Figure 2.
Consecutive identical stimulation trains cause region- and time-specific variations in the BOLD response. A, The hippocampal regions selected for BOLD measurements are depicted in an anatomical MRI (top left). B, Calculation of the average BOLD responses in the ipsilateral dentate gyrus (red line), ipsilateral subiculum/entorhinal cortex (blue line), contralateral subiculum/entorhinal cortex (green line), and contralateral dentate gyrus (black line). Each line represents the average BOLD response to all 15 identical stimulus trains. The gray box indicates the time window of the stimulation train. C, Time-dependent variations in the BOLD responses during electrical stimulation of the right perforant pathway (the stimulation pattern of one train is depicted in the scheme above). Whereas in the ipsilateral subiculum/entorhinal cortex region, clear BOLD responses were detectable during all stimulus trains, obvious BOLD responses in the ipsilateral dentate gyrus became detectable only after the second stimulation train. In contrast, within the contralateral subiculum/entorhinal cortex, significant BOLD responses to the stimulation were only detectable during the initial stimulation trains. No clear positive BOLD responses were observed in the contralateral dentate gyrus region. Each inset represents the averaged BOLD response of five individual animals. D, Calculation of a general linear model of regions with significant stimulus-dependent signal intensity changes revealed a time-dependent variation in the activation pattern. Early stimulation trains (train 1–2) triggered significant BOLD responses only in the ipsilateral and contralateral entorhinal cortex regions. Subsequent stimulation trains caused a spreading of the BOLD response to the entire ipsilateral hippocampus, which was followed by a more focused BOLD response to the dentate gyrus region at the end of the experiment.