Clinical Application Study Of Brain Structural And Functional Magnetic Resonance Imaging In Patients With Somatoform Disorder

Background and Purpose:Somatoform disorders(SFD)is a kind of mental disease of which the incidence is increasing year by year.SFD is characterized by the lasting worry about or believe in somatization symptoms.In patients who have been diagnosed with soma to form disorders,medical test results are either normal or do not explain the patients’ symptoms,which can neither reassure the patients nor ease the somatic symptoms.In clinic,a diagnosis of SFD is based on the tenth edition of the international classification of diseases,as well as the fourth edition of the American psychiatric diagnostic and Statistical Manual,which defined and classified SFD into seven categories,including physical disabilities,pain barriers,etc.Although there are a number of studies about pathophysiological mechanism and clinical diagnosis and treatment of SFD,the etiology and pathogenesis of SFD are still not clear.In recent years,functional and structural magnetic resonance imaging methods are increasingly applied to the study of SFD.Resting state functional magnetic resonance imaging(rs-fMRI)provides a convenient and practical technique for the study of SFD.In contrast to task-based fMRI studies,resting-state fMRI requires(rs-fMRI)neither stimulation nor response and reflects the spontaneous neuronal activity or the background neurophysiological processes of the human brain network,which is widely used in the studies on varieties of neuropsychiatric disorders and mental illness.Structural magnetic resonance imaging(sMRI)can visualize and measure the change of the anatomical structure directly and accurately,which provides anatomical evidence for the blood oxygen signal hypothesis.Functional and structural magnetic resonance imaging are both widely used to study pathological mechanism,diagnosis,treatment and prognosis of all kinds of diseases.In this study,in order to find the potential neuroimaging markers for the development of SFD and explore the pathological mechanism of SFD,rs-f MRI technique was used to analyze the differences in spontaneous brain activity between 21 patients with SFD and 21 normal controls.Subsequently,the VBM and SBM techniques were used to analyze the differences in brain structure between 21 patients with SFD and 21 normal controls.Firstly,Alff analyses were used to detect the altered spontaneous brain activity.Subsequently,the brain regions with altered Alff were defined as region of interest(ROI),and the functional connectivity changes of SFD patients were thereafter measured using the ROI-seed based functional connectivity analyses throughout the whole brain.Finally,the brain structural alterations of SFD patients were analyzed based on VBM and SBM approaches.Meanwhile the correlations between the MRI parameters and clinical variables were analyzed.Materials and Methods:21 patients with somatoform disorder(SFD)who came to the psychology for the first time and were diagnosed by two 5-year-experienced psychologists were recruited from June 2014 to June 2015.As well,21 age-,sex-and education-matched normal controls(NC)were selected.All MRI data(including T2 WI,3D-T1 and rs-f MRI imaging)were performed with 3.0-Tesla MR scanner(Trio Tim system;Siemens,Erlangen,Germany)at the Department of Radiology,Southwest Hospital.Firstly,The ALFF maps within and between two groups were compared using t-test with the AlphaSim(P < 0.01,clusters > 40).The correlations between altered ALFF values and clinical variables such as clinical course,SCL-90 scale scores and MoCA Scale scores were analyzed by Pearson and Spearman analysis.All the statistical analyses were performed via SPSS software.We extracted the significant brain regions as region of interest(ROI)to perform seed-based correlation analysis.Then the Fisher Z-score trans-formation was used to transform the Pearson correlation coefficient r value into the z value which represent functional strength between the ROI and each voxel.The differences in functional connectivity between NC group and SFD group were compared via REST1.8 software package(Alphasim correction for multiple comparisons,P < 0.01,voxel size > 40).Finally,extract z values of SFD group with difference brain areas and correlation analysis was performed with clinical parameters.Twenty-one patients with somatoform disorder and Twenty-one normal controls with eligible high resolution structure images were recruited in the structural analyses.Firstly,VBM approach with DARTEL were used to analyzed the gray matter alterations as the following processing:(1)checking for scanner