RESUMO
Flexible cognitive functions, such as working memory (WM), usually require a balance between localized and distributed information processing. However, it is challenging to uncover how local and distributed processing specifically contributes to task-induced activity in a region. Although the recently proposed activity flow mapping approach revealed the relative contribution of distributed processing, few studies have explored the adaptive and plastic changes that underlie cognitive manipulation. In this study, we recruited 51 healthy volunteers (31 females) and investigated how the activity flow and brain activation of the frontoparietal systems was modulated by WM load and training. While the activation of both executive control network (ECN) and dorsal attention network (DAN) increased linearly with memory load at baseline, the relative contribution of distributed processing showed a linear response only in the DAN, which was prominently attributed to within-network activity flow. Importantly, adaptive training selectively induced an increase in the relative contribution of distributed processing in the ECN and also a linear response to memory load, which were predominantly due to between-network activity flow. Furthermore, we demonstrated a causal effect of activity flow prediction through training manipulation on connectivity and activity. In contrast with classic brain activation estimation, our findings suggest that the relative contribution of distributed processing revealed by activity flow prediction provides unique insights into neural processing of frontoparietal systems under the manipulation of cognitive load and training. This study offers a new methodological framework for exploring information integration versus segregation underlying cognitive processing.
Assuntos
Função Executiva , Imageamento por Ressonância Magnética , Memória de Curto Prazo , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Memória de Curto Prazo/fisiologia , Função Executiva/fisiologia , Mapeamento Encefálico , Atenção/fisiologia , Cognição/fisiologia , Encéfalo/fisiologia , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Lobo Parietal/fisiologiaRESUMO
Significant research has investigated synchronisation in brain networks, but the bulk of this work has explored the contribution of brain networks at the macroscale. Here we explore the effects of changing network topology on functional dynamics in spatially constrained random networks representing mesoscale neocortex. We use the Kuramoto model to simulate network dynamics and explore synchronisation and critical dynamics of the system as a function of topology in randomly generated networks with a distance-related wiring probability and no preferential attachment term. We show networks which predominantly make short-distance connections smooth out the critical coupling point and show much greater metastability, resulting in a wider range of coupling strengths demonstrating critical dynamics and metastability. We show the emergence of cluster synchronisation in these geometrically-constrained networks with functional organisation occurring along structural connections that minimise the participation coefficient of the cluster. We show that these cohorts of internally synchronised nodes also behave en masse as weakly coupled nodes and show intra-cluster desynchronisation and resynchronisation events related to inter-cluster interaction. While cluster synchronisation appears crucial to healthy brain function, it may also be pathological if it leads to unbreakable local synchronisation which may happen at extreme topologies, with implications for epilepsy research, wider brain function and other domains such as social networks.
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Conectoma , Neocórtex , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/patologia , EncéfaloRESUMO
MOTIVATION: Agent-based modeling is an indispensable tool for studying complex biological systems. However, existing simulation platforms do not always take full advantage of modern hardware and often have a field-specific software design. RESULTS: We present a novel simulation platform called BioDynaMo that alleviates both of these problems. BioDynaMo features a modular and high-performance simulation engine. We demonstrate that BioDynaMo can be used to simulate use cases in: neuroscience, oncology and epidemiology. For each use case, we validate our findings with experimental data or an analytical solution. Our performance results show that BioDynaMo performs up to three orders of magnitude faster than the state-of-the-art baselines. This improvement makes it feasible to simulate each use case with one billion agents on a single server, showcasing the potential BioDynaMo has for computational biology research. AVAILABILITY AND IMPLEMENTATION: BioDynaMo is an open-source project under the Apache 2.0 license and is available at www.biodynamo.org. Instructions to reproduce the results are available in the supplementary information. SUPPLEMENTARY INFORMATION: Available at https://doi.org/10.5281/zenodo.5121618.
