During the last several years, the focus of research on resting-state functional magnetic resonance imaging (fMRI) has shifted from the analysis of functional connectivity averaged over the duration ...of scanning sessions to the analysis of changes of functional connectivity within sessions. Although several studies have reported the presence of dynamic functional connectivity (dFC), statistical assessment of the results is not always carried out in a sound way and, in some studies, is even omitted. In this study, we explain why appropriate statistical tests are needed to detect dFC, we describe how they can be carried out and how to assess the performance of dFC measures, and we illustrate the methodology using spontaneous blood-oxygen level-dependent (BOLD) fMRI recordings of macaque monkeys under general anesthesia and in human subjects under resting-state conditions. We mainly focus on sliding-window correlations since these are most widely used in assessing dFC, but also consider a recently proposed non-linear measure. The simulations and methodology, however, are general and can be applied to any measure. The results are twofold. First, through simulations, we show that in typical resting-state sessions of 10min, it is almost impossible to detect dFC using sliding-window correlations. This prediction is validated by both the macaque and the human data: in none of the individual recording sessions was evidence for dFC found. Second, detection power can be considerably increased by session- or subject-averaging of the measures. In doing so, we found that most of the functional connections are in fact dynamic. With this study, we hope to raise awareness of the statistical pitfalls in the assessment of dFC and how they can be avoided by using appropriate statistical methods.
•Not widely recognized is the need for proper statistical testing to assess dynamic functional connectivity in resting-state fMRI.•This study describes how to test and how not to test for dynamic functional connectivity.•Large-scale dynamic functional networks are found in macaque monkeys under anesthesia.•Dynamic functional networks comprise both cortical and sub-cortical regions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Hippocampal ripples, episodic high-frequency field-potential oscillations primarily occurring during sleep and calmness, have been described in mice, rats, rabbits, monkeys and humans, and so far ...they have been associated with retention of previously acquired awake experience. Although hippocampal ripples have been studied in detail using neurophysiological methods, the global effects of ripples on the entire brain remain elusive, primarily owing to a lack of methodologies permitting concurrent hippocampal recordings and whole-brain activity mapping. By combining electrophysiological recordings in hippocampus with ripple-triggered functional magnetic resonance imaging, here we show that most of the cerebral cortex is selectively activated during the ripples, whereas most diencephalic, midbrain and brainstem regions are strongly and consistently inhibited. Analysis of regional temporal response patterns indicates that thalamic activity suppression precedes the hippocampal population burst, which itself is temporally bounded by massive activations of association and primary cortical areas. These findings suggest that during off-line memory consolidation, synergistic thalamocortical activity may be orchestrating a privileged interaction state between hippocampus and cortex by silencing the output of subcortical centres involved in sensory processing or potentially mediating procedural learning. Such a mechanism would cause minimal interference, enabling consolidation of hippocampus-dependent memory.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The decision as to the treatment of incidental IAs is complex. There are no certain quantitative methods that can be used to evaluate the risk of rupture in IAs. In recent years, CFD technology has ...been recognized as a potential risk-analysis tool. The aim of this article was to propose a hemodynamic parameter, EL, to determine the effects of stable unruptured aneurysms and of those that ruptured during the subsequent observation period.
Four incidentally found ICA-PcomA aneurysms ruptured during the period of observation (ruptured-IAs). Another 26 unruptured aneurysms (stable-IAs) with similar location, size, and morphology were compared for the differences in hemodynamic factors, such as EL and WSS.
The EL calculated at the ruptured-IAs was nearly 5 times higher on average than that at the stable-IAs (ruptured, 0.00374 ± 0.0011; stable, 0.000745 ± 0.0001 mW/mm(3), P < .001). However, there was no difference between the ruptured and stable groups according to the results of time-averaged WSS (P = .8) for ruptured- and stable-IAs. According to flow visualization, though the mean average inflow speed of ruptured-IAs was 2 times higher than that of the stable-IAs, the flow inside ruptured-IAs appeared to undergo longer resident tracks, with stronger impact on the aneurysm wall. On the contrary, the flow inside stable-IAs passed smoothly through the aneurysms.
These preliminary results indicated that EL may be a useful parameter for the quantitative estimation of the risks of rupture for IAs.
Cochlear development is a complex process with precise spatiotemporal patterns. A detailed understanding of this process is important for studies of congenital hearing loss and regenerative medicine. ...However, much of our understanding of cochlear development is based on rodent models. Animal models that bridge the gap between humans and rodents are needed. In this study, we investigated the development of hearing organs in a small New World monkey species, the common marmoset (Callithrix jacchus). We describe the general stages of cochlear development in comparison with those of humans and mice. Moreover, we examined more than 25 proteins involved in cochlear development and found that expression patterns were generally conserved between rodents and primates. However, several proteins involved in supporting cell processes and neuronal development exhibited interspecific expression differences. Human fetal samples for studies of primate‐specific cochlear development are extremely rare, especially for late developmental stages. Our results support the use of the common marmoset as an effective alternative for analyses of primate cochlear development.