artifacts and gross anatomical abnormalities for each subject;(2)setting the image origin to the anterior commissure;(3)segmenting MR images into GM,WM and cerebrospinal fluid(CSF)in SPM8 toolbox;(4)using the DARTEL toolbox on SPM8 to produce a high-dimensional normalization protocol and registering to the tissue probability maps the Montreal Neurological Institute(MNI)space transformation;(5)smoothing images with an 4 mm full width at half maximum Gaussian kernel.An independent two-sample t-test was used to find the brain regions where there were differences in gray matter volume between the SFD group and NC group,and the correlations between the altered gray matter volume and clinical data were analyzed thereafter.Then the SBM analyses were performed by the Free Surfer software package under the Linux system.The left and right cerebral hemisphere were analyzed separately as the following processing:(1)cranial defect;(2)automatic volume markings;(3)white matter segmentation;(4)subcortical structures cut filling;(5)automatic error correction;(6)artificial edit/delete,topology error and irregular surface.The gray matter cortical surface of each subject was thereafter obtained,and the differences in cortical thickness between SFD patients and normal controls were compared using Free Surfer and visualized by anatomical template location markers.Results:1.ALFF Results:Compared with NC group,the increased brain regions of ALFF values of SFD group were focused on: bilateral prefrontal cortex,bilateral anterior cingulate cortex.Compared with NC group,the decreased brain regions of ALFF values of SFD group were focused on: the left insula,the right temporal lobe,the left paracentral lobule,bilateral posterior central gyrus.The results of correlation analysis showed that in SFD group,the ALFF values of left ventral medial prefrontal cortex,left insula and right temporal lobe were negatively correlated with the MoCA Scale scores(r =-0.564,P = 0.008),the SCL-90 scores(r =-0.505,P = 0.020)and the duration(r =-0.514,P = 0.017).2.Functional connectivity Results:Compared with NC group,the significant brain regions of functional connectivity of SFD group:(1)The decreased functional connectivity of the left medial prefrontal lobe was shown in the right superior temporal gyrus,the left middle temporal gyrus,the left parahippocampal gyrus,the left posterior central gyrus;(2)The decreased functional connectivity of the right medial prefrontal lobe was shown in the left medial superior frontal gyrus,left dorsolateral superior frontal gyrus;(3)The decreased functional connectivity of the left anterior cingulate gyrus was shown in the left insula,the left middle temporal gyrus,the left orbital inferior frontal gyrus,the left supramarginal gyrus,the left dorsolateral superior frontal gyrus,the right anterior cingulate gyrus and the right complementary activities areas;(4)The decreased functional connectivity of the right temporal gyrus was shown in the bilateral temporal lobe and right inferior frontal gyrus,The increased functional connectivity of the right temporal gyrus was shown in the left anterior cingulate gyrus and the right cerebellum;(5)The decreased functional connectivity of the left insula was shown in the left posterior central gyrus and the left paracentral lobule.Meanwhile,the functional connectivity z value between the insular cortex and the left posterior central gyrus was significantly negatively correlated with SCL-90 scores(r =-0.674,P= 0.001).3.VBM ResultsCompared with NC group,the gray matter volume decreased in bilateral hippocampal,bilateral insula lobe,left thalamus,left occipital,while increased in bilateral cerebellum of SFD group.In addition,the left insular cortex was negatively correlated with SCL-90 scores(r=-0.658,P=0.001),and the right hippocampus was negatively correlated with SCL-90 scores(r=-0.690,P =0.001).4.SBM ResultsCompared with NC group,the cortical thickness increased in medial frontal cortex and superior parietal lobule,while decreased in inferior parietal lobule,hippocampus,triangular part of the inferior frontal gyrus and posterior central gyrus of the right hemisphere in SFD group.The cortical thickness decreased in frontal lobe,temporal lobe,insula,frontal gyrus,inferior frontal gyrus and precentral of left hemisphere in SFD group.Conclusion:1.In the first part of the study,we used low-frequency amplitude approach to detect whether it exists abnormal spontaneous brain activation or not in SFD patients.The results showed that the ALFF values increased in bilateral frontal lobe and bilateral anterior cingulate in SFD patients,and the ALFF values of the left ventral medial