Elise Leroux

Functional hemispheric lateralization for language in patients with schizophrenia.

BACKGROUND It is widely reported that patients with schizophrenia exhibit decreased hemispheric lateralization. However, no study has evaluated relationships between the hemispheric anatomical and functional asymmetry in language areas. The present study aimed to determine whether decreased leftward hemispheric lateralization could be related to asymmetry of the grey matter volume in patients with schizophrenia. This investigation was the first to use a functional index of laterality to analyze the global functional network specifically involved in the language task. METHODS Twenty-seven right-handed patients with schizophrenia and 54 right-handed control subjects underwent a session of a functional magnetic resonance imaging (fMRI) with a speech listening paradigm. Functional laterality indices (FLI) were calculated (Wilke, M. and Lidzba, K., 2007. LI-tool: a new toolbox to assess lateralization in functional MR-data. J Neurosci Methods. 163, 128-136). The indices of asymmetry in the volume of grey matter (GVAIs) were computed from the functional language network. RESULTS Patients with schizophrenia exhibited significantly decreased leftward hemispheric lateralization. There was a positive correlation between GVAIs and FLIs in healthy subjects, while no such correlation was seen in patients with schizophrenia. DISCUSSION This study reports for the first time a significant relationship between the anatomical and functional asymmetry in healthy subjects, but not in patients with schizophrenia. While decreased leftward functional lateralization for language was observed in patients with schizophrenia compared to the control group, this functional abnormality was not related to asymmetry in the volume of grey matter.

Left fronto-temporal dysconnectivity within the language network in schizophrenia: An fMRI and DTI study

Schizophrenia is a mental disorder characterized by language disorders. Studies reveal that both a functional dysconnectivity and a disturbance in the integrity of white matter fibers are implicated in the language process in patients with schizophrenia. Here, we investigate the relationship between functional connectivity within a language-comprehension network and anatomical connectivity using fiber tracking in schizophrenia. We hypothesized that patients would present an impaired functional connectivity in the language network due to anatomical dysconnectivity. Participants comprised 20 patients with DSM-IV schizophrenia and 20 healthy controls who were studied with functional magnetic resonance imaging and diffusion tensor imaging. The temporal correlation coefficient and diffusion values between the left frontal and temporal clusters, belonging to the language network, were individually extracted, in order to study the relationships of anatomo-functional connectivity. In patients, functional connectivity was positively correlated with fractional anisotropy, but was negatively correlated with radial diffusivity and/or mean diffusivity, in the left arcuate fasciculus and part of the inferior occipitofrontal fasciculus, determined as the fronto-temporal tracts. Our findings indicate a close relationship between functional and anatomical dysconnectivity in patients with schizophrenia. The disturbance in the integrity of the left fronto-temporal tracts might be one origin of the functional dysconnectivity in the language-comprehension network in schizophrenia.

Functional and structural brain asymmetries in patients with schizophrenia and bipolar disorders

OBJECTIVES This study aimed to compare the functional and gray matter asymmetries in patients with schizophrenia (SZ), patients with bipolar disorders (BD), and healthy controls (HCs) to test whether decreased leftward functional hemispheric lateralization and gray matter volume asymmetry could mark the boundary between schizophrenia and bipolar disorder. METHODS A total of 31 right-handed SZ and 20 right-handed BD underwent a session of functional MRI with a speech listening paradigm. Participants were matched with HCs for gender, age, and education. Functional laterality indices (FLI) and gray matter volume asymmetry indices (GVAI) were computed from the individual functional language network. Correlations between the FLI and GVAI indices were also examined. RESULTS SZ exhibited significantly decreased leftward functional hemispheric lateralization whereas BD did not. The GVAIs did not differ significantly between SZ and HCs or between BD and HCs. There were positive correlations between GVAIs and FLIs in all groups. CONCLUSIONS Loss of laterality for language comprehension with retention of gray matter volume asymmetry indicates that gray matter loss alone will not account for the pathophysiology of schizophrenia. Impaired leftward functional hemispheric lateralization for language but not gray matter volume asymmetry can be considered a biomarker of SZ.

