Connectivity In Schizophrenia Patients Research Articles

Temporal hyper-connectivity and frontal hypo-connectivity within gamma band in schizophrenia: A resting state EEG study

ObjectiveThe brain network serves as the physiological foundation for information processing of the brain. Many studies have reported abnormalities of gamma oscillations in Schizophrenia. The aim of this study was to investigate the gamma-band connectivity in Schizophrenia patients. MethodsWe recorded the resting state electroencephalogram (EEG) for 15 schizophrenia patients with refractory auditory hallucinations and 14 healthy controls, with eyes open and closed. The brain network was constructed based on weighted phase lag index for gamma band. Whole scalp metrics (clustering coefficient, global efficiency and local efficiency) and local region metrics (degree and betweenness centrality) in the frontal and temporal lobes were computed. Correlation analyses between network metrics and symptom scales were examined to find associations with symptom severity. ResultsSchizophrenia patients had larger global efficiency and local efficiency (p < 0.05) with eyes closed, probably representing greater brain activity and information exchange. For degree and betweenness centrality, schizophrenia patients showed an increase (p < 0.05) in the temporal lobe but a decrease (p < 0.05) in the frontal lobe with eyes closed and open, potentially account for the patients' symptoms such as hallucinations and thought disorders. Local efficiency and frontal lobe degree were positively and negatively correlated with the scales, respectively (both p < 0.05). ConclusionsAltered connectivity of the resting state brain network has been revealed and may be associated with the core symptoms of schizophrenia. Our study provides promising evidence for the investigation of the pathological basis of Schizophrenia and could aid in objective diagnosis.

Association between urban upbringing and functional brain connectivity in schizophrenia.

Environmental factors considerably influence the development of the human cortex during the perinatal period, early childhood, and adolescence. Urban upbringing in the first 15 years of life is a known risk factor for schizophrenia (SCZ). Though the risk of urban birth and upbringing is well-examined from an epidemiological perspective, the biological mechanisms underlying urban upbringing remain unknown. The effect of urban birth and upbringing on functional brain connectivity in SCZ patients is not yet examined. This is a secondary data analysis of three studies that included 87 patients with SCZ and 70 healthy volunteers (HV) aged 18 to 50 years. We calculated the developmental urbanicity index using a validated method in earlier studies. Following standard pre-processing of resting functional magnetic resonance imaging (fMRI) scans, seed-return on investment (ROI) functional connectivity analysis was performed. The results showed a significant association between urban birth and upbringing on functional connectivity in SCZ patients and HV (P < 0.05). In SCZ patients, connections from the right caudate, anterior cingulate cortex, left and right intracalcarine cortices, left and right lingual gyri, left posterior parahippocampal cortex to the cerebellum, fusiform gyri, lateral occipital cortex, and amygdala were significantly associated with the urbanicity index (P < 0.05). These study findings suggest a significant association between urban birth and upbringing on functional brain connectivity in regions involved in reward processing and social cognition in SCZ. Assessment of social cognition could have implications in developing an in-depth understanding of this impairment in persons with SCZ.

Neural substrates of verbal memory impairment in schizophrenia: A multimodal connectomics study.

While verbal memory is among the most compromised cognitive domains in schizophrenia (SZ), its neural substrates remain elusive. Here, we explored the structural and functional brain network correlates of verbal memory impairment in SZ. We acquired diffusion and resting-state functional MRI data of 49 SZ patients, classified as having preserved (VMP, n=22) or impaired (VMI, n=26) verbal memory based on the List Learning task, and 55 healthy controls (HC). Structural and functional connectivity matrices were obtained and analyzed to assess associations with disease status (SZ vs. HC) and verbal memory impairment (VMI vs. VMP) using two complementary data-driven approaches: threshold-free network-based statistics (TFNBS) and hybrid connectivity independent component analysis (connICA). TFNBS showed altered connectivity in SZ patients compared with HC (p < .05, FWER-corrected), with distributed structural changes and functional reorganization centered around sensorimotor areas. Specifically, functional connectivity was reduced within the visual and somatomotor networks and increased between visual areas and associative and subcortical regions. Only a tiny cluster of increased functional connectivity between visual and bilateral parietal attention-related areas correlated with verbal memory dysfunction. Hybrid connICA identified four robust traits, representing fundamental patterns of joint structural-functional connectivity. One of these, mainly capturing the functional connectivity profile of the visual network, was significantly associated with SZ (HC vs. SZ: Cohen's d=.828, p < .0001) and verbal memory impairment (VMP vs. VMI: Cohen's d=-.805, p=.01). We suggest that aberrant connectivity of sensorimotor networks may be a key connectomic signature of SZ and a putative biomarker of SZ-related verbal memory impairment, in consistency with bottom-up models of cognitive disruption.

