Supplementary Information Appendix: Default Mode Contributions to Automated Information Processing

Similar documents
Supplementary Information Methods Subjects The study was comprised of 84 chronic pain patients with either chronic back pain (CBP) or osteoarthritis

Supporting Online Material for

SUPPLEMENT: DYNAMIC FUNCTIONAL CONNECTIVITY IN DEPRESSION. Supplemental Information. Dynamic Resting-State Functional Connectivity in Major Depression

Twelve right-handed subjects between the ages of 22 and 30 were recruited from the

Supplementary Figure 1. Histograms of original and phase-randomised data

Supplementary materials. Appendix A;

This is a repository copy of Default Mode Contributions to Automated Information Processing.

Supplementary Online Content

Supplemental Information. Triangulating the Neural, Psychological, and Economic Bases of Guilt Aversion

Comparing event-related and epoch analysis in blocked design fmri

Supplementary Materials for

Supporting Information

Supporting online material. Materials and Methods. We scanned participants in two groups of 12 each. Group 1 was composed largely of

Supplementary information Detailed Materials and Methods

QUANTIFYING CEREBRAL CONTRIBUTIONS TO PAIN 1

Supporting online material for: Predicting Persuasion-Induced Behavior Change from the Brain

Supplementary Information

Supplementary Material S3 Further Seed Regions

Functional MRI Mapping Cognition

WHAT DOES THE BRAIN TELL US ABOUT TRUST AND DISTRUST? EVIDENCE FROM A FUNCTIONAL NEUROIMAGING STUDY 1

Supplementary Online Content

Effects Of Attention And Perceptual Uncertainty On Cerebellar Activity During Visual Motion Perception

Classification and Statistical Analysis of Auditory FMRI Data Using Linear Discriminative Analysis and Quadratic Discriminative Analysis

Investigations in Resting State Connectivity. Overview

2017, Joule Inc. or its licensors Online appendices are unedited and posted as supplied by the authors.

Supplementary Online Content

Supplementary Digital Content

Task-Related Functional Connectivity Analysis of Emotion Discrimination in a Family Study of Schizophrenia

Investigating directed influences between activated brain areas in a motor-response task using fmri

Experimental Design. Outline. Outline. A very simple experiment. Activation for movement versus rest

Supplementary Online Material Supplementary Table S1 to S5 Supplementary Figure S1 to S4

A possible mechanism for impaired joint attention in autism

Title of file for HTML: Supplementary Information Description: Supplementary Figures, Supplementary Tables and Supplementary References

Group-Wise FMRI Activation Detection on Corresponding Cortical Landmarks

Temporal preprocessing of fmri data

Personal Space Regulation by the Human Amygdala. California Institute of Technology

How to report my result using REST slice viewer?

smokers) aged 37.3 ± 7.4 yrs (mean ± sd) and a group of twelve, age matched, healthy

Validation of non- REM sleep stage decoding from resting state fmri using linear support vector machines

Temporal preprocessing of fmri data

Text to brain: predicting the spatial distribution of neuroimaging observations from text reports (submitted to MICCAI 2018)

Functional Magnetic Resonance Imaging with Arterial Spin Labeling: Techniques and Potential Clinical and Research Applications

GENDER-SPECIFIC SENSITVITY TO TIME-DISCREPANT TASK CONDITIONS OF REASONING DURING fmri

Face-specific resting functional connectivity between the fusiform gyrus and posterior superior temporal sulcus

Theory of mind skills are related to gray matter volume in the ventromedial prefrontal cortex in schizophrenia

Resistance to forgetting associated with hippocampus-mediated. reactivation during new learning

Supporting Information

Tracing tremor: Neural correlates of essential tremor and its treatment Buijink, A.W.G.

