Lateralization In Schizophrenia Research Articles

Figurative Language Comprehension in Schizophrenia and Its Neural Basis

Schizophrenia is a kind of serious mental disease, which may cause major impairment in patients’ social-cognitive ability. It has been found that pragmatic ability in schizophrenic patients is often impaired, especially for figurative language comprehension. Figurative language refers to irony, metaphor, idiom and the like. People with schizophrenia tend to interpret figurative language as its literal meaning, which is called schizophrenic concretism. By reviewing extant literature, we found that the literature concerning this topic mainly consists of two parts: behavioral studies and brain-imaging studies. The behavioral studies mainly explore how clinical factors and cognitive ability have an impact on figurative language comprehension. Brain-imaging studies mainly discuss hemisphere lateralization in schizophrenia and whether theory of mind network in schizophrenic patients is different from that of normal groups. We conclude that future research should further explore the relationship among figurative language comprehension, cognitive ability and clinical factors, and also reveal related neural mechanism.

Functional brain lateralization in schizophrenia based on the variability of resting-state fMRI signal

Abnormal brain lateralization has been implicated in schizophrenia but few studies have focused on the variability of resting-state fMRI signal and its lateralization in schizophrenia. Here we utilized standard deviations (SD) to quantify the variability of resting-state fMRI signal and measured the lateralization index (LI), on the basis of SD of the resting-state fMRI signal in order to assess the difference of brain signal variability across the hemispheres. We recruited 180 patients with schizophrenia and 358 age- and sex-matched healthy volunteers. Between-group comparison revealed that in comparison to healthy volunteers, schizophrenia patients have significantly higher SD of resting-state fMRI activity in left inferior temporal, left fusiform, and right superior medial frontal cortex, and lower SD in right precuneus, posterior cingulum on both sides, right lingual, and left calcarine in the occipital region. Using region of interest approach, most brain regions showed increased leftward lateralization in patients with schizophrenia, as compared with healthy controls. SD and LI were also found to be correlated to age of onset or duration of illness. These results provide further evidence that abnormal variability and lateralization exist in schizophrenia patients, and abnormality in fusiform, lingual and inferior temporal could have potential help to identify the dysfunctional brain lateralization in schizophrenia.

Auditory Hallucinations and Reduced Language Lateralization in Schizophrenia: A Meta-analysis of Dichotic Listening Studies

Reduced left-hemispheric language lateralization has been proposed to be a trait marker for schizophrenia, but the empirical evidence is ambiguous. Recent studies suggest that auditory hallucinations are critical for whether a patient shows reduced language lateralization. Therefore, the aim of the study was to statistically integrate studies investigating language lateralization in schizophrenia patients using dichotic listening. To this end, two meta-analyses were conducted, one comparing schizophrenia patients with healthy controls (n = 1407), the other comparing schizophrenia patients experiencing auditory hallucinations with non-hallucinating controls (n = 407). Schizophrenia patients showed weaker language lateralization than healthy controls but the effect size was small (g = -0.26). When patients with auditory hallucinations were compared to non-hallucinating controls, the effect size was substantially larger (g = -0.45). These effect sizes suggest that reduced language lateralization is a weak trait marker for schizophrenia as such and a strong trait marker for the experience of auditory hallucinations within the schizophrenia population.

Arcuate Fasciculus Abnormalities and Their Relationship with Psychotic Symptoms in Schizophrenia

Disruption of fronto-temporal connections involving the arcuate fasciculus (AF) may underlie language processing anomalies and psychotic features such as auditory hallucinations in schizophrenia. No study to date has specifically investigated abnormalities of white matter integrity at particular loci along the AF as well as its regional lateralization in schizophrenia. We examined white matter changes (fractional anisotropy (FA), axial diffusivity (AD), asymmetry indices) along the whole extent of the AF and their relationship with psychotic symptoms in 32 males with schizophrenia and 44 healthy males. Large deformation diffeomorphic metric mapping and Fiber Assignment Continuous Tracking were employed to characterize FA and AD along the geometric curve of the AF. Our results showed that patients with schizophrenia had lower FA in the frontal aspects of the left AF compared with healthy controls. Greater left FA and AD lateralization in the temporal segment of AF were associated with more severe positive psychotic symptoms such as delusions and hallucinations in patients with schizophrenia. Disruption of white matter integrity of the left frontal AF and accentuation of normal left greater than right asymmetry of FA/AD in the temporal AF further support the notion of aberrant fronto-temporal connectivity in schizophrenia. AF pathology can affect corollary discharge of neural signals from frontal speech/motor initiation areas to suppress activity of auditory cortex that may influence psychotic phenomena such as auditory hallucinations and facilitate elaboration of delusional content.

