Superior Temporal Gyrus In Schizophrenia Research Articles

Reduced gray matter volume of left superior temporal gyrus in schizophrenia with auditory verbal hallucinations: a voxel-based morphometry study

Auditory verbal hallucinations (AVHs) which are the core psychopathology symptoms in schizophrenia patients cause amounts of distress, functional disability and behavioral dys-control. However, the neural mechanism with the onset of AVHs in schizophrenia remains unclear. In the present study, we recruited 30 schizophrenia patients with AVHs, 20 schizophrenia patients with non-AVHs (nAVHs), and 50 healthy controls. Structure magnetic resonance imaging was obtained, and voxel-based morphometry (VBM) was used to analyse the gray matter volume (GMV) in the three groups. We found that the GMV of anterior cingulate cortex (ACC), left superior temporal gyrus (STG), and left middle temporal gyrus (MTG) significantly decreased in schizophrenia patients compared to healthy controls. In addition, the left STG with significantly decreased volume was found in nAVHs compared to AVHs, but no significant changes of GMV in ACC and left MTG were found between AVHs and nAVHs. Our current study identified the abnormal GMV of the left STG in schizophrenia patients with AVHs. Our findings further supported the view that, whilst mild reduced GMV of the left STG might still enable the emergence of AVHs, more severe alterations may prevent the occurrence of AVHs experience.

Prominent increased calcineurin immunoreactivity in the superior temporal gyrus in schizophrenia: A postmortem study.

Many neuroimaging studies have demonstrated structural changes in the superior temporal gyrus (STG) in patients with schizophrenia. Several postmortem studies have reported on the pathogenesis of schizophrenia, but few reports have investigated alterations in molecules in the STG. In addition, several studies have suggested that calcineurin (CaN) inadequacy may be a risk factor for schizophrenia, but no reports about CaN expression in the STG in schizophrenia have been published. We compared the density of CaN-immunoreactive (CaN-IR) neurons in the STG from 11 patients with schizophrenia with that of 11 sex- and age-matched controls. We used immunohistochemical analysis with rabbit polyclonal antibodies against human CaN. In the STG, the density of CaN-IR neurons in layers II - VI in the group with schizophrenia was significantly higher than that in the control group. Our results confirmed pathological changes in the STG in patients with schizophrenia, suggesting that alterations in the CaN pathway play a role in the pathogenesis of schizophrenia.

PM469. Structural Alterations of the Superior Temporal Gyrus in Schizophrenia: Detailed Subregional Differences

PM469. Structural Alterations of the Superior Temporal Gyrus in Schizophrenia: Detailed Subregional Differences

Structural alterations of the superior temporal gyrus in schizophrenia: Detailed subregional differences

BackgroundReduced gray matter volumes in the superior temporal gyrus (STG) have been reported in patients with schizophrenia. Such volumetric abnormalities might denote alterations in cortical thickness, surface area, local gyrification or all of these factors. The STG can be anatomically divided into five subregions using automatic parcellation in FreeSurfer: lateral aspect of the STG, anterior transverse temporal gyrus of Heschl gyrus (HG), planum polare (PP) of the STG, planum temporale (PT) of the STG and transverse temporal sulcus. MethodsWe acquired magnetic resonance imaging (MRI) 3T scans from 40 age- and sex-matched patients with schizophrenia and 40 healthy subjects, and the scans were automatically processed using FreeSurfer. General linear models were used to assess group differences in regional volumes and detailed thickness, surface area and local gyrification. ResultsAs expected, patients with schizophrenia had significantly smaller bilateral STG volumes than healthy subjects. Of the five subregions in the STG, patients with schizophrenia showed significantly and marginally reduced volumes in the lateral aspect of the STG and PT of the STG bilaterally compared with healthy subjects. The volumetric alteration in bilateral lateral STG was derived from both the cortical thickness and surface area but not local gyrification. There was no significant laterality of the alteration in the lateral STG between patients and controls and no correlation among the structures and clinical characteristics. ConclusionsThese findings suggest that of five anatomical subregions in the STG, the lateral STG is one of the most meaningful regions for brain pathophysiology in schizophrenia.

Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders.

Abnormalities in brain-derived neurotrophic factor (BDNF)/trkB signaling have been implicated in the etiology of schizophrenia and mood disorders. Patients with schizophrenia, bipolar disorder (BPD) and major depression (MDD) have reduced levels of neurotrophins in their brains when compared with normal unaffected individuals; however, only a few brain areas have been examined to date. Owing to the broad range of symptoms manifested in these disorders, we hypothesized that multiple associative areas of the neocortex may be implicated and that the degree of change in BDNF and trkB−TK+ mRNA expression and the cortical region or layers involved may vary according to Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis. We compared BDNF and trkB−TK+ mRNA levels across all layers of the prefrontal cortex (dorsolateral prefrontal cortex, DLPFC), orbital frontal cortex (OFC), anterior cingulate cortex (ACC), inferior temporal gyrus (ITG) and superior temporal gyrus (STG) in four groups: schizophrenia, BPD, MDD and unaffected controls (n=60). BDNF mRNA levels were significantly decreased in layers IV and V of DLPFC in schizophrenia patients, in layer VI of ACC in schizophrenia and MDD and in layer VI of ITG in schizophrenia, BPD and MDD. BDNF mRNA levels were also significantly decreased in layer V and/or VI of STG in schizophrenia, BPD and MDD. TrkB−TK+ mRNA levels were only significantly decreased in the cortical layer VI of OFC in BPD. The shared and distinct patterns of neurotrophin transcript reductions, with some specific to each group, may compromise the function and plasticity of distinct cortical areas to various degrees in the different groups and contribute to the range and overlap of symptoms manifested across the diagnoses.

Morphometry of superior temporal gyrus and planum temporale in schizophrenia and psychotic bipolar disorder

Structural abnormalities in temporal lobe, including the superior temporal gyrus (STG) and planum temporale (PT), have been reported in schizophrenia (SCZ) and bipolar disorder (BPD) patients. While most MRI studies have suggested gray matter volume and surface area reduction in temporal lobe regions, few have explored changes in laminar thickness in PT and STG in SCZ and BPD. ROI subvolumes of the STG from 94 subjects were used to yield gray matter volume, gray/white surface area and laminar thickness for STG and PT cortical regions. Morphometric analysis suggests that there may be gender and laterality effects on the size and shape of the PT in BPD (n=36) and SCZ (n=31) with reduced laterality in PT in subjects with SCZ but not in BPD. In addition, PT surface area was seen to be larger in males, and asymmetry in PT surface area was larger in BPD. Subjects with SCZ had reduced thickness and smaller asymmetry in PT volume. Thus, the PT probably plays a more sensitive role than the STG in structural abnormalities seen in SCZ.

The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing

Schizophrenia (SZ) is a complex disease characterized by impaired neuronal functioning. Although defective alternative splicing has been linked to SZ, the molecular mechanisms responsible are unknown. Additionally, there is limited understanding of the early transcriptomic responses to neuronal activation. Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders.

Cerebral responses to vocal attractiveness and auditory hallucinations in schizophrenia: a functional MRI study

