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10 result(s) for "Brochier, Thomas G."
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Mapping Horizontal Spread of Activity in Monkey Motor Cortex Using Single Pulse Microstimulation
Anatomical studies have demonstrated that distant cortical points are interconnected through long range axon collaterals of pyramidal cells. However, the functional properties of these intrinsic synaptic connections, especially their relationship with the cortical representations of body movements, have not been systematically investigated. To address this issue, we used multielectrode arrays chronically implanted in the motor cortex of two rhesus monkeys to analyze the effects of single-pulse intracortical microstimulation (sICMS) applied at one electrode on the neuronal activities recorded at all other electrodes. The temporal and spatial distribution of the evoked responses of single and multiunit activities was quantified to determine the properties of horizontal propagation. The typical responses were characterized by a brief excitatory peak followed by inhibition of longer duration. Significant excitatory responses to sICMS could be evoked up to 4 mm away from the stimulation site, but the strength of the response decreased exponentially and its latency increased linearly with the distance. We then quantified the direction and strength of the propagation in relation to the somatotopic organization of the motor cortex. We observed that following sICMS the propagation of neural activity is mainly directed rostro-caudally near the central sulcus but follows medio-lateral direction at the most anterior electrodes. The fact that these interactions are not entirely symmetrical may characterize a critical functional property of the motor cortex for the control of upper limb movements. Overall, these results support the assumption that the motor cortex is not functionally homogeneous but forms a complex network of interacting subregions.
Decoding covert shifts of attention induced by ambiguous visuospatial cues
Simple and unambiguous visual cues (e.g., an arrow) can be used to trigger covert shifts of visual attention away from the center of gaze. The processing of visual stimuli is enhanced at the attended location. Covert shifts of attention modulate the power of cerebral oscillations in the alpha band over parietal and occipital regions. These modulations are sufficiently robust to be decoded on a single trial basis from electroencephalography (EEG) signals. It is often assumed that covert attention shifts are under voluntary control, and that they also occur in more natural and complex environments, but there is no direct evidence to support this assumption. We address this important issue by using random-dot stimuli to cue one of two opposite locations, where a visual target is presented. We contrast two conditions, one in which the random-dot motion is predictive of the target location, and the other, in which it provides ambiguous information. Behavioral results show attention shifts in anticipation of the visual target, in both conditions. In addition, using the common spatial patterns (CSPs) algorithm, we extract EEG power features in the alpha-band (around 10 Hz) that best discriminate the attended location in single trials. We obtain a significant decoding accuracy in 7/10 subjects using a cross-validation procedure applied in the predictive condition. Interestingly, similar accuracy (significant in 5/10 subjects) is obtained when the CSPs trained in the predictive condition are tested in the ambiguous condition. In agreement with this result, we find that the CSPs show very similar topographies in both conditions. These results shed a new light on the behavioral and EEG correlates of visuospatial attention in complex visual environments. This study demonstrates that alpha-power features could be used in brain-computer interfaces to decode covert attention shifts in an environment containing ambiguous spatial information.
Handling Metadata in a Neurophysiology Laboratory
To date, non-reproducibility of neurophysiological research is a matter of intense discussion in the scientific community. A crucial component to enhance reproducibility is to comprehensively collect and store metadata, that is, all information about the experiment, the data, and the applied preprocessing steps on the data, such that they can be accessed and shared in a consistent and simple manner. However, the complexity of experiments, the highly specialized analysis workflows and a lack of knowledge on how to make use of supporting software tools often overburden researchers to perform such a detailed documentation. For this reason, the collected metadata are often incomplete, incomprehensible for outsiders or ambiguous. Based on our research experience in dealing with diverse datasets, we here provide conceptual and technical guidance to overcome the challenges associated with the collection, organization, and storage of metadata in a neurophysiology laboratory. Through the concrete example of managing the metadata of a complex experiment that yields multi-channel recordings from monkeys performing a behavioral motor task, we practically demonstrate the implementation of these approaches and solutions with the intention that they may be generalized to other projects. Moreover, we detail five use cases that demonstrate the resulting benefits of constructing a well-organized metadata collection when processing or analyzing the recorded data, in particular when these are shared between laboratories in a modern scientific collaboration. Finally, we suggest an adaptable workflow to accumulate, structure and store metadata from different sources using, by way of example, the odML metadata framework.
