Biology subjects

Manos, T.

Publications and source records attributed to Manos, T..

5 recordsLinked to original sources

bioRxiv2026

Using Disinhibition versus Direct Control in a Spiking Neural Model of Dopamine-Driven Reinforcement Learning

Dopaminergic signalling is central to value learning and decision making. It has been observed that multiple pathways with different patterns of connectivity project to midbrain dopaminergic neurons, some involving direct excitatory projections while others involve disinhibition. However, the respective contributions of these patterns to dopamine control, and their computational and functional advantages remain unclear. In the current work we simulate and evaluate two fully spiking neural models of dopaminergic control, based either solely on disinhibition, or solely on direct inhibitory and excitatory projections. We compare these models in terms of their engineering properties, their resulting spiking profiles, and their ability to successfully acquire representations of expected value in a 3-armed bandit task. We find that both models are able to operate at an asynchronous-irregular firing regime, but that the firing profile of the direct integration model is less resilient to disruption and more sensitive to incoming signals. In addition, the disinhibition model performs better in the learning task. We conclude that while the direct model is more parsimonious, disinhibition-based control remains advantageous in the operational context. Our results have implications for the study of decision-making brain circuits as well as for the design of brain-inspired systems.

neuroscience↗

bioRxiv2023

An exploratory computational analysis in mice brain networks of widespread epileptic seizure onset locations along with potential strategies for effective intervention and propagation control

Mean-field models have been developed to replicate key features of epileptic seizure dynamics. However, the precise mechanisms and the role of the brain area responsible for seizure onset and propagation remain incompletely understood. In this study, we employ computational methods within The Virtual Brain framework and the Epileptor model to explore how the location and connectivity of an Epileptogenic Zone (EZ) in a mouse brain are related to focal seizures (seizures that start in one brain area and may or may not remain localized), with a specific focus on the hippocampal region known for its association with epileptic seizures. We then devise computational strategies to confine seizures (prevent widespread propagation), simulating medical-like treatments such as tissue resection and the application of an anti-seizure drugs or neurostimulation to suppress hyperexcitability. Through selectively removing (blocking) specific connections informed by the structural connectome and graph network measurements or by locally reducing outgoing connection weights of EZ areas, we demonstrate that seizures can be kept constrained around the EZ region. We successfully identified the minimal connections necessary to prevent widespread seizures, with a particular focus on minimizing surgical or medical intervention while simultaneously preserving the original structural connectivity and maximizing brain functionality.

neuroscience↗

bioRxiv2023

Enhanced simulations of whole-brain dynamics using hybrid resting-state structural connectomes

The human brain, composed of billions of neurons and synaptic connections, is an intricate network coordinating a sophisticated balance of excitatory and inhibitory activity between brain regions. The dynamical balance between excitation and inhibition is vital for adjusting neural input/output relationships in cortical networks and regulating the dynamic range of their responses to stimuli. To infer this balance using connectomics, we recently introduced a computational framework based on the Ising model, first developed to explain phase transitions in ferromagnets, and proposed a novel hybrid resting-state structural connectome (rsSC). Here, we show that a generative model based on the Kuramoto phase oscillator can be used to simulate static and dynamic functional connectomes (FC) with rsSC as the coupling weight coefficients, such that the simulated FC well aligns with the observed FC when compared to that simulated with traditional structural connectome. Simulations were performed using the open source framework The Virtual Brain on High Performance Computing infrastructure.

neuroscience↗

bioRxiv2017

Short-term dosage regimen for stimulation-induced long-lasting desynchronization

In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e. an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g. if the CR stimulation frequency (i.e. stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long-term desynchronization at comparably short stimulation duration and low integral stimulation duration. Currently, clinical proof of concept is available for deep brain CR stimulation for Parkinsons therapy and acoustic CR stimulation for tinnitus therapy. Promising first in human data is available for vibrotactile CR stimulation for Parkinsons treatment. For the clinical development of these treatments it is mandatory to perform dose-finding studies to reveal optimal stimulation parameters and dosage regimens. Our findings can straightforwardly be tested in human dose-finding studies.

neuroscience↗

bioRxiv2017

How stimulation frequency and intensity impact on the long-lasting effects of coordinated reset stimulation

Several brain diseases are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR) stimulation was computationally designed to specifically counteract abnormal neuronal synchronization processes by desynchronization. In the presence of spike-timing-dependent plasticity (STDP) this may lead to a decrease of synaptic excitatory weights and ultimately to an anti-kindling, i.e. unlearning of abnormal synaptic connectivity and abnormal neuronal synchrony. The long-lasting desynchronizing impact of CR stimulation has been verified in pre-clinical and clinical proof of concept studies. However, as yet it is unclear how to optimally choose the CR stimulation frequency, i.e. the repetition rate at which the CR stimuli are delivered. This work presents the first computational study on the dependence of the acute and long-term outcome on the CR stimulation frequency in neuronal networks with STDP. For this purpose, CR stimulation was applied with Rapidly Varying Sequences (RVS) as well as with Slowly Varying Sequences (SVS) in a wide range of stimulation frequencies and intensities. Our findings demonstrate that acute desynchronization, achieved during stimulation, does not necessarily lead to long-term desynchronization after cessation of stimulation. By comparing the long-term effects of the two different CR protocols, the RVS CR stimulation turned out to be more robust against variations of the stimulation frequency. However, SVS CR stimulation can obtain stronger anti-kindling effects. We revealed specific parameter ranges that are favorable for long-term desynchronization. For instance, RVS CR stimulation at weak intensities and with stimulation frequencies in the range of the neuronal firing rates turned out to be effective and robust, in particular, if no closed loop adaptation of stimulation parameters is (technically) available. From a clinical standpoint, this may be relevant in the context of both invasive as well as non-invasive CR stimulation.\n\nAuthor SummaryAbnormally strong neuronal synchronization is found in a number of brain disorders. To specifically counteract abnormal neuronal synchrony and, hence, related symptoms, Coordinated Reset (CR) stimulation was developed. CR stimulation employs basic plasticity and dynamic self-organization principles of the nervous system. Its fundamental goal is to induce long-lasting desynchronizing effects that persist cessation of stimulation. The latter are key to reducing side effects of invasive therapies such as deep brain stimulation. Furthermore, sustained stimulation effects pave the way for non-invasive neuromodulation treatments, where a few hours of stimulation delivered regularly or occasionally may provide substantial relief. Long-lasting CR-induced desynchronizing therapeutic effects have been verified in several pre-clinical and clinical studies. However, we here present the first computational study that systematically investigates the impact of key stimulation parameters on the stimulation outcome. Our results provide experimentally testable predictions that are relevant for pre-clinical and clinical studies. Furthermore, our results may contribute to stimulation techniques that enable to probe the functional role of brain rhythms in general.

neuroscience↗