HST.583 Functional Magnetic Resonance Imaging: Data Acquisition and Analysis Fall 2008

Procedia - Social and Behavioral Sciences 159 ( 2014 ) WCPCG 2014

SUPPLEMENTARY METHODS. Subjects and Confederates. We investigated a total of 32 healthy adult volunteers, 16

Supplemental Information. Differential Representations. of Prior and Likelihood Uncertainty. in the Human Brain. Current Biology, Volume 22

Spatial Normalisation, Atlases, & Functional Variability

SUPPLEMENTARY MATERIALS: Appetitive and aversive goal values are encoded in the medial orbitofrontal cortex at the time of decision-making

O Connor 1. Appendix e-1

Supplemental Data. Inclusion/exclusion criteria for major depressive disorder group and healthy control group

Cover Page. The handle holds various files of this Leiden University dissertation

Changes in Default Mode Network as Automaticity Develops in a Categorization Task

The Cognitive Control of Memory: Age Differences in the Neural Correlates of Successful Remembering and Intentional Forgetting

Category: Life sciences Name: Seul Lee SUNetID: seul

FUNCTIONAL MAGNETIC RESONANCE EVIDENCE OF CORTICAL ALTERATIONS IN A CASE OF REVERSIBLE CONGENITAL LYMPHEDEMA OF THE LOWER LIMB: A PILOT STUDY

The interaction between motor fatigue and cognitive task performance van Duinen, Hiske

Experimental design. Experimental design. Experimental design. Guido van Wingen Department of Psychiatry Academic Medical Center

Stuttering Research. Vincent Gracco, PhD Haskins Laboratories

Altered effective connectivity network of the thalamus in post traumatic stress disorder: a resting state FMRI study with granger causality method

fmri and Voxel-based Morphometry in Detection of Early Stages of Alzheimer's Disease

DIADEM Instructions for Use

Differential contributions of subregions of medial temporal lobe to memory system in. amnestic mild cognitive impairment: insights from fmri study

Task-induced deactivations during successful paired associates learning: An effect of age but not Alzheimer s disease

Hippocampal brain-network coordination during volitionally controlled exploratory behavior enhances learning

Funding: NIDCF UL1 DE019583, NIA RL1 AG032119, NINDS RL1 NS062412, NIDA TL1 DA

Common Neural Substrates for Ordinal Representation in Short-Term Memory, Numerical and Alphabetical Cognition

Combining tdcs and fmri. OHMB Teaching Course, Hamburg June 8, Andrea Antal

Power-Based Connectivity. JL Sanguinetti

Topographical functional connectivity patterns exist in the congenitally, prelingually deaf

The Neural Correlates of Moral Decision-Making in Psychopathy

Journal of Clinical Neuroscience

Brain gray matter volume changes associated with motor symptoms in patients with Parkinson s disease

doi: /brain/aws024 Brain 2012: 135; Altered brain mechanisms of emotion processing in pre-manifest Huntington s disease

Advanced Data Modelling & Inference

Functional topography of a distributed neural system for spatial and nonspatial information maintenance in working memory

Cover Page. The handle holds various files of this Leiden University dissertation

Functional Specialisation and Effective Connectivity in Cerebral Motor Cortices: An fmri Study on Seven Right Handed Female Subjects

Supporting Online Material for

Hallucinations and conscious access to visual inputs in Parkinson s disease

Dissociation between Dorsal and Ventral Posterior Parietal Cortical Responses to Incidental Changes in Natural Scenes

Neural activity to positive expressions predicts daily experience of schizophrenia-spectrum symptoms in adults with high social anhedonia

Investigations in Resting State Connectivity. Overview. Functional connectivity. Scott Peltier. FMRI Laboratory University of Michigan

Network-based pattern recognition models for neuroimaging

Tracing tremor: Neural correlates of essential tremor and its treatment Buijink, A.W.G.

The Critical Relationship between the Timing of Stimulus Presentation and Data Acquisition in Blocked Designs with fmri

Behavioural Brain Research

Overt Verbal Responding during fmri Scanning: Empirical Investigations of Problems and Potential Solutions

Supporting Information

The Role of Working Memory in Visual Selective Attention

Distinct neural bases of disruptive behavior and autism symptom severity in boys with autism spectrum disorder.

HHS Public Access Author manuscript Nat Neurosci. Author manuscript; available in PMC 2015 November 01.

