The Relationship Between Dynamic Changes Of Low-frequency Amplitude And Cognitive Impairmentin Patients With Cerebral Small-vessel Disease:A MRI Study

Background and Purpose:Patients with cerebrovascular disease(cerebralsmallvesseldisease,CSVD)showed different degrees of cognitive impairment.Low frequency oscillation amplitude(alterationsintheamplitudeoflow-frequency,ALFF)is one of the indicators of resting state functional magnetic resonance imaging(resting-statefunctionalmagneticresonance,rs-fMRI).The amplitude of spontaneous brain activity in resting state is evaluated by calculating the square root of power spectrum(usually in the frequency range of 0.01-0.08HZ).ALFF has been proved by many studies to effectively reflect the local spontaneous neuronal activity in humans and animals from the perspective of energy metabolism,but previous studies have relied on an implicit assumption that brain activity remains unchanged during fMRI scanning.With the development of technology,more and more studies have shown that in a resting state,the inherent activity of the brain still changes over time.Dynamic low frequency amplitude(dynamicalterationsintheamplitudeoflow-frequency,dALFF)combinesALFF with sliding window technique to reflect the temporal dynamics of intrinsic brain activity(intrinsicbrainactivity,iBA).The purpose of this study was to explore the temporal dynamic characteristics of regional brain activity in patients with cognitive impairment in CSVD and its relationship with cognitive impairment,so as to deepen the understanding of the neuroimaging mechanism of cognitive impairment in patients with CSVD.Methods:This study included 104 patients with CSVD and 63 healthy elderly with matched age,sex and education(HealthControl,HC).According to the performance of cognitive function,patients with CSVD can be divided into cognitive normal(CSVD-NC,n=52)and cognitive impairment(CSVD-CI,n=52).All subjects underwent a series of neuropsychological scale measurements and blood oxygen level dependent functional magnetic resonance imaging(bloodoxygenLevelDependentfMRI,BOLD-fMRI).After the demographic data,neuropsychological scale and image data are collected,the data are processed and statistically analyzed by SPM12 and SPSS25.0 software packages.The main steps are as follows:(1)according to the statistical type,the demographic data and neuropsychological scale are analyzed by one-way analysis of variance(one-wayANOVA),chi-square test(chi-squaretest)and independent sample t-test.(2)the DPARSF4.3AvancedEdition module of DPABI software package was used to preprocess the fMRI data and get the static low frequency amplitude(thestatealterationsintheamplitudeoflow-frequency,sALFF).On this basis,the whole brain dALFF was analyzed by DynamicBC software.(3)the spatial distribution differences of dALFF values in CSVD-CI group,CSVD-NC group and HC group were obtained by single sample t-test.(4)the differences of dALFF and sALFF among the three groups were compared by voxel-based single factor analysis of variance,with age,sex and years of education as covariables,and error detection rate(FamilyWiseErrorcluster,FWE)based on cluster level for multiple comparison correction,which was considered to be statistically significant by P<0.001.The differences among groups were evaluated by post-event double-sample t-test,and multiple comparison correction was carried out by FWE based on cluster level,which was considered to be statistically significant(P<0.001).(5)the dALFF values of brain regions with significant differences among the three groups were extracted and analyzed by partial correlation with the scores of neuropsychological scale(P<0.05).Age,sex and education level were taken as covariables.Result:(1)there was no significant difference in age((P=0.120),gender(P=0.673)and education(P=0.067)level among CSVD-CI,CSVD-NC and HC groups,but there were significant differences in hypertension and diabetes prevalence among the three groups(P<10-3).The scores of simple mental energy scale(minimentalstateexamination,MMSE),Rey auditory language learning test(Rey’sAuditoryVerbalLearningTest,RAVLT),immediate memory,delayed memory and recognition among the three groups were significantly different.There were significant differences among Boston naming test score(Bostonnamingtest,BNT),clock drawing test score(ClockDrawingTest,CDT)and wiring test score(TrailMakingTest,TMT)(P<10-3)(2)the spatial differences of dynamic low frequency amplitudes among CSVD-CI,CSVD-NC and HC groups were similar.The brain regions with low variability were located in bilateral parietal lobe,frontal lobe,temporal lobe,occipital lobe,and high variability brain areas were located in bilateral hippocampus,bilateral cingulate gyrus and cuneate lobe.DALFF variability in frontal lobe,cuneate lobe,anterior cuneate lobe,cingulate gyrus,hippocampus and parahippocampal gyrus in HC group was significantly higher than that in CSVD group,and the overall dALFF variability of HC was higher than that in CSVD group.