Impaired self-monitoring and abnormalities of cognitive bias have been implicated as cognitive mechanisms of hallucination; regions fundamental to these processes including inferior frontal gyrus (IFG) and superior temporal gyrus (STG) are abnormally activated in individuals that hallucinate. A recent study showed activation in IFG-STG to be modulated by auditory attractiveness, but no study has investigated whether these IFG-STG activations are impaired in schizophrenia. We aimed to clarify the cerebral function underlying the perception of auditory attractiveness in schizophrenia patients. Cerebral activation was examined in 18 schizophrenia patients and 18 controls when performing Favorability Judgment Task (FJT) and Gender Differentiation Task (GDT) for pairs of greetings using event-related functional MRI. A full-factorial analysis revealed that the main effect of task was associated with activation of left IFG and STG. The main effect of Group revealed less activation of left STG in schizophrenia compared with controls, whereas significantly greater activation in schizophrenia than in controls was revealed at the left middle frontal gyrus (MFG), right temporo-parietal junction (TPJ), right occipital lobe, and right amygdala (p < 0.05, FDR-corrected). A significant positive correlation was observed at the right TPJ and right MFG between cerebral activation under FJT minus GDT contrast and the score of hallucinatory behavior on the Positive and Negative Symptom Scale. Findings of hypo-activation in the left STG could designate brain dysfunction in accessing vocal attractiveness in schizophrenia, whereas hyper-activation in the right TPJ and MFG may reflect the process of mentalizing other person's behavior by auditory hallucination by abnormality of cognitive bias.

Effective surgical intervention for schizophrenia‐like symptoms and low event‐related potentials caused by arachnoid cyst

ARACHNOID CYSTS CAN occur wherever there is arachnoid tissue, although nearly half of all arachnoid cysts arise in the temporal fossa–Sylvian fissure. In general, clinical manifestations of arachnoid cyst are often mild. Several articles have suggested that there is an etiological relationship between arachnoid cyst and psychiatric symptoms.1 A 24-year-old man first presented with compulsive checking at the age of 21 years. In addition, he had experienced delusions of persecution and auditory hallucinations. He had no neurological abnormality and was treated with antipsychotic medication. The antipsychotics, however, did not improve the psychotic symptoms. At that time, computed tomography showed an arachnoid cyst in his left middle cranial fossa. The basic rhythm on electroencephalogram (EEG) was posterior dominant alpha wave. The psychotic symptoms were considered to be caused by the arachnoid cyst because of the antipsychotics' low effectiveness. Magnetic resonance imaging (MRI) showed a large anteromedial left temporal fossa arachnoid cyst (80 mm in diameter) expanding into the left Sylvian fissure. Event-related potentials (ERP), such as P300, and mismatch negativity (MMN) were low in amplitude. Some reports have suggested that surgical intervention for arachnoid cyst improved psychotic symptoms.2 Therefore, endoscopic fenestration of the cyst was performed. The delusions and hallucinations improved postoperatively, and the patient was discharged. The delusions of persecution, however, later increased. MRI using time–spatial labeling inversion pulse showed inadequate flow of cerebrospinal fluid through the fenestra. Hence, another craniotomy was performed. Fenestra closure caused by arachnoid regeneration was found during this procedure. After partial removal of the cyst wall, the delusions remitted partially. The amplitude of P300 and MMN in the frontocentral region increased after each surgery. In contrast, MMN amplitude in the bilateral mastoid region showed no change. There was no difference between the basic rhythm and amplitudes of EEG before and after surgery. This patient provided written, informed consent. In some reports, left temporal arachnoid cysts were found to be associated with schizophrenia-like symptoms.2 Recent studies have demonstrated volume loss in the left superior temporal gyrus in schizophrenia.3 The temporal lobe is regarded as an important region for P300 and MMN, the amplitudes of which are reduced in schizophrenia and the other psychoses. This is one of the reproducible abnormal biological findings in schizophrenia. Therefore, small P300 and MMN amplitude, schizophrenia-like psychotic symptoms, and left temporal lobe volume loss are closely related.3 In the present case, the compressed and/or defective development of the temporal lobe due to the arachnoid cyst probably caused the low P300 and MMN amplitudes. If low ERP were of organic origin, the amplitudes would improve.

