Dynamic Functional Connectivity between order and randomness and its evolution across the human adult lifespan.

Functional Connectivity (FC) during resting-state or task conditions is not static but inherently dynamic. Yet, there is no consensus on whether fluctuations in FC may resemble isolated transitions between discrete FC states rather than continuous changes. This quarrel hampers advancing the study of dynamic FC. This is unfortunate as the structure of fluctuations in FC can certainly provide more information about developmental changes, aging, and progression of pathologies. We merge the two perspectives and consider dynamic FC as an ongoing network reconfiguration, including a stochastic exploration of the space of possible steady FC states. The statistical properties of this random walk deviate both from a purely "order-driven" dynamics, in which the mean FC is preserved, and from a purely "randomness-driven" scenario, in which fluctuations of FC remain uncorrelated over time. Instead, dynamic FC has a complex structure endowed with long-range sequential correlations that give rise to transient slowing and acceleration epochs in the continuous flow of reconfiguration. Our analysis for fMRI data in healthy elderly revealed that dynamic FC tends to slow down and becomes less complex as well as more random with increasing age. These effects appear to be strongly associated with age-related changes in behavioural and cognitive performance.

Modular slowing of resting-state dynamic functional connectivity as a marker of cognitive dysfunction induced by sleep deprivation.

Dynamic Functional Connectivity (dFC) in the resting state (rs) is considered as a correlate of cognitive processing. Describing dFC as a flow across morphing connectivity configurations, our notion of dFC speed quantifies the rate at which FC networks evolve in time. Here we probe the hypothesis that variations of rs dFC speed and cognitive performance are selectively interrelated within specific functional subnetworks. In particular, we focus on Sleep Deprivation (SD) as a reversible model of cognitive dysfunction. We found that whole-brain level (global) dFC speed significantly slows down after 24h of SD. However, the reduction in global dFC speed does not correlate with variations of cognitive performance in individual tasks, which are subtle and highly heterogeneous. On the contrary, we found strong correlations between performance variations in individual tasks -including Rapid Visual Processing (RVP, assessing sustained visual attention)- and dFC speed quantified at the level of functional sub-networks of interest. Providing a compromise between classic static FC (no time) and global dFC (no space), modular dFC speed analyses allow quantifying a different speed of dFC reconfiguration independently for sub-networks overseeing different tasks. Importantly, we found that RVP performance robustly correlates with the modular dFC speed of a characteristic frontoparietal module.

Different patterns of intrinsic functional connectivity at the default mode and attentional networks predict crystalized and fluid abilities in childhood.

Crystallized abilities are skills used to solve problems based on experience, while fluid abilities are linked to reasoning without evoke prior knowledge. To what extent crystallized and fluid abilities involve dissociated or overlapping neural systems is debatable. Due to often deployed small sample sizes or different study settings in prior work, the neural basis of crystallized and fluid abilities in childhood remains largely unknown. Here we analyzed within and between network connectivity patterns from resting-state functional MRI of 2707 children between 9 and 10 years from the ABCD study. We hypothesized that differences in functional connectivity at the default mode network (DMN), ventral, and dorsal attentional networks (VAN, DAN) explain differences in fluid and crystallized abilities. We found that stronger between-network connectivity of the DMN and VAN, DMN and DAN, and VAN and DAN predicted crystallized abilities. Within-network connectivity of the DAN predicted both crystallized and fluid abilities. Our findings reveal that crystallized abilities rely on the functional coupling between attentional networks and the DMN, whereas fluid abilities are associated with a focal connectivity configuration at the DAN. Our study provides new evidence into the neural basis of child intelligence and calls for future comparative research in adulthood during neuropsychiatric diseases.

Dynamic Functional Connectivity as a complex random walk: Definitions and the dFCwalk toolbox.

