Research Of The Relationship Between Basal Ganglia-thalamus-cortex Circuits And Negative Symptoms Of Schizophrenia

Schizophrenia is a complex group of chronic diseases with unknown etiology.There are two types of the clinical symptoms: positive symptoms and negative symptoms.Positive symptoms involve hallucinations,delusions and thinking disorders,while negative symptoms mainly include poor thinking,emotional apathy,lack of will,slow movement and social withdrawal.These obstacles involving perception,emotion,thinking and behavior,and incoordination of mental activities greatly affect the daily life of patients and have a greater social impact.The current anti-schizophrenia drug treatment has relatively effective control of its positive symptoms,but its effect on its negative symptoms is very limited.In recent years,physical intervention is commonly used as adjuvant therapy,and repeated transcranial magnetic stimulation(rTMS)technique has been gradually used to treat negative symptoms of schizophrenia,which is non-invasive and relatively safe.At present,there is a idea that schizophrenia is a mental disease caused by brain connectivity disorders.There are many hypotheses about the pathogenesis of schizophrenia,among which the Basal ganglia-prefrontal dopamine hypothesis has been initially recognized by the academic community.Previous studies have found abnormalities in the structural and functional connections of the brain in schizophrenia.In particular,studies have shown that there are abnormalities in the structural and functional organization of basal ganglia,thalamus and cortical regions in schizophrenia,which may be related to the generation of negative symptoms,which also provides imaging evidence to support the dopamine hypothesis.However,the relationship between negative symptoms and abnormal thalamocortical connections in patients remains unclear.Therefore,this study intends to use magnetic resonance imaging(MRI)data to construct the basal ganglia-thalamic-cortex connection loop from the perspective of structure and function,investigate the structural and functional abnormalities of the loop,and preliminarily explore the role of rTMS in the function of the loop.In study 1,we included resting state f MRI data and diffusion-weighted structural MRI data of 72 schizophrenia and 87 healthy controls.First,through TBSS analysis we find that there are white matter microstructural changes in each major fibrous tract skeleton in patients with schizophrenia.Subsequently,we used probabilistic tracing and multimodal data fusion segmented construction methods to construct the basal gangliathalamus-frontal cortex white matter fiber tract connection pathway and the basal ganglia structure weighted thalamus-whole brain functional connection pathway.It is found that there are certain abnormal changes in the structural and functional connections between the subcortex and the frontal cortex.In addition,there are functional connectivity abnormalities in the subcortex-corner gyrus,supplementary motor cortex,central anterior gyrus,precuneus,insula,and middle temporal gyrus and those correspond to different basal ganglia sub-regions.These abnormal connection patterns may be related to the negative symptoms of schizophrenia.In study 2,we collected the clinical scale and MR data at baseline and 1 month after treatment for 23 patients with schizophrenia treated with anti-schizophrenia drug and 24 patients with schizophrenia treated with anti-schizophrenia drug and high-frequency DLPFC rTMS,and found that patients treated with rTMS showed a more significant decrease in negative symptom scores compared with the group treated with antischizophrenia drug.The basal ganglia-thalamus-cortex loop was constructed using multimodal data fusion.It is found that there are differences in the functional connections between the thalamus and the cingulate,fusiform gyrus and frontotemporal region under the weight of the structural connection of different basal ganglia-thalamus.In addition,correlation analysis results show that the change rate of the negative symptom score of the PANSS scale was negatively correlated with the right pallidum-thalamus structure connection weighted thalamus-left inferior frontal gyrus functional connection in the rTMS treatment group.This study further verifies the effect of rTMS in the improvement of negative symptoms of schizophrenia,emphasizes the importance of frontal lobe in the negative symptoms of schizophrenia,locking the thalamus-inferior frontal gyrus may be one of the important pathways for the treatment of negative symptoms.In summary,the abnormal connections of basal ganglia-thalamic-cortical circuits in schizophrenia were found in structure-function MRI fusion,providing further imaging evidence for the dopamine hypothesis.At the same time,we further verified that high frequency rTMS stimulation on DLPFC can improve negative symptoms of schizophrenia,and its stimulation effect can penetrate into the subcortical nuclei and have a certain influence on the subcortical-cortical functional connection.In addition,a series of findings in this study suggest that the thalamus-inferior frontal gyrus connection may be one of the potential targeted pathways for ameliorating negative symptoms of schizophrenia.