Study Of Resting State Brain Function Integration In Schizophrenia

With the rapid development of socioeconomy, people’s living standards have largelybeen improved. Yet, the state of mental health is emerging as a hidden threat toindividual’s living qualities and to the stability of the whole society. Schizophrenia is themost affected severe mental illness, making1%of the total population worldwide livewith sufferings. The most vulnerable period of being attacked by the disease is fromadolescent to young adults. Patients have low cure rate but high relapse likelihood, leavingmany patients rely on medications throughout their lives. Schizophrenia is damage tosufferers’ cognitive functions and social adaptabilities. The ability loss can hardly be fullyrecovered, leading to a high disability rate among patients. Moreover, the ubiquity ofprejudice and discrimination against mental illness makes patients and their families livein the shadow of shame and embarrassment. Too often, they have to fight with theunbearable pressure and heavy financial burden at the same time.The insights of biological psychiatry make people realize that schizophrenia is part ofa biological problem with central nervous system lesions. Early brain imaging studieshave discovered that patients have ventricle enlargement, brain volume decrease and graymatter/white matter atrophy in many areas. The widespread neuropathological changes and the complex behavior symptoms cannot be explained by focal brain injuries. Instead,researchers came up with the “dysconnectivity hypothesis” of schizophrenia, whichfacilitated a better understanding of the extensive local aberrances and the corepathological symptoms from a perspective of functional integration. Mounting evidencesupported this theory. Functional integration can be reflected in different levels of neuralsystem activities. The two studies of this thesis focus on functional integrationimpairments in schizophrenia at the level of brain network as well as inter-hemisphericconnectivity, respectively.Resting state functional magnetic resonance imaging (rs-fMRI) is adopted in thecurrent study, which is acquired when participants were told to stay relaxed in the scanner,with no other special requirements. This method has been extensively applied in clinicalneuroscience, due to its capability to characterize the inherent property of neural systemand its convenience to perform on patients. In the work of this thesis, the brain functionalnetwork and voxel-mirrored homotopic connectivity (VMHC) were derived from rs-fMRIdata, to detect resting state functional dysconnectivity in schizophrenia. Results andconclusions of the two studies are presented as follows:Study one collected resting state functional images from patients with schizophrenia,their unaffected siblings and healthy controls. Each group has25individuals. Fourcomponents of interest (the anterior and posterior part of default mode network, as well asthe left-and right-lateralized fronto-parietal network) were constructed by independentcomponent analysis (ICA). Groups were compared on the spatial extend(intra-connectivity) and connectivity between components (inter-connectivity). Resultsshowed that patients and siblings shared intra-connectivity abnormalities in threesubsystems apart from the posterior part of default mode network. Meanwhile, onlypatients had higher connectivity between right-lateralized fronto-parietal network andanterior part of default mode network than the controls in inter-connectivity comparisons.These results corroborated that schizophrenia was characterized by intra-connectivitydisruptions in higher order cognitive processing networks, which was partly modulated bygenetic factors. The impairments of network subsystems in the patients and siblings may underlie their shared cognitive behavioral defects. Inter-connectivity abnormality wasspecific to patients, which might relate to their psychotic symptoms. The differentliabilities to disease risk and distinct inter-connectivity alterations between networksubsystems explicitly suggested their differentiating roles to the disease susceptibility andmanifestation.Study two collected rs-fMRI data from18schizophrenic patients with auditoryhallucination,18schizophrenic patients without auditory hallucination and20healthycontrols. Voxel-mirrored homotopic connectivity (VMHC) were computed in all subjectsand compared among the three groups. Results showed that patients without auditoryhallucination have aberrances in superior temporal gyrus (Wernicke’s area) and precentralgyrus. While, patients with auditory hallucination have more widespread impairmentsincluding inferior frontal gyrus (Broca’s area), anterior cingulate cortex, precuneus cortex,superior partial lobule and anterior lobe of cerebellum. The overlap disruptions were instriatum and hippocampus. Consistent with previous studies, our research confirmed thatschizophrenic patients have impairments in inter-hemispheric functional integration intemporal lobe. Expending prior knowledge, this study evidenced that such disruption wasapparent in the baseline activity of neural systems. Patients with auditory hallucinationhave dysconnectivity in Broca’s area, which according to the corollary discharge (CDs)theory, may result in abnormal activation in temporal area during language related tasksand worsen cognitive performances. Besides Wernicke’s area and Broca’s area, otherregions may also contribute to the illness and hallucinating symptom. The convergentabnormal areas in striatum and hippocampus may relate to nonspecific changes in thedisease. Correlation analysis between connectivity strength and clinical symptom scoresrevealed that connectivity in striatum area was negatively correlated with scores assessedby Auditory Hallucinations Rating Scale (AHRS) in the hallucination group. This findingwas in line with the hypothesis that striatum abnormality was related to positive symptomseverity in schizophrenia.In general, Study one and study two evidenced function integration abnormality inschizophrenia during rest. Study one focused on subsystems of higher order cognitive processing networks in patients and their siblings, delineating the specific aberrancepatterns in different regions of a network. Meanwhile, study one also probed the possiblerole from genetic factors to disease pathology. Study two found patients with auditoryhallucination and patients without this symptom had not only shared abnormalities butalso distinct impairments in terms of inter-hemispheric functional connectivity. Theseconnectivity abnormalities may reflect nonspecific changes and symptom related neuralmechanism in schizophrenia, respectively.