Effects of aging on the morphologies of Heschl's gyrus and the superior temporal gyrus in schizophrenia: A postmortem study

The etiology of schizophrenia has been proposed to be neurodevelopmental based on neuroimaging and molecular biological studies. If there is neuronal vulnerability based on neurodevelopment failures in schizophrenic brains, then the impact of aging may have a greater effect on schizophrenic brains than on normal brains. To determine the impact of aging on schizophrenic brains, we investigated the age-related morphological changes of the cross-sectional area of the gray matter (GM) in the left Heschl's gyrus (HG) and the left superior gyrus (STG) in 22 schizophrenic and 24 age- and sex-matched normal control postmortem brains two-dimensionally. The subject groups were divided into younger groups (30–54years of age) and older groups (65–84years of age) on the basis of age at death. Both in schizophrenic and control subjects, the GM area in HG and the STG was significantly smaller in the older group than in the younger group, however, no significant differences were observed between the schizophrenic and control subjects. In the STG, the cross-sectional area of the white matter (WM) was also measured. In the older group, the ratio of the GM area to the WM area in the STG was significantly larger in schizophrenic subjects than controls, although there was no significant difference between the schizophrenic and control subjects in the younger group. These findings indicate that the impact of aging has a greater effect on the WM in the STG in schizophrenic subjects than in normal individuals, although the pathological basis is still unclear.

Altered DARPP-32 expression in the superior temporal gyrus in schizophrenia

Many neuroimaging studies have revealed structural abnormalities in the superior temporal gyrus (STG) in schizophrenia (Kasai et al., 2003a, 2003b; Sun et al., 2009). Neurophysiological studies of mismatch negativities (MMN) generated in the STG have suggested impaired function of N-methyl-d-aspartate (NMDA) receptors (Javitt et al., 1996). Although many postmortem studies have been conducted on the pathogenesis of schizophrenia, relatively few reports have studied molecular alterations in the STG (Bowden et al., 2008; Deng and Huang, 2006; Kang et al., 2009; Katsel et al., 2005; Le Corre et al., 2000; Nudmamud and Reynolds, 2001; Sokolov et al., 2000). The STG shows pronounced changes in gene expression when compared to other regions implicated in schizophrenia (Katsel et al., 2005). Dopamine and a cAMP-regulated phosphoprotein of molecular weight 32kDa (DARPP-32) is thought to be closely associated with pathophysiological changes in the dopamine and glutamate systems in schizophrenia because, when activated by phosphorylation, DARPP-32 acts as a critical regulator of D1 dopamine receptor and NMDA receptor activity (Greengard et al., 1999). The molecular pathways involving DARPP-32 appear important in the pathogenesis of schizophrenia. Here, we show dramatic alterations in DARPP-32 expression in the STG of postmortem brains from patients with schizophrenia. To clarify the detailed histological and cellular expression of DARPP-32 in the STG in schizophrenia, we immunohistochemically examined postmortem brains by using specific antibodies. We compared the density of immunoreactive cells of the STG (BA22) from 11 schizophrenia patients with those from 11 age- and sex-matched controls, and found significantly lower densities of DARPP-32-immunoreactive (IR) cells and threonine (Thr) 34-phosphorylated DARPP-32-IR cells in the STG in the schizophrenia group. Thus, the DARPP-32-related pathogenesis in schizophrenia may be more severe in the STG than previously found in the prefrontal cortex.

Decreased density of serotonin 2A receptors in the superior temporal gyrus in schizophrenia-a postmortem study

The superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In this study, using in situ quantitative autoradiography in postmortem tissue, we investigated the binding of the [ 3H]ketanserin to 5-HT 2A receptors and [ 3H]mesulergine to 5-HT 2C receptors in the left STG of 8 male schizophrenic patients compared to 8 control subjects. A strong [ 3H]ketanserin binding was observed in the STG, however there was a very weak [ 3H]mesulergine binding in the STG. A significant decrease in binding of [ 3H]ketanserin was clearly observed in schizophrenia patients in comparison with control subjects. There were no significant correlations between 5-HT 2A binding density and age, postmortem intervals, or brain pH. These results suggest that the alterations of the 5-HT 2A receptors contribute to the pathophysiology of the STG in schizophrenia. Furthermore, there is a clear tendency for a positive correlation between 5-HT 2A and muscarinic M1 receptor bindings, and for negative correlations between 5-HT 2A and GABA A receptor bindings and between muscarinic M1 and GABA A receptor bindings. This provides a possible mechanism of auditory hallucinations through interactions between 5-HT 2A, acetylcholine muscarinic and GABA transmissions in the STG in schizophrenia.

