Functional Connectivity In Schizophrenia Research Articles

T135. ABERRANT EXECUTIVE CONTROL AND AUDITORY NETWORKS IN RECENT-ONSET SCHIZOPHRENIA - A GROUP ICA DUAL REGRESSION ANALYSIS

BackgroundA great number of studies using resting-state functional MRI (rsfMRI) have been conducted for revealing altered functional connectivity in schizophrenia. Although the default mode network has been predominantly investigated, other resting-state networks (RSNs) can be networks of interest for unveiling the neurobiological basis of schizophrenia. Our study investigated changes in functional connectivity in the nine RSNs in recent-onset schizophrenia.MethodsWe performed a rsfMRI in 46 patients with recent-onset schizophrenia and 22 healthy controls. In the preprocessing steps, independent component analysis (ICA)-based automatic removal of motion artifacts was applied to eliminate motion-related components from an individual-level ICA. Group ICA and dual regression were performed for voxel-wise comparisons between the groups with the non-parametric permutation test using threshold-free cluster enhancement and a corrected-p < 0.05 for multiple comparisons. We used the Positive and Negative Syndrome Scale scores for the correlation analysis of symptom severity with functional connectivity in the patient group.ResultsThe control group had areas with a significant group difference in activity compared to that of the patient group in which it existed in the left supplementary motor cortex and supramarginal gyrus (the executive control network) and the right postcentral gyrus (the auditory network). There were no significant correlations of symptom severity with the functional connectivity of these regions.DiscussionThe left supplementary motor cortex, supramarginal gyrus, and right postcentral gyrus having areas with a significant group difference may have a role in the pathophysiology of schizophrenia, given their language and auditory information processing functions.

The Role of Sex Differences in Cortico-Striatal Functional Connectivity in Schizophrenia

The Role of Sex Differences in Cortico-Striatal Functional Connectivity in Schizophrenia

The Role of Hippocampal Functional Connectivity on Multisystem Subclinical Abnormalities in Schizophrenia.

Schizophrenia is associated with excess medical mortality: patients have an average life expectancy one to two decades shorter than the general population. This study investigates the relationship between aberrant hippocampal resting-state functional connectivity in schizophrenia and cumulative subclinical effects of chronic stress on metabolic, cardiovascular, and immune function using the allostatic load index. Cumulative stress was estimated using allostatic load total score (range, 0-13) in 46 patients with schizophrenia and 31 controls matched for age and sex (patients: age = 36.1 [13.7] years, sex = 32/14 male/female; controls: age = 35.5 [14.1], sex = 21/10 male/female). Hippocampal functional connectivity was assessed using resting-state functional magnetic resonance imaging; hippocampal structural connectivity was assessed using fornix fractional anisotropy. Linear regression analysis was used a) to test the hypothesis that aberrant hippocampal resting-state functional connectivity in schizophrenia (identified in analysis of schizophrenia - control differences) is associated with elevated allostatic load scores in patients and b) to determine the association between fornix fractional anisotropy with allostatic load. In patients, higher allostatic load was significantly associated with reduced resting functional connectivity between the left hippocampus and right cingulate cortex and left precentral gyrus, but higher connectivity between the right hippocampus and left cerebellum lobe VI (corrected p values <. 05). In controls, reductions in both hippocampal structural connectivity and hippocampal-cingulate functional connectivity were associated with higher allostatic load scores. These findings support basic neuroscience evidence that cumulative stress and hippocampal function are closely connected and suggest that abnormal hippocampal functional communication in schizophrenia may be related to elevated multisystem subclinical medical issues in patients as indexed by allostatic load.

One-Year Stability of Frontoparietal Cognitive Control Network Connectivity in Recent Onset Schizophrenia: A Task-Related 3T fMRI Study.

