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. Author manuscript; available in PMC: 2017 Feb 1.
Published in final edited form as: Magn Reson Imaging. 2015 Oct 31;34(2):209–218. doi: 10.1016/j.mri.2015.10.036

A human brain atlas derived via n-cut parcellation of resting-state and task-based fMRI data

G Andrew James 1, Onder Hazaroglu 2, Keith A Bush 2
PMCID: PMC4837649  NIHMSID: NIHMS734852  PMID: 26523655

Abstract

The growth of functional MRI has led to development of human brain atlases derived by parcellating resting-state connectivity patterns into functionally independent regions of interest (ROIs). All functional atlases to date have been derived from resting-state fMRI data. But given that functional connectivity between regions varies with task, we hypothesized that an atlas incorporating both resting-state and task-based fMRI data would produce an atlas with finer characterization of task-relevant regions than an atlas derived from resting-state alone. To test this hypothesis, we derived parcellation atlases from twenty-nine healthy adult participants enrolled in the Cognitive Connectome project, an initiative to improve functional MRI’s translation into clinical decision-making by mapping normative variance in brain-behavior relationships. Participants underwent resting-state and task-based fMRI spanning nine cognitive domains: motor, visuospatial, attention, language, memory, affective processing, decision-making, working memory, and executive function. Spatially constrained n-cut parcellation derived brain atlases using (1) all participants’ functional data (Task) or (2) a single resting-state scan (Rest). An atlas was also derived from random parcellation for comparison purposes (Random). Two methods were compared: (1) a parcellation applied to the group’s mean edge weights (mean), and (2) a two-stage approach with parcellation of individual edge weights followed by parcellation of mean binarized edges (two-stage). The resulting Task and Rest atlases had significantly greater similarity with each other (mean Jaccard indices JI= 0.72–0.85) than with the Random atlases (JI=0.59–0.63; all p<0.001 after Bonferroni correction). Task and Rest atlas similarity was greatest for the two-stage method (JI=0.85), which has been shown as more robust than the mean method; these atlases also better reproduced voxelwise seed maps of the left dorsolateral prefrontal cortex during rest and performing the n-back working memory task (r=0.75–0.80) than the Random atlases (r=0.64–0.72), further validating their utility. We expected regions governing higher-order cognition (such as frontal and anterior temporal lobes) to show greatest difference between Task and Rest atlases; contrary to expectations, these areas had greatest similarity between atlases. Our findings indicate that atlases derived from parcellation of task-based and resting-state fMRI data are highly comparable, and existing resting-state atlases are suitable for task-based analyses. We introduce an anatomically labeled fMRI-derived whole-brain human atlas for future Cognitive Connectome analyses.

1. Introduction

The recent growth of functional neuroimaging research has led to development of human brain atlases that accurately reflect the brain’s functional organization. Several such atlases have been generated by applying parcellation approaches to functional magnetic resonance imaging (fMRI) data [17]. These approaches identify functionally independent brain regions by first calculating the functional connectivity between all voxels (i.e. the correlation of each voxel’s activity timeseries with all other voxels), then using parcellation algorithms (such as the n-cut method, cite) that maximize within-cluster voxels’ correlations while minimizing between-cluster voxels’ correlations.

All functional atlases to date – whether encompassing the entire brain [14] or specific cortical regions [57] – have been derived from resting-state fMRI scans in which participants lie awake in the scanner while not engaged in overt tasks. But functional connectivity patterns change with cognitive task, raising the possibility that atlases derived solely from resting-state data may be suboptimal for studying task-dependent brain activity. As examples, functional connectivity between Broca’s and Wernicke’s areas dramatically increases during a reading task compared to tongue-movement or rest [8], and connectivity among motor regions increases with finger tapping compared to rest [9]. In both examples, functional connectivity seed maps show clearer boundaries during task than rest, suggesting that a parcellation approach incorporating both resting-state and task-based functional connectivity may produce an atlas with finer characterization of task-relevant regions than an atlas derived solely from resting-state data.

We addressed this potential barrier by deriving two whole-brain atlases from fMRI data acquired through the Cognitive Connectome project [10], an initiative to translate fMRI into patient care by bridging clinical neuropsychology and functional neuroimaging. We derived two atlases: one atlas incorporating data from a single resting-state scan (similar to existing atlases), and a comparison atlas incorporating data from resting-state and task-based scans encompassing motor performance, visual perception, visuospatial judgment, emotional processing, verbal memory, visual memory, working memory, language fluency, attentional conflict, reward processing, and executive function. We hypothesize that a parcellation incorporating both resting-state and task-based fMRI data (a Task atlas) will substantially differ from an atlas derived from resting-state data alone (Rest). Specifically, we predict that regions recruited during higher-order cognition (such as prefrontal and temporal regions for executive function, language, and memory) will substantially differ in size and shape between atlases, whereas regions involved in less demanding tasks (such as visual and motor regions) will be similar across atlases. We also predict that voxelwise connectivity seed maps of task-based fMRI scans will show stronger spatial correspondence to seed maps derived from the task-based atlas than the resting-state atlas. Finally, we provide the atlas as an anatomically labeled tool for future analyses of the Cognitive Connectome project data.

2. Materials and Methods

2.1. Cognitive Connectome

All Cognitive Connectome study procedures were conducted in the Brain Imaging Research Center at the University of Arkansas for Medical Sciences. Study participation was typically conducted in two sessions on separate days. Session 1 included informed consent, a structured clinical interview (SCID-IV/NP) to determine exclusionary criteria, behavioral surveys and questionnaires (such as the State-Trait Anxiety Inventory and Big Five Personality Inventory), and the first of two hour-long neuroimaging session (with neuroimaging session order counterbalanced across subjects). Session 2 included neuropsychological assessment and the second neuroimaging session. Cognitive Connectome project study procedures are described in full detail elsewhere [10].

2.2. Participants

Thirty-five participants completed both fMRI sessions. (Five additional pilot participants completed both fMRI sessions, but are excluded due to substantial task redesign based upon their feedback.) Table 1 and Supplementary Materials provide descriptions of each fMRI scan, including task design and scan duration. Scans with excessive head motion (i.e. greater than 3mm lateral movement in any direction) were excluded from analyses. Of these 35 participants, 29 were included in the final analysis: 7 with useable data from 12 scans, and 22 with useable data from all 13 scans. The excluded scans included a second resting-state scan (n=2), visual memory (n=2), motor performance (n=1), visual perception (n=1), and executive function (n=1). The twenty-nine participant sample had the following demographics: mean(sd) age = 31(9.9), range 20–50; 10 (34%) male, 19 (66%) female; 19 (66%) self-reporting as White or Caucasian, 12 (41%) as Black or African-American, 1 (3%) as Hispanic or Latino, including 1 participant who self-identified as both Caucasian and African-American; mean(sd) education = 16(2.2) years, range 10–19. All participants were recruited with approval and oversight by the UAMS Institutional Review Board (protocol #130825).

Table 1.

Descriptions of fMRI tasks

Task Session Duration Description
Controlled Oral Word Association Task (COWAT) A 5m 0s Alternating 15s blocks of Letter or Category word generation separated by 15s rest
Rating affective images (IAPS affect) A 5m 14s 45 IAPS images (negative, neural, positive) presented in random order for 2.5s with 2–6s inter-stimulus interval
Recognizing affective images (IAPS recognition) A 10m 12s 90 IAPS images (45 previously seen, 45 new) presented in random order for 2.5s with 2–6s interstimulus interval
Judgment of Line Orientation task (JLOT) A 4m 16s 15 JLOT trials (self-paced, up to 15s duration) with rest at start of task and each trial completion
N-back A 8m 0s Alternating 45s blocks of 0-back or 2-back trials separated by 15s rest
Resting-state A 7m 30s Passive viewing of a black fixation cross upon light gray background
Iowa Gambling Task B 8m 6s – 11m 42s (me an 9m 14s) Self-paced, participant draws 100 cards of varying reward/loss from 4 decks
Finger tapping B 3m 0s 18s blocks of index finger tapping (left-right-right-left-right-left) separated by 10s rest
Multi-source Interference Task (MSIT) B 8m 0s Alternating 48s blocks of Congruent or Incongruent MSIT trials with 30s rest at start, middle, and end of task
Verbal Paired Associates B 2m 0s Ten word pairs presented as consecutive 6s blocks with 30s rest at start and end of task
Resting-state B 7m 30s Passive viewing of a black fixation cross upon light gray background
Tower of London B 3m 26s – 7m 30s (me an 4m 20s) Self-paced, 24 Tower of London trials (2-, 3- and 4-move) starting with 5s planning phase and ending with 6s rest
Flashing visual checkerboard B 2m 0s Four 18s blocks of 4Hz flashing checkerboard separated by 10s rest

Session order was counterbalanced across participants. Each session began with a resting-state scan, and IAPS affect/IAPS recognition were the second and final scans of session A; otherwise, within-session task order was also counterbalanced across participants.

2.3. Image Acquisition and Preprocessing

2.3.1. Image Acquisition

Imaging data were acquired using a Philips 3T Achieva X-series MRI scanner (Philips Healthcare, Eindhoven, The Netherlands). Anatomic images were acquired with a MPRAGE sequence (matrix = 256 × 256, 220 sagittal slices, TR/TE/FA = shortest/shortest/8°, final resolution =0.94 × 0.94 × 1 mm3 resolution). Functional images for early participants (001–050) were acquired using an 8-channel head coil with an echo planar imaging (EPI) sequence (TR/TE/FA = 2000 ms/30 ms/90°, FOV=240 × 240 mm, matrix = 80 × 80, 37 oblique slices parallel to orbitofrontal cortex to reduce sinus artifact, interleaved ascending slice acquisition, slice thickness = 4 mm, final resolution 3.0 × 3.0 × 4.0 mm3). For these subjects, one session’s resting-state scan was acquired with 3-mm slice thickness to be consistent with data acquired for other BIRC studies. Functional images for later participants (051–079) were acquired using a 32-channel head coil with the following EPI sequence parameters: TR/TE/FA = 2000 ms/30 ms/90°, FOV = 240 × 240 mm, matrix = 80 × 80, 37 oblique slices, ascending sequential slice acquisition, slice thickness = 2.5 mm with 0.5 mm gap, final resolution 3.0 × 3.0 × 3.0 mm3. Parameters for the 32-channel coil were selected to reduce orbitofrontal signal loss due to sinus artifact. To assess head coil as a potential confound, we regressed head coil against participants’ functional connectivity data (measured as voxelwise seed maps with the dorsolateral prefrontal cortex, see below) to evaluate if choice of head coil significantly influenced functional connectivity (and thus, atlas generation).

2.3.2. Image Preprocessing

All MRI data preprocessing was conducted in AFNI unless otherwise noted [11]. Anatomic data underwent skull stripping, spatial normalization to the icbm452 brain atlas, and segmentation into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) with FSL [12]. Functional data underwent despiking; slice correction; deobliquing (to 3×3×3 mm3 voxels); motion correction (using the 10th timepoint); transformation to the spatially normalized anatomic image; regression of motion parameters, mean timecourse of WM voxels, and mean timecourse of CSF voxels; spatial smoothing with a 6-mm FWHM Gaussian kernel; and scaling to percent signal change. Resting-state scans also underwent bandpass filtering (0.01–0.10 Hz) to remove physiological artifact relating to noise. fMRI scans with head motion exceeding 3mm lateral movement were excluded from subsequent scans. Participants’ binarized GM masks were averaged to generate a group-level gray matter mask; voxels with a group mean GM value ≥ 0.5 were included in the parcellation approach described below.

2.4. Analyses

2.4.1. Parcellation

MRI data parcellation utilized the normalized cut (n-cut) approach [1]. This approach used a refinement of graph cutting algorithms that attempt to partition undirected, weighted graphs by assigning the graph’s partitions according to a minimized cut cost. The cut cost, cut(A,B), represents the sum of the weights of edges that must be removed from the graph to completely partition the subset of nodes, A, from a disjoint subset of nodes, B. The n-cut algorithm modifies the cut cost by dividing the total sum of edge weights associated with subsets A and B, respectively, thus normalizing the influence between densely and sparsely connected nodes. In application to MRI, graph nodes were represented by individual voxels and graph edges include only those voxels in the 3-dimensional (face and edge adjacent) neighborhood, resulting in 26 edges per voxel. Edge weights were set equal to voxel pair-wise Pearson correlations over the voxels’ time-courses. In other words, n-cut searched for “fissures” of weak connectivity between neighboring voxels, and set these fissures as boundaries to maximize within-cluster correlations among voxels and minimize correlations of voxels belonging to neighboring clusters.

This n-cut approach also allows two algorithms for group-level parcellation. The group mean algorithm averages edge weights across the group prior to the n-cut parcellation. The group two-stage algorithm first parcellates each subject’s MRI based on their edge weights, then digitizes the first-stage parcellations to produce binary (0 or 1) edge weights which are averages across the group prior to the second n-cut parcellation. Both methods were explored here.

Three region of interest (ROI) group atlases were generated for each method. The first atlas (Rest) was constructed entirely from one resting-state scan (comparable to experiments conducted in [1]). The second atlas (Task) was constructed from combined resting-state and task scans, which are concatenated into a single image as follows. Each individual scan was first z-scored voxel-wise; then the scans were concatenated in the time dimension; then the combined scan was z-scored. The third atlas (Random) was constructed by setting the edge weights between neighboring voxels to 1 rather than the voxels’ Pearson correlation. Thus there are no “fissures” of weak connectivity to guide parcellation, causing voxels to randomly parcellate into equally sized clusters.

All n-cut parcellations were conducted using the experimental source code for the work published in [1] available at https://www.nitrc.org/projects/cluster_roi/. Normalization and concatenation calculations were conducted using Matlab. All experiments were executed on a Hewlett Packard ProLiant DL980 G7 Server (80 processors and 4TB single-addressable memory). Scripts and data are available upon request.

2.4.2. Comparing ROIs across atlases

We compared the similarity (homology) of ROIs across atlas parcellations as follows. Let set I equal all voxels comprising an ROI in Atlas A (ROIA). The voxels spatially corresponding to the voxels in set I were identified in Atlas B. The values of these voxels indicate the ROI(s) in Atlas B with partial overlap with ROIA, and the mode of these voxels’ values identify the ROI in Atlas B (ROIB) with the greatest overlap of ROIA. Letting set J equal all voxel comprising ROIB, the similarity of ROIB and ROIB was calculated using the Jaccard index, or the number of voxels shared by ROIA and ROIB divided by the total number of voxels in ROIA and ROIB (i.e. intersection I∩J/union I∪J).

2.4.3. Comparing connectivity seed-maps across atlases

We compared the atlases’ ability to replicate connectivity seed maps for the left dorsolateral prefrontal cortex (LDLPFC) across two conditions: during wakeful rest and during performance of the n-back working memory task. The LDLPFC was identified from group-level analysis of the n-back task: brain activity was contrasted between 2-back and 0-back conditions for each participant using general linear modeling (GLM) with AFNI’s 3dDeconvolve, residual maximum likelihood (REML) analyses accounted for influence of temporal autocorrelation with 3dREMLfit, and mixed-effects meta-analysis identified group-level differences between 2-back and 0-back conditions with 3dMEMA (all scripts available upon request). A 6mm radius spherical ROI was centered upon the LDLPFC (MNI coordinates −44, 23, 31; Figure 3), and voxelwise seed maps were generated by correlating each voxels’ activation timeseries with the mean activation timeseries of voxels within the ROI. Atlas seed maps were generated by identifying the atlas seed ROI containing the most voxels from the task-defined ROI, extracting the mean timeseries of voxels comprising each ROI, correlating each ROI timeseries with the atlas seed ROI timeseries, and backprojecting these correlations to GM voxels comprising each atlas. The resulting seed maps (voxelwise, Task atlas, Rest atlas) were Fisher z-transformed so that the voxels’ correlations approximated linearity, and the three seed maps were compared via pairwise spatial correlation.

Figure 3. Validation of atlases via task-based and resting-state replications of seed maps.

Figure 3

(Top) The n-back task elicited greater group-level bilateral dorsolateral prefrontal (DLPFC) and parietal activity for 2-back condition than 0-back condition. Results are displayed a p<0.005 uncorrected and contiguous cluster size>2,050mm3 (76 contiguous voxels) for AlphaSim corrected q<0.01. We identified the left DLPFC seed as a 6mm radius ROI centered upon MNI coordinates (−44, 23, 21), indicated by blue crosshairs. (Bottom) Correlation seed maps were generated for the n-back and resting-state data using voxelwise data and mean timecourses of the Random, Resting, and Task-based parcellation atlases. All three atlas seed maps correlated with the voxelwise seed map, although correlations were significantly higher for the Resting and Task atlases (r=0.75–0.80) than the Random atlas (r=0.64–0.72). Note that the left DLPFC ROIs identified from Resting and Task atlases are centered upon the n-back task derived ROI, whereas the Random atlas DLPFC ROI is not, probably owing to the incorporation of fMRI data.

3. Results

3.1. Evaluating ROI sizes

ROIs encompassing fewer than 5 voxels (135 mm3) were removed from each parcellation, as these ROIs were too small to be biologically meaningful. ROIs which were three standard deviations larger than the mean were also removed from each parcellation. This includes a cluster composed of over 2,300 voxels (62,100 mm3) identified for the Task, group two-stage method which covered much of the brain’s circumference. Similar implausibly large ROIs have been identified and omitted from other brain atlases [1]. ROI sizes did not significantly differ between atlases, either before removal of artifactual clusters [F(5,1169)=0.09, p<0.99] or after removal [F(5,1161)=1.08, p<0.37]. After removal, mean ROI size ranged from 177–186 voxels across parcellations, with standard deviations ranging from 42–50 voxels.

3.2. Evaluating similarity

3.2.1. ROI similarity across all atlases

Table 1 provides mean Jaccard indices (JI) for ROI similarity between atlases. Each combination of dataset and parcellation method yielded an atlas with strong similarity to the random parcellation (mean JI 0.59–0.63). Jaccard indices were skewed toward the highest possible value of 1, prompting use of nonparametric statistics to compare ROI similarity between atlases. ROI JIs were much greater for atlases generated using the same method or same data than for the randomly generated atlases (all Wilcoxon rank sum tests values > 4, all p < 0.001 after Bonferonni correction for 8 comparisons). This was particularly true for the group two-stage method Task and Rest atlases; ROI JIs were greater for these atlases (μ=0.846) than for the random parcellation (μ=0.645; z-value>10, p<0.001). We replicated these analyses using the Dice coefficient similarity index and found almost perfect correlation (r=0.99), supporting our use of the Jaccard index.

3.2.2. Similarity between All and Rest atlas ROIs

Figure 1 depicts ROIs for the Task, group two-stage atlas, and Figure 2 depicts the JI for each ROI compared to its homolog in the Rest, group two-stage atlas. 47% of these ROIs had a JI ≥0.90, and 79% had JI ≥0.80. Contrary to hypotheses, greatest similarity was observed for prefrontal cortex, cingulate gyrus, left parietal lobe, and left temporal lobe. Only 5% of ROIs had a JI <0.50. Table 2 lists all ROIs of the Task, group two-stage atlas ranked by their similarity to the Rest, group two-stage atlas. Regions with lowest similarity (JI<0.50) included right sensorimotor area (middle primary sensory cortex (S1), JI=0.34; inferior S1, JI=0.41; lateral premotor area, JI=0.37;), left sensorimotor area (left S1, JI=0.48; and adjacent left inferior parietal lobule, JI=0.49), regions bordering ventricles (left caudate, JI=0.42; septum pellucidum, JI=0.47; thalamus, JI=0.42), right middle temporal gyrus (medial region, JI=0.33; lateral region, JI=0.33), and right posterior superior parietal lobule (JI=0.40).

Figure 1. Regions comprising the Task, group two-stage atlas.

Figure 1

The parcellation derived from 29 healthy participants using the Group two-stage method and all task-based and resting-state data is depicted across axial slices (MNI coordinates z=−24 to z=69). Regions of interest (ROIs) are color-coded to maximize contrast between parcellation boundaries. ROIs demonstrate strong bilateral symmetry of ROIs between hemispheres.

Figure 2. Strong similarity between Task and Rest atlases.

Figure 2

The parcellation derived using the group, two-stage method and all task-based and resting-state data was compared to the parcellation derived using the group, two-stage method but a single resting-state session for each participant. The Jaccard Index (JI) reported overall strong similarity between parcellations (mean JI= 0.85). Contrary to hypotheses, regions associated with higher-order cognition (such as prefrontal and temporal regions) showed strong similarity across task-based and resting-state parcellations. Poorest similarity was observed for ROIs in right sensorimotor area, right superior temporal sulcus, and regions bordering left lateral ventricle.

Table 2.

Jaccard Similarity Indices across Atlases

Atlas 1 Atlas 2 Jaccard Index
mean sd

Comparison to Random atlas
Rest, Random All, Random 0.645 0.230
Rest, group two-stage Rest, Random 0.632 0.216
Rest, mean Rest, Random 0.611 0.228
Task, group two-stage Task, Random 0.607 0.211
Task, mean Task, Random 0.588 0.203
Comparison of Atlases by Method
Task, group two-stage Rest, group two-stage 0.846 0.144
Task, mean Rest, mean 0.716 0.221
Comparison of Atlases by Data
Rest, group two-stage Resting, mean 0.720 0.200
Task, group two-stage Task, mean 0.719 0.203

3.3. Seed map comparisons

Figure 3 and Table 3 compare left DLPFC seed maps derived via parcellation-atlases or voxelwise approaches. All parcellation-derived seed maps were significantly correlated with voxewise seed maps (r= 0.64–0.80, all p<0.001). Voxelwise seed maps had stronger correlation (and thus higher replication) with Task and Rest atlas seed maps (r= 0.75–0.80) than Random atlas seed maps (r= 0.64–0.72). Additionally, Task and Rest atlas seed maps were highly correlated for resting-state (r=0.89) and n-back task (r=0.92), further emphasizing these atlases’ similarity.

Table 3.

Regions of Interest for Task, Group Two-Stage atlas ranked by similarity to Rest, Group Two-stage Atlas

Region Jaccard Index MNI Coordinates Lobe Volume (in mm3) Label
X Y Z
38 100 −32.5 35.9 −3 Visual 2106 LaOFG_38
59 100 −0.2 −0.6 34.9 Cingulate 3618 MidCingulate_59
132 100 −17.1 −13.3 25.3 Subcortical 729 Lpo_Caudate_132
35 99 −9.2 −20.4 43.8 Motor 4482 Lpo_pericingulate_35
60 99 −9.5 59.8 24.9 Frontal 4428 LrmPFC/LvmPFC_60
102 99 −47.4 31.7 3.5 Frontal 4509 LIFG_BA45_102
155 99 −0.3 23.4 26.3 Cingulate 4158 dACC_155
73 98 −25.5 56.5 15.6 Frontal 3726 LavlPFC_73
80 98 −25.8 5.8 −13.8 Temporal 4239 LOlfC_80
91 98 18.8 −8.4 −14.8 Temporal 3807 RHPC_CA/Amyg_91
94 98 −11.2 −27.8 10.5 Subcortical 2808 Lthalamus_94
103 98 17.3 −34.3 −18.6 Visual 5373 Rculmen_103
125 98 −34.5 22.4 10.5 Frontal 4617 Lsup_AIns_125
128 98 29.5 −19.6 −13.2 Temporal 3699 RHPC_body_128
197 98 −13.8 3.1 21.2 Subcortical 1809 Lacaudate_197
49 97 45.1 29.3 3.4 Frontal 4293 RIFG_BA45_49
115 97 5.7 33 35.5 Frontal 4752 RAperiCing_95
131 97 −40.1 46.2 12.4 Frontal 4212 LvlPFC_131
143 97 35.1 19.9 −6.8 Frontal 4320 Rinf_AIns_143
186 97 12.2 19.2 8.6 Subcortical 2619 RaCaudate_186
15 96 24.4 8.5 3.6 Subcortical 2646 RAputamen_15
26 96 9.2 −28 10.1 Subcortical 2349 Rthalamus_26
34 96 −1.2 −40.3 −14.6 Cerebellum 2997 Vermis_34
41 96 6.2 42.4 19.8 Cingulate 5130 RrostralACC_MPFC_41
47 96 −7.9 40.5 26.5 Cingulate 5265 LrostralACC_MPFC_47
54 96 −10.5 34.6 53.5 Frontal 3942 LsupFG_54
57 96 6.3 58.5 12.6 Frontal 3321 RvmPFC_57
62 96 −39.1 6.9 35.1 Frontal 4833 LpodlPFC_62
71 96 39.1 46.7 6.3 Frontal 3213 RvlPFC_71
82 96 −10 −39.5 45.9 Parietal 5454 LSPL_5C
85 96 −10 49.4 42 Frontal 3861 LdmPFC_85
113 96 −36.9 20 −5.5 Frontal 5265 Linf_AIns_113
118 96 8.3 7.2 63.7 Cingulate 4509 RpreSMA_118
130 96 34.4 19.6 10.1 Temporal 4509 Rsup_AIns_130
136 96 −7.4 0.2 48.3 Cingulate 4941 LpreSMA/dACC_136
181 96 −25.4 8.3 4.3 Subcortical 3024 LAputamen_181
193 96 29.2 6.4 −15.4 Temporal 3834 ROlfC_193
185 92 46.1 5.2 −14.5 Temporal 4104 RTempPole_185
188 92 −26.5 −36.7 −0.4 Temporal 3294 LHPC_tail_188
190 92 −39.6 −7.9 −0.4 Temporal 5913 Linf_MidIns_190
5 91 −1.1 −51 13 Cingulate 5292 retrosplenial_cortex_5
14 91 −46.8 −55.9 41.3 Parietal 5940 LIPC_PGa_14
19 91 24.4 47.2 34.4 Frontal 5292 RrlPFC_19
40 91 −59.6 −19.7 27.6 Parietal 5751 LIPC_Pfop_40
53 91 −53.8 6.4 27.2 Motor 5400 LdlPFC_53
89 91 8.2 −31.9 43.9 Cingulate 5373 RSPL_5C
158 91 −9.5 −54 35.4 Visual 5265 Lprecu_158
160 91 −26.3 6.1 58 Motor 5778 LFEF_160
27 90 −12.6 −19.7 69.5 Motor 5049 LlatSMA_27
56 90 23.5 −51.2 −10.9 Visual 4887 Rfusiform_56
66 90 42.9 −54.9 18.2 Parietal 5238 RTPOJ_66
70 90 −41.6 −18 14.9 Temporal 4833 LIns_OP1_70
112 90 −54.6 −2.3 −5.2 Temporal 5130 LAinfMTG_112
120 90 −25 23.5 50 Frontal 5454 LsupDLPFC_120
134 90 −25.3 −86.1 17.8 Visual 5049 Locc_BA18_134
140 90 57.1 −9.2 14.1 Motor 5913 R_OP4_140
149 90 32.6 −36.5 −14.9 Visual 4239 Rfusiform/PHG_149
168 90 −50.8 13.2 8 Frontal 5832 LIFG_BA44_168
11 89 10.5 −43.1 −3.1 Visual 4698 RALingual_11
31 89 −29.2 −53.6 57.1 Parietal 6156 LSPL_7A_31
42 89 22.7 −68.9 −9.1 Visual 5022 Rpofusiform_42
43 89 38.2 −22.5 43.3 Motor 5670 RM1_43
52 89 10.7 −64.2 58.3 Parietal 5022 RSPL_52
167 89 50.4 8.5 2.6 Frontal 5454 RIFG_BA44_167
174 89 41.2 −50.5 −15.8 Visual 5913 Rfusiform/RITG_174
33 88 −39.7 1.1 12.4 Motor 4401 Lsup_MidIns_33
76 88 −30.6 −66.4 41.6 Parietal 6615 LpoIPL_76
87 88 −26.9 −33.6 61.4 Motor 6102 Lmedial_CentralSulcus_87
148 88 3.7 −52.4 48.8 Visual 6129 SPL_7A_148
151 88 −26.5 50.4 29.6 Frontal 4968 LrlPFC_151
163 88 25.3 −36 60.5 Motor 6021 Rmedial_CentralSulcus_163
170 88 0.6 −60.7 −3 Cerebellum 6534 medcbell_170
22 87 −17.5 −33 −17.1 Cerebellum 5076 Lculmen_22
36 87 51 20.1 16.5 Frontal 5076 RIFG_BA44_36
13 86 −12.1 −53.4 61.1 Parietal 5292 LSPL_7A_13
16 86 23.5 13.2 56.5 Frontal 5778 RFEF_16
61 86 52.9 5.3 25.3 Motor 5589 RdlPFC_61
86 86 −56.9 −44.6 25.5 Parietal 6102 LpoSTS_121
95 95 −7.4 21.1 40.6 Cingulate 4968 LAperiCing_95
96 95 −7.1 48.7 6.8 Frontal 4482 LvmPFC/LpgACC_96
105 95 40 40.4 21.4 Frontal 5454 RrlPFC_105
139 95 27.2 37.8 −2.8 Frontal 1404 RaOFG_139
144 95 9.3 46.4 45 Frontal 4266 RdmPFC_144
156 95 −0.4 −21.7 2.5 N/A 2025 3rdVent_156
162 95 6.2 13.6 44.1 Cingulate 4995 RdorsalperiCing_162
172 95 27.3 53.8 17.7 Frontal 4374 RavlPFC_172
28 94 −0.3 −22.9 32.2 Cingulate 3348 PCC_28
88 94 14.6 −10.4 24.9 N/A 1080 Rpo_Caudate_88
117 94 7.2 45.6 4.2 Frontal 3240 RvmPFC/RpgACC_117
119 94 19.8 −57 4.2 Visual 4401 Rlingual_119
129 94 23 30.1 48.4 Frontal 5724 RsupDLPFC_129
138 94 −12.3 −47.3 −3.1 Visual 5157 Llingual_138
141 94 −18.1 −67.3 23.9 Visual 6561 LlatPrecuneus/V3A_141
166 94 −10.9 16.2 61.7 Frontal 4482 RsupFG_166
177 94 −1.3 −24.7 57.6 Cingulate 5373 midline_SMA_177
178 94 −43.8 8.4 −14.3 Temporal 4482 LTempPole_178
179 94 15.6 −62.2 18.8 Visual 4590 RlatPrecuneus/V3A_179
198 94 −0.5 −2.6 −5.5 N/A 2295 3rdVent_198
199 94 −45.3 −72.2 9.3 Visual 5238 Llatocc_199
18 93 −3.9 −91.1 8.3 Visual 6507 LpoV1_18
21 93 −59.7 −25.6 11.6 Temporal 5724 LSTG_TE3_21
37 93 −1 31.5 0.3 Cingulate 3429 rostralACC_37
64 93 14.7 10.5 −7.5 Subcortical 2970 RNacc_64
67 93 −20.4 −59.8 6.2 Visual 5022 Llingual_67
104 93 9.4 57.6 30.1 Frontal 3780 RrmPFC_104
106 93 −11.4 −2.1 66.8 Cingulate 4590 LpreSMA_106
133 93 −57.6 −5.8 13.3 Motor 5913 L_OP4_133
152 93 −46 −59.2 21 Parietal 5940 LTPOJ_152
175 93 12.2 7.2 18.9 Subcortical 2457 RpoCaudate_175
183 93 7.5 28.1 56.8 Frontal 4779 RsupFG_54
195 93 32.9 −45.9 41.6 Parietal 5913 RSMG_195
200 93 5.5 −8.7 49.9 Cingulate 5400 RpreSMA/dACC_200
9 92 −56.5 −20.3 −4 Temporal 4617 LmidMTG_9
50 92 −39 −74.9 26.9 Visual 6480 Llat_midOcc_50
58 92 33.1 −83.6 −1.1 Visual 3618 RV3/V4_58
68 92 39.3 −1.6 13.3 Temporal 4212 RsupMidIns_68
75 92 24.6 −36.9 1.5 Temporal 2727 RHPC_tail_75
142 92 −11.4 −38.3 67.8 Motor 4752 LSPL_5L_142
165 92 −43 −32.6 17.9 Motor 5130 LpoIns_165
93 86 −54.6 −35.9 0.6 Motor 4995 LpoMTG_93
107 86 7 −85.8 −2.6 Visual 8829 RpoV1_107
32 85 −43.3 −21.4 57.5 Motor 4779 LlateralCentral_Sulcus_32
78 85 9.9 −74.7 7.6 Visual 5967 RV1_78
79 85 9.5 −11 68.4 Cingulate 4698 RlatSMA_79
81 85 −44.8 −46.3 −14.3 Temporal 3726 LITG_81
83 85 22.6 −67.9 31.9 Visual 6048 RlatPrecuneus_V3A_83
101 85 45.6 23.6 31.4 Frontal 5373 RrostMPFC_101
154 85 58.5 −26.6 13.3 Temporal 4779 RSTG_TE3_154
189 85 58.2 −22.8 30.1 Visual 5697 RIPC_Pfop_189
10 84 39.4 15.8 47.7 Frontal 5616 RsupdlPFC_10
17 84 −32.1 −43.6 −24.4 Cerebellum 5913 LlatCbell_17
29 84 −26.4 37.1 40.2 Frontal 5427 LsupFG_29
63 84 −31.9 −84.2 1 Visual 4320 LV3/V4_63
110 84 −1 −40.7 28.9 Cingulate 3618 dPCC_110
116 84 −15.1 −68.2 52.7 Parietal 5778 LSPL_116
145 84 −41.3 −4.1 51.7 Motor 5076 LLPM_lat_145
146 84 41.9 −74.6 13.6 Visual 5400 Rlatocc_146
44 83 −42.5 −39.4 54.4 Motor 4644 LsupS1_44
69 83 −8.9 −86.4 26.1 Visual 5211 Lcuneus_69
97 83 9.3 −46.3 65.6 Motor 5643 RSPL_5L_97
123 83 −53.7 −7.4 39.1 Motor 5400 LlatM1_BA4a_123
159 83 43.7 −67.6 −4.2 Visual 5319 Rinf_OccG_159
171 83 33 32.4 36.4 Frontal 5373 RsupFG_171
191 83 6.4 −53.9 32.6 Visual 4941 Rprecu_191
46 82 −27.3 −50.3 −11.1 Visual 5049 Lfusiform_46
84 82 −41.2 13.8 48.3 Frontal 4806 LsupdlPFC_84
126 82 −11.2 −75.7 5.2 Visual 6048 RV1_126
164 82 10.7 −86.5 27.6 Visual 6210 RlatCuneus_164
65 81 −54.3 −32.4 41.1 Parietal 6507 LIPC_PF_65
121 81 58.4 −43.7 21.2 Temporal 5562 RpoSTS_121
150 80 −20.9 −80.8 38 Visual 6075 LmidOccG_150
180 80 24.3 −4.3 58.5 Motor 5994 RLPM_med_180
7 79 −26.9 −12.9 59.7 Motor 6534 LLPM_med_7
20 79 9.8 −29.6 70 Motor 4320 RsupM1_20
90 79 −39.2 38.3 27.8 Frontal 5589 LsupFG_90
77 78 25.8 −19.3 64.1 Motor 5157 RLPM_77
153 78 38.5 −5.7 −1.1 Temporal 5265 Rinf_MidIns_153
74 77 54.8 −7.9 −4.7 Temporal 4212 RAinfMTG_74
127 77 −32.2 −26.7 −13.3 Temporal 4266 LHPC_body/PHG_127
192 77 −0.9 −68.7 20.7 Visual 5697 midV2_192
99 75 13.8 −76.1 45.2 Parietal 4941 RSPL_99
6 74 53.6 −57.4 6.8 Temporal 5211 RpoMTG_6
182 74 −1.5 −72.3 39.5 Visual 5589 midV3/V3A_182
98 73 −54.1 −51.3 8.2 Temporal 5319 LinfTPOJ_98
39 72 25.1 −55.8 57.2 Parietal 6561 RSPL_7P_39
111 72 52.2 −50.5 35.6 Parietal 5265 RIPC_Pga_111
194 72 42.7 −33.4 20.6 Temporal 4860 RpoIns_194
48 71 51.7 −5.5 38 Motor 5643 RlatM1_BA4a_48
122 69 24.7 −85.9 15.1 Visual 4752 Rocc_BA18_122
184 69 30 −81.5 30.8 Visual 5454 RmidOccG_30
187 68 −45.8 −62.9 −5.1 Visual 5751 Linf_OccG_159
3 67 −49.2 27 21.4 Frontal 4779 LAdlPFC_3
23 66 −42.8 22.9 35.6 Frontal 4860 LrostMPFC_23
196 62 −11.4 15.7 −2.3 Subcortical 2889 LNAcc_196
100 56 41.7 −52 51 Parietal 5103 RIPL_PGa_100
109 56 39.3 −19.4 14 Temporal 4887 RIns_OP1_109
2 55 36.9 6.2 36.1 Frontal 5049 RpodlPFC_2
45 55 57.2 −22.4 −3.6 Temporal 3321 RmidMTG_45
157 55 47.5 −67.3 28.3 Parietal 5913 Rlat_midocc_157
51 54 −25 −10.1 −16.1 Temporal 6048 LHPC_CA/Amyg_51
147 53 53 −34.7 43 Parietal 5454 RIPC_PF_147
169 49 −35.4 −45.2 40.4 Parietal 5238 LSMG_169
124 48 −12.9 16.8 12 N/A 2943 Lpocaudate_124
176 48 −40.7 −21.6 42.8 Motor 5319 LmidS1_176
114 47 0.1 7 5 N/A 3807 SubgenCing_114
135 42 −0.5 −13.1 15.3 Subcortical 2403 thalamus_135
12 41 41 −31.9 56.7 Motor 4428 Rlateral_CentralSulcus_41
30 40 33.2 −68.6 44.7 Visual 6291 RpoIPL_30
24 38 57.8 −39.8 0.7 Temporal 3996 RpoMTG_24
161 37 39.5 −2.7 52.5 Motor 5211 RLPM_lat_161
92 34 47.5 −17.5 50.9 Motor 4347 RlatM1/S1_92
173 33 47.3 −30.4 2.5 Temporal 4644 RpoMTG_173
55 1 −23 −68.7 −9 Visual 4617 Lpofusiform_55
1 0 0 0 0 N/A 0 Garbage_1
4 0 0 0 0 N/A 0 Garbage_4
8 0 0 0 0 N/A 0 Garbage_8
25 0 0 0 0 N/A 0 Garbage_25
72 0 0 0 0 N/A 0 Garbage_72
108 0 0 0 0 N/A 0 Garbage_108
137 0 0 0 0 N/A 0 Garbage_137

Finally, the regression of head coil against DLPFC connectivity seed maps showed no consistent pattern of coil-related differences in connectivity (Table 4). During the n-back task, the 32-channel head coil was associated with greater LDLPFC connectivity among two regions: one located at pre-SMA/dACC and another in right SMA (AlphaSim corrected q<0.05). These regions corresponded with the Task atlas’s ROIs #200 and #79 – which were highly replicable across Task and Rest atlases (Table 3, JI=0.93 and 0.85, respectively). Furthermore, no regions showed coil-related significant differences in DLPFC connectivity for the resting-state scans. The lack of replicable, systemic coil-related differences in connectivity across these two tasks suggests that head coil is not influencing functional connectivity patterns, and thus not confounding atlas generation. This finding is consistent with our past findings that head-coil does not significantly influence task-related brain activity [10]

Table 4.

Regions of increased voxelwise connectivity to left DLPFC for 32- vs 8-channel head coil (q<0.05)

Cluster MNI Coordinates Volume (in mm3) Corresponding Region in Task Atlas
x y z Region Label Jaccard index with Rest Atlas
1 8 −16 42 8046 200 Right pre-SMA/dorsal cingulate 93
2 5 −16 66 2,133 79 Right SMA 85

Differences reported for n-back task only; no significant coil-related differences observed during resting-state

4. Discussion

We report strong similarity between atlases derived via parcellation of resting-state data and atlases derived via parcellation of both resting-state and task-based data. Our findings are consistent with past research suggesting that brain networks are consistently organized across task and rest [13]; we expand upon those findings to suggest that the brain’s functionally independent subunits (“nodes”) are also consistently represented across task and rest. The similarity between Task and Resting atlases may partially stem from the necessary incorporation of baseline conditions in fMRI tasks to model task-related changes in brain activity or connectivity. These baseline conditions are low-level cognitive control tasks (such as the 0-back condition of the n-back task) and/or resting-state epochs, which may enforce similar connectivity structure between task-based and resting-state fMRI scans. Nonetheless, the similarity between atlases remains striking given that resting-state epochs compose less than half of the tasks’ timepoints.

We also report strong similarity of these atlases to the random parcellations (mean JI=0.59–0.63). Although initially surprising, this may be explained by our decision to constrain the parcellation approach to gray matter voxels, which causes white matter to form consistent boundaries across all parcellations. For example, regions with multiple white matter boundaries (such as the cingulate, which is bounded by white matter to the left, right, and inferior surfaces) have greater constraint in how they may be parcellated, potentially explaining the strong Jaccard Indices between atlases observed in Figure 2.

Leave-one out cross-validation has shown that the group two-stage approach generates atlases that are more representative across individuals than the group mean approach [1]. We thus limited our comparison of task-based and resting-state parcellations to atlases generated using the group two-stage approach. Contrary to hypotheses, task-based and resting-state parcellations had strong similarity (JI≥0.90) for regions involved in higher-order cognition, including prefrontal cortices, cingulate, and left temporal lobe. We interpret this as evidence that the cognitive processes occurring in the absence of overt task (such as rumination, autobiographical memory retrieval, introspection and theory of mind) are sufficiently similar across rest and diverse tasks to map these regions with high consistency [14;15].

Conversely, we report least similarity for (a) three regions in right sensorimotor cortex, (b) two regions in right superior temporal sulcus, and (c) two regions bordering the left lateral ventricle. The sensorimotor cortex encodes the neural representation of the hand, with significantly greater activity for contralateral hand movement but greater variability for ipsilateral hand movement [16], particularly in the context of changing task demand [17]. Given the variety of tasks performed (with 7 tasks requiring right hand responses and 2 requiring both left and right hand responses), greater heterogeneity (less similarity) in right sensorimotor cortex is not surprising given this predominantly (90%) right-hand dominant sample.

The role of the right STG is not as clearly established as the left STG, which is strongly associated with auditory processing [18;19]. Right STG has been implicated in diverse processes such as encoding auditory rhythms [20], multisensory integration [21], and contextual awareness [22]. These processes may be more strongly engaged during task than rest, resulting in variable recruitment of the right STG across tasks and thus dissimilar representation of right STG between task and rest. Perhaps more surprising is the dissimilarity between atlases for striatal regions bordering left lateral ventricle, which show bilateral recruitment for processes such as learning, reward processing, and motor processing [2328]. Future work will evaluate asymmetric striatal recruitment across tasks to evaluate which cognitions could be leading to the discrepancy in striatal representation between atlases.

Finally, we demonstrate that voxelwise seed maps of left dorsolateral prefrontal cortex (LDLPFC) functional connectivity are more consistently reproduced by the All and Rest atlas than the Random atlas. Interestingly, the All and Rest parcellations produced a LDLPFC ROI that strongly corresponds to the LDLPFC region identified by the n-back task, as indicated by the blue crosshairs in Figure 3. Conversely, the Random atlas LDLPFC ROI shows poor correspondence with the task-defined ROI. This finding both reinforces the similarity of the Task and Rest atlases while demonstrating their superiority over the Random atlas in capturing underlying neural organization.

An important caveat is that our parcellations were constrained to brain regions covered across all participants and sessions. Our conservative approach led to incomplete coverage of the inferior orbitofrontal cortex, a region notoriously difficult to image with fMRI due to proximity of air in the sinus cavity which distorts magnetic signal in this region. While combined spin-echo and echo-planar sequences have been developed to optimally image this region [29], these sequences suffer a 50% reduction in temporal resolution, prompting our selection of the standard echo-planar sequence. We contend that our atlas is well-suited for analyzing Cognitive Connectome project data and other fMRI datasets, the majority of which also rely upon echo-planar sequences. However, given the strong similarity between atlases derived from task-based and resting-state data, we conclude that previously published atlases derived from combined spin-echo/echo-planar sequences are likewise suitable for task-based analyses.

5. Conclusions

We have uploaded a fully labeled atlas to the Neuroinformatics Tool and Resources Center (https://www.nitrc.org/) for public use.1 Our findings indicate that this atlas is well-suited for analysis of both resting-state and task-based data. Our findings further suggest that existing atlases derived solely from resting-state data are equally suitable for resting-state and task-based analyses.

Acknowledgments

This research was supported by the Translational Research Institute (TRI) at the University of Arkansas for Medical Sciences (UAMS) which is funded by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program (UL1TR000039); the CTSA KL2 Scholars Program (KL2TR000063; to GAJ). We additionally thank Mr. Jonathan Young and Mrs. Sonet Smitherman for assistance with data collection and maintaining institutional compliance. All authors contributed to the interpretation and writing of this manuscript.

Footnotes

1

Atlas will be uploaded to NITRC upon acceptance of manuscript and/or made available upon the Magnetic Resonance Imaging website, pending further discussion with editors

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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