Modulation of dorsal premotor cortex differentially influences I‐wave excitability in primary motor cortex of young and older adults

First published: 16 May 2023Previous research using transcranial magnetic stimulation (TMS) has demonstrated weakened connectivity between dorsal premotor cortex (PMd) and motor cortex (M1) with age. While this alteration is probably mediated by changes in the communication between the two regions, the effect of age on the influence of PMd on specific indirect (I) wave circuits within M1 remains unclear. The present study therefore investigated the influence of PMd on early and late I-wave excitability inM1of young and older adults. Twenty-two young (mean±SD, 22.9±2.9 years) and 20 older (66.6 ± 4.2 years) adults participated in two experimental sessions involving either intermittent theta burst stimulation (iTBS) or sham stimulation over PMd. Changes within M1 following the intervention were assessed with motor-evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. We applied posterior–anterior (PA) and anterior–posterior (AP) current single-pulse TMS to assess corticospinal excitability (PA1mV; AP1mV; PA0.5mV, early; AP0.5mV, late), and paired-pulse TMS short intracortical facilitation for I-wave excitability (PA SICF, early; AP SICF, late). Although PMd iTBS potentiated PA1mV and AP1mV MEPs in both age groups (both P < 0.05), the time course of this effect was delayed for AP1mV in older adults (P = 0.001). Furthermore, while AP0.5mV, PA SICF and AP SICF were potentiated in both groups (all P < 0.05), potentiation of PA0.5mV was only apparent in young adults (P < 0.0001).While PMd influences early and late I-wave excitability in young adults, direct PMdmodulation of the early circuits is specifically reduced in older adults.Wei-Yeh Liao, George M. Opie, Ulf Ziemann, and John G. Semmle

The dawn of the dead : (improbable) art after aI-zombie apocalypse

In recent years there has been growing interest in artificial neural networks (ANNs) which are quickly becoming the primary device for machine learning. Used for finding patterns in large data sets, ANNs were also recently employed in many artistic contexts: as tools for artists, semi-independent creators of content, and even as invisible "critics" which / who predict our aesthetic preferences. The aim of this paper is to speculate about the disruptive effect of these ‘alien agencies’ on the (modernist) aesthetic regime of art centred around the notion of autonomy. The author examines how neural networks and connectionist epistemologies may potentially affect the most common ways of producing, circulating, and valorising art. He claims that the possibility of automatizing creativity and art criticism may lead to the emergence of a new aesthetic regime based on forms of dynamic, distributed and probabilistic governance

Electrocardiographic diagnosis of left ventricular hypertrophy in aortic valve disease: evaluation of ECG criteria by cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Left ventricular hypertrophy (LVH) is a hallmark of chronic pressure or volume overload of the left ventricle and is associated with risk of cardiovascular morbidity and mortality. The purpose was to evaluate different electrocardiographic criteria for LVH as determined by cardiovascular magnetic resonance (CMR). Additionally, the effects of concentric and eccentric LVH on depolarization and repolarization were assessed.</p> <p>Methods</p> <p>120 patients with aortic valve disease and 30 healthy volunteers were analysed. As ECG criteria for LVH, we assessed the Sokolow-Lyon voltage/product, Gubner-Ungerleider voltage, Cornell voltage/product, Perugia-score and Romhilt-Estes score.</p> <p>Results</p> <p>All ECG criteria demonstrated a significant correlation with LV mass and chamber size. The highest predictive values were achieved by the Romhilt-Estes score 4 points with a sensitivity of 86% and specificity of 81%. There was no difference in all ECG criteria between concentric and eccentric LVH. However, the intrinsicoid deflection (V6 37 ± 1.0 ms vs. 43 ± 1.6 ms, p < 0.05) was shorter in concentric LVH than in eccentric LVH and amplitudes of ST-segment (V5 -0.06 ± 0.01 vs. -0.02 ± 0.01) and T-wave (V5 -0.03 ± 0.04 vs. 0.18 ± 0.05) in the anterolateral leads (p < 0.05) were deeper.</p> <p>Conclusion</p> <p>By calibration with CMR, a wide range of predictive values was found for the various ECG criteria for LVH with the most favourable results for the Romhilt-Estes score. As electrocardiographic correlate for concentric LVH as compared with eccentric LVH, a shorter intrinsicoid deflection and a significant ST-segment and T-wave depression in the anterolateral leads was noted.</p

Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics

We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10−9), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients’ fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: −2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: −1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients

ALSgeneScanner: a pipeline for the analysis and interpretation of DNA sequencing data of ALS patients

Amyotrophic lateral sclerosis (ALS, MND) is a neurodegenerative disease of upper and lower motor neurons resulting in death from neuromuscular respiratory failure, typically within two years of first symptoms. Genetic factors are an important cause of ALS, with variants in more than 25 genes having strong evidence, and weaker evidence available for variants in more than 120 genes. With the increasing availability of next-generation sequencing data, non-specialists, including health care professionals and patients, are obtaining their genomic information without a corresponding ability to analyze and interpret it. Furthermore, the relevance of novel or existing variants in ALS genes is not always apparent. Here we present ALSgeneScanner, a tool that is easy to install and use, able to provide an automatic, detailed, annotated report, on a list of ALS genes from whole-genome sequencing (WGS) data in a few hours and whole exome sequence data in about 1 h on a readily available mid-range computer. This will be of value to non-specialists and aid in the interpretation of the relevance of novel and existing variants identified in DNA sequencing data

ALSgeneScanner: a pipeline for the analysis and interpretation of DNA sequencing data of ALS patients

Amyotrophic lateral sclerosis (ALS, MND) is a neurodegenerative disease of upper and lower motor neurons resulting in death from neuromuscular respiratory failure, typically within two years of first symptoms. Genetic factors are an important cause of ALS, with variants in more than 25 genes having strong evidence, and weaker evidence available for variants in more than 120 genes. With the increasing availability of next-generation sequencing data, non-specialists, including health care professionals and patients, are obtaining their genomic information without a corresponding ability to analyze and interpret it. Furthermore, the relevance of novel or existing variants in ALS genes is not always apparent. Here we present ALSgeneScanner, a tool that is easy to install and use, able to provide an automatic, detailed, annotated report, on a list of ALS genes from whole-genome sequencing (WGS) data in a few hours and whole exome sequence data in about 1 h on a readily available mid-range computer. This will be of value to non-specialists and aid in the interpretation of the relevance of novel and existing variants identified in DNA sequencing data

Telomere length is greater in ALS than in controls: a whole genome sequencing study

BACKGROUND: Amyotrophic lateral sclerosis is a neurodegenerative disease of motor neurons resulting in progressive paralysis and death, typically within 3-5 years. Although the heritability of ALS is about 60%, only about 11% is explained by common gene variants, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication and shorten naturally with age. Gender and age are risk factors for ALS and also associated with telomere length. We therefore investigated telomere length in ALS. METHODS: We estimated telomere length by applying a bioinformatics analysis to whole genome sequence data of leukocyte-derived DNA from people with ALS and age and gender-matched matched controls in a UK population. We tested the association of telomere length with ALS and ALS survival. RESULTS: There were 1241 people with ALS and 335 controls. The median age for ALS was 62.5 years and for controls, 60.1 years, with a male-female ratio of 62:38. Accounting for age and sex, there was a 9% increase of telomere length in ALS compared to matched controls. Those with longer telomeres had a 16% increase in median survival. Of nine SNPs associated with telomere length, two were also associated with ALS: rs8105767 near the ZNF208 gene (p = 1.29 × 10-4) and rs6772228 (p = 0.001), which is in an intron for the PXK gene. CONCLUSIONS: Longer telomeres in leukocyte-derived DNA are associated with ALS, and with increased survival in those with ALS

A randomised, controlled trial of a dietary intervention for adults with major depression (the "SMILES" trial): study protocol

Despite increased investment in its recognition and treatment, depression remains a substantial health and economic burden worldwide. Current treatment strategies generally focus on biological and psychological pathways, largely neglecting the role of lifestyle. There is emerging evidence to suggest that diet and nutrition play an important role in the risk, and the genesis, of depression. However, there are limited data regarding the therapeutic impact of dietary changes on existing mental illness. Using a randomised controlled trial design, we aim to investigate the efficacy and cost-efficacy of a dietary program for the treatment of Major Depressive Episodes. <br /