Language-related Symptoms Research Articles

Analyzing language ability in first-episode psychosis and their unaffected siblings: A diffusion tensor imaging tract-based spatial statistics analysis study

Schizophrenia (SZ) is a highly heritable mental disorder, and language dysfunctions play a crucial role in diagnosing it. Although language-related symptoms such as disorganized speech were predicted by the polygenic risk for SZ which emphasized the common genetic liability for the disease, few studies investigated possible white matter integrity abnormalities in the language-related tracts in those at familial high-risk for SZ. Also, their results are not consistent. In this current study, we examined possible aberrations in language-related white matter tracts in patients with first-episode psychosis (FEP, N = 20), their siblings (SIB, N = 20), and healthy controls (CON, N = 20) by applying whole-brain Tract-Based Spatial Statistics and region-of-interest analyses. We also assessed language ability by Thought and Language Index (TLI) using Thematic Apperception Test (TAT) pictures and verbal fluency to see whether the scores of these language tests would predict the differences in these tracts. We found significant alterations in language-related tracts such as inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF) among three groups and between SIB and CON. We also proved partly their relationship with the language test as indicated by the significant correlation detected between TLI Impoverished thought/language sub-scale and ILF. We could not find any difference between FEP and CON. These results showed that the abnormalities, especially in the ILF and UF, could be important pathophysiological vulnerability indexes of schizophrenia. Further studies are required to understand better the role of language as a possible endophenotype in schizophrenia with larger samples.

Prenatal Exposure to Per- and Polyfluoroalkyl Substances and ASD-Related Symptoms in Early Childhood: Mediation Role of Steroids.

Previous studies regarding the associations between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and autism spectrum disorder (ASD) have yielded inconsistent results, with the underlying mechanisms remaining unknown. In this study, we quantified 13 PFAS in cord serum samples from 396 neonates and followed the children at age 4 to assess ASD-related symptoms. Our findings revealed associations between certain PFAS and ASD-related symptoms, with a doubling of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) concentrations associated with respective increases of 1.79, 1.62, and 1.45 units in language-related symptoms and PFDA exhibiting an association with higher score of sensory stimuli. Nonlinear associations were observed in the associations of 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES) and 8:2 Cl-PFAES with ASD-related symptoms. Employing weighted quantile sum (WQS) regression, we observed significant mixture effects of multiple PFAS on all domains of ASD-related symptoms, with PFNA emerging as the most substantial contributor. Assuming causality, we found that 39-40% of the estimated effect of long-chain PFAS (PFUnDA and PFDoDA) exposure on sensory stimuli was mediated by androstenedione. This study provides novel epidemiological data about prenatal PFAS mixture exposure and ASD-related symptoms.

Naturalistic Developmental Behavioral Interventions for Developmental Language Disorder.

Naturalistic-developmental-behavioral interventions (NDBIs) are a widely accepted and validated approach for treating language-related symptoms in autism spectrum disorder, including deficits in vocabulary, social skills, and grammar. The purpose of this article is to define the elements naturalistic, developmental, and behavioral as applied to children with developmental language disorder (DLD) and to provide an example of how this type of intervention can be implemented to teach vocabulary and test cross-modal generalization between expressive and receptive modalities. A vocabulary intervention using hybrid NDBI methods (storybook reading and conversational recast interaction) was provided to three participants with DLD using a single-case design. The results indicated that all participants successfully learned receptive and expressive vocabulary targets with extensive cross-modal generalization. However, generalization was limited in some of the participants. This article provided definitions of key elements of NDBI (naturalistic, developmental, and behavioral) including a rationale for extending NDBI procedures to language intervention for children with DLD. In addition, a single-case design demonstrated that NDBI can be implemented in DLD and that broadly defined naturalistic-developmental applied behavior analysis techniques are applicable to language interventions for children with language disorders. Moreover, diverse naturalistic and developmental procedures meet the highest standards for evidence-based practice to treat DLD.

Polygenic risk for schizophrenia and the language network: Putative compensatory reorganization in unaffected siblings

Language-related symptoms, such as disorganized, impoverished speech and communicative behaviors, are one of the core features of schizophrenia. These features most strongly correlate with cognitive deficits and polygenic risk among various symptom dimensions of schizophrenia. Nevertheless, unaffected siblings with genetic high-risk fail to show consistent deficits in language network (LN), indicating that either (1) polygenic risk has no notable effect on LN and/or (2) siblings show compensatory changes in opposing direction to patients. To answer this question, we related polygenic risk scores (PRS) to the region-level, tract-level, and systems-level structure (cortical thickness and fiber connectivity) of LN in 182 patients, 48 unaffected siblings and 135 healthy controls. We also studied the relationships between symptoms, language-related cognition, social functioning and LN structure. We observed a significantly lower thickness in LN (especially the Broca's, Wernicke's area and their right homologues) in patients. Siblings had a distinctly higher thickness in parts of the LN and a more pronounced small-world-like structural integration within the LN. Patients with reduced LN thickness had higher PRS, more disorganization and impoverished speech with lower language-related cognition and social functioning. We conclude that the genetic susceptibility and putative compensatory changes for schizophrenia operate, in part, via key regions in the Language Network.

