Biology subjects

Goldman, S.

Publications and source records attributed to Goldman, S..

5 recordsLinked to original sources

bioRxiv2021

Microstates and power envelope hidden Markov modeling probe bursting brain activity at different timescales

State modeling of whole-brain electroencephalography (EEG) or magnetoencephalography (MEG) allows to investigate transient, recurring neurodynamical events. Two widely-used techniques are the microstate analysis of EEG signals and hidden Markov modeling (HMM) of MEG power envelopes. Both reportedly lead to similar state lifetimes on the 100 ms timescale, suggesting a common neural basis. We addressed this issue by using simultaneous MEG/EEG recordings at rest and comparing the spatial signature and temporal activation dynamics of microstates and power envelope HMM states obtained separately from EEG and MEG. Results showed that microstates and power envelope HMM states differed both spatially and temporally. Microstates tend to exhibit spatio-temporal locality, whereas power envelope HMM states disclose network-level activity with 100-200 ms lifetimes. Further, MEG microstates do not correspond to the canonical EEG microstates but are better interpreted as split HMM states. On the other hand, both MEG and EEG HMM states involve the (de)activation of similar functional networks. Microstate analysis and power envelope HMM thus appear sensitive to neural events occurring over different spatial and temporal scales. As such, they represent complementary approaches to explore the fast, sub-second scale bursting electrophysiological dynamics in spontaneous human brain activity.

neuroscience↗

bioRxiv2020

Tumor edge architecture in glioblastoma is constructed by inter-cellular signals from vascular endothelial cells

One of the hallmarks of glioblastoma (GBM) is extensive neovascularization. In addition to supplying blood and nutrients, vascular endothelial (VE) cells provide trophic support to GBM cells via paracrine signaling, the precise mechanisms of which are being unraveled. Here, using patient-derived GBM and VE cells as well as orthotopic GBM mouse models, we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity. Mechanistically, Endocan exerts at least part of its functions via direct binding and activation of the PDGFRA receptor. Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing highly stable phenotypic changes in GBM cells. Furthermore, Endocan confers a radioprotection phenotype in GBM cells, both in vitro and in vivo. Inhibition of Endocan-PDGFRA signaling with ponatinib increases survival in the Esm1 wild-type but not in the Esm1 knock-out mouse GBM model. Our findings identify Endocan and its downstream signaling axis as a potential target to subdue the recurrence of GBM and further highlight the importance of vascular to tumor cell signaling for GBM biology. Significance statementIdentification of the Endocan/PDGFRA/Myc axis demonstrates an important role of VE cells in GBM malignancy. The contribution of Endocan to the development of GBM cell populations with different phenotypes reveal an additional pathway underlying the origin of GBM intratumoral heterogeneity. Targeting Endocan-mediated crosstalk may enhance the efficacy of GBM treatment.

cancer biology↗

bioRxiv2020

Alterations in resting-state network dynamics along the Alzheimer's disease continuum: a combined MEG-PET/MR approach

Human brain activity is intrinsically organized into resting-state networks (RSNs) that transiently activate or deactivate at the sub-second timescale. Few neuroimaging studies have addressed how Alzheimers disease (AD) affects these fast temporal brain dynamics, and how they relate to the cognitive, structural and metabolic abnormalities characterizing AD. We aimed at closing this gap by investigating both brain structure and function using magnetoencephalography (MEG) and hybrid positron emission tomography-magnetic resonance (PET/MR) in 10 healthy elders, 10 patients with Subjective Cognitive Decline (SCD), 10 patients with amnestic Mild Cognitive Impairment (aMCI) and 10 patients with typical Alzheimers disease with dementia (AD). The fast activation/deactivation state dynamics of RSNs were assessed using hidden Markov modeling (HMM) of power envelope fluctuations at rest measured with MEG. HMM patterns were related to participants cognitive test scores, whole hippocampal grey matter volume and regional brain glucose metabolism. The posterior default-mode network (DMN) was less often activated and for shorter durations in AD patients than matched healthy elders. No significant difference was found in patients with SCD or aMCI. The time spent by participants in the activated posterior DMN state did not correlate significantly with cognitive scores. However, it correlated positively with the whole hippocampal volume and regional glucose consumption in the right temporo-parietal junctions and dorsolateral prefrontal cortex, and negatively with glucose consumption in the cerebellum. In AD patients, alterations of posterior DMN power activation dynamics at rest correlate with structural and neurometabolic abnormalities. These findings represent an additional electrophysiological correlate of AD-related synaptic and neural dysfunction.

neuroscience↗

bioRxiv2020

Changes in electrophysiological static and dynamic human brain functional architecture from childhood to late adulthood

This magnetoencephalography study aimed at characterizing age-related changes in resting-state functional brain organization from mid-childhood to late adulthood. We investigated neuromagnetic brain activity at rest in 105 participants divided into three age groups: children (6-9 years), young adults (18-34 years) and healthy elders (53-78 years). The effects of age on static resting-state functional integration were assessed using band-limited power envelope correlation, whereas those on transient functional dynamics were disclosed using hidden Markov modeling of power envelope activity. Brain development from childhood to adulthood came with (i) a strengthening of functional integration within and between resting-state networks and (ii) an increased temporal stability of transient (100-300 ms lifetime) and recurrent states of network activation or deactivation mainly encompassing lateral or medial associative neocortical areas. Healthy aging was characterized by decreased static resting-state functional integration and dynamical stability within the visual network. These results based on electrophysiological measurements free of neurovascular biases suggest that functional brain integration mainly evolves during brain development, with limited changes in healthy aging. These novel electrophysiological insights into human brain functional architecture across the lifespan pave the way for future clinical studies investigating how brain disorders affect brain development or healthy aging.

neuroscience↗

bioRxiv2020

Intrinsic/extrinsic duality of large-scale neural functional integration in the human brain

Human brain activity is not merely responsive to environmental context but includes intrinsic dynamics, as suggested by the discovery of functionally meaningful neural networks at rest, i.e., even without explicit engagement of the corresponding function. Yet, the neurophysiological coupling mechanisms distinguishing intrinsic (i.e., task-invariant) from extrinsic (i.e., task-dependent) brain networks remain indeterminate. Here, we investigated functional brain integration using magnetoencephalography throughout rest and various tasks recruiting different functional systems and modulating perceptual/cognitive loads. We demonstrated that two distinct modes of neural communication continually operate in parallel: extrinsic coupling supported by phase synchronization and intrinsic integration encoded in amplitude correlation. Intrinsic integration also contributes to phase synchronization, especially over short (second-long) timescales, through modulatory effects of amplitude correlation. Our study establishes the foundations of a novel conceptual framework for human brain function that fundamentally relies on electrophysiological features of functional integration. This framework blurs the boundary between resting-state and task-related neuroimaging.

neuroscience↗