Online Left-Hemispheric In-Phase Frontoparietal Theta tACS Modulates Theta-Band EEG Source-Based Large-Scale Functional Network Connectivity in Patients with Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5-7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS.

Impact of low-frequency repetitive transcranial magnetic stimulation on functional network connectivity in schizophrenia patients with auditory verbal hallucinations

Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has shown potential in the treatment of AVH. However, the underlying neural mechanismof rTMS in the treatment of AVH remains largely unknown. In this study, we used a static and dynamic functional network connectivity approach to investigate the connectivity changes among the brain functional networks in schizophrenia patients with AVH receiving 1 Hz rTMS treatment. The static functional network connectivity (sFNC) analysis revealed that patients at baseline had significantly decreased connectivity between the default mode network (DMN) and language network (LAN), and within the executive control network (ECN) as well as within the auditory network (AUD) compared to controls. However, the abnormal network connectivity patterns were normalized or restored after rTMS treatment in patients, instead of increased connectivity between the ECN and LAN, as well as within the AUD. Moreover, the dynamic functional network connectivity (dFNC) analysis showed that the patients at baseline spent more time in this state that was characterized by strongly negative connectivity between the ENC and AUD, as well as within the AUD relative to controls. While after rTMS treatment, the patients showed a higher occurrence rate in this state that was characterized by strongly positive connectivity among the LAN, DMN, and ENC, as well as within the ECN. In addition, the altered static and dynamic connectivity properties were associated with reduced severity of clinical symptoms. Both sFNC and dFNC analyses provided complementary information and suggested that low-frequency rTMS treatment could induce intrinsic functional network alternations and contribute to improvements in clinical symptoms in patients with AVH.

M164. RESTING-STATE CEREBRAL BLOOD FLOW IN SCHIZOPHRENIA PATIENTS WITH PSYCHOMOTOR SLOWING

BackgroundSchizophrenia patients who are suffering from psychomotor slowing (PS) present reduced levels of spontaneous motor activity, as well as slowing of gait and of fine motor dexterity. These motor abnormalities predict poor clinical outcomes for the patients. Recently, MRI studies have shown both aberrant functional and structural connectivity in schizophrenia patients with PS especially in the basal ganglia and the motor/premotor cortex. Arterial spin labeling imaging (ASL) perfusion MRI allows for quantitative measurement of cerebral blood flow (CBF). We used this approach to assess the difference in resting-state CBF between schizophrenia patients with psychomotor slowing and healthy controls as well as the relationships between CBF and motor symptoms in patients. In the current study, we included patients with moderate to severe PS. We hypothesized the intensity of the motor impairment in the patients would be linked to an abnormal increase of the CBF in several areas of the motor system, including basal ganglia, parietal cortex, and motor/premotor cortex.Methods30 participants (13 healthy controls and 17 schizophrenia patients with PS) took part in an MRI session during which we acquired ASL perfusion MRI. We also evaluated psychomotor slowing in patients using 3 distinct measures (a self-report of motor activity using the International Physical Activity Questionnaire (IPAQ), an observer rating using the Salpêtrière Retardation Rating Scale (SRRS), and an objective measure of the global level of activity using wrist actigraphy). First, we assessed differences between groups in quantitative resting CBF. Then, in patients, we explored the association between the 3 different motor disorder measures and the whole-brain resting CBF.ResultsA group comparison showed significantly increased CBF in the right inferior temporal gyrus in patients compared to healthy controls (two samples t-test: t=3.44, p<0.001 (uncorrected), cluster-level correction (kE=75): p(FWE-corr)=0.028, q(FDR-corr)=0.005). Increased severity of psychomotor slowing as measured by SRRS was associated with higher CBF in a widespread network (Multiple regression Z>4, p<0.001 (uncorrected), cluster-level correction (kE=75) p(FWE-corr)<0.001, q(FDR-corr)<0.001)) including the basal ganglia (i.e. striatum and putamen), the right lateral premotor cortex, bilateral Insulas, anterior cingulate cortices, inferior temporal gyri, parietal cortices, and the right parahippocampus. Both IPAQ and actigraphy failed to correlate with the resting CBF.DiscussionThese findings suggest that schizophrenia patients with PS presented an alteration of the resting cerebral blood flow compared to healthy controls. Moreover, in line with our hypothesis, the severity of the psychomotor slowing seems to be associated with increased blood flow in schizophrenia patients in a large network including basal ganglia, parietal cortex, and lateral premotor cortex. Finally among the 3 distinct measures used in the current study, only the SRRS seems to be associated with an abnormal increase of the cerebral blood flow. These findings confirm that psychomotor slowing is associated with an alteration of the cerebral blood flow in the motor/premotor network. We expect refined results as we include more subjects in the running study.

