bioRxiv ScienceSearch

bioRxiv · 10.1101/837815

Simultaneous assessment of P50, MMN, ERN and P300 event-related potentials among patients with Schizophrenia - an exploratory study

Abstract

PurposeP50 suppression (sensory gating or inhibition), MMN (mismatch negativity; bottom-up detection of change), ERN (error related negativity; conflict monitoring) and P300 (attention allocation and memory updating for salient events) are event related potentials (ERPs) widely reported to show abnormal cognitive functioning among patients with schizophrenia. In real-life scenarios the brain processing underlying these ERPs occur simultaneously, and yet prior ERP studies have evaluated them in isolation. The current study uses a novel paradigm that can examine these multiple ERPs simultaneously, and explore if the reported ERP deficits would hold true during a more realistic setting.\n\nMethodData from 21 patients with schizophrenia and 25 age- and gender-matched healthy controls were used, who underwent ERP recordings during the Assessing Neurocognition via Gamified Experimental Logic (ANGEL) paradigm. This is a gamified visual odd-ball paradigm that generates P300, the error responses generate ERN, and paired-tone audio distractors generate P50 and MMN. Peak-peak amplitude, mean amplitude and area-under-curve measures of ERP were measured at electrodes reflecting best morphology.\n\nResultsThough patients showed apparent ERP morphology differences relative to the controls, the standard ERP measures were comparable between groups, except for reduced ERN among patients. Interestingly, significant group differences were seen in N1-P2 complex suppression, despite comparable P50 suppression.\n\nContribution of the researchThe current study is the first to report multiple ERP component measures simultaneously evoked among patients with schizophrenia, and shows greater signs for impaired prediction mechanism. The findings of the study would provide a more ecologically valid evaluation of ERP-based cognitive functioning, and need to be replicated in a larger sample as well as other mental disorders.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Sasidharan, A., Nair, A. K., Marigowda, V., Lukose, A., John, J. P., Kutty, B. M.. 2019-11-11. Simultaneous assessment of P50, MMN, ERN and P300 event-related potentials among patients with Schizophrenia - an exploratory study. https://doi.org/10.1101/837815

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience