| Background and objective:Low back pain(LBP)is an common disorder,and treatment for it is often unsatisfactory.Structural and functional plasticity of the central nervous system plays critical role in pain chronification.Recently,brain changes such as abnormal function along with impaired structure in patients with nonspecific LBP have been confirmed in several studies by using resting-state functional magnetic resonance imaging(rs-fMRI),which is an essential way for identifying central plasticity.It currently remains unclear how central functional and structural alterations contributed to persisting low-back related leg pain(LBLP)due to lumbar disc herniation,a specific condition.In addition,past rs-fMRI studies were mainly based on oscillations within specific low-frequency ranges(typically defined as 0.01 – 0.1 Hz),while fluctuations in relatively high-frequency bands have been considered as simple physiological noises and thus unexplored.However,a growing evidence revealed that alterations in relatively high-frequency bands may be of physiological importance in pain.According to Buzsáki’s framework,oscillatory blood-oxygenation level-depen-dent(BOLD)waves can be divided into the following five specific frequency bands:slow-6(0–0.01 Hz),slow-5(0.01-0.027 Hz),slow-4(0.027-0.073 Hz),slow-3(0.073-0.198 Hz)and slow-2(0.198-0.25 Hz).In the present study,rs-fMRI was applied to reveal the change of brain function(i.e.,local or short-distance functional interactions,interhemispheric functional coordination)in five specific frequency bands and full-frequency bands in LBLP patients compared with healthy controls,and hence elucidate the central mechanisms underlying LBLP and provide theoretical foundation guiding precision treatment for LBLP in clinical practice.Participants and methods:Two groups of participants were recruited for this prospective study,including LBLP patients and age-,gender-,and education-matched healthy controls(HCs).After rs-fMRI scanning,methods such as amplitude of low frequency fluctuation(ALFF),regional homogeneity(Re Ho)and voxel-mirrored homotopic connectivity(VMHC)were applied to quantify features of brain intrinsic functional architecture.At first,a cohort of LBLP patients(n=25)and well-matched HCs(n=27)were recruited and underwent MRI scanning and a battery of clinical tests.Amplitude of fluctuations(AF)in five specific frequency bands and the full-frequency band were calculated and compared between the LBLP and HC groups using ALFF.Then,the associations between the AF in the five specific frequency bands and disease status were further assessed.Besides,this study adopted voxelwise Kendall’s coefficient of concordance(KCC)and coherence(Cohe)regional homogeneity(Re Ho)in the typical and five specific frequency bands to analyze individual whole-brain rs-fMRI scans in 25 LBLP patients and 26 HCs.Altered Re Ho was correlated with clinical metrics,which were assessed using partial correlational analysis.Finally,rs-fMRI data were obtained from 25 LBLP patients and 27 HCs,and symmetrical interhemispheric voxel’s time series in the two groups were further calculated as VMHC.In consideration of the frequency property,alterations of VMHC in the typical frequency band and five specific frequency bands were analyzed and compared using voxel-based analyses.Moreover,interactions between clinical metrics(as well as disease status)and the five specific frequency bands were demonstrated with full-factorial analysis.Results:Compared with healthy controls,LBLP patients exhibited a significantly altered AF in multiple brain regions at five specific frequencies.The regions with alterations in the five frequency bands were selected for full-frequency band analyses,including the right and left middle and inferior temporal gyri(MTG/ITG),bilateral precuneus(PCUN),right anterior insula/frontal operculum(a INS/f O),right or left inferior parietal lobule/postcentral gyrus(IPL/Po CG),posterior lobe of the right cerebellum(CPL)and bilateral caudate(CAU).the LBLP patients consistently exhibited a trend showing an increase in the AF in the right CPL and a decrease in the AF in the bilateral PCUN,CAU and right IPL/Po CG from the low-to high-frequency bands.A significant interaction was identified between the frequency bands and disease status in the bilateral rectal gyrus.Moreover,AF alterations in specific regions at specific frequency band were correlated with visual analogue scale(VAS)scores and two-point tactile discrimination(TPTD)performance.In addition,between-group differences demonstrated significant alterations in the Re Ho in LBLP patients in the typical and five specific frequency bands,respectively.KCC-Re Ho detected more regions than Cohe-Re Ho in both typical and five specific frequency bands.Further analyses showed significant interactions between disease status and the five specific frequency bands in the right CPL,brainstem,basal ganglia(BG),medial prefrontal cortex(m PFC),precuneus and IPL.However,no correlations were found between any of the clinical indices and altered Re Ho in the typical frequency bands.Moreover,there were pain-related alterations in Re Ho in the specific frequency bands(slow-2,slow-4,slow-5,slow-6)related to disease duration,VAS score,Fugl-Meyer assessment along with TPTD performance.Significantly altered VMHC values in the typical and five specific frequency bands were identified in patients with LBLP.Simultaneously,seed-based functional connectivity analysis revealed lower heterotopic connectivity patterns of the regions with reduced VMHC in LBLP patients.Besides,significant interactions between disease status and the five specific frequency bands were shown in several brain regions including the cerebellum anterior lobe(CAL),MTG and the anterior cingulate cortex(ACC).Change of the status of interhemispheric connectivity showed a great ability to distinguish the LBLP disease from HCs.Significant relationship was observed between the altered VMHC and the clinical metrics,such as the disease duration,VAS score,Fugl-Meyer assessment and TPPD performance,at typical frequency bands(slow-2,slow-4)in specific brain regions.Conclusion:Altered of spontaneous brain activity,disrupted multiscale frequency-related local connectivity and interhemispheric coordination implied in this study,provided novel evidence for understanding central plasticity responsible for LBLP.The pain-related changes in AF,Re Ho,and VMHC were frequency-dependent,and such alterations in specific region and frequency ranges were related to clinical indices with pathological importance.These findings suggest that the exact frequency band(including high-frequency band)and detailed analysis method should be considered for exploring pain-related intrinsic activity in future studies. |
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