White matter lesions relate to tract-specific reductions in functional connectivity

Langen, Carolyn D.; Zonneveld, Hazel I.; White, Tonya; Huizinga, Wyke; Cremers, Lotte G.M.; Groot, Marius de; Ikram, M. Arfan; Niessen, Wiro J.; Vernooij, Meike W.

doi:10.1016/j.neurobiolaging.2016.12.004

Cited by 35 publications

(25 citation statements)

References 41 publications

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“…An impairment of the frontoparietal network in cerebral SVD was also reported in resting-state fMRI studies ( Schaefer et al , 2014 ). Moreover, higher tract specific white matter lesion load has been shown to be related to lower functional connectivity in the corresponding brain regions ( Langen et al , 2017 ). Apart from functional changes, previous studies have observed a decline of structural connectivity in SVD patients ( Lawrence et al , 2014 ; Kim et al , 2015 ; Tuladhar et al , 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity

Quandt

Fischer

Schröder

et al. 2020

Brain Communications

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Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging are white matter hyperintensities. We studied high-resolution resting state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment, however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioral impairment.

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Section: Discussionmentioning

confidence: 99%

Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity

Quandt

Fischer

Schröder

et al. 2020

Brain Communications

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“…To our knowledge, only a few studies of brain ageing have specifically analysed WM tracts intersecting with WMH (Langen et al, 2017;Maillard et al, 2015;Seiler et al, 2018;Taylor et al, 2017). They generally found the largest rates of overlap in the anterior thalamic radiation, inferior longitudinal fasciculus, forceps major, posterior thalamic radiation and the inferior fronto-occipital fasciculus.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that cortical "disconnection" due to the loss of WM fibres may play an important role in age-related cognitive decline (O'Sullivan et al, 2001;Ritchie et al, 2015a), and this disconnection could be the consequence of WMH within WM tracts. In support of this, several studies observed associations between WMH volume within specific WM tracts and cognitive performance (Biesbroek, 2016;Reginold et al, 2015) and functional connectivity (Langen et al, 2017;Taylor et al, 2017). These studies suggest that WMH may directly damage tracts and understanding the influence of WMH on WM tracts is therefore important in investigating age-related cognitive decline.…”

Section: Introductionmentioning

confidence: 87%

Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age

Maniega

Meijboom

Chappell

et al. 2018

Preprint

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Brain white matter hyperintensities (WMH), common in older adults, may contribute to cortical disconnection and cognitive dysfunction. The presence of WMH within white matter (WM) tracts indicates underlying microstructural WM changes that may also affect the normal-appearing WM (NAWM) of a tract. We performed an exploratory study using diffusion magnetic resonance imaging of 52 healthy participants from the Lothian Birth Cohort 1936 (age 72.2 ± 0.7 years) selected to include a range of WMH burden, to quantify microstructural changes of tracts intersecting WMH. We reconstructed tracts using automated tractography and identified intersections with WMH. Tissue volumes and water diffusion tensor parameters (mean diffusivity (MD) and fractional anisotropy (FA)) were established for tract-WMH and tract-NAWM. MD and FA were also measured for tract-NAWM at 2 mm incremental distances from the tract-WMH edge, and from the edge of nearby, non-intersecting, WMH. We observed microstructural changes in tract-WMH suggestive of tissue damage. Tract-NAWM also showed a spatial gradient of FA and MD abnormalities, which diminished with distance from the tract-WMH. Nearby WMH lesions, not directly crossed by the tract, also affected tract microstructure with a similar pattern. Additionally, both FA and MD changes in tract-NAWM were predicted by FA and MD changes respectively in tract-WMH. FA was also predicted by tract-WMH overlap volume, whereas MD was better predicted by whole-brain WMH load. These results suggest that tract-NAWM microstructure is affected by the pathological process underlying WMH, when WMH are either within or near to the tract. The changes in NAWM tract tissue may indicate future lesion progression and may play an important role in cognitive ageing.

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“…After introduction of resting-state functional MRI, we have explored how (change in) brain structure drive brain function, and found that white matter pathology can decrease tract-specific functional connectivity, both in direct and indirect connections [ 462 ]. These results provide further evidence for the so-called “connectivity hypothesis”.…”

Section: Imaging Studiesmentioning

confidence: 99%

The Rotterdam Study: 2018 update on objectives, design and main results

et al. 2017

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The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1500 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.

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White matter lesions relate to tract-specific reductions in functional connectivity

Cited by 35 publications

References 41 publications

Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity

Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity

Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age

The Rotterdam Study: 2018 update on objectives, design and main results

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