Network Analysis of Language Disorganization in Patients with Schizophrenia.
Ontology highlight
ABSTRACT:
SUBMITTER: Park SC
PROVIDER: S-EPMC7393296 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Network Analysis of Language Disorganization in Patients with Schizophrenia.
Park Seon Cheol SC Kim Kiwon K Jang Ok Jin OJ Yoon Hyung Jun HJ Jang Seung Ho SH Kim Sung Wan SW Lee Bong Ju BJ Park Jae Hong JH Lee Kang Uk KU Choi Joonho J
Yonsei medical journal 20200801 8
Language disorganization, an objective component of formal thought process abnormality, has been regarded as a core symptom of schizophrenia from an evolutionary psychopathology perspective. However, to the best of our knowledge, the network structure of language disorganization has rarely been examined in patients with schizophrenia. Thus, our preliminary study aimed to evaluate the network structure using the Clinical Language Disorder Rating Scale (CLANG) in 167 inpatients with schizophrenia. ...[more]
Similar Datasets
Project description:ObjectivesSchizophrenia is a mental illness that presents with thought disorders including delusions and disorganized speech. Thought disorders have been regarded as a consequence of the loosening of associations between semantic concepts since the term "schizophrenia" was first coined by Bleuler. However, a mechanistic account of this cardinal disturbance in terms of functional dysconnection has been lacking. To evaluate how aberrant semantic connections are expressed through brain activity, we characterized large-scale network structures of concept representations using functional magnetic resonance imaging (fMRI).Study designWe quantified various concept representations in patients' brains from fMRI activity evoked by movie scenes using encoding modeling. We then constructed semantic brain networks by evaluating the similarity of these semantic representations and conducted graph theory-based network analyses.Study resultsNeurotypical networks had small-world properties similar to those of natural languages, suggesting small-worldness as a universal property in semantic knowledge networks. Conversely, small-worldness was significantly reduced in networks of schizophrenia patients and was correlated with psychological measures of delusions. Patients' semantic networks were partitioned into more distinct categories and had more random within-category structures than those of controls.ConclusionsThe differences in conceptual representations manifest altered semantic clustering and associative intrusions that underlie thought disorders. This is the first study to provide pathophysiological evidence for the loosening of associations as reflected in randomization of semantic networks in schizophrenia. Our method provides a promising approach for understanding the neural basis of altered or creative inner experiences of individuals with mental illness or exceptional abilities, respectively.
| S-EPMC10016409 | biostudies-literature
Project description:In terms of thought disorder, the language of patients with schizophrenia itself could be a valuable resource. Some valuable studies on the language of patients with schizophrenia have been performed. However, most such studies have been confined to English-speaking countries, or at least those where Indo-European languages are spoken. Therefore, we investigated linguistic anomalies in the language of Korean patients with schizophrenia. Short texts written by 69 patients with schizophrenia from a single mental hospital and matched normal control participants were analyzed. We evaluated these texts in terms of semantic and syntactic errors. Then, we compared the error rates adjusted for text length between patients and normal control participants. We also divided the patients with schizophrenia into two groups by their duration of illness and compared these two groups to investigate the relationship between the duration of illness and linguistic anomalies. The patients with schizophrenia committed a total of 1.86 (2.52) semantic errors and 1.37 (1.79) syntactic errors per 100 characters, which were significantly more frequent than errors committed by normal control participants. Furthermore, there was a notably high number of semantic errors relative to syntactic errors in the language of patients with schizophrenia. Our study results are consistent with previous studies from English-speaking countries, implying that the linguistic anomalies of patients with schizophrenia are not confined to a single language. Because language is essential in mental function, further research on linguistic anomalies in patients with schizophrenia is recommended.
| S-EPMC9661510 | biostudies-literature
Project description:Schizophrenia is a severe and heritable brain disorder. Language impairment has been hypothesized to spur its onset and underlie the characteristic symptoms. In this study, we investigate whether altered topological pattern of the language processing brain network exists and could be a potential biomarker of schizophrenia. We hypothesized that both patients with schizophrenia and the genetic high risk population would show significantly weakened efficiencies of the network hubs for normal language processing, especially at left inferior frontal and bilateral temporal lobes.Language task-based fMRI data from 21 patients with schizophrenia, 22 genetic high risk subjects and 36 controls were analyzed. Graph theoretic and post hoc analyses of the fMRI data, and correlations between the functional network features and scores of language tests were carried out.Compared to controls, patients with schizophrenia and the high risk subjects showed significantly weakened network hubs in left inferior frontal and right fusiform gyri. A unique topology of super active and intercommunicating network hubs at left fusiform gyrus and right inferior/middle frontal gyri, which were associated with the behavioral language impairment was found in the patient group, compared to the high risk and control groups.Aberrant systems-level topology of language processing network, especially significantly weakened network hubs in left inferior frontal and right fusiform gyri, may serve as a candidate biomarker of schizophrenia. Supported by existing findings, the hyperactive left fusiform gyrus communicating with right frontal lobe might be the key neurophysiological component causing hallucinations in schizophrenia. These findings provided a new systems-level diagnostic target for the disorder.