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Algoritmos , Software , Simulação por Computador , Biologia Computacional/métodos , Design de SoftwareRESUMO
Visual hallucinations are a common feature of Lewy body dementia. Previous studies have shown that visual hallucinations are highly specific in differentiating Lewy body dementia from Alzheimer's disease dementia and Alzheimer-Lewy body mixed pathology cases. Computational models propose that impairment of visual and attentional networks is aetiologically key to the manifestation of visual hallucinations symptomatology. However, there is still a lack of experimental evidence on functional and structural brain network abnormalities associated with visual hallucinations in Lewy body dementia. We used EEG source localization and network based statistics to assess differential topographical patterns in Lewy body dementia between 25 participants with visual hallucinations and 17 participants without hallucinations. Diffusion tensor imaging was used to assess structural connectivity between thalamus, basal forebrain and cortical regions belonging to the functionally affected network component in the hallucinating group, as assessed with network based statistics. The number of white matter streamlines within the cortex and between subcortical and cortical regions was compared between hallucinating and not hallucinating groups and correlated with average EEG source connectivity of the affected subnetwork. Moreover, modular organization of the EEG source network was obtained, compared between groups and tested for correlation with structural connectivity. Network analysis showed that compared to non-hallucinating patients, those with hallucinations feature consistent weakened connectivity within the visual ventral network, and between this network and default mode and ventral attentional networks, but not between or within attentional networks. The occipital lobe was the most functionally disconnected region. Structural analysis yielded significantly affected white matter streamlines connecting the cortical regions to the nucleus basalis of Meynert and the thalamus in hallucinating compared to not hallucinating patients. The number of streamlines in the tract between the basal forebrain and the cortex correlated with cortical functional connectivity in non-hallucinating patients, while a correlation emerged for the white matter streamlines connecting the functionally affected cortical regions in the hallucinating group. This study proposes, for the first time, differential functional networks between hallucinating and not hallucinating Lewy body dementia patients, and provides empirical evidence for existing models of visual hallucinations. Specifically, the outcome of the present study shows that the hallucinating condition is associated with functional network segregation in Lewy body dementia and supports the involvement of the cholinergic system as proposed in the current literature.
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Doença de Alzheimer , Doença por Corpos de Lewy , Doença de Alzheimer/patologia , Encéfalo/patologia , Imagem de Tensor de Difusão , Alucinações/etiologia , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/patologiaRESUMO
One of the most characteristic properties of many vertebrate neural systems is the layered organization of different cell types. This cytoarchitecture exists in the cortex, the retina, the hippocampus, and many other parts of the central nervous system. The developmental mechanisms of neural layer formation have been subject to substantial experimental efforts. Here, we provide a general computational model for cortical layer formation in 3D physical space. We show that this multiscale, agent-based model, comprising two distinct stages of apoptosis, can account for the wide range of neuronal numbers encountered in different cortical areas and species. Our results demonstrate the phenotypic richness of a basic state diagram structure. Importantly, apoptosis allows for changing the thickness of one layer without automatically affecting other layers. Therefore, apoptosis increases the flexibility for evolutionary change in layer architecture. Notably, slightly changed gene regulatory dynamics recapitulate the characteristic properties observed in neurodevelopmental diseases. Overall, we propose a novel computational model using gene-type rules, exhibiting many characteristics of normal and pathological cortical development.
Assuntos
Simulação por Computador , Córtex Somatossensorial/fisiologia , Lobo Temporal/fisiologia , Córtex Visual/fisiologia , Animais , Córtex Cerebral/citologia , Córtex Cerebral/fisiologia , Humanos , Macaca , Camundongos , Ratos , Córtex Somatossensorial/citologia , Especificidade da Espécie , Lobo Temporal/citologia , Córtex Visual/citologiaRESUMO
Flexibility is a hallmark of human intelligence. Emerging studies have proposed several flexibility measurements at the level of individual regions, to produce a brain map of neural flexibility. However, flexibility is usually inferred from separate components of brain activity (i.e., intrinsic/task-evoked), and different definitions are used. Moreover, recent studies have argued that neural processing may be more than a task-driven and intrinsic dichotomy. Therefore, the understanding to neural flexibility is still incomplete. To address this issue, we propose a multifaceted definition of neural flexibility according to three key features: broad cognitive engagement, distributed connectivity, and adaptive connectome dynamics. For these three features, we first review the advances in computational approaches, their functional relevance, and their potential pitfalls. We then suggest a set of metrics that can help us assign a flexibility rating to each region. Subsequently, we present an emergent probabilistic view for further understanding the functional operation of individual regions in the unified framework of intrinsic and task-driven states. Finally, we highlight several areas related to the multifaceted definition of neural flexibility for future research. This review not only strengthens our understanding of flexible human brain, but also suggests that the measure of neural flexibility could bridge the gap between understanding intrinsic and task-driven brain function dynamics.
