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Executive function network's white matter alterations relate to Parkinson's disease motor phenotype.

ABSTRACT: Parkinson's disease (PD) patients with postural instability and gait disorder phenotype (PIGD) are at high risk of cognitive deficits compared to those with tremor dominant phenotype (TD). Alterations of white matter (WM) integrity can occur in patients with normal cognitive functions (PD-N). However, the alterations of WM integrity related to cognitive functions in PD-N, especially in these two motor phenotypes, remain unclear. Diffusion tensor imaging (DTI) is a non-invasive neuroimaging method to evaluate WM properties and by applying DTI tractography, one can identify WM tracts connecting functional regions. Here, we 1) compared the executive function (EF) in PIGD phenotype with normal cognitive functions (PIGD-N) and TD phenotype with normal cognitive functions (TD-N) phenotypes; 2) used DTI tractography to evaluated differences in WM alterations between these two phenotypes within a task-based functional network; and 3) examined the WM integrity alterations related to EF in a whole brain network for PD-N patients regardless of phenotypes. Thirty-four idiopathic PD-N patients were classified into two groups based on phenotypes: TD-N and PIGD-N, using an algorithm based on UPDRS part III. Neuropsychological tests were used to evaluate patients' EF, including the Trail making test part A and B, the Stroop color naming, the Stroop word naming, the Stroop color-word interference task, as well as the FAS verbal fluency task and the animal category fluency tasks. DTI measures were calculated among WM regions associated with the verbal fluency network defined from previous task fMRI studies and compared between PIGD-N and TD-N groups. In addition, the relationship of DTI measures and verbal fluency scores were evaluated for our full cohort of PD-N patients within the whole brain network. These values were also correlated with the scores of the FAS verbal fluency task. Only the FAS verbal fluency test showed significant group differences, having lower scores in PIGD-N when compared to TD-N phenotype (p < 0.05). Compared to the TD-N, PIGD-N group exhibited significantly higher MD and RD in the tracts connecting the left superior temporal gyrus and left insula, and those connecting the right pars opercularis and right insula. Moreover, compared to TD-N, PIGD-N group had significantly higher RD in the tracts connecting right pars opercularis and right pars triangularis, and the tracts connecting right inferior temporal gyrus and right middle temporal gyrus. For the entire PD-N cohort, FAS verbal fluency scores positively correlated with MD in the superior longitudinal fasciculus (SLF). This study confirmed that PIGD-N phenotype has more deficits in verbal fluency task than TD-N phenotype. Additionally, our findings suggest: (1) PIGD-N shows more microstructural changes related to FAS verbal fluency task when compared to TD-N phenotype; (2) SLF plays an important role in FAS verbal fluency task in PD-N patients regardless of motor phenotypes.

SUBMITTER: Yang Q

PROVIDER: S-EPMC7750296 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:A growing body of evidence links socioeconomic status (SES) to children's brain structure. Few studies, however, have specifically investigated relations of SES to white matter structure. Further, although several studies have demonstrated that family SES is related to development of brain areas that support executive functions (EF), less is known about the role that white matter structure plays in the relation of SES to EF. One possibility is that white matter differences may partially explain SES disparities in EF (i.e., a mediating relationship). Alternatively, SES may differentially shape brain-behavior relations such that the relation of white matter structure to EF may differ as a function of SES (i.e., a moderating relationship). METHOD:In a diverse sample of 1082 children and adolescents aged 3-21 years, we examined socioeconomic disparities in white matter macrostructure and microstructure. We further investigated relations between family SES, children's white matter volume and integrity in tracts supporting EF, and performance on EF tasks. RESULTS:Socioeconomic status was associated with fractional anisotropy (FA) and volume in multiple white matter tracts. Additionally, family income moderated the relation between white matter structure and cognitive flexibility. Specifically, across multiple tracts of interest, lower FA or lower volume was associated with reduced cognitive flexibility among children from lower income families. In contrast, children from higher income families showed preserved cognitive flexibility in the face of low white matter FA or volume. SES factors did not mediate or moderate links between white matter and either working memory or inhibitory control. CONCLUSIONS:This work adds to a growing body of literature suggesting that the socioeconomic contexts in which children develop not only shape cognitive functioning and its underlying neurobiology, but may also shape the relations between brain and behavior.

Project description:Diffusion magnetic resonance imaging is increasingly used as a non-invasive method to investigate white matter structure in neurological and neuropsychiatric disease. However, many options are available for the acquisition sequence and analysis method. Here we used Parkinson's disease as a model neurodegenerative disorder to compare imaging protocols and analysis options. We investigated fractional anisotropy and mean diffusivity of white matter in patients and age-matched controls, comparing two datasets acquired with different imaging protocols. One protocol prioritised the number of b value acquisitions, whilst the other prioritised the number of gradient directions. The dataset with more gradient directions was more sensitive to reductions in fractional anisotropy in Parkinson's disease, whilst the dataset with more b values was more sensitive to increases in mean diffusivity. Moreover, the areas of reduced fractional anisotropy were highly similar to areas of increased mean diffusivity in PD patients. Next, we compared two widely used analysis methods: tract-based spatial statistics identified reduced fractional anisotropy and increased mean diffusivity in Parkinson's disease in many of the major white matter tracts in the frontal and parietal lobes. Voxel-based analyses were less sensitive, with similar patterns of white matter pathology observed only at liberal statistical thresholds. We also used tract-based spatial statistics to identify correlations between a test of executive function (phonemic fluency), fractional anisotropy and mean diffusivity in prefrontal white matter in both Parkinson's disease patients and controls. These findings suggest that in Parkinson's disease there is widespread pathology of cerebral white matter, and furthermore, pathological white matter in the frontal lobe may be associated with executive dysfunction. Diffusion imaging protocols that prioritised the number of directions versus the number of b values were differentially sensitive to alternative markers of white matter pathology, such as fractional anisotropy and mean diffusivity.

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Executive function network's white matter alterations relate to Parkinson's disease motor phenotype.

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