Impaired language processing is one of the most replicated findings in functional brain studies of schizophrenia (SCH). This is demonstrated by reduced activations in left prefrontal language areas (i.e., BA44/45, the inferior frontal gyrus, IFG) presented as decreased language lateralization. This finding was documented both in chronic as well as in first-episode SCH patients, arguing for a neurobiological marker for SCH. In a previous study, we demonstrated the specificity of this finding to SCH patients when compared to obsessive-compulsive disorder (OCD) patients in whom language processing was similar to healthy controls. Since a sizable proportion of SCH patients also meet DSM-IV criteria for OCD, we further sought to elucidate whether OCD attenuates abnormal prefrontal language lateralization in this unique group of schizo-obsessive patients compared to their non-OCD-SCH counterparts.
Schizophrenia is a devastating psychiatric illness characterized by deterioration of cognitive and emotional processing. It has been hypothesized that aberrant cortical connectivity is implicated in the disease (Friston, 1998), yet previous studies of functional connectivity (FC) in schizophrenia have shown mixed results (Garrity et al., 2007; Jafri et al., 2008; Lynall et al., 2010). We measured FC using fMRI in human schizophrenia patients and healthy controls during two different tasks and a rest condition, and constructed a voxel-based global FC index. We found a striking FC decrease in patients compared with controls. In the task conditions, relatively weaker FC was specific to regions of cortex not active during the task. In the rest condition, the FC difference between patients and controls was larger and allowed a case-by-case separation between individuals of the two groups. The results suggest that the relative reduction of FC in schizophrenia is dependent on the state of cortical activity, with voxels not activated by the task showing higher levels of FC deficiency. This novel finding may shed light on previous reports of FC in schizophrenia. Whether this neural characteristic is related to the development of the disorder remains to be established.
A consistent brain imaging finding in schizophrenia is decreased language-asymmetry, already evident in first episode patients, thus arguing for a biomarker of the disorder. Nonetheless, its specificity to schizophrenia is questionable. Furthermore, while previous studies suggested that enhanced right hemisphere activation underlies this diminished asymmetry, the mechanism for this anomaly is yet unknown. This study aimed to examine the role of inter-hemispheric relations in such abnormality through functional connectivity analysis driven by left inferior frontal gyrus (IFG) activation. To test for disorder specificity we compared schizophrenia patients not only to healthy controls but also to patients with obsessive compulsive disorder (OCD).
Despite an exponential increase in the use of brain imaging in neuroscience, it has as yet hardly been integrated into clinical psychiatry. Our aim is to examine the potentials and perspectives of functional brain imaging in the diagnosis and treatment of mental disorders.
Patients with schizophrenia exhibit a decrease or loss of normal anatomical brain asymmetry that also extends to functional levels. We applied functional magnetic resonance imaging (fMRI) to investigate language lateralization in patients with schizophrenia during their first episode of illness, thus excluding effects of chronic illness and treatment. Brain regions activated during language tasks of verb generation and passive music listening were explored in 12 first-episode patients with schizophrenia and 17 healthy controls. Regions of interest corresponded to Brocas area in the inferior frontal gyrus (IFG) and Wernickes area in the superior temporal sulcus (STS). Patients with schizophrenia had significantly smaller lateralization indices in language-related regions than controls. A similar effect was observed in their IFG and STS regions. There was no difference between the groups in the auditory cortex for the music task. Patients with schizophrenia demonstrated greater activation than the controls in temporal regions: the difference was larger in patients with more severe positive symptom subscores. In conclusion, patients with schizophrenia demonstrated loss of normal functional brain asymmetry, as reflected in diminished lateralization of language-related activation in frontal and temporal regions. This phenomenon was already present during their first episode of psychosis, possibly reflecting developmental brain abnormalities of the illness.
Blunted, inappropriate affective-social behavior is a hallmark of early schizophrenia, possibly corresponding to reduced ability to recognize and express emotions. It is yet unknown if this affective deficiency relates to disturbed neural sensitivity to facial expressions or to overall face processing. In a previous imaging study, healthy subjects showed less suppression of the fusiform gyrus (FG) to repeated presentation of the same transfigured-bizarre face relative to regular face. We assumed that the FG in schizophrenia will show reduced repetition related sensitivity to transfigured-bizarre faces, while having overall normal response to faces.
Obsessive-compulsive disorder (OCD) patients suffer from risk aversion, which may be mediated by their exaggerated response to threat and diminished response to reward. In this study, 13 OCD patients and 13 healthy matched controls underwent functional magnetic resonance imaging (fMRI) while playing an interactive risky choice game encompassing distinct intervals of threat and reward; as well as anatomical diffusion tensor imaging (DTI). Compared to healthy controls OCD patients were reluctant to make risky choices during the game. Furthermore, they displayed higher amygdala activation to threat; lower nucleus accumbens (Nacc) activation to reward and reduced functional connectivity of the amygdala and Nacc to two frontal regions, the orbito-frontal cortex (OFC) and the dorsal anterior cingulate cortex (dACC), respectively. OCD patients also displayed reduced structural integrity in clusters within the uncinate and cingulum fiber tracts. Finally, these deficits in limbic-frontal connectivity pathways, both at the functional and structural level, were associated with severity of OCD symptoms, as well as with each other. Our results thus suggest that risk aversion in OCD is mediated by abnormal limbic responses to threatening and rewarding stimuli, as well as by deficient functional and structural limbic-frontal connectivity. Such deficiency characterization may aid in identifying neural predictors for treatment response and localizing individual targets for direct neural intervention treatments.
Reduced functional connectivity (FC) in schizophrenia has been demonstrated either in task related or default network areas, but not between these networks, which interact meaningfully. We examined the role of FC between the inferior frontal gyrus (IFG) and medial prefrontal cortex (mPFC) in determining language-lateralization during a language task, and its association with structural integrity of the corpus-callosum. Only schizophrenia patients presented increased mPFC-IFG FC during task, which additionally corresponded to decreased white-matter organization of the corpus-callosum. These findings suggest that inability to suppress irrelevant internally-generated information while processing external stimuli might be the basis of functional psychopathology in schizophrenia.
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