The Impact of Atlas Parcellation on Functional Connectivity Analysis Across Six Psychiatric Disorders

Abstract

Neuropsychiatric disorders are associated with altered functional connectivity (FC); however, the reported regional patterns of functional alterations suffered from low replicability and high variability. This is partly because of differences in the atlas and delineation techniques used to measure FC-related deficits within/across disorders. We systematically investigated the impact of the brain parcellation approach on the FC-based brain network analysis. We focused on identifying the replicable FCs using three structural brain atlases, including Automated Anatomical Labeling (AAL), Brainnetome atlas (BNA) and HCP_MMP_1.0, and four functional brain parcellation approaches: Yeo-Networks (Yeo), Gordon parcel (Gordon) and two Schaefer parcelletions, among correlation, group difference, and classification tasks in six neuropsychiatric disorders: attention deficit and hyperactivity disorder (ADHD, n = 340), autism spectrum disorder (ASD, n = 513), schizophrenia (SZ, n = 200), schizoaffective disorder (SAD, n = 142), bipolar disorder (BP, n = 172), and major depression disorder (MDD, n = 282). Our cross-atlas/disorder analyses demonstrated that frontal-related FC deficits were reproducible in all disorders, independent of the atlasing approach; however, replicable FC extraction in other areas and the classification accuracy were affected by the parcellation schema. Overall, functional atlases with finer granularity performed better in classification tasks. Specifically, the Schaefer atlases generated the most repeatable FC deficit patterns across six illnesses. These results indicate that frontal-related FCs may serve as potential common and robust neuro-abnormalities across 6 psychiatric disorders. Furthermore, in order to improve the replicability of rsfMRI-based FC analyses, this study suggests the use of functional templates at larger granularity.

Keywords: brain atlases; brain network analysis; functional connectivity; psychiatry; replicability.

FIGURE 1

Analysis framework of this study. (a) Brain atlases compared, including 3 structural and 4 functional atlases. (b) 6 brain disorders studied, including ADHD (n = 340), ASD (n = 513), SZ (n = 200), SAD (n = 142), BP (n = 172) and MDD (n = 282). (c) FC analysis, including I. correlation between FC and symptom scores, II. group difference between patients and HCs, and III. classification between patients and HCs. (d) Replicable FCs identification in correlation, group difference, diagnosis, as well as across atlases, disorders, and analysis methods.

FIGURE 2

FC‐based correlations with symptom scores. Significant FCs correlated with symptoms in 3 structural atlases (a) and 2 functional atlases (b and c). Black/gray lines represent positive/negative correlations with symptom scores (FDR corrected, Supporting Information “FDR correction and permutation test”). Statistical significance that passed the FDR correction was denoted with an asterisk (*). Blue/green blocks represent replicable FCs of the structural/functional atlases. Deep‐colored blocks represent replicable FCs across all atlases, medium‐colored blocks represent across at least two atlases and light‐colored blocks represent absence of significant FCs. $\mid r\mid$ represents the mean of the absolute value of the correlation of significant FCs associated with symptom scores.

FIGURE 3

FC‐based group difference between patients and controls. Significant FCs in group difference in 3 structural atlases (a) and 2 functional atlases (b and c). Black/gray lines represent significant hyper−/hypo‐connectivity in patients compared with HCs (FDR corrected). Blue/green blocks represent replicable FCs of the structural/functional atlases. Deep‐colored blocks represent replicable FCs across all atlases, medium‐colored blocks represent across at least two atlases and light‐colored blocks represent absence of significant FCs. $\mid d\mid$ represents the mean of the absolute Cohen's d values for significant FC with group differences.

FIGURE 4

FC‐based classification. The top 0.5% contributing FCs in classification tasks in 3 structural atlases (a) and 2 functional atlases (b and c). Blue/green blocks represent replicable FCs of the structural/functional atlases. Deep‐colored blocks represent replicable FCs across all atlases, medium‐colored blocks represent across at least two atlases and light‐colored blocks represent absence of significant FCs.