24 research outputs found
Functional near-infrared spectroscopy:A novel tool for detecting consciousness after acute severe brain injury
Recent advancements in functional neuroimaging have demonstrated that some unresponsive patients in the intensive care unit retain a level of consciousness that is inconsistent with their behavioral diagnosis of awareness. Functional near-infrared spectroscopy (fNIRS) is a portable optical neuroimaging method that can be used to measure neural activity with good temporal and spatial resolution. However, the reliability of fNIRS for detecting the neural correlates of consciousness remains to be established. In a series of studies, we evaluated whether fNIRS can record sensory, perceptual, and command-driven neural processing in healthy participants and in behaviorally nonresponsive patients. At the individual healthy subject level, we demonstrate that fNIRS can detect commonly studied resting state networks, sensorimotor processing, speech-specific auditory processing, and volitional command-driven brain activity to a motor imagery task. We then tested fNIRS with three acutely brain injured patients and found that one could willfully modulate their brain activity when instructed to imagine playing a game of tennis—providing evidence of preserved consciousness despite no observable behavioral signs of awareness. The successful application of fNIRS for detecting preserved awareness among behaviorally nonresponsive patients highlights its potential as a valuable tool for uncovering hidden cognitive states in critical care settings.</p
Cholinergic Surveillance over Hippocampal RNA Metabolism and Alzheimer's-Like Pathology
The relationship between long-term cholinergic dysfunction and risk of developing dementia is poorly understood. Here we used mice with deletion of the vesicular acetylcholine transporter (VAChT) in the forebrain to model cholinergic abnormalities observed in dementia. Whole-genome RNA sequencing of hippocampal samples revealed that cholinergic failure causes changes in RNA metabolism. Remarkably, key transcripts related to Alzheimer's disease are affected. BACE1, for instance, shows abnormal splicing caused by decreased expression of the splicing regulator hnRNPA2/B1. Resulting BACE1 overexpression leads to increased APP processing and accumulation of soluble Aβ1-42. This is accompanied by age-related increases in GSK3 activation, tau hyperphosphorylation, caspase-3 activation, decreased synaptic markers, increased neuronal death, and deteriorating cognition. Pharmacological inhibition of GSK3 hyperactivation reversed deficits in synaptic markers and tau hyperphosphorylation induced by cholinergic dysfunction, indicating a key role for GSK3 in some of these pathological changes. Interestingly, in human brains there was a high correlation between decreased levels of VAChT and hnRNPA2/B1 levels with increased tau hyperphosphorylation. These results suggest that changes in RNA processing caused by cholinergic loss can facilitate Alzheimer's-like pathology in mice, providing a mechanism by which decreased cholinergic tone may increase risk of dementia
The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.
RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. OBJECTIVES: This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. METHODS: The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. CONCLUSION: This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The authors thank Charlotte Oomen for valuable comments on the manuscript.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4007-
An Analysis of Canadian Institute for Health Research Funding for Research on Autism Spectrum Disorder
We examined patterns of Canadian Institute for Health Research (CIHR) funding on autism spectrum disorder (ASD) research. From 1999 to 2013, CIHR funded 190 ASD grants worth $48 million. Biomedical research received 43% of grants (46% of dollars), clinical research 27% (41%), health services 10% (7%), and population health research 8% (3%). The greatest number of grants was given in 2009, but 2003 saw the greatest amount. Funding is clustered in a handful of provinces and institutions, favouring biomedical research and disfavouring behavioural interventions, adaptation, and institutional response. Preference for biomedical research may be due to the detriment of clinical research
ПРИБЛИЖЕННОЕ К ПРИРОДЕ ЛЕСОВОДСТВО – ОСНОВА УСТОЙЧИВОГО ВЕДЕНИЯ ЛЕСНОГО ХОЗЯЙСТВА В УКРАИНЕ
Close-to-nature forestry is the system of forest management that favours a continuous renewal and formation of stands which most similar in structure and genesis to natural ones. The methodological basis of it is 8 principles which cover the evaluation of the processes of reproduction and formation of stable, natural, all-aged forests with continuous forest cover, biodiversity conservation, maintenance of the ecological functions of forests, an increase in the growing stock, harvesting of target trees, the greening of felling techniques and timber skidding. The existing set of pan-European criteria and indicators for sustainable forest management according to the standards of FSC sertification provides a basis to implement in Ukraine the system of close-to-nature forestry that is most relevant to the nature of the forest and, therefore, is the most promising in terms of environmental, economic and social aspects of multifunctional Forestry.Наближене до природи лісівництво – система організації та ведення лісового господарства, за якої досягається безперервне відновлення і формування деревостанів, максимально близьких за структурою і генезисом до природних. Методологічною основою його є 8 принципів, які оцінюють процеси відтворення і формування стійких природних різновікових лісів за безперервного лісового покриву, збереження біорізноманіття, підтримання екологічних функцій лісів, збільшення запасу насаджень і заготовку цільових дерев, екологізацію способів заготовки та трелювання деревини. Наявний набір загальноєвропейських критеріїв та індикаторів сталого ведення лісового господарства за схемами сертифікації FSC дає підставу імплементувати систему наближеного до природи лісівництва в Україні як таку, що найбільшою мірою відповідає природі лісу і тому є найперспективнішою з екологічної, економічної та соціальної компонент багатофункціонального лісівництва.Приближенное к природе лесоводство – система организации и ведения лесного хозяйства, при которой достигается непрерывное восстановление и формирование древостоев, максимально близких по структуре и генезису к естественным. Методологической основой его является 8 принципов, которые включают оценку процессов воспроизводства и формирования устойчивых природных разновозрастных лесов при непрерывном лесном покрове, сохранение биоразнообразия, поддержание экологических функций лесов, увеличение запаса насаждений и заготовку целевых деревьев, экологизацию способов заготовки и трелевки древесины. Существующий набор общеевропейских критериев и индикаторов устойчивого ведения лесного хозяйства по схемам сертификации FSC дает основание имплементировать систему приближенного к природе лесоводства в Украине как таковую, что в наибольшей степени соответствует природе леса и потому является наиболее перспективной с экологической, экономической и социальной составляющих многофункционального лесоводства