Neural correlates of two imagined egocentric transformations

Supplementary Online Content

Transcription:

Supplementary Information Appendix: Default Mode Contributions to Automated Information Processing Authors: Deniz Vatansever a,b,c,1, David K. Menon a,d, Emmanuel A. Stamatakis a,b,d Affiliations: a Division of Anaesthesia, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom, CB2 0QQ. b Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom, CB2 0QQ. c Department of Psychology, University of York, Heslington, York, United Kingdom, YO10 5DD. d Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom, CB2 0QQ. 1 Corresponding author: Deniz Vatansever, PhD Division of Anaesthesia University of Cambridge Box 93, Addenbrooke's Hospital Hills Road, Cambridge, UK CB2 0QQ E-mail: ddsv2@cam.ac.uk Tel: +44 (0) 1223 217892 Table of Contents Supplementary Materials and Methods... 2 Supplementary Results... 6 Supplementary Tables... 7 Supplementary References... 13

Supplementary Materials and Methods Participants Ethical approval for this study was obtained from the Cambridge Psychology Research Ethics committee in accordance with the Declaration of Helsinki. All volunteers gave informed consent prior to their participation. The exclusion criteria included lefthandedness, any history of drug and/or alcohol abuse, psychiatric/neurodegenerative conditions or head injury, use of contraindicated medication (e.g. anti-depressants), motor handicap that may impede task performance, contraindication to MRI scanning, severe claustrophobia, incidental MRI findings and pregnancy. One participant s data was excluded due to an incidental finding. Consequently, a group of 28 healthy controls participated in this functional magnetic resonance imaging (fmri) study (22 34 years old, mean = 26.8, SD = 2.8, 13/15 female to male ratio) with an average National Adult Reading Test (NART) score of 121.22 (SD = 3.17). Experimental Paradigm Specifications The experimental paradigm was a variant of the Wisconsin Card Sorting Task (WCST) (1) that was modified for the scanner environment utilizing a mixed design. Stimuli were delivered and responses recorded using an open source software package called PsychoPy (http://www.psychopy.org/) (Version 1.83). A short training session was first provided before the fmri scan in order to familiarize the participants with the task design. Inside the scanner, the paradigm commenced with 20 seconds of instructions, reminding the participants about the nature of the task. In this variant of the WCST, the participants were presented with four permanent reference cards on the upper half of the screen together with an alternating target card on the bottom half. The four reference cards consisted of a red triangle, two green circles, three blue crosses and four yellow stars, respectively. The target cards were randomly drawn from a pool of 60 cards based on the permutation of four shapes (triangle, circle, cross, star), four colors (red, green, blue, yellow), four possibilities for the number of objects present (1, 2, 3, 4), but excluding the four cards that were identical to the reference cards. The goal of this task was to sort the target card to one of the reference cards using four corresponding buttons on a button-box placed under the participant s right hand. While the sorting dimensions for the task included shape, number and color, the rule for the control condition was identity i.e. the target card was identical to one of the reference cards. Thus, the control condition matched the task conditions in visuospatial and motor aspects as well as simple cognitive components such as response selection. Following the 1500 ms presentation of a white font prompt Sort according to color, shape, number or identity against a black background, the reference and target cards appeared on the screen, commencing the trials. Participants were allowed a maximum of 3500 ms seconds to make their selection and the variable response time provided the necessary jittering in our experimental design. Subsequently, visual feedback appeared for 1500 ms replacing the target stimulus, and indicated whether the selection was correct or incorrect with a 2

