Group activation maps.

<p>Overview of group activation patterns (T-maps) for three tasks. The figure was split into panels A and B as combining activation overlays obscured too much detail due to overlap. Panel A at the left shows event related anti vs prosaccade activation in blue and saccades in darkness activation in red. Panel B at the right shows activation for visual stimulation vs rest in green and again for saccades in darkness vs rest in red. Overlap is rendered in yellow. In the upper row of panel A and B group activation is rendered in 3D on top of a high-quality individual (MNI normalized) skull stripped brain, only to indicate the location of activation with respect to the main sulci and gyri. In the right 3D rendering in panels A and B the anterior upper right part of the brain is cut out to show activation in deeper sulci and along the medial wall of the cortex. In the lower rows activation is overlaid on selected 2D slices through the T1 weighted normalized anatomical scan averaged over all participants, providing a more realistic impression of anatomical precision after normalization. Slice MNI coordinates are given for each slice at the upper right hand side (z-coordinate for axial slices, y for coronal and x for sagittal slices). Activation for all renderings is thresholded at T = 3.5, implying that also some stronger trends are displayed for the sake of completeness. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029517#pone-0029517-t001" target="_blank">table 1</a> for an overview of statistics. Slices are displayed in neurological convention (left = left). Labels are indicating regions of interest or sulci. Lateral and medial FEF (frontal eye fields): two foci activated during saccades in darkness vs rest; antisaccade FEF: preferentially activated for antisaccades vs prosaccades (note that FEF label is only used for sake of simplicity; lateral activations are probably not part of the human FEF homologue). SEF: supplementary eye fields; PUT: Putamen; CS: central sulcus; SFS: superior frontal sulcus; CS: central sulcus.</p

ROI activation timecourse.

<p>The average peri-stimulus-time-histograms (PSTHs; BOLD time courses) are shown for several ROIs: the clusters activated for saccades in darkness vs rest in left and right precentral sulcus/premotor cortex (‘lateral and medial FEF’) and the left and right putamen and SEF, and the left and right clusters in the FEF more active for anti as compared to prosaccades (‘antisaccade FEF’). The aforementioned group activation patterns from which the ROIs were taken are depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029517#pone-0029517-g004" target="_blank">figure 4</a>. PSTHs were averaged over voxels in the ROIs and then participants, and aligned at target stimulus onset. Saccade onset typically follows within 300 ms, therefore PSTHs aligned at saccade onset would have been largely identical. Data for the left hemisphere are given in the left panels and data for the right hemisphere in the right panels. In each panel, average PSTHs are presented for pro and antisaccades (gray squares and black circles) to the left and right (solid and dashed lines with open and solid symbols). The unit on the ordinate is global % signal change. The absolute magnitude of this unit is not directly meaningful and should not be compared over regions, as averaging took place over different numbers of voxel per region and within different brain areas. Absolute BOLD measures are known to vary considerably over regions. Differences between conditions within a region can be compared. Except the bilateral putamen, the right ‘lateral FEF’ and left SEF, peak activation in all ROIs was significantly larger for antisaccades as compared to prosaccades (p<0.05). The left SEF exhibited larger responses for antisaccades at trend level, T(12) = 1.59;p = 0.06. Further tests on single timepoints of interest are presented in the text of the results section.</p

Field of view (FOV).

<p>The field of view used for fMRI acquisition during task performance, indicated as a blue translucent square overlaid on a sagittal slice through the anatomical scan of one of the participants. Care was taken that the striatum, midbrain, FEF and SEF were in the field of view. In between functional runs, the angulation was checked regularly and adjusted if required.</p

Cue evoked activation maps.

<p>Two axial slices with group activation patterns (T-maps) for the second GLM analysis are shown comparing antisaccade cue induced vs prosaccade cue induced activation (from task 1) in blue. Data is overlaid on the T1 weighted anatomical scan averaged over all participants. The z-coordinates (MNI space) is given for each slice at the upper right hand side. Activation is thresholded at T = 3.5. Slices are displayed in neurological convention (left = left).</p

Step-wise results of DTI analysis.

