ausblenden:
Schlagwörter:
Pupillometry, fear conditioning, fear extinction, fMRI, dorsal anterior cingulate cortex, Salience network
Zusammenfassung:
Background: Fear conditioning and extinction are prevailing experimental
and etiological models for normal and pathological anxiety. Pupil
dilations in response to conditioned stimuli are increasingly used as a
robust psychophysiological readout of fear learning, but their neural
correlates remain unknown. We aimed at identifying the neural correlates
of pupil responses to threat and safety cues during a fear learning
task.
Methods: Thirty-four healthy subjects underwent a fear conditioning and
extinction paradigm with simultaneous functional magnetic resonance
imaging (fMRI) and pupillometry. After a stringent preprocessing and
artifact rejection procedure, trial-wise pupil responses to threat and
safety cues were entered as parametric modulations to the fMRI general
linear models.
Results: Trial-wise magnitude of pupil responses to both conditioned and
safety stimuli correlated positively with activity in dorsal anterior
cingulate cortex (dACC), thalamus, supramarginal gyrus and insula for
the entire fear learning task, and with activity in the dACC during the
fear conditioning phase in particular. Phasic pupil responses did not
show habituation, but were negatively correlated with tonic baseline
pupil diameter, which decreased during the task. Correcting phasic pupil
responses for the tonic baseline pupil diameter revealed thalamic
activity, which was also observed in an analysis employing a linear
(declining) time modulation.
Conclusion: Pupil dilations during fear conditioning and extinction
provide useful readouts to track fear learning on a trial-by-trial
level, particularly with simultaneous fMRI. Whereas phasic pupil
responses reflect activity in brain regions involved in fear learning
and threat appraisal, most prominently in dACC, tonic changes in pupil
diameter may reflect changes in general arousal.