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Encéfalo/fisiologia , Vias Neurais/fisiologia , Plasticidade Neuronal/fisiologia , Cognição/fisiologia , Conectoma , Humanos , Inteligência , Imageamento por Ressonância Magnética , Rede Nervosa/fisiologiaRESUMO
Natural vision engages a wide range of higher-level regions that integrate visual information over the large-scale brain network. How interareal connectivity reconfigures during the processing of ongoing natural visual scenes and how these dynamic functional changes relate to the underlaying anatomical links between regions is not well understood. Here, we hypothesized that macaque visual brain regions are poly-functional sharing the capacity to change their configuration state depending on the nature of visual input. To address this hypothesis, we reconstructed networks from in-vivo diffusion-weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) data obtained in four alert macaque monkeys viewing naturalistic movie scenes. At first, we characterized network properties and found greater interhemispheric density and greater inter-subject variability in free-viewing networks as compared to structural networks. From the structural connectivity, we then captured modules on which we identified hubs during free-viewing that formed a widespread visuo-saccadic network across frontal (FEF, 46v), parietal (LIP, Tpt), and occipitotemporal modules (MT, V4, TEm), and that excluded primary visual cortex. Inter-subject variability of well-connected hubs reflected subject-specific configurations that largely recruited occipito-parietal and frontal modules. Across the cerebral hemispheres, free-viewing networks showed higher correlations among long-distance brain regions as compared to structural networks. From these findings, we hypothesized that long-distance interareal connectivity could reconfigure depending on the ongoing changes in visual scenes. Testing this hypothesis by applying temporally resolved functional connectivity we observed that many structurally defined areas (such as areas V4, MT/MST and LIP) were poly-functional as they were recruited as hub members of multiple network states that changed during the presentation of scenes containing objects, motion, faces, and actions. We suggest that functional flexibility in macaque macroscale brain networks is required for the efficient interareal communication during active natural vision. To further promote the use of naturalistic free-viewing paradigms and increase the development of macaque neuroimaging resources, we share our datasets in the PRIME-DE consortium.
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Mapeamento Encefálico/métodos , Córtex Visual/diagnóstico por imagem , Animais , Encéfalo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Macaca , Imageamento por Ressonância Magnética , Estimulação LuminosaRESUMO
Finding clear connectome biomarkers for temporal lobe epilepsy (TLE) patients, in particular at early disease stages, remains a challenge. Currently, the whole-brain structural connectomes are analyzed based on coarse parcellations (up to 1,000 nodes). However, such global parcellation-based connectomes may be unsuitable for detecting more localized changes in patients. Here, we use a high-resolution network (~50,000-nodes overall) to identify changes at the local level (within brain regions) and test its relation with duration and surgical outcome. Patients with TLE (n = 33) and age-, sex-matched healthy subjects (n = 36) underwent high-resolution (~50,000 nodes) structural network construction based on deterministic tracking of diffusion tensor imaging. Nodes were allocated to 68 cortical regions according to the Desikan-Killany atlas. The connectivity within regions was then used to predict surgical outcome. MRI processing, network reconstruction, and visualization of network changes were integrated into the NICARA (https://nicara.eu). Lower clustering coefficient and higher edge density were found for local connectivity within regions in patients, but were absent for the global network between regions (68 cortical regions). Local connectivity changes, in terms of the number of changed regions and the magnitude of changes, increased with disease duration. Local connectivity yielded a better surgical outcome prediction (Mean value: 95.39% accuracy, 92.76% sensitivity, and 100% specificity) than global connectivity. Connectivity within regions, compared to structural connectivity between brain regions, can be a more efficient biomarker for epilepsy assessment and surgery outcome prediction of medically intractable TLE.