Kraepelinian theory posits that schizophrenia (SZ) is a degenerative disorder that worsens throughout the lifespan. Behavioral studies of cognition have since challenged that viewpoint, particularly in the early phases of illness. Nonetheless, the extent to which cognition remains functionally stable during the early course of illness is unclear, particularly with regard to task-associated connectivity in cognition-related brain networks. In this study, we examined the 1-year stability of the frontoparietal control network during the AX-Continuous Performance Task (AX-CPT) from a new baseline sample of 153 participants scanned at 3T, of which 29 recent onset individuals with SZ and 42 healthy control (HC) participants had follow-up data available for analysis. Among individuals that had both baseline and follow-up data, reduced functional connectivity in SZ was observed between the dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex (SPC) during the high control (B cue) condition. Furthermore, this deficit was stable over time, as no significant time × diagnosis interaction or effects of time were observed and intraclass correlation coefficients were greater than 0.6 in HCs and SZ. Previous 1.5T findings showing stable deficits with no evidence of degeneration in performance or DLPFC activation in an independent SZ sample were replicated. Overall, these results suggest that the neuronal circuitry supporting cognitive control is stably impaired during the early course of illness in SZ across multiple levels of analysis with no evidence of functional decline.

Distinct hemispheric specialization of functional connectivity in schizophrenia with and without auditory verbal hallucinations.

As a basic organizing principle of the human brain, hemispheric specialization is an important perspective to explore the pathology of schizophrenia. However, it remains unclearly whether the hemispheric specialization of functional connectivity plays a role in mediating auditory verbal hallucinations in schizophrenia. In this study, 18 schizophrenic patients with auditory verbal hallucinations, 18 patients without auditory verbal hallucinations, and 18 matched healthy controls underwent resting-state functional MRI scans, and seed-based voxel-wise functional connectivity was calculated to quantify the degree of hemispheric specialization. The results revealed that both the auditory verbal hallucinations and non-auditory verbal hallucinations groups exhibited significantly increased specialization in the left middle temporal gyrus and left precuneus, and significantly reduced specialization in the right precuneus relative to healthy controls, and that the auditory verbal hallucinations severity was significantly correlated with the hemispheric specialization of the right precuneus in the auditory verbal hallucinations group. Moreover, the left frontal lobe exhibited reduced hemispheric specialization in the auditory verbal hallucinations group compared with non-auditory verbal hallucinations group, and the patients with and without auditory verbal hallucinations could be clustered into two groups with an accuracy of 80.6% based on the brain regions exhibiting significant specialization changes. The findings indicate that the hemispheric specialization of the aforementioned regions may play a role in mediating auditory verbal hallucinations in schizophrenia, and the distinct hemispheric specialization patterns of functional connectivity may provide a potential biomarker to differentiate schizophrenic patients with and without auditory verbal hallucinations.

Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia

RationaleThere is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce.ObjectivesThe aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC).MethodsIn a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions.ResultsCompared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6).ConclusionsThese findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.

Association between NRGN gene polymorphism and resting-state hippocampal functional connectivity in schizophrenia

BackgroundBased on genome-wide association studies, a single-nucleotide polymorphism in the NRGN gene (rs12807809) is considered associated with schizophrenia (SZ). Moreover, hippocampal dysfunction is associated with rs12807809. In addition, converging evidence suggests that hippocampal dysfunction is involved in SZ pathophysiology. However, the association among rs12807809, hippocampal dysfunction and SZ pathophysiology is unknown. Therefore, this study investigated the association between rs12807809 and hippocampal functional connectivity at rest in SZ.MethodsIn total, 158 participants were studied, including a C-carrier group carrying the non-risk C allele (29 SZ patients and 46 healthy controls) and a TT homozygous group carrying the risk T allele (30 SZ patients and 53 healthy controls). All participants were scanned using resting-state functional magnetic resonance imaging. Hippocampal functional connectivity was computed and compared among the 4 groups.ResultsSignificant main effects of diagnosis were observed in the functional connectivity between the hippocampus and bilateral fusiform gyrus, bilateral lingual gyrus, left inferior temporal gyrus, left caudate nucleus, bilateral thalamus and bilateral anterior cingulate gyri. In contrast, no significant main effect of genotype was found. In addition, a significant genotype by diagnosis interaction in the functional connectivity between the hippocampus and left anterior cingulate gyrus, as well as bilateral middle cingulate gyri, was observed, with TT homozygotes with SZ showing less functional connectivity than C-carriers with SZ and healthy control TT homozygotes.ConclusionsThese findings are the first to suggest an association between rs12807809 and abnormal Papez circuit function in patients with SZ. This study also implicates NRGN variation and abnormal Papez circuit function in SZ pathophysiology.

Dynamic functional connectivity in schizophrenia and autism spectrum disorder: Convergence, divergence and classification.

