17 research outputs found
Inferring collective dynamical states from widely unobserved systems
When assessing spatially-extended complex systems, one can rarely sample the
states of all components. We show that this spatial subsampling typically leads
to severe underestimation of the risk of instability in systems with
propagating events. We derive a subsampling-invariant estimator, and
demonstrate that it correctly infers the infectiousness of various diseases
under subsampling, making it particularly useful in countries with unreliable
case reports. In neuroscience, recordings are strongly limited by subsampling.
Here, the subsampling-invariant estimator allows to revisit two prominent
hypotheses about the brain's collective spiking dynamics:
asynchronous-irregular or critical. We identify consistently for rat, cat and
monkey a state that combines features of both and allows input to reverberate
in the network for hundreds of milliseconds. Overall, owing to its ready
applicability, the novel estimator paves the way to novel insight for the study
of spatially-extended dynamical systems.Comment: 7 pages + 12 pages supplementary information + 7 supplementary
figures. Title changed to match journal referenc
Homeostatic plasticity and external input shape neural network dynamics
In vitro and in vivo spiking activity clearly differ. Whereas networks in
vitro develop strong bursts separated by periods of very little spiking
activity, in vivo cortical networks show continuous activity. This is puzzling
considering that both networks presumably share similar single-neuron dynamics
and plasticity rules. We propose that the defining difference between in vitro
and in vivo dynamics is the strength of external input. In vitro, networks are
virtually isolated, whereas in vivo every brain area receives continuous input.
We analyze a model of spiking neurons in which the input strength, mediated by
spike rate homeostasis, determines the characteristics of the dynamical state.
In more detail, our analytical and numerical results on various network
topologies show consistently that under increasing input, homeostatic
plasticity generates distinct dynamic states, from bursting, to
close-to-critical, reverberating and irregular states. This implies that the
dynamic state of a neural network is not fixed but can readily adapt to the
input strengths. Indeed, our results match experimental spike recordings in
vitro and in vivo: the in vitro bursting behavior is consistent with a state
generated by very low network input (< 0.1%), whereas in vivo activity suggests
that on the order of 1% recorded spikes are input-driven, resulting in
reverberating dynamics. Importantly, this predicts that one can abolish the
ubiquitous bursts of in vitro preparations, and instead impose dynamics
comparable to in vivo activity by exposing the system to weak long-term
stimulation, thereby opening new paths to establish an in vivo-like assay in
vitro for basic as well as neurological studies.Comment: 14 pages, 8 figures, accepted at Phys. Rev.
Tailored ensembles of neural networks optimize sensitivity to stimulus statistics
The dynamic range of stimulus processing in living organisms is much larger
than a single neural network can explain. For a generic, tunable spiking
network we derive that while the dynamic range is maximal at criticality, the
interval of discriminable intensities is very similar for any network tuning
due to coalescence. Compensating coalescence enables adaptation of
discriminable intervals. Thus, we can tailor an ensemble of networks optimized
to the distribution of stimulus intensities, e.g., extending the dynamic range
arbitrarily. We discuss potential applications in machine learning.Comment: 6 pages plus supplemental materia
Description of spreading dynamics by microscopic network models and macroscopic branching processes can differ due to coalescence
Spreading processes are conventionally monitored on a macroscopic level by
counting the number of incidences over time. The spreading process can then be
modeled either on the microscopic level, assuming an underlying interaction
network, or directly on the macroscopic level, assuming that microscopic
contributions are negligible. The macroscopic characteristics of both
descriptions are commonly assumed to be identical. In this work, we show that
these characteristics of microscopic and macroscopic descriptions can be
different due to coalescence, i.e., a node being activated at the same time by
multiple sources. In particular, we consider a (microscopic) branching network
(probabilistic cellular automaton) with annealed connectivity disorder, record
the macroscopic activity, and then approximate this activity by a (macroscopic)
branching process. In this framework, we analytically calculate the effect of
coalescence on the collective dynamics. We show that coalescence leads to a
universal non-linear scaling function for the conditional expectation value of
successive network activity. This allows us to quantify the difference between
the microscopic model parameter and established macroscopic estimates. To
overcome this difference, we propose a non-linear estimator that correctly
infers the model branching parameter for all system sizes.Comment: 13 page
Dynamic Adaptive Computation: Tuning network states to task requirements
Neural circuits are able to perform computations under very diverse
conditions and requirements. The required computations impose clear constraints
on their fine-tuning: a rapid and maximally informative response to stimuli in
general requires decorrelated baseline neural activity. Such network dynamics
is known as asynchronous-irregular. In contrast, spatio-temporal integration of
information requires maintenance and transfer of stimulus information over
extended time periods. This can be realized at criticality, a phase transition
where correlations, sensitivity and integration time diverge. Being able to
flexibly switch, or even combine the above properties in a task-dependent
manner would present a clear functional advantage. We propose that cortex
operates in a "reverberating regime" because it is particularly favorable for
ready adaptation of computational properties to context and task. This
reverberating regime enables cortical networks to interpolate between the
asynchronous-irregular and the critical state by small changes in effective
synaptic strength or excitation-inhibition ratio. These changes directly adapt
computational properties, including sensitivity, amplification, integration
time and correlation length within the local network. We review recent
converging evidence that cortex in vivo operates in the reverberating regime,
and that various cortical areas have adapted their integration times to
processing requirements. In addition, we propose that neuromodulation enables a
fine-tuning of the network, so that local circuits can either decorrelate or
integrate, and quench or maintain their input depending on task. We argue that
this task-dependent tuning, which we call "dynamic adaptive computation",
presents a central organization principle of cortical networks and discuss
first experimental evidence.Comment: 6 pages + references, 2 figure
Assessing criticality in pre-seizure single-neuron activity of human epileptic cortex
Epileptic seizures are characterized by abnormal and excessive neural
activity, where cortical network dynamics seem to become unstable. However,
most of the time, during seizure-free periods, cortex of epilepsy patients
shows perfectly stable dynamics. This raises the question of how recurring
instability can arise in the light of this stable default state. In this work,
we examine two potential scenarios of seizure generation: (i) epileptic
cortical areas might generally operate closer to instability, which would make
epilepsy patients generally more susceptible to seizures, or (ii) epileptic
cortical areas might drift systematically towards instability before seizure
onset. We analyzed single-unit spike recordings from both the epileptogenic
(focal) and the nonfocal cortical hemispheres of 20 epilepsy patients. We
quantified the distance to instability in the framework of criticality, using a
novel estimator, which enables an unbiased inference from a small set of
recorded neurons. Surprisingly, we found no evidence for either scenario:
Neither did focal areas generally operate closer to instability, nor were
seizures preceded by a drift towards instability. In fact, our results from
both pre-seizure and seizure-free intervals suggest that despite epilepsy,
human cortex operates in the stable, slightly subcritical regime, just like
cortex of other healthy mammalians.Comment: 19 pages, 8 Figure
Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study
Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe