Impact of the day/night cycle on functional connectome in ageing male and female mice.

To elucidate how time of day, sex, and age affect functional connectivity (FC) in mice, we aimed to examine whether the mouse functional connectome varied with the day/night cycle and whether it depended on sex and age. We explored C57Bl6/J mice (6♀ and 6♂) at mature age (5 ± 1 months) and middle-age (14 ± 1 months). Each mouse underwent Blood Oxygen-Level-Dependent (BOLD) resting-state functional MRI (rs-fMRI) on a 7T scanner at four different times of the day, two under the light condition and two under the dark condition. Data processing consisted of group independent component analysis (ICA) and region-level analysis using resting-state networks (RSNs) derived from literature. Linear mixed-effect models (LMEM) were used to assess the effects of sex, lighting condition and their interactions for each RSN obtained with group-ICA (RSNs-GICA) and six bilateral RSNs adapted from literature (RSNs-LIT). Our study highlighted new RSNs in mice related to day/night alternation in addition to other networks already reported in the literature. In mature mice, we found sex-related differences in brain activation only in one RSNs-GICA comprising the cortical, hippocampal, midbrain and cerebellar regions of the right hemisphere. In males, brain activity was significantly higher in the left hippocampus, the retrosplenial cortex, the superior colliculus, and the cerebellum regardless of lighting condition; consistent with the role of these structures in memory formation and integration, sleep, and sex-differences in memory processing. Experimental constraints limited the analysis to the impact of light/dark cycle on the RSNs for middle-aged females. We detected significant activation in the pineal gland during the dark condition, a finding in line with the nocturnal activity of this gland. For the analysis of RSNs-LIT, new variables "sexage" (sex and age combined) and "edges" (pairs of RSNs) were introduced. FC was calculated as the Pearson correlation between two RSNs. LMEM revealed no effect of sexage or lighting condition. The FC depended on the edges, but there were no interaction effects between sexage, lighting condition and edges. Interaction effects were detected between i) sex and lighting condition, with higher FC in males under the dark condition, ii) sexage and edges with higher FC in male brain regions related to vision, memory, and motor action. We conclude that time of day and sex should be taken into account when designing, analyzing, and interpreting functional imaging studies in rodents.

Altered spread of waves of activities at large scale is influenced by cortical thickness organization in temporal lobe epilepsy: a magnetic resonance imaging-high-density electroencephalography study.

Temporal lobe epilepsy is a brain network disorder characterized by alterations at both the structural and the functional levels. It remains unclear how structure and function are related and whether this has any clinical relevance. In the present work, we adopted a novel methodological approach investigating how network structural features influence the large-scale dynamics. The functional network was defined by the spatio-temporal spreading of aperiodic bursts of activations (neuronal avalanches), as observed utilizing high-density electroencephalography in patients with temporal lobe epilepsy. The structural network was modelled as the region-based thickness covariance. Loosely speaking, we quantified the similarity of the cortical thickness of any two brain regions, both across groups and at the individual level, the latter utilizing a novel approach to define the subject-wise structural covariance network. In order to compare the structural and functional networks (at the nodal level), we studied the correlation between the probability that a wave of activity would propagate from a source to a target region and the similarity of the source region thickness as compared with other target brain regions. Building on the recent evidence that large-waves of activities pathologically spread through the epileptogenic network in temporal lobe epilepsy, also during resting state, we hypothesize that the structural cortical organization might influence such altered spatio-temporal dynamics. We observed a stable cluster of structure-function correlation in the bilateral limbic areas across subjects, highlighting group-specific features for left, right and bilateral temporal epilepsy. The involvement of contralateral areas was observed in unilateral temporal lobe epilepsy. We showed that in temporal lobe epilepsy, alterations of structural and functional networks pair in the regions where seizures propagate and are linked to disease severity. In this study, we leveraged on a well-defined model of neurological disease and pushed forward personalization approaches potentially useful in clinical practice. Finally, the methods developed here could be exploited to investigate the relationship between structure-function networks at subject level in other neurological conditions.

Spontaneous neuronal avalanches as a correlate of access consciousness.

Decades of research have advanced our understanding of the biophysical mechanisms underlying consciousness. However, an overarching framework bridging between models of consciousness and the large-scale organization of spontaneous brain activity is still missing. Based on the observation that spontaneous brain activity dynamically switches between epochs of segregation and large-scale integration of information, we hypothesize a brain-state dependence of conscious access, whereby the presence of either segregated or integrated states marks distinct modes of information processing. We first review influential works on the neuronal correlates of consciousness, spontaneous resting-state brain activity and dynamical system theory. Then, we propose a test experiment to validate our hypothesis that conscious access occurs in aperiodic cycles, alternating windows where new incoming information is collected but not experienced, to punctuated short-lived integration events, where conscious access to previously collected content occurs. In particular, we suggest that the integration events correspond to neuronal avalanches, which are collective bursts of neuronal activity ubiquitously observed in electrophysiological recordings. If confirmed, the proposed framework would link the physics of spontaneous cortical dynamics, to the concept of ignition within the global neuronal workspace theory, whereby conscious access manifest itself as a burst of neuronal activity.

Neuronal Cascades Shape Whole-Brain Functional Dynamics at Rest.

At rest, mammalian brains display remarkable spatiotemporal complexity, evolving through recurrent functional connectivity (FC) states on a slow timescale of the order of tens of seconds. While the phenomenology of the resting state dynamics is valuable in distinguishing healthy and pathologic brains, little is known about its underlying mechanisms. Here, we identify neuronal cascades as a potential mechanism. Using full-brain network modeling, we show that neuronal populations, coupled via a detailed structural connectome, give rise to large-scale cascades of firing rate fluctuations evolving at the same time scale of resting-state networks (RSNs). The ignition and subsequent propagation of cascades depend on the brain state and connectivity of each region. The largest cascades produce bursts of blood oxygen level-dependent (BOLD) co-fluctuations at pairs of regions across the brain, which shape the simulated RSN dynamics. We experimentally confirm these theoretical predictions. We demonstrate the existence and stability of intermittent epochs of FC comprising BOLD co-activation (CA) bursts in mice and human functional magnetic resonance imaging (fMRI). We then provide evidence for the existence and leading role of the neuronal cascades in humans with simultaneous EEG/fMRI recordings. These results show that neuronal cascades are a major determinant of spontaneous fluctuations in brain dynamics at rest.