Activity In Human Subjects Research Articles

Longitudinal assessment of human antibody binding to hemagglutinin elicited by split-inactivated influenza vaccination over six consecutive seasons.

Participants between the ages of 10-86 years old were vaccinated with split-inactivated influenza vaccine (Fluzone®) in six consecutive influenza seasons from 2016-2017 to 2021-2022. Vaccine effectiveness varies from season to season as a result of both host immune responses as well as evolutionary changes in the influenza virus surface glycoproteins that provide challenges to vaccine manufacturers to produce more effective annual vaccines. Next generation influenza vaccines are in development and may provide protective immune responses against a broader number of influenza viruses and reduce the need for annual vaccination. An improved understanding how current influenza vaccines are influenced by human host immune responses in people of different ages and co-morbidities is necessary for designing the next-generation of 'universal' or broadly-protective influenza vaccines. Overall, pre-existing immune responses to previous influenza virus exposures, either by past infections or vaccinations, is a critical factor influencing host responses to seasonal influenza vaccination. Participants vaccinated in consecutive seasons had reduced serum hemagglutination-inhibition (HAI) activity against strains included in the vaccine compared to participants that had not been vaccinated in the preceding 1-2 years prior to entering this study. The magnitude and breadth of these antibody responses were also modulated by the age of the participant. Elderly participants over 65 years of age, in general, had lower pre-existing HAI titers each season prior to vaccination with lower post-vaccination titers compared to children or young adults under the age of 35. The administration of higher doses (HD) of the split-inactivated vaccine enhanced the antibody titers in the elderly. This report showcases 6 consecutive years of antibody HAI activity in human subjects receiving seasonal split-inactivated influenza vaccine.

Exploring the Potential of Metformin as a Novel Nutritional Intervention for Mitigating Arterial Thrombotic Risk in Human Subjects.

Metformin is extensively prescribed as a first-line medication for the management of type 2 diabetes (T2D), a condition frequently coexisting with kidney disease, cardiovascular diseases (CVDs), and retinopathy. The widespread use of metformin is attributed to its well-established safety profile. Notably, platelets play a crucial role in arterial thrombosis, a significant factor contributing to the development of CVDs and cerebrovascular diseases. Our previous study has demonstrated that metformin may reduce collagen-induced platelet activation in human subjects, indicating a positive impact on platelet function. However, its mechanisms in platelet activation stimulated by other agonists remain not fully understood, especially regarding the effect of metformin on thrombininduced platelet activation. In this study, metformin inhibited platelet aggregation stimulated by thrombin in a concentration-dependent manner. Metformin suppressed P-selectin expression, [Ca2+]i mobilization, ATP-release, and as well as protein kinase C (PKC), Akt and p38 mitogen-activated protein kinase (MAPK). In conclusion, metformin can potentially function as a nutritional agent for long-term use at a low dose to prevent cardiovascular diseases (CVDs) or other chronic diseases.

Simulation of background neuronal activity and noise in human intracranial microwire recordings

BackgroundHuman intracranial microwire recordings allow measurement of neuronal activity in human subjects at a fine temporal and spatial scale. The recorded extracellular potentials represent a mixture of action potentials from nearby neurons, local field potentials, and other noise sources. Signal processing of these recordings is used to separate the activity of putative single neurons from other background and noise. To better understand the separation of single neuron activity, one approach is to simulate the signals produced by neurons firing action potentials combined with background activity and noise. New methodThis paper characterizes the background activity and noise in human intracranial microwire recordings and presents an accurate and efficient method of simulation using an infinite impulse response filter to color white noise. Results and comparisonThis method reproduces the power spectral density of the background activity and noise over a frequency range of 1–5000 Hz and is over 200 times faster than previously used methods. It thus facilitates large scale studies of variation of noise sources, field potentials, and processing parameters. It performs equivalently in terms of spike sorting to simulation using white noise. Another advantage is that the simulated signals are known to arise from a pseudorandom number generator and cannot be the result of detecting simulated background spiking activity. ConclusionsThis approach provides a rapid and accurate method of simulating background noise and neural activity in human intracranial microwire recordings. It is suitable for use in large scale simulations to study spike sorting in this type of recording.

