Effects of Variations in Interstimulus Interval on Activation–Flow Coupling Response and Somatosensory Evoked Potentials with Forepaw Stimulation in the Rat

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Abstract
In functional neuroimaging studies, the hemodynamic response to functional activation is used as a surrogate marker for neuronal activity, typically in response to task paradigms that use periodic stimuli. With use of a model system of electrical forepaw stimulation in rats (n = 14) with laser-Doppler (LD) monitoring of cerebral blood flow (CBF) changes in the somatosensory cortex, the effects of variations in the interstimulus interval (ISI) on the hemodynamic response to periodic stimuli were examined. A characteristic peak flow response was seen for 4-second stimuli and a peak and plateau response were seen for all 8-second stimuli regardless of ISI. However, both the amplitude of the LDCBF response and the integrated response were significantly reduced for shorter ISIs, whereas the baseline flow was not altered. Somatosensory evoked potential responses were also recorded in some rats (n = 8) and remained unchanged for the various ISIs for a particular stimulus duration. These results suggest that the decrease in the LDCBF responses observed with shorter ISIs likely represents a refractoriness of the hemodynamic response and not neuronal function. These results may have important implications for the optimization and interpretation of functional activation paradigms that use periodic stimuli.