Brain and neuroscience advances最新文献

A recent study by Blank, Alink and Büchel, uses multivariate neuroimaging to investigate how the human brain processes the strength of face-related expectations and explores whether these expectations are represented in the same regions that process facial stimuli. In line with predictive coding theories, their study presents compelling evidence that the brain adjusts its processing based on the certainty of expectations. This occurs exclusively within high-level face-sensitive regions, rather than across the entire processing hierarchy. Here we critically discuss these findings and outline potential directions for future research to better understand how the human brain expects, processes, and perceives images.

This article presents edited highlights from a special session at the BNA International Festival of Neuroscience held in Brighton in April 2023. The session involved Desert Island Disc-style interviews between early career researchers and established investigators, discussing papers that influenced their neuroscience careers.

Depression is a debilitating illness, and stigma associated with it often prevents people from seeking support. Easy-to-administer and culturally- inclusive tools can allow for early screening for depressive symptoms in primary care clinics, especially in resource-limited settings. In this pre-registered pilot study (Stage 1 Report available at DOI: 10.3389/fpsyt.2022.840912), we produced an open-access isiXhosa-language version of the nine-item Patient Health Questionnaire (PHQ-9), a well-validated measure of depression incidence and severity, using a transcultural translation framework. We validated this isiXhosa PHQ-9 in a sample of N = 47 adolescents living with and without HIV in Cape Town, South Africa who speak isiXhosa at home. Reliability, convergent validity, and criterion validity were assessed, with T scores on the Achenbach System of Empirically Based Assessment Youth Self Report (YSR) form completed previously as reference standard. Our isiXhosa PHQ-9 exhibited satisfactory reliability, with Cronbach's $\alpha =0.866$, inter-item correlations ranging from 0.229 to 0.730, and mean item-total correlation of 0.69. PHQ-9 score and Withdrawn/Depressed component T scores on the Youth Self Report were moderately associated (Spearman's $\rho =0.40,p=0.011)$, indicating acceptable convergent validity. The isiXhosa PHQ-9 showed satisfactory criterion validity (area under the receiver operating characteristic curve, AUC = 0.706), but these analyses were under-powered. Principal component analysis revealed a one-factor solution, with 45.8% of variance explained by the first principal component and all factor loadings above conventional thresholds. Our isiXhosa translation of the PHQ-9 thus exhibited satisfactory psychometric properties in this pilot validation study and performed comparably to other PHQ-9 versions validated in different languages in African and global contexts. This questionnaire may serve as an invaluable culturally-inclusive screening tool for measuring depressive symptoms among isiXhosa speakers. Caution must be exercised as screening tools including the PHQ-9 may over- or under-estimate prevalence of depression. Further validation in larger, independent cohorts may enable wider use of our isiXhosa PHQ-9 as a screening tool in clinics, research studies, and mental health non-profits who serve amaXhosa.

As a leading cause of mortality and morbidity, stroke and its management have been studied extensively. Despite numerous pre-clinical studies identifying therapeutic targets, development of effective, specific pharmacotherapeutics remain limited. One significant limitation is a break in the translational pipeline - promising pre-clinical results have not always proven replicable in the clinic. Recent developments in virtual reality technology might help generate a better understanding of injury and recovery across the whole research pipeline in search of optimal stroke management. Here, we review the technologies that can be applied both clinically and pre-clinically to stroke research. We discuss how virtual reality technology is used to quantify clinical outcomes in other neurological conditions that have potential to be applied in stroke research. We also review current uses in stroke rehabilitation and suggest how immersive programmes would better facilitate the quantification of stroke injury severity and patient recovery comparable to pre-clinical study design. By generating continuous, standardised and quantifiable data from injury onset to rehabilitation, we propose that by paralleling pre-clinical outcomes, we can apply a better reverse-translational strategy and apply this understanding to animal studies. We hypothesise this combination of translational research strategies may improve the reliability of pre-clinical research outcomes and culminate in real-life translation of stroke management regimens and medications.