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Córtex Cerebral/patologia , Imagem de Tensor de Difusão , Epilepsia/patologia , Rede Nervosa/patologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
MOTIVATION: Flux balance analysis (FBA) based bilevel optimization has been a great success in redesigning metabolic networks for biochemical overproduction. To date, many computational approaches have been developed to solve the resulting bilevel optimization problems. However, most of them are of limited use due to biased optimality principle, poor scalability with the size of metabolic networks, potential numeric issues or low quantity of design solutions in a single run. RESULTS: Here, we have employed a network interdiction model free of growth optimality assumptions, a special case of bilevel optimization, for computational strain design and have developed a hybrid Benders algorithm (HBA) that deals with complicating binary variables in the model, thereby achieving high efficiency without numeric issues in search of best design strategies. More importantly, HBA can list solutions that meet users' production requirements during the search, making it possible to obtain numerous design strategies at a small runtime overhead (typically â¼1 h, e.g. studied in this article). AVAILABILITY AND IMPLEMENTATION: Source code implemented in the MATALAB Cobratoolbox is freely available at https://github.com/chang88ye/NIHBA. CONTACT: math4neu@gmail.com or natalio.krasnogor@ncl.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Engenharia Metabólica , Redes e Vias Metabólicas , Algoritmos , Biologia Computacional , Hemoglobina A , Modelos Biológicos , SoftwareRESUMO
Structural covariance analysis is a widely used structural MRI analysis method which characterises the co-relations of morphology between brain regions over a group of subjects. To our knowledge, little has been investigated in terms of the comparability of results between different data sets of healthy human subjects, as well as the reliability of results over the same subjects in different rescan sessions, image resolutions, or FreeSurfer versions. In terms of comparability, our results show substantial differences in the structural covariance matrix between data sets of age- and sex-matched healthy human adults. These differences persist after univariate site correction, they are exacerbated by low sample sizes, and they are most pronounced when using average cortical thickness as a morphological measure. Down-stream graph theoretic analyses further show statistically significant differences. In terms of reliability, substantial differences were also found when comparing repeated scan sessions of the same subjects, image resolutions, and even FreeSurfer versions of the same image. We could further estimate the relative measurement error and showed that it is largest when using cortical thickness as a morphological measure. Using simulated data, we argue that cortical thickness is least reliable because of larger relative measurement errors. Practically, we make the following recommendations (1) combining subjects across sites into one group should be avoided, particularly if sites differ in image resolutions, subject demographics, or preprocessing steps; (2) surface area and volume should be preferred as morphological measures over cortical thickness; (3) a large number of subjects (nâ«30 for the Desikan-Killiany parcellation) should be used to estimate structural covariance; (4) measurement error should be assessed where repeated measurements are available; (5) if combining sites is critical, univariate (per ROI) site-correction is insufficient, but error covariance (between ROIs) should be explicitly measured and modelled.
Assuntos
Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Neocortical circuits exhibit a rich dynamic repertoire, and their ability to achieve entrainment (adjustment of their frequency to match the input frequency) is thought to support many cognitive functions and indicate functional flexibility. Although previous studies have explored the influence of various circuit properties on this phenomenon, the role of divisive gain modulation (or divisive inhibition) is unknown. This gain control mechanism is thought to be delivered mainly by the soma-targeting interneurons in neocortical microcircuits. In this study, we use a neural mass model of the neocortical microcircuit (extended Wilson-Cowan model) featuring both soma-targeting and dendrite-targeting interneuronal subpopulations to investigate the role of divisive gain modulation in entrainment. Our results demonstrate that the presence of divisive inhibition in the microcircuit, as delivered by the soma-targeting interneurons, enables its entrainment to a wider range of input frequencies. Divisive inhibition also promotes a faster entrainment, with the microcircuit needing less time to converge to the fully entrained state. We suggest that divisive inhibition, working alongside subtractive inhibition, allows for more adaptive oscillatory responses in neocortical circuits and, thus, supports healthy brain functioning.NEW & NOTEWORTHY We introduce a computational neocortical microcircuit model that features two inhibitory neural populations, with one providing subtractive and the other divisive inhibition to the excitatory population. We demonstrate that divisive inhibition widens the range of input frequencies to which the microcircuit can become entrained and diminishes the time needed to reach full entrainment. We suggest that divisive inhibition enables more adaptive oscillatory activity, with important implications for both normal and pathological brain function.
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Interneurônios/fisiologia , Modelos Neurológicos , Neocórtex/fisiologia , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Redes Neurais de Computação , Animais , HumanosRESUMO
The diagnosis of dementia with Lewy bodies (DLB) versus Alzheimer's disease (AD) can be difficult especially early in the disease process. However, one inexpensive and non-invasive biomarker which could help is electroencephalography (EEG). Previous studies have shown that the brain network architecture assessed by EEG is altered in AD patients compared with age-matched healthy control people (HC). However, similar studies in Lewy body diseases, that is, DLB and Parkinson's disease dementia (PDD) are still lacking. In this work, we (a) compared brain network connectivity patterns across conditions, AD, DLB and PDD, in order to infer EEG network biomarkers that differentiate between these conditions, and (b) tested whether opting for weighted matrices led to more reliable results by better preserving the topology of the network. Our results indicate that dementia groups present with reduced connectivity in the EEG α band, whereas DLB shows weaker posterior-anterior patterns within the ß-band and greater network segregation within the θ-band compared with AD. Weighted network measures were more consistent across global thresholding levels, and the network properties reflected reduction in connectivity strength in the dementia groups. In conclusion, ß- and θ-band network measures may be suitable as biomarkers for discriminating DLB from AD, whereas the α-band network is similarly affected in DLB and PDD compared with HC. These variations may reflect the impairment of attentional networks in Parkinsonian diseases such as DLB and PDD.