Deuterium metabolic imaging for 3D mapping of glucose metabolism in humans with central nervous system lesionsat 3T.

To explore the potential of 3T deuterium metabolic imaging (DMI) using a birdcage 2 H radiofrequency (RF) coil in both healthy volunteers and patients with central nervous system (CNS) lesions. A modified gradient filter, home-built 2 H volume RF coil, and spherical k-space sampling were employed in a three-dimensional chemical shift imaging acquisition to obtain high-quality whole-brain metabolic images of 2 H-labeled water and glucose metabolic products. These images were acquired in a healthy volunteer and three subjects with CNS lesions of varying pathologies. Hardware and pulse sequence experiments were also conducted to improve the signal-to-noise ratio of DMI at 3T. The ability to quantify local glucose metabolism in correspondence to anatomical landmarks across patients with varying CNS lesions is demonstrated, and increased lactate is observed in one patient with the most active disease. DMI offers the potential to examine metabolic activity in human subjects with CNS lesions with DMI at 3T, promising for the potential of the future clinical translation of this metabolic imaging technique.

The Role of Coproporphyrins as Endogenous Biomarkers for Organic Anion Transporting Polypeptide 1B Inhibition - progress from 2016 to 2023.

Since the initial clinical study investigating CP-I and CP-III as endogenous biomarkers for OATP inhibition DDIs published in 2016, significant progress has been made in confirming the usefulness of the CPs, particularly the CP-I, as biomarkers in assessing OATP inhibition DDIs. CP-I exhibits selectivity towards OATP1B activity in human subjects with genetic variants of OATP1B1. Its sensitivity to a broad spectrum of clinical OATP1B inhibitors has been established, from weak to vigorous. Dose-dependent CP-I changes in healthy human subjects show agreement with DDI magnitudes of probe substrates by rifampin treatment. PBPK models have been established for concentration changes of plasma CP-I with OATP inhibitors, demonstrating the usefulness of supporting the quantitative translation of the effect of CP-I levels into the DDI risk assessment of potential OATP inhibitors. As plasma CP-I's sensitivity, specificity, and selectivity have been validated in humans, monitoring CP-I levels in single and multiple clinical phase I dose escalation studies is recommended for early assessment of DDI risks and understanding the full dose-response of an investigational drug to OATP inhibitions. A decision tree is proposed to preclude the need to conduct a dedicated DDI study by administering a probe substrate drug to human subjects. Significance Statement The mini-review summarized the validation paths of CP-I and CP-III as biomarkers of OATP1B inhibition in humans for their selectivity, specificity, and sensitivity. The utility of monitoring CP-I to assess drug-drug interactions of OATP1B inhibition in early drug development is proposed. Changes in plasma CP-I in phase I dose range studies can be used to frame plans for late-stage development and facilitate the mechanistic understanding of complex drug-drug interactions.

Phenotyping Indices of CYP450 and P-Glycoprotein in Human Volunteers and in Patients Treated with Painkillers or Psychotropic Drugs.

