Anticonvulsant vs. Proconvulsant Effect of in situ Deep Brain Stimulation at the Epileptogenic Focus

Since deep brain stimulation (DBS) at the epileptogenic focus (in situ) denotes long-term repetitive stimulation of the potentially epileptogenic structures, such as the amygdala, the hippocampus, and the cerebral cortex, a kindling effect and aggravation of seizures may happen and complicate the clinical condition. It is, thus, highly desirable to work out a protocol with an evident quenching (anticonvulsant) effect but free of concomitant proconvulsant side effects. We found that in the basolateral amygdala (BLA), an extremely wide range of pulsatile stimulation protocols eventually leads to the kindling effect. Only protocols with a pulse frequency of ≤1 Hz or a direct current (DC), with all of the other parameters unchanged, could never kindle the animal. On the other hand, the aforementioned DC stimulation (DCS), even a pulse as short as 10 s given 5 min before the kindling stimuli or a pulse given even to the contralateral BLA, is very effective against epileptogenicity and ictogenicity. Behavioral, electrophysiological, and histological findings consistently demonstrate success in seizure quenching or suppression as well as in the safety of the specific DBS protocol (e.g., no apparent brain damage by repeated sessions of stimulation applied to the BLA for 1 month). We conclude that in situ DCS, with a novel and rational design of the stimulation protocol composed of a very low (∼3% or 10 s/5 min) duty cycle and assuredly devoid of the potential of kindling, may make a successful antiepileptic therapy with adequate safety in terms of little epileptogenic adverse events and tissue damage.

Optogenetic activation of CA1 pyramidal neurons in vivo induces hypersynchronous and low voltage fast seizures

ABSTRACTIncreasing evidence supports the idea that the CA1 of the hippocampus plays an important role in the pathogenesis of temporal lobe epilepsy (TLE). There is however a lack of proof that the over-excitation of CA1 alone is sufficient in inducing seizures in vivo. Furthermore, the relevance of the seizures induced from the over-excitation of CA1 to the pathophysiology of TLE is undetermined. Here, we employed optogenetics to activate pyramidal neurons (PNs) in CA1, which reliably induced generalized seizures in freely moving non-epileptic mice. We showed that repeated photostimulations had a kindling effect. In addition, seizures induced by over-active CA1 PNs were dominated by two distinctive onset patterns, i.e. hypersynchronous (HYP) and low voltage fast (LVF) activities, which are widely recorded in patients with and animal models of TLE. In our study, HYP seizures were predominantly associated with the first photostimulation and were entirely replaced by the LVF type afterwards. This phenomenon suggests that the activation of CA1 PNs, when occurring after the first seizure, could lead to the recruitment of GABAergic interneurons to participate in the seizure generation. These findings suggest that seizures induced from the over-excitation of CA1 PNs likely involved the same hippocampal networks and cellular mechanisms underlying TLE.

Stochastic resonance and the homoeopathic effect

Potentization of homoeopathic medicines by successive dilutions and succussion at each step is interpreted in terms of stochastic resonance, a non-linear response of certain systems when perturbed by noise and a weak periodic signal, which increasingly enhanced at the output as the magnitude of the noise grows towards an optimal value for maximum signal amplification. The possible relevance of stochastic resonance in other physiological phenomena like the kindling effect, where epileptic convulsions are induced in rats and other animals by periodic stimulation of the brain with weak electric signals, is also considered.