corresponding smiley or sad face. If the participants did not respond by the allotted time, a Time Out prompt replaced the target card. Finally, a crosshair fixation period randomized between 1000 ms and 2000 ms seconds was shown on the screen until the beginning of the next trial. The variable duration for the crosshair presentation was selected to provide extra jittering and to make stimulus presentation less regular. In line with the experimental question, the sorting rule remained the same for a total of 10 trials, changing only at the presentation of another Sort prompt. Although the participants were informed about the point at which the rule was changed, they were not told what the new sorting dimension was. Thus, during the first few trials following the rule change, participants had to rely on feedback to deduce the context and make appropriate selections (i.e. trial-and-error). This we defined to be the acquisition (learning) phase of each block. However, once the rule was firmly established, the participants could then rely on the learned responses from memory for choosing the appropriate card, here referred to as the application phase. We operationally stratified the task into these two phases after completion of half the trials, to produce subsets of trials (n=5), maximized for acquisition and application. A total of 160 trials (16 blocks of 10 trials) were presented with four blocks of 10 trials for each of the three task sorting dimensions as well as the control sorting dimension, all presented in a pseudorandom order for each participant. Behavioral Data Analysis In order to test whether the experimental manipulation has produced the expected behavioral results, we calculated the percent correct responses as well as the reaction time to correct responses for both the acquisition and the application phases of the task as well as the control blocks. The reaction time to correct responses was chosen as the behavioral measure that was representative of the participants purposeful and consistent responses to the given stimuli, thus eliminating wrong or missed feedback in either phase of the WCST. Paired t-tests were employed in order to statistically assess the mean differences in percent correct responses and reaction time to correct responses for the overall task and control conditions as well as the stratified acquisition and application phases (Bonferroni corrected for multiple comparisons). This information was later used to investigate a potential brain-behavior relationship. MRI Data Acquisition The participants were scanned in a Siemens MAGNETOM Tim Trio 3T scanner (32- channel head coil) at the Wolfson Brain Imaging Centre, Cambridge. The scanning session started with a high resolution T1-weighted, magnetization-prepared rapid gradient-echo (MPRAGE) structural scan (TR = 2300 ms, TE = 2.98 ms, slice thickness = 1.00 mm). The echo planar imaging (EPI) sequence parameters for the WCST functional data acquisition were as follows: 37 slices in each volume, 3.0 mm slice thickness, 3.0 x 3.0 x 3.0 voxel size, TR = 2000 ms, TE = 30 ms, flip angle = 78 degrees. The number of 3D volumes varied according to the speed of the participants response to the task (mean = 347 volumes, SD = 12). 3

MRI Data Preprocessing The image analysis was carried out using SPM software package (http://www.fil.ion.ucl.ac.uk/spm/) (Version 12.0), based on the MATLAB platform (http://www.mathworks.co.uk/products/matlab/) (Version 15a). The first five volumes were removed to eliminate saturation effects and achieve steady state magnetization. The remaining functional images were first corrected for the differences in slice timing. The motion artifacts caused by volunteer movement inside the scanner were removed using six degrees of freedom, the average values of which are provided in Table S1. Neck tissue was removed from the high-resolution T1 weighted structural data using an MRIcron-based cropping tool (www.nitrc.org/projects/mricron), which was then coregistered to the mean motion-corrected functional image, and was subsequently segmented into probabilistic grey matter, white matter and cerebrospinal fluid maps. Next, all the corrected EPI volumes were spatially normalized through the unifiedsegmentation algorithm and utilizing the parameters calculated from transforming the grey matter map into MNI space. This procedure combines tissue segmentation, bias correction, and spatial normalization in a single unified model (2). Finally, all the functional images were smoothed using an 8 mm FWHM Gaussian kernel. Table S1. Average (absolute) motion parameters for the functional scans. X (mm) Y (mm) Z (mm) Pitch (radian) Roll (radian) Yaw (radian) Average (absolute) 0.118 0.260 0.454 0.008 0.003 0.003 Standard Deviation 0.087 0.259 0.407 0.013 0.002 0.002 MRI Data Analysis Task-evoked Activation Analysis The main objective of the initial task-evoked activation analysis was to confirm that the task, in comparison with the control condition, produced the expected activations as reported in the existing literature (3). For that purpose, first-level analyses with the appropriate contrasts were set up for each participant using the general linear model (GLM). For the task > control and task < control contrasts the design matrix included the onsets and durations of the task and control conditions as well as the six-movement parameters. Moreover, using another task-evoked activation model, we aimed to assess the hypothesis on the relative engagement of DMN regions in the application versus acquisition phases of the task condition. When comparing these two phases, the design matrix included the onsets of the correct/incorrect responses for the acquisition / application phases of the task and control conditions (modeled as impulses with a fixed duration of zero second) as well as the six-movement parameters. The jittered fixation periods were not modeled in order to avoid a rank deficient design. For the acquisition > application and acquisition < application contrasts, only the correct responses were taken into account. In both GLMs, a default high-pass filter of 128 seconds was employed, which removed the low-frequency signal drifts. The resulting subject-specific contrast maps were carried forward onto group-level analysis using one-sample t-tests. Functional Connectivity Analysis In addition to the task-evoked activation analysis, our next objective was to assess whether the DMN and DAN, the two robustly anti-correlated networks that are hypothesized to be driven by internal and external mentation (4, 5), respectively, would 4

