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Behavior, Psychology and Sociology

Contrasting dorsal caudate functional connectivity patterns between frontal and temporal cortex with BMI increase: link to cognitive flexibility



Obesity is associated with brain intrinsic functional reorganization. However, little is known about the BMI-related interhemispheric functional connectivity (IHFC) alterations, and their link with executive function in young healthy adults.


We examined voxel-mirrored homotopic connectivity (VMHC) patterns in 417 young adults from the Human Connectome Project. Brain regions with significant association between BMI and VMHC were identified using multiple linear regression. Results from these analyses were then used to determine regions for seed-voxel FC analysis, and multiple linear regression was used to explore the brain regions showing significant association between BMI and FC. The correlations between BMI-related executive function measurements and VMHC, as well as seed-voxel FC, were further examined.


BMI was negatively associated with scores of Dimensional Change Card Sort Test (DCST) assessing cognitive flexibility (r = −0.14, p = 0.006) and with VMHC of bilateral inferior parietal lobule, insula and dorsal caudate. The dorsal caudate emerged as a nexus for BMI-related findings: greater BMI was associated with greater FC between caudate and hippocampus and lower FC between caudate and several prefrontal nodes (right inferior frontal gyrus, anterior cingulate cortex, and middle frontal gyrus). The FC between right caudate and left hippocampus was negatively associated with scores of DCST (r = −0.15, p = 0.0018).


Higher BMI is associated with poorer cognitive flexibility performance and IHFC in an extensive set of brain regions implicated in cognitive control. Larger BMI was associated with higher caudate-medial temporal lobe FC and lower caudate-dorsolateral prefrontal cortex FC. These findings may have relevance for executive function associated with weight gain among otherwise healthy young adults.

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Fig. 1: Brain mapping of VMHC demonstrated a significant association with BMI (PFWE = 0.05, family-wise error correction).
Fig. 2: Brain mapping of functional connectivity (FC) with bilateral caudate demonstrated a significant association with BMI (PFWE = 0.05, family-wise error correction).
Fig. 3: The scatter plot of functional connectivity of caudate-hippocampus and scores of cognitive flexibility, as assessed with the Dimensional Cord Sort Test.


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Data were provided by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. This work was supported by the National Natural Science Foundation of China under Grant No. 81601563, Key Industrial Innovation Chain Project in Agricultural Domain (Grant No. 2019ZDLNY02–05).

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JZ, JG, HS, PZ, PZ, FS, ZD, CL analyzed the data and performed the statistical analysis, JZ, PM, GJW wrote the first draft of the manuscript, GJW and DH contributed the conception and design of the study.

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Correspondence to Jizheng Zhao, Gene-Jack Wang or Dongjian He.

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The datasets were shared with the approval of Washington University institutional review board. The participants provided their written informed consent to participate in this study.

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The authors declare no competing interests.

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Zhao, J., Manza, P., Gu, J. et al. Contrasting dorsal caudate functional connectivity patterns between frontal and temporal cortex with BMI increase: link to cognitive flexibility. Int J Obes 45, 2608–2616 (2021).

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