Drug-metabolizing enzymes and drug transporters are key determinants of drug pharmacokinetics and response. The cocktail-based cytochrome P450 (CYP) and drug transporter phenotyping approach consists in the administration of multiple CYP or transporter-specific probe drugs to determine their activities simultaneously. Several drug cocktails have been developed over the past two decades in order to assess CYP450 activity in human subjects. However, phenotyping indices were mostly established for healthy volunteers. In this study, we first performed a literature review of 27 clinical pharmacokinetic studies using drug phenotypic cocktails in order to determine 95%,95% tolerance intervals of phenotyping indices in healthy volunteers. Then, we applied these phenotypic indices to 46 phenotypic assessments processed in patients having therapeutic issues when treated with painkillers or psychotropic drugs. Patients were given the complete phenotypic cocktail in order to explore the phenotypic activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A, and P-glycoprotein (P-gp). P-gp activity was evaluated by determining AUC0-6h for plasma concentrations over time of fexofenadine, a well-known substrate of P-gp. CYP metabolic activities were assessed by measuring the CYP-specific metabolite/parent drug probe plasma concentrations, yielding single-point metabolic ratios at 2 h, 3 h, and 6 h or AUC0-6h ratio after oral administration of the cocktail. The amplitude of phenotyping indices observed in our patients was much wider than those observed in the literature for healthy volunteers. Our study helps define the range of phenotyping indices with "normal" activities in human volunteers and allows classification of patients for further clinical studies regarding CYP and P-gp activities.

Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L)

Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state.

Spectral Fingerprints of Cortical Neuromodulation.

Pupil size has been established as a versatile marker of noradrenergic and cholinergic neuromodulation, which has profound effects on neuronal processing, cognition, and behavior. However, little is known about the cortical control and effects of pupil-linked neuromodulation. Here, we show that pupil dynamics are tightly coupled to temporally, spectrally, and spatially specific modulations of local and large-scale cortical population activity in the human brain. We quantified the dynamics of band-limited cortical population activity in resting human subjects using magnetoencephalography and investigated how neural dynamics were linked to simultaneously recorded pupil dynamics. Our results show that pupil-linked neuromodulation does not merely affect cortical population activity in a stereotypical fashion. Instead, we identified three frontal, precentral, and occipitoparietal networks, in which local population activity with distinct spectral profiles in the theta, beta, and alpha bands temporally preceded and followed changes in pupil size. Furthermore, we found that amplitude coupling at ∼16 Hz in a large-scale frontoparietal network predicted pupil dynamics. Our results unravel network-specific spectral fingerprints of cortical neuromodulation in the human brain that likely reflect both the causes and effects of neuromodulation.SIGNIFICANCE STATEMENT Brain function is constantly affected by modulatory neurotransmitters. Pupil size has been established as a versatile marker of noradrenergic and cholinergic neuromodulation. However, because the cortical correlates of pupil dynamics are largely unknown, fundamental questions remain unresolved. Which cortical networks control pupil-linked neuromodulation? Does neuromodulation affect cortical activity in a stereotypical or region-specific fashion? To address this, we quantified the dynamics of cortical population activity in human subjects using magnetoencephalography. We found that pupil dynamics are coupled to highly specific modulations of local and large-scale cortical activity in the human brain. We identified four cortical networks with distinct spectral profiles that temporally predicted and followed pupil size dynamics. These effects likely reflect both the cortical control and effect of neuromodulation.

Insulin resistance is linked to a specific profile of immune activation in human subjects

We tested the hypothesis that a particular immune activation profile might be correlated with insulin resistance in a general population. By measuring 43 markers of immune, endothelial, and coagulation activation, we have previously shown that five different immune activation profiles may be distinguished in 150 volunteers. One of these profiles, Profile 2, characterized by CD4+ T cell senescence, inflammation, monocyte, B cell, and endothelial activation, presented elevated insulinemia, glycemia, triglyceridemia, and γ-glutamyl transferase, a marker of liver injury, in comparison with other profiles. Our data are compatible with a model in which a particular immune activation profile might favor the development of insulin resistance and metabolic syndrome. In this hypothesis, identification of this profile, that is feasible with only 3 markers with an error rate of 5%, might allow to personalize the screening and prevention of metabolic syndrome-driven morbidities as liver steatosis.

From State-to-Trait Meditation: Reconfiguration of Central Executive and Default Mode Networks.

While brain default mode network (DMN) activation in human subjects has been associated with mind wandering, meditation practice has been found to suppress it and to increase psychological well-being. In addition to DMN activity reduction, experienced meditators (EMs) during meditation practice show an increased connectivity between the DMN and the central executive network (CEN). However, the gradual change between DMN and CEN configuration from pre-meditation, during meditation, and post-meditation is unknown. Here, we investigated the change in DMN and CEN configuration by means of brain activity and functional connectivity (FC) analyses in EMs across three back-to-back functional magnetic resonance imaging (fMRI) scans: pre-meditation baseline (trait), meditation (state), and post-meditation (state-to-trait). Pre-meditation baseline group comparison was also performed between EMs and healthy controls (HCs). Meditation trait was characterized by a significant reduction in activity and FC within DMN and increased anticorrelations between DMN and CEN. Conversely, meditation state and meditation state-to-trait periods showed increased activity and FC within the DMN and between DMN and CEN. However, the latter anticorrelations were only present in EMs with limited practice. The interactions between networks during these states by means of positive diametric activity (PDA) of the fractional amplitude of low-frequency fluctuations (fALFFs) defined as [Formula: see text] revealed no trait differences but significant increases during meditation state that persisted in meditation state-to-trait. The gradual reconfiguration in DMN and CEN suggest a neural mechanism by which the CEN negatively regulates the DMN and is probably responsible for the long-term trait changes seen in meditators and reported psychological well-being.

Differential Effect of the Physical Embodiment on the Prefrontal Cortex Activity as Quantified by Its Entropy

Computer-mediated-communication (CMC) research suggests that unembodied media can surpass in-person communication due to their utility to bypass the nonverbal components of verbal communication such as physical presence and facial expressions. However, recent results on communicative humanoids suggest the importance of the physical embodiment of conversational partners. These contradictory findings are strengthened by the fact that almost all of these results are based on the subjective assessments of the behavioural impacts of these systems. To investigate these opposing views of the potential role of the embodiment during communication, we compare the effect of a physically embodied medium that is remotely controlled by a human operator with such unembodied media as telephones and video-chat systems on the frontal brain activity of human subjects, given the pivotal role of this region in social cognition and verbal comprehension. Our results provide evidence that communicating through a physically embodied medium affects the frontal brain activity of humans whose patterns potentially resemble those of in-person communication. These findings argue for the significance of embodiment in naturalistic scenarios of social interaction, such as storytelling and verbal comprehension, and the potential application of brain information as a promising sensory gateway in the characterization of behavioural responses in human-robot interaction.

Complement therapeutics meets nanomedicine: overcoming human complement activation and leukocyte uptake of nanomedicines with soluble domains of CD55

Complement activation plays an important role in pharmacokinetic and performance of intravenously administered nanomedicines. Significant efforts have been directed toward engineering of nanosurfaces with low complement activation, but due to promiscuity of complement factors and redundancy of pathways, it is still a major challenge. Cell membrane-anchored Decay Accelerating Factor (DAF, a.k.a. CD55) is an efficient membrane bound complement regulator that inhibits both classical and alternative C3 convertases by accelerating their spontaneous decay. Here we tested the effect of various short consensus repeats (SCRs, “sushi” domains) of human CD55 on nanoparticle-mediated complement activation in human sera and plasma. Structural modeling suggested that SCR-2, SCR-3 and SCR-4 are critical for binding to the alternative pathway C3bBb convertase, whereas SCR-1 is dispensable. Various domains were expressed in E.coli and purified by an affinity column. SCRs were added to lepirudin plasma or sera from different healthy subjects, to monitor nanoparticle-mediated complement activation as well as C3 opsonization. Using superparamagnetic iron oxide nanoworms (SPIO NWs), we found that SCR-2-3-4 was the most effective inhibitor (IC50 ~0.24 μM for C3 opsonization in sera), followed by SCR-1-2-3-4 (IC50 ~0.6 μM), whereas shorter domains (SCR-3, SCR-2-3, SCR-3-4) were ineffective. SCR-2-3-4 also inhibited C5a generation (IC50 ~0.16 μM in sera). In addition to SPIO NWs, SCR-2-3-4 effectively inhibited C3 opsonisation and C5a production by clinically approved nanoparticles (Feraheme, LipoDox and Onivyde). SCR-2-3-4 inhibited both lectin and alternative pathway activation by nanoparticles. When added to lepirudin-anticoagulated blood from healthy donors, it significantly reduced the uptake of SPIO NWs by neutrophils and monocytes. These results suggest that soluble domains of membrane-bound complement inhibitors are potential candidates for preventing nanomedicine-mediated complement activation in human subjects.

Effect of distance vision and refractive error on the spontaneous eye blink activity in human subjects in primary eye gaze

PurposeTo evaluate whether visual target character and visibility affects spontaneous eye blink rate (SEBR) in primary eye gaze and silence. MethodsVideo recordings were made of young healthy adults who were either emmetropic (n=32) or who wore spectacles for refractive error (range −4.75D and +4.50D (n=31). Emmetropes had 5min recordings made whilst seated and looking towards a distant whiteboard. For spectacle wearers, recordings were made whilst looking towards the whiteboard with a 35mm sized cross, and repeated after spectacle removal. The average number of eye blinks over 5min was assessed, and its intra-subject variability as the coefficient of variation (COV). ResultsOver 5min without a distance target, an average SEBR of 10.4blinks/min was observed in emmetropes with a of COV=38.1%, and a significant increase in SEBR over the 5th minute to 13.6blinks/min. Hyperopes being asked to look towards a distant target showed the essentially same blinking rate of 11.1/min with or without spectacle wear with the intra-subject variability (COV) being 21.3%. Myopic subjects showed a slightly higher SEBR if looking towards a target without their spectacles (12.4 vs. 11.0blinks/min), with the COV being 18.8%. ConclusionsThe studies indicate that some form of visual target could be useful to promote constancy of spontaneous eye blink activity over time, but that a distance visual target (when provided) does not need to be seen clearly.

Prefrontal cortical activation while viewing urban and garden scenes: A pilot fNIRS study.

Recent studies have shown that pleasant and unpleasant emotions could be detected through functional Near-Infrared Spectroscopy (fNIRS). This study investigates the prefrontal cortical activation in human subjects while they were viewing urban and garden scenes. A multi-channel continuous wave fNIRS system was used to record the prefrontal cortical activations from seven subjects. During the data collection, the subjects viewed 40 trials of video clips. In each trial, the subjects viewed a video of randomized urban or garden scenes for 30s followed by 30s of idle scene which showed a dark blue progress bar on black background on the screen. NIRS-SPM is employed to work out the changes of hemoglobin response and the prefrontal cortical activations were generated using group analysis based on the contrasts of urban versus idle, garden versus idle and urban versus garden. The activation for the contrast of urban versus garden showed an increase of oxy-hemoglobin on the right area of the prefrontal cortex with p <; 0.05. This preliminary result showed that the garden scene might provide a pleasant and less stressful experience as compared to the urban scene for subjects. This suggests the possibility of using a NIRS-based Brain-Computer Interface to detect subject preferences of different scenes.

Synchronization of Human Autonomic Nervous System Rhythms with Geomagnetic Activity in Human Subjects.

A coupling between geomagnetic activity and the human nervous system’s function was identified by virtue of continuous monitoring of heart rate variability (HRV) and the time-varying geomagnetic field over a 31-day period in a group of 10 individuals who went about their normal day-to-day lives. A time series correlation analysis identified a response of the group’s autonomic nervous systems to various dynamic changes in the solar, cosmic ray, and ambient magnetic field. Correlation coefficients and p values were calculated between the HRV variables and environmental measures during three distinct time periods of environmental activity. There were significant correlations between the group’s HRV and solar wind speed, Kp, Ap, solar radio flux, cosmic ray counts, Schumann resonance power, and the total variations in the magnetic field. In addition, the time series data were time synchronized and normalized, after which all circadian rhythms were removed. It was found that the participants’ HRV rhythms synchronized across the 31-day period at a period of approximately 2.5 days, even though all participants were in separate locations. Overall, this suggests that daily autonomic nervous system activity not only responds to changes in solar and geomagnetic activity, but is synchronized with the time-varying magnetic fields associated with geomagnetic field-line resonances and Schumann resonances.