display changes in their functional connectivity profiles in response to the acquisition and application phases of the task. For that purpose, the MNI coordinates of two seed regions representing DAN and DMN (5) were selected from the literature. The closest local peaks to these coordinates (in terms of Euclidean distance) were identified in the acquisition > application (for DAN) and acquisition < application (for DMN) contrasts of the grouplevel task-evoked activation analysis. Subsequently, 6 mm (radius) spheres were constructed around the MNI coordinates of the left frontal eye field (FEF) [-25-8 50] for the DAN and left posterior cingulate cortex/precuneus (PCC/PCUN) [-12-54 18] for the DMN. A strict temporal preprocessing pipeline of nuisance regression included motion and CompCor components attributable to the signal from white matter and cerebrospinal fluid (6) as well as a linear detrending term, eliminating the need for global signal normalization (7). The subject-specific six realignment parameters, the main effect of task-conditions and their first order derivatives were also included in the analysis as potential confounds. In addition to the low-frequency fluctuations that characterized early resting state investigations (4), recent studies indicate the detectable presence of largescale brain networks at high frequencies during task conditions (8). Thus, given the mixed design of this WCST task condition, a low-pass temporal filter was not employed. The Conn functional connectivity toolbox (9) (Version 15.h) was used in order to assess phase-specific changes in functional connectivity (acquisition versus application) using the weighted GLM method. For this purpose, the BOLD time series were first divided into event-specific scans as implemented by the Conn toolbox pipeline. This method accounts for the delay in hemodynamic response by convolving the event regressors (impulse onsets) for each task condition with a rectified hemodynamic response function (HRF). For each event, the scans that were associated with nonzero effects in the resulting time series were weighted by the value of the corresponding time series. This procedure not only adds the expected hemodynamic delay to different task conditions, but also de-weights the initial and final scans within when computing functional correlation measures in order to avoid spurious jumps in BOLD signal, and to minimize the potential cross-talk between adjacent task conditions (9). Following this procedure, seed-based functional connectivity analyses were performed for each subject using the average signal from the 6 mm (radius) spheres placed on the MNI coordinates for the 2 ROIs described above. Group-level analyses were carried out using t-statistics in which a one-sample t-test assessed the group-level spatial extent of DMN and DAN connectivity in the acquisition and application phases, whereas a paired t-test between these phases examined any changes in these networks functional connectivity. Brain and Behavior Correlation Analysis The final question to answer was whether the functional connectivity of the DAN and DMN in the acquisition and application phases of the task condition, respectively, would correlate with better performance as measured by the reaction time to correct responses. This consistency measure is believed to represent the participants purposeful and coherent decisions, and has been previously shown to constitute a reliable response set in WCST (10). The voxel-based correlation analysis involved using the maps obtained from 5

the seed-based functional connectivity analyses for the two phases in separate linear regressions with the reaction times to correct responses used as the variable of interest. All reported findings for the MRI data analyses were uncorrected at the voxel-level (p = 0.001) and multiple comparison corrected at the cluster level using the Family Wise Error (FWE) detection technique (p = 0.05). The statistical maps are available on the open access Neurovault repository (https://neurovault.org/collections/2969/). Supplementary Results Behavioral Results Table S2 summarizes the behavioral results obtained for the task and control conditions, as well as the acquisition and application phases. In comparison with the control condition, the participants had a smaller percentage of correct responses (t (27) = -14.46, p < 0.0001) and a longer reaction time to correct responses (t (27) = 20.03, p < 0.0001) in the task condition. In regards to the stratified phases of this WCST variant, the participants were less accurate (t (27) = 17.64, p < 0.0001) and slower (t (27) = 8.28, p < 0.0001) in the acquisition phase in comparison with the application phase of the task. This phasespecific result of a slower response (t (27) = 6.82, p < 0.0001) was also significant in the control condition; however, after multiple comparison correction, no significant difference was observed in accuracy (t (27) = -2.12, p = 0.17). Task-Evoked Activation Analysis Results Table S3 summarizes the differences in brain activity between the task and control conditions. The task > control contrast demonstrated greater activity in a number of cortico-striatal brain regions, all of which have been previously implicated in cognitive flexibility tasks. However, no clusters reached significance in the control > task contrast. Tables S4 and S5 summarize the differential brain activity observed in the acquisition > application and acquisition < application contrasts, respectively. Functional Connectivity Analysis Results While Tables S6-7 summarize the peak clusters in the functional connectivity of the left frontal eye field (FEF) seed for the DAN connectivity; Tables S9-10 report the peak clusters in the functional connectivity of the left posterior cingulate cortex/precuneus (PCC/PCUN) seed for the DMN connectivity. The results of the differential comparison of these two networks between the acquisition and the application phases of the task are given in Tables S8 and S11, respectively. Brain and Behavior Correlation Analysis Results Tables S12-13 summarize the peak clusters in the correlation of reaction time to correct responses with the functional connectivity of the left FEF seed for the DAN connectivity (acquisition phase), and PCC/PCUN seed for the DMN connectivity (application phase), respectively. 6