Altered Domain Functional Network Connectivity Strength and Randomness in Schizophrenia.

Functional connectivity is one of the most widely used tools for investigating brain changes due to schizophrenia. Previous studies have identified abnormal functional connectivity in schizophrenia patients at the resting state brain network level. This study tests the existence of functional connectivity effects at whole brain and domain levels. Domain level refers to the integration of data from several brain networks grouped by their functional relationship. Data integration provides more consistent and accurate information compared to an individual brain network. This work considers two domain level measures: functional connectivity strength and randomness. The first measure is simply an average of connectivities within the domain. The second measure assesses the unpredictability and lack of pattern of functional connectivity within the domain. Domains with less random connectivity have higher chance of exhibiting a biologically meaningful connectivity pattern. Consistent with prior observations, individuals with schizophrenia showed aberrant domain connectivity strength between subcortical, cerebellar, and sensorial brain areas. Compared to healthy volunteers, functional connectivity between cognitive and default mode domains showed less randomness, while connectivity between default mode-sensorial areas showed more randomness in schizophrenia patients. These differences in connectivity patterns suggest deleterious rewiring trade-offs among important brain networks.

12.4 THE BODILY SELF IN PSYCHOSIS: SENSORIMOTOR INDUCTION OF AUDITORY MISATTRIBUTION IN PSYCHOSIS IS LINKED TO NEURAL DISCONNECTIVITY

Abstract Background Psychosis is often depicted as a disruption of the self-model. Patients suffering from psychosis report many symptoms relating to deficiencies in the minimal self, including loss of the sense of control over their actions (Sense of Agency) as well as numerous disturbances of body representation (e.g. Body Ownership). Positive symptoms of psychosis such as passivity symptoms and auditory hallucinations (termed first-rank symptoms) are characterized by a diminished demarcation of self-other boundaries, causing misattribution of self-generated actions to external sources. It has been suggested that this deficiency in self-monitoring in schizophrenia is due to abnormal sensorimotor prediction mechanisms, causing a loss of agency for actions and thoughts. While the neurobiological underpinnings of schizophrenia are yet unclear, many studies have reported aberrant neural connectivity in schizophrenia patients which may impact sensorimotor prediction and integration. Methods Recently, we have shown that introducing sensorimotor conflict (SMC) can induce psychosis like symptoms in healthy patients. Employing a master-slave robotic system we induced a conflict by introducing a delay between the participants’ movements and the haptic feedback. The SMC caused a feeling of a Presence (FoP) which is a first rank symptom of psychosis. The FoP is also found in neurological patients with lesions in cortical regions of the temporoparietal cortex, insular cortex and fronto-parietal cortex related to abnormal bodily self-representation. Here, we tested if SMC may cause misattribution of auditory stimuli and if this is related to neural connectivity. We tested first episode psychosis patients (N=31) with and without first rank symptoms (related to the sense of control over actions and thoughts) as well as healthy participants (N=20) on an auditory attribution task while inducing conflict with the master-slave robot. Results We found that when a SMC was introduced patients with first rank symptoms showed a decrease in their ability to judge if the auditory stimuli were in their own voice or the voice of another person. Resting state functional connectivity analysis indicated that the first rank patients had reduced connectivity in the network related to the SMC, but not in other control regions. Furthermore, the reduced functional connectivity correlated with the rates of auditory misattribution. Conclusions Our results show that induction of SMC can cause auditory misattributions, and that this is related to reduced cortical communication in regions related to sensorimotor body representation. These findings connect two influential theories of psychosis linking cognitive theories of sensorimotor prediction error in schizophrenia with systems level theories of neural disconnectivity. Understanding these neurocognitive mechanisms underlying the disruption of the self-model in psychosis may allow novel approaches in early diagnosis and treatment of these conditions.

