STDP in Oscillatory Recurrent Networks: Theoretical Conditions for Desynchronization and Applications to Deep Brain Stimulation

Highly synchronized neural networks can be the source of various pathologies such as Parkinson's disease or essential tremor. Therefore, it is crucial to better understand the dynamics of such networks and the conditions under which a high level of synchronization can be observed. One of the key factors that influences the level of synchronization is the type of learning rule that governs synaptic plasticity. Most of the existing work on synchronization in recurrent networks with synaptic plasticity are based on numerical simulations and there is a clear lack of a theoretical framework for studying the effects of various synaptic plasticity rules. In this paper we derive analytically the conditions for spike-timing dependent plasticity (STDP) to lead a network into a synchronized or a desynchronized state. We also show that under appropriate conditions bistability occurs in recurrent networks governed by STDP. Indeed, a pathological regime with strong connections and therefore strong synchronized activity, as well as a physiological regime with weaker connections and lower levels of synchronization are found to coexist. Furthermore, we show that with appropriate stimulation, the network dynamics can be pushed to the low synchronization stable state. This type of therapeutical stimulation is very different from the existing high-frequency stimulation for deep brain stimulation since once the stimulation is stopped the network stays in the low synchronization regime

Desynchronizing electrical and sensory coordinated reset neuromodulation

Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders

Alien Registration- Papa, Tass (Auburn, Androscoggin County)

https://digitalmaine.com/alien_docs/30159/thumbnail.jp

Modified Pulse Shapes for Effective Neural Stimulation

The electrical stimulation of neuronal structures is used as a treatment for many neurological disorders, e.g., for the treatment of Parkinson’s disease via deep brain stimulation (DBS). To reduce side effects, to avoid tissue or electrode damage, and to increase battery lifetimes, an effective but gentle electrical stimulation is of prime importance. We studied different modified pulse shapes for application in DBS with respect to their efficiency to initiate neuronal activity. Numerical simulations of two mathematical neuron models were performed to investigate the effectiveness of different modified pulse shapes. According to our results, the pulse shapes considered showed a considerably increased efficiency in terms of both activation and entrainment of neural activity. We found that the introduction of a gap with a specific and optimized duration in a biphasic pulse and the reversal of the standard pulse phase order yielded stimulation protocols that could increase the efficiency and therefore reduce the energy consumption of stimulation. The improvements were achieved by simple modifications of existing stimulation techniques. The modification of the pulse shapes resulted in an improvement of up to 50% for both the activation of resting neurons and the entrainment of bursting neurons

Friedrich Adolph Wilhelm Diesterweg (1790-1866): Zum 200. Geburtstag

The loss of segregation of neuronal signal processing pathways is an important hypothesis for explaining the origin of functional deficits as associated with Parkinson's disease. Here we use a modeling approach which is utilized to study the influence of deep brain stimulation on the restoration of segregated activity in the target structures. Besides the spontaneous activity of the target network, the model considers a weak sensory input mimicking signal processing tasks, electrical deep brain stimulation delivered through a standard DBS electrode and synaptic plasticity. We demonstrate that the sensory input is capable of inducing a modification of the network structure which results in segregated microcircuits if the network is initialized in the healthy, desynchronized state. Depending on the strength and coverage, the sensory input is capable of restoring the functional sub-circuits even if the network is initialized in the synchronized, pathological state. Weak coordinated reset stimulation, applied to a network featuring a loss of segregation caused by global synchronization, is able to restore the segregated activity and to truncate the pathological, synchronized activity

Endoscopic Resection and Topical 5-Fluorouracil as an Alternative Treatment to Craniofacial Resection for the Management of Primary Intestinal-Type Sinonasal Adenocarcinoma

Introduction. Intestinal-type adenocarcinoma of the sinonasal tract is very rare and is responsible for less than 4% of tumours of the sinuses. Craniofacial resection has been the mainstay of treatment for many years; however, techniques for endoscopic resection are constantly being developed. Discussion. The use of transnasal endoscopic resection (TER) and topical chemotherapy applications as an alternative to cranio-facial resection (CFR) is discussed. TER offers advantages over CFR in terms of fewer intra-operative complications and an improved cosmetic outcome. Survival and metastatic rates are similar between both procedures. Patients with locally invasive tumours are better managed with CFR. Topical applications of 5-Fluorouracil has been shown to be effective in increasing survival in patients with sino-nasal malignancy. Conclusion. Trans-nasal endoscopic resection and topical 5-Fluorouracil could potentially offer an acceptable alternative treatment to the standard of cranio-facial resection. This should be investigated in trials with a longer followup period than this paper in order to directly compare the two treatment modalities

Revealing Network Connectivity From Dynamics

We present a method to infer network connectivity from collective dynamics in networks of synchronizing phase oscillators. We study the long-term stationary response to temporally constant driving. For a given driving condition, measuring the phase differences and the collective frequency reveals information about how the oscillators are interconnected. Sufficiently many repetitions for different driving conditions yield the entire network connectivity from measuring the dynamics only. For sparsely connected networks we obtain good predictions of the actual connectivity even for formally under-determined problems.Comment: 10 pages, 4 figure

Phase resetting of collective rhythm in ensembles of oscillators

Phase resetting curves characterize the way a system with a collective periodic behavior responds to perturbations. We consider globally coupled ensembles of Sakaguchi-Kuramoto oscillators, and use the Ott-Antonsen theory of ensemble evolution to derive the analytical phase resetting equations. We show the final phase reset value to be composed of two parts: an immediate phase reset directly caused by the perturbation, and the dynamical phase reset resulting from the relaxation of the perturbed system back to its dynamical equilibrium. Analytical, semi-analytical and numerical approximations of the final phase resetting curve are constructed. We support our findings with extensive numerical evidence involving identical and non-identical oscillators. The validity of our theory is discussed in the context of large ensembles approximating the thermodynamic limit.Comment: submitted to Phys. Rev.