Familial sinistrality and handedness in patients with first episode schizophrenia: The EUFEST study

The population with schizophrenia is characterised by a leftward shift in handedness—sinistrality. However, findings are inconsistent in chronic patients, and familial sinistrality (FS), defined as the presence of left-handed close relatives, might contribute to the discrepancies. Therefore the aim of this study was to investigate the strength of manual lateralisation in patients with first episode schizophrenia, taking into account familial sinistrality. The Edinburgh Inventory (EI) allowed us to categorise 179 patients from the EUFEST study and 189 controls presenting “strong handedness” (SH: EI absolute value between ∣81∣ and ∣100∣) or “weak-handedness” (WH: EI value between −80 and +80). The nominal logistic regression did not show an FS effect, but a nearly significant interaction between illness and FS (p =.07). There were fewer participants without FS presenting SH among patients (99/151: 65.6%) than among controls (134/164: 81.7%, p =.001). In contrast, the number of participants with FS presenting SH was similar between controls (68%) and patients (75%, p =.57). The presence of left-handed relatives (FS + ) tended to reduce manual lateralisation, but only in controls. This supports the notion that reduced manual lateralisation in schizophrenia is related to the illness rather than to familial left-handedness.

Antithetical asymmetry in schizophrenia and bipolar affective disorder: a line bisection study

Evolutionary theories link the pathogenesis of psychosis with anomalous brain asymmetry. Research shows that aberrant lateralization is linked to schizophrenia with elevated rates of left-handedness and reversal of normal cerebral asymmetries. However, lateralization is underexamined in bipolar affective disorder (BPAD) and the available literature suggests the possibility of greater lateralization, which is diametrically opposite to what is observed in schizophrenia. For the first time, we report concurrent analyses of asymmetry in BPAD and schizophrenia using a line bisection task. We examined 164 subjects (31 patients with BPAD in remission, 30 patients with schizophrenia, and 103 healthy controls) using a two-hand line bisection task with established methodology. Raters with good inter-rater reliability (intraclass correlation coefficient > 0.8) measured deviation from the center. Task performance was compared using analysis of covariance with age, sex, and education as covariates. Study groups did not differ significantly on age, sex, and handedness (p > 0.06). Patients (both schizophrenia and BPAD) had significantly more errors in identifying the center than controls (p < 0.001). Patients with schizophrenia bisected fewer lines at center than controls and BPAD subjects (p < 0.001). Using their right hand, schizophrenia patients had significant rightward deviation and BPAD patients had leftward deviation (p = 0.001). A significant interaction between diagnosis and direction of deviation (p = 0.01) was noted, with significant rightward deviation in schizophrenia and a trend toward leftward deviation in BPAD. Study findings suggest attenuation of normal pseudoneglect in schizophrenia and accentuation of normal pseudoneglect in BPAD, indicating lesser lateralization in schizophrenia and possibly greater lateralization in BPAD. From an evolutionary perspective, schizophrenia and BPAD might have antithetical origins.

Evidence for reduced somatosensory lateralisation and focalisation in schizophrenia

Neuroimaging studies indicate diminished lateralisation of cerebral activity during motor tasks and language processing in schizophrenia. Some evidence also indicates that decreased lateralisation is accompanied by more diffuse intra-hemispheric activation, suggesting that diminished lateralisation might be part of a more general diminution of regional functional specialisation. In the case of passive processing of elementary somatosensory stimuli, evidence for decreased lateralisation derived from event-related potential studies, is conflicting. The greater spatial resolution of functional magnetic resonance imaging (fMRI) offers the potential to resolve this conflict. We report an fMRI study of 22 right-handed individuals with schizophrenia, 21 right-handed healthy individuals and 10 non-right-handed healthy individuals, designed to test the hypothesis that in schizophrenia there is a diminution of both lateralisation and intra-hemispheric focalisation during the passive processing of vibrotactile stimuli delivered to the right index finger. Significantly reduced lateralisation of activity in primary somatosensory cortex (SI) was observed in the schizophrenia group as compared to the healthy right-handed group. There was a trend for a reduction in SI lateralisation in the schizophrenia group compared to the healthy non-right-handed group. Contralateral SI focalisation was also significantly reduced in the schizophrenia group compared to both healthy groups. SI focalisation was negatively correlated with severity of disorganisation symptoms in the schizophrenia group. These results support the hypothesis that a generalised loss of functional specialisation is fundamental to schizophrenia.