Deep morphological analysis of muscle biopsies from type III glycogenesis (GSDIII), debranching enzyme deficiency, revealed stereotyped vacuolar myopathy and autophagy impairment
Glycogen storage disorder type III (GSDIII), or debranching enzyme (GDE) deficiency, is a rare metabolic disorder characterized by variable liver, cardiac, and skeletal muscle involvement. GSDIII manifests with liver symptoms in infancy and muscle involvement during early adulthood. Muscle biopsy is mainly performed in patients diagnosed in adulthood, as routine diagnosis relies on blood or liver GDE analysis, followed by AGL gene sequencing. The GSDIII mouse model recapitulate the clinical phenotype in humans, and a nearly full rescue of muscle function was observed in mice treated with the dual AAV vector expressing the GDE transgene. In order to characterize GSDIII muscle morphological spectrum and identify novel disease markers and pathways, we performed a large international multicentric morphological study on 30 muscle biopsies from GSDIII patients. Autophagy flux studies were performed in human muscle biopsies and muscles from GSDIII mice. The human muscle biopsies revealed a typical and constant vacuolar myopathy, characterized by multiple and variably sized vacuoles filled with PAS-positive material. Using electron microscopy, we confirmed the presence of large non-membrane bound sarcoplasmic deposits of normally structured glycogen as well as smaller rounded sac structures lined by a continuous double membrane containing only glycogen, corresponding to autophagosomes. A consistent SQSTM1/p62 decrease and beclin-1 increase in human muscle biopsies suggested an enhanced autophagy. Consistent with this, an increase in the lipidated form of LC3, LC3II was found in patients compared to controls. A decrease in SQSTM1/p62 was also found in the GSDIII mouse model. In conclusion, we characterized the morphological phenotype in GSDIII muscle and demonstrated dysfunctional autophagy in GSDIII human samples. These findings suggest that autophagic modulation combined with gene therapy might be considered as a novel treatment for GSDIII.
Case finding of Influenza A(H1N1)2009 in Belgium in the early pandemic
Together with the medical epidemiologist on call of the Scientific Institute of Public Health (WIV-ISP), the decision was made to take or not to take a sample. Each day, the medical doctor on call at the former Epidemiology Unit of the WIV-ISP informed the prescribers and brought all epidemiological information together with final diagnoses in order to inform health authorities allowing them to take protective measures according to the procedure. [...]individual laboratory diagnoses were still performed by the NIC, as by others labs where the diagnose capacity was delocalised, responding to the time needed for adaptation from one strategy to another or to the necessity in some cases to have a confirmed diagnose (e.g. pregnant women, chronically ill patients, patients with unfavourable evolution). According to the Influenza Preparedness Plan, only patients fulfilling criteria for a possible case should have been selected for laboratory testing.
Brain Charts for the Rhesus Macaque Lifespan
Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.
Spontaneous spiking statistics form unique area-specific fingerprints and reflect the hierarchy of cerebral cortex
The cerebral cortex, from sensory to higher cognitive areas, is hierarchically organised1–4. Several dynamical5–7 and anatomical1–4 measures, such as timescales and neurotransmitter receptor expression, have independently been linked to the cortical hierarchy. However, a systematic quantitative link between anatomical markers of the cortical hierarchy and single-neuron dynamics has not yet been established. Here, we hypothesise that the single-neuron spontaneous spiking statistics uniquely characterise each cortical area, and that they quantitatively correlate with the cortical hierarchy. We consider the spontaneous activity of neurons in seven cortical areas (V1, V4, DP, 7A, M1, PMd, PFC) in macaques8–11 in the eyes-open and eyes-closed conditions. First, we show that the firing rate, inter-spike interval variation, and cross-correlation form a unique fingerprint of the cortical areas, but only when considering them in combination. Second, we find that the differences between the spiking statistics strongly correlate with multiple anatomical markers1,2,4,12–16 of the cortical hierarchy, especially in the eyes-closed condition. We also observe a correlation between autocorrelation timescales and the anatomical hierarchy, consistent with previous findings5,17,18. In conclusion, we demonstrate that spontaneous single-neuron spiking activity reflects the hierarchical organisation of the cerebral cortex: distinct spiking statistics for hierarchically distant areas; similar statistics for nearby areas. Our results thus add a new dynamical dimension to the concept of the cortical hierarchy.