Functional neuroimaging of associative learning and generalization in specific phobia

Iris Lange*, Liesbet Goossens, Jindra Bakker, Stijn Michielse, Machteld Marcelis, Marieke Wichers, Jim van Os, Therese van Amelsvoort, Koen Schruers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Theoretical models have implicated classical fear conditioning, fear generalization, and extinction learning in the development of anxiety disorders. To date, it is largely unknown to what extent these mechanisms and the underlying neurobiology may be altered in specific phobia, a disorder characterized by focal fears. The current study systematically examined fear conditioning, fear generalization, extinction learning, and extinction recall in a sample of individuals with a specific phobia.
Participants with a specific phobia (SP) of spiders (n = 46) and healthy controls (HC) (n = 48) underwent a 3-day fMRI cue-conditioning protocol, including a fear acquisition and a fear generalization phase (day 1), an extinction learning phase (day 2), and an extinction recall phase (day 3). Stimuli were phobia-irrelevant, as geometrical shapes served as conditioned threat (CS+) and safety stimuli (CS-), and an electrical shock as the unconditioned stimulus (US). Self-reported fear, US expectancy, and blood-oxygen-level dependent responses were measured.
Behavioral results only revealed enhanced CS+/CS-differentiation in fear scores during acquisition retention in SP. Some neural differences were observed during other task phases. During early fear acquisition, SP showed enhanced differential activation in the angular gyrus and lateral occipital cortex, and during extinction recall, more precuneus deactivation was found in SP compared to HC. There were no clear indications of altered neural fear generalization or extinction learning mechanisms in the SP group.
Results indicate that spider phobia may be characterized by enhanced differential fear retention and altered brain activation patterns during fear acquisition and extinction recall. The findings provide insight into the nature of fear learning alterations in specific phobia, and how these may differ from those found in disorders characterized by broad anxious distress.
Original languageEnglish
Pages (from-to)275-285
Number of pages11
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Publication statusPublished - 8 Mar 2019
Externally publishedYes


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