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Demência/fisiopatologia , Eletroencefalografia/métodos , Rede Nervosa/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Ritmo alfa , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Atenção , Ritmo beta , Biomarcadores , Demência/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Reprodutibilidade dos Testes , Ritmo TetaRESUMO
Lewy body dementia includes dementia with Lewy bodies and Parkinson's disease dementia and is characterized by transient clinical symptoms such as fluctuating cognition, which might be driven by dysfunction of the intrinsic dynamic properties of the brain. In this context we investigated whole-brain dynamics on a subsecond timescale in 42 Lewy body dementia compared to 27 Alzheimer's disease patients and 18 healthy controls using an EEG microstate analysis in a cross-sectional design. Microstates are transiently stable brain topographies whose temporal characteristics provide insight into the brain's dynamic repertoire. Our additional aim was to explore what processes in the brain drive microstate dynamics. We therefore studied associations between microstate dynamics and temporal aspects of large-scale cortical-basal ganglia-thalamic interactions using dynamic functional MRI measures given the putative role of these subcortical areas in modulating widespread cortical function and their known vulnerability to Lewy body pathology. Microstate duration was increased in Lewy body dementia for all microstate classes compared to Alzheimer's disease (P < 0.001) and healthy controls (P < 0.001), while microstate dynamics in Alzheimer's disease were largely comparable to healthy control levels, albeit with altered microstate topographies. Correspondingly, the number of distinct microstates per second was reduced in Lewy body dementia compared to healthy controls (P < 0.001) and Alzheimer's disease (P < 0.001). In the dementia with Lewy bodies group, mean microstate duration was related to the severity of cognitive fluctuations (ρ = 0.56, PFDR = 0.038). Additionally, mean microstate duration was negatively correlated with dynamic functional connectivity between the basal ganglia (r = - 0.53, P = 0.003) and thalamic networks (r = - 0.38, P = 0.04) and large-scale cortical networks such as visual and motor networks in Lewy body dementia. The results indicate a slowing of microstate dynamics and disturbances to the precise timing of microstate sequences in Lewy body dementia, which might lead to a breakdown of the intricate dynamic properties of the brain, thereby causing loss of flexibility and adaptability that is crucial for healthy brain functioning. When contrasted with the largely intact microstate dynamics in Alzheimer's disease, the alterations in dynamic properties in Lewy body dementia indicate a brain state that is less responsive to environmental demands and might give rise to the apparent slowing in thinking and intermittent confusion which typify Lewy body dementia. By using Lewy body dementia as a probe pathology we demonstrate a potential link between dynamic functional MRI fluctuations and microstate dynamics, suggesting that dynamic interactions within the cortical-basal ganglia-thalamic loop might play a role in the modulation of EEG dynamics.
Assuntos
Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Doença por Corpos de Lewy/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Mapeamento Encefálico/métodos , Estudos Transversais , Eletroencefalografia , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
Simulations of neural networks can be used to study the direct effect of internal or external changes on brain dynamics. However, some changes are not immediate but occur on the timescale of weeks, months, or years. Examples include effects of strokes, surgical tissue removal, or traumatic brain injury but also gradual changes during brain development. Simulating network activity over a long time, even for a small number of nodes, is a computational challenge. Here, we model a coupled network of human brain regions with a modified Wilson-Cowan model representing dynamics for each region and with synaptic plasticity adjusting connection weights within and between regions. Using strategies ranging from different models for plasticity, vectorization and a different differential equation solver setup, we achieved one second runtime for one second biological time.
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Dynamic DNA nanodevices are designed to perform structure-encoded motion actuated by a variety of different physicochemical stimuli. In this context, hybrid devices utilizing other components than DNA have the potential to considerably expand the library of functionalities. Here, the reversible reconfiguration of a DNA origami structure using the stimulus sensitivity of elastin-like polypeptides is reported. To this end, a rectangular sheet made using the DNA origami technique is functionalized with these peptides and by applying changes in salt concentration the hydrophilic-hydrophobic phase transition of these peptides actuate the folding of the structure. The on-demand and reversible switching of the rectangle is driven by externally imposed temperature oscillations and appears at specific transition temperatures. Using transmission electron microscopy, it is shown that the structure exhibits distinct conformational states with different occupation probabilities, which are dependent on structure-intrinsic parameters such as the local number and the arrangement of the peptides on the rectangle. It is also shown through ensemble fluorescence resonance energy transfer spectroscopy that the transition temperature and thus the thermodynamics of the rectangle-peptide system depends on the stimuli salt concentration and temperature, as well as on the intrinsic parameters.
