Walker S. Pedersen

The effects of stimulus novelty and negativity on BOLD activity in the amygdala, hippocampus, and bed nucleus of the stria terminalis

Abstract The amygdala responds to stimulus novelty, which may correspond to an evaluation of novel stimuli for potential threat, and trait anxiety may modulate this response. The bed nucleus of the stria terminalis (BNST) may also be sensitive to novelty as it responds to both uncertainty and threat. If so, a BNST novelty response may also be affected by trait anxiety and interact with stimulus negativity. We presented participants with novel and repeated negative and neutral images while measuring brain activity via fMRI, and assessed participants’ self-reported trait anxiety. We expected to replicate past findings of novelty responses in the hippocampus and amygdala that are independent of stimulus negativity. We also expected BNST novelty-sensitivity and that trait anxiety would predict greater sensitivity to both novelty and negativity in the amygdala and BNST, but not the hippocampus. Our a priori analyses replicated past findings of a novelty response that was independent of valence in the hippocampus and amygdala. The BNST exhibited a novelty response for negative, but not neutral, images. Trait anxiety did not modulate the response to novelty or negativity in any of the ROIs investigated. Our findings suggest that the BNST plays a role in the detection of novelty. Key words: novelty; bed nucleus of the stria terminalis; BNST; amygdale; fMRI; BST

BAS Reward Responsiveness: A unique predictor of positive psychological functioning

Previous research on Reinforcement Sensitivity Theory has well-characterized the Behavioral Inhibition System in terms of its behavioral and emotional manifestations, but the Behavioral Approach System (BAS) is less well-defined, particularly regarding the prominence of reward sensitivity versus impulsivity. Furthermore, few researchers evaluate both systems in one model. We evaluated the relationship between Carver and Whites (1994) BIS/BAS Scales and areas of psychological functioning including internalizing, externalizing, affect regulation, and well-being. 497 undergraduates completed a battery of self-report measures. Two structural equation models indicate that the Reward Responsiveness subscale uniquely predicts adaptive functioning across all domains. Reward Responsiveness may be a more pure measure of BAS than other BAS traits and may be important for resilience from maladaptive psychological functioning.

Cortical Gyrification Patterns Associated with Trait Anxiety

Dispositional anxiety is a stable personality trait that is a key risk factor for internalizing disorders, and understanding the neural correlates of trait anxiety may help us better understand the development of these disorders. Abnormal cortical folding is thought to reflect differences in cortical connectivity occurring during brain development. Therefore, assessing gyrification may advance understanding of cortical development and organization associated with trait anxiety. Previous literature has revealed structural abnormalities in trait anxiety and related disorders, but no study to our knowledge has examined gyrification in trait anxiety. We utilized a relatively novel measure, the local gyrification index (LGI), to explore differences in gyrification as a function of trait anxiety. We obtained structural MRI scans using a 3T magnetic resonance scanner on 113 young adults. Results indicated a negative correlation between trait anxiety and LGI in the left superior parietal cortex, specifically the precuneus, reflecting less cortical complexity among those high on trait anxiety. Our findings suggest that aberrations in cortical gyrification in a key region of the default mode network is a correlate of trait anxiety and may reflect disrupted local parietal connectivity.

Neural circuitry governing anxious individuals’ mis-allocation of working memory to threat

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.

Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala–BNST connectivity during periods of threat vs safety

Abstract Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants’ self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala–BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism.

Cortico-limbic connectivity changes following fear extinction and relationships with trait anxiety

Abstract Fear extinction is a powerful model of adaptive and anxiety‐related maladaptive fear inhibition. This learning process is dependent upon plastic interactions between the amygdala, the anterior midcingulate cortex (aMCC), the hippocampus, and the ventromedial prefrontal cortex (vmPFC). With regard to the amygdala, the basolateral (BLA) and centromedial amygdala (CMA) serve unique roles in fear extinction. In a large sample (N = 91), the current study examined pre‐ to post‐extinction changes in resting state functional connectivity (RSFC) of fear inhibition and expression pathways. We also examined how trait anxiety and extinction performance were associated with extinction‐related changes within these neural pathways. We found stronger pre‐ to post‐extinction RSFC in pathways known to play a role in the down‐regulation of fear responses (BLA‐hippocampus, aMCC‐hippocampus, CMA‐hippocampus, CMA‐aMCC). We also found that trait anxiety was associated with strengthening of a BLA‐aMCC circuit supporting fear expression following extinction learning. Furthermore, we found that physiological indices of poorer extinction learning were linked to weaker pre‐ to post‐extinction RSFC of a BLA‐hippocampus pathway important for fear extinction consolidation. Our results highlight the network changes that occur during extinction, the separable role of CMA and BLA‐based circuitry and a key pathway linked to risk for anxiety pathology.

Moderating effects of harm avoidance on resting-state functional connectivity of the anterior insula

As an index of behavioral inhibition and an individual’s propensity to avoid, rather than seek, potentially dangerous situations, harm avoidance has been linked to internalizing psychopathology. Altered connectivity within intrinsic functional neural networks (i.e., default mode [DMN], central executive [CEN] and salience networks [SN]) has been related to internalizing psychopathology; however, less is known about the effects of harm avoidance on functional connectivity within and between these networks. Importantly, harm avoidance may be distinguishable from trait anxiety and have clinical relevance as a risk factor for internalizing psychopathology. A sample of young adults (n = 99) completed a resting state functional magnetic resonance imaging (fMRI) scan and self-report measures of harm avoidance and trait anxiety. Whole brain seed-to-voxel and seed-to-network connectivity analyses were conducted using anterior insula seeds to examine associations between harm avoidance/trait anxiety and connectivity. After adjusting for sex and age, there was a significant negative effect of harm avoidance on connectivity between the anterior insula and clusters in the precuneus/posterior cingulate cortex (PCC) left superior/middle frontal gyrus, dorsal anterior cingulate cortex (dACC) and bilateral inferior parietal lobule (IPL)/angular gyrus. Seed-to-network analyses indicated a negative effect of harm avoidance on connectivity between the right anterior insula and anterior and posterior DMN. There were no effects of trait anxiety on functional connectivity of the anterior insula. Overall, the results indicate that individual differences in harm avoidance relate to disruptions in internetwork connectivity that may contribute to deficits in appropriately modulating attentional focus.