Altered gene expression in the superior temporal gyrus in schizophrenia

BackgroundThe superior temporal gyrus (STG), which encompasses the primary auditory cortex, is believed to be a major anatomical substrate for speech, language and communication. The STG connects to the limbic system (hippocampus and amygdala), the thalamus and neocortical association areas in the prefrontal cortex, all of which have been implicated in schizophrenia.ResultsTo identify altered mRNA expression in the superior temporal gyrus (STG) in schizophrenia, oligonucleotide microarrays were used with RNA from postmortem STG tissue from 7 individuals with schizophrenia and 7 matched non-psychiatric controls. Overall, there was a trend towards down-regulation in gene expression, and altered expression of genes involved in neurotransmission, neurodevelopment, and presynaptic function was identified. To confirm altered expression identified by microarray analysis, the mRNA expression levels of four genes, IPLA2γ, PIK31R1, Lin-7b and ATBF1, were semi-quantitatively measured using relative real-time PCR. A number of genes with altered expression in the STG were also shown to have similar changes in expression as shown in our previous study of peripheral blood lymphocytes in schizophrenia.ConclusionThis study has identified altered expression of genes in the STG involved in neurotransmission and neurodevelopment, and to a lesser extent presynaptic function, which further support the notion of these functions playing an integral role in the development of schizophrenia.

No changes in densities of cannabinoid receptors in the superior temporal gyrus in schizophrenia

In recent years, abnormal changes in the endocannabinoid system have been found in schizophrenia. The superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In this study, we investigated the binding density of cannabinoid CB1 receptors in the STG of schizophrenia patients compared to control subjects. Quantitative autoradiography was used to investigate the binding densities of [(3)H]SR141716A (a selective antagonist) and [(3)H]CP-55940 (an agonist) to the CB1 receptors in the STG. Post-mortem brain tissue was obtained from the NSW Tissue Resource Centre (Australia). Contrasting to previous findings in the alterations of CB1 receptor densities in the prefrontal, anterior and posterior cingulate cortex of schizophrenia, which were suggested to be associated to impairment of cognition function, no significant difference was found between the schizophrenia and control cases in both [(3)H]SR141716A and [(3)H]CP-55940 binding. We suggest that CB1 receptors in the STG are not involved in the pathology of schizophrenia and the auditory hallucination symptom of this disease.

Altered expression of regulator of G-protein signalling 4 (RGS4) mRNA in the superior temporal gyrus in schizophrenia

To identify altered mRNA expression of regulator of G-protein signalling 4 (RGS4) in the superior temporal gyrus (STG) in schizophrenia mRNA expression of RGS4 was measured from post-mortem STG tissue from 13 individuals with schizophrenia and 13 matched non-psychiatric controls using relative real-time PCR. Significantly decreased expression of RGS4 mRNA in the STG in schizophrenia was identified in 10 of the 13 matched pairs. Altered expression of RGS4 in cortical regions previously implicated in schizophrenia, such as the STG further supports the notion of RGS4 as a potential genetic and functional biological marker of schizophrenia.