(3)there were significant differences in dALFF values among CSVD-CI,CSVD-NC and HC groups in the following brain regions(P<0.05):bilateral parahippocampal gyrus,bilateral hippocampus,bilateral insular,right cuneate anterior lobe,right postcentral gyrus,left orbital inferior frontal gyrus,left straight gyrus.Further intergroup analysis showed that compared with HC group,the dALFF value of left straight gyrus,left superior orbital frontal gyrus,left left orbital middle frontal gyrus,left paraphapocampal gyrus and right insular increased in CSVD-NC group,while dALFF decreased in right postcentral gyrus.Compared with HC,in CSVD-CI group,the dALFF values were higher in bilateral parahippocampal gyrus,bilateral hippocampus,left superior orbital frontal gyrus,left middle orbital frontal gyrus,left dorsolateral superior frontal gyrus and right middle orbital frontal gyrus,but decreased in right postcentral gyrus and left postcentral gyrus.CSVD-NC and CSVD-CI did not pass the FWE correction of voxel level at cluster level,so we extracted the dALFF values of different brain regions according to the results of analysis of variance,and then conducted a double-sample t-test of dALFF values between CSVD-NC and CSVD-CI groups.It was found that there were significant differences in dALFF values in bilateral parahippocampal gyrus,bilateral hippocampus,right orbital middle frontal gyrus and left insular lobe between CSVD-NC and CSVD-CI groups(P<0.05 Bonferroni correction,double-tail test).(4)sALFF analysis showed that there were significant differences in FEW values in the following brain regions among the three groups(P<0.05):bilateral parahippocampal gyrus,bilateral hippocampus,bilateral cingulate gyrus,bilateral postcentral gyrus,left straight gyrus,left orbital middle frontal gyrus,left triangular inferior frontal gyrus,left dorsolateral superior frontal gyrus,right middle frontal gyrus,right middle temporal gyrus,right middle frontal gyrus,right inferior orbital frontal gyrus.Further analysis and comparison between groups showed thatcompared with HC group,the sALFF value of bilateral hippocampus,bilateral parahippocampal gyrus and left orbital middle frontal gyrus increased and sALFF decreased in right middle temporal gyrus,left postcentral gyrus,right precentral gyrus,bilateral triangular inferior frontal gyrus,left dorsolateral superior frontal gyrus and right middle frontal gyrus in CSVD-NC group.Compared with HC group,the sALFF values of bilateral hippocampus,bilateral parahippocampal gyrus,left inferior temporal gyrus and bilateral middle frontal gyrus of CSVD-CI group were higher,while those of left lingual gyrus,right infratemporal gyrus,bilateral postcentral gyrus and bilateral cingulate gyrus were lower in CSVD-CI group.CSVD-NC and CSVD-CI did not pass the FWE correction of voxel level at cluster level,so we extracted the sALFF values of these brain regions according to the results of analysis of variance,and then compared the Salf values between CSVD-NC and CSVD-CI groups.It was found that there were significant differences in sALFF in bilateral hippocampus,bilateral parahippocampal gyrus,right postcentral gyrus and left dorsolateral superior frontal gyrus between CSVD-NC and CSVD-CI groups(P<0.05 Bonferroni correction,double-tailed detection).(5)the patients with CSVD showed the following clinical correlation.The dALFF value of the left insular was positively correlated with the score of RAVLT delayed memory(r=0.291,P=0.047),negatively correlated with the score of RAVLT recognition(r=-0.321,P=0.028),and positively correlated with the score of MMSE.(r=0.323,P=0.027);The dALFF value of the right insular was negatively correlated with the RAVLT recognition score(r=-0.350,P=0.016),and positively correlated with the MMSE score(r=0.365,P=0.012),the dALFF value of the right orbital middle frontal gyrus was negatively correlated with the CDT score(r=-0.416,P=0.004),and negatively correlated with the BNT score(r=-0.463,P=0.001).The dALFF value of the left postcentral gyrus was negatively correlated with the CDT score(r=-0.317,P=0.030).The value of dALFF in the right postcentral gyrus was negatively correlated with the score of RAVLT recognition(r=-0.320,P=0.028).Conclusions:(1)Studies have shown that there are dynamic abnormalities of brain spontaneous activity in patients with CSVD,mainly in bilateral parahippocampal gyrus,bilateral hippocampus,bilateral insular and frontal lobe regions.(2)The functional changes of bilateral parahippocampal gyrus and bilateral hippocampus were found in sALFF and dALFF analysis,suggesting that bilateral parahippocampal gyrus and bilateral hippocampus may be the key brain regions in the pathogenesis of CSVD.(3)The dALFF values of bilateral insular and right postcentral gyrus were significantly correlated with cognitive function in patients with CSVD.The dALFF of right orbital middle frontal gyrus was correlated with executive function and language function,and that of left postcentral gyrus was related to cognitive function.Bilateral insular,bilateral postcentral gyrus and right middle orbital gyrus may be related to CSVD symptoms and have certain significance in the evaluation of disease.