<p>The subsequent steps in DTI fiber analysis are outlined in 4 panels. In panel A, the normalized fiber tracts originating from the left and right putamen and caudate nucleus are rendered in blue for one participant together with orthogonal slices from the normalized T1 weighted scan. The manually segmented ROIs for the caudate nucleus and putamen are also rendered in red. Panel B shows a 3D representation of the average probability (over participants) for a voxel to be connected to the caudate nucleus (in red) or putamen (in blue) or both (purple). In yellow the zones activated for antisaccades and in green the zone activated for saccades in darkness are rendered. For each participant, it was then investigated which fibers from the 4 fiber bundles originating in the left and right putamen and caudate nucleus were connected to the most important cortical fMRI activation clusters observed in 4. See panel C for example results from individual participants: fibers connecting the caudate nucleus and SEF are shown in the left rendering, fibers connecting the putamen and antisaccade zone in the FEF in the right rendering, and the lower left rendering shows fibers connecting the areas activated for saccades in darkness (‘lateral and medial FEF’) with the putamen. The manually segmented caudate nucleus and putamen are also shown in yellow and green, respectively. Panels C is presented in order to illustrate the fiber processing steps, and are not necessarily representative. Panel D shows for how many participants (out of 12) regions were connected at all. ‘FEF motor’ refers to zones along the precentral sulcus activated for saccades in darkness (that is, ‘lateral FEF’ and ‘medial FEF’ taken together), ‘FEF anti’ refers to zones activated for antisaccades vs prosaccades. Line thickness also indicates the number of subjects with connections. The diagram is overlayed onto a blurred slice from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029517#pone-0029517-g004" target="_blank">figure 4</a>, only to roughly indicate the location.</p

Details on the observed clusters of activation for contrasts from all three tasks are presented.

<p>From left to right, columns represent the label for each area as used throughout the paper, the MNI coordinates of the voxel in each cluster with maximal T-value, the maximum T-value and the number of voxels in each cluster. The contrast for which the clusters are listed are named on top of each list of activations. At the right side of each contrast name the minimum cluster size is given for a cluster to be considered significant at the group level. That is, clusters with a lower cluster size are statistical trends. Trends are presented for the sake of completeness, and only discussed further when confirmed by significant findings from PSTH analysis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029517#pone-0029517-g005" target="_blank">figure 5</a>). The quoted regions ‘lateral and medial FEF’ and ‘antisaccade FEF’ are also referred to as such in the text and further explored in the PSTHs, and where labeled such for sake of simplicity. Technically it is of course debatable whether all regions could be considered part of a single human FEF region. In general, when a label contains ‘FEF’ it is meant that it was located somewhere along the precentral sulcus or premotor cortex. Abbreviations: FEF: frontal eye fields, SEF: supplementary eye fields, PUT: putamen, CN: caudate nucleus, SC: superior colliculus, SNpr: substantia nigra pars reticulata, RN: red nucleus.</p

Significant tissue expansion: Significant Jacobian values > 1 overlaid on the model brain.

<p>Values range from 1.02 (purple) to 1.30 (bright red). Expansion was observed in regions covering the arcuate fasciculus (E), cerebellar penduncle (A), cinguli (C) , corpus callosum (B,C), cortical spinal tract (B,F), uncinate fasciculus (D) and on the gray matter / cerebral spinal fluid boundary (A-F), the latter likely representing brain growth. For visualization purposes, values were resampled to model brain resolution.</p

Sample characteristics of the full sample (left) and of the subset of children for which longitudinal data was available (right).

<p>MZ  =  monozygotic, DZ  =  dizygotic, FA  =  fractional anisotropy, R = right-handed, WM  =  white matter.</p>*<p>White matter was segmented reliably in 187 children at baseline, and 117 children at follow-up.</p>**<p>105 children had reliable white matter segmentations and DTI measurements at both time-points. The last column displays p-values of the differences in sample characteristics for children who participated only once, versus children who participated twice.</p

The relationship between <i>changes</i> in pure white matter fractional anisotropy and <i>changes</i> in white matter volume in the three-year interval.

<p>The relationship between <i>changes</i> in pure white matter fractional anisotropy and <i>changes</i> in white matter volume in the three-year interval.</p

Heritability and unique environmental influences for white matter volume, mean fractional anisotropy in pure white matter, white matter surface area and fractional anisotropy in fiber bundles at ages 9 and 12.

<p>Values in brackets are 95% confidence intervals. Common environmental influences did not play a role in explaining variation in fiber bundles (based on both the Akaike criterion and Chi-square differences): only the results from the model incorporating genetic and unique environmental influences are displayed here. FA =  fractional anisotropy, L = left, R = right, ILF = inferior longitudinal fasciculus, IFO = inferior fronto-occipital fasciculus.</p