Long-term anti-kindling effects of desynchronizing brain stimulation: a theoretical study

Abstract

In a modeling study we show that desynchronization stimulation may have powerful anti-kindling effects. For this, we incorporate spike-timing-dependent plasticity into a generic network of coupled phase oscillators, which serves as a model network of synaptically interacting neurons. Two states may coexist under spontaneous conditions: a state of uncorrelated firing and a state of pathological synchrony. Appropriate stimulation protocols make the network learn or unlearn the pathological synaptic interactions, respectively. Low-frequency periodic pulse train stimulation causes a kindling. Permanent high-frequency stimulation, used as golden standard for deep brain stimulation in medically refractory movement disorders, basically freezes the synaptic weights. In contrast, desynchronization stimulation, e.g., by means of a multi-site coordinated reset, has powerful long-term anti-kindling effects and enables the network to unlearn pathologically strong synaptic interactions. We propose desynchronization stimulation for the therapy of movement disorders and epilepsies.

Unlearning tinnitus-related cerebral synchrony with acoustic coordinated reset stimulation: theoretical concept and modelling

“…Previously, it was shown that electrical CR stimulation robustly causes an anti-kindling in different networks with and without inhibition, but without afferent input (Tass and Majtanik 2006;Hauptmann 2007, 2009;Hauptmann and Tass 2007). In the present study, our simulations are intended to illustrate the concept of CRinduced anti-kindling for the therapy of tinnitus.…”

“…As shown theoretically, as an average 'net' effect of STDP, the synaptic weight of excitatory synapses is up-regulated if pre-and postsynaptic neurons preferentially fire in synchrony, whereas it is down-regulated if they fire in an uncorrelated manner, e.g. due to desynchronizing stimulation (see Tass and Majtanik 2006;Hauptmann and Tass 2007). STDP contributes to a self-stabilization of synchronized and desynchronized states (see below).…”

“…Spike timing-dependent plasticity (STDP) up-or down-regulates synaptic weights depending on the relative timing of pre-and post-synaptic spikes (Gerstner et al 1996;Markram et al 1997). A striking feature of neural and phase oscillator networks with STDP is their multistablility (Tass and Majtanik 2006;Hauptmann 2007, 2009;Hauptmann and Tass 2007): Different attractors coexist which differ with respect to their fast neuronal dynamics and their slow synaptic dynamics (i.e. connectivity pattern).…”

“…In particular, desynchronizing coordinated reset (CR) stimulation (Tass 2003b,a) shifts a network from a synchronized state with strong coupling (i.e. mean synaptic weight) to a desynchronized state with weak coupling (Tass and Majtanik 2006;Hauptmann 2007, 2009;Hauptmann and Tass 2007). In other words, under CR stimulation the network gets reshaped and unlearns up-regulated synchrony.…”

Impact of Nonlinear Delayed Feedback on Synchronized Oscillators

“…However, this type of therapy has relevant limitations, e.g., in terms of nonresponders and side effects [16]. Thus, there is a significant clinical need for mild stimulation techniques that restore desynchronized, i.e., normal [17], dynamics in networks of oscillatory neurons [6,[18][19][20].…”