In the grip of worry: cerebral blood flow changes during worry induction and reappraisal in late-life generalized anxiety disorder

Severe worry includes a complex blend of maladaptive affective and cognitive processes. Contrary to other forms of anxiety, there is no consensus in the field regarding the neural basis of worry. To date, no study has looked at neural patterns associated specifically with in-scanner induction and reappraisal of worry. In this study, we attempt to describe distinct components of the 'neural phenomenology' of worry: induction, maintenance, severity and reappraisal, by using a personalized, in-scanner worry script. Twenty older, non-anxious participants and twenty late-life generalized anxiety disorder (GAD) participants were included. Whole-brain axial pseudo-continuous arterial spin-labeling scans were collected. We used a voxel-wise two-way ANOVA to test the group-by-block interaction. Worry induction was associated with greater cerebral blood flow (CBF) in the visual cortex, thalamus, caudate and medial frontal cortex compared with the rest. Reappraisal was associated with greater CBF in similar regions, whereas the orbital frontal gyrus showed lower CBF relative to rest. Relative to non-anxious participants, GAD had greater CBF in multiple regions during worry induction (visual and parietal cortex, middle and superior frontal) and lower CBF during reappraisal in the supplemental motor area, middle cingulate gyrus, insula and putamen. Except for the thalamus, there was no change in CBF throughout the five blocks of worry induction and reappraisal. Severe worry is distinctly associated with increased CBF in several neocortical regulatory regions. We present new data supporting the view of worry as a complex process, engaging multiple regions in the initiation, maintenance and reappraisal of worry.