We investigated cochlear development in a small New World monkey species, the common marmoset (Callithrix jacchus). We found that expression patterns of the proteins involved in cochlear development were generally conserved between rodents and primates. However, several proteins involved in supporting cell processes and neuronal development exhibited interspecific expression differences. Our results support the use of the common marmoset as an effective alternative for analyses of primate cochlear development.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The new Horizontal Wind Model (HWM07) provides a statistical representation of the horizontal wind fields of the Earth's atmosphere from the ground to the exosphere (0–500 km). It represents over 50 ...years of satellite, rocket, and ground‐based wind measurements via a compact Fortran 90 subroutine. The computer model is a function of geographic location, altitude, day of the year, solar local time, and geomagnetic activity. It includes representations of the zonal mean circulation, stationary planetary waves, migrating tides, and the seasonal modulation thereof. HWM07 is composed of two components, a quiet time component for the background state described in this paper and a geomagnetic storm time component (DWM07) described in a companion paper.
Precise cochlear neuronal development is vital to hearing ability. Understanding the developmental process of the spiral ganglion is useful for studying hearing loss aimed at aging or regenerative ...therapy. Although interspecies differences have been reported between rodents and humans, to date, most of our knowledge about the development of cochlear neuronal development has been obtained from rodent models because of the difficulty in using human fetal samples in this field. In this study, we investigated cochlear neuronal development in a small New World monkey species, the common marmoset (Callithrix jacchus). We examined more than 25 genes involved in the neuronal development of the cochlea and described the critical developmental steps of these neurons. We also revealed similarities and differences between previously reported rodent models and this primate animal model. Our results clarified that this animal model of cochlear neuronal development is more similar to humans than rodents and is suitable as an alternative for the analysis of human cochlear development. The time course established in this report will be a useful tool for studying primate‐specific neuronal biology of the inner ear, which could eventually lead to new treatment strategies for human hearing loss.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression ...of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type.
The natural history and therapeutic management of dissecting vertebrobasilar aneurysms without ischemic or hemorrhagic stroke (nonstroke dissecting vertebrobasilar aneurysms) are not ...well-established. We conservatively followed patients with nonstroke dissecting vertebrobasilar aneurysms and evaluated the factors related to clinical and morphologic deterioration.
One hundred thirteen patients were enrolled and divided by clinical presentation at diagnosis: asymptomatic (group 1, n = 52), pain only (group 2, n = 56), and mass effect (group 3, n = 5). Patients were conservatively managed without intervention and antithrombotic therapy. Clinical outcomes and morphologic changes were analyzed.
A total of 113 patients who were diagnosed with nonstroke dissecting vertebrobasilar aneurysm had a mean follow-up of 2.9 years (range, 27 days to 8 years). Throughout that period, 1 patient in group 1 (1.9%) and 1 patient in group 2 (1.8%) showed clinical deterioration due to mass effect, and 1 patient in group 3 (20%) developed ischemic stroke followed by subarachnoid hemorrhage. Most patients (97.3%) were clinically unchanged. Three patients who had clinical deterioration showed aneurysm enlargement (P < .001). Aneurysms remained morphologically unchanged in 91 patients (80.5%). Aneurysm enlargement was seen in 5 patients (4.4%); risk of enlargement was significantly associated with either maximum diameter (hazard ratio = 1.30; 95% CI, 1.11-11.52; P = .001) or aneurysm ≥10 mm (hazard ratio = 18.0; 95% CI, 1.95-167; P = .011).
The natural course of these lesions suggests that acute intervention is not always required and close follow-up without antithrombotic therapy is reasonable. Patients with symptoms due to mass effect or aneurysms of >10 mm may require treatment.
Recently we published a novel method of thrombus preparation for use in a swine model for evaluation of thrombectomy designs. The clot (fibrin rich clot) is characterized by its similarity in ...histologic characteristics to the thromboemboli recovered from stroke patients. The purpose of this latest study was to evaluate if the performance of a mechanical thrombectomy device was affected by the histologic characteristics of thromboembolus. Erythrocyte rich clot, which was created using exogenous thrombin, and the novel experimental clot with abundance of fibrin/cellular component were used for comparison. The Merci clot retriever was used for the evaluation and the angiographic outcomes were analyzed.
Two histologically different types of experimental clot, a conventionally used thrombin-induced clot (erythrocyte-rich clot) and a novel experimental clot that is similar in histologic characteristics to the thromboemboli recovered from patients with stroke (fibrin-rich clot), were prepared. Eight extracranial arteries in swine were occluded with erythrocyte-rich clot (group A), and 8 were occluded with fibrin-rich clot (group B), and MT by using the Merci clot retriever device was performed. Angiographic results in each group were evaluated.
A total of 48 attempts at MT were made. The average number of attempts to achieve TIMI grade II or III recanalization was 2.75 times in group A and 4.5 times in group B (P < .001), respectively. The mean time to achieve recanalization was 15.5 minutes in group A and 81.5 minutes in group B (P < .01). Every vessel in group A showed recanalization (100%), whereas only 3 of 8 samples (37.5%) achieved recanalization in group B.
In this model, arteries occluded by fibrin-rich clot demonstrated a significantly lower recanalization rate, lower final TIMI score, and a longer mean recanalization time than did arteries occluded by erythrocyte-rich clot. The angiographic outcome of MT by using the Merci clot retriever system was influenced by the histologic characteristics of the occluding thromboembolus.
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