Common increased hippocampal volume but specific changes in functional connectivity in schizophrenia patients in remission and non-remission following electroconvulsive therapy: A preliminary study.

Electroconvulsive therapy (ECT) is considered a treatment option in patients with drug-resistant schizophrenia (SZ). However, approximately one-third of patients do not benefit from ECT in the clinic. Thus, it is critical to investigate differences between ECT responders and non-responders. Accumulated evidence has indicated that one region of ECT action is the hippocampus, which also plays an important role in SZ pathophysiology. To date, no studies have investigated differences in ECT effects in the hippocampus between treatment responders and non-responders. This study recruited twenty-one SZ patients treated for four weeks with ECT (MSZ, n = 21) and twenty-one SZ patients who received pharmaceutical therapy (DSZ, n = 21). The MSZ group was further categorized into responders (MSR, n = 10) or non-responders (MNR, n = 11) based on treatment outcomes by the criterion of a 50% reduction in the Positive and Negative Syndrome Scale total scores. Using structural and resting-state functional MRI, we measured the hippocampal volume and functional connectivity (FC) in all SZ patients (before and after treatment) and 23 healthy controls. In contrast to pharmaceutical therapy, ECT induced bilateral hippocampal volume increases in the MSZ. Both the MSR and MNR exhibited hippocampal expansion after ECT, whereas a lower baseline volume in one of hippocampal subfield (hippocampus-amygdala transition area) was found in the MNR. After ECT, increased FC between the hippocampus and brain networks associated with cognitive function was only observed in the MSR. The mechanism of action of ECT in schizophrenia is complex. A combination of baseline impairment level, ECT-introduced morphological changes and post-ECT FC increases in the hippocampus may jointly contribute to the post-ECT symptom improvements in patients with SZ.

An approach to directly link ICA and seed-based functional connectivity: Application to schizophrenia

Independent component analysis (ICA) and seed-based analyses are widely used techniques for studying intrinsic neuronal activity in task-based or resting scans. In this work, we show there is a direct link between the two, and show that there are some important differences between the two approaches in terms of what information they capture. We developed an enhanced connectivity-matrix independent component analysis (cmICA) for calculating whole brain voxel maps of functional connectivity, which reduces the computational complexity of voxel-based connectivity analysis on performing many temporal correlations. We also show there is a mathematical equivalency between parcellations on voxel-to-voxel functional connectivity and simplified cmICA. Next, we used this cost-efficient data-driven method to examine the resting state fMRI connectivity in schizophrenia patients (SZ) and healthy controls (HC) on a whole brain scale and further quantified the relationship between brain functional connectivity and cognitive performances measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery. Current results suggest that SZ exhibit a wide-range abnormality, primarily a decrease, in functional connectivity both between networks and within different network hubs. Specific functional connectivity decreases were associated with MATRICS performance deficits. In addition, we found that resting state functional connectivity decreases was extensively associated with aging regardless of groups. In contrast, there was no relationship between positive and negative symptoms in the patients and functional connectivity. In sum, we have developed a novel mathematical relationship between ICA and seed-based connectivity that reduces computational complexity, which has broad applicability, and showed a specific application of this approach to characterize connectivity changes associated with cognitive scores in SZ.

Impaired cortico-limbic functional connectivity in schizophrenia patients during emotion processing.

Functional dysconnection is increasingly recognized as a core pathological feature in schizophrenia. Aberrant interactions between regions of the cortico-limbic circuit may underpin the abnormal emotional processing associated with this illness. We used a functional magnetic resonance imaging paradigm designed to dissociate the various components of the cortico-limbic circuit (i.e. a ventral automatic circuit that is intertwined with a dorsal cognitive circuit), to explore bottom-up appraisal as well as top-down control during emotion processing. In schizophrenia patients compared with healthy controls, bottom-up processes were associated with reduced interaction between the amygdala and both the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex. Contrariwise, top-down control processes led to stronger connectivity between the ventral affective and the dorsal cognitive circuits, i.e. heightened interactions between the ventral ACC and the dorsolateral prefrontal cortex as well as between dorsal and ventral ACC. These findings offer a comprehensive view of the cortico-limbic dysfunction in schizophrenia. They confirm previous results of impaired propagation of information between the amygdala and the prefrontal cortex and suggest a defective functional segregation in the dorsal cognitive part of the cortico-limbic circuit.

