Figure 1 Visuomotor grip force-tracking set-up and conditions

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Figure 1 Visuomotor grip force-tracking set-up and conditions Figure 1 Visuomotor grip force-tracking set-up and conditions. Set-up for the visuomotor task: subjects were seated in ... Figure 1 Visuomotor grip force-tracking set-up and conditions. Set-up for the visuomotor task: subjects were seated in front of a 22” computer screen, set at eye level at a distance of 60 cm with head stabilized (forehead and chin rest). The screen displayed the visuomotor force-tracking tasks. Grip force was displayed as a red cursor moving vertically and in real-time as a function of the exerted grip force. The target force was displayed as a right-to-left scrolling coloured line. A trial consisted of a single ramp-hold-and-release sequence. Trials with different cognitive load were presented pseudo-randomly: (i) single-task trial (Single): grip force-tracking; (ii) dual-task distraction trial (Dual-DIST): during force-tracking, distractors, consisting of white-filled shapes (square, star, triangle, 2 × 2 cm), were randomly displayed for 500 ms in the four periods at specific times (1500 ms into Rest; 380 ms before Ramp onset; 1500 ms into Hold; and 380 ms before Release); (iii) dual-task addition trial (Dual-ADD): while subjects performed the force-tracking task, numbers (from 1 to 9, 2 × 2 cm) were displayed for 500 ms with onset times identical to the Dual-DIST trials. Subjects were instructed to focus on the tracking task and to inhibit saccades toward irrelevant visual stimuli (distractors), but to make saccades toward relevant stimuli (numbers). They were asked to mentally sum the successive numbers, and report the sum when given a cue. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Brain, awz127, https://doi.org/10.1093/brain/awz127 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 2 Force control accuracy Figure 2 Force control accuracy. (A) Raw data of single trials of grip force-tracking for a patient with schizophrenia ... Figure 2 Force control accuracy. (A) Raw data of single trials of grip force-tracking for a patient with schizophrenia (PSZ) and a healthy control subject (HC) for (i) the single-task force-tracking condition (Single) and the dual-task condition with (ii) dual-task distraction trial (Dual-DIST) and (iii) dual-task addition trial (Dual-ADD). Exerted force = solid line; target force (ramp-hold-and-release profile) = dotted grey line. Although the patient with schizophrenia seemed to perform the force matching task with less accuracy, the task was achieved; the overall modulation of force follows the target force throughout the trial, the force modulation is neither flat nor random, and the target hold-force level was reached (see Supplementary material for detailed analysis). (B) Mean RMS tracking-error (estimated marginal mean ± vertical bars: 95% confidence interval, CI) during Single (grey), Dual-DIST (pink) and Dual-ADD trials (cyan) for the three groups: patients with schizophrenia, healthy controls and siblings (SIB). Triangles represent data points of the individual subjects in each group and condition. Significant differences (LSD fisher post hoc tests for between group comparisons are shown as horizontal black brackets and within group comparisons as horizontal grey dashed brackets with: *P < 0.05; **P < 0.01, ***P < 0.001. For clarity, significant differences for between-group comparisons are only indicated between patients and healthy controls. Post hoc tests for between-group comparisons revealed that patients had increased error in the three conditions compared to controls (patients with schizophrenia versus healthy controls, Single: P = 0.03; Dual-DIST: P = 0.001; Dual-ADD: P < 0.001), but also to siblings (patients with schizophrenia versus siblings, Single: P = 0.04; DIST: P = 0.002; Dual-ADD: P < 0.001). Post hoc tests for within group comparisons revealed that DIST condition led to increased error compared to Single-task condition only in the patients with schizophrenia group (patient with schizophrenia: P = 0.003; healthy controls: P = 0.24; siblings: P = 0.88). However, Dual-ADD trials led to increased error compared to Single-task trials in all groups (patient with schizophrenia: P < 0.001; healthy controls: P < 0.001; siblings: P < 0.001). Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Brain, awz127, https://doi.org/10.1093/brain/awz127 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 3 Saccadic execution Figure 3 Saccadic execution. (A) Raw data of vertical eye position recorded during the visuomotor grip force-tracking ... Figure 3 Saccadic execution. (A) Raw data of vertical eye position recorded during the visuomotor grip force-tracking task for a patient with schizophrenia (PSZ) and a healthy control subject (HC). Example trials show saccades (solid line) relative to the appearance of a visual stimulus (dotted grey line) during the dual-task condition: (i) dual-task distraction trial (Dual-DIST) where subjects had to inhibit saccades toward visual distractors; and (ii) dual-task addition trial (Dual-ADD) where subjects had to exert a saccade toward the stimulus (number). Initial gaze position corresponds to the vertical cursor (force-tracking) position; maximal gaze amplitude corresponds to vertical position of the number or distractor. (B) Mean percentage of exerted saccades toward visual stimuli (estimated marginal mean ± vertical bars: 95% CI) during Dual-DIST (displayed in pink) and Dual-ADD trials (displayed in cyan) for the three groups: patients with schizophrenia, healthy controls and siblings (SIB). Triangles represent data points of the individual subjects in each group and condition. Significant differences (LSD fisher post hoc tests for between group comparisons are shown as horizontal black brackets and within group comparisons as horizontal grey dashed brackets with: *P < 0.05; **P < 0.01, ***P < 0.001. For clarity, significant differences for between-group comparisons are only indicated between patients and healthy controls. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Brain, awz127, https://doi.org/10.1093/brain/awz127 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 4 Cortical excitability Figure 4 Cortical excitability. (A) Raw data of MEPs recorded during the visuomotor grip force-tracking task (hold ... Figure 4 Cortical excitability. (A) Raw data of MEPs recorded during the visuomotor grip force-tracking task (hold period) for a patient with schizophrenia (PSZ) and a healthy control subject (HC). Example trials show an unconditioned MEP (dark line) and a conditioned MEP (grey line) of the 1DI for (i) the single-task force-tracking condition (Single) and the dual-task condition with (ii) dual-task distraction trial (Dual-DIST) and (iii) dual-task addition trial (Dual-ADD). (B) Mean normalized amplitude of MEPs for the hold period (estimated marginal mean ± vertical bars: 95% CI) during Single (grey), Dual-DIST (pink) and Dual-ADD (cyan) trials for the three groups: patients with schizophrenia, healthy controls and siblings (SIB). Triangles represent data points of the individual subjects in each group and condition. Significant differences (LSD fisher post hoc tests for between-group comparisons are shown as horizontal black brackets and within-group comparisons as horizontal grey dashed bracket with: *P < 0.05; **P < 0.01, ***P < 0.001. For clarity, significant differences for between-group comparisons are only indicated between patients and healthy controls. Post hoc tests for between-group comparisons (not indicated) revealed that patients with schizophrenia showed an increased excitability only in single-task condition compared to healthy controls (patients with schizophrenia versus healthy controls: P = 0.02), this was not significantly different compared to siblings (patients with schizophrenia versus siblings: P = 0.08). Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Brain, awz127, https://doi.org/10.1093/brain/awz127 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 5 Modulation of cortical excitability and inhibition, relation to clinical score (PANSS). (A) Strength of ... Figure 5 Modulation of cortical excitability and inhibition, relation to clinical score (PANSS). (A) Strength of modulation of cortical excitability (CE Modulation) for dual-task addition (Dual-ADD) compared to single-task trials (Single). This delta score (MEP<sub>Dual-ADD</sub> − MEP<sub>Single</sub>) corresponds to the mean MEP amplitude in Dual-ADD minus that in Single (estimated marginal mean ± vertical bars: 95% CI). For patients with schizophrenia (PSZ, grey), healthy control subjects (HC, dark grey) and siblings (SIB, white). Triangles represent data points of the individual subjects in each group. Significant differences between groups (LSD fisher post hoc tests) shown as horizontal brackets with: *P < 0.05, ***P < 0.001. (B) Strength of SICI modulation (CI Modulation); as in A but for (SICI<sub>Dual-ADD</sub> − SICI<sub>Single</sub>). (C) Spearman’s correlation between delta score of cortical excitability (CE-M) and symptom severity: PANSS disorganization subscore for patients with schizophrenia (r = − 0.69, P = 0.001). Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Brain, awz127, https://doi.org/10.1093/brain/awz127 The content of this slide may be subject to copyright: please see the slide notes for details.