| S-EPMC3463735 | biostudies-literature
Project description:Schizophrenia is a neurocognitive illness of synaptic and brain network-level dysconnectivity that often reaches a persistent chronic stage in many patients. Subtle language deficits are a core feature even in the early stages of schizophrenia. However, the primacy of language network dysconnectivity and language-related genetic variants in the observed phenotype in early stages of illness remains unclear. This study used two independent schizophrenia dataset consisting of 138 and 53 drug-naïve first-episode schizophrenia (FES) patients, and 112 and 56 healthy controls, respectively. A brain-wide voxel-level functional connectivity analysis was conducted to investigate functional dysconnectivity and its relationship with illness duration. We also explored the association between critical language-related genetic (such as FOXP2) mutations and the altered functional connectivity in patients. We found elevated functional connectivity involving Broca's area, thalamus and temporal cortex that were replicated in two FES datasets. In particular, Broca's area - anterior cingulate cortex dysconnectivity was more pronounced for patients with shorter illness duration, while thalamic dysconnectivity was predominant in those with longer illness duration. Polygenic risk scores obtained from FOXP2-related genes were strongly associated with functional dysconnectivity identified in patients with shorter illness duration. Our results highlight the criticality of language network dysconnectivity, involving the Broca's area in early stages of schizophrenia, and the role of language-related genes in this aberration, providing both imaging and genetic evidence for the association between schizophrenia and the determinants of language.
| S-EPMC7930279 | biostudies-literature
Project description:Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.
| S-EPMC9976988 | biostudies-literature
Project description:Although schizophrenia (SZ) represents a complex multiform psychiatric disorder, one of its most striking symptoms are auditory verbal hallucinations (AVH). While the neurophysiological origin of this pervasive symptom has been extensively studied, there is so far no consensus conclusion on the neural correlates of the vulnerability to hallucinate. With a network-based fMRI approach, following the hypothesis of altered hemispheric dominance (Crow, 1997), we expected that LN alterations might result in self-other distinction impairments in SZ patients, and lead to the distressing subjective experiences of hearing voices. We used the independent component analysis of resting-state fMRI data, to first analyze LN connectivity in three groups of participants: SZ patients with and without hallucinations (AVH/D+ and AVH/D-, respectively), and a matched healthy control (HC) group. Then, we assessed the fMRI fluctuations using additional analyses based on fractional Amplitude of Low Frequency-Fluctuations (fALFF), both at the network- and region of interest (ROI)-level. Specific LN nodes were recruited in the right hemisphere (insula and Broca homologous area) for AVH/D+ , but not for HC and AVH/D-, consistent with a left hemisphere deficit in AVH patients. The fALFF analysis at the ROI level showed a negative correlation between fALFF Slow-4 and P1 Delusions PANSS subscale and a positive correlation between the fALFF Slow-5 and P3 Hallucination PANSS subscale for AVH/D+ only. These effects were not a consequence of structural differences between groups, as morphometric analysis did not evidence any group differences. Given the role of language as an emerging property resulting from the integration of many high-level cognitive processes and the underlying cortical areas, our results suggest that LN features from fMRI connectivity and fluctuations can be a marker of neurophysiological features characterizing SZ patients depending on their vulnerability to hallucinate.
| S-EPMC10616281 | biostudies-literature
Project description:Background and hypothesisActive inference has become an influential concept in psychopathology. We apply active inference to investigate conceptual disorganization in first-episode schizophrenia. We conceptualize speech production as a decision-making process affected by the latent "conceptual organization"-as a special case of uncertainty about the causes of sensory information. Uncertainty is both minimized via speech production-in which function words index conceptual organization in terms of analytic thinking-and tracked by a domain-general salience network. We hypothesize that analytic thinking depends on conceptual organization. Therefore, conceptual disorganization in schizophrenia would be both indexed by low conceptual organization and reflected in the effective connectivity within the salience network.Study designWith 1-minute speech samples from a picture description task and resting state fMRI from 30 patients and 30 healthy subjects, we employed dynamic causal and probabilistic graphical models to investigate if the effective connectivity of the salience network underwrites conceptual organization.Study resultsLow analytic thinking scores index low conceptual organization which affects diagnostic status. The influence of the anterior insula on the anterior cingulate cortex and the self-inhibition within the anterior cingulate cortex are elevated given low conceptual organization (ie, conceptual disorganization).ConclusionsConceptual organization, a construct that explains formal thought disorder, can be modeled in an active inference framework and studied in relation to putative neural substrates of disrupted language in schizophrenia. This provides a critical advance to move away from rating-scale scores to deeper constructs in the pursuit of the pathophysiology of formal thought disorder.