Supplementary Tables Table S2. Behavioral results for the employed variant of the WCST. The average percent correct responses and reaction time to correct responses are given for both the task and control conditions as well as the stratified acquisition and application phases. Behavioral Measure Condition/Phase Mean Standard Deviation Percent correct responses (%) Task 95.38 1.64 Reaction time to correct responses (ms) Acquisition 91.92 2.49 Application 98.84 1.15 Control 99.96 0.11 Acquisition 99.91 0.22 Application 100.00 0.00 Task 1185.80 142.45 Acquisition 1252.31 144.37 Application 1119.30 152.81 Control 897.44 114.23 Acquisition 956.63 137.70 Application 838.24 106.54 Table S3. Task-evoked activity results for the task > control contrast in this variant of the WCST. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. The reverse (control > task) contrast did not reveal any significant results. Task > Control size Peak MNI coordinates AAL label 0 8834 8.15-39 -2 34 Left precentral gyrus 0 20766 8.07 0-60 -22 Lobule VI of vermis 0 4073 6.8 11-28 -8 Right lingual gyrus 0 2087 6.32 42 46 18 Right middle frontal gyrus 0.026 269 4.52 27-56 44 Right angular gyrus Table S4. Task-evoked activity results for the acquisition > application contrast in the task condition. The table represents the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. Acquisition > Application size Peak MNI coordinates AAL label 0 83695 16.61-28 -60 46 Left superior parietal lobule 7

Table S5. Task-evoked activity results for the acquisition < application contrast in the task condition. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. Acquisition < Application size Peak MNI Coordinates AAL label 0 6451 9.58-26 -38 78 Left postcentral gyrus 0 2689 7.89 0 34-16 Left gyrus rectus 0 2160 7.82-12 -54 18 Left precuneus 0 4607 7.76 42-22 22 Right Rolandic operculum 0 3415 7.32-68 -16 4 Left superior temporal gyrus 0.012 282 6.64-43 -70 30 Left angular gyrus 0.001 441 5.61-24 -16-18 Left hippocampus Table S6. Functional connectivity results for the left frontal eye field seed (DAN) in the acquisition phase of the task condition in this variant of the WCST. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. DAN Acquisition size Peak MNI coordinates AAL label 0 14936 13.23-26 -8 50 Left middle frontal gyrus 0 459 9.26-58 8 34 Left precentral gyrus 0.002662 164 7.02 60 10 30 Right precentral gyrus 0.00168 176 6.74 14-74 -44 Right lobule VIIB of cerebellar hemisphere 0.001956 172 5.08-38 48 26 Left middle frontal gyrus 0.011872 127 4.98 36 48 32 Right middle frontal gyrus 0.035143 102-4.82 46-62 56 Right angular gyrus 0.029408 106-5.26 18 34 61 Right superior frontal gyrus 0.005213 147-5.28 52 12 50 Right middle frontal gyrus 0.000272 226-5.51-4 38 38 Left medial frontal gyrus 0.000044 280-6.62-22 26 62 Left superior frontal gyrus 0 615-6.78-40 -62 46 Left angular gyrus 0 461-9.55 44-4 21 Right Rolandic operculum 8

