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Neural mechanism of processing speed decline induced by anatomically connected white matter tract damage and cortical function abnormality
Shuyue Wang1, Jiaerken Yeerfan1, Peiyu Huang1, Xinfeng Yu1, Yong Zhang2, and Minming Zhang1

1Department of radiology, 2nd affiliated hospital of Zhejiang university school of medicine, Hangzhou, China, 2GE Healthcare, Shanghai, China

Synopsis

White matter hyper-intensities (WMH) is considered as an important source of morbidity associated with dementia, stroke and increased mortality risk. Previous studies have suggested that WMH always leads to the decline of information processing speed, which have an impact on activities of daily living. Current hypothesis is that the dysfunctions caused by WMH is the result of “disconnection”, while the connection between the structural and functional alteration has not been fully investigated. We aimed to explore the underlying pathway of information processing speed decline via combining the spatial distribution of WMH, microstructural changes based tractography and cortical activity alterations. The results from different modalities converged in the occipital lobe with precise spatial overlappings. Results show regional WMH may indicate disrupted tract integrity and cause altered brain activities, leading to impaired function. This WMH-tract-function-behavior link is critical for WMH induced dysfunctions and treatment strategies.

Introdunction

White matter hyper-intensities (WMH), a common sign in elder population, appeared as hyper-intensity patches in the white matter on T2 and T2FLAIR image1-2. WMH is considered as an important source of morbidity associated with dementia, stroke and increased mortality risk3-5. Previous studies suggested that WMH always leads to executive dysfunctions, especially the decline of information processing speed, which have an impact on activities of daily living6-8. There are several ways to explore the underlying pathway of dysfunction caused by WMH - for example analyzing the distribution of WMH lesion and the integrity of specific white matter tracts9-18, or assessing the connectivity of brain networks11,19. While most previous studies only analyzed the relationship between information processing ability and only one or two of the three above-mentioned aspects, without fully exploring the WMH-Tract-Function-Behavior link13,16-17,20-23. In order to better understand the underlying pathway between the anatomical and spatial proximity of WMH lesion, white matter tract damage and cortical damage related with a specific domain, we aimed to investigate how WMH leads to information processing dysfuntion through a comprehensive assessment of brain features.

Methods

We included sixty elder adults. Information processing ability was assessed by the trail making test part A (TMT-A), and multi-modal magnetic resonance images were acquired. Workflow of multi-modalities imaging pre-processing was presented in Fig. 1. For analyzing the distribution of WMH volumes, we extracted WMH volumes in frontal, occipital, temporal, parietal lobe and suncortical region based on T2FLAIR. TRACULA (TRActs Constrained by UnderLying Anatomy)24, a probabilistic tractographic method was used to obtain the mean fractional anisotropy (FA) values of 18 major tracts. Whereas voxel-wise global analysis of cortical function was estimated by the fractional Amplitude of Low-Frequency Fluctuations (fALFF) value based on fMRI. Correlation analysis was performed to assess the relationship between TMT-A and several brain features, including WMH volumes in each brain lobe, diffusivity parameters in major white matter tracts, and regional brain activities across the whole brain. Finally, a multiple linear regression analysis was used to demonstrate the contribution of each index to information processing speed alterations.

Results

We found that the WMH volume in occipital lobe(Table 1) and FA of forceps major, an occipital association fiber, were significantly correlated with TMT-A scores(Fig. 2). Besides, resting-state brain activities in the visual association cortex connected to the forceps major were also correlated with TMT-A scores(Fig. 3). Multiple linear regression showed that FA of forceps major and regional brain activities were significant predictors of TMT-A scores.

Discussion

In this study, we performed a combined analysis of macrostructure, microstructure, and cortical function assessment to explore the mechanism of information processing speed changes induced by WMH. Interestingly, results from the three modalities converged in the occipital lobe, with precise spatial overlappings in visual association cortex (Fig. 4). Besides, multiple regression analysis revealed that FA in FMajor and local fALFF could predict the TMT-A score. We suggest that in subjects with WMH, the poorer TMT performance was largely due to damaged visual-spatial information processing abilities. Furthermore, we identified consistent alterations in the occipital lobe. We suggest that the WMH in occipital lobe might lead to the impairment of the forceps major integrity, and the neural circuit between the visual association cortex connected by WM tracts may be broken. That caused a decline in visual information conduction efficiency, which ultimately resulted in the alteration of visuospatial information processing ability. These findings provided strong support for the the WMH-Tract-Function-Behavior theoretical framework about the WMH-mediated dysfunction.In summary, the underlying pathway of information processing dysfunction caused by WMH may involve in multi-domain, but the alteration of visuospatial information processing ability is remarkable in our WMH population. The degradation of the WM microstructures and neural disconnection may further disrupt the parietal-occipital network and frontal-occipital network. Our results indicated that the processing of WMH-mediated changes in information processing ability could have a strategic mechanism, which may implicate a structural-functional pathway highly corresponding in anatomical structure and function. However, future studies are needed to confirm such a hypothesis.

Conclusion

In conclusion, this study explored the underlying mechanism of WMH-related information processing speed deline using a multi-modality approach. A variety of structural and functional alterations were found related to information processing ability, and results from different modalities converged in the occipital lobe, highlighting that visuospatial dysfunction is important for trail-making speed. Besides, the precise spatial overlapping of lesion-tract-function results provided a unique opportunity for understanding how WMH pathologies lead to brain dysfunction. Given the link between WMH and neurovascular disease, exploring the neural mechanism of information processing speed changes induced by WMH could also provide evidence on preventive and treatment strategies.

Acknowledgements

No acknowledgement found.

References

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Figures

Fig. 1 Workflow of multi-modalities imaging pre-processing

Table 1 Correlations between lobar WMH volumes and TMT_A completion time

Fig. 2 FibersTracts showing significantly correlation with TMT-A scores (top), and the scatter plot of the association between TMT_A completion time and each white matter tract(bottom).

Fig. 3 The cluster where fALFF values were negatively correlated with TMT-A scores (FDR corrected). It was located in the occipital lobe, including part of the superior occipital gyrus and middle occipital gyrus.

Fig. 4 The spatial overlappings of results from the three modalities converged in the occipital lobe.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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