Frontotemporal Lobar Degeneration: A Historical Overview of the Concept

Arnold Pick described a focal cortical syndrome caused by focal temporal and/or frontal cortical atrophy, later reffered to as Pick's disease (PiD), a prototype of frontotemporal lobar degeneration (FTLD). In contrast to the current concept of PiD, the presence of Pick bodies (tau-positive inclusions) was not thought to be necessary for the diagnosis of PiD. Four out of the seven patients in his original paper had predominant left temporal atrophy and language related symptoms corresponding to semantic dementia. It is now known that most patients with semantic dementia have transactive response DNA-binding protein 43kDa (TDP-43) pathology rather than tau pathology. The original concept of PiD was substantially similar to the current concept of FTLD, which has heterogeneous molecular pathology including tau, TDP-43 and fused in sarcoma (FUS).

The Arcuate Fasciculus in Schizophrenia

Language related symptoms are very common in schizophrenia. The arcuate fasciculus is a white matter tract that mediates Broca’s area and Wernicke’s area which are both critical in language processing. The arcuate fasciculi are often treated as a part of the superior longitudinal fasciculi, whose abnormalities in schizophrenia has often been reported. We have recently established a method to isolate the tract specifically between Broca’s and Wernicke’s areas.

P20-T Networks associated with clinical responses evoked by high-frequency intracranial stimulation

Pre surgical evaluation in drug resistant epilepsy is based also on invasive EEG recordings in order to accurately establish the epileptogenic zone for surgical resection as well as the eloquent cortex that should be spared. During intracranial session we record ictal events and we apply different stimulation protocols to study functional cortex. In our centre we use the stereo-EEG method to identify the epileptogenic networks and mainly high frequency (50 Hz) stimulation for cortical mapping. By modulating the properties of the stimulation waveforms, in conjunction with the nonlinear response of the tissue to electrical stimulation, we were able to recover the physiological responses during the course of the stimulation train. The activation of the networks at stimulation levels evoking a clinical symptom was compared with the below-threshold stimulation, that did not elicit any clinical effects, allowing to evidence a selective recruitment of pathways associated with a particular symptom. The method is used for identification of physiologic networks associated with various somatosensory, motor or language-related symptoms, to investigate the impact of epileptogenic zone to functional cortex as well as to predict a possible post surgical deficit.

Injury of the Arcuate Fasciculus in the Dominant Hemisphere in Patients With Mild Traumatic Brain Injury: A Retrospective Cross-Sectional Study.

Little is known about injury of the arcuate fasciculus (AF) in patients with mild traumatic brain injury (TBI). We investigated injury of the AF in the dominant hemisphere in patients with mild TBI, using diffusion tensor tractography (DTT).We recruited 25 patients with injury of the left AF among 64 right-handed consecutive patients with mild TBI and 20 normal control subjects. DTTs of the left AF were reconstructed, and fractional anisotropy (FA), apparent diffusion coefficient (ADC), and fiber number of the AF were measured.Among 64 consecutive patients, 25 (39%) patients showed injury of the left AF. The patient group showed lower FA value and fiber number with higher ADC value than the control group (P < 0.05). On K-WAB evaluation, aphasia quotient and language quotient were 95.9 ± 4.1 (range 85–100) and 95.0 ± 5.4 (range 80–100), respectively. However, 23 (92.0%) of 25 patients complained of language-related symptoms after TBI; paraphasia in 12 (48.0%) patients, deficits of comprehension in 4 (16.0%) patients, deficits of speech production in 1 (4.0%) patient, and >2 language symptoms in 6 (24.0%) patients.We found that a significant number (39%) of patients with mild TBI had injury of the AF in the dominant hemisphere and these patients had mild language deficit. These results suggest that DTT could provide useful information in detecting injury of the AF and evaluation of the AF using DTT would be necessary even in the case of a patient with mild TBI who complains of mild language deficit.

Second language acquisition and schizophrenia

Schizophrenia is a complex mental disorder that results in language-related symptoms at various discourse levels, ranging from semantics (e.g. inventing words and producing nonsensical strands of similar-sounding words) to pragmatics and higher-level functioning (e.g. too little or too much information given to interlocutors, and tangential discourse). Most of the literature concerning people with schizophrenia who acquire a second or foreign language suggests that these linguistic deficits are not as prominent (in some instances, altogether absent) when patients use their non-dominant language, a phenomenon that has been used to support different claims posited by psychologists and linguists about schizophrenia and second language learning alike. This review explores the relationship between second language acquisition and schizophrenia, and discusses how empirical findings regarding multilingual individuals with a diagnosis of schizophrenia inform current notions regarding second language acquisition.

