Biology subjects

Craske, M. G.

Publications and source records attributed to Craske, M. G..

4 recordsLinked to original sources

bioRxiv2025

Computational modelling reveals slower safety learning and threat extinction are associated with higher anxiety severity in remote fear conditioning

Anxiety disorders are are chronic, pervasive, and debilitating; characterised by a persistent or exaggerated response to distal or abstract threats. Impaired threat discrimination (distinguishing safe from threatening stimuli) and impaired threat extinction (learning a once threatening stimulus is now safe), are known risk factors in the development and persistence of anxiety disorders. These effects can be experimentally elicited through fear conditioning. First, repeated trials of paired aversive and neutral stimuli are delivered during a fear acquisition phase, followed by repeated trials with no aversive stimuli in a fear extinction phase. The effects are typically measured through comparison of end-phase data points, or simple descriptive or statistical models. Computational modelling, by contrast, can offer a hypothesis-driven, trial-by-trial mechanistic account of fear conditioning. This unmasks within subject task variance by estimating the rate of threat learning, safety learning, and threat extinction, examining individual differences in the cognitive mechanisms behind anxiety. A normative sample (n = 145) underwent a differential fear conditioning task on a bespoke smartphone app, in addition to completing an anxiety severity measure (GAD-7). Computational models fitted to task data estimated learning rates. Whilst the threat learning rate showed no association, the threat extinction and safety learning rates showed small negative associations with anxiety severity (r = -0.218, p = 0.008 & r = -0.214, p = 0.01 respectively). These findings are in keeping with prior studies using traditional analytical approaches, and indicate that anxious individuals are not quicker to develop fear of a stimulus, but take more time than their non-anxious counterparts to learn that a stimulus is safe. This study strengthens the evidence for impairments in fear extinction in those with anxiety, and the importance of learning rates as an index of anxiety severity, a previously hidden cognitive mechanism underlying anxiety persistence.

neuroscience↗

bioRxiv2023

Broadening the scope: Multiple functional connectivity networks underlying threat and safety signaling

IntroductionThreat learning and extinction processes are thought to be foundational to anxiety and fear-related disorders. However, the study of these processes in the human brain has largely focused on a priori regions of interest, owing partly to the ease of translating between these regions in human and non-human animals. Moving beyond analyzing focal regions of interest to whole-brain dynamics during threat learning is essential for understanding the neuropathology of fear-related disorders in humans. Methods223 participants completed a 2-day Pavlovian threat conditioning paradigm while undergoing fMRI. Participants completed threat acquisition and extinction. Extinction recall was assessed 48 hours later. Using a data-driven group independent component analysis (ICA), we examined large-scale functional connectivity networks during each phase of threat conditioning. Connectivity networks were tested to see how they responded to conditional stimuli during early and late phases of threat acquisition and extinction and during early trials of extinction recall. ResultsA network overlapping with the default mode network involving hippocampus, vmPFC, and posterior cingulate was implicated in threat acquisition and extinction. Another network overlapping with the salience network involving dACC, mPFC, and inferior frontal gyrus was implicated in threat acquisition and extinction recall. Other networks overlapping with parts of the salience, somatomotor, visual, and fronto-parietal networks were involved in the acquisition or extinction of learned threat responses. ConclusionsThese findings help confirm previous investigations of specific brain regions in a model-free fashion and introduce new findings of spatially independent networks during threat and safety learning. Rather than being a single process in a core network of regions, threat learning involves multiple brain networks operating in parallel coordinating different functions at different timescales. Understanding the nature and interplay of these dynamics will be critical for comprehensive understanding of the multiple processes that may be at play in the neuropathology of anxiety and fear-related disorders.

neuroscience↗

bioRxiv2020

Evidence for distinct genetic and environmental influences on fear acquisition and extinction

BackgroundAnxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioning. We conducted a remote fear conditioning paradigm in monozygotic and dizygotic twins to determine the degree and extent of overlap between genetic and environmental influences on fear acquisition and extinction. Methods1937 twins aged 22-25 years, including 538 complete pairs from the Twins Early Development Study (TEDS) took part in a fear conditioning experiment delivered remotely via the Fear Learning and Anxiety Response (FLARe) smartphone app. In the fear acquisition phase participants were exposed to two neutral shape stimuli, one of which was repeatedly paired with a loud aversive noise, while the other was never paired with anything aversive. In the extinction phase the shapes were repeatedly presented again, this time without the aversive noise. Outcomes were participant ratings of how much they expected the aversive noise to occur when they saw either shape, throughout each phase. ResultsTwin analyses indicated a significant contribution of genetic effects to the initial acquisition and consolidation of fear, and the extinction of fear (15%, 30% and 15% respectively) with the remainder of variance due to the non-shared environment. Multivariate analyses revealed that the development of fear and fear extinction show moderate genetic overlap (genetic correlations .4-.5). ConclusionsFear acquisition and extinction are heritable, and share some, but not all of the same genetic influences.

genetics↗

bioRxiv2019

Posttraumatic Stress Disorder and the Social Brain: Affect-Related Disruption of the Default and Mirror Networks

BackgroundSocial impairments, specifically in mentalizing and emotion recognition, are common and debilitating symptoms of posttraumatic stress disorder (PTSD). Despite this, little is known about the neural underpinnings of these impairments, as there have been no published neuroimaging investigations of social inference in PTSD. MethodsTrauma-exposed veterans with and without PTSD (N = 20 each) performed the Why/How social inference task during functional magnetic resonance imaging (fMRI). The PTSD group had two fMRI sessions, between which they underwent affect labeling training. We probed the primary networks of the "social brain"--the default mode network (DMN) and mirror neuron system (MNS)--by examining neural activity evoked by mentalizing and action identification prompts, which were paired with emotional and non-emotional targets. ResultsHyperactivation to emotional stimuli differentiated PTSD patients from controls, correlated with symptom severity, and predicted training outcomes. Critically, these effects were generally non-significant for non-emotional stimuli. PTSD-related effects were widely distributed throughout DMN and MNS. Effects were strongest in regions associated with the dorsal attention, ventral attention, and frontoparietal control networks. Unexpectedly, effects were non-significant in core affect regions. ConclusionsThe array of social cognitive processes subserved by DMN and MNS may be inordinately selective for emotional stimuli in PTSD. This selectivity may be tightly linked with attentional processes, as effects were strongest in attention-related regions. Putatively, we propose an attentional account of social inference dysfunction in PTSD, in which affective attentional biases drive widespread affect-selectivity throughout the social brain. This account aligns with numerous findings of affect-biased attentional processing in PTSD.

neuroscience↗