Schizotypal personality traits and multisensory integration: An investigation using the McGurk effect.

Multisensory integration, the process by which sensory information from different sensory modalities are bound together, is hypothesized to contribute to perceptual symptomatology in schizophrenia, in whom multisensory integration differences have been consistently found. Evidence is emerging that these differences extend across the schizophrenia spectrum, including individuals in the general population with higher levels of schizotypal traits. In the current study, we used the McGurk task as a measure of multisensory integration. We measured schizotypal traits using the Schizotypal Personality Questionnaire (SPQ), hypothesizing that higher levels of schizotypal traits, specifically Unusual Perceptual Experiences and Odd Speech subscales, would be associated with decreased multisensory integration of speech. Surprisingly, Unusual Perceptual Experiences were not associated with multisensory integration. However, Odd Speech was associated with multisensory integration, and this association extended more broadly across the Disorganized factor of the SPQ, including Odd or Eccentric Behaviour. Individuals with higher levels of Odd or Eccentric Behaviour scores also demonstrated poorer lip-reading abilities, which partially explained performance in the McGurk task. This suggests that aberrant perceptual processes affecting individuals across the schizophrenia spectrum may relate to disorganized symptomatology.

The Relationship Between Multisensory Temporal Processing and Schizotypal Traits.

Recent literature has suggested that deficits in sensory processing are associated with schizophrenia (SCZ), and more specifically hallucination severity. The DSM-5's shift towards a dimensional approach to diagnostic criteria has led to SCZ and schizotypal personality disorder (SPD) being classified as schizophrenia spectrum disorders. With SCZ and SPD overlapping in aetiology and symptomatology, such as sensory abnormalities, it is important to investigate whether these deficits commonly reported in SCZ extend to non-clinical expressions of SPD. In this study, we investigated whether levels of SPD traits were related to audiovisual multisensory temporal processing in a non-clinical sample, revealing two novel findings. First, less precise multisensory temporal processing was related to higher overall levels of SPD symptomatology. Second, this relationship was specific to the cognitive-perceptual domain of SPD symptomatology, and more specifically, the Unusual Perceptual Experiences and Odd Beliefs or Magical Thinking symptomatology. The current study provides an initial look at the relationship between multisensory temporal processing and schizotypal traits. Additionally, it builds on the previous literature by suggesting that less precise multisensory temporal processing is not exclusive to SCZ but may also be related to non-clinical expressions of schizotypal traits in the general population.

Schizotypal traits are not related to multisensory integration or audiovisual speech perception.

Multisensory integration, the binding of sensory information from different sensory modalities, may contribute to perceptual symptomatology in schizophrenia, including hallucinations and aberrant speech perception. Differences in multisensory integration and temporal processing, an important component of multisensory integration, are consistently found in schizophrenia. Evidence is emerging that these differences extend across the schizophrenia spectrum, including individuals in the general population with higher schizotypal traits. In the current study, we investigated the relationship between schizotypal traits and perceptual functioning, using audiovisual speech-in-noise, McGurk, and ternary synchrony judgment tasks. We measured schizotypal traits using the Schizotypal Personality Questionnaire (SPQ), hypothesizing that higher scores on Unusual Perceptual Experiences and Odd Speech subscales would be associated with decreased multisensory integration, increased susceptibility to distracting auditory speech, and less precise temporal processing. Surprisingly, these measures were not associated with the predicted subscales, suggesting that these perceptual differences may not be present across the schizophrenia spectrum.

Dissociable involvement of estrogen receptors in perirhinal cortex-mediated object-place memory in male rats.

Estrogens and the estrogen receptors (ER) - ERα, ERß, and the G-protein coupled estrogen receptor (GPER) - are implicated in various forms of hippocampus (HPC)-dependent memory. However, the involvement of ER-related mechanisms in perirhinal cortex (PRh), which is necessary for object memory, remains much less clear. Moreover, there is a paucity of data assessing ER contributions to cognition in males,despite documented sex differences at the cellular level.We hypothesized that estrogens in PRh are important for object memory in males, assessingthe role of 17-ßestradiol (E2), ERα, ERß, GPER, and their downstream signaling pathways, in PRh-mediated object-in-place (OiP) memory in gonadally-intact male rats. Intra-PRh administration of E2 enhanced both long-term memory (LTM; 24 h) and short-term memory (STM; 20 min). Conversely, aromatase inhibition with letrozole impaired LTM and STM. The semi-selective ER inhibitor ICI 182780 impaired LTM, but not STM. This effect may be due to inhibition of ERß, as the ERßagonist DPN, but not ERαagonist PPT, enhanced LTM. GPER was also found to be necessary in PRh, as the antagonist G15 impaired both LTM and STM. Western blot analyses demonstrated that phosphorylation levels of the extracellular signal-related kinase (ERK2 isoform), awell-establisheddownstream signaling pathway activated by estrogens through ERα/ERß, was elevated in PRh 5 min following OiP learning.We also reportincreased levels of c-Jun N-terminal kinase (JNK; p46 and p54 isoforms) phosphorylation in PRh 5 min following learning,consistent with recent research linking GPER activation and JNK signaling in the HPC. This effect was abolished by intra-PRh administration of G15, but not letrozole, suggesting that JNK signaling is triggered via GPER activation during OiP learning, and is possibly E2-independent, similar to findings in the HPC. These results, therefore, reveal interesting dissociations between the roles of various ERs, possibly involving both estrogen-dependent and independent mechanisms, in PRh-mediated object-place learning in male rats.

Disruption of the C/EBPα-miR-182 balance impairs granulocytic differentiation.

Transcription factor C/EBPα is a master regulator of myelopoiesis and its inactivation is associated with acute myeloid leukemia. Deregulation of C/EBPα by microRNAs during granulopoiesis or acute myeloid leukemia development has not been studied. Here we show that oncogenic miR-182 is a strong regulator of C/EBPα. Moreover, we identify a regulatory loop between C/EBPα and miR-182. While C/EBPα blocks miR-182 expression by direct promoter binding during myeloid differentiation, enforced expression of miR-182 reduces C/EBPα protein level and impairs granulopoiesis in vitro and in vivo. In addition, miR-182 expression is highly elevated particularly in acute myeloid leukemia patients with C-terminal CEBPA mutations, thereby depicting a mechanism by which C/EBPα blocks miR-182 expression. Furthermore, we present miR-182 expression as a prognostic marker in cytogenetically high-risk acute myeloid leukemia patients. Our data demonstrate the importance of a controlled balance between C/EBPα and miR-182 for the maintenance of healthy granulopoiesis.C/EBPα is a critical transcription factor involved in myelopoiesis and its inactivation is associated with acute myeloid leukemia (AML). Here the authors show a negative feedback loop between C/EBPα and miR-182 and identify this miRNA as a marker of high-risk AML.