Abstract
Dispositional anxiety is a trait-like phenotype that confers increased risk for a range of debilitating neuropsychiatric disorders. Like many patients with anxiety disorders, individuals with elevated levels of dispositional anxiety are prone to intrusive and distressing thoughts in the absence of immediate threat. Recent electrophysiological research suggests that these symptoms are rooted in the mis-allocation of working memory (WM) resources to threat-related information. Here, functional MRI was used to identify the network of brain regions that support WM for faces and to quantify the allocation of neural resources to threat-related distracters in 81 young adults. Results revealed widespread evidence of mis-allocation. This was evident in both face-selective regions of the fusiform cortex and domain-general regions of the prefrontal and parietal cortices. This bias was exaggerated among individuals with a more anxious disposition. Mediation analyses provided compelling evidence that anxious individuals’ tendency to mis-allocate WM resources to threat-related distracters is statistically explained by heightened amygdala reactivity. Collectively, these results provide a neurocognitive framework for understanding the pathways linking anxious phenotypes to the development of internalizing psychopathology and set the stage for developing improved intervention strategies.
Highlights
Heightened levels of dispositional anxiety confer increased risk for the development of internalizing disorders, including anxiety and co-morbid depression[1]
If threat-related distracters more readily infiltrate working memory (WM), we would expect load-sensitive regions of the Posterior Parietal Cortex (PPC), dlPFC, and Fusiform Face Area (FFA) to track this mis-allocation of resources (Fig. 2a,b)
Similar levels of activation were evident in all three regions during the maintenance of threat-related and neutral facial expressions when they were task-relevant targets (2 Neutral Targets ≅ Neutral Target + they were targets (Threat) Target), ts(80) < 1.22, ps > 0.22. These findings demonstrate that WM resources in the PPC, dlPFC, and FFA are mis-allocated to threat-related information when it is irrelevant to on-going task demands, extending the results of earlier electrophysiological research[7]
Summary
Heightened levels of dispositional anxiety confer increased risk for the development of internalizing disorders, including anxiety and co-morbid depression[1]. A number of studies have examined ‘emotional’ WM12, 13, the neural circuitry underlying mis-allocation of emotional WM, a key feature of the anxious phenotype, has never before been examined using neuroimaging techniques and remains unknown Addressing this question is important for understanding the mechanisms that confer risk for psychopathology, for optimizing interventions, and for clarifying the biological bases of dispositional anxiety. Subjects performed a separate ‘localizer’ task[15], enabling us to independently identify regions involved in face perception Using these data, we tested whether WM resources are mis-allocated to threat-related distracters and the degree to which this is enhanced among individuals with a more anxious disposition. The amygdala is known to play a key role in biasing attention to threat-related information and is more reactive to threat among individuals with elevated levels of dispositional anxiety or anxiety disorders[22]. A statistical mediation framework was used[23] to rigorously test whether anxious individuals’ biased allocation of WM resources can be explained by heightened amygdala reactivity to threat
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