Fig 1.
(a) The quadri-polar DBS-electrode was stereotactically implanted in the right hippocampus (AP -5.6, DV -7.4, ML +5.2 relative to Bregma [43]) together with four anchor screws. The outer two electrodes are used for stimulation and the inner two electrodes for iEEG. The red dot represents the electrode insertion location on the skull. The black dots indicate anchor screw positions. (b) Illustration of the quadri-polar DBS-electrode. The MRI-compatible electrode is custom made by twisting together four platina iridium wires. The unused connection pin is reserved for connection to a ground-electrode, which is subcutaneously implanted in the neck. (c) Illustration of the DBS-electrode after fixation to the skull.
Fig 2.
Timeline of the experimental imaging protocol.
The animals were allowed one week of post-surgical recovery, after which the seizure threshold was determined. One day after threshold, the 1st series of fMRI datasets were acquired. The 2nd and 3rd series of fMRI datasets were acquired 1 to 4 days after the first set was acquired, depending on scanner availability. Finally rats were sacrificed, the DBS-electrode was removed with high caution and an MR-scan was acquired.
Fig 3.
Illustration of electrode-artifact on MR-images.
(a) structural MRI of axial slice at height of electrode. (b) functional MRI of axial slice through forebrain. (c) functional MRI of axial slice at height of electrode. (d) post-mortem structural MRI at height of the electrode path. The post-mortem MRI is used to verify the electrode track position. For all rats the electrode track was located in the right hippocampus.
Table 1.
Inter-subject reproducibility.
Fig 4.
Representative whole-brain BOLD fRMI response-maps of one subject resulting from ICA and GLM analysis.
Listed separately in (a) and (b) respectively. All activation maps are thresholded with a Bonferroni corrected p-value < 0.05. Every response map displays the DBS-induced BOLD-response of 5 different stimulation intensities. Every row in the activation map represents a single intensity, listed from top to bottom, from 10% of the seizure threshold to 90% of the seizure threshold. Every row displays the mean of 6 fMRI-datasets for the specific stimulation intensity. Axial anatomical scans are co-registered with the corresponding activation maps. Slices progress from most anterior at the left to most posterior at the right. The hippocampal structures (HC), lateral thalamic structures (lThal), medial thalamic structures (mThal), septal nuclei (septum), striatum, hypothalamus (hypoT), medial forebrain (mFB), sensory cortex (SC), mammillary bodies (MM), ventral tegmental area (VTA), and ectorhinal cortex (EC) are labeled with white arrows. (a) ICA-based response maps. The intensity of the color corresponds to the level of significance of the BOLD response, indicated by a z-score in the color bar on the right. (b) SPM-based response maps. The intensity of the color corresponds to the level of correlation of the voxel’s timecourse to the stimulus, indicated by an F-value in the color bar on the right.
Fig 5.
BOLD responses at different stimulation intensities in one subject.
The graph depicts the mean timeseries per stimulation intensity in the volume of interest with the highest significance, per stimulation intensity, in one subject. The volume of interest increased with increasing stimulation intensity.