Combining fMRI with a pharmacokinetic model to determine which brain areas activated by painful stimulation are specifically modulated by XXXX .

@entity1337 @entity158 @entity1937
We present a method for investigating the dynamic pharmacological modulation of @entity158 -related brain activity, measured by BOLD-contrast fMRI. Noxious thermal stimulation was combined with a single infusion and washout of @entity1937 , a short-acting opioid analgesic agent. The temporal profile of the effect site concentration of @entity1937 , estimated from a pharmacokinetic model, was incorporated into a linear model of the fMRI data. The methodology was tested in nine healthy male subjects. During each imaging session the subjects received noxious thermal stimulation to the back of the left hand, prior to infusion, during infusion to a @entity1937 effect site concentration of 1.0 ng/ml, and during washout of the @entity1937 . Infusions were repeated with saline. @entity1937 -induced @entity1337 was confirmed from subjective @entity158 intensity scores. @entity158 -related brain activity was identified in a matrix of regions using a linear model of the transient BOLD responses to noxious stimulation. Of those regions, there was a significant fractional reduction in the amplitude of the @entity158 response in the insular cortex contralateral to the stimulus, the ipsilateral insular cortex, and the anterior cingulate cortex. Statistical parametric mapping of the component of @entity158 responses that was linearly scaled by @entity1937 concentration confirmed the contralateral insular cortex as the @entity158 -processing region most significantly modulated by @entity1937 compared to saline. The mapping of specific modulation of @entity158 -related brain activity is directly relevant for understanding pharmacological @entity1337 . The method of examining time-dependent pharmacological modulation of specific brain activity may be generalized to other drugs that modulate brain activity other than that associated with @entity158 .
