bioRxiv ScienceSearch

bioRxiv · 10.1101/2020.03.03.974725

Visuospatial n-back test for early detection of mild cognitive impairment in patients with Parkinsons Disease : an fMRI study

Abstract

BackgroundCognitive impairment is a common symptom in the patients with Parkinsons disease (PD). In delineating a therapeutic plan, the early diagnosis of mild cognitive impairment in PD (PD-MCI) is important. Patients with PD-MCI have severe impairment in frontal executive function and/or visuospatial recognition. However, the clinical assessment of these functions is not routinely performed. MethodIn this study, we aimed to clarify the advantage of visuospatial version of the n-back test as a tool for the early detection of neuropsychological change in the patients with PD-MCI. The score of 0-back test reflects visuospatial recognition, and the scores of 1-back and 2-back reflect visuospatial working memory. PD-MCI was classified according to the criteria provided by the Movement Disorder Society Task Force for mild cognitive impairment in PD. We recruited 13 patients with PD-MCI, and 15 patients with cognitive normal PD. Using functional MRI (fMRI), we also aimed to clarify the specific brain regions associated with the impairment of visuospatial working memory. ResultWe demonstrated that the correct answer rate of patients with PD-MCI was lower in the 2-back test than patients with PD-CN. However, we did not find statistical difference in the 0-back test. These results indicate the preservation of visuospatial recognition and the impairment of visuospatial working memory in the patients with PD-MCI. We revealed the reduced activation within the middle frontal gyrus (MFG) and the inferior parietal lobule (IPL) during the 2-back test in the patients with PD-MCI. It may be associated with the severity of cortico-striatal dysfunction in the dopaminergic neural network which is associated with Lewy body pathology. ConclusionThe visuospatial n-back test has advantages for use in rapid and early detection of impaired visual recognition and working memory. The combination of functional neuroimaging and neuropsychological tests may provide markers for the increased risk of dementia before the development of an irreversible disease-specific pathology.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kawashima, S., Shimizu, Y., Ueki, Y., Matsukawa, N.. 2020-03-03. Visuospatial n-back test for early detection of mild cognitive impairment in patients with Parkinsons Disease : an fMRI study. https://doi.org/10.1101/2020.03.03.974725

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