Computational protocol: Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study

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Protocol publication

[…] Single-subject preprocessing was carried out using FEAT (FMRI Expert Analysis Tool), Version 6.00, part of FSL v 5.0.4 (FMRIB’s Software Library Prestatistical processing consisted of motion correction using MCFLIRT [], brain extraction using BET [] and spatial smoothing using a Gaussian kernel of full-width at half-maximum (FWHM) of 8 mm. Large signal drifts (due to scanner instabilities or systemic physiological fluctuations) were attenuated by applying a high-pass filtering cut-off, set at 150 seconds [–]. Registration to high resolution structural and/or standard space images was carried out using FLIRT [, ]. EPI volumes were registered to the individual’s structural scan using FLIRT_BBR (Boundary-Based Registration) tool []. Registration from high resolution structural to standard space was then further refined using FNIRT nonlinear registration [, ].Resting state functional connectivity (RSFC) analysis was carried out using a seed-ROI based approach [, –]. Based on previous evidence of local functional alterations of resting state fMRI measurements in Parkinson’s Disease patients [], we explored the changes of functional connectivity with the supplementary motor area (SMA), primary sensory-motor cortices (as on the FSL implemented Harvard-Oxford Cortical Structural Atlas) [], cerebellum (as on the MNI Structural Atlas), and basal ganglia (left and right nucleus striatum or left and right globus pallidus or left and right thalamus) []. Regions of Interest (ROIs) positioned on these areas were used as the seeds for resting state functional connectivity. Basal ganglia ROIs were labeled and calculated from each subject’s high resolution T1-weighted structural scan using FMRIB’s integrated registration and segmentation tool (FIRST) [], part of FSL. To be more restrictive in ROIs segmentation, we chose an arbitrary inclusion threshold of 30% for the primary sensory-motor cortices and cerebellum, and of only 5% for the SMA (in an attempt to include both SMA proper and pre-SMA components, known to be altered from resting state studies conducted on patients with Parkinson’s Disease) [, ]. An expert neuroradiologist (CCQ) visually inspected the chosen ROIs in order to validate anatomical correspondence. EPI-to-standard registration parameters were inverted and used to report all seed-ROIs to individual subject space, applying both linear and non-linear transformation matrices from standard and high resolution space. Mean BOLD time series of each native space seed-ROI were obtained and used to define the reference time course, after which a correlation analysis between each reference time course and the signal time series in each voxel within the acquired whole-brain image set was computed.Seeds of cerebro-spinal fluid (CSF) and white matter (WM) were also individually defined in the lateral ventricles and in the centrum semi-ovale on the functional EPI images, and their time courses were added, as non-interest covariate (nuisance), into the voxel-wise correlation analyses, to remove for non-neural contributions to the BOLD signal and enhance specificity [].Analyses were conducted both without and with inclusion of 6 head motion parameters into the voxel-wise correlation analysis to control for effects of transient head motion of patients on our results [].Z-score functional connectivity (FC) maps were generated for each subject by displaying all those voxels whose time series were correlated with the seed region (p<0.05). Maps of individual FC differences for pre- and post-effective AMPS (treatment) and pre- and post-sham conditions were initially obtained and entered in respective higher-level one-sample t-test analyses using FEAT (cluster level p<0.05 corrected for family wise error—FWE) to investigate for the mean effect of PMS and sham conditions on FC, separately. Then, a second higher-level analysis was conducted performing a paired T-test between maps of individual FC differences in effective and sham conditions. Higher level analyses were carried out using the FLAME (FMRIB's Local Analysis of Mixed Effects) mixed-effects model, stage 1 [–]. Z-statistic images were set using clusters determined by Z>2.3 and a corrected cluster significance threshold of p < 0.05 []. Anatomical localization of significant clusters was established according to the Harvard-Oxford cortical and subcortical structural atlases and the Juelich Histological Atlas included in the FSL ( Clinical scores before an after sham or effective AMPS were tested with the Wilcoxon-signed rank test for paired data by means of the SPSS software package 19.0. […]

Pipeline specifications

Software tools FreeSurfer, SPSS
Applications Miscellaneous, Connectivity analysis
Organisms Homo sapiens
Diseases Cerebellar Diseases, Parkinson Disease