BackgroundOver the recent years there has been a growing debate regarding the extent and nature of the overlap in neuropathology between schizophrenia (SZ) and autism spectrum disorder (ASD). Dynamic functional network connectivity (dFNC) is a recent analysis method that explores temporal patterns of functional connectivity (FC). We compared resting-state dFNC in SZ, ASD and healthy controls (HC), characterized the associations between temporal patterns and symptoms, and performed a three-way classification analysis based on dFNC indices.MethodsResting-state fMRI was collected from 100 young adults: 33 SZ, 33 ASD, 34 HC. Independent component analysis (ICA) was performed, followed by dFNC analysis (window = 33 s, step = 1TR, k-means clustering). Temporal patterns were compared between groups, correlated with symptoms, and classified via cross-validated three-way discriminant analysis.ResultsBoth clinical groups displayed an increased fraction of time (FT) spent in a state of weak, intra-network connectivity [p < .001] and decreased FT in a highly-connected state [p < .001]. SZ further showed decreased number of transitions between states [p < .001], decreased FT in a widely-connected state [p < .001], increased dwell time (DT) in the weakly-connected state [p < .001], and decreased DT in the highly-connected state [p = .001]. Social behavior scores correlated with DT in the widely-connected state in SZ [r = 0.416, p = .043], but not ASD. Classification correctly identified SZ at high rates (81.8%), while ASD and HC at lower rates.ConclusionsResults indicate a severe and pervasive pattern of temporal aberrations in SZ (specifically, being “stuck” in a state of weak connectivity), that distinguishes SZ participants from both ASD and HC, and is associated with clinical symptoms.

Aberrant Frontostriatal Connectivity in Negative Symptoms of Schizophrenia.

Negative symptoms represent a distinct component of psychopathology in schizophrenia (SCZ) and are a stable construct over time. Although impaired frontostriatal connectivity has been frequently described in SCZ, its link with negative symptoms has not been carefully studied. We tested the hypothesis that frontostriatal connectivity at rest may be associated with the severity of negative symptoms in SCZ. Resting state functional connectivity (rsFC) data from 95 mostly medicated patients with SCZ and 139 healthy controls (HCs) were acquired. Negative symptoms were assessed using the Brief Negative Symptom Scale. The study analyzed voxel-wise rsFC between 9 frontal "seed regions" and the entire striatum, with the intention to reduce potential biases introduced by predefining any single frontal or striatal region. SCZ showed significantly reduced rsFC between the striatum and the right medial and lateral orbitofrontal cortex (OFC), lateral prefrontal cortex, and rostral anterior cingulate cortex compared with HCs. Further, rsFC between the striatum and the right medial OFC was significantly associated with negative symptom severity. The involved striatal regions were primarily at the ventral putamen. Our results support reduced frontostriatal functional connectivity in SCZ and implicate striatal connectivity with the right medial OFC in negative symptoms. This task-independent resting functional magnetic resonance imaging study showed that medial OFC-striatum functional connectivity is reduced in SCZ and associated with severity of negative symptoms. This finding supports a significant association between frontostriatal connectivity and negative symptoms and thus may provide a potential circuitry-level biomarker to study the neurobiological mechanisms of negative symptoms.

Insula Functional Connectivity in Schizophrenia: Subregions, Gradients, and Symptoms

BackgroundThe insular cortex is connected to a diverse network of cortical and subcortical areas. This study aimed to investigate whether the diversity in functional connectivity across the insula’s topography is altered in individuals with schizophrenia and relates to the clinical symptoms of the disorder. MethodsInsula-to-whole-brain functional connectivity was mapped using resting-state functional magnetic resonance imaging at the resolution of voxels in individuals with schizophrenia (n = 49) and healthy comparison individuals (n = 52). Diversity in functional connectivity across the insula’s topography was represented as discrete subregions and gradients of continuous variation. Canonical correlation analysis was used to relate interindividual variation in insula connectivity to clinical symptoms. ResultsInsula connectional diversity was parcellated into two subregions: dorsoanterior and ventroposterior. Compared with the healthy comparison group, subjects with schizophrenia were associated with an overall reduction in insula functional connectivity as well as reduced differentiation in connectivity profiles between these subregions. A significant interaction effect between diagnosis and insula subregion indicated that the anterior subregion in schizophrenia was connected with increased strength to the somatosensory, motor, occipital, and parietal cortices, whereas the posterior subregion showed increased connectivity with the thalamus and prefrontal cortex. Insula connectivity with the anterior cingulate and auditory cortices was significantly associated with cognitive impairment, negative symptoms, poor psychosocial functioning, and longer duration of illness (r = .64, p = .03). ConclusionsDiversity in functional connectivity across the insula’s rostrocaudal axis is reduced in schizophrenia, resulting in reduced differentiation between anterior and posterior insula. Interindividual variation in insula connectivity explains variability in some of the clinical symptoms of schizophrenia.