422. Fronto-Parietal Effective Connectivity in Schizophrenia Patients and Participants with Subclinical Delusional Ideation

422. Fronto-Parietal Effective Connectivity in Schizophrenia Patients and Participants with Subclinical Delusional Ideation

Decreased hemispheric connectivity and decreased intra- and inter- hemisphere asymmetry of resting state functional network connectivity in schizophrenia.

Many studies have shown that schizophrenia patients have aberrant functional network connectivity (FNC) among brain regions, suggesting schizophrenia manifests with significantly diminished (in majority of the cases) connectivity. Schizophrenia is also associated with a lack of hemispheric lateralization. Hoptman et al. (2012) reported lower inter-hemispheric connectivity in schizophrenia patients compared to controls using voxel-mirrored homotopic connectivity. In this study, we merge these two points of views together using a group independent component analysis (gICA)-based approach to generate hemisphere-specific timecourses and calculate intra-hemisphere and inter-hemisphere FNC on a resting state fMRI dataset consisting of age- and gender-balanced 151 schizophrenia patients and 163 healthy controls. We analyzed the group differences between patients and healthy controls in each type of FNC measures along with age and gender effects. The results reveal that FNC in schizophrenia patients shows less hemispheric asymmetry compared to that of the healthy controls. We also found a decrease in connectivity in all FNC types such as intra-left (L_FNC), intra-right (R_FNC) and inter-hemisphere (Inter_FNC) in the schizophrenia patients relative to healthy controls, but general patterns of connectivity were preserved in patients. Analyses of age and gender effects yielded results similar to those reported in whole brain FNC studies.

Abnormalities of localized connectivity in schizophrenia patients and their unaffected relatives: a meta-analysis of resting-state functional magnetic resonance imaging studies.

ObjectiveThe localized dysfunction of specialized brain regions in schizophrenia patients and their unaffected relatives has been identified in a large-scale brain network; however, evidence is inconsistent. We aimed to identify abnormalities in the localized connectivity in schizophrenia patients and their relatives by conducting a meta-analysis of regional homogeneity (ReHo) studies.MethodsFourteen studies on resting-state functional magnetic resonance imaging, with 316 schizophrenia patients, 342 healthy controls, and 66 unaffected relatives, were included in the meta-analysis. This analysis was performed using anisotropic effect-size-based signed differential mapping software.ResultsSchizophrenia patients showed increased ReHo in right superior frontal gyrus and right superior temporal gyrus, as well as decreased ReHo in left fusiform gyrus, left superior temporal gyrus, left postcentral gyrus, and right precentral gyrus. Unaffected relatives showed decreased ReHo in right insula and right superior temporal gyrus. These results remained widely unchanged in both sensitivity and subgroup analyses.ConclusionSchizophrenia patients and their unaffected relatives had extensive abnormal localized connectivity in cerebrum, especially in superior temporal gyrus, which were the potential diagnostic markers and expounded the pathophysiological hypothesis for the disorder.

Cross-Frequency rs-fMRI Network Connectivity Patterns Manifest Differently for Schizophrenia Patients and Healthy Controls.

Patterns of resting state fMRI functional network connectivity in schizophrenia patients have been shown to differ markedly from that of healthy controls. While some studies have explored connectivity within fixed frequency bands, the question of network phase synchrony across disparate frequency bands, or cross-frequency connectivity, has remained surprisingly underexplored. Computational modeling at the neuronal scale however has long acknowledged the existence of coupled fast and slow subsystems. Here we present preliminary evidence that cross-frequency coupling exists at the network level, that it patterns in meaningful ways over functional domains, and that this patterning differs between the healthy population and individuals with diagnosed schizophrenia.

Disturbed macro-connectivity in schizophrenia linked to oligodendrocyte dysfunction: from structural findings to molecules.

Schizophrenia is a severe psychiatric disorder with multi-factorial characteristics. A number of findings have shown disrupted synaptic connectivity in schizophrenia patients and emerging evidence suggests that this results from dysfunctional oligodendrocytes, the cells responsible for myelinating axons in white matter to promote neuronal conduction. The exact cause of this is not known, although recent imaging and molecular profiling studies of schizophrenia patients have identified changes in white matter tracts connecting multiple brain regions with effects on protein signaling networks involved in the myelination process. Further understanding of oligodendrocyte dysfunction in schizophrenia could lead to identification of novel drug targets for this devastating disease.