Assuntos
DNA/química , Nanoestruturas/química , Transferência Ressonante de Energia de Fluorescência , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Nanotecnologia/métodos , Conformação de Ácido Nucleico , Transição de Fase , TermodinâmicaRESUMO
The folding of the cortex in mammalian brains across species has recently been shown to follow a universal scaling law that can be derived from a simple physics model. However, it was yet to be determined whether this law also applies to the morphological diversity of different individuals in a single species, in particular with respect to factors, such as age, sex, and disease. To this end, we derived and investigated the cortical morphology from magnetic resonance images (MRIs) of over 1,000 healthy human subjects from three independent public databases. Our results show that all three MRI datasets follow the scaling law obtained from the comparative neuroanatomical data, which strengthens the case for the existence of a common mechanism for cortical folding. Additionally, for comparable age groups, both male and female brains scale in exactly the same way, despite systematic differences in size and folding. Furthermore, age introduces a systematic shift in the offset of the scaling law. In the model, this shift can be interpreted as changes in the mechanical forces acting on the cortex. We also applied this analysis to a dataset derived from comparable cohorts of Alzheimer's disease patients and healthy subjects of similar age. We show a systematically lower offset and a possible change in the exponent for Alzheimer's disease subjects compared with the control cohort. Finally, we discuss implications of the changes in offset and exponent in the data and relate it to existing literature. We, thus, provide a possible mechanistic link between previously independent observations.
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Repeated presentations of sensory stimuli generate transient gamma-frequency (30-80 Hz) responses in neocortex that show plasticity in a task-dependent manner. Complex relationships between individual neuronal outputs and the mean, local field potential (population activity) accompany these changes, but little is known about the underlying mechanisms responsible. Here we show that transient stimulation of input layer 4 sufficient to generate gamma oscillations induced two different, lamina-specific plastic processes that correlated with lamina-specific changes in responses to further, repeated stimulation: Unit rates and recruitment showed overall enhancement in supragranular layers and suppression in infragranular layers associated with excitatory or inhibitory synaptic potentiation onto principal cells, respectively. Both synaptic processes were critically dependent on activation of GABAB receptors and, together, appeared to temporally segregate the cortical representation. These data suggest that adaptation to repetitive sensory input dramatically alters the spatiotemporal properties of the neocortical response in a manner that may both refine and minimize cortical output simultaneously.
Assuntos
Ritmo Gama/fisiologia , Neocórtex/fisiologia , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Receptores de GABA-B/metabolismo , Transmissão Sináptica/fisiologia , Potenciais de Ação/fisiologia , Animais , Células Cultivadas , Estimulação Elétrica/métodos , Neurônios GABAérgicos/fisiologia , Ratos , Ratos WistarRESUMO
Dementia with Lewy bodies (DLB) is a common form of dementia and is characterized by cognitive fluctuations, visual hallucinations, and Parkinsonism. The phenotypic expression of the disease may, in part, relate to alterations in functional connectivity within and between brain networks. This resting-state study sought to clarify this in DLB, how networks differed from Alzheimer's disease (AD), and whether they were related to clinical symptoms in DLB. Resting-state networks were estimated using independent component analysis. We investigated functional connectivity changes in 31 DLB patients compared to 31 healthy controls and a disease comparator group of 29 AD patients using dual regression and FSLNets. Within-network connectivity was generally decreased in DLB compared to controls, mainly in motor, temporal, and frontal networks. Between-network connectivity was mainly intact; only the connection between a frontal and a temporal network showed increased connectivity in DLB. Differences between AD and DLB were subtle and we did not find any significant correlations with the severity of clinical symptoms in DLB. This study emphasizes the importance of reduced connectivity within motor, frontal, and temporal networks in DLB with relative sparing of the default mode network. The lack of significant correlations between connectivity measures and clinical scores indicates that the observed reduced connectivity within these networks might be related to the presence, but not to the severity of motor and cognitive impairment in DLB patients. Furthermore, our results suggest that AD and DLB may show more similarities than differences in patients with mild disease.