ROI analysis: Group effect in the Emotion Model.

<p><i>Upper panel</i>: Activation in the amygdalae in response to emotional faces showing a group effect (CD patents > healthy controls). Statistical maps have been thresholded at p<0.005 uncorrected for display purposes. A significant increased activity was found in the left amygdala (FWEp = 0.027, z = 3.3, [–22–8–14]). Of note, the right amygdala activation displayed here did not reach conventional levels of significance after correction for multiple comparisons (FWE p = 0.078 at MNI [22–4–14]). <i>Lower panel</i>: Graph showing contrast estimates for left amygdala activation in response to each negative emotion (sad, fear) separately for the 2 groups: CD patients (in orange) and healthy controls (in green).</p

Subjects’ Characteristics.

<p><i>* Fisher’s exact test</i></p><p>^†<i>Student’s t-test</i></p><p>Subjects’ Characteristics.</p

Whole-brain analysis: Group effect (CD > controls) in the Emotion Model.

<p>SMA: supplementary motor area</p><p>Whole-brain analysis: Group effect (CD > controls) in the Emotion Model.</p

ROI analysis: Interaction effect in the Linear-change Model.

<p>Graph showing group-level beta estimates for the linear change in the responsiveness of the left amygdala to the presentation of emotional stimuli. Here a positive beta indicates a linear increase in the magnitude of the response elicited by stimuli following repeated exposure. Negative betas indicate the response amplitude reduced over time (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123273#pone.0123273.s001" target="_blank">S1 Fig</a> for a graphical representation of the predicted BOLD time series scaled by these group beta coefficients).</p

Whole-brain analysis: Group effect in the Emotion Model.

<p>Statistical maps have been thresholded at p<0.001 uncorrected. <i>Upper left panel</i>: Activation in a frontal cluster showing a significant group effect (CD patients > healthy controls). <i>Upper right panel</i>: Plots of beta estimates at MNI [–16 22 60] (left supplementary motor area).<i>Lower left panel</i>: Activation in a midbain cluster (including the periaqueducal grey area) showing a significant group effect (CD patients > healthy controls). <i>Lower right panel</i>: Plots of beta estimates at MNI [–4–28–20] (midbrain).</p

Schematic timeline of the experimental design.

<p>ASL: arterial spin labelling, WM: working memory.</p

Representative MEGA-PRESS spectra.

<p>(A) Averaged MEGA-PRESS spectra (averaged across the subject group) acquired at rest (left) and during the WM task. The GABA peak at 3.0 ppm appears to increase between the resting spectrum and the first WM spectrum, and then decrease during performance of the WM task (panels 2-5). The dashed line marks the resting state peak. Glx: glutamate + glutamine concentration, GABA: gamma-aminobutyric acid, NAA: N-acetylaspartate, IU: institutional units. (B) LCModel output for a single subject: the fit is shown in red, superimposed on the edited spectrum (in black). The top panel shows the residuals between the MRS data and the spectral fit.</p

Areas of significant perfusion change during the WM task (p<0.001, uncorrected, k = 150).

<p>The location of the left DLPFC voxel (white rectangle) is shown for comparison. Results are presented on an axial slice (MNI z-coordinate = 24) of a T1-weighted image from a single subject.</p

Contrast estimates in frontoparietal regions.

<p>The figure shows contrast estimates for each of the EYE_PLAY, HAND_PLAY and OBS conditions (against fixation condition) in five representative voxels (superimposed on the conjunction analysis image): left inferior parietal lobule [−56 −28 46]; left premotor cortex [−28 −10 50]; supplementary motor area [−10 2 52]; right premotor cortex [28 −2 60]; right inferior parietal lobule [60 −24 40]. Error bars depict the standard error. In all cases, activations were statistically significantly higher in both EYE_PLAY and HAND_PLAY conditions when compared with the OBS condition. No significant difference was observed between EYE_PLAY and HAND_PLAY conditions. Circles and ellipses indicate locations of frontoparietal areas mentioned in the present study: FEF = frontal eye fields; SEF = supplementary eye field; S1/M1 = left primary somatosensory and primary motor cortex (arm/hand motor area); PC = precuneus; SMG = supramarginal gyrus.</p

Experimental setup.

<p>(A) The digital game. The participants controlled a paddle to hit an approaching ball. The display has a 3D feel, so the more distant computer’s paddle is smaller and further away. In the first run they controlled the paddle using an fMRI-compatible eye tracking system; in the second run, the paddle was controlled by moving one LED that slid over a custom support (B). (C) Schematic representation of a run. The lower row shows the duration of the task or stimulus represented in the upper row. Each run consisted of 6 observation blocks (OBS BLOCK; represented in blue) and 6 execution blocks (PLAY BLOCK; represented in green). Execution and observation blocks were preceded by a fixation task where participants stared at a grey cross in the middle of a black screen for 19s (fixation condition; represented by the + sign). After each fixation task, an advisory word (“play” or “watch”) appeared for 1s to inform the subject about the next phase.</p