Synchronized electrical stimulation of the rat medial forebrain bundle and perforant pathway generates an additive BOLD response in the nucleus accumbens and prefrontal cortex

To study how a synchronized activation of two independent pathways affects the fMRI response in a common targeted brain region, blood oxygen dependent (BOLD) signals were measured during electrical stimulation of the right medial forebrain bundle (MFB), the right perforant pathway (PP) and concurrent stimulation of the two fiber systems. Repetitive electrical stimulations of the MFB triggered significant positive BOLD responses in the nucleus accumbens (NAcc), septum, anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), ventral tegmental area/substantia nigra (VTA/SN), right entorhinal cortex (EC) and colliculus superior, which, in general, declined during later stimulation trains. At the same time, negative BOLD responses were observed in the striatum. Thus, the same stimulus caused region-specific hemodynamic responses. An identical electrical stimulation of the PP generated positive BOLD responses in the right dentate gyrus/hippocampus proper/subiculum (DG/HC), the right entorhinal cortex and the left entorhinal cortex, which remained almost stable during consecutive stimulation trains. Co-stimulation of the two fiber systems resulted in an additive activation pattern, i.e., the BOLD responses were stronger during the stimulation of the two pathways than during the stimulation of only one pathway. However, during the simultaneous stimulation of the two pathways, the development of the BOLD responses to consecutive trains changed. The BOLD responses in regions that were predominantly activated by MFB stimulation (i.e., NAcc, septum and ACC/mPFC) did not decline as fast as during pure MFB stimulation, thus an additive BOLD response was only observed during later trains. In contrast, in the brain regions that were predominantly activated by PP stimulation (i.e., right EC, DG/HC), co-stimulation of the MFB only resulted in an additive effect during early trains but not later trains. Consequently, the development of the BOLD responses during consecutive stimulations indicates the presence of an interaction between the two pathways in a target region, whereas the observed averaged BOLD responses do not.