Increased density of GABAA receptors in the superior temporal gyrus in schizophrenia

The superior temporal gyrus (STG) is strongly implicated in the pathophysiology of schizophrenia, particularly with regards to auditory hallucinations. In a previous study we reported a decrease in the density of M1 and M2/M4 muscarinic receptors in the STG in schizophrenia. In this study, we investigated the density of GABA(A) receptors in the left STG of schizophrenia patients compared to control subjects. We used quantitative autoradiography to investigate the binding of the agonist [(3)H] muscimol to GABA(A )receptors in the STG. A significantly higher density of [(3)H] muscimol binding was observed in the upper three quarters of the STG grey matter (corresponding to layers I-IV) than in the lower one-quarter (layers V-VI) in both groups. A significant increase (about 30%, P<0.05) in binding of [(3)H] muscimol was clearly observed in schizophrenia patients compared to control subjects. There were no significant correlations between [(3)H] muscimol binding density and age, post-mortem interval, brain pH or final recorded antipsychotic drug use. These results suggest an increase of GABA(A) receptor densities in the STG of schizophrenia patients.

Interstitial white matter neuron density in the dorsolateral prefrontal cortex and parahippocampal gyrus in schizophrenia

Alterations in the density or distribution of interstitial white matter neurons are taken as evidence in support of an early developmental component to schizophrenia. However, the existence and nature of interstitial white matter neuron changes in schizophrenia remain inconclusive. Recently, we reported that interstitial white matter neuron density is increased in the superficial white matter of the superior temporal gyrus in schizophrenia, but unchanged in deep white matter. This study extends our investigations to the dorsolateral prefrontal cortex and parahippocampal gyrus. Using the specific neuronal antibody NeuN, interstitial white matter neuron density was found to be increased in schizophrenia in the superficial white matter of the dorsolateral prefrontal cortex, with no significant changes elsewhere. As interstitial white matter neurons are presumed to be remnants of the embryonic cortical subplate, these findings provide additional evidence supportive of an early developmental abnormality in schizophrenia.

Decreased density of muscarinic receptors in the superior temporal gyrusin schizophrenia

Recent studies have indicated that muscarinic receptors are involved in the pathophysiology in schizophrenia, particularly in cognitive deficits. The superior temporal gyrus (STG) is an area that has also been strongly implicated in the pathophysiology of schizophrenia. Therefore, in this study, we investigated the binding density of two muscarinic antagonists, [(3)H]pirenzepine and [(3)H]AF-DX 384, in the STG of schizophrenia patients compared with controls. A significant decrease (44% in the superficial layers and 48% in the deep layers, P<0.01) in binding density of [(3)H]pirenzepine was observed in schizophrenia patients, which suggested a reduction of muscarinic M1 and M4 receptor densities in the STG of schizophrenia patients. A tendency toward decreased [(3)H]AF-DX 384 binding density (34%, P=0.09) was also observed in schizophrenia patients compared with controls. Because of the positive correlation between [(3)H]pirenzepine and [(3)H]AF-DX 384 binding, and, insofar as both ligands have high affinities for the M4 receptor, the involvement of M4 receptor alteration is also suggested in the STG in schizophrenia. These results suggest that changes of the muscarinic receptors M1 and M4 might contribute to the STG pathology in schizophrenia.

Increased levels of expression of an NMDARI splice variant in the superior temporal gyrus in schizophrenia.

Expression patterns of mRNAs for the NMDARI subunit (NRI) carboxy-terminus isoforms were investigated in postmortem brain tissue using isotopic in situ hybridization. Three brain regions (superior temporal, middle frontal and visual cortices) were examined in patients with schizophrenia (n = 6) and control subjects (n = 6). A 22% higher level of expression of the NRI isoform that contains neither spliced exon was observed in the superior temporal gyrus of patients with schizophrenia compared with controls (p = 0.01). No differences were observed in the expression of the other isoforms in the three regions studied. These data suggest that NRI alternative splicing might be abnormal in schizophrenia and reinforce previous findings implicating the superior temporal gyrus as a site of neural dysfunction in schizophrenia.

Identification of neural circuits underlying P300 abnormalities in schizophrenia.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.