Papers by Jasiara Carla de Oliveira
Epilepsy & Behavior
Electrical stimulation of the central nervous system is a promising alternative for the treatment... more Electrical stimulation of the central nervous system is a promising alternative for the treatment of pharmacoresistant epilepsy. Successful clinical and experimental stimulation is most usually carried out as continuous trains of current or voltage pulses fired at rates of 100 Hz or above, since lower frequencies yield controversial results. On the other hand, stimulation frequency should be as low as possible, in order to maximize implant safety and battery efficiency. Moreover, the development of stimulation approaches has been largely empirical in general, while they should be engineered with the neurobiology of epilepsy in mind if a more robust, efficient, efficacious, and safe application is intended. In an attempt to reconcile evidence of therapeutic effect with the understanding of the underpinnings of epilepsy, our group has developed a nonstandard form of low-frequency stimulation with randomized interpulse intervals termed nonperiodic stimulation (NPS). The rationale was that an irregular temporal pattern would impair neural hypersynchronization, which is a hallmark of epilepsy. In this review, we start by briefly revisiting the literature on the molecular, cellular, and network level mechanisms of epileptic phenomena in order to highlight this often-overlooked emergent property of cardinal importance in the pathophysiology of the disease. We then review our own studies on the efficacy of NPS against acute and chronic experimental seizures and also on the anatomical and physiological mechanism of the method, paying special attention to the hypothesis that the lack of temporal regularity induces desynchronization. We also put forward a novel insight regarding the temporal structure of NPS that may better encompass the set of findings published by the group: the fact that intervals between stimulation pulses have a distribution that follows a power law and thus may induce natural-like activity that would compete with epileptiform discharge for the recruitment of networks. We end our discussion by mentioning ongoing research and future projects of our lab.
Epilepsy Research
Electrical stimulation (ES) of the nervous system is a promising alternative for the treatment of... more Electrical stimulation (ES) of the nervous system is a promising alternative for the treatment of refractory epilepsy. Based on the understanding that seizures are the expression of neural hypersynchronism, our group developed and tested a non-standard form of low-energy temporally unstructured ES termed NPS (Non-periodic stimulation), with pseudo-randomized inter-pulse intervals. Previous investigation demonstrated that NPS applied to the amygdala has a robust anticonvulsant effect against both acute and chronic seizures, and suggested that its therapeutic effect is based on direct desynchronization of ictogenic neural circuits. Further mechanistic investigation using functional magnetic resonance imaging has shown that NPS also activates nucleus ac-cumbens (NAc) in seizure-free rats, raising the hypothesis of an alternative therapeutic mechanism: NPS-enhanced indirect inhibition / desynchronization of ictogenic circuits by NAc. In order to investigate this idea, here we evaluated behavior and cortical electrographic activity from animals submitted to pentylenetetrazole (PTZ) induced seizures, treated with NPS and with or without bilateral electrolytic lesion of NAc. NPS-treated animals with bilateral lesion of NAc expressed unexpected straub tail in addition to other stereotypical convulsive behavior , displayed increased susceptibility to PTZ (lower drug threshold), and had a much longer electrographic seizure, with a greater number of spikes, firing at a higher rate. Moreover, analysis of spike morphology showed an increase in amplitude and slope in these animals, suggesting that ablation of NAc results in disinhibition and/ or increase of neural synchronism within ictogenic circuits. NPS had no therapeutic effect whatsoever in lesioned animals, while it displayed a mild anticonvulsant effect in those with intact brains. Results corroborate the notion that NAc has a key role in controlling aberrant epileptiform activity in ictogenic circuits through indirect polysynaptic connections that may enroll the ventral pallidum and ventral tegmental area. They also point to the possibility that NPS may enhance this effect, putatively by benefiting from the structure's property of detecting saliences.
Fiep Bulletin on Line, 2010
Fiep Bulletin on Line, 2010
Arquivos de Neuro-Psiquiatria, 2007
O objetivo do presente estudo foi avaliar os efeitos da estimulação elétrica funcional na assimet... more O objetivo do presente estudo foi avaliar os efeitos da estimulação elétrica funcional na assimetria cortical inter-hemisférica. Para tal, simultaneamente ao registro da atividade eletroencefalográfica, realizou-se eletroestimulação no antebraço direito para estimulação da extensão do indicador. A