| S-EPMC10031740 | biostudies-literature
Project description:Schizophrenia (SZ) is a widespread psychiatric disorder that is traditionally characterized by positive and negative symptoms. However, recent focus has shifted to cognitive deficits as a crucial aspect. The cerebellum, conventionally tied to motor coordination, is now recognized as pivotal in the pathophysiology of SZ cognitive impairments. Proposed disruptions in the cortico-cerebellar-thalamic-cortico circuit contribute to these deficits. Despite evidence of cerebellar abnormalities, within-cerebellum functional connectivity is often overlooked. This study explores spontaneous functional interactions within the cerebellum and their link to cognitive deficits in SZ. Using a multi-domain task battery (MDTB) parcellation, fMRI data from SZ patients and healthy controls were analyzed. Significant differences in cerebellar connectivity emerged, particularly in regions related to attention, language, and memory processing. Correlations between connectivity values and SZ symptomatology were identified. A post hoc analysis, considering the patients' hallucination vulnerability, revealed distinct connectivity patterns. Non-hallucinating and low-hallucinating SZ patients exhibited higher cerebellar connectivity than high-hallucinating patients, especially in language and motor control regions. These findings suggest a gradient of cerebellar connectivity alterations corresponding to hallucination vulnerability in SZ patients. This study offers novel insights into cerebellar impairments in SZ, highlighting the role of within-cerebellum connectivity in cognitive deficits. The observed connectivity patterns in language-related regions contribute to understanding language development and auditory verbal hallucinations in SZ.
| S-EPMC10968155 | biostudies-literature
Project description:Individuals with 22q11.2 Deletion Syndrome (22q11.2 DS) are a specific high-risk group for developing schizophrenia (SZ), schizoaffective disorder (SAD) and autism spectrum disorders (ASD). Several genes in the deleted region have been implicated in the development of SZ, e.g., PRODH and DGCR8. However, the mechanistic connection between these genes and the neuropsychiatric phenotype remains unclear. To elucidate the molecular consequences of 22q11.2 deletion in early neural development, we carried out RNA-seq analysis to investigate gene expression in early differentiating human neurons derived from induced pluripotent stem cells (iPSCs) of 22q11.2 DS SZ and SAD patients.Eight cases (ten iPSC-neuron samples in total including duplicate clones) and seven controls (nine in total including duplicate clones) were subjected to RNA sequencing. Using a systems level analysis, differentially expressed genes/gene-modules and pathway of interests were identified. Lastly, we related our findings from in vitro neuronal cultures to brain development by mapping differentially expressed genes to BrainSpan transcriptomes.We observed ~2-fold reduction in expression of almost all genes in the 22q11.2 region in SZ (37 genes reached p-value?<?0.05, 36 of which reached a false discovery rate?<?0.05). Outside of the deleted region, 745 genes showed significant differences in expression between SZ and control neurons (p?<?0.05). Function enrichment and network analysis of the differentially expressed genes uncovered converging evidence on abnormal expression in key functional pathways, such as apoptosis, cell cycle and survival, and MAPK signaling in the SZ and SAD samples. By leveraging transcriptome profiles of normal human brain tissues across human development into adulthood, we showed that the differentially expressed genes converge on a sub-network mediated by CDC45 and the cell cycle, which would be disrupted by the 22q11.2 deletion during embryonic brain development, and another sub-network modulated by PRODH, which could contribute to disruption of brain function during adolescence.This study has provided evidence for disruption of potential molecular events in SZ patient with 22q11.2 deletion and related our findings from in vitro neuronal cultures to functional perturbations that can occur during brain development in SZ.
| S-EPMC5111260 | biostudies-other
Project description:This study aimed to shed light on the linguistic style affecting the communication discourse in first-episode schizophrenia (FES) by investigating the analytic thinking index in relation to clinical scores of conceptual and thought disorganization (Positive and Negative Syndrome Scale, PANSS-P2 and Thought and Language Index, TLI). Using robust Bayesian modeling, we report three major findings: (1) FES subjects showed reduced analytic thinking, exhibiting a less categorical linguistic style than healthy control (HC) subjects (Bayes factor, BF10 > 1000), despite using the same proportion of function and content words as HCs; (2) the lower the analytic thinking score, the higher the symptoms scores of conceptual disorganization (PANSS-P2, BF = 22.66) and global disorganization of thinking (TLI, BF10 = 112.73); (3) the linguistic style is a better predictor of conceptual disorganization than the cognitive measure of processing speed in schizophrenia (SZ). These findings provide an objectively detectable linguistic style with a focus on Natural Language Processing Analytics of transcribed speech samples of patients with SZ that require no clinical judgment. These findings also offer a crucial insight into the primacy of linguistic structural disruption in clinically ascertained disorganized thinking in SZ. Our work contributes to an emerging body of literature on the psychopathology of SZ using a first-order lexeme-level analysis and a hypothesis-driven approach. At a utilitarian level, this has implications for improving educational and social outcomes in patients with SZ.
| S-EPMC8072135 | biostudies-literature