Altered lateralisation of emotional prosody processing in schizophrenia

Alterations of cerebral lateralisation in schizophrenia have been reported consistently, and a reduced left-lateralisation has been suggested for language functions. Speech contains non-verbal information, e.g. prosody, and on a behavioural level, the extraction of emotional information from prosody is often impaired in schizophrenia. A previous functional magnetic resonance imaging study suggests increased left-lateralisation in schizophrenia during prosody processing, but did not disentangle effects of speech processing as such and emotional prosody processing. Here, we used meaningless syllables spoken with neutral, angry or fearful speech melody and measured blood oxygen level-dependent (BOLD) responses in 15 in-patients with schizophrenia and 15 healthy control participants matched for age and gender. Lateralisation indices were calculated for responses to emotional versus neutral prosody, and for all types of prosody versus baseline. Compared to control participants, patients with schizophrenia showed an increased right-lateralisation of emotional and non-emotional prosody processing in the temporal and parietal cortex. This right-lateralisation was increased in patients with reduced right-handedness and decreased in patients with stronger negative symptoms, particularly affective blunting, and with longer hospitalisation. Although patients with schizophrenia performed worse in emotion identification, this deficit was not related to lateralisation indices. Enhanced right-lateralisation to prosody resembles previous findings on laterality changes in speech processing and might suggest a common underlying cause in the organization of language functions.

Abnormal brain lateralization and connectivity in Schizophrenia

Schizophrenia is a complex disorder mainly characterized by thought disturbances, hallucinations, and decay of social and cognitive performances. From past attempts to identify the exclusive brain lesions responsible for specific domains of schizophrenia symptoms such as delusion and auditory hallucinations, recent data pointed towards network alterations leading to abnormal brain asymmetry and connectivity as important determinants of schizophrenia pathophysiology. Several contributions have reported reduced brain lateralization in schizophrenia, causing a failure of left hemisphere dominance. Evidence of altered connectivity among distinct cortical areas is also accumulating. The aim of the present article is to critically review such contributions.

Asymmetry of language activation in families with multiple incidence of schizophrenia

1. Sommer IEC, Ramsey NF, Kahn RS. Language lateralization in schizophrenia an fMRI study. Schizophrenia research 52 (2001) 57–67. 2. Li X, Craig AB, Ardekani BA, Bertisch H, Hicks C, DeLisi LE. fMRI study of language activation in schizophrenia, schizoafektive disorder and in individuals genetically at high risk. Schizophrenia research 96 (2007) 14–24. To find out that lack of the normal asymmetry of language activation is present in schizophrenic patients.

Auditory lateralization in schizophrenia – Mismatch negativity and behavioral evidence of a selective impairment in encoding interaural time cues

Objective Behavioural evidence suggests that individuals with schizophrenia may exhibit impairment in the encoding of cues to sound location. There are three primary cues used by the auditory system to locate the position of a sound in space: interaural differences in the arrival-time (ITD), phase (IPD), and the loudness (ILD) of the sound at the two ears. The goal in this study was to obtain an electrophysiological index of preattentive detection of change in sound lateralization created by these cues. Methods The amplitude of mismatch negativity (MMN) was measured in 18 individuals with schizophrenia and 19 healthy comparison subjects to changes in sound lateralization produced by interaural temporal cues (ITD and IPD) and interaural loudness cues (ILD). Performance was also investigated on a target detection task, where targets were defined by ITD, IPD, or ILD cues. Results Individuals with schizophrenia had reduced MMN amplitudes and decreased hit rates when deviants were created by interaural temporal cues, but not when loudness cues were used. Conclusions Results from both the MMN and behavioural task revealed a selective impairment in the use of temporal cues to sound lateralization in individuals with schizophrenia. Significance This finding supports previous research that suggests impairment in the encoding of the temporal information in schizophrenia.

