Human Cerebral Activation during Steady-State Visual-Evoked Responses

Flicker stimuli of variable frequency (2-90 Hz) elicit a steady-state visual-evoked response (SSVER) in the electroencephalogram (EEG) with the same frequency as the stimulus. In humans, the amplitude of this response peaks at approximately 15 Hz, decreasing at higher stimulation frequencies. It was not known whether this peak response corresponds to increased synaptic activity in the visual cortex or to other mechanisms [for instance, the temporal coherence (phase summation) of evoked responses]. We studied the SSVER in 16 normal volunteers by means of visual stimulation at 14 different frequencies (from 5 to 60 Hz) while recording the EEG. In nine subjects of the group, we measured regional cerebral blood flow (rCBF) with positron emission tomography (PET)-H2(15)O at rest and during visual stimulation at five different frequencies: 5, 10, 15, 25, and 40 Hz. We confirmed that the amplitude of the SSVER in occipital regions peaks at 15 Hz stimulation. Applying to the PET rCBF data a contrast weighted by the amplitude of the SSVER, we determined that the primary visual cortex rCBF follows an activation pattern similar to the SSVER. This finding suggests that the amplitude of the SSVER corresponds to increased synaptic activity, specifically in Brodmann's area 17. Additionally, this study showed that visual stimulation at 40 Hz causes selective activation of the macular region of the visual cortex, and that a region in the dorsal aspect of the Crus I lobule of the left cerebellar hemisphere is activated during repetitive visual stimulation

Topography of Cortical Activation Differs for Fundamental and Harmonic Frequencies of the Steady-State Visual-Evoked Responses. An EEG and PET H15 2 O Study

In humans, visual flicker stimuli of graded frequency (2--90 Hz) elicit an electroencephalographic (EEG) steady-state visual-evoked response (SSVER) with the same fundamental frequency as the stimulus and, in addition, a series of harmonic responses. The fundamental component of the SSVER is generated by increased synaptic activity in primary visual cortex (V1). We set out to determine the cortical origin of the harmonic responses in humans. For this purpose, we recorded the SSVERs at 5 different frequencies (5, 10, 15, 25, and 40 Hz) and measured regional cerebral blood flow (rCBF) with positron emission tomography-H15 2 O at rest and during visual stimulation at the same frequencies. The rCBF contrast weighted by the amplitude of the SSVERs first harmonics showed activation of a swath of cortex perpendicular to V1, including mostly the inferior half of the parietooccipital sulcus. This area overlapped minimally with the primary visual cortex activated by the fundamental frequency. A different method, estimating EEG cortical source current density with lowresolution brain electromagnetic tomography, gave the same results. Our finding suggests that the inferior portion of the banks of the parieto-occipital sulci contains association visual cortex involved in the procparieto-occipital sulcus

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

La neuroimagen en la enfermedad de Alzheimer: perspectiva actual

Clinically, computerized tomography scanning and magnetic resonance imaging (MRI) are the neuroimaging techniques most frequently used in the work up of progressive cognitive impairment, in order to rule out tumors or other treatable etiologies. However, as we move closer to having more effective treatments for Alzheimer's disease (AD), we experience a greater need to use markers of early brain injury. Among them is neuroimaging. In this review we give some examples of the role of MRI and of functional MRI (fMRI) as markers of early brain changes. DEVELOPMENT: Regional metabolism, studied with positron emission tomography (PET) can also be used advantageously to depict early cortical changes in mild cognitive impairment (MCI) and even presymptomatic AD. SPECT, less expensive than PET, has a lower sensitivity, but has been extensively studied and using quantification methods can help even in MCI. Newer PET markers allow for the evaluation of activated microglia in vivo, as well as for the study of amyloid deposition in the brain and the activity of enzymes such as acetyl-cholinesterase. CONCLUSION: Future refinements in the neuroimaging techniques seem likely to help in the early diagnosis, evaluation of potential treatments and clarification of pathogenetic mechanisms in AD

La neuroimagen en la enfermedad de Alzheimer: perspectiva actual

Clinically, computerized tomography scanning and magnetic resonance imaging (MRI) are the neuroimaging techniques most frequently used in the work up of progressive cognitive impairment, in order to rule out tumors or other treatable etiologies. However, as we move closer to having more effective treatments for Alzheimer's disease (AD), we experience a greater need to use markers of early brain injury. Among them is neuroimaging. In this review we give some examples of the role of MRI and of functional MRI (fMRI) as markers of early brain changes. DEVELOPMENT: Regional metabolism, studied with positron emission tomography (PET) can also be used advantageously to depict early cortical changes in mild cognitive impairment (MCI) and even presymptomatic AD. SPECT, less expensive than PET, has a lower sensitivity, but has been extensively studied and using quantification methods can help even in MCI. Newer PET markers allow for the evaluation of activated microglia in vivo, as well as for the study of amyloid deposition in the brain and the activity of enzymes such as acetyl-cholinesterase. CONCLUSION: Future refinements in the neuroimaging techniques seem likely to help in the early diagnosis, evaluation of potential treatments and clarification of pathogenetic mechanisms in AD

