Generative models of the human connectome

The human connectome represents a network map of the brain's wiring diagram and the pattern into which its connections are organized is thought to play an important role in cognitive function. The generative rules that shape the topology of the human connectome remain incompletely understood. Earlier work in model organisms has suggested that wiring rules based on geometric relationships (distance) can account for many but likely not all topological features. Here we systematically explore a family of generative models of the human connectome that yield synthetic networks designed according to different wiring rules combining geometric and a broad range of topological factors. We find that a combination of geometric constraints with a homophilic attachment mechanism can create synthetic networks that closely match many topological characteristics of individual human connectomes, including features that were not included in the optimization of the generative model itself. We use these models to investigate a lifespan dataset and show that, with age, the model parameters undergo progressive changes, suggesting a rebalancing of the generative factors underlying the connectome across the lifespan.Comment: 38 pages, 5 figures + 19 supplemental figures, 1 tabl

Distinct and dissociable EEG networks are associated with recovery of cognitive function following anesthesia-induced unconsciousness

The temporal trajectories and neural mechanisms of recovery of cognitive function after a major perturbation of consciousness is of both clinical and neuroscientific interest. The purpose of the present study was to investigate network-level changes in functional brain connectivity associated with the recovery and return of six cognitive functions after general anesthesia. High-density electroencephalograms (EEG) were recorded from healthy volunteers undergoing a clinically relevant anesthesia protocol (propofol induction and isoflurane maintenance), and age-matched healthy controls. A battery of cognitive tests (motor praxis, visual object learning test, fractal-2-back, abstract matching, psychomotor vigilance test, digital symbol substitution test) was administered at baseline, upon recovery of consciousness (ROC), and at half-hour intervals up to 3 h following ROC. EEG networks were derived using the strength of functional connectivity measured through the weighted phase lag index (wPLI). A partial least squares (PLS) analysis was conducted to assess changes in these networks: (1) between anesthesia and control groups; (2) during the 3-h recovery from anesthesia; and (3) for each cognitive test during recovery from anesthesia. Networks were maximally perturbed upon ROC but returned to baseline 30-60 min following ROC, despite deficits in cognitive performance that persisted up to 3 h following ROC. Additionally, during recovery from anesthesia, cognitive tests conducted at the same time-point activated distinct and dissociable functional connectivity networks across all frequency bands. The results highlight that the return of cognitive function after anesthetic-induced unconsciousness is task-specific, with unique behavioral and brain network trajectories of recovery

The Functional Connectivity Landscape of the Human Brain

Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short- and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment.</p

Extracting Message Inter-Departure Time Distributions from the Human Electroencephalogram

The complex connectivity of the cerebral cortex is a topic of much study, yet the link between structure and function is still unclear. The processing capacity and throughput of information at individual brain regions remains an open question and one that could potentially bridge these two aspects of neural organization. The rate at which information is emitted from different nodes in the network and how this output process changes under different external conditions are general questions that are not unique to neuroscience, but are of interest in multiple classes of telecommunication networks. In the present study we show how some of these questions may be addressed using tools from telecommunications research. An important system statistic for modeling and performance evaluation of distributed communication systems is the time between successive departures of units of information at each node in the network. We describe a method to extract and fully characterize the distribution of such inter-departure times from the resting-state electroencephalogram (EEG). We show that inter-departure times are well fitted by the two-parameter Gamma distribution. Moreover, they are not spatially or neurophysiologically trivial and instead are regionally specific and sensitive to the presence of sensory input. In both the eyes-closed and eyes-open conditions, inter-departure time distributions were more dispersed over posterior parietal channels, close to regions which are known to have the most dense structural connectivity. The biggest differences between the two conditions were observed at occipital sites, where inter-departure times were significantly more variable in the eyes-open condition. Together, these results suggest that message departure times are indicative of network traffic and capture a novel facet of neural activity

Communication Efficiency and Congestion of Signal Traffic in Large-Scale Brain Networks

<div><p>The complex connectivity of the cerebral cortex suggests that inter-regional communication is a primary function. Using computational modeling, we show that anatomical connectivity may be a major determinant for global information flow in brain networks. A macaque brain network was implemented as a communication network in which signal units flowed between grey matter nodes along white matter paths. Compared to degree-matched surrogate networks, information flow on the macaque brain network was characterized by higher loss rates, faster transit times and lower throughput, suggesting that neural connectivity may be optimized for speed rather than fidelity. Much of global communication was mediated by a “rich club” of hub regions: a sub-graph comprised of high-degree nodes that are more densely interconnected with each other than predicted by chance. First, macaque communication patterns most closely resembled those observed for a synthetic rich club network, but were less similar to those seen in a synthetic small world network, suggesting that the former is a more fundamental feature of brain network topology. Second, rich club regions attracted the most signal traffic and likewise, connections between rich club regions carried more traffic than connections between non-rich club regions. Third, a number of rich club regions were significantly under-congested, suggesting that macaque connectivity actively shapes information flow, funneling traffic towards some nodes and away from others. Together, our results indicate a critical role of the rich club of hub nodes in dynamic aspects of global brain communication.</p></div

Kinetics and mechanism of the reaction of substituted 4-pyrimidine carboxylic acids with diazodiphenylmethane in dimethylformamide

Correlation of the data for the reaction of 11 substituted 4-pyrimidine carboxylic acids with diazodiphenylmethane (DDM) in dimethylformamide (DMF) with calculated atomic charges on the carboxylic group showed that the reaction in this solvent may proceed via a concerted transition state

System-level statistics.

<p>Simulations were run for three different scenarios: CoCoMac brain (top), small-world network (middle) and rich-club network (bottom) and their respective randomized (green) and latticized (red) control networks. For each network, the mean transit time, utilization, blocking probability and throughput are plotted at four different intensities. For the starting networks in each scenario (CoCoMac, lattice and rich-club), the curves represent the average over 100 simulations. For the randomized/latticized versions of each network, the curves represent the average across 100 simulations on 100 realizations of each network.</p