Losing the chain of thought: A meta-analysis of functional neuroimaging studies using verbal tasks in schizophrenia.

BACKGROUND: Disorganization symptoms are a main feature of schizophrenia, which include illogical and incoherent thinking, circumstantiality, tangentiality and loose associations. As these symptoms entail language deficits, several functional neuroimaging studies have been performed in schizophrenia using verbal tasks, producing somewhat heterogenous results. Hence, we performed a meta-analysis seeking to identify the most reliable neural alterations observed in schizophrenia patients during such tasks. METHODS: Web of Sciences, PubMed, and EMBASE were searched for functional neuroimaging studies during verbal tasks (e.g. verbal fluency and semantic processing) in schizophrenia. Out of 795 screened articles, 33 were eligible for this meta-analysis. A coordinated-based meta-analysis was performed with the activation likelihood estimation (ALE) approach, using the cluster-level family-wise error (FWE) correction set at p < 0.05. RESULTS: In schizophrenia, hyperactivations were observed in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) and hypoactivations were observed in the right IFG, the precentral gyrus and the left caudate nucleus. Another analysis pooling hyper- and hypoactivations revealed altered activations, firstly, in the left IFG and MFG, secondly, in the left precentral gyrus, IFG and insula, and, thirdly, in the left angular gyrus and precuneus. In the light of these results, not only classic language-related regions are abnormally activated during verbal tasks in schizophrenia, but also brain regions involved in executive functions, autobiographical memory and, unexpectedly, in motor functions. Further functional neuroimaging studies are needed to investigate the role of the striatum in linguistic sequencing in schizophrenia.

Regional cerebral blood flow at rest in schizophrenia and major depressive disorder: A functional neuroimaging meta-analysis.

Severe mental disorders (SMDs) such as schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BD) are associated with altered brain function. Neuroimaging studies have illustrated spontaneous activity alterations across SMDs, but no meta-analysis has directly compared resting-state regional cerebral blood flow (rCBF) with one another. We conducted a meta-analysis of PET, SPECT and ASL neuroimaging studies to identify specific alterations of rCBF at rest in SMDs. Included are 20 studies in MDD, and 18 studies in SCZ. Due to the insufficient number of studies in BD, this disorder was left out of the analyses. Compared to controls, the SCZ group displayed reduced rCBF in the triangular part of the left inferior frontal gyrus and in the medial orbital part of the bilateral superior frontal gyrus. After correction, only a small cluster in the right inferior frontal gyrus exhibited reduced rCBF in MDD, compared to controls. Differences were found in these brain regions between SCZ and MDD. SCZ displayed reduced rCBF at rest in regions associated with default-mode, reward processing and language processing. MDD was associated with reduced rCBF in a cluster involved in response inhibition. Our meta-analysis highlights differences in the resting-state rCBF alterations between SCZ and MDD.

A Meta-Analysis of Functional Neuroimaging Studies of Ketamine Administration in Healthy Volunteers.

Ketamine administration leads to a psychotomimetic state when taken in large bolus doses, making it a valid model of psychosis. Therefore, understanding ketamine's effects on brain functioning is particularly relevant. This meta-analysis focused on neuroimaging studies that examined ketamine-induced brain activation at rest and during a task. Included are 10 resting-state studies and 23 task-based studies, 9 of which were measuring executive functions. Using a stringent statistical threshold (TFCE <0.05), the results showed increased activity at rest in the dorsal anterior cingulate cortex (ACC), and increased activation of the right Heschl's gyrus during executive tasks, following ketamine administration. Uncorrected results showed increased activation at rest in the right (anterior) insula and the right-fusiform gyrus, as well as increased activation during executive tasks in the rostral ACC. Rest-state studies highlighted alterations in core hubs of the salience network, while task-based studies suggested an impact on task-irrelevant brain regions. Increased activation in the rostral ACC may indicate a failure to deactivate the default mode network during executive tasks following ketamine administration. The results are coherent with alterations found in schizophrenia, which confer external validity to the ketamine model of psychosis. Studies investigating the neural mechanisms of ketamine's antidepressant action are warranted.

Isolation and characterization of gelatin-binding bison seminal vesicle secretory proteins.

Bovine seminal plasma (BSP) contains a family of major proteins designated BSP-A1/A2, BSP-A3, and BSP-30kDa (collectively called BSP proteins) that bind to sperm at ejaculation and potentiate sperm capacitation. Homologous proteins have been identified in stallion, boar, goat, and ram seminal plasma. We report here the isolation and characterization of homologous proteins from bison seminal vesicle secretions. Seminal vesicle secretory proteins were precipitated by adding cold ethanol and recovered by centrifugation. The precipitates were resuspended in ammonium bicarbonate, dialyzed, and lyophilized. Lyophilized proteins were dissolved in 0.05 M phosphate buffer (PB) and loaded onto a gelatin-agarose column. The unadsorbed proteins and adsorbed proteins were eluted with PB and 5 M urea in PB, respectively. The gelatin-adsorbed fraction was analyzed by SDS-PAGE and revealed the presence of four major proteins designated BiSV-16kDa, BiSV-17kDa, BiSV-18kDa, and BiSV-28kDa (BiSV: bison seminal vesicle proteins). Heparin-Sepharose chromatography allowed the separation of BiSV-16kDa, which did not bind heparin from other BiSV proteins, which bound heparin. Immunoblotting revealed that BiSV-16kDa cross-reacted with BSP-A3 antibodies, BiSV-17kDa and BiSV-18kDa cross-reacted with BSP-A1/-A2 antibodies, and BiSV-28kDa cross-reacted with BSP-30kDa antibodies. Radioimmunoassays indicated that approximately 25% of bison seminal vesicle total proteins are related to BSP proteins. The amino-terminal sequencing indicated that BiSV proteins share almost 100% sequence identity with BSP proteins. In addition, BiSV proteins bind to low-density lipoproteins isolated from hen's egg yolk. These results confirm that BSP protein homologs are present in mammalian seminal plasma and they may share the same biological role.