The Study Of The Resting-state Functional Magnetic Resonance Imaging In Spinocerebellar Ataxia Type3Patients

Background Spinocerebellar ataxia type3(SCA3), also known as Machado Joseph disease (MJD), is the most common subtype in Hereditary spinocerebellar ataxia and mostly appears as autosomal dominantly. It is a clinically heterogeneous, neurodegenerative disorder characterized by varying degrees of ataxia, dysarthria,ophthalmoplegia, extrapyramidal and pyramidal dysfunction. Recently years, functional magnetic resonance imaging(fMRI) is a hot topic in neuroimaging, in order to probe the spontaneous brain activity or background activities of physiological mechanism in the human brain. The current analysis methods of resting state fMRI data contain regional homogeneity(ReHo), amplitude of low fluctuation(ALFF) and functional connection. ReHo and ALFF are two measures which quantify the function of the brain locally can be implemented in resting-state fMRI studies. ReHo reflects the synchronization of regional neuronal activities and ALFF measures amplitude of spontaneous activity of each pixel in regional sites under resting condition and characterize regional cerebral function, while functional connectivity explores the correlation of activities in different brain regions or explains the relationship of activities between one and the other brain regions. Until now, little is known about how brain systems may be altered in SCA3/MJD. Hence, studying resting state of spontaneous activity of SCA3/MJD patients’brain is in order to to find the neurobiological mechanisms of SCA3/MJD.Objective The present study investigated the intrinsic brain functional activities using functional magnetic resonance imaging (fMRI) under resting state and identified neurobiological mechanisms of the disorder and targets for intervention.Methods Gathering21SCA3/MJD patients and21age-,gender-matched healthy controls as well as18premorbid SCA3/MJD parients (pre-SCA3) and18age-,gender-matched healthy controls (SCA3/MJD patients confired by genetic diagnosis in China’s genetic laboratory) took part in the resting state fMRI scans. We analyzed resting fMRI data using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation(ALFF) as well as functional connectivity measures. Using two sample t-test, we analyzed the differences of ReHo, ALFF and functional connectivity between the premorbid SCA3/MJD parients and comparison groups as well as between SCA3/MJD patients and healty controls during the resting state.Results1. pre-SCA3patients presented enhanced regional homogeneity signals in right lingual gyrus and posterior lobe of cerebellum(Crus1_R) compared with healthy controls(P<0.01, Alphasim corrected). SCA3/MJD patients presented increased in right medulla oblongata, lingual gyrus and posterior lobe of cerebellum(Crus1R) and decreased in right posterior lobe of cerebellum(Crus2_R), left anterior lobe of cerebellum, right lingual gyrus, right superior temporal gyrus, and right middle frontal gyrus relative to healthy controls (P<0.01, Alphasim corrected). Significantly different ReHo values in SCA3/MJD patients have no coreelaiton with SARA, ICARS, MMSE and MoCA sore(P>0.05).2. pre-SCA3patients showed decreased ALFF values in the right posterior lobe of cerebellum(Crus1_R and Crus2_R), left posterior lobe of cerebellum(Crus2_L), left superior frontal gyrus,left superior parietal gyrus and left precentral gyrus compared with healthy controls(P<0.01, Alphasim corrected). SCA3/MJD patients presented depressed ALFF values in the left posterior lobe of cerebellum(Crus2_L), right inferior and middle temporal gyrus in relative to healthy controls(P<0.01, Alphasim corrected). The mean ALFF values in the right middle temporal gyrus were negatively corrected with SARA sore (r=-0.441,P=0.046) and ICARS sore(r=-0.523,P=0.015).3. In the pre-SCA3group, the right inferior frontal gyrus showed decreased positive functional connectivity to the right middle temproral gurus, the right supplementary motor cortex to the right thalamus, as well as the superior frontal gyrus to the right middle temporal gyrus(P<0.001,not corrected). In the SCA3/MJD group, the left and right inferior frontal gyrus,the left and the right rectus gyrus to the left parietal lobe showed decreased positive functional connectivity(P<0.001,not corrected).And SCA3/MJD patients presented decreased positive functional connectivity in the right supplementary motoxr cortex to the cerebelar vermis (P<0.001,not corrected). The left parietal lobe presented enhanced functional connectivity with the left anterior lobe of cerebellum in the SCA3group(P<0.001,not corrected). The strength of functional connectivity of abnomaly connective region showed no correlatin with SARA, ICARS, MMSE and t MoCA sore(P>0.05). Conclusions1. Premorbid SCA3/MJD parients have altered regional function in cerebellum, frontal lobe, temporal lobe and parietal lobe as well as abnormal functional connections linking frontal lobe to temporal lobe and supplementary motoxr cortex to thalamus.2. SCA3/MJD parients showed altered regional function predominantly in cerebellum and the right-hemisphere, including frontal lobe, temporal lobe, parietal lobe as well as abnormal functional connections linking the frontal lobe to temporal lobe, and supplementary motoxr cortex to the cerebelar vermis.