Response time as a proxy of ongoing mental state: A combined fMRI and pupillometry study in Generalized Anxiety Disorder

Elena Makovac; Sabrina Fagioli; David R Watson; Frances Meeten; Jonathan Smallwood; Hugo D Critchley; Cristina Ottaviani

doi:10.1016/j.neuroimage.2019.02.038

Response time as a proxy of ongoing mental state: A combined fMRI and pupillometry study in Generalized Anxiety Disorder

Neuroimage. 2019 May 1:191:380-391. doi: 10.1016/j.neuroimage.2019.02.038. Epub 2019 Feb 21.

Authors

Elena Makovac¹, Sabrina Fagioli², David R Watson³, Frances Meeten⁴, Jonathan Smallwood⁵, Hugo D Critchley⁶, Cristina Ottaviani⁷

Affiliations

¹ Centre for Neuroimaging Science, Kings College London, London, UK; Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, University of Sussex, Falmer, UK; Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy. Electronic address: elena.makovac@kcl.ac.uk.
² Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Education, University of Roma Tre, Rome, Italy.
³ Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, University of Sussex, Falmer, UK.
⁴ Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, University of Sussex, Falmer, UK; School of Psychology, University of Sussex, Falmer, UK.
⁵ Department of Psychology, York Neuroimaging Centre, University of York, York, UK.
⁶ Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, University of Sussex, Falmer, UK; Psychiatry, BSMS Department of Neuroscience, Brighton and Sussex Medical School (BSMS), University of Sussex, Falmer, UK.
⁷ Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Psychology, Sapienza University of Rome, Rome, Italy.

PMID: 30798009
DOI: 10.1016/j.neuroimage.2019.02.038

Abstract

In Generalized Anxiety Disorder (GAD), fluctuations in ongoing thoughts (i.e., mind-wandering) often take the form of rigid and intrusive perseverative cognition, such as worry. Here, we sought to characterise the neural correlates of mind-wandering and perseverative cognition, alongside autonomic nervous system indices of central arousal, notably pupil dilation. We implemented a protocol incorporating the dynamic delivery of thought-probes within a functional neuroimaging task. Sixteen individuals with GAD and sixteen matched healthy controls (HC) underwent functional magnetic resonance imaging with concomitant pupillometry. Participants performed a series of low-demand tracking tasks, responding to occasional changes in a target stimulus. Such a task is typically accompanied by self-generated, off-task thinking. Thought-probes were triggered based on an individual's response time (RT) when responding to the change in the target. Subjective reports showed that long RT predicted off-task thinking/mind-wandering. Moreover, long RT and mind-wandering were also associated with larger pupil diameter. This effect was exaggerated in GAD patients during perseverative cognition. Within brain, during both pre-target periods and target events, there were distinct neural correlates for mind-wandering (e.g., anterior cingulate and paracingulate activation at target onset) and perseverative cognition (e.g., opposite patterns of activation in posterior cingulate and cerebellum at target onset in HC and GAD). Results suggest that not only attention systems but also sensory-motor cortices are important during off-task states. Interestingly, changes across the 'default mode network' also tracked fluctuations in pupillary size. Autonomic expression in pupillary changes mirrors brain activation patterns that occur during different forms of repetitive thinking.

Keywords: Generalized anxiety disorder; Mind-wandering; Perseverative cognition; Pupil; Response time.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anxiety Disorders / physiopathology*
Arousal / physiology
Brain / physiopathology*
Female
Humans
Magnetic Resonance Imaging
Male
Pupil
Reaction Time / physiology*