Longitudinal Study Of RTMS Treatment For Idiopathic Tinnitus Based On RS-fMRI And Analysis Of TCM Syndrome Types And Brain Functio

Objective1.Part I: By collecting and analyzing the resting state f MRI data of patients with subjective idiopathic tinnitus and using methods of Amplitude of Low Frequency Fluctuation(ALFF)and Functional Connectivity(FC)to analyze the abnormal brain regions that are most related to tinnitus,and to explore the abnormal spontaneous neuronal activity and brain functional connectivity in patients with tinnitus.The target regions of the brain for precise treatment of neuronavigation r TMS were identified according to the research results.2.Part II: By combing with resting state functional magnetic resonance technology,and according to the precise brain region targets determined in Part 1,the stereotactic localization and navigation guidance are used to accurately locate the key brain regions,so as to evaluate the clinical efficacy of neuronavigation r TMS precise target in the treatment of tinnitus.We have conducted a longitudinal follow-up study on the treatment of tinnitus by f MRI to investigate the neurobiological mechanism of the treatment of tinnitus by neuronavigational r TMS.3.Part III: To classify tinnitus patients according to different syndromes of TCM,to analyze the clinical characteristics of tinnitus patients with different symptoms,and to explore the differences of spontaneous neuronal activity between tinnitus patients with different syndromes and healthy people by ALFF.The FC values of liver fire disturbance group and renal essence deficit group were compared and analyzed to explore the differences in brain functional connectivity between the two groups of syndrome type tinnitus patients.Methods1.Part I: Thirty-six patients with idiopathic tinnitus and 30 healthy controls who were treated in the Tinnitus and Allergic Hearing Center of Yue yang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Chinese Medicine from November 16,2017 February 4,2021 were collected and analyzed for f MRI data in the resting state.ALFF and FC methods were used to analyze the distribution of abnormal functional brain regions and functional connections between tinnitus patients and healthy people,and to detect the correlation between them and the clinical indicators of tinnitus.According to the results,the best stimulation target of neuronavigation r TMS was determined for tinnitus patients.2.Part II: The accurate brain area treatment of r TMS is achieved under the guidance of Neuronavigation system through the identified stimulation target area on 12(male: 6cases,female: 6 cases)patients which were selected from the 36 tinnitus patients of Part1.At the same time,the other 24 patients with tinnitus,as control group,to be treated by routine r TMS treatment,the two groups are arranged to accept the same period of treatment with10 times of stimulation treatment,In order to observe the clinical effect between the two groups and each group.30 healthy people from Part 1 were selected as the control group,and the ALFF and FC values of f MRI data of the Neuronavigation r TMS treatment group are analyzed before and after treatment,and the changes of abnormal neuronal activity and brain functional connections in the tinnitus patients in the group are observed through longitudinal follow-up study.3.Part III: According to the theory of dialectical classification of traditional Chinese medicine,the patients with liver fire type(14)and kidney essence deficit type(12)were selected from 36 patients with tinnitus as the research objects,In order to analyze their clinical characteristics.The third group is consisted of 30 healthy people with matched indexes.ALFF is used to compare and analyze the differences of brain function between the spontaneous neuron activity of the patients with liver fire and renal seminal deficit tinnitus and the normal ones.FC is used to compare and analyze the difference of brain functional connectivity between hepatocirrhosis group and renal sperm deficit group.Results1.Part I: 1.There are many abnormal functional brain regions in tinnitus patients.The results of ALFF analysis show that the enhanced brain regions in tinnitus group,compared with the normal control group,were the right middle temporal gyrus,right parahippocampal gyrus;right thalamus;left fusiform gyrus;left thalamus and right middle cingulate gyrus.The correlation results show that there is a positive correlation between ALFF value of right parhippocampal gyrus with the score of item E(affective)in tinnitus disability assessment scale(R =0.498,P =0.002)in the tinnitus group.According to the research results,the right middle temporal gyrus(MTG)was identified as the stimulation target of the key brain region(x=66,y=-12,z=-21).2.By using the right middle temporal gyrus(MTG)(coordinate x=66,y=-12,z=-21)as the seed point,the whole brain FC analysis shows that the brain regions with FC enhancement in tinnitus patients were the right superior temporal gyrus;right central sulcus cap;right hippocampus;left middle temporal gyrus and left hippocampus.The right MTG has extensive abnormal functional connections to both the auditory and non-auditory regions.2.Part II: 2 cases of tinnitus patients fell out in the navigation treatment group,a total of10 patients(male: 5,female: 5)were