Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning

Behav Neurosci. 2007 Aug;121(4):635-42. doi: 10.1037/0735-7044.121.4.635.


During Pavlovian fear conditioning a conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (UCS). In many studies the CS and UCS are paired on every trial, whereas in others the CS and UCS are paired intermittently. To better understand the influence of the CS-UCS pairing rate on brain activity, the experimenters presented continuously, intermittently, and non-paired CSs during fear conditioning. Amygdala, anterior cingulate, and fusiform gyrus activity increased linearly with the CS-UCS pairing rate. In contrast, insula and left dorsolateral prefrontal cortex responses were larger during intermittently paired CS presentations relative to continuously and non-paired CSs. These results demonstrate two distinct patterns of activity in disparate brain regions. Amygdala, anterior cingulate, and fusiform gyrus activity paralleled the CS-UCS pairing rate, whereas the insula and dorsolateral prefrontal cortex appeared to respond to the uncertainty inherent in intermittent CS-UCS pairing procedures. These findings may further clarify the role of these brain regions in Pavlovian fear conditioning.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Acoustic Stimulation
  • Adult
  • Analysis of Variance
  • Area Under Curve
  • Brain / blood supply
  • Brain / physiology*
  • Brain Mapping
  • Conditioning, Classical / physiology*
  • Dose-Response Relationship, Radiation
  • Fear*
  • Female
  • Functional Laterality
  • Galvanic Skin Response / physiology
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Oxygen / blood
  • Time Factors


  • Oxygen