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TaggedAPTARAEnd236                                                                             X.R. Tan et al.
             time = 2000 ms, echo time = 30 ms, field of view = 256  Where significant motion was seen in the motion parameters,
             mm £ 256 mm, matrix size = 64 £ 64. During imaging,  or where the non-motion corrected data were significantly
             the participant performed the Stroop color-naming task. 19  affected by motion, label/non-label data pairs containing
             A color word was presented on the projector screen,  motion were removed and regeneration of cerebral blood flow
             where the participant was instructed to select for the ink  images were performed on the truncated set. GLM results
             color of the word, instead of its semantic meaning, using  were obtained using a 1-sample group mean GLM with vertex-
             a 4-button box (Lumina LU444-RH; Cedrus, San Pedro,  wise threshold p < 0.05 and cluster correction at p < 0.05,
             CA, USA) with their right hand. Stimuli consisted of  correcting for 2 spaces (left and right hemispheres). Extraction
             words printed in 1 of 4 colors (red, blue, green, or  of regions of interest averaged data was performed using in-
             yellow), and the congruent or incongruent stimuli were  house built Matlab scripts, and regions of interest generated
             presented in random sequence. The proportion of   from Freesurfer parcellation (surfaces transformed to volume
             congruent or incongruent stimuli presented was approxi-  space). To obtain the normalized values accounting for circa-
             mately equal. The stimuli were presented centrally for  dian-related changes, the % perfusion values were subtracted
             1 min and repeated for 4 cycles. A solid black cross was  with time-matched CT values, and comparisons were made
             presented on a white background as control stimulus for  between baseline and post scans. Similar analysis was applied
             1 min prior to each Stroop cycle, as intervals between the  for task response accuracy and reaction time. fMRI data were
             cycles, and at the end of the 4 cycles (total duration = 9  analyzed using the Freesurfer Functional Analysis STream
             min; Fig. 1G). Single subject level analysis was  (FS-FAST,   http://www.surfer.nmr.mgh.harvard.edu).  The
             performed using general linear model (GLM) analysis  pipeline involves motion correction of fMRI data to the
             with the motion regressor (on/off). The hemodynamic  middle time-point of each run, registration of the anatomical
             response function was modeled during the presentation of  and fMRI images, intensity then spatial normalization (to Free-
             stimuli, and was compared to the baseline signal when  surfer “fsaverage”) using a 6-parameter affine transformation
                                                               and smoothing (5-mm full width at half maximum). Individual
             the control cross was displayed.TaggedAPTARAEnd
                                                               participant/visit scans were analyzed, using a GLM,
                                                               convolving the task regressor with a canonical hemodynamic
         TaggedAPTARAH22.4. MRI data analysisTaggedAPTARAEnd
                                                               response function (g function with delay d = 2.25 s and decay
                                                                                 25
            TaggedAPTARAPRaw Digital Imaging and Communications in Medicine  time constant t = 1.25 ).TaggedAPTARAEnd
         (DICOM) data were converted to Neuroimaging Informatics  TaggedAPTARAPFor the ergometer paradigm, an event-related design was
         Technology Initiative (NIfTI) using MCverter (Lewis Centre  used with 4 contrasts (20%, 40%, 60%, and 80% maximal
                                                               voluntary contraction) and rest. Positive clusters were
         for Neuroimaging, University of Oregon, Eugene, OR, USA).TaggedAPTARAEnd
               1
            TaggedAPTARAPFor H MRS, Siemens Twix data were analyzed using in-house  extracted for 60% + 80% vs. rest using vertexwise threshold
         built Matlab scripts, which included 2 Hz exponential line  (p < 0.001), with clusterwise threshold (p < 0.05) and
         broadening and phase correction. The brain temperature (T br )  correcting for 2 spaces. Individual participant’s % signal
         was estimated for each individual acquisition from the  change was extracted from the activated clusters. Data were
         frequency shift between the water and N-acetylaspartate  normalized with time-matched CT values and compared
         (NAA) peaks using an equation from Cady et al. 20  (T br = 286.9  between baseline and post scans.TaggedAPTARAEnd
          94.0 DH 2 0-NAA) and then averaged across individual   TaggedAPTARAPFor Stroop-task fMRI analysis, the comparison across all
         spectra. The data were compared to T re as recorded during the  trials was performed for (a) all stimuli vs. neutral stimuli, and
                                                         1
         scan corresponding to the same timepoint at which the H  (b) incongruent stimuli vs. congruent stimuli to generate the
                                                               task-induced regions with vertexwise (p < 0.001) and cluster-
         MRS scan was conducted.TaggedAPTARAEnd
            TaggedAPTARAPIndividual subjects’ MPRAGE images were run through the  wise (p < 0.05) thresholds. For trial-to-trial comparison (PA
         Freesurfer longitudinal analysis pipeline 21,22  to parcellate the  S2 vs. CT S2), voxelwise paired comparisons were made
         brain for coregistration and further analysis. For ASL, image  between scans with the clusterwise threshold set to 0.05.TaggedAPTARAEnd
         preprocessing was performed with Matlab R2014a Package
         (FIL Methods Group, London, UK) and Statistical Parametric
                                                               TaggedAPTARAH22.5. Statistical analysisTaggedAPTARAEnd
         Mapping version 12.0 (SPM12). ASL data were split into
         label/non-label pairs before motion correction and averaging.  TaggedAPTARAPStatistical Package for Social Sciences (SPSS) Version 22.0
         Label and non-label images were coregistered to the   (IBM Corp., Armonk, NY, USA) was used to compute all
         MPRAGE images using Advanced Normalization Tools 23   data, and 2-tailed paired Student’s t tests were performed to
         based on the non-label coregistration parameters, before  test for statistical differences between trial conditions. For
         projection to the cortical surface and application of surface  time-by-trial interaction effects, 2-way repeated-measures
         smoothing (10 mm). These smoothed cortical signals were  analysis of variance was performed to test for significance
         used to generate the difference and perfusion images for  between trial conditions. Where significant interaction effects
         further analysis by normalizing with relaxation-corrected  were established, pairwise differences were identified using
         label-off image and performing quantification correction. 24  To  the Bonferroni post hoc analysis adjusted for multiple compar-
         remove motion artifacts, a second set of data was generated  isons. Significance level was set at p < 0.05. All values were
         without motion correction, and a comparison was made.  expressed as mean § SD.TaggedAPTARAEnd
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