The Psychophysiology of Fear and Anxiety

National Institute Of Mental Health

Investigators

Linked publications & trials

Abstract

The lab focuses on understanding several aspects of normal and pathological anxiety. Our research includes neuroimaging to understand brain mechanisms; psychophysiology to explore emotional reactivity; affective neuroscience to investigate cognitive processes; and psychopharmacology to screen new treatments. In addition, the COVID-19 pandemic gave us the opportunity to examine risk factors of anxiety in response to a chronic environmental threat. To study attentional problems caused by anxiety, we have developed a research program that explores the interaction between anxiety and working memory (WM). WM refers to the temporary storage and manipulation of information (e.g., remembering a phone number when dialing the number). WM not only helps keep in mind our current goals, but it also gives rise to the conscious experience of anxiety. In past studies, we have identified brain structures of a frontoparietal control network that play important roles in the interaction between anxiety and WM. More recently, we implemented a pharmacological manipulation using a cognitive enhancer, methylphenidate (MPH), to investigate the impact of improving cognition on anxiety. We showed that MPH increases overall WM performance and strengthened the engagement of the frontoparietal control network while also reducing the default mode network deactivation. The facilitation of neural activation can be interpreted as an expansion of cognitive resources, which could foster both the representation and integration of anxiety-provoking stimuli as well as the top-down regulatory processes to protect against the detrimental effect of anxiety. This year, we expanded our knowledge of the anxiety-related effects of MPH during WM on brain function, using a computational analysis. This analysis, Topological Data Analysis (TDA)-based Mapper. . Findings showed that MPH facilitated greater differential engagement of neural resources (brain activity) across low and high working memory load conditions. Furthermore, load-based differential management of neural resources reflected enhanced efficiency. These results provide novel insights regarding brain mechanisms that facilitate cognitive enhancement under MPH and, in future research, may be used to help mitigate anxiety-related cognitive underperformance. We have pursued the fear conditioning thematic. We reframe components of fear conditioning as prediction errors and report how neural circuits reflect prediction errors during aversive Pavlovian learning. We queried the periaqueductal gray matter (PAG), a structure exquisitely linked to fear responses. Results of this study suggest that the PAG and mid-cingulate cortex play a role in processing salient information related to safety during differential conditioning and may function to attenuate and regulate defensive responses to conditioned threat stimuli. Expanding research on the interaction of anxiety with inhibitory/attentional processes, we reanalyzed past data using the drift-diffusion computational model (DDM). The DDM analysis showed that induced anxiety was associated with an amplified drift rate process, which reflects increased informational uptake. Moreover, these changes in drift rate during the anxiety condition were associated with enhanced BOLD responses within the posterior cingulate cortex during Go trials. Collectively, these results shed light on the mechanisms underlying facilitated task performance and suggest that anxiety can improve cognitive processing by enhancing information uptake and increasing activity within the posterior cingulate cortex. The DDM approach is currently applied to a larger sample of both healthy volunteers and individuals with an anxiety disorder. Another direction of the lab has focused on decision-making in anxiety. Two projects have been dedicated to this theme. The first project examined loss aversion, an economic concept that has been extensively studied in the general population. Our goal was to examine how loss aversion was affected by the presence of anxiety, both clinical anxiety and experimentally induced anxiety. We found that high ratings of symptoms of anxiety arousal, but not of symptoms of psychological distress, were associated with worsened loss aversion. This was found only in individuals with anxiety, independently of the threat or safe context. These findings underscore the importance of the subjective experience of physical symptoms of anxiety in decision-making for patients with clinical anxiety. In the past year, the lab has increased research in the neuroimaging analysis of intrinsic functional connectivity. Analysis of resting state fMRI data has gained prominence as a tool to infer functional connectivity (fc) in brain networks. Functional connectivity is defined as the level of coherence in neural activity of anatomically distinct brain regions. Surprisingly, one underlying assumption of most fc analyses is temporal stationarity, i.e., no phase difference between the signals considered. However, there is increasing evidence that challenges this assumption. There are several methods that capture the dynamic nature of the fc. Our lab has implemented a new technique based on dynamic time warping (DTW). This technique was found to be more efficient in assessing the separability of the SNc-cortical and VTA-cortical network compared to traditional methods. We expanded this study by enrolling individuals with anxiety. Finally, we have initiated a project that examines the effects of the COVID-19 pandemic on mental health, particularly risk factors and protective factors, in three different samples, general population (sample of convenience), individuals who had been participated in an NIH resting state neuroimaging study prior to the pandemic, and a sample of patients with a diagnosis of Congenital Adrenal Hyperplasia. Specifically, this project examines the effects of a severe chronic environmental threat (pandemic) on mental health and cognitive processes of attention bias and motivation. A number of studies have been planned: (1) The examination of sexual dimorphism in mental health responses, with an emphasis on a comparison of individuals with a history of excess testosterone in utero (CAH), which is expected to affect responses of stress; (2) The examination of neural predictors of mental health outcomes using data from the NIH sample; (3) Longitudinal data analysis of changes in stress responses to the pandemic, at an average of 6 months intervals; and (4) Relationships between attention bias to threat (on-line dot-probe task) and motivation to approach or avoid outcomes (online finger-tapping task) with stress responses to the pandemic.