Nicotine in action: cigarette smoking modulated homotopic functional connectivity in schizophrenia.

Cigarette smoking is intimately associated with both early onset and increased severity of schizophrenia. The self-medication hypothesis suggests that nicotine can relieve or restore neurocognitive deficits and symptoms associated with schizophrenia. Schizophrenia patients and healthy subjects who smoked showed deficits in communication between their hemispheres. These homotopic connectivity mechanisms associated with both schizophrenia and smoking comorbidity were largely unknown until now. A mixed sample including patients with schizophrenia (22 smokers and 27 non-smokers) and healthy controls (22 smokers and 21 non-smokers) based on clinical diagnoses and cigarette dependence were recruited for the current study. All subjects underwent resting-state functional magnetic resonance imaging to determine possible interactions between schizophrenia and smoking, and to determine the main effects of schizophrenia and smoking on homotopic functional connectivity. Decreased homotopic functional connectivity of the subgenual anterior cingulate cortex suggested a main effect of schizophrenia and smoking-an additive effect. Furthermore, we found an antagonistic interaction effect between schizophrenia and smoking located in the ventrolateral prefrontal cortex (VLPFC). In addition, the connectivity strength of the bilateral VLPFC was negatively correlated with the Positive and Negative Syndrome Scale Negative scores and positively correlated with lifetime smoking. These results suggest that smoking has multiple effects on the modulation of interhemispheric connectivity in schizophrenia. Our findings provide valuable information underlying the pathophysiological mechanisms of schizophrenia and offer a potential target for future clinical treatment of schizophrenia and smoking comorbidity.

Addendum: Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry

Addendum: Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry

Anterior Cingulate Glutamate and GABA Associations on Functional Connectivity in Schizophrenia.

The underlying neurobiological mechanism for abnormal functional connectivity in schizophrenia (SCZ) remains unknown. This project investigated whether glutamate and GABA, 2 metabolites that contribute to excitatory and inhibitory functions, may influence functional connectivity in SCZ. Resting-state functional magnetic resonance imaging and proton magnetic resonance spectroscopy were acquired from 58 SCZ patients and 61 healthy controls (HC). Seed-based connectivity maps were extracted between the anterior cingulate cortex (ACC) spectroscopic voxel and all other brain voxels. Magnetic resonance spectroscopy (MRS) spectra were processed to quantify glutamate and GABA levels. Regression analysis was performed to describe relationships between functional connectivity and glutamate and GABA levels. Reduced ACC functional connectivity in SCZ was found in regions associated with several neural networks including the default mode network (DMN) compared to HC. In the HC, positive correlations were found between glutamate and both ACC-right inferior frontal gyrus functional connectivity and ACC-bilateral superior temporal gyrus functional connectivity. A negative correlation between GABA and ACC-left posterior cingulate functional connectivity was also observed in HC. These same relationships were not statistically significant in SCZ. The present investigation is one of the first studies to examine links between functional connectivity and glutamate and GABA levels in SCZ. Results indicate that glutamate and GABA play an important role in the functional connectivity modulation in the healthy brain. The absence of glutamate and GABA correlations in areas where SCZ showed significantly reduced functional connectivity may suggest that this chemical-functional relationship is disrupted in SCZ.

