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1.
Cell ; 148(4): 780-91, 2012 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-22341448

RESUMO

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.


Assuntos
Neoplasias Faciais/veterinária , Instabilidade Genômica , Marsupiais/genética , Mutação , Animais , Evolução Clonal , Espécies em Perigo de Extinção , Neoplasias Faciais/epidemiologia , Neoplasias Faciais/genética , Neoplasias Faciais/patologia , Feminino , Estudo de Associação Genômica Ampla , Masculino , Dados de Sequência Molecular , Tasmânia/epidemiologia
2.
Angew Chem Int Ed Engl ; 62(42): e202309618, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37549374

RESUMO

Transition-metal nitrides/nitrenes are highly promising reagents for catalytic nitrogen-atom-transfer reactivity. They are typically prepared in situ upon optically induced N2 elimination from azido precursors. A full exploitation of their catalytic potential, however, requires in-depth knowledge of the primary photo-induced processes and the structural/electronic factors mediating the N2 loss with birth of the terminal metal-nitrogen core. Using femtosecond infrared spectroscopy, we elucidate here the primary molecular-level mechanisms responsible for the formation of a unique platinum(II) nitrene with a triplet ground state from a closed-shell platinum(II) azide precursor. The spectroscopic data in combination with quantum-chemical calculations provide compelling evidence that product formation requires the initial occupation of a singlet excited state with an anionic azide diradical ligand that is bound to a low-spin d8 -configured PtII ion. Subsequent intersystem crossing generates the Pt-bound triplet azide diradical, which smoothly evolves into the triplet nitrene via N2 loss in a near barrierless adiabatic dissociation. Our data highlight the importance of the productive, N2 -releasing state possessing azide ππ* character as a design principle for accessing efficient N-atom-transfer catalysts.

3.
Bioinformatics ; 37(23): 4559-4561, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34623383

RESUMO

SUMMARY: A main task in computational cancer analysis is the identification of patient subgroups (i.e. cohorts) based on metadata attributes (patient stratification) or genomic markers of response (biomarkers). Coral is a web-based cohort analysis tool that is designed to support this task: Users can interactively create and refine cohorts, which can then be compared, characterized and inspected down to the level of single items. Coral visualizes the evolution of cohorts and also provides intuitive access to prevalence information. Furthermore, findings can be stored, shared and reproduced via the integrated session management. Coral is pre-loaded with data from over 128 000 samples from the AACR Project GENIE, the Cancer Genome Atlas and the Cell Line Encyclopedia. AVAILABILITY AND IMPLEMENTATION: Coral is publicly available at https://coral.caleydoapp.org. The source code is released at https://github.com/Caleydo/coral. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Antozoários , Neoplasias , Animais , Genoma , Software , Internet
4.
Dev Psychobiol ; 63(6): e22149, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34173236

RESUMO

The present study examined testosterone (T) and cortisol (Cort) in fathers engaged with caregiving. We collected saliva samples in the mornings and evenings of two consecutive days in 150 fathers of 1- to 5-year-old children. Fathers completed questionnaires on socioeconomic status, family structure and life, sleep characteristics and body mass index (BMI), and reported on their engagement in childcare. Fathers used smartphone-based experience sampling throughout 1 week to sample ongoing activities with their children, including times of supervision, joint play, rough-and-tumble play, and cuddling episodes. External observers rated father-child attachment during a home visit. We began by testing for widely characterized covariates of T and excluded seasonal variations and known predictors associated with lowered T, such as older fathers and those with multiple and young children, lower BMI, shorter sleep duration, and sexual activity before sampling. Most interestingly, however, fathers' engagement in childcare and attachment to the child appeared more pronounced the greater the diurnal decline in T. Cuddling predicted a similar negative association, whereas joint play and rough-and-tumble play (RTP) showed enhancing effects on declining T. Interestingly, all fathering behaviors (except RTP) were positively related to lower Cort. In contrast, supervision was ineffective on both Cort and T.