Language functions in right-hemisphere damage and schizophrenia: apparently similar pragmatic deficits may hide profound differences

Sir, In a recent article discussing the cognitive roots of schizophrenic communicative behaviour, Mitchell and Crow (2005) emphasized the importance of full access to right hemisphere language functions to ensure successful social communication. Based on the literature describing communicative deficits among right-hemisphere-damaged (RHD) patients, as well as on the literature reporting functional neuroimaging studies of healthy individuals, these authors suggested that ‘the core deficit in psychosis is a failure of segregation of right from left hemisphere functions’ (p. 963). In other words, Mitchell and Crow (2005) argue for a reduction of the language lateralization in schizophrenia (SZ). The role of so-called ‘RH functions’ in the pathophysiology of SZ proposed by Mitchell and Crow (2005) could prove crucial to an understanding of SZ from a neurobiological point of view; this proposal may also account for the presence of social communication deficits in SZ. However, the apparent similarities noted by Mitchell and Crow (2005) between the pragmatic deficits following RH damage and those present in patients with SZ seem to be only at the surface level. Indeed, the underlying cognitive dysfunctions appear to be quite different in these two populations. As Mitchell and Crow (2005) rightly remind us in their article, language requires more than the classical syntax, phonology and …

Cerebral lateralization in schizophrenia and dyslexia: neuromagnetic responses to auditory stimuli

Many studies have shown altered hemispheric asymmetry—particularly in perisylvian regions—in schizophrenia patients as well as in individuals with dyslexia. Here we explore the similarity of these findings comparing the localization of the magnetic auditory N100m to the German syllable [ba:] in schizophrenia patients, dyslexic adults, and healthy control subjects. Control subjects showed the typical finding of more anterior sources in the right than in the left perisylvian region. In contrast, both schizophrenia patients and dyslexic subjects displayed a symmetrical N100m source configuration. While in people with dyslexia the alteration appears to originate in the right hemisphere, left-hemispheric deviations might contribute to reduced asymmetry in schizophrenia patients. Our results indicate that an absence of lateralized auditory responses in the temporal lobes may reflect a common deviance present in dyslexia and schizophrenia. The nonspecific finding of reduced cerebral laterality may be accounted for by population-specific differences in the functional organization of perisylvian sites.

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Language lateralization in female patients with schizophrenia: an fMRI study

Gender differences in schizophrenia are among the most consistently reported findings in schizophrenia research. However, the biological substrate underlying these gender differences is still largely unknown. Differences in language lateralization between men and women may underlie some gender differences in schizophrenia. In previous functional imaging studies, language lateralization was found to be decreased in male schizophrenia patients as compared to healthy males, which was due to enhanced language activation of the right hemisphere as compared to the healthy males. It could be hypothesized that decreased language lateralization in schizophrenia is gender specific, i.e. decreased lateralization in male patients and normal lateralization in female patients. To test this hypothesis, language activation was measured in 12 right-handed female patients with schizophrenia and 12 healthy females, and compared to findings in 12 male patients and 12 male controls of an earlier study. Language lateralization was significantly lower in the female patients (0.44) as compared to the female controls (0.75), which was due to increased activation of the right-sided language areas (patients: 19 voxels; controls: 8 voxels), while left hemisphere activation was similar in patients and controls. When these data are compared to the male patients and controls, both patient groups had lower lateralization than their healthy counterparts, but there was no difference between male and female patients. In both sexes, decreased lateralization resulted from increased right hemispheric language activation, which suggests a failure to inhibit nondominant language areas in schizophrenia. These findings indicate that lower language lateralization in women is not likely to underlie gender differences in schizophrenia.

Abnormal motor asymmetry only during bimanual movement in schizophrenic patients compared with healthy subjects

In schizophrenia, research on motor asymmetry has focused on the direction and the degree of handedness using unimanual motor tests and tasks. However, typically both hands collaborate in the production of most manual movements. This study explored motor asymmetry exhibited during unimanual and bimanual tasks in schizophrenic and healthy subjects using a new experimental motor battery. Specifically, the authors investigated the motor indices of laterality during finger-tapping and hand-turning tasks in four unimanual and four bimanual conditions in 84 schizophrenic and 31 healthy subjects, all right-handed. The schizophrenic patients showed reduced motor asymmetries only during bimanual tapping compared with healthy subjects due to reduction in right-hand performance. These results stress the importance of considering bimanual conditions in the assessment of motor asymmetries, and suggest that it is necessary to use bimanual tasks to test hypotheses about abnormal motor lateralization in schizophrenia.