Teriflunomide is an oral disease-modifying therapy for relapsing-remitting multiple sclerosis patients. A decline in physical and cognitive functions, which negatively impacts their quality of life (QoL), is observed in relapsing-remitting multiple sclerosis patients. The aim of this study was to characterise adult Portuguese relapsing-remitting multiple sclerosis patients treated with teriflunomide in routine clinical practice concerning their quality of life, comorbidities, treatment effectiveness, satisfaction, compliance and safety. TeriLIVE-QoL was a multicentre, non-interventional, prospective cohort study that collected demographic and clinical characteristics, patient-reported outcomes and adverse events from patients treated with teriflunomide of 14 mg over 2 years. Notably, around 18 months of this period occurred during the COVID-19 pandemic. Of the 99 participants, 25% were treatment-naïve. Annualised relapse rate and the score for the Hospital Anxiety and Depression Scale decreased after 1 (p = 0.01) and 2 years of treatment (p < 0.001), respectively. Convenience (p = 0.001), effectiveness (p = 0.002) and global satisfaction scores (p < 0.001) presented high values (up to 95.6) and continued to improve along the study. Treatment persistence was 77%, and compliance reached 82% 2 years after initiation. Three patients experienced serious adverse events. TeriLIVE-QoL provides real-world evidence of clinical effectiveness, high treatment satisfaction, consistent safety and improved psychiatric outcomes, associated with elevated treatment persistence and compliance in patients treated with teriflunomide.iance reached 82% 2 years after initiation. Three patients experienced serious adverse events.

Professor Sir Colin Blakemore was a remarkable neuroscientist, persuasive communicator, and brave advocate for animal research who, sadly, passed away in June 2022 from amyotrophic lateral sclerosis. His work helped establish the concept of neuronal plasticity, which was fundamental to our understanding of the postnatal brain and continues to impact our outlook on neurodegenerative disorders. The BNA2023 Festival of Neuroscience dedicated its last plenary session in his honour, bringing together five prominent neuroscientists whose careers were shaped by Professor Blakemore. Here, we summarise the speakers' reflections on how Colin's support, generosity, and foresight influenced their academic paths, inspired their research, and changed their outlook on life.

A key hallmark of Alzheimer's disease (AD) is the accumulation of hyperphosphorylated tau in neurofibrillary tangles. This occurs alongside neuroinflammation and neurodegeneration. Pathological tau propagates through the AD brain in a defined manner, which correlates with neuron and synapse loss and cognitive decline. One proposed mechanism of tau spread is through synaptically connected brain structures. Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset AD and is associated with increased tau burden. Whether the apolipoprotein E (APOE) genotype influences neurodegeneration via tau spread is currently unknown. Here, we demonstrate that virally expressed human tau (with the P301L mutation) injected into mouse entorhinal cortex at 5-6 months or 15-16 months of age spreads trans-synaptically to the hippocampus by 14 weeks post-injection. Injections of tau in mice expressing human APOE2, APOE3 or APOE4, as well as APOE knock-outs, showed that tau can spread trans-synaptically in all genotypes and that APOE genotype and age do not affect the spread of tau. These data suggest that APOE genotype is not directly linked to synaptic spread of tau in our model, but other mechanisms involving non-cell autonomous manners of tau spread are still possible.

Short-term synaptic plasticity represents a fundamental mechanism in neural information processing and is regulated by neuromodulators. Here, using field recordings from the CA1 region of adult rat hippocampal slices, we show that excitatory synaptic transmission is suppressed by strong but not moderate activation of adenosine A₁ receptors by 2-Chloro-N⁶-cyclopentyladenosine (CCPA) more in the dorsal than the ventral hippocampus; in contrast, both mild and strong activation of GABA_B receptors by baclofen (1 μM, 10 μM) suppress synaptic transmission more in the ventral than the dorsal hippocampus. Using a 10-pulse stimulation train of variable frequency, we found that CCPA modulates short-term synaptic plasticity independently of the suppression of synaptic transmission in both segments of the hippocampus and at stimulation frequencies greater than 10 Hz. However, specifically regarding the paired-pulse ratio (PPR) and frequency facilitation/depression (FF/D) we found significant drug action before but not after adjusting conditioning responses to control levels. Activation of GABA_BRs by baclofen suppressed synaptic transmission more in the ventral than the dorsal hippocampus. Furthermore, relatively high (10 μM) but not low (1 μM) baclofen concentration enhanced both PPR and FF in both hippocampal segments at stimulation frequencies greater than 1 Hz, independently of the suppression of synaptic transmission by baclofen. These results show that A₁Rs and GABA_BRs control synaptic transmission more effectively in the dorsal and the ventral hippocampus, respectively, and suggest that these receptors modulate PPR and FF/D at different frequency bands of afferent input, in both segments of the hippocampus.