Assuntos
Hidrocortisona , Testosterona , Cuidado da Criança , Pré-Escolar , Relações Pai-Filho , Humanos , Masculino , Poder Familiar , Comportamento Paterno
5.
J Vis ; 21(12): 2, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34727165

RESUMO

Many studies have investigated the causal relevance of brain oscillations using rhythmic stimulation, either through direct-brain or sensory stimulation. Yet, how intrinsic rhythms interact with the externally generated rhythm is largely unknown. We presented a flickered (60 Hz) visual grating or its correspondent unflickered stimulus in a psychophysical change detection task during simultaneous magnetoencephalography recordings to humans to test the effect of visual entrainment on induced gamma oscillations. Notably, we generally observed the coexistence of the broadband induced gamma rhythm with the entrained flicker rhythm (reliably measured in each participant), with the peak frequency of the induced response remaining unaltered in approximately half of participants-relatively independently of their native frequency. However, flicker increased broadband induced gamma power, and this was stronger in participants with a native frequency closer to the flicker frequency (resonance) and led to strong phase entrainment. Presence of flicker did not change behavior itself but profoundly altered brain behavior correlates across the sample: While broadband induced gamma oscillations correlated with reaction times for unflickered stimuli (as known previously), for the flicker, the amplitude of the entrained flicker rhythm (but no more the induced oscillation) correlated with reaction times. This, however, strongly depended on whether a participant's peak frequency shifted to the entrained rhythm. Our results suggests that rhythmic brain stimulation leads to a coexistence of two partially independent oscillations with heterogeneous effects across participants on the downstream relevance of these rhythms for behavior. This may explain the inconsistency of findings related to external entrainment of brain oscillations and poses further questions toward causal manipulations of brain oscillations in general.


Assuntos
Encéfalo , Percepção Visual , Humanos , Magnetoencefalografia , Estimulação Luminosa
6.
Hippocampus ; 30(10): 1021-1043, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32396678

RESUMO

Reduced inhibitory GABA function, so-called neural disinhibition, has been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline. We previously showed in rats that hippocampal disinhibition by local microinfusion of the GABA-A receptor antagonist picrotoxin disrupted memory and attention and enhanced hippocampal multi-unit burst firing recorded around the infusion site under isoflurane anesthesia. Here, we analyzed the hippocampal local field potential (LFP) recorded alongside the multi-unit data. We predicted frequency-specific LFP changes, based on previous studies implicating GABA in hippocampal oscillations, with the weight of evidence suggesting that disinhibition would facilitate theta and disrupt gamma oscillations. Using a new semi-automated method based on the kurtosis of the LFP peak-amplitude distribution as well as on amplitude envelope thresholding, we separated three distinct hippocampal LFP states under isoflurane anesthesia: "burst" and "suppression" states-high-amplitude LFP spike bursts and the interspersed low-amplitudeperiods-and a medium-amplitude "continuous" state. The burst state showed greater overall power than suppression and continuous states and higher relative delta/theta power, but lower relative beta/gamma power. The burst state also showed reduced functional connectivity across the hippocampal recording area, especially around theta and beta frequencies. Overall neuronal firing was higher in the burst than the other two states, whereas the proportion of burst firing was higher in burst and continuous states than the suppression state. Disinhibition caused state- and frequency-dependent LFP changes, tending to increase power at lower frequencies (<20 Hz), but to decrease power and connectivity at higher frequencies (>20 Hz) in burst and suppression states. The disinhibition-induced enhancement of multi-unit bursting was also state-dependent, tending to be more pronounced in burst and suppression states than the continuous state. Overall, we characterized three distinct hippocampal LFP states in isoflurane-anesthetized rats. Disinhibition changed hippocampal LFP oscillations in a state- and frequency-dependent way. Moreover, the disinhibition-induced enhancement of multi-unit bursting was also LFP state-dependent.


Assuntos
Potenciais de Ação/fisiologia , Anestésicos Inalatórios/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Hipocampo/fisiologia , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Hipocampo/efeitos dos fármacos , Injeções Intraventriculares , Isoflurano/administração & dosagem , Masculino , Rede Nervosa/efeitos dos fármacos , Inibição Neural/efeitos dos fármacos , Picrotoxina/administração & dosagem , Ratos
7.
Cereb Cortex ; 29(6): 2668-2681, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29897408

RESUMO

Event-related fluctuations of neural oscillatory amplitude are reported widely in the context of cognitive processing and are typically interpreted as a marker of brain "activity". However, the precise nature of these effects remains unclear; in particular, whether such fluctuations reflect local dynamics, integration between regions, or both, is unknown. Here, using magnetoencephalography, we show that movement induced oscillatory modulation is associated with transient connectivity between sensorimotor regions. Further, in resting-state data, we demonstrate a significant association between oscillatory modulation and dynamic connectivity. A confound with such empirical measurements is that increased amplitude necessarily means increased signal-to-noise ratio (SNR): this means that the question of whether amplitude and connectivity are genuinely coupled, or whether increased connectivity is observed purely due to increased SNR is unanswered. Here, we counter this problem by analogy with computational models which show that, in the presence of global network coupling and local multistability, the link between oscillatory modulation and long-range connectivity is a natural consequence of neural networks. Our results provide evidence for the notion that connectivity is mediated by neural oscillations, and suggest that time-frequency spectrograms are not merely a description of local synchrony but also reflect fluctuations in long-range connectivity.


Assuntos
Encéfalo/fisiologia , Modelos Neurológicos , Rede Nervosa/fisiologia , Neurônios/fisiologia , Adulto , Simulação por Computador , Feminino , Humanos , Magnetoencefalografia , Masculino , Desempenho Psicomotor/fisiologia
8.
Radiology ; 289(3): 775-785, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30204076

RESUMO

Purpose To determine whether functional connectivity (FC) mapping of nucleus basalis of Meynert (NBM) cholinergic network (hereafter, NBM FC) could provide a biomarker of central cholinergic deficits with predictive potential for response to cholinesterase inhibitor (ChEI) treatment. Materials and Methods The Alzheimer's Disease Neuroimaging Initiative (ADNI) was approved by the institutional review boards of all participating sites. All participants and their representatives gave written informed consent prior to data collection. NBM FC was examined in 33 healthy control participants, 102 patients with mild cognitive impairment (MCI), and 33 patients with AD by using resting-state functional MRI data from the ADNI database. NBM FC was compared between groups before and after 6 months of ChEI treatment in MCI. Associations between baseline NBM FC and baseline cognitive performance as well as cognitive outcomes after treatment were investigated. Results Compared with the healthy control group, NBM FC was decreased in patients with untreated MCI and increased in patients with AD treated with ChEI (corrected P ˂ .05). Global cognition (Alzheimer's Disease Assessment Scale-Cognitive subscale score) was associated with NBM FC (r = -0.349; P ˂ .001). NBM FC was higher 6 months after ChEI compared with before ChEI in treated MCI (corrected P ˂ .05), but did not change at 6 months in patients with untreated MCI (corrected P ˂ .05). Baseline NBM FC in MCI strongly predicted cognitive outcomes 6 months after ChEI (R2 = 0.458; P = .001). Conclusion Functional dissociation of the nucleus basalis of Meynert from a cortical network may explain the cognitive deficits in dementia and allow for the selection of individuals who are more likely to respond to cholinesterase inhibitors at early disease stages. © RSNA, 2018 Online supplemental material is available for this article.


Assuntos
Núcleo Basal de Meynert/diagnóstico por imagem , Núcleo Basal de Meynert/fisiopatologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Idoso , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
9.
Waste Manag Res ; 36(5): 445-453, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29576012

RESUMO

In recent years, an increasing number of studies have revealed that plastics and their components (e.g. plasticisers) pose an environmental risk. However, it is hard to imagine how our industrialised society could do without these materials, since the fields of application are manifold. One possible approach to tackle this mounting problem is the implementation of a comprehensive and well-functioning collection and recycling system. An international comparison shows that only a small proportion of the total plastics in circulation is collected and recycled. The investigations conducted under the present research project, 'Plastic Reborn', focused on both identification and analysis of the discharge paths of polyolefin-rich waste streams, under the Austrian waste management system. Another objective was determining the utilisation potential of the output fractions of these polyolefin-rich waste streams, generated from a wet mechanical processing pilot plant. Experiments have shown that the polyolefins are successfully separated from the waste streams and that a total polyolefin potential of 429,000 t y-1 remains unexploited in the Austrian waste management system. Thus, these separated plastic fractions can make a significant contribution to the implementation of the European Circular Economy Directive. The residual fractions meet the legal and company-specific requirements for their use as solid recovered fuels in co-combustion plants.


