Project description:BackgroundGenome sequences and genome annotation data have become available at ever increasing rates in response to the rapid progress in sequencing technologies. As a consequence the demand for methods supporting comparative, evolutionary analysis is also growing. In particular, efficient tools to visualize-omics data simultaneously for multiple species are sorely lacking. A first and crucial step in this direction is the construction of a common coordinate system. Since genomes not only differ by rearrangements but also by large insertions, deletions, and duplications, the use of a single reference genome is insufficient, in particular when the number of species becomes large.ResultsThe computational problem then becomes to determine an order and orientations of optimal local alignments that are as co-linear as possible with all the genome sequences. We first review the most prominent approaches to model the problem formally and then proceed to showing that it can be phrased as a particular variant of the Betweenness Problem. It is NP hard in general. As exact solutions are beyond reach for the problem sizes of practical interest, we introduce a collection of heuristic simplifiers to resolve ordering conflicts.ConclusionBenchmarks on real-life data ranging from bacterial to fly genomes demonstrate the feasibility of computing good common coordinate systems.
Project description:Cortical thickness (CTh) via surface-based morphometry analysis is a popular method to characterize brain morphometry. Many studies have been performed to investigate CTh abnormalities in migraine. However, the results from these studies were not consistent and even conflicting. These divergent results hinder us to obtain a clear picture of brain morphometry regarding CTh alterations in migraine. Coordinate-based meta-analysis (CBMA) is a promising technique to quantitatively pool individual neuroimaging studies to identify consistent brain areas involved. Electronic databases (PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, WanFang, and SinoMed) and other sources (bioRxiv and reference lists of relevant articles and reviews) were systematically searched for studies that compared regional CTh differences between patients with migraine and healthy controls (HCs) up to May 15, 2020. A CBMA was performed using the Seed-based d Mapping with Permutation of Subject Images approach. In total, we identified 16 studies with 17 datasets reported that were eligible for the CBMA. The 17 datasets included 872 patients with migraine (average sample size 51.3, mean age 39.6 years, 721 females) and 949 HCs (average sample size 59.3, mean age 44.2 years, 680 females). The CBMA detected no statistically significant consistency of CTh alterations in patients with migraine relative to HCs. Sensitivity analysis and subgroup analysis verified this result to be robust. Metaregression analyses revealed that this CBMA result was not confounded by age, gender, aura, attack frequency per month, and illness duration. Our CBMA adds to the evidence of the replication crisis in neuroimaging research that is increasingly recognized. Many potential confounders, such as underpowered sample size, heterogeneous patient selection criteria, and differences in imaging collection and methodology, may contribute to the inconsistencies of CTh alterations in migraine, which merit attention before planning future research on this topic.
Project description:Large-amplitude sleep slow oscillations group faster neuronal oscillations and are of functional relevance for memory performance. However, relatively little is known about the impact of slow oscillations on functionally coupled networks. Here, we provide a comprehensive view on how human slow oscillatory dynamics influence various measures of brain processing. We demonstrate that slow oscillations coordinate interregional cortical communication, as assessed by phase synchrony in the sleep spindle frequency range and cross-frequency coupling between spindle and beta activity. Furthermore, we show that the organizing role of slow oscillations is restricted to circumscribed topographical areas. These findings add importantly to our basic understanding of the orchestrating role of slow oscillations. In addition, they are of considerable relevance for accounts of sleep-dependent memory reprocessing and consolidation.
Project description:Parkinson's disease (PD) is a common age-related neurodegenerative disease that affects the structural architecture of the cerebral cortex. Cortical thickness (CTh) via surface-based morphometry (SBM) analysis is a popular measure to assess brain structural alterations in the gray matter in PD. However, the results of CTh analysis in PD lack consistency and have not been systematically reviewed. We conducted a comprehensive coordinate-based meta-analysis (CBMA) of 38 CTh studies (57 comparison datasets) in 1,843 patients with PD using the latest seed-based d mapping software. Compared with 1,172 healthy controls, no significantly consistent CTh alterations were found in patients with PD, suggesting CTh as an unreliable neuroimaging marker for PD. The lack of consistent CTh alterations in PD could be ascribed to the heterogeneity in clinical populations, variations in imaging methods, and underpowered small sample sizes. These results highlight the need to control for potential confounding factors to produce robust and reproducible CTh results in PD.
