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. 2021 Jul:233:101-110.
doi: 10.1016/j.schres.2021.06.013. Epub 2021 Jun 29.

Lower functional connectivity of white matter during rest and working memory tasks is associated with cognitive impairments in schizophrenia

Yurui Gao  1 , Muwei Li  2 , Anna S Huang  3 , Adam W Anderson  4 , Zhaohua Ding  5 , Stephan H Heckers  6 , Neil D Woodward  7 , John C Gore  8
Affiliations

Lower functional connectivity of white matter during rest and working memory tasks is associated with cognitive impairments in schizophrenia

Yurui Gao et al. Schizophr Res. 2021 Jul.

Abstract

Background: Schizophrenia can be understood as a disturbance of functional connections within brain networks. However, functional alterations that involve white matter (WM) specifically, or their cognitive correlates, have seldomly been investigated, especially during tasks.

Methods: Resting state and task fMRI images were acquired on 84 patients and 67 controls. Functional connectivities (FC) between 46 WM bundles and 82 cortical regions were compared between the groups under two conditions (i.e., resting state and during working memory retention period). The FC density of each WM bundle was then compared between groups. Associations of FC with cognitive scores were evaluated.

Results: FC measures were lower in schizophrenia relative to controls for external capsule, cingulum (cingulate and hippocampus), uncinate fasciculus, as well as corpus callosum (genu and body) under the rest or the task condition, and were higher in the posterior corona radiata and posterior thalamic radiation during the task condition. FC for specific WM bundles was correlated with cognitive performance assessed by working memory and processing speed metrics.

Conclusions: The findings suggest that the functional abnormalities in patients' WM are heterogeneous, possibly reflecting several underlying mechanisms such as structural damage, functional compensation and excessive effort on task, and that WM FC disruption may contribute to the impairments of working memory and processing speed. This is the first report on WM FC abnormalities in schizophrenia relative to controls and their cognitive associates during both rest and task and highlights the need to consider WM functions as components of brain functional networks in schizophrenia.

Keywords: Cognitive associate; Functional connectivity; Resting-state fMRI; Spatial working memory task; White matter.

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Conflict of interest statement

Declarations of interest: none

Figures

Fig. 1.
Fig. 1.
Schematic diagram of spatial working memory task, atlases of white matter (WM)/gray matter (GM) ROIs, and tissue masks. (A) One task scan comprised eight trials, of which five were memory trials (dark gray blocks) and the other three were non-memory trials (light gray blocks). (B) Each memory trial lasted 38s, including 4s of fixation, 3.5s of encoding, 16s of retention, 1s of probe and 13.5s of interval. The non-memory trial had the same sequence of events, except that the subjects were instructed not to remember the target locations. (C) WM parcellation atlas and (D) GM parcellation atlas in MNI space were used to initially define WM and GM ROIs. See Table 2 for the lists of these ROIs. (E) Whole-brain WM and GM tissue masks of one subject that were used to further constrain WM and GM ROIs to avoid partial volume effect.
Fig. 2.
Fig. 2.
Group mean of functional correlation matrix (mFCM) within CON group and SCZ group under two conditions: (A, B) resting state and (C, D) retention period during the spatial working memory task. The blue/red numbers labeling columns of mFCM indicate the indices of Brodmann area (BA) in left/right hemisphere. The blue/green/red abbreviations labeling rows of mFCM indicate the WM bundles in left/middle/right portion of brain. See Table 2 for the lists of these ROIs.
Fig. 3.
Fig. 3.
Differences and effect sizes of FCM between CON group and SCZ group under two conditions. Difference of subtracting mFCM of SCZ from mFCM of CON and effect size of the difference under two conditions: (A, B) resting state and (C, D) working memory task. The differences of FCM elements with pFDR>0.05 were set to zero and the corresponding effect sizes were also set to zero. The blue/red numbers labeling columns indicate indices of Brodmann areas in left/right hemisphere. The blue/green/red abbreviations labeling rows indicate WM bundles in left/middle/right portion of brain. See Table 2 for the lists of these ROIs.
Fig. 4.
Fig. 4.
Comparison of WM FC density between CON group and SCZ group under two conditions. Mean and standard deviation of FC density within CON group (light gray bar and error bar) and SCZ group (dark gray bar and error bar) under two conditions: (A) resting state and (B) working memory task. * indicates p<0.05 (uncorrected significance level) and ** indicates p<1/N=0.022 (corrected significance level). See Supplementary Table 1 for a summary of group mean, standard deviation and p-values of each WM bundle.
Fig. 5.
Fig. 5.
Correlation coefficients between FC and cognitive scores under two conditions: (A) resting state and (B) working memory task. Given one WM bundle and one score, the correlation coefficient shown here is the one with maximum amplitude among all 82 correlation coefficients between the score and 82 FC that the WM bundle corresponds to. All the coefficients with |r|<0.3 or p>0.05 are set to zero. * indicates p<0.05 (uncorrected significance level) and ** indicates p <1/N=0.022 (corrected significance level).
See this image and copyright information in PMC

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