Altered intrinsic functional connectivity in language-related brain regions in association with verbal memory performance in euthymic bipolar patients.

Potential abnormalities in the structure and function of the temporal lobes have been studied much less in bipolar disorder than in schizophrenia. This may not be justified because language-related symptoms, such as pressured speech and flight of ideas, and cognitive deficits in the domain of verbal memory are amongst the hallmark of bipolar disorder (BD), and contribution of temporal lobe dysfunction is therefore likely. In the current study, we examined resting-state functional connectivity (FC) between the auditory cortex (Heschl’s gyrus [HG], planum temporale [PT]) and whole brain using seed correlation analysis in n = 21 BD euthymic patients and n = 20 matched healthy controls and associated it with verbal memory performance. In comparison to controls BD patients showed decreased functional connectivity between Heschl’s gyrus and planum temporale and the left superior and middle temporal gyrus. Additionally, fronto-temporal functional connectivity with the right inferior frontal/precentral gyrus and the insula was increased in patients. Verbal episodic memory deficits in the investigated sample of BD patients and language-related symptoms might therefore be associated with a diminished FC within the auditory/temporal gyrus and a compensatory fronto-temporal pathway.

Unusual clinical presentation and neuropathology in two subjects with fused-in sarcoma (FUS) positive inclusions

We report two unusual autopsy cases with frontotemporal lobar degeneration (FTLD) that were hyperphosphorylated-tau- and TAR DNA binding protein 43 (TDP-43)- negative. The behavioral symptoms in both cases were compatible with frontotemporal dementia, but they exhibited more prominent speech and language related symptoms than previously reported. Moreover, they displayed a short duration of the disease; the male case had a disease onset age of 45 years, and duration of 5 years, and the female case suffered even shorter disease duration and a later onset of the symptoms, at the age of 67 years. Moreover, the motor functions had deteriorated in different ways in these cases. The male patient showed progressive motor symptoms, weakness of extremities and bulbar muscles suggesting motor neuron disease with a muscle biopsy supporting neurogenic deficits, whereas the female patient exhibited dyskinesias and tremor with progressive swallowing disorders. The father of the male case displayed dementia of similar type at the age of 68 years. In both cases, neuropathological examination showed fused-in sarcoma (FUS)-positive pathology. The male patient had intensely FUS-positive cytoplasmic and intranuclear inclusions that resembled the characteristics previously reported in FTLD FUS, whereas the female patient did not exhibit any cytoplasmic inclusions but had roundish, dense FUS-positive intranuclear inclusions. She also displayed a plethora of other pathologies including α-synuclein, hyperphosphorylated-tau, β-amyloid aggregation and some neuronal polyglutamine aggregation (1C2) but no well-demarcated inclusions were observed. We conclude that clinical phenotypes of FUS pathologies also include elderly patients and are more variable with motor and speech disorders than previously reported.

A computerized technique to assess language use patterns in patients with frontotemporal dementia

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder that affects language. We applied a computerized information-theoretic technique to assess the type and severity of language-related FTLD symptoms. Audio-recorded samples of 48 FTLD patients from three participating medical centers were elicited using the Cookie-Theft picture stimulus. The audio was transcribed and analyzed by calculating two measures: a perplexity index and an out-of-vocabulary (OOV) rate. The perplexity index represents the degree of deviation in word patterns used by FTLD patients compared to patterns of healthy adults. The OOV rate represents the proportion of words used by FTLD patients that were not used by the healthy speakers to describe the stimulus. In this clinically well-characterized cohort, the perplexity index and the OOV rate were sensitive to spontaneous language manifestations of semantic dementia and the distinction between semantic dementia and progressive logopenic aphasia variants of FTLD. Our study not only supports a novel technique for the characterization of language-related symptoms of FTLD in clinical trial settings, it also validates the basis for the clinical diagnosis of semantic dementia as a distinct syndrome.

