Cerebro-cerebellar connectivity is increased in primary lateral sclerosis.

Avner Meoded,Mary Kay Floeter,Rohan Katipally,Olivia Schanz,Arthur E Morrissette,Stephen J Gotts

doi:10.1016/j.nicl.2014.12.009

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https://doi.org/10.1016/j.nicl.2014.12.009

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Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Connectivity matrices were constructed from resting state fMRI in 16 PLS patients to identify areas of differing connectivity between patients and healthy controls. Probabilistic fiber tracking was used to examine structural connections between regions of differing connectivity. PLS patients had 12 regions with increased functional connectivity compared to controls, with a predominance of cerebro-cerebellar connections. Increased functional connectivity was strongest between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex. Fiber tracking detected no difference in connections between regions with increased functional connectivity. We conclude that functional connectivity changes are not strongly based in structural connectivity. Increased functional connectivity may be caused by common inputs, or by reduced selectivity of cortical activation, which could result from loss of intracortical inhibition when cortical afferents are intact.

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Functional connectivity in resting state networks is decreased in many neurodegenerative and neuropsychiatric disorders (AlexanderBloch et al, 2013; Chhatwal and Sperling, 2012; Damoiseaux et al, 2012; Gotts et al, 2012)
The Diffusion tensor imaging (DTI) data were adequate for structural connectivity analysis in 15 primary lateral sclerosis (PLS) patients and 13 healthy controls
The identification of the cerebellum in the functional network resulted from our data-driven approach to identify areas that differed most from controls, and examining functional and structural connections between the identified regions

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Introduction

Functional connectivity in resting state networks is decreased in many neurodegenerative and neuropsychiatric disorders (AlexanderBloch et al, 2013; Chhatwal and Sperling, 2012; Damoiseaux et al, 2012; Gotts et al, 2012). In motor neuron disorders such as amyotrophic lateral sclerosis (ALS), some studies report that functional connectivity is increased compared to healthy controls, in the regional sensorimotor network Functional connectivity may be affected by the stage of disease and the structural integrity of long-range white matter tracts in the brain. In ALS, functional connectivity was inversely related to the diffusion tensor imaging measures of the structural integrity of cortical white matter tracts (Douaud et al, 2011; Verstraete et al, 2011)

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