T224. THE FUNCTIONAL CONNECTIVITY DERIVED WITH BIVARIATE ANALYSIS, COHERENCE AND PHASE LOCKING VALUE IN PATIENTS WITH SCHIZOPHRENIA UNDER CLOZAPINE

BackgroundCoherence (COH) and Phase Locking Value (PLV) may have considerable potentials for investigating anomalies of functional connectivity in schizophrenia but results are still conflicting. This study is aimed to investigate relationships between plasma levels of clozapine (p-CZP) and norclozapine (p-NCZP), and total and cognitive factor scores of Positive and Negative Syndrome Scale (PANSS-T, -C), and functional connectivity by COH and PLV.MethodsFifty-eight patients who were diagnosed as schizophrenia with DSM-5 criteria and under CZP were recruited (duration of illness, 15.5 ± 8.0 years; duration of CZP, 6.8 ± 4.6 years; mean daily dose of CZP, 233.6 ± 88.4 mg). COH and PLV were calculated with Neurophysiological Biomarker Toolbox from qEEG and were averaged from the signals of electrodes in the designated brain regions, frontal (F), temporal (T), central (C) and occipitoparietal (OP). For interhemispheric connectivity, electrodes except all midline channels were combined into Odd (O) and Even (E). The results were presented at ≥0.30 of Spearman correlation.Results1) Correlation coefficient between p-CZP and p-NCZP was 0.84, and those of CZP dose with p-CZP and p-NCZP were 0.38 and 0.53, respectively. 2) p-CZP showed correlations with OCEC in delta and alpha, OTEC in delta, OCEOP in theta, OTEF in alpha, and OOPEF in gamma band in COH, and OOPEOP in beta band in PLV. 3) p-NCZP showed correlations with ETEOP in delta, theta, and gamma, OCEC in delta and alpha, OFOC and OCEOP in delta, OFET and OTET in alpha, OCEF in beta, OOPEC in gamma band in COH, and with ETEOP in delta, theta, and beta, OTET and OCEC in alpha, OCEF in beta band in PLV. 4) CZP dose showed correlations with ETEC in beta and gamma, ETEOP in theta, OCEF in alpha, OTET in beta, OOPEF and OOPET in gamma band in COH, and with OTET in alpha and beta, ETEOP in theta, OTEOP in alpha, ETEC in beta, OFOC in gamma band in PLV. 5) PANSS-T showed correlations with OFEOP and EFEOP in alpha, OCEOP in beta, OTOC and OTEF in gamma band in COH, and with OTEF in beta and gamma, OFET in delta, OOPEF in beta, OTOC and OCEOP in gamma band in PLV. 6) PANSS-C showed correlations with EFEOP in delta, theta, alpha, and beta, OOPEOP in delta, alpha, and beta, OFET and OTEF both in alpha and beta, OOPEF in delta, OFEOP in alpha, OFEC and OCEOP in beta, OTOC in gamma band in COH, and with EFEOP in theta, alpha, and beta, OFEOP and OOPEOP both in alpha and beta, OFET in delta and beta, OTOC, OOPEF, OOPEOP in beta, OTOC and OCEOP in PLV. 7) PANSS-T and -C showed no correlations with p-CZP, p-NCZP and CZP dose. 8) However, the clinical and drug variables showed significant simultaneous correlation with certain functional connectivity, but sometimes the direction correlation was opposite.DiscussionThe relationship between functional connectivity and clozapine parameters seems to demonstrate inter- and intra-hemispheric connections in brain regions. However, there were same and/or opposite directions of correlations between COH and PLV dependent EEG band frequencies and clinical and drug variables. Taken together, investigating the functional connectivity with COH and PLV could give the information about p-CZP and p-NCZP before the laboratory reports, the degree of psychopathology in patients with schizophrenia under CZP, and the differentiations of surface symptoms whether derived from pathophysiology of schizophrenia or from clozapine effects.

2. MICROCIRCUITS, MACROCIRCUITS, AND CORTICOL DYSFUNCTION IN SCHIZOPHRENIA: A COMPUTATIONAL AND TRANSLATIONAL NEUROSCIENCE PERSPECTIVE

Overall : Computational neuroscience may be a critical component of the effort to understand how cortical micro- and macro-circuits support behavior and express the symptoms of neuropsychiatric disorders. This presentation will present an update on an ongoing interdisciplinary effort to understand the role of compromised glutamate synaptic signaling, particularly related to the NMDA glutamate receptor, for the pathophysiology of schizophrenia. This presentation will draw on studies in animal models, healthy humans, and schizophrenia patients. It will draw parallels between the effects of the NMDA receptor antagonist, ketamine, and working memory impairment and abnormalities in cortical functional connectivity in schizophrenia. In so doing, it will highlight examples where computational approaches have affirmed hypotheses arising from experimental work or contributed new predictions that could be tested experimentally. Lastly, it will illustrate a prediction about novel therapeutics for schizophrenia that are embedded in an emerging developmental model for this disorder.

