Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.02.05.578871

A new approach for estimating effective connectivity from activity in neural networks

Abstract

Inferring and understanding the underlying connectivity structure of a system solely from the observed activity of its constituent components is a challenge in many areas of science. In neuroscience, techniques for estimating connectivity are paramount when attempting to understand the network structure of neural systems from their recorded activity patterns. To date, no universally accepted method exists for the inference of effective connectivity, which describes how the activity of a neural node mechanistically affects the activity of other nodes. Here, focussing on purely excitatory networks of small to intermediate size and continuous node dynamics, we provide a systematic comparison of different approaches for estimating effective connectivity. Starting with the Hopf neuron model in conjunction with known ground truth structural connectivity, we reconstruct the systems connectivity matrix using a variety of algorithms. We show that, in sparse non-linear networks with delays, combining a lagged-cross-correlation (LCC) approach with a recently published derivative-based covariance analysis method provides the most reliable estimation of the known ground truth connectivity matrix. We outline how the parameters of the Hopf model, including those controlling the bifurcation, noise, and delay distribution, affect this result. We also show that in linear networks, LCC has comparable performance to a method based on transfer entropy, at a drastically lower computational cost. We highlight that LCC works best for small sparse networks, and show how performance decreases in larger and less sparse networks. Applying the method to linear dynamics without time delays, we find that it does not outperform derivative-based methods. We comment on this finding in light of recent theoretical results for such systems. Employing the Hopf model, we then use the estimated structural connectivity matrix as the basis for a forward simulation of the system dynamics, in order to recreate the observed node activity patterns. We show that, under certain conditions, the best method, LCC, results in higher trace-to-trace correlations than derivative-based methods for sparse noise-driven systems. Finally, we apply the LCC method to empirical biological data. Choosing a suitable threshold for binarization, we reconstruct the structural connectivity of a subset of the nervous system of the nematode C. Elegans. We show that the computationally simple LCC method performs better than another recently published, computationally more expensive reservoir computing-based method. We apply different methods to this dataset and find that they all lead to similar performances. Our results show that a comparatively simple method can be used to reliably estimate directed effective connectivity in sparse neural systems in the presence of spatio-temporal delays and noise. We provide concrete suggestions for the estimation of effective connectivity in a scenario common in biological research, where only neuronal activity of a small set of neurons, but not connectivity or single-neuron and synapse dynamics, are known.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Laasch, N., Braun, W., Knoff, L., Bielecki, J., Hilgetag, C. C.. 2024-02-06. A new approach for estimating effective connectivity from activity in neural networks. https://doi.org/10.1101/2024.02.05.578871

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Functional validation of allele-specific LMNB1 silencing in patient-derived astrocytes as a therapeutic option for Autosomal Dominant Leukodystrophy

Adult-onset Autosomal Dominant Leukodystrophy (ADLD) is a rare fatal leukodystrophy caused by increased LMNB1 gene dosage, most commonly resulting from duplication of the LMNB1 locus. Because ADLD is a gene dosage disorder, selective reduction of pathological LMNB1 expression represents a rational therapeutic strategy. Although allele-specific RNA interference has previously been shown to lower LMNB1 levels in patient-derived fibroblasts and directly reprogrammed neurons, its therapeutic effects have not been evaluated in disease-relevant human glial cells or using functional efficacy endpoints. Here, we established human induced pluripotent stem cell-derived astrocytes from ADLD patients as a human glial model in which to validate allele-specific LMNB1 silencing across molecular, cellular, and functional readouts. ADLD astrocytes recapitulated increased LMNB1 expression and characteristic nuclear abnormalities and displayed transcriptional alterations affecting extracellular matrix organization, calcium homeostasis, metabolism and RNA processing. Functionally, these cells also exhibited functional phenotypes suitable for therapeutic evaluation: astrocyte-conditioned medium impaired the viability of both murine and human oligodendroglial cultures, while conditioned-medium and direct astrocyte-seeding paradigms revealed impaired post-lesion myelin recovery in lysolecithin-treated cerebellar organotypic slices. Allele-specific LMNB1 silencing restored physiological LMNB1 levels, corrected nuclear abnormalities, attenuated astrocyte-mediated oligodendroglial toxicity, improved post-lesion myelin recovery, and was associated with selective transcriptional programs associated with extracellular support and cholesterol metabolism. Together, these findings provide molecular, cellular, and functional validation of allele-specific LMNB1 dosage correction in patient-derived human astrocytes and offer key support for LMNB1-lowering strategies in disease-relevant human glial cells.

neuroscience↗

Perceptual integration of multisensory haptic, visual, and auditory feedback for roughness discrimination in augmented reality

Understanding how our different senses interact to shape our perception is essential to design realistic and immersive virtual and augmented reality (VR/AR) experiences. The present study investigated how roughness perception can be modulated through haptic, visual, and auditory cues in AR using a vibrotactile wristband. Participants compared virtual textures varying in vibration frequency/amplitude, visual grain size, and friction sound. Results revealed strong linear relationships between stimulus parameters and perceived roughness, with haptic frequency and visual cues driving the highest discrimination performance. Adding non-informative sensory feedback reduced perceptual sensitivity, acting as noise. Individual differences emerged: participants who rated haptic as the easiest modality showed greater sensitivity to haptic variations, while visual-reliant participants performed better with visual cues. We conclude that roughness in AR can be systematically manipulated, but is vulnerable to perceptual interference from irrelevant inputs, where our work provides actionable insights for implementing optimized and adaptive AR/VR interfaces.

neuroscience↗

Structural and functional MRI signatures of Gambling Disorder: a case-control study

Gambling disorder (GD) is a behavioural addiction that may help identify addiction-related neural features without the direct neurobiological effects of a primary substance of dependence. We examined regional grey matter volume (GMV) and resting-state functional connectivity (rsFC) in the same well-characterised sample. Eighteen men with GD and 21 matched healthy controls underwent high-resolution structural and resting-state functional MRI. GMV was quantified across 214 cortical and subcortical regions, and seed-based rsFC analyses focused on striatal subdivisions and mesocorticolimbic regions. Group differences were evaluated using permutation testing and cluster-corrected mixed-effects modelling. GD was associated with lower GMV in the ventromedial prefrontal cortex, orbitofrontal regions and other cortical and subcortical areas, alongside higher GMV in a subset of limbic and default-mode regions. Participants with GD also showed lower connectivity between the limbic striatum and the hippocampus, thalamus and putamen. In exploratory analyses, somatomotor connectivity was positively associated with gambling severity (Problem Gambling Severity Index: Spearman's rho = 0.71, p = 0.003, false-discovery-rate-adjusted q = 0.016). Structural and functional findings overlapped spatially in regions associated with valuation, memory, reward and habit formation, but regional GMV did not mediate group differences in rsFC. These findings are broadly consistent with corticostriatal models of GD and identify candidate circuit-level differences for independent replication. Larger, more diverse and longitudinal samples are required to establish their reproducibility, temporal direction and clinical relevance.

neuroscience↗