Abstracts

Rationale: Resting-state fMRI (rs-fMRI) connectivity is a 'task-free' paradigm that is less demanding than task-based fMRI, and thus can be employed in patients with neurological and cognitive deficits. Memory impairments are common in adults with temporal lobe epilepsy (TLE); therefore, rs-fMRI may be a valuable tool to assess hippocampal functional connectivity (FC) to the memory network. Previous studies in TLE have shown discrepant results, with both reduced and increased FC ipsilateral to temporal seizure foci. We used a novel acquisition method for rs-fMRI to compare hippocampal FC in adults with TLE and typically developing (TD) controls.  Methods: Fourteen patients with TLE (8 L, 6 R; M age: 34.1 years) referred to the Clinical Epilepsy Section at National Institute of Neurological Disorders and Stroke, National Institutes of Health for presurgical evaluation and 14 TD controls (M age: 26.6 years) completed multi-echo rs-fMRI (TR = 2500 ms). Multi-echo rs-fMRI optimizes BOLD signal, particularly for inferior temporal and orbitofrontal cortex. All resting state echoes were despiked, slice-time corrected to beginning of TR, blip-corrected, and aligned to the participant's MPRAGE. Each TR was aligned to the TR in the run with minimum outlier fraction as compared to MPRAGE. Echoes were combined using AFNI's optimal combination method and then blurred to 4mm. Voxels were scaled (each voxel in timeseries had mean of 100, range of 0-200). We regressed the following from the entire timeseries: motion parameters, 5 components accounting for most variance in ventricles and white matter, and bandpass regressors (0-0.08 Hz). Each MPRAGE was segmented in Freesurfer. We calculated the correlation between each Freesurfer ROI's timeseries using AFNI. We ran a Mixed Model ANOVA in SPSS separately for left and right hippocampal FC to memory network ROIS (parahippocampal, entorhinal, fusiform, amygdala, thalamus, isthmus/posterior cingulate, and frontal and parietal regions) and compared hippocampal connectivity between LTLE, RTLE, and TD.  Results: We found a main effect of memory network ROI separately for each hippocampus (L, R; p's<0.001); however, we did not find an effect of group (LTLE, RTLE, TD) or side (L, R) of target memory network connections for either left or right hippocampi. For each hippocampus, one of the strongest connections was with the contralateral hippocampus (TD r=0.71, LTLE r=0.46, RTLE r=0.49). Overall left and right hippocampi were connected to similar memory network ROIs (r=0.63, p<0.001). However, for TDs the correlation was particularly strong (r=0.8, p<0.001) and 100% of the top ten memory network ROIs for each hippocampus overlapped (contralateral hippocampus, L/R parahippocampi, L/R amygdala, L/R isthmus of cingulate, right orbitofrontal, L/R middle temporal). Similarly, when LTLE and RTLE were combined, we found a main effect of group (p<0.02), with TLE < TD for left hippocampal FC to the memory network, not right FC.  Conclusions: During rs-fMRI, the left and right hippocampi are likely working in concert. Not only were both hippocampi connected to similar ROIs in the larger memory network, but no ipsilateral or contralateral pattern was observed for the comparison of LTLE, RTLE, and TD. However, the combined TLE group showed reduced left hippocampal FC. Preliminary results are encouraging of a strong typical bilateral hippocampal memory network, which may be affected more on the left in TLE. This bilateral network and how it is affected by TLE may be useful in predicting postoperative memory deficits.  Funding: This work was supported by K23 NS093152 from NINDS to LNS and NINDS Division of Intramural Research.