T140. RESTING STATE NETWORKS ALTERATION IN SCHIZOPHRENIA

BackgroundWhile functional MRI and PET studies have shown altered task-related brain activity in schizophrenia, recent studies suggest that such differences might also be found in the resting state (RS). Here we used ICA based analysis to investigate RS fMRI data to compare connectivity of 11 well known networks (Auditory, Cerebellum, DMN, Exectutive Control, Fronto-parietal 1, Fronto-parietal 2, Salience, Sensorimotor, Visual1, Visual2, Visual3 network) between patients with schizophrenia and healthy controls suggesting deficits in related neuropsychological functions.MethodsWe obtained RS fMRI series (3T, 3x3x3mm resolution, 45 slices, TR 2.55s, 210 volumes) in 25 schizophrenia patients (mean age 30a±7.3), on stable antipsychotic medication and 25 matched healthy controls (30.3a±8.6). Subjects were asked to lie in the scanner keeping eyes closed with no further specific instructions. Data were pre-processed; we applied FSL MELODIC (pICA) yielding IC, we used FIX to auto-classify ICA components which represent artifacts and an automated routine to select for each subject the component matching the anatomical definition of resting state networks. SPM12 was used for second level analysis, we used two sample t-test to compare networks functional connectivity between groups. We then analysed the power spectrum density (PSD) for the extracted networks, estimating the power of the signal at different frequencies.ResultsOur method reliably identified all networks in every control and patients. We found significant differences in the anatomical pattern of areas. Patients showed decreased functional connectivity in comparison to healthy controls in portions of Cerebellum, DMN, Executive Control, Fronto-parietal1 and sensorimotor networks; in addition patients showed increased functional connectivity in comparison to healthy controls in portions of DMN network. Finally, PSD was found altered in patients with Schizophrenia when compared to healthy controls in Fronto-parietal1, Sensorimotor, visual1and visual2 networks.DiscussionWell known resting state networks were reliable identified from RS fMRI in Schizophrenia patients. The differences in anatomical distribution point to possible alterations in functional connectivity in Schizophrenia, which suggests disruption in Cerebellum, DMN, Executive control, Fronto-parietal and sensorimotor activity. The comparison of the PSD suggests changes in Fronto-parietal1, Sensorimotor and in addition visual1, visual2 networks.

Music Intervention Leads to Increased Insular Connectivity and Improved Clinical Symptoms in Schizophrenia.

Schizophrenia is a syndrome that is typically accompanied by delusions and hallucinations that might be associated with insular pathology. Music intervention, as a complementary therapy, is commonly used to improve psychiatric symptoms in the maintenance stage of schizophrenia. In this study, we employed a longitudinal design to assess the effects of listening to Mozart music on the insular functional connectivity (FC) in patients with schizophrenia. Thirty-six schizophrenia patients were randomly divided into two equal groups as follows: the music intervention (MTSZ) group, which received a 1-month music intervention series combined with antipsychotic drugs, and the no-music intervention (UMTSZ) group, which was treated solely with antipsychotic drugs. Resting-state functional magnetic resonance imaging (fMRI) scans were performed at the following three timepoints: baseline, 1 month after baseline and 6 months after baseline. Nineteen healthy participants were recruited as controls. An FC analysis seeded in the insular subregions and machine learning techniques were used to examine intervention-related changes. After 1 month of listening to Mozart music, the MTSZ showed increased FC in the dorsal anterior insula (dAI) and posterior insular (PI) networks, including the dAI-ACC, PI-pre/postcentral cortices, and PI-ACC connectivity. However, these enhanced FCs had vanished in follow-up visits after 6 months. Additionally, a support vector regression on the FC of the dAI-ACC at baseline yielded a significant prediction of relative symptom remission in response to music intervention. Furthermore, the validation analyses revealed that 1 month of music intervention could facilitate improvement of the insular FC in schizophrenia. Together, these findings revealed that the insular cortex could potentially be an important region in music intervention for patients with schizophrenia, thus improving the patients' psychiatric symptoms through normalizing the salience and sensorimotor networks.

