Repetitive Transcranial Magnetic Stimulation Intervention On Dynamic Brain Networks In Schizophrenia

Schizophrenia（SCZ）is a serious and complex neuropsychiatric disorder characterized by positive symptoms,negative symptoms and cognitive impairment.Drug therapy and other interventions have long been the subject of psychiatry research.Due to the difficulty of drug treatment in chronic schizophrenia,non-invasive stimulation therapy has gradually attracted people’s attention.In this thesis,repeated transcranial magnetic stimulation（r TMS）,was used to study the brain network connection of patients based on resting state functional magnetic resonance.First,27 patients with schizophrenia（TSZ group）received stimulation of the left dorsolateral prefrontal cortex（DLPFC）at a frequency of 10 Hz for 4 weeks,5 days/week,1000 pulses/day with stable antipsychotic medication treatment.Meanwhile,26 patients in the drug control group（DSZ group）received undifferentiated antipsychotic medication treatment only.All subjects were assessed by magnetic resonance image（MRI）scan and PANSS scale before and after treatment.It also included only baseline MRI data from24 healthy controls.All patients’ function magnetic resonance image（f MRI）data were under clustering analysis after separated into gray matter masks and white matter masks based on T1 image.Then static and dynamic functional connections between the clusters were calculated.For statistical analysis,repeated measure ANOVA was performed to explore the influence of r TMS on the gray matter and white matter brain networks connections in schizophrenia.It was found that in gray matter,significant interactions were showed in static connection between the sensorimotor network and the temporalorbitofrontal network,and in dynamic connection with cerebellar anterior network and the visual network.Post-hoc examination found that the drug control group showed a trend that significantly differed from normal people,while the r TMS group inhibited the abnormity to a certain extent.The static connections of the anterior orbitofrontal network with the tempo-frontal network and the callosum network of the white matter,the frontoparietal network and the ventral attention network of the gray matter showed significant interaction effects.Post-hoc examination found that the r TMS group showed a significant decrease in the trend close to normal people.In addition,the dynamic connection between the sensorimotor network of grey matter and the anterior and posterior central gyrus network of white matter also showed significant interaction.The abnormal increase in the drug control group was also inhibited in the r TMS group.Correlation analysis with clinical features also found that partial brain network connections were significantly associated with reduction in negative symptoms.This study suggests that r TMS intervention can be used as an adjunctive means to activate or inhibit the abnormities of the connections between the corresponding brain networks to improve negative symptoms of patients when drug therapy alone cannot eliminate or inhibit all abnormal trends.In consideration of the analysis results mostly related to frontal area which is near to our r TMS stimulation site,then analyzed connectivity on voxel level from stimulation site to the whole brain.According to the results to select the interaction significant area for region of interest level analysis of the dynamic connection.The changes between remote network pathways triggered by stimulus site were explored.Then the correlation with clinical features was analyzed as in previous studies.The results of voxel level showed that the connections between dorsolateral prefrontal cortex and default mode network,sensorimotor network,frontal parietal network,visual network,limbic network,basal ganglia network and cerebellar network were significantly reduced.Analysis of region of interest levels revealed changes in the left DLPFC-thalamo-cerebellar pathway.To sum up,this study explored the connectivity within white matter and grey matter,found r TMS assisted intervention effectively inhibited the development trend of abnormal disconnection between sensorimotor network and other networks in patients,and enhanced the stability of connections between networks.Moreover,the abnormal activation of the frontal lobe from the surface white matter to grey matter and the deep white matter was effectively reduced.Its correlation with negative scores also validated the efficacy of frontal r TMS in the treatment of negative symptoms.Stimulation of the frontal lobe effectively regulated the cortical to subcortical pathway from the thalamic center to the cerebellum,providing evidence for the reduction of functional connectivity variability induced by r TMS.The effect of r TMS not only affects the variability of functional connectivity in the frontal region of the stimulus site,but also may affect other networks associated at a more remote distance through the subcortical gray matter,suggesting that r TMS regulates symptoms by coordinating the heterogeneity of brain regions.