range of mental health staff including psychiatrists, psychologists, social workers, mental health nurses, and chaplains. There was no overall consensus in the allocation of mental health disciplines in theatre. All countries (except the US) provided troops with a third location decompression (TLD) stop after deployment, which aimed to recognize what the deployed units had been through and to prepare them for transition home. The US conducted in-garrison ‘decompression’, or ‘reintegration training’ in the US, with a similiar focus to TLD. All had a reasonably comparable infrastructure in the field of mental healthcare. Shared bottlenecks across countries included perceived stigma and barriers to care around mental health problems as well as the need for improving the awareness and recognition of mental health problems among service members. among service personnel as well as the need for improving the awareness and recognition of symptoms as being indicative of a mental health problems among service members. Conclusion This analysis demonstrated that in all five partners state-of-the-art preventative mental healthcare was included in the last deployment in Afghanistan, including a positive approach towards strengthening the mental resilience, a focus on self-regulatory skills and self-empowerment, and several initiatives that were well-integrated in a military context. These initiatives were partly/completely implemented by the military/colleagues/supervisors and applicable during several phases of the deployment cycle. Important new developments in operational mental health support are recognition of the role of social leadership and enhancement of operational peer support. This requires awareness of mental problems that will contribute to reduction of the barriers to care in case of problems. Finally, comparing mental health support services across countries can contribute to optimal preparation for the challenges of military deployment.

Alpha oscillation neurofeedback modulates amygdala complex connectivity and arousal in posttraumatic stress disorder

Objective Electroencephalogram (EEG) neurofeedback aimed at reducing the amplitude of the alpha-rhythm has been shown to alter neural networks associated with posttraumatic stress disorder (PTSD), leading to symptom alleviation. Critically, the amygdala is thought to be one of the central brain regions mediating PTSD symptoms. In the current study, we compare directly patterns of amygdala complex connectivity using fMRI, before and after EEG neurofeedback, in order to observe subcortical mechanisms associated with behavioural and alpha oscillatory changes among patients. Method We examined basolateral (BLA), centromedial (CMA), and superficial (SFA) amygdala complex resting-state functional connectivity using a seed-based approach via SPM Anatomy Toolbox. Amygdala complex connectivity was measured in twenty-one individuals with PTSD, before and after a 30-minute session of EEG neurofeedback targeting alpha desynchronization. Results EEG neurofeedback was associated with a shift in amygdala complex connectivity from areas implicated in defensive, emotional, and fear processing/memory retrieval (left BLA and left SFA to the periaqueductal gray, and left SFA to the left hippocampus) to prefrontal areas implicated in emotion regulation/modulation (right CMA to the medial prefrontal cortex). This shift in amygdala complex connectivity was associated with reduced arousal, greater resting alpha synchronization, and was negatively correlated to PTSD symptom severity. Conclusion These findings have significant implications for developing targeted non-invasive treatment interventions for PTSD patients that utilize alpha oscillatory neurofeedback, showing evidence of neuronal reconfiguration between areas highly implicated in the disorder, in addition to acute symptom alleviation.

Neurofeedback Tunes Scale-Free Dynamics in Spontaneous Brain Activity

Brain oscillations exhibit long-range temporal correlations (LRTCs), which reflect the regularity of their fluctuations: lowxa0values representing more random (decorrelated) while high values more persistent (correlated) dynamics. LRTCs constitute supporting evidence that the brain operates near criticality, a state where neuronal activities are balanced between order and randomness. Here, healthy adults used closed-loop brain training (neurofeedback, NFB) to reduce the amplitude of alpha oscillations, producing a significant increase in spontaneous LRTCs post-training. This effect was reproduced in patients with post-traumatic stress disorder, where abnormally random dynamics were reversed byxa0NFB, correlating with significant improvements in hyperarousal. Notably, regions manifesting abnormally low LRTCs (i.e., excessive randomness) normalized toward healthy population levels, consistent with theoretical predictions about self-organized criticality. Hence, when exposed to appropriate training, spontaneous cortical activity reveals a residual capacity for self-tuning its own temporal complexity, despite manifesting the abnormal dynamics seen in individuals with psychiatric disorder. Lastly, we observed an inverse-U relationship between strength of LRTC and oscillation amplitude, suggesting a breakdown of long-range dependence at high/low synchronization extremes, in line with recent computational models. Together, our findings offer a broader mechanistic framework for motivating research and clinical applications of NFB, encompassing disorders with perturbed LRTCs.

Concerns Over Divergent Approaches in the Diagnostics of Posttraumatic Stress Disorder

CME Article Concerns Over Divergent Approaches in the Diagnostics of Posttraumatic Stress Disorder Copyrighted material. Not for distribution. Eric Vermetten, MD, PhD; Dewleen G. Baker, MD; Rakesh Jetly, MD; and Alexander C. McFarlane, MD, PhD ABSTRACT Since the inception of posttraumatic stress disorder (PTSD) in the Diagnostic and Statisti- cal Manual of Mental Disorders, third edition (DSM-III), there has been an ongoing polemic debate about the veracity, assessment, neurobiology, and longitudinal course of the disor- der. As a consequence, its clinical utility has been the subject of a significant amount of con- flicting opinion due to the competing interests involving clinicians, insurance companies, victim’s groups, and governments. This article reviews some of the current divergent ap- proaches in the diagnosis of PTSD, including the debate on the condition itself, claims that it is overdiagnosed, the usefulness of the “A” criterion, equivalence of cluster criteria, the role of combat and civilian PTSD, the role of biomarkers, incongruences in diagnostic practice, and the need for a consistent approach that ensures diagnostic congruence. Critical drivers of di- vergent diagnostic systems are that they should not produce significantly different rates or produce high levels of discordance. However, one of the concerns is that the anticipated In- ternational Statistical Classification of Diseases and Related Health Problems, eleventh edition (ICD-11) has moved away from this primary aim and taken a markedly divergent approach that is incompatible with the advancement of consensus within this critical field. This article explores some of the primary arguments and evidence cited for this approach in ICD-11 and recent changes in DSM-5. [Psychiatr Ann. 2016;46(9):498-509.]

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

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 (PTSDu2009+u2009DS) often exhibit increased mPFC top–down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSDu2009+u2009DS 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, PTSDu2009+u2009DS, 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 [nu2009=u200962]; PTSDu2009+u2009DS [nu2009=u200941]; age‐matched healthy trauma‐unexposed controls [nu2009=u200952]). 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, PTSDu2009+u2009DS 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 PTSDu2009+u2009DS 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.

Battlefield ethics training: integrating ethical scenarios in high-intensity military field exercises

There is growing evidence that modern missions have added stresses and ethical complexities not seen in previous military operations and that there are links between battlefield stressors and ethical lapses. Military ethicists have concluded that the ethical challenges of modern missions are not well addressed by current military ethics educational programs. Integrating the extant research in the area, we propose that scenario-based operational ethics training in high-intensity military field training settings may be an important adjunct to traditional military ethics education and training. We make the case as to why this approach will enhance ethical operational preparation for soldiers, supporting their psychological well-being as well as mission effectiveness.