Assessment of cerebral perfusional and functional connectivity in schizophrenia using magnetic resonance imaging

Schizophrenia is a significant mental disorder that compromises structural and functional aspects of the brain, with an extreme effect on the patient’s thoughts, feelings, and behavior. Physiologically, in addition to functional and structural abnormalities, changes in neuronal activity are reported. Since the cerebral blood flow (CBF) is directly related to neuronal activity, the magnetic resonance imaging (MRI) technique called arterial spin labeling (ASL), which allows the quantification of CBF, is a useful tool in brain perfusional evaluation. In addition, ASL can be used to assess functional connectivity, which is efficient in investigating functional impairment between regions of the brain. Pseudo-continuous arterial spin labeling (pCASL) images were acquired from 28 schizophrenia patients in treatment and 28 age-matched healthy controls. Static CBF and connectivity patterns were assessed. Decreased CBF and functional connectivity were observed in regions that forms two resting brain networks, default mode (DMN) and salience (SN), for schizophrenia patients. Previous studies related the features of this pathology with altered resting CBF and functional disconnections. Therefore, using a noninvasive technique, we were able to find CBF deficits and altered functional organization of the brain in schizophrenia patients that are associated with the symptoms and characteristics of the disorder.

Schizophrenia Shows Disrupted Links between Brain Volume and Dynamic Functional Connectivity.

Studies featuring multimodal neuroimaging data fusion for understanding brain function and structure, or disease characterization, leverage the partial information available in each of the modalities to reveal data variations not exhibited through the independent analyses. Similar to other complex syndromes, the characteristic brain abnormalities in schizophrenia may be better understood with the help of the additional information conveyed by leveraging an advanced modeling method involving multiple modalities. In this study, we propose a novel framework to fuse feature spaces corresponding to functional magnetic resonance imaging (functional) and gray matter (structural) data from 151 schizophrenia patients and 163 healthy controls. In particular, the features for the functional and structural modalities include dynamic (i.e., time-varying) functional network connectivity (dFNC) maps and the intensities of the gray matter (GM) maps, respectively. The dFNC maps are estimated from group independent component analysis (ICA) network time-courses by first computing windowed functional correlations using a sliding window approach, and then estimating subject specific states from this windowed data using temporal ICA followed by spatio-temporal regression. For each subject, the functional data features are horizontally concatenated with the corresponding GM features to form a combined feature space that is subsequently decomposed through a symmetric multimodal fusion approach involving a combination of multiset canonical correlation analysis (mCCA) and joint ICA (jICA). Our novel combined analyses successfully linked changes in the two modalities and revealed significantly disrupted links between GM volumes and time-varying functional connectivity in schizophrenia. Consistent with prior research, we found significant group differences in GM comprising regions in the superior parietal lobule, precuneus, postcentral gyrus, medial/superior frontal gyrus, superior/middle temporal gyrus, insula and fusiform gyrus, and several significant aberrations in the inter-regional functional connectivity strength as well. Importantly, structural and dFNC measures have independently shown changes associated with schizophrenia, and in this work we begin the process of evaluating the links between the two, which could shed light on the illness beyond what we can learn from a single imaging modality. In future work, we plan to evaluate replication of the inferred structure-function relationships in independent partitions of larger multi-modal schizophrenia datasets.

Decreased functional connectivity in schizophrenia: The relationship between social functioning, social cognition and graph theoretical network measures

Schizophrenia is a complex disorder in which abnormalities in brain connectivity and social functioning play a central role. The aim of this study is to explore small-world network properties, and understand their relationship with social functioning and social cognition in the context of schizophrenia, by testing functional connectivity differences in network properties and its relation to clinical behavioral measures. Resting-state fMRI time series data were acquired from 23 patients diagnosed with schizophrenia and 23 healthy volunteers. The results revealed that patients with schizophrenia show significantly decreased connectivity between a range of brain regions, particularly involving connections among the right orbitofrontal cortex, bilateral putamen and left amygdala. Furthermore, topological properties of functional brain networks in patients with schizophrenia were characterized by reduced path length compared to healthy controls; however, no significant difference was found for clustering coefficient, local efficiency or global efficiency. Additionally, we found that nodal efficiency of the amygdala and the putamen were significantly correlated with the independence-performance subscale of social functioning scale (SFC), and Reading the Mind in the Eyes test; however, the correlations do not survive correction for multiple comparison. The current results help to clarify the relationship between social functioning deficits and topological brain measures in schizophrenia.