Left-hemisphere lateralization for language and interhemispheric fiber tracking in patients with schizophrenia

BACKGROUND It has been suggested that the degree of hemispheric specialization (HS) depends on the structural connectivity between the two hemispheres, that is to say the corpus callosum (CC). Studies, performed only on healthy participants, investigated this anatomo-functional relationship. Nevertheless, it has never been studied in schizophrenia. We therefore propose to study the anatomo-functional relationships between the integrity of interhemispheric connectivity and leftward functional lateralization for language in patients with schizophrenia compared with healthy participants, driven by a multimodal approach combining fMRI and DTI-based fiber tractography. We hypothesized that reduced leftward functional lateralization for language in patients with schizophrenia could be related to a callosal hypoconnectivity. MATERIALS AND METHODS Seventeen patients based on the DSM-IV, and 17 controls were included. The functional laterality index and interhemispheric diffusion values between homologue temporal regions, belonging to the language network, were individually extracted in order to study the anatomo-functional relationships. RESULTS In the patients, higher mean and radial diffusivity (RD) values (thicker myelin sheaths) were associated with less leftward lateralization. In contrast, the controls presented higher RD values and lower fractional anisotropy values (axonal loss) with more leftward lateralization. CONCLUSIONS Our study revealed a relationship between the CC and the HS for language, but did not provide evidence clarifying the direction of the relationship between callosal connectivity and functional lateralization for language. In particular, the present findings showed that the loss of integrity in interhemispheric callosal fibers was associated with reduced leftward cerebral dominance for language in patients with schizophrenia.

Functional and white matter abnormalities in the language network in patients with schizophrenia: A combined study with diffusion tensor imaging and functional magnetic resonance imaging

BACKGROUND Schizophrenia is a mental disorder characterized by functional abnormalities in the language network. Anatomical white matter (WM) abnormalities (volume and integrity) have also been reported for this pathology. Nevertheless, few studies have investigated anatomo-functional relationships in schizophrenia, and none has focused on the language comprehension network in relation to various diffusion parameters. We hypothesized that the WM abnormalities that are reflected by several diffusion parameters underlie functional deficits in the language network. METHODS Eighteen DSM-IV patients with schizophrenia and 18 healthy controls without any significant differences in sex, age, or level of education were included. First, functional brain activation within the language network was estimated. Then, using diffusion tensor imaging, fractional anisotropy (FA), radial diffusivity (RD), and mean diffusivity (MD) values were extracted within WM regions adjacent to this network and their anatomo-functional relationships were investigated. RESULTS Compared with healthy participants, both functional and diffusion deficits were observed in patients with schizophrenia. Primarily, an altered diffusion-functional relationship was observed in patients in the left middle temporal region: functional activations were positively correlated with FA, but were negatively correlated with RD. CONCLUSIONS Our findings indicate a close relationship between diffusion and functional deficits in patients with schizophrenia, suggesting that WM integrity disturbance might be one cause of functional alterations in the language network in patients with schizophrenia. Thus, the present multimodal study improves our understanding of the pathophysiology of schizophrenia.

Reduced functional cerebral lateralization: a biomarker of schizophrenia?

Functional magnetic resonance imaging (fMRI) studies using language tasks have sought biomarkers to discriminate schizophrenia (SZ) and bipolar disorder (BP) (1, 2). Nevertheless, the question of the specificity of such cerebral markers must be considered in light of the debate around the nosological delimitation of both disorders (3). In patients with SZ, the diminution of leftward functional hemispheric lateralization for language has been consistently reported (4–9). However, it is unclear whether this characteristic is specific to SZ or associated with psychosis in general. To our knowledge, no study has investigated functional lateralization in patients with both SZ and BP. The present study aimed to determine whether reduced functional leftward lateralization for language is specific to patients with SZ. Twenty-seven patients with SZ, 13 patients with BP (DSM-IV), and 54 healthy control subjects (HC), who were all right-handed, were recruited after informed written consent and agreement of the local ethics committee. All patients were stabilized, with no change of treatment during the previous four months. The clinical state of patients with SZ was evaluated using the Positive and Negative Syndrome Scale (Table 1). The paradigm consisted of listening to a factual story in French, alternated with the same story in Tamil, a task known to activate high-level language areas such as the semantic network (6). Presentation of the stimulus followed a block design, with nine alternating 32-sec blocks of speech in either Tamil (five blocks) or French (four blocks). Participants were instructed to passively and attentively listen to the story. Shortly after scanning, subjects were asked to answer a 16-item questionnaire which provided a comprehension score for each subject, rated on a 20-point scale. Anatomical T1-weighted and T2-weighted volumes and T2*-weighted functional volumes were acquired using a 3-Tesla scanner (Philips Healthcare France, Suresnes, France). The native T1-weighted volumes of each participant were non-linearly and spatially normalized to the Montreal Neurological Institute template, using SPM5 software (Statistical Parametric Mapping, Wellcome Department of Cognitive Neurology, London, UK, http://www.fil.ion.ucl.ac.uk/spm). The fMRI data from each functional run were corrected for differences in time acquisition between slices and for head motion, and then registered rigidly onto the structural T2-weighted image which, in turn, registered to the T1-weighted image. Data