How modern neurophysiology can help to understand schizophrenia

Modern clinical neurophysiology with the new techniques of functional brain imaging has enormously contributed to the understanding of normal and pathological brain functions in the last decade. In our opinion, one of themost important insights is the fact that even the most complex brain functions such as emotions and language are related to the activity of different and definable specialised regions. To explain these intricate psychic functions, however, higher order processes must be assumed which rely on the dynamically concerted activity of several specialised regions. In psychiatry this systemic level of brain function is particularly interesting for schizophrenia with its complex and manifold symptoms which occur in the most characteristically human domains of experience and behaviour. We are convinced that the progress in understanding the biological fundaments of this psychosis will help to improve treatment, social support and empathy for the affected individuals. Based on the simple assumption that variation of behaviour and experience are associated with different patterns of brain activation and, on the other hand, that complex psychic functions cannot be simply and statically localised in single sites of the brain, we deduce that relevant research must be guided by psychopathological concepts and symptom definitions which are closely related to the natural neurophysiological mechanisms of the human brain. This approach is believed to be a necessary condition to find more homogenous patient groups in terms of the related brain dysfunctions. Even if these symptoms are state dependent, transient and dynamically changing, this strategy is necessary to target functional brain research to specialised functional brain circuits efficiently, i.e. with reasonable numbers of patients and simple paradigms. We argue that current symptom definitions were not empirically developed but are based on and through their definitions essentially still bond to historical theories of schizophrenia and therefore may well be questioned for their validity in modern neurophysiological research and also be challenged by competitive and testable alternatives. Relying on the current knowledge of brain structure and functions, we propose to reformulate psychopathology in terms of neurophysiologically meaningful patterns of behaviour and subjective experience. The goal is possibly less difficult to achieve than commonly expected if one applies simple descriptive terms such as excitation or inhibition and follows human abilities, which depend on well-known specialised brain circuits such as language or emotions. We provide concrete examples of possible meaningful symptom definitions including the description of their potential neurophysiological background. In the last part of the article, the successful example of auditory hallucinations is described where the targeted investigation of a neurophysiologically meaningful symptom allowed to reveal specific functional and structural anomalies in those brain circuits which are involved in the generation and understanding of language. Further, we present a scientifically testable model of language-related dysfunctions in schizophrenia which summarises the current findings on verbal hallucinations and additional findings which involve language-related symptoms and structures of the brain.

ワーキングメモリをめぐる最近の動向

Baddeley and Hitch proposed a fundamental framework for working memory in 1974, emphasizing its transiently activated memory aspect for performing various cognitive tasks. This concept of working memory is quite useful in understanding human cognitive processes and has been widely used in the fields of cognitive and developmental psychology and neuropsychology. The idea of working memory has also been introduced to consider cognitive rehabilitation for patients with brain damage. In the present review, we first described a current theoretical framework of working memory and then reported on recent studies on the conceptualization of working memory. We subsequently reviewed neural substrates of working memory subsystems, i. e., the phonological loop, the visuospatial sketch pad and the central executive. We further referred to the contribution of working memory in understanding various language-related symptoms in patients with aphasia, one of the major targets in the field of cognitive rehabilitation. Working memory plays a crucial role in the everyday life of brain damaged patients. Future research is warranted to focus on the improvement of deficient working memory in order to ameliorate clinical problems of brain damaged patients.

Superior temporal gyrus abnormalities in early-onset schizophrenia: similarities and differences with adult-onset schizophrenia.

The superior temporal gyrus is associated with developmental mechanisms of brain lateralization and the pathogenesis of language-related schizophrenic symptoms. It therefore lends itself to investigation of developmental deviance in the early onset of schizophrenia. Using stereological methods, the authors obtained bilateral measurements of the superior temporal gyrus (total, gray matter, and white matter volumes) from 40 adolescents with recent-onset schizophrenia and an equal number of matched healthy volunteers. Symptoms were rated by using the Positive and Negative Syndrome Scale. The total and gray matter volume of the right superior temporal gyrus was significantly lower in patients with early-onset schizophrenia than in the healthy volunteers, even after differences in whole brain volume were controlled. Bilateral superior temporal gyrus volumes were positively correlated with the age at onset of psychosis, while severity of thought disorder and hallucinations were inversely related to right superior temporal gyrus volume. In patients with early-onset schizophrenia, the predominantly right-sided volumetric abnormalities found in the superior temporal gyrus may reflect a particularly early neurodevelopmental disruption. The relationship between language-related symptoms and superior temporal gyrus volume is similar to that seen in adult-onset cases but not as lateralized.

Language-Related Symptoms in Persons with Schizophrenia and How Deaf Persons May Manifest These Symptoms

Disturbances in language have long been viewed as a principal identifying characteristic of schizophrenia. The language-processing deficits of persons with schizophrenia are manifested in a variety of ways. Historically, analyses of schizophrenic patients� language disorders have focused almost entirely on speech. Deaf persons, however, constitute a portion of the population that is diagnosed as schizophrenic, and sign languages are often their principal means of communication. In recent years, preliminary observations have been reported that indicate that there are a number of similarities between the linguistic deficits of signing Deaf persons with schizophrenia and those evident in the speech of hearing schizophrenic patients. Systematic investigations of schizophrenic Deaf persons� signing need to be conducted both to improve treatment programs for Deaf patients and to increase our understanding of the language aspects of schizophrenia.