included in the study and 24 patients completed the study in the conventional treatment group.Before the treatment,there is no difference regarding the basic condition among the three groups(P>0.05).Clinical efficacy evaluation of navigation therapy group and conventional treatment group: T-test results between the two groups indicate that the scores of sleep disorders scale in navigation therapy group are better than those in conventional r TMS group(P < 0.05),and there are no differences in THI,TEQ and VAS scores(P>0.05).There are no significant differences in THI and TEQ(P>0.05).Results of navigation therapy group after treatment: the total THI score,C,F,THI grade and TEQ score of tinnitus patients are significantly different from the navigation treatment group(P < 0.05).There is no difference between VAS and sleep disorder scale(P>0.05).The results of conventional r TMS group after treatment and before treatment: total TEQ score and VAS are different(P < 0.05)and there were significant differences in THI and TEQ(P < 0.05),but no differences in other indexes(P>0.05).Before treatment,the ALFF values of brain region in the navigation group are higher than those in the healthy control group are bilateral middle temporal gyrus,bilateral hippocampal gyrus,and right putamen.After r TMS treatment,the ALFF values brain region of the patients in this group are higher than those in the healthy control group including the right middle temporal gyrus;bilateral hippocampus;right putamen and thalamus and right insula.In the navigation treatment group,the ALFF values of brain regions are lower than those after treatment are right middle temporal gyrus;right parhippocampal gyrus;right central sulcus capus;left inferior occipital gyrus;right inferior temporal gyrus and right inferior frontal gyrus.Results of Pearson correlation analysis: After navigation treatment,the ALFF value of the left hippocampus is positively correlated with the item E score of tinnitus disability assessment scale(r=0.348,P =0.037).After treatment,FC value is decreased in the following brain regions: right inferior frontal gyrus;right putamen;right thalamus;left inferior temporal gyrus and left precuneus.3.Part III: The clinical characteristics of liver fire disturbance group and kidney essence deficiency group: there is a difference in age between the two groups.The average age of the group with renal spermatorrhea deficit is higher(t=-3.72,P < 0.05).There is no significant difference in other clinical evaluation indexes(p=>0.05).Compared with the healthy control group,the ALFF value of the group with hepatocirrhous disturbance is significantly increased in the following areas: the left para-hippocampal gyrus;right inferior temporal gyrus;right thalamus and bilateral putamen.Compared with the healthy control group,the ALFF value is significantly reduced in the right middle frontal gyrus.Compared with the healthy control group,the ALFF value of the renal spermatozoa deficit group is significantly increased in the following areas: bilateral hippocampus;right middle temporal gyrus and right putamen.The ALFF value is decreased significantly in the nephroseminal deficit group: the left superior frontal gyrus and left middle frontal gyrus.Compared with hepatocirrhosis,the FC value is increased significantly in the renal sperm deficit group: left superior temporal gyrus and left middle temporal gyrus.The areas of FC value which are decreased significantly in renal spermatic deficit group including right superior frontal gyrus;left superior frontal gyrus;right inferior temporal gyrus and right middle frontal gyrus.Conclusion1.Part I: There are abnormal increase of ALFF and FC values in several brain regions of tinnitus patients.The abnormal ALFF in right hippocampus of tinnitus patients is correlated with the severity of tinnitus.According to the research results,the key brain regions were selected as the targets for the precise treatment of navigational r TMS,So as to provide a research basis for longitudinal observation of the neurobiological mechanism of tinnitus.2.Part II: 1.Navigation r TMS precision treatment of tinnitus has obvious efficacy,especially in the improvement of patients’ sleep disorders that are compared with the conventional treatment group.2.In the navigation treatment group,A number of clinical scores are decreased significantly after treatment,and ALFF and FC values in some related areas are decreased after treatment.3.By longitudinal observation of the changes of ALFF and FC values in the navigation treatment group before and after treatment,we identified that neuronavigation r TMS is able to play its advantage in the treatment of tinnitus by changing the abnormal spontaneous neuronal activities and functional connections in the brain region.3.Part III: 1.According to the results of ALFF value,tinnitus patients with different TCM syndromes have different brain regions,and the clinical characteristics of tinnitus patients with different TCM syndromes may be correlated with the spontaneous neuronal activities in abnormal brain regions to some extent.2.Through the comparative analysis of FC values among different syndromes,the differences of abnormal brain functional connectivity are identified.The neuroimaging analysis method may be helpful for the clinical differentiation of TCM syndromes.