Altered hemispheric asymmetry and positive symptoms in schizophrenia: equivalent current dipole of auditory mismatch negativity

The abnormality of mismatch negativity (MMN) in schizophrenia is thought to be associated with perceptional disturbance and cognitive dysfunction. The purpose of the present study was to investigate the change of the normal functional hemispheric lateralization in schizophrenia by employing the equivalent current dipole (ECD) model of auditory MMN with individual MRI and high-density electroencephalography (EEG). The MMNs resulting from auditory stimuli with passive oddball paradigm in a group of schizophrenics ( n=15), and also a group of age-, sex-, and handedness-matched normal controls, were recorded by 128 channel EEG. The location and power of ECD sources at the peak point were calculated. Individual 3-D brain magnetic resonance images (MRI) were used for realistic head modeling and for source localization. For both groups, the MMN source was determined to be located in the superior temporal gyrus (STG). However, the normal functional hemispheric asymmetry of ECD power was significantly altered in the schizophrenics ( χ 2 test=16.13, p<0.001). Left MMN ECD power and the asymmetry coefficient (AC) were negatively correlated with the positive scores from Positive and Negative Syndrome Scale (PANSS) ( r=−0.673, p=0.008), especially with the hallucinatory behavior subscale ( r=−0.677, p=0.008). These findings support the deficits in preattentive automatic processing of auditory stimuli, especially in the left hemisphere, and indicate the correlation between positive symptoms, especially auditory hallucination, and left temporal lobe dysfunction in schizophrenia.

Language lateralization in schizophrenia, an fMRI study

Anatomical studies have shown that cerebral asymmetry is reduced in schizophrenia. Functional asymmetry appears to be reduced also, as was shown with dichotic listening studies. These studies, however, have not revealed whether reduced lateralization is the result of decreased language activity of the left hemisphere or whether it is the consequence of increased language-related activity in the right hemisphere. To elucidate this, we examined hemispheric dominance for language processing by means of functional MRI. Twelve schizophrenic patients and twelve healthy controls were scanned while they were engaged in a verb-generation and a semantic decision task. Activation was measured bilaterally in the frontal, temporal and temporo-parietal language areas, and a laterality index was derived from activity in these regions of interest in the left and the right hemispheres. Clinical symptoms were rated at the time of scanning. The results indicate that language processing is less lateralized in patients than in controls (a mean laterality index of 0.35 versus 0.63, respectively, difference p<0.01). Analysis of variance of the extent of activity, i.e. numbers of active voxels, revealed a significant hemisphere by group interaction ( F(1,22)=11.2, p<0.001), which was due to increased activation in the right hemisphere of the patients (post hoc t-test p<0.05). We found no evidence of reduced activity in the left hemisphere. Further analysis of clinical symptoms rated prior to scanning revealed that decreased language lateralization was associated with more severe hallucinations ( r=−0.54, p<0.05). We postulate that decreased language lateralization in schizophrenia may result from failure to inhibit the right hemisphere.

Handedness, language lateralisation and anatomical asymmetry in schizophrenia: meta-analysis.

Cerebral lateralisation appears to be decreased in schizophrenia. Results of studies investigating this, however, are equivocal. To review quantitatively the literature on decreased lateralisation in schizophrenia. Meta-analyses were conducted on 19 studies on handedness, 10 dichotic listening studies and 39 studies investigating anatomical asymmetry in schizophrenia. The prevalence of mixed- and left-handedness ('non-right-handedness') was significantly higher in patients with schizophrenia as compared to healthy controls, and also as compared to psychiatric controls. The analysis of dichotic listening studies revealed no significant difference in lateralisation in schizophrenia. However, when analysis was restricted to studies using consonant-vowel or fused word tasks, significantly decreased lateralisation in schizophrenia emerged. Asymmetry of the planum temporale and the Sylvian fissure was significantly decreased in schizophrenia, while asymmetry of the temporal horn of the lateral ventricle was not. Strong evidence is provided for decreased cerebral lateralisation in schizophrenia.

Altered hemispheric asymmetry of auditory magnetic fields to tones and syllables in schizophrenia

Background: A growing body of literature suggests that schizophrenic patients often do not show the normal brain hemispheric asymmetry. We have found this for simple tones presented to the right ear in a previous study. In this study we extended this investigation to left ear stimulation and verbal stimuli. Methods: With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked magnetic fields in response to tones (1000 Hz) and to the syllables (“ba”) delivered to the left and right ears in separate runs were compared between schizophrenic patients ( n = 17) and healthy control subjects ( n = 15). Results: In response to tones, all control subjects showed the expected asymmetry (contralateral predominance) of the auditory-evoked magnetic N100m (dipole moment). In the patient sample asymmetry was reversed following tones presented to the left ear in 47% and following tones to the right ear in 24%. In response to syllables, the asymmetry was similar between groups. In patients compared with control subjects the N100m was located more anterior without asymmetry between hemispheres. Conclusions: Results suggest that deviation from the normal functional lateralization in schizophrenia appears in a proportion of patients at a basic stage of auditory processing, but may be compensated for at higher levels such as the processing of syllables.