Assuntos
Polienos/química , Reciclagem , Eliminação de Resíduos , Áustria , Plásticos , Resíduos Sólidos , Gerenciamento de Resíduos
10.
Neuroimage ; 132: 175-189, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26921713

RESUMO

This paper shows that it is possible to estimate the subjective precision (inverse variance) of Bayesian beliefs during oculomotor pursuit. Subjects viewed a sinusoidal target, with or without random fluctuations in its motion. Eye trajectories and magnetoencephalographic (MEG) data were recorded concurrently. The target was periodically occluded, such that its reappearance caused a visual evoked response field (ERF). Dynamic causal modelling (DCM) was used to fit models of eye trajectories and the ERFs. The DCM for pursuit was based on predictive coding and active inference, and predicts subjects' eye movements based on their (subjective) Bayesian beliefs about target (and eye) motion. The precisions of these hierarchical beliefs can be inferred from behavioural (pursuit) data. The DCM for MEG data used an established biophysical model of neuronal activity that includes parameters for the gain of superficial pyramidal cells, which is thought to encode precision at the neuronal level. Previous studies (using DCM of pursuit data) suggest that noisy target motion increases subjective precision at the sensory level: i.e., subjects attend more to the target's sensory attributes. We compared (noisy motion-induced) changes in the synaptic gain based on the modelling of MEG data to changes in subjective precision estimated using the pursuit data. We demonstrate that imprecise target motion increases the gain of superficial pyramidal cells in V1 (across subjects). Furthermore, increases in sensory precision - inferred by our behavioural DCM - correlate with the increase in gain in V1, across subjects. This is a step towards a fully integrated model of brain computations, cortical responses and behaviour that may provide a useful clinical tool in conditions like schizophrenia.


Assuntos
Mapeamento Encefálico/métodos , Percepção de Movimento/fisiologia , Acompanhamento Ocular Uniforme , Córtex Visual/fisiologia , Adolescente , Adulto , Teorema de Bayes , Medições dos Movimentos Oculares , Feminino , Humanos , Magnetoencefalografia , Masculino , Modelos Neurológicos , Estimulação Luminosa , Desempenho Psicomotor , Processamento de Sinais Assistido por Computador , Análise de Sistemas , Adulto Jovem
11.
Neuroimage ; 126: 120-30, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26584867

RESUMO

Correlative evidence provides support for the idea that brain oscillations underpin neural computations. Recent work using rhythmic stimulation techniques in humans provide causal evidence but the interactions of these external signals with intrinsic rhythmicity remain unclear. Here, we show that sensorimotor cortex follows externally applied rhythmic TMS (rTMS) stimulation in the beta-band but that the elicited responses are strongest at the intrinsic individual beta peak frequency. While these entrainment effects are of short duration, even subthreshold rTMS pulses propagate through the network and elicit significant cortico-spinal coupling, particularly when stimulated at the individual beta-frequency. Our results show that externally enforced rhythmicity interacts with intrinsic brain rhythms such that the individual peak frequency determines the effect of rTMS. The observed downstream spinal effect at the resonance frequency provides evidence for the causal role of brain rhythms for signal propagation.


Assuntos
Ritmo beta/fisiologia , Eletroencefalografia/métodos , Eletromiografia/métodos , Potencial Evocado Motor/fisiologia , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Feminino , Mãos/fisiologia , Humanos , Masculino , Atividade Motora/fisiologia , Tratos Piramidais/fisiologia , Fatores de Tempo , Adulto Jovem
12.
Hum Brain Mapp ; 37(7): 2493-511, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27061243

RESUMO

Movement induced modulation of the beta rhythm is one of the most robust neural oscillatory phenomena in the brain. In the preparation and execution phases of movement, a loss in beta amplitude is observed [movement related beta decrease (MRBD)]. This is followed by a rebound above baseline on movement cessation [post movement beta rebound (PMBR)]. These effects have been measured widely, and recent work suggests that they may have significant importance. Specifically, they have potential to form the basis of biomarkers for disease, and have been used in neuroscience applications ranging from brain computer interfaces to markers of neural plasticity. However, despite the robust nature of both MRBD and PMBR, the phenomena themselves are poorly understood. In this study, we characterise MRBD and PMBR during a carefully controlled isometric wrist flexion paradigm, isolating two fundamental movement parameters; force output, and the rate of force development (RFD). Our results show that neither altered force output nor RFD has a significant effect on MRBD. In contrast, PMBR was altered by both parameters. Higher force output results in greater PMBR amplitude, and greater RFD results in a PMBR which is higher in amplitude and shorter in duration. These findings demonstrate that careful control of movement parameters can systematically change PMBR. Further, for temporally protracted movements, the PMBR can be over 7 s in duration. This means accurate control of movement and judicious selection of paradigm parameters are critical in future clinical and basic neuroscientific studies of sensorimotor beta oscillations. Hum Brain Mapp 37:2493-2511, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Ritmo beta/fisiologia , Encéfalo/fisiologia , Contração Isométrica/fisiologia , Movimento/fisiologia , Adulto , Feminino , Humanos , Magnetoencefalografia , Masculino , Dinamômetro de Força Muscular , Fatores de Tempo , Punho/fisiologia
13.
Nature ; 463(7278): 191-6, 2010 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-20016485

RESUMO

All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.