Connectivity-based whole brain dual parcellation by group ICA reveals tract structures and decreased connectivity in schizophrenia.

Mapping brain connectivity based on neuroimaging data is a promising new tool for understanding brain structure and function. In this methods paper, we demonstrate that group independent component analysis (GICA) can be used to perform a dual parcellation of the brain based on its connectivity matrix (cmICA). This dual parcellation consists of a set of spatially independent source maps, and a corresponding set of paired dual maps that define the connectivity of each source map to the brain. These dual maps are called the connectivity profiles of the source maps. Traditional analysis of connectivity matrices has been used previously for brain parcellation, but the present method provides additional information on the connectivity of these segmented regions. In this paper, the whole brain structural connectivity matrices were calculated on a 5 mm(3) voxel scale from diffusion imaging data based on the probabilistic tractography method. The effect of the choice of the number of components (30 and 100) and their stability were examined. This method generated a set of spatially independent components that are consistent with the canonical brain tracts provided by previous anatomic descriptions, with the high order model yielding finer segmentations. The corpus-callosum example shows how this method leads to a robust parcellation of a brain structure based on its connectivity properties. We applied cmICA to study structural connectivity differences between a group of schizophrenia subjects and healthy controls. The connectivity profiles at both model orders showed similar regions with reduced connectivity in schizophrenia patients. These regions included forceps major, right inferior fronto-occipital fasciculus, uncinate fasciculus, thalamic radiation, and corticospinal tract. This paper provides a novel unsupervised data-driven framework that summarizes the information in a large global connectivity matrix and tests for brain connectivity differences. It has the potential for capturing important brain changes related to disease in connectivity-based disorders.

Reduced default mode network connectivity in schizophrenia patients

In the present study, we explored possible alterations in the default mode network (DMN) and its functional connectivity in 41 schizophrenia patients and 42 age-matched healthy controls. Schizophrenia patients displayed reduced activation in the ventromedial prefrontal cortex, left superior temporal gyrus including auditory cortex and temporal pole. Psychophysiological interaction analysis revealed reduced connectivity between left superior temporal gyrus including auditory cortex and the left temporal pole in schizophrenia patients compared to healthy subjects.

A splitting brain: Imbalanced neural networks in schizophrenia

Dysconnectivity between key brain systems has been hypothesized to underlie the pathophysiology of schizophrenia. The present study examined the pattern of functional dysconnectivity across whole-brain neural networks in 121 first-episode, treatment-naïve patients with schizophrenia by using resting-state functional magnetic resonance imaging (rsfMRI). Group independent component analysis (ICA) was first applied to rsfMRI data to extract 90 functional components of the brain. The functional connectivity between these ICA components was then evaluated and compared between the patient and control groups. To examine the functional roles of significantly altered between-component connections in patients, each ICA component was ascribed to one of 10 previously well-defined brain networks/areas. Relative to findings in healthy controls (n=103), 29 altered functional connections including 19 connections with increased connectivity and 10 connections with decreased connectivity in schizophrenia patients were found. Increased connectivity was mainly within the default mode network (DMN) and between the DMN and cognitive networks, whereas decreased connectivity was predominantly associated with sensory networks. Given the key roles of the DMN in internal mental processes and sensory networks in inputs from the external environment, these patterns of altered brain network connectivity could suggest imbalanced neural processing of internal and external information in schizophrenia.

Abnormal asymmetry of brain connectivity in schizophrenia.

Recently, a growing body of data has revealed that beyond a dysfunction of connectivity among different brain areas in schizophrenia patients (SCZ), there is also an abnormal asymmetry of functional connectivity compared with healthy subjects. The loss of the cerebral torque and the abnormalities of gyrification, with an increased or more complex cortical folding in the right hemisphere may provide an anatomical basis for such aberrant connectivity in SCZ. Furthermore, diffusion tensor imaging studies have shown a significant reduction of leftward asymmetry in some key white-matter tracts in SCZ. In this paper, we review the studies that investigated both structural brain asymmetry and asymmetry of functional connectivity in healthy subjects and SCZ. From an analysis of the existing literature on this topic, we can hypothesize an overall generally attenuated asymmetry of functional connectivity in SCZ compared to healthy controls. Such attenuated asymmetry increases with the duration of the disease and correlates with psychotic symptoms. Finally, we hypothesize that structural deficits across the corpus callosum may contribute to the abnormal asymmetry of intra-hemispheric connectivity in schizophrenia.