•We have developed a framework to describe the dynamics of Functional Connectivity (dFC) estimated from brain activity time-series as a complex random walk in the space of possible functional networks. This conceptual and methodological framework considers dFC as a smooth reconfiguration process, combining "liquid" and "coordinated" aspects. Unlike other previous approaches, our method does not require the explicit extraction of discrete connectivity states.•In our previous work, we introduced several metrics for the quantitative characterization of the dFC random walk. First, dFC speed analyses extract the distribution of the time-resolved rate of reconfiguration of FC along time. These distributions have a clear peak (typical dFC speed, that can already serve as a biomarker) and fat tails (denoting deviations from Gaussianity that can be detected by suitable scaling analyses of FC network streams). Second, meta-connectivity (MC) analyses identify groups of functional links whose fluctuations co-vary in time and that define veritable dFC modules organized along specific dFC meta-hub controllers (differing from conventional FC modules and hubs). The decomposition of whole-brain dFC by MC allows performing dFC speed analyses separately for each of the detected dFC modules.•We present here blocks and pipelines for dFC random walk analyses that are made easily available through a dedicated MATLABⓇ toolbox (dFCwalk), openly downloadable. Although we applied such analyses mostly to fMRI resting state data, in principle our methods can be extended to any type of neural activity (from Local Field Potentials to EEG, MEG, fNIRS, etc.) or even non-neural time-series.

Cerebrospinal fluid examination may be useful in diagnosing neurosyphilis in asymptomatic HIV+ patients with syphilis.

Lumbar puncture in neurologically asymptomatic HIV+ patients is still under debate. There are different criteria for detecting neurosyphilis through cerebrospinal fluid (CSF), especially in cases that are negative through the Venereal Disease Research Laboratory (VDRL), regarding cellularity and protein content. However, a diagnosis of neurosyphilis can still exist despite negative VDRL. Treponema pallidum hemagglutination assay (TPHA) titers and application of the TPHA index in albumin and IgG improve the sensitivity, with a high degree of specificity. Thirty-two patients were selected for this study. VDRL was positive in five of them. The number of diagnoses reached 14 when the other techniques were added. It was not determined whether cellularity and increased protein levels were auxiliary tools in the diagnosis. According to our investigation, CSF analysis using the abovementioned techniques may be useful in diagnosing neurosyphilis in these patients.

Cerebrospinal fluid examination may be useful in diagnosing neurosyphilis in asymptomatic HIV+ patients with syphilis / El examen del líquido céfalo raquídeo puede ser útil en el diagnóstico de neurosífilis en pacientes VIH + asintomáticos con sífilis

ABSTRACT Lumbar puncture in neurologically asymptomatic HIV+ patients is still under debate. There are different criteria for detecting neurosyphilis through cerebrospinal fluid (CSF), especially in cases that are negative through the Venereal Disease Research Laboratory (VDRL), regarding cellularity and protein content. However, a diagnosis of neurosyphilis can still exist despite negative VDRL. Treponema pallidum hemagglutination assay (TPHA) titers and application of the TPHA index in albumin and IgG improve the sensitivity, with a high degree of specificity. Thirty-two patients were selected for this study. VDRL was positive in five of them. The number of diagnoses reached 14 when the other techniques were added. It was not determined whether cellularity and increased protein levels were auxiliary tools in the diagnosis. According to our investigation, CSF analysis using the abovementioned techniques may be useful in diagnosing neurosyphilis in these patients.

RESUMO La punción lumbar (PL) en pacientes VIH+ neurológicamente asintomáticos es controversial. Existen diferentes criterios para detectar en el líquido cefalorraquídeo (LCR) neurosífilis (NS): el examen Venereal Disease Research Laboratory (VDRL) en primer lugar, en caso de negatividad: la celularidad y el tenor de proteinas. Sin embargo el diagnóstico de NS puede ser sostenido a pesar de la negatividad de las técnicas mencionadas. La titulación del Treponema pallidum hemagglutination assay (TPHA) y la aplicación del índice de TPHA en Albúmina e Ig G mejoran la sensibilidad asociando elevado grado de especificidad. 32 pacientes fueron seleccionados para este estudio, el VDRL fue positivo en 5. El diagnóstico se elevó a 14 cuando se sumaron el resto de las técnicas. No se evidenció que la celularidad y el aumento de proteínas fueran herramientas auxiliares para el diagnóstico. De acuerdo a nuestro trabajo el estudio del LCR con las técnicas señaladas puede ser de utilidad en el diagnóstico de NS en estos pacientes.