Assuntos
Genes Neoplásicos/genética , Genoma Humano/genética , Mutação/genética , Neoplasias/genética , Adulto , Linhagem Celular Tumoral , Dano ao DNA/genética , Análise Mutacional de DNA , Reparo do DNA/genética , Dosagem de Genes/genética , Humanos , Perda de Heterozigosidade/genética , Masculino , Melanoma/etiologia , Melanoma/genética , MicroRNAs/genética , Mutagênese Insercional/genética , Neoplasias/etiologia , Polimorfismo de Nucleotídeo Único/genética , Medicina de Precisão , Deleção de Sequência/genética , Raios Ultravioleta
14.
J Neurosci ; 34(48): 16117-25, 2014 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-25429152

RESUMO

The brain adapts to dynamic environments by adjusting the attentional gain or precision afforded to salient and predictable sensory input. Previous research suggests that this involves the regulation of cortical excitability (reflected in prestimulus alpha oscillations) before stimulus onset that modulates subsequent stimulus processing (reflected in stimulus-bound gamma oscillations). We present two spatial attention experiments in humans, where we first replicate the classic finding of prestimulus attentional alpha modulation and poststimulus gamma modulation. In the second experiment, the task-relevant target was a stimulus change that occurred after stimulus onset. This enabled us to show that attentional alpha modulation reflects the predictability (precision) of an upcoming sensory target, rather than an attenuation of alpha activity induced by neuronal excitation related to stimulus onset. In particular, we show that the strength of attentional alpha modulations increases with the predictability of the anticipated sensory target, regardless of current afferent drive. By contrast, we show that the poststimulus attentional gamma enhancement is stimulus-bound and decreases when the subsequent target becomes more predictable. Hence, this pattern suggests that the strength of gamma oscillations is not merely a function of cortical excitability, but also depends on the relative mismatch of predictions and sensory evidence. Together, these findings support recent theoretical proposals for distinct roles of alpha/beta and gamma oscillations in hierarchical perceptual inference and predictive coding.


Assuntos
Ritmo alfa/fisiologia , Atenção/fisiologia , Ritmo beta/fisiologia , Ritmo Gama/fisiologia , Estimulação Luminosa/métodos , Adulto , Feminino , Humanos , Magnetoencefalografia/métodos , Masculino , Adulto Jovem
15.
J Neurosci ; 34(47): 15735-42, 2014 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-25411501

RESUMO

The exact mechanisms whereby the cholinergic neurotransmitter system contributes to attentional processing remain poorly understood. Here, we applied computational modeling to psychophysical data (obtained from a spatial attention task) under a psychopharmacological challenge with the cholinesterase inhibitor galantamine (Reminyl). This allowed us to characterize the cholinergic modulation of selective attention formally, in terms of hierarchical Bayesian inference. In a placebo-controlled, within-subject, crossover design, 16 healthy human subjects performed a modified version of Posner's location-cueing task in which the proportion of validly and invalidly cued targets (percentage of cue validity, % CV) changed over time. Saccadic response speeds were used to estimate the parameters of a hierarchical Bayesian model to test whether cholinergic stimulation affected the trial-wise updating of probabilistic beliefs that underlie the allocation of attention or whether galantamine changed the mapping from those beliefs to subsequent eye movements. Behaviorally, galantamine led to a greater influence of probabilistic context (% CV) on response speed than placebo. Crucially, computational modeling suggested this effect was due to an increase in the rate of belief updating about cue validity (as opposed to the increased sensitivity of behavioral responses to those beliefs). We discuss these findings with respect to cholinergic effects on hierarchical cortical processing and in relation to the encoding of expected uncertainty or precision.


