Model Based Development of Novel Deep Brain Stimulation Techniques

Pathological synchronization is a hallmark of several neurological diseases like Parkinson's disease (PD) or essential tremor [Alberts et al., Nature 1969; 221: 670; Nini et al., J Neurophys 1995; 74: 1800]. For example, a pacemaker-like population of neurons, which fires in a synchronized and periodical manner, provokes the Parkinsonian resting tremor [Alberts et al., Nature 1969; 221: 670]. In contrast, an uncorrelated, i.e., desynchronized firing pattern of these neuronal populations is characteristic in healthy subjects [Nini et al., J Neurophys 1995; 74: 1800]. In medically intractable patients, electrical deep brain stimulation (DBS) is administered via depth electrodes chronically implanted in the subthalamic nucleus of the thalamic ventralis intermedius nucleus [Benabid et al., Lancet 1991; 337: 403]. For that purpose, a permanent high-frequency (>100Hz) periodic pulse train stimulation is used. Up to now the mechanism of high-frequency DBS is not yet sufficiently understood [Benabid et al., Lancet 1991; 337: 403]. We initiated a model-based development of novel stimulation protocols to find milder and more effective DBS techniques [Tass, Phase Resetting in Medicine and Biology, Springer, 1999; Tass, Biol Cyb 2003; 89: 81]. In a first clinical study performed during electrode implantation, we have shown that the coordinated reset via multiple/several sites can suppress the peripheral tremor, even if the standard high-frequency DBS has no tremor suppressive effect at all [Tass et al., submitted (2004)]. Here we present a technique for the desynchronization of a strongly synchronized target population which we expect to be even more effective and milder. For this, delayed mean field potentials are administered at different sites within a neuronal population to establish a desynchronized state. According to detailed theoretical investigations and simulations, we expect the novel desynchronization technique to be considerably milder, to act in a demand-controlled way and to be simple in realization. We use a microscopic model of a neuronal population in a relevant target area to show that the method is robust and does not require time consuming calibration. It is suggested that the novel technique is used for deep brain stimulation in patients suffering from Parkinson's disease, essential tremor or epilepsy.