Project description:Curvature is one of many visual features shown to be important for visual perception. We recently showed that curvilinear features provide sufficient information for categorizing animate vs. inanimate objects, while rectilinear features do not (Zachariou et al., 2018). Results from our fMRI study in rhesus monkeys (Yue et al., 2014) have shed light on some of the neural substrates underlying curvature processing by revealing a network of visual cortical patches with a curvature response preference. However, it is unknown whether a similar network exists in human visual cortex. Thus, the current study was designed to investigate cortical areas with a preference for curvature in the human brain using fMRI at 7T. Consistent with our monkey fMRI results, we found a network of curvature preferring cortical patches-some of which overlapped well-known face-selective areas. Moreover, principal component analysis (PCA) using all visually-responsive voxels indicated that curvilinear features of visual stimuli were associated with specific retinotopic regions in visual cortex. Regions associated with positive curvilinear PC values encompassed the central visual field representation of early visual areas and the lateral surface of temporal cortex, while those associated with negative curvilinear PC values encompassed the peripheral visual field representation of early visual areas and the medial surface of temporal cortex. Thus, we found that broad areas of curvature preference, which encompassed face-selective areas, were bound by central visual field representations. Our results support the hypothesis that curvilinearity preference interacts with central-peripheral processing biases as primary features underlying the organization of temporal cortex topography in the adult human brain.
Project description:The cortical visual hierarchy communicates in different oscillatory ranges. While gamma waves influence the feedforward processing, alpha oscillations travel in the feedback direction. Little is known how this oscillatory cortical communication depends on an alternative route that involves the pulvinar nucleus of the thalamus. We investigated whether the oscillatory coupling between the primary visual cortex (area 17) and area 21a depends on the transthalamic pathway involving the pulvinar in cats. To that end, visual evoked responses were recorded in areas 17 and 21a before, during and after inactivation of the pulvinar. Local field potentials were analyzed with Wavelet and Granger causality tools to determine the oscillatory coupling between layers. The results indicate that cortical oscillatory activity was enhanced during pulvinar inactivation, in particular for area 21a. In area 17, alpha band responses were represented in layers II/III. In area 21a, gamma oscillations, except for layer I, were significantly increased, especially in layer IV. Granger causality showed that the pulvinar modulated the oscillatory information between areas 17 and 21a in gamma and alpha bands for the feedforward and feedback processing, respectively. Together, these findings indicate that the pulvinar is involved in the mechanisms underlying oscillatory communication along the visual cortex.
Project description:Most brain functions involve interactions among multiple, distinct areas or nuclei. For instance, visual processing in primates requires the appropriate relaying of signals across many distinct cortical areas. Yet our understanding of how populations of neurons in interconnected brain areas communicate is in its infancy. Here we investigate how trial-to-trial fluctuations of population responses in primary visual cortex (V1) are related to simultaneously recorded population responses in area V2. Using dimensionality reduction methods, we find that V1-V2 interactions occur through a communication subspace: V2 fluctuations are related to a small subset of V1 population activity patterns, distinct from the largest fluctuations shared among neurons within V1. In contrast, interactions between subpopulations within V1 are less selective. We propose that the communication subspace may be a general, population-level mechanism by which activity can be selectively routed across brain areas.
Project description:Acetylcholine (ACh) release in the cortex is critical for learning, memory, attention, and plasticity. Here, we explore the cholinergic and noncholinergic projections from the basal forebrain (BF) to the auditory cortex using classical retrograde and monosynaptic viral tracers deposited in electrophysiologically identified regions of the auditory cortex. Cholinergic input to both primary (A1) and nonprimary auditory cortical (belt) areas originates in a restricted area in the caudal BF within the globus pallidus (GP) and in the dorsal part of the substantia innominata (SId). On the other hand, we found significant differences in the proportions of cholinergic and noncholinergic projection neurons to primary and nonprimary auditory areas. Inputs to A1 projecting cholinergic neurons were restricted to the GP, caudate-putamen, and the medial part of the medial geniculate body, including the posterior intralaminar thalamic group. In addition to these areas, afferents to belt-projecting cholinergic neurons originated from broader areas, including the ventral secondary auditory cortex, insular cortex, secondary somatosensory cortex, and the central amygdaloid nucleus. These findings support a specific BF projection pattern to auditory cortical areas. Additionally, these findings point to potential functional differences in how ACh release may be regulated in the A1 and auditory belt areas.
Project description:Summary The disruption of cortical assembly activity has been associated with anesthesia-induced loss of consciousness. However, the relationship between cortical assembly activity and the variations in consciousness associated with natural vigilance states remains unclear. Here, we address this by performing vigilance state-specific clustering analysis on 2-photon calcium imaging data from the sensorimotor cortex in combination with global electroencephalogram (EEG) microstate analysis derived from multi-EEG signals obtained over widespread cortical locations. We report no difference in the structure of assembly activity during quiet wakefulness (QW), non-rapid eye movement sleep (NREMs), or REMs, despite the latter two vigilance states being associated with significantly reduced levels of consciousness relative to QW. However, we describe a significant coordination between global EEG microstate dynamics and general local cortical assembly activity during periods of QW, but not sleep. These results suggest that the coordination of cortical assembly activity with global brain dynamics could be a key factor of sustained conscious experience. Graphical abstract Highlights • The somatosensory cortex is imaged across the full sleep-wake cycle in mice• Cortical neural assembly activity is not different during quiet wake vs. sleep• Assembly activity is only coordinated with global brain dynamics during wake Boyce et al. show that local cortical neural assembly activity coordinates with global brain dynamics during wakefulness, but not during sleep, when consciousness is significantly reduced. This suggests that the coordination of local cortical assembly activity with global brain dynamics may be a key mechanism behind sustained conscious experience.
Project description:ObjectiveGamma synchrony is a fundamental functional property of the cerebral cortex, impaired in multiple neuropsychiatric conditions (i.e. schizophrenia, Alzheimer's disease, stroke etc.). Auditory stimulation in the gamma range allows to drive gamma synchrony of the entire cortical mantle and to estimate the efficiency of the mechanisms sustaining it. As gamma synchrony depends strongly on the interplay between parvalbumin-positive interneurons and pyramidal neurons, we hypothesize an association between cortical thickness and gamma synchrony. To test this hypothesis, we employed a combined magnetoencephalography (MEG) - Magnetic Resonance Imaging (MRI) study.MethodsCortical thickness was estimated from anatomical MRI scans. MEG measurements related to exposure of 40 Hz amplitude modulated tones were projected onto the cortical surface. Two measures of cortical synchrony were considered: (a) inter-trial phase consistency at 40 Hz, providing a vertex-wise estimation of gamma synchronization, and (b) phase-locking values between primary auditory cortices and whole cortical mantle, providing a measure of long-range cortical synchrony. A correlation between cortical thickness and synchronization measures was then calculated for 72 MRI-MEG scans.ResultsBoth inter-trial phase consistency and phase locking values showed a significant positive correlation with cortical thickness. For inter-trial phase consistency, clusters of strong associations were found in the temporal and frontal lobes, especially in the bilateral auditory and pre-motor cortices. Higher phase-locking values corresponded to higher cortical thickness in the frontal, temporal, occipital and parietal lobes.Discussion and conclusionsIn healthy subjects, a thicker cortex corresponds to higher gamma synchrony and connectivity in the primary auditory cortex and beyond, likely reflecting underlying cell density involved in gamma circuitries. This result hints towards an involvement of gamma synchrony together with underlying brain structure in brain areas for higher order cognitive functions. This study contributes to the understanding of inherent cortical functional and structural brain properties, which might in turn constitute the basis for the definition of useful biomarkers in patients showing aberrant gamma synchronization.