Lesion to Hippocampus changes resting state functional connectivity in rat brain reflecting structural damage

Temporal lobe epilepsy (TLE) is associated with pathologic changes in hippocampal physiology and morphology. Resting state functional connectivity (rsFC) is known to reflect structural connectivity, but also allows exploring interactions between remote regions. We will try to disambiguate the effect of the epileptogenic lesion from a normal surgery. The purpose of this study is to trace changes in rsFC using BOLD-­fMRI after inducing a unilateral left hippocampal lesion in rats. Male Sprague Dawley rats (n=19, 250-275 g) were anesthetized (induction 5% isoflurane, s.c. bolus medetomidine (0.05 mg/kg), followed by continuous s.c. infusion medetomidine (0.1 mg/kg/h)) and were inserted into the MR scanner (7T Bruker Pharmascan, Ettlingen, Germany). Anatomical (voxel size 0.156 x 0.156 x 0.156 mm3) and fMRI (voxel size 0.375 x 0.375 x 1.1 mm3) data were acquired. Afterwards, kainic acid (0,4 µg/0,1 µl) was injected into the right hippocampus under isoflurane anesthesia (5% induction, 2% sustenance). This resulted in lesions in ipsilateral hippocampus, thalamus and cortex. Four days and 3 months after the injection the animals were scanned again using the protocol described above. Seventeen ROIs were segmented in each rat using anatomical MRI: cingulate, retrosplenial and septum; and sensorimotor, auditory visual cortexes, striatum, hippocampus, thalamus, hypothalamus, colliculus and amygdala/enthorinal/piriform (AEP) cortex bilaterally. Mean time series were extracted from realigned, detrended and filtered (bandpass, 0.01~0.1HZ) rs-fMRI data in the ROIs before and after the lesion was induced. ROI based functional connectivity and voxel wise functional connectivity density was compared in each of these rats in pre- and two post-lesion scans (the first one after 4 days, the second one after 3 months). The rsFC analysis found generally reduced functional connectivity between different areas, ipsilateral but also contralateral to the lesion. Functional connectivity density revealed voxel-wise reorganization in rat brain where less connected voxels disappear 4 days post-lesion and a number of more dense connected voxels decreases 3 months post-lesion. We conclude that functional connectivity measures in resting state fMRI are a valuable tool to map brain dynamics and its reliability when we act on some specific nodes via targeted lesions