Nanoparticle‐based biosensors for the detection of lecithin:cholesterol acyltransferase activity

BackgroundLecithin:cholesterol acyltransferase (LCAT) is an enzyme that catalyzes the esterification of free cholesterol carried in high‐density lipoproteins (HDL). Esterification of cholesterol results in internalization of cholesteryl ester (CE) within the core of maturing HDLs. Of the HDL species, increased levels of CE‐rich HDLs are inversely correlated with the development of cardiovascular disease. Prior research has established that the activity of LCAT is influenced by numerous external physiological stimuli. Our lab has previously developed nanoparticles (HDL‐NP) that mimic natural HDLs with regard to size, shape, surface chemistry, and cholesterol binding function. Herein, we describe the application of HDL‐NP as specific activators of LCAT and biosensors for assaying LCAT activity.MethodsHDL‐NP were synthesized using 5 nm diameter gold nanoparticles (AuNP) as a scaffold for the assembly of a lipid bilayer containing a mixture of phosphotidylcholine (PC), phosphotidylethanolamine (PE), and apolipoportein A‐I (apoAI). ApoAI, found in natural HDL, serves as a cofactor for LCAT. 10% of total nanoparticle phospholipid content consisted of a PC lipid labeled with the fluorophore, TopFluor, thus forming TopFluor‐labeled HDL‐NP (TF‐NP). A subset of HDL‐NP was formulated without apoAI, having only the phospholipid bilayer (BL‐NP), to serve as a control to demonstrate specificity for LCAT. These nanoparticle groups were incubated for 24 hours in PBS with cholesterol, LCAT, or cholesterol and LCAT. In addition, the particles were incubated in dilute serum. An increase in the fluorescence intensity was used as a measure of LCAT activity, presumably, due to a reduced quenching effect of the core AuNP on the TopFluor‐labeled PC.ResultsTF‐NP and BL‐NP were incubated with cholesterol alone, LCAT alone, or a mixture of cholesterol and LCAT (Fig. A). A significant increase in fluorescent signal was observed for the TF‐NP incubated with cholesterol and LCAT over that of the TF‐NP alone (p=0.0000005) indicating activity of LCAT on TF‐NP. Interestingly, the presence of cholesterol alone with TF‐NP and BL‐NP results in a fluorescence response, independent of apoAI content. The importance of apoAI as a cofactor for promoting LCAT activity is apparent through comparing the fluorescent response of TF‐NP and BL‐NP where the apoAI‐containing TF‐NP exhibits significantly increased fluorescence over BL‐NP when incubated with both cholesterol and LCAT (p=0.00012). Next, TF‐NP and BL‐NP were incubated in samples of diluted serum for 24 hours (Fig. B), demonstrating a dose‐response whereby increased serum resulted in a stronger fluorescent response from the nanoparticles. Furthermore, this study further confirms the specificity of LCAT towards apoAI‐containing TF‐NP, where fluorescence intensity was significantly increased over BL‐NP groups for all serum dilutions.ConclusionThese results demonstrate the ability of fluorescent HDL‐NP to serve as biosensors for detecting LCAT activity, and that detection of LCAT activity directly from serum samples is possible using this technology. Future work will aim to better understand cholesterol and cholesteryl binding to HDL‐NP through the observed quenching and de‐quenching fluorescent response, and to apply this biosensor for the detection of LCAT activity changes in response to both acute and prolonged exercise, both previously demonstrated to induce changes in LCAT activity in human subjects.Support or Funding InformationAFRL FA8650‐15‐2‐5518