prefrontal cortex were significantly negatively correlated with Mo CA scores,which suggested that aforementioned brain areas might compensate for the processing of cognitive impairment,collision detection,pain information process,empathize and empathy.While the ALFF values decreased in the right temporal lobe temporal gyrus,the left insula,the left paracentral lobule,bilateral posterior central gyrus in SFD patients.Moreover,the ALFF values in the left insula were significantly negatively correlated with SCL-90 scores,which suggested the function of insula was defected in SFD patients,which led to long-term pain and discomfort in SFD patients,as the pain cannot be effectively treated.The ALFF values in right temporal lobe were significantly negatively correlated with the clinical course,which suggested that with occurrence and development of SFD,emotional,cognitive function of temporal lobe gradually impaired gradually.In addition,neuronal activity inhibition in the bilateral posterior central gyrus and the left paracentral lobule and somatosensory sensitivity enhancement,both contributed to pain disorder in SFD patients.2.In the second part we found that the functional connectivity of bilateral prefrontal cortex,bilateral anterior cingulate cortex,left insula,bilateral temporal lobe,left parahippocampal gyrus,left supramarginal gyrus,left postcentral,left paracentral lobule was reduced,which are not only the important parts of the limbic system,but also constitute the basis of the default mode network nodes.The reduced connections of default mode network may involve the patient’s mood cognitive deficits,memory loss and physiological responses of persistent pain.In addition,suppressed status of the default mode network may relate to introverted personality traits of SFD.The reduced functional connectivity of the right medial prefrontal lobe was shown in the left medial superior frontal gyrus,left dorsolateral superior frontal gyrus,suggesting frontoparietal network in the inhibitory state.In the present study,it may be associated with language comprehension,memory storage,sensory disturbances of SFD.The reduced functional connectivity of the left anterior cingulate cortex was shown in the dorsolateral superior frontal gyrus,the supramarginal gyrus,suggesting the executive control network was suppressed,it may be associated with memory,attention and mood disorders.The reduced functional connectivity of the left anterior cingulate cortex was shown in the right anterior cingulate cortex and the left insula,suggesting the salience network was suppressed.Increased negative interpretation on things caused by reduced connectivity of the salience network may exacerbate paranoia and depression with patients of SFD.The reduced functional connectivity of the left insula was shown in left postcentral gyrus,suggesting the the somatosensory network was suppressed.The insula was damaged,the balance of the internal receptor was disturbed,the perception of pain and somatosensory processing system were offset,which led to persistent pain in SFD patients can not be relieved.3.In the third part of the study we analyzed the structural alterations of SFD patients by VBM and SBM approach.The VBM results showed the gray matter volume decreased in bilateral insula and left thalamus in SFD patients,and there was a significant negative correlation between SCL-90 scores and gray matter volume of left insula(r=-0.658,P= 0.001).The SBM results showed the cortical thickness reduced in left insula lobe and right inferior parietal lobe,bilateral frontal lobe and primary sensory cortex,which may associate with the pain,negative emotion integration conduction disturbance and symptom severity in SFD patients.The gray matter volume and cortical thickness both decreased in hippocampal,and the gray matter volume of right hippocampal showed a significant negative correlation with SCL-90 scores(r=-0.690,P= 0.001),suggesting that these structural alterations associated with the memory deficits,cognitive disorder and affective empathy reduction in SFD patients.The cortical thickness increased in right superior parietal lobule and medial frontal cortex,which indicated increased compensatory in the control network and the association with the cognitive regulation of SFD.Moreover,the increased gray matter volume in bilateral cerebellum may contribute to the improvement of social and communication barriers in SFD patients.All the results suggested that SFD patients have not only a wild range of functional deficits,but also a definite structural lesions in brain,which provides powerful imaging evidences for the diagnosis,treatment and prognosis of SFD.