Table S7. Functional connectivity results for the left frontal eye field seed (DAN) in the application phase of the task condition in this variant of the WCST. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. DAN Application size Peak MNI coordinates AAL label 0 20426 15.11-26 -10 50 Left middle frontal gyrus 0 513 8.02-54 6 30 Left precentral gyrus 0 486 6.77 36 46 24 Right middle frontal gyrus 0.000002 407 5.77 16-58 -14 Right lobule VI of cerebellar hemisphere 0.00449 161 5.61-54 -66-6 Left inferior temporal gyrus 0.000008 358 5.56 24-64 -54 Right lobule VIII of cerebellar hemisphere 0.000093 276 5.49-46 40 28 Left middle frontal gyrus 0.029223 113 5.32-20 -64-50 Left lobule VIII of cerebellar hemisphere 0.001194 198-4.79-33 -76 50 Left inferior parietal lobule 0.00521 157-4.83 44-70 38 Right angular gyrus 0.021085 121-4.9 42 14 58 Right middle frontal gyrus 0.042498 104-4.95 28-99 -10 Right inferior occipital cortex 0.004659 160-4.97-4 -54 22 Left precuneus 0.00018 255-5.29 2 46 51 Left medial frontal gyrus 0.001236 197-5.69-55 32-6 Left inferior frontal gyrus, pars orbitalis 0 540-6.22-16 -96-10 Left lingual gyrus 0.000011 347-6.86-22 32 52 Left superior frontal gyrus Table S8. Comparison of the left frontal eye field (DAN) functional connectivity in the acquisition vs. application phases of the task. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. DAN Acquisition > Application size Peak MNI Coordinates AAL label 0.001548 155-5.89-64 -10 6 Left superior temporal gyrus 0.049844 83-5.89-52 -40 12 Left middle temporal gyrus 0.000182 206-6.43-48 -24 42 Left inferior parietal lobule 0.014554 107-6.5-38 -44 66 Left superior parietal lobule 9

Table S9. Functional connectivity results for the left posterior cingulate cortex/precuneus seed (DMN) in the acquisition phase of the task condition in this variant of the WCST. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. DMN Acquisition size Peak MNI Coordinates AAL label 0 20369 21-10 -52 18 Left precuneus 0 7979 13.49-4 52-4 Left medial orbitofrontal cortex 0 3693 11.2 64-2 -18 Right middle temporal gyrus 0.000009 335 8.06-31 10-12 Left insula 0.036656 102 6.37-2 -16 4 Left thalamus 0.00935 134 6.25 44 24-30 Right superior temporal pole 0.005748 146-4.93-50 26 32 Left inferior frontal gyrus, pars triangularis 0.003063 162-5.03 8-82 -26 Right crus II of cerebellar hemisphere 0.001665 178-5.23-10 14 48 Left supplementary motor area 0.000741 200-5.5 52-36 -10 Right middle temporal gyrus 0 851-5.58 54-48 48 Right inferior parietal lobule 0.000057 275-5.6 54 16 38 Right inferior frontal gyrus, pars opercularis 0.000956 193-5.72-26 -76-48 Left crus II of cerebellar hemisphere 0.000057 275-5.74-48 -40 44 Left inferior parietal lobule 0.001331 184-6.09 20 10 72 Right superior frontal gyrus 0 456-6.86 40-66 -34 Right crus I of cerebellar hemisphere 0 438-7.18-28 56-4 Left superior frontal gyrus, orbital part 0 1674-7.81 32 58 6 Right middle frontal gyrus 10

Table S10. Functional connectivity results for the left posterior cingulate cortex/precuneus seed (DMN) in the application phase of the task condition in this variant of the WCST. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. DMN Application size Peak MNI Coordinates AAL label 0 28149 23.02-12 -54 16 Left precuneus 0 1676 11.82 48-68 30 Right middle occipital gyrus 0 2012 10.06-58 -6-18 Left middle temporal gyrus 0 1437 9.48 58-4 -14 Right middle temporal gyrus 0 550 8.33-6 -52-42 Left lobule IX of cerebellar hemisphere 0 664 8.28 24 28 44 Right middle frontal gyrus 0.000272 237-5.67-44 -64-28 Left crus I of cerebellar hemisphere 0.003416 165-6.04 54-26 -22 Right inferior temporal gyrus 0.035851 106-6.35 32-64 -32 Right crus I of cerebellar hemisphere 0.00001 344-6.91 32-76 -48 Right crus II of cerebellar hemisphere 0 1419-6.93-28 -64 52 Left superior parietal lobule 0 591-6.98-36 -60-40 Left crus II of cerebellar hemisphere 0.000028 309-7.5 0-84 -28 Left crus II of cerebellar hemisphere 0 1965-8.64-40 60-2 Left middle frontal gyrus, orbital part 0 2344-9.17 42-58 60 Right inferior parietal lobule 0 899-9.49-34 18-6 Left insula 0 7885-11.44-4 0 62 Left supplementary motor area Table S11. Comparison of the left posterior cingulate cortex/precuneus seed (DMN) functional connectivity in the acquisition vs. application phases of the task. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. DMN Acquisition < Application size Peak MNI Coordinates AAL label 0 978 6.78 2 56-2 Right medial orbitofrontal cortex 0 743 6.18 0-50 38 Left precuneus 0 398 5.44-44 -74 42 Left angular gyrus 0.026511 99-5 48 46 2 Right inferior frontal gyrus, pars triangularis 0 495-6.02 58-30 30 Right supramarginal gyrus 0.000125 225-6.1 2 12 62 Right supplementary motor area 0.000222 210-6.33-60 -42 30 Left supramarginal gyrus 0.000006 309-7.06-42 16 0 Left insula 0 1059-7.47 40-8 -2 Right insula 11

Table S12. Correlation of the left frontal eye field (DAN) connectivity and reaction time to correct responses in the acquisition phase of the task. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. FEF Connectivity (DAN) Correlation with Reaction Time in Acquisition Phase size Peak MNI Coordinates AAL Label (T) (x,y,z mm) 0.049521 93 2-16 74 Right paracentral lobule Table S13. Correlation of the left posterior cingulate cortex/precuneus seed (DMN) connectivity and reaction time to correct responses in the application phase of the task. The table outlines the local peaks identified in the analysis, which have been named according to the Automated Anatomical Labeling (AAL) atlas. The associated FWE-corrected (cluster-level) p value, cluster size, effect size (T value) and MNI coordinates are listed below. PCC/PCUN Connectivity (DMN) Correlation with Reaction Time in Application Phase size Peak MNI Coordinates AAL label (T) (x,y,z mm) 0.000007 349-24 -100-10 Left inferior occipital cortex 0.000007 346-28 -2-26 Left amygdala 0.018665 119 44-86 -6 Right inferior occipital cortex 12

Supplementary References 1. Berg EA (1948) A simple objective technique for measuring flexibility in thinking. J. Gen. Psychol. 39:15-22. 2. Ashburner J & Friston KJ (2005) Unified segmentation. Neuroimage 26(3):839-851. 3. Buchsbaum BR, Greer S, Chang WL, & Berman KF (2005) Meta-analysis of neuroimaging studies of the Wisconsin card-sorting task and component processes. Hum. Brain Mapp. 25(1):35-45. 4. Fox MD, et al. (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc. Natl. Acad. Sci. U. S. A. 102(27):9673-9678. 5. Vincent JL, Kahn I, Snyder AZ, Raichle ME, & Buckner RL (2008) Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. J. Neurophysiol. 100(6):3328-3342. 6. Behzadi Y, Restom K, Liau J, & Liu TT (2007) A component based noise correction method (CompCor) for BOLD and perfusion based fmri. Neuroimage 37(1):90-101. 7. Chai XJ, Castanon AN, Ongur D, & Whitfield-Gabrieli S (2012) Anticorrelations in resting state networks without global signal regression. Neuroimage 59(2):1420-1428. 8. Cole MW, Bassett DS, Power JD, Braver TS, & Petersen SE (2014) Intrinsic and task-evoked network architectures of the human brain. Neuron 83(1):238-251. 9. Whitfield-Gabrieli S & Nieto-Castanon A (2012) Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connectivity 2(3):125-141. 10. Provost JS & Monchi O (2015) Exploration of the dynamics between brain regions associated with the default-mode network and frontostriatal pathway with regards to task familiarity. Eur. J. Neurosci. 41(6):835-844. 13