P166 Evidence for state dependent direct effects of alpha band transcranial alternating current stimulation

Introduction Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. Objectives In the current study we examine entrainment effects caused by tACS at the individual alpha frequency (IAF) in humans. Material & methods We analyze magnetoencephalographic (MEG) data transformed to source space following a method we recently showed to diminish the tACS artifact, which makes analysis of brain activity during tACS possible. Using source level data from our previous study here we investigate the phase relationship (coherence) between the external tACS and the neural signal in two resting state condition. Results We find proof of entrainment in visual cortex areas. Interestingly, this entrainment is only significant when subjects had their eyes open; visual areas were not significantly entrained to tACS when subjects closed their eyes. Furthermore, we find considerable variation across subjects in the delay between tACS and the entrained brain activity. Conclusion In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices, however, in a state dependent manner as this effect can only clearly be observed with eyes open.

Manipulating stored phonological input during verbal working memory.

Verbal working memory (vWM), involves storing and manipulating information in phonological sensory input. An influential theory of vWM proposes that manipulation is carried out by a central executive while storage is performed by two interacting systems: A phonological input buffer that captures sound-based information and an articulatory rehearsal system that controls speech motor output. Whether, when, and how neural activity in the brain encodes these components remains unknown. Here, we read-out the contents of vWM from neural activity in human subjects as they manipulate stored speech sounds. As predicted, we identify storage systems that contain both phonological sensory and articulatory motor representations. Surprisingly however, we find that manipulation does not involve a single central executive but rather involves two systems with distinct contributions to successful manipulation. We propose, therefore, that multiple subsystems comprise the central executive needed to manipulate stored phonological input for articulatory motor output in vWM.

Assessment of muscle function using hybrid PET/MRI: comparison of 18F-FDG PET and T2-weighted MRI for quantifying muscle activation in human subjects

PurposeThe aim of this study was to determine the relationship between relative glucose uptake and MRI T2 changes in skeletal muscles following resistance exercise using simultaneous PET/MRI scans.MethodsTen young healthy recreationally active men (age 21 – 28 years) were injected with 18F-FDG while activating the quadriceps of one leg with repeated knee extension exercises followed by hand-grip exercises for one arm. Immediately following the exercises, the subjects were scanned simultaneously with 18F-FDG PET/MRI and muscle groups were evaluated for increases in 18F-FDG uptake and MRI T2 values.ResultsA significant linear correlation between 18F-FDG uptake and changes in muscle T2 (R2 = 0.71) was found. for both small and large muscles and in voxel to voxel comparisons. Despite large intersubject differences in muscle recruitment, the linear correlation between 18F-FDG uptake and changes in muscle T2 did not vary among subjects.ConclusionThis is the first assessment of skeletal muscle activation using hybrid PET/MRI and the first study to demonstrate a high correlation between 18F-FDG uptake and changes in muscle T2 with physical exercise. Accordingly, it seems that changes in muscle T2 may be used as a surrogate marker for glucose uptake and lead to an improved insight into the metabolic changes that occur with muscle activation. Such knowledge may lead to improved treatment strategies in patients with neuromuscular pathologies such as stroke, spinal cord injuries and muscular dystrophies.

Eyes wide shut: Transcranial alternating current stimulation drives alpha rhythm in a state dependent manner.

Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. The present study aims to investigate the phase relationship between the external tACS signal and concurrent brain activity. Subjects were stimulated with tACS at individual alpha frequency during eyes open and eyes closed resting states. Electrodes were placed at Cz and Oz, which should affect parieto-occipital areas most strongly. Source space magnetoencephalography (MEG) data were used to estimate phase coherence between tACS and brain activity. Phase coherence was significantly increased in areas in the occipital pole in eyes open resting state only. The lag between tACS and brain responses showed considerable inter-individual variability. In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices. Interestingly, this effect is state dependent and is clearly observed with eyes open but only to a lesser extent with eyes closed.