Assuntos
Atenção/efeitos dos fármacos , Agonistas Colinérgicos/farmacologia , Percepção Espacial/efeitos dos fármacos , Adulto , Teorema de Bayes , Sinais (Psicologia) , Movimentos Oculares/efeitos dos fármacos , Feminino , Galantamina/farmacologia , Humanos , Aprendizagem/efeitos dos fármacos , Masculino , Estimulação Luminosa , Adulto Jovem
16.
Neuroimage ; 115: 85-95, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25899137

RESUMO

Resting state networks (RSNs) are of fundamental importance in human systems neuroscience with evidence suggesting that they are integral to healthy brain function and perturbed in pathology. Despite rapid progress in this area, the temporal dynamics governing the functional connectivities that underlie RSN structure remain poorly understood. Here, we present a framework to help further our understanding of RSN dynamics. We describe a methodology which exploits the direct nature and high temporal resolution of magnetoencephalography (MEG). This technique, which builds on previous work, extends from solving fundamental confounds in MEG (source leakage) to multivariate modelling of transient connectivity. The resulting processing pipeline facilitates direct (electrophysiological) measurement of dynamic functional networks. Our results show that, when functional connectivity is assessed in small time windows, the canonical sensorimotor network can be decomposed into a number of transiently synchronising sub-networks, recruitment of which depends on current mental state. These rapidly changing sub-networks are spatially focal with, for example, bilateral primary sensory and motor areas resolved into two separate sub-networks. The likely interpretation is that the larger canonical sensorimotor network most often seen in neuroimaging studies reflects only a temporal aggregate of these transient sub-networks. Our approach opens new frontiers to study RSN dynamics, showing that MEG is capable of revealing the spatial, temporal and spectral signature of the human connectome in health and disease.


Assuntos
Rede Nervosa/fisiologia , Recrutamento Neurofisiológico/fisiologia , Descanso/fisiologia , Adulto , Conectoma , Feminino , Humanos , Magnetoencefalografia , Masculino , Memória de Curto Prazo/fisiologia , Córtex Motor/fisiologia , Desempenho Psicomotor/fisiologia , Reprodutibilidade dos Testes , Córtex Somatossensorial/fisiologia , Adulto Jovem
17.
J Neurophysiol ; 113(6): 1752-62, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25540223

RESUMO

Sensory consequences of one's own actions are perceived as less intense than identical, externally generated stimuli. This is generally taken as evidence for sensory prediction of action consequences. Accordingly, recent theoretical models explain this attenuation by an anticipatory modulation of sensory processing prior to stimulus onset (Roussel et al. 2013) or even action execution (Brown et al. 2013). Experimentally, prestimulus changes that occur in anticipation of self-generated sensations are difficult to disentangle from more general effects of stimulus expectation, attention and task load (performing an action). Here, we show that an established manipulation of subjective agency over a stimulus leads to a predictive modulation in sensory cortex that is independent of these factors. We recorded magnetoencephalography while subjects performed a simple action with either hand and judged the loudness of a tone caused by the action. Effector selection was manipulated by subliminal motor priming. Compatible priming is known to enhance a subjective experience of agency over a consequent stimulus (Chambon and Haggard 2012). In line with this effect on subjective agency, we found stronger sensory attenuation when the action that caused the tone was compatibly primed. This perceptual effect was reflected in a transient phase-locked signal in auditory cortex before stimulus onset and motor execution. Interestingly, this sensory signal emerged at a time when the hemispheric lateralization of motor signals in M1 indicated ongoing effector selection. Our findings confirm theoretical predictions of a sensory modulation prior to self-generated sensations and support the idea that a sensory prediction is generated in parallel to motor output (Walsh and Haggard 2010), before an efference copy becomes available.


Assuntos
Movimento , Desempenho Psicomotor , Córtex Sensório-Motor/fisiologia , Adulto , Antecipação Psicológica , Feminino , Lateralidade Funcional , Mãos/fisiologia , Humanos , Masculino
18.
Cereb Cortex ; 24(6): 1436-50, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23322402

RESUMO

Inferring the environment's statistical structure and adapting behavior accordingly is a fundamental modus operandi of the brain. A simple form of this faculty based on spatial attentional orienting can be studied with Posner's location-cueing paradigm in which a cue indicates the target location with a known probability. The present study focuses on a more complex version of this task, where probabilistic context (percentage of cue validity) changes unpredictably over time, thereby creating a volatile environment. Saccadic response speed (RS) was recorded in 15 subjects and used to estimate subject-specific parameters of a Bayesian learning scheme modeling the subjects' trial-by-trial updates of beliefs. Different response models-specifying how computational states translate into observable behavior-were compared using Bayesian model selection. Saccadic RS was most plausibly explained as a function of the precision of the belief about the causes of sensory input. This finding is in accordance with current Bayesian theories of brain function, and specifically with the proposal that spatial attention is mediated by a precision-dependent gain modulation of sensory input. Our results provide empirical support for precision-dependent changes in beliefs about saccade target locations and motivate future neuroimaging and neuropharmacological studies of how Bayesian inference may determine spatial attention.


