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.

Academic Medical Organization of Southwestern Ontario.

In healthy individuals, direct eye contact initially leads to activation of a fast subcortical pathway, which then modulates a cortical route eliciting social cognitive processes. The aim of this study was to gain insight into the neurobiological effects of direct eye-to-eye contact using a virtual reality paradigm in individuals with posttraumatic stress disorder (PTSD) related to prolonged childhood abuse. We examined 16 healthy comparison subjects and 16 patients with a primary diagnosis of PTSD using a virtual reality functional magnetic resonance imaging paradigm involving direct vs averted gaze (happy, sad, neutral) as developed by Schrammel et al. in 2009. Irrespective of the displayed emotion, controls exhibited an increased blood oxygenation level-dependent response during direct vs averted gaze within the dorsomedial prefrontal cortex, left temporoparietal junction and right temporal pole. Under the same conditions, individuals with PTSD showed increased activation within the superior colliculus (SC)/periaqueductal gray (PAG) and locus coeruleus. Our findings suggest that healthy controls react to the exposure of direct gaze with an activation of a cortical route that enhances evaluative 'top-down' processes underlying social interactions. In individuals with PTSD, however, direct gaze leads to sustained activation of a subcortical route of eye-contact processing, an innate alarm system involving the SC and the underlying circuits of the PAG.

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.

BackgroundInformation technologies such as websites, mobile phone applications, and virtual reality programs have been shown to deliver innovative and effective treatments for mental illness. Much of the research studying electronic mental health interventions focuses on symptom reduction; however, to facilitate the implementation of electronic interventions in usual mental health care, it is also important to investigate the perceptions of clients who will be using the technologies. To this end, a qualitative analysis of focus group discussions regarding the Mental Health Engagement Network, a web-based personal health record and smartphone intervention, is presented here.MethodsIndividuals living in the community with a mood or psychotic disorder (n = 394) were provided with a smartphone and access to an electronic personal health record, the Lawson SMART Record, for 12 to 18 months to manage their mental health. This study employed a delayed-implementation design and obtained both quantitative and qualitative data through individual interviews and focus group sessions. Participants had the opportunity to participate in voluntary focus group sessions at three points throughout the study to discuss their perceptions of the technologies. Qualitative data from 95 focus group participants were analysed using a thematic analysis.ResultsFour overarching themes emerged from focus group discussions: 1) Versatile functionality of the Lawson SMART Record and smartphone facilitated use; 2) Aspects of the technologies as barriers to use; 3) Use of the Mental health Engagement Network technologies resulted in perceived positive outcomes; 4) Future enhancement of the Lawson SMART Record and intervention is recommended.DiscussionThese qualitative data provide a valuable contribution to the understanding of how smarttechnologies can be integrated into usual mental health care. Smartphones are extremely portable andcommonplace in society. Therefore, clients can use these devices to manage and track mental health issuesin any place at almost any time without feeling stigmatized.ConclusionsAssessing clients’ perspectives regarding the use of smart technologies in mental health care provides an invaluable addition to the current literature. Qualitative findings support the feasibility of implementing a smartphone and electronic personal health record intervention with individuals who are living in the community and experiencing a mental illness, and provide considerations for future development and implementation.

BackgroundCurrent psychometric measures of childhood trauma history generally fail to assess the relational-socioecological context within which childhood maltreatment occurs, including the relationship of abusers to abused persons, the emotional availability of caregivers, and the respondent's own thoughts, feelings, and actions in response to maltreatment.ObjectiveTo evaluate a computerized approach to measuring the relational-socioecological context within which childhood maltreatment occurs.MethodThe psychometric properties of a Childhood Attachment and Relational Trauma Screen (CARTS) were evaluated as a retrospective survey of childhood maltreatment history designed to be appropriate for completion by adults. Participants were undergraduates (n=222), an internet sample (n=123), and psychiatric outpatients (n=30).ResultsThe internal reliability, convergent, and concurrent validity of the CARTS were supported across samples. Paired differences in means and correlations between rated item-descriptiveness to self, mothers, and fathers also accorded with findings of prior attachment and maltreatment research, illustrating the utility of assessing the occurrence and effects of maltreatment within a relational-socioecological framework.ConclusionsResults preliminarily support a new survey methodology for assessing childhood maltreatment within a relational-socioecological framework. Further psychometric evaluation of the CARTS is warranted.

Objective: Long-acting injectable risperidone represents the first clinically available depot atypical antipsychotic. The present study used positron emission tomography (PET) to evaluate its dopamine D 2 binding profile at doses of 25, 50, or 75 mg administered every 2 weeks. Method:After achieving stabilization with one of the doses, nine patients with a diagnosis of schizophrenia or schizoaffective disorder underwent [ 11 C]raclopride PET to measure D 2 occupancy. Participants were scanned twice during the 2-week injection interval: within 3 days after injection (postinjection) and within 5 days before the next injection (preinjection). At the same time, plasma was collected for measurements of risperidone plus 9-hydroxyrisperidone.Results: Mean post-and preinjection D 2 occupancy levels for the 25-, 50-, and 75-mg doses were 71.0% and 54.0%, 74.4% and 65.4%, and 81.5% and 75.0%, respectively. There was a significant correlation between dose and plasma concentrations of risperidone plus 9-hydroxyrisperidone, and the estimated plasma concentration asso ciated with 50% D 2 occupancy (ED 50 ) was 11.06 ng/ml. Prolactin levels were not correlated with drug levels or D 2 occupancy.Conclusions: All three doses of injectable risperidone showed peak D 2 occupancy levels above the 65% threshold associated with optimal clinical response; the 75-mg dose approximated the 80% threshold linked to increased risk of extrapyramidal symptoms. Doses of 25 or 50 mg should provide therapeutic efficacy while minimizing the risk of extrapyramidal symptoms.

Humor is a complex cognitive function which often leads to laughter. Contemporary humor theorists have begun to formulate hypotheses outlining the possible innate cognitive structures underlying humor. Humor's conspicuous presence in the behavioral repertoire of humankind invites adaptive explanations. This article explores the possible adaptive features of humor and ponders its evolutionary path through hominid history. Current humor theories and previous evolutionary ideas on humor are reviewed. In addition, scientific fields germane to the evolutionary study of humor are examined: animal models, genetics, children's humor, humor in pathological conditions, neurobiology, humor in traditional societies and cognitive archeology. Candidate selection pressures and associated evolutionary mechanisms are considered. The authors conclude that several evolutionary-related topics such as the origins of language, cognition underlying spiritual feelings, hominid group size, and primate teasing could have special relevance to the origins of humor.