S183. ABNORMALITIES OF FRONTO-SUBCORTICAL PATHWAYS IN SCHIZOPHRENIA AND THE DIFFERENTIAL IMPACTS OF ANTIPSYCHOTIC TREATMENT: A DTI-BASED TRACTOGRAPHY STUDY

Abstract Background The fronto-striato-thalamic circuitry is a key network associated with several symptoms observed in patients with schizophrenia (SZPs). In this study, we use diffusion tensor imaging (DTI) to investigate the integrity of white matter (WM) pathways involved in this network in SZPs relative to healthy controls (HCs). We also evaluate the differential impact of chronic exposure to clozapine as well as other atypical and typical antipsychotics on fasciculi integrity in this network in schizophrenia. Methods 63 HCs and 41 SZPs were included in this study. Of the SZPs, 16 were treated with clozapine (SZPsC), 17 with atypical antipsychotics (SZPsA), and 8 with typical antipsychotics (SZPsT). We reconstructed three tracts belonging to the fronto-striato-thalamic network in the left hemisphere using tractography: one fronto-subcortical tract (FSC), one prefronto-subcortical tract (PFSC), and one prefronto-frontal tract (PFF). Diffusion parameters were individually extracted in each tract. Results SZPs exhibited lower integrity in both the FSC and PFSC relative to HCs, and SZPsT patients showed altered integrity compared to SZPsC patients. There were no WM integrity differences in the PFF between SZP groups or between SZPs and HCs. Discussion These results suggest that SZPs exhibit structural connectivity abnormalites in the prefronto-fronto-subcortical network that are specifically and differentially impacted by the type of antipsychotic treatment. Additional studies are needed to separate the contributions of clozapine-mediated neuroprotection, neurotoxicity related to typical antipsychotics, and the illness itself to the observed differences.

Effects of low- and high-frequency repetitive transcranial magnetic stimulation on long-latency auditory evoked potentials

Long-latency auditory event potentials (LLAEPs) involving local and global auditory processes have been investigated to examine the impact of low-frequency (LF) and high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) on the cortical excitability of the temporal cortex. We hypothesized that both stimulation frequencies have the same modulation effect, in accordance with clinical data showing a reduction in auditory verbal hallucinations (AVHs) after LF and HF temporal rTMS in patients with schizophrenia. With 30 right-handed healthy volunteer participants enrolled in a crossover trial, we analyzed LLAEPs before and after LF- and HF-rTMS of the left temporal cortex. While we observed no changes in latencies, we did observe a similar inhibitory action of both rTMS frequencies on LLAEP amplitudes. Analysis of surface potential maps and cortical generators revealed some differences regarding auditory processes: HF-rTMS produced earlier, more diffuse, and more right-lateralized effects than LF-rTMS. Beyond a local impact, rTMS exerted a remote modulation influence on the frontal cortex that might be involved in attentional processes. This association could explain the therapeutic effect of temporal HF-rTMS on AVH.

Relationships between corpus callosum and language lateralization in patients with schizophrenia and bipolar disorders

The question of whether there is a continuum or a dichotomy among patients with schizophrenia (SZ) and bipolar disorders (BD) has not been clearly resolved and remains a challenge. Thus, the identification of specific biomarkers of these disorders might be helpful. The present study investigated the volume of the corpus callosum (CC) and functional lateralization for language as potential biomarkers and their relationships in SZ and BD.