Assuntos
Atenção , Teorema de Bayes , Aprendizagem , Modelos Psicológicos , Movimentos Sacádicos , Percepção Espacial , Adulto , Algoritmos , Sinais (Psicologia) , Medições dos Movimentos Oculares , Feminino , Fixação Ocular , Humanos , Masculino , Testes Neuropsicológicos , Probabilidade , Tempo de Reação , Reprodutibilidade dos Testes , Análise e Desempenho de Tarefas , Adulto Jovem
19.
J Neurosci ; 33(2): 442-51, 2013 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-23303925

RESUMO

Optimal decision making requires that we integrate mnemonic information regarding previous decisions with value signals that entail likely rewards and punishments. The fact that memory and value signals appear to be coded by segregated brain regions, the hippocampus in the case of memory and sectors of prefrontal cortex in the case of value, raises the question as to how they are integrated during human decision making. Using magnetoencephalography to study healthy human participants, we show increased theta oscillations over frontal and temporal sensors during nonspatial decisions based on memories from previous trials. Using source reconstruction we found that the medial temporal lobe (MTL), in a location compatible with the anterior hippocampus, and the anterior cingulate cortex in the medial wall of the frontal lobe are the source of this increased theta power. Moreover, we observed a correlation between theta power in the MTL source and behavioral performance in decision making, supporting a role for MTL theta oscillations in decision-making performance. These MTL theta oscillations were synchronized with several prefrontal sources, including lateral superior frontal gyrus, dorsal anterior cingulate gyrus, and medial frontopolar cortex. There was no relationship between the strength of synchronization and the expected value of choices. Our results indicate a mnemonic guidance of human decision making, beyond anticipation of expected reward, is supported by hippocampal-prefrontal theta synchronization.


Assuntos
Sincronização Cortical , Tomada de Decisões/fisiologia , Córtex Pré-Frontal/fisiologia , Lobo Temporal/fisiologia , Adulto , Antecipação Psicológica , Comportamento/fisiologia , Feminino , Hipocampo/fisiologia , Humanos , Aprendizagem/fisiologia , Magnetoencefalografia , Masculino , Memória/fisiologia , Desempenho Psicomotor/fisiologia , Reforço Psicológico , Recompensa , Ritmo Teta/fisiologia , Adulto Jovem
20.
J Cogn Neurosci ; 26(11): 2540-51, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24800633

RESUMO

The perceived intensity of sensory stimuli is reduced when these stimuli are caused by the observer's actions. This phenomenon is traditionally explained by forward models of sensory action-outcome, which arise from motor processing. Although these forward models critically predict anticipatory modulation of sensory neural processing, neurophysiological evidence for anticipatory modulation is sparse and has not been linked to perceptual data showing sensory attenuation. By combining a psychophysical task involving contrast discrimination with source-level time-frequency analysis of MEG data, we demonstrate that the amplitude of alpha-oscillations in visual cortex is enhanced before the onset of a visual stimulus when the identity and onset of the stimulus are controlled by participants' motor actions. Critically, this prestimulus enhancement of alpha-amplitude is paralleled by psychophysical judgments of a reduced contrast for this stimulus. We suggest that alpha-oscillations in visual cortex preceding self-generated visual stimulation are a likely neurophysiological signature of motor-induced sensory anticipation and mediate sensory attenuation. We discuss our results in relation to proposals that attribute generic inhibitory functions to alpha-oscillations in prioritizing and gating sensory information via top-down control.


Assuntos
Ritmo alfa/fisiologia , Antecipação Psicológica/fisiologia , Estimulação Luminosa/métodos , Autoestimulação/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Mapeamento Encefálico , Feminino , Humanos , Magnetoencefalografia , Masculino , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia , Psicofísica , Adulto Jovem
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