Neural Responses During Trace Conditioning with Face and Non-Face Stimuli Recorded with Magnetoencephalography

During fear conditioning a subject is presented with an initially innocuous stimulus like an image (conditioned stimulus; CS) that predicts an aversive outcome like a mild electric shock (unconditioned stimulus; UCS). Subjects rapidly learn that the CS predicts the UCS, and show autonomic fear responses (CRs) during the presentation of the CS. When the CS and the UCS coterminate, as is the case for delay conditioning, individuals can acquire CRs even if they are unable to predict the occurrence of the UCS. However when there is a temporal gap between the CS and the UCS, CR expression is typically dependent upon explicit awareness of the CS-UCS pairing. Research with non-human animals suggests that both the hippocampus and the prefrontal cortex are needed for trace but not delay fear conditioning, and that communication between these areas may help to maintain the CS during the trace interval. We tested this hypothesis by exposing subjects to differential delay and trace fear conditioning while we recorded their brain activity with magnetoencephalography. Faces and houses served as CSs and an aversive electrical stimulation served as the UCS. As predicted, subjects show evidence of conditioning on both implicit and explicit measures. In addition, there is a learning related increase in theta coherence between the left parahippocampal gyrus and several frontal and parietal cortical regions for trace but not delay conditioning. These results suggest that trace conditioning recruits a network of cortical regions, and that the activity of these regions is coordinated by the medial temporal lobe

Responding to uncertain threat:A potential mediator for the effect of mindfulness on anxiety

Mindfulness-based interventions have gained extensive support for their application in the treatment of anxiety. However, their mechanisms remain largely unexplored. Excessive reactivity to uncertainty plays a central role in anxiety, and may represent a mechanism for the effect of mindfulness on anxiety, as mindfulness training fosters an open and accepting stance towards all aspects of experience. The present study sought to investigate both (i) self-reported intolerance of uncertainty (IU) as well as (ii) physiological and subjective responding to uncertain threat in a threat-of-shock paradigm, the NPU-threat test, as mediators for the relationship between mindfulness and anxiety in a cross-sectional study of healthy participants (N = 53). The results indicated that IU mediated the effect of mindfulness on some anxiety symptoms. In contrast, scores of physiological as well as subjective responses to uncertain threat from the NPU-threat test were largely unrelated to mindfulness, anxiety, or the IU self-report measure. The results provide initial evidence that reactions to uncertainty may play a role in the mindfulness-anxiety relationship and suggest that studies are needed to address how methodological variations of the NPU-threat test affect perceived levels of uncertainty and uncertainty-related anxiety

Toward personalized circuit-based closed-loop brain-interventions in psychiatry: using symptom provocation to extract EEG-markers of brain circuit activity

Symptom provocation is a well-established component of psychiatric research and therapy. It is hypothesized that specific activation of those brain circuits involved in the symptomatic expression of a brain pathology makes the relevant neural substrate accessible as a target for therapeutic interventions. For example, in the treatment of obsessive-compulsive disorder (OCD), symptom provocation is an important part of psychotherapy and is also performed prior to therapeutic brain stimulation with transcranial magnetic stimulation (TMS). Here, we discuss the potential of symptom provocation to isolate neurophysiological biomarkers reflecting the fluctuating activity of relevant brain networks with the goal of subsequently using these markers as targets to guide therapy. We put forward a general experimental framework based on the rapid switching between psychiatric symptom states. This enable neurophysiological measures to be derived from EEG and/or TMS-evoked EEG measures of brain activity during both states. By subtracting the data recorded during the baseline state from that recorded during the provoked state, the resulting contrast would ideally isolate the specific neural circuits differentially activated during the expression of symptoms. A similar approach enables the design of effective classifiers of brain activity from EEG data in Brain-Computer Interfaces (BCI). To obtain reliable contrast data, psychiatric state switching needs to be achieved multiple times during a continuous recording so that slow changes of brain activity affect both conditions equally. This is achieved easily for conditions that can be controlled intentionally, such as motor imagery, attention, or memory retention. With regard to psychiatric symptoms, an increase can often be provoked effectively relatively easily, however, it can be difficult to reliably and rapidly return to a baseline state. Here, we review different approaches to return from a provoked state to a baseline state and how these may be applied to different symptoms occurring in different psychiatric disorders

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the enigma-anxiety working group

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology

The effect of threat on novelty evoked amygdala responses.

A number of recent papers have suggested that the amygdala plays a role in the brain's novelty detection circuit. In a recent study, we showed that this role may be specific to certain classes of biologically-relevant stimuli, such as human faces. The purpose of the present experiment was to determine whether other biologically-relevant stimuli also evoke novelty specific amygdala responses. To test this idea, we presented novel and repeated images of snakes and flowers while measuring BOLD. Surprisingly, we found that novel images of snakes and flowers evoke more amygdala activity than repeated images of snakes and flowers. Our results further confirm the robustness of the novelty evoked amygdala responses, even when compared with effects more traditionally associated with the amygdala. In addition, our results suggest that threatening stimuli may prime the amygdala to respond to other types of stimuli as well