Human Cerebral Activation during Steady-State Visual-Evoked Responses

Flicker stimuli of variable frequency (2-90 Hz) elicit a steady-state visual-evoked response (SSVER) in the electroencephalogram (EEG) with the same frequency as the stimulus. In humans, the amplitude of this response peaks at approximately 15 Hz, decreasing at higher stimulation frequencies. It was not known whether this peak response corresponds to increased synaptic activity in the visual cortex or to other mechanisms [for instance, the temporal coherence (phase summation) of evoked responses]. We studied the SSVER in 16 normal volunteers by means of visual stimulation at 14 different frequencies (from 5 to 60 Hz) while recording the EEG. In nine subjects of the group, we measured regional cerebral blood flow (rCBF) with positron emission tomography (PET)-H2(15)O at rest and during visual stimulation at five different frequencies: 5, 10, 15, 25, and 40 Hz. We confirmed that the amplitude of the SSVER in occipital regions peaks at 15 Hz stimulation. Applying to the PET rCBF data a contrast weighted by the amplitude of the SSVER, we determined that the primary visual cortex rCBF follows an activation pattern similar to the SSVER. This finding suggests that the amplitude of the SSVER corresponds to increased synaptic activity, specifically in Brodmann's area 17. Additionally, this study showed that visual stimulation at 40 Hz causes selective activation of the macular region of the visual cortex, and that a region in the dorsal aspect of the Crus I lobule of the left cerebellar hemisphere is activated during repetitive visual stimulation

Using videoclips to improve theoretical anatomy teaching.

_The introduction of multimedia technology into teaching has brought important changes in university teaching. This study seeks to evaluate whether the use of videoclips as an aid in theoretical lessons, improves students' performance. This study compares the results obtained in the scores of Locomotive System Anatomy for two consecutive groups of students that took the First Course of Descriptive Anatomy in the degree in Biology at the Faculty of Health and Life Sciences at the "Universitat Pompeu Fabra" of Barcelona. In the first group (G1 n=72) theoretical teaching was performed through conventional lectures supported with Power Point slides. In the second group (G2 n=70), during the same period of time, teaching was done by a combination of theoretical explanations, slides and multimedia anatomy videos, which were used in order to reinforce the key issues of all lectures. The evaluation of theoretical knowledge was achieved through a multiple-choice test of 30 questions (70% of final mark), completing with a test of 15 short questions (30% of the final mark). Evaluation was performed done selectively based on the same items in 2 examinations using different questions. Comparison of the results revealed that students receiving video input performed significantly better (G1:76 % vs. G2: 93 %). Results of students opinion performed between two groups find out to be similar in each group (G1: 5.7 vs. G2: 5.9). The adequacy of the teaching material was (G1: 7.9 vs. G2: 7.5) and general satisfaction with the teaching methods was (G1: 6.8 vs. G2: 6.8). In conclusion, it was found that using videoclips for teaching Human Anatomy significantly improves students' comprehension of theoretical contents

Topography of Cortical Activation Differs for Fundamental and Harmonic Frequencies of the Steady-State Visual-Evoked Responses. An EEG and PET H15 2 O Study

In humans, visual flicker stimuli of graded frequency (2--90 Hz) elicit an electroencephalographic (EEG) steady-state visual-evoked response (SSVER) with the same fundamental frequency as the stimulus and, in addition, a series of harmonic responses. The fundamental component of the SSVER is generated by increased synaptic activity in primary visual cortex (V1). We set out to determine the cortical origin of the harmonic responses in humans. For this purpose, we recorded the SSVERs at 5 different frequencies (5, 10, 15, 25, and 40 Hz) and measured regional cerebral blood flow (rCBF) with positron emission tomography-H15 2 O at rest and during visual stimulation at the same frequencies. The rCBF contrast weighted by the amplitude of the SSVERs first harmonics showed activation of a swath of cortex perpendicular to V1, including mostly the inferior half of the parietooccipital sulcus. This area overlapped minimally with the primary visual cortex activated by the fundamental frequency. A different method, estimating EEG cortical source current density with lowresolution brain electromagnetic tomography, gave the same results. Our finding suggests that the inferior portion of the banks of the parieto-occipital sulci contains association visual cortex involved in the procparieto-occipital sulcus

Spatial and diel patterns of volatile organic compounds, DMSP-derived compounds, and planktonic microorganisms around a tropical scleractinian coral colony

21 pages, 8 figures, supplementary material https://www.frontiersin.org/articles/10.3389/fmars.2022.944141/full#supplementary-material.-- Data availability statement: The datasets presented in this study can be found in online repositories. DMSPC and VOC concentrations can be found at https://zenodo.org/badge/DOI/10.5281/zenodo.7043105.svg. Raw sequences are available at the European Nucleotide Archive (http://www.ebi.ac.uk/ena) under project numbers PRJEB54595 (16S rDNA metabarcoding), PRJEB54596 (18S rDNA metabarcoding) and PRJEB54597 (metagenomics)Volatile organic compounds (VOCs) are constituents of marine ecosystems including coral reefs, where they are sources of atmospheric reactivity, indicators of ecosystem state, components of defense strategies, and infochemicals. Most VOCs result from sunlight-related processes; however, their light-driven dynamics are still poorly understood. We studied the spatial variability of a suite of VOCs, including dimethylsulfide (DMS), and the other dimethylsulfoniopropionate-derived compounds (DMSPCs), namely, DMSP, acrylate, and dimethylsulfoxide (DMSO), in waters around colonies of two scleractinian corals (Acropora pulchra and Pocillopora sp.) and the brown seaweed Turbinaria ornata in Mo’orean reefs, French Polynesia. Concentration gradients indicated that the corals were sources of DMSPCs, but less or null sources of VOCs other than DMS, while the seaweed was a source of DMSPCs, carbonyl sulfide (COS), and poly-halomethanes. A focused study was conducted around an A. pulchra colony where VOC and DMSPC concentrations and free-living microorganism abundances were monitored every 6 h over 30 h. DMSPC concentrations near the polyps paralleled sunlight intensity, with large diurnal increases and nocturnal decrease. rDNA metabarcoding and metagenomics allowed the determination of microbial diversity and the relative abundance of target functional genes. Seawater near coral polyps was enriched in DMS as the only VOC, plus DMSP, acrylate, and DMSO, with a large increase during the day, coinciding with high abundances of symbiodiniacean sequences. Only 10 cm below, near the coral skeleton colonized by a turf alga, DMSPC concentrations were much lower and the microbial community was significantly different. Two meters down current from the coral, DMSPCs decreased further and the microbial community was more similar to that near the polyps than that near the turf alga. Several DMSP cycling genes were enriched in near-polyp with respect to down-current waters, namely, the eukaryotic DMS production and DMS oxidation encoding genes, attributed to the coral and the algal symbiont, and the prokaryotic DMS production gene dddD, harbored by coral-associated Gammaproteobacteria. Our results suggest that solar radiation-induced oxidative stress caused the release of DMSPCs by the coral holobiont, either directly or through symbiont expulsion. Strong chemical and biological gradients occurred in the water between the coral branches, which we attribute to layered hydrodynamicsThis project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement #834162, SUMMIT Advanced Grant to RS). It was also funded by the Spanish Ministry of Science and Innovation (MCIN/AEI, doi: 10.13039/501100011033) through the BIOGAPS grant (CTM2016-81008-R) to RS, the TRAITS grant (PID2019-110011RB-C32) to JMG, the “Severo Ochoa Centre of Excellence” accreditation (CEX2019-000298-S) to the ICM, and predoctoral grants to MM-N (BES-2017-080048) and MC-B (FPU16-01925). LX and DK were supported by funding from the National Science Foundation Chemical Oceanography program (CO-1756907) to DK. SG was supported by an Australian Government Endeavour Research FellowshipPeer reviewe

Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP

Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65years) Alzheimer’s disease (AD). We performed a screening for mutations in the coding regions of presenilins, as well as exons 16 and 17 of the APP gene in a total of 231 patients from the Iberian peninsular with a clinical diagnosis of early onset AD (mean age at onset of 52.9 years; range 31– 64). We found three novel mutations in PSEN1, one novel mutation in PSEN2, and a novel mutation in the APP gene. Four previously described mutations in PSEN1 were also found. The same analysis was carried in 121 elderly healthy controls from the Iberian peninsular, and a set of 130 individuals from seven African populations belonging to the Centre d’Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP), in order to determine the extent of normal variability in these genes. Interestingly, in the latter series, we found five new nonsynonymous changes in all three genes and a presenilin 2 variant (R62H) that has been previously related to AD. In some of these mutations, the pathologic consequence is uncertain and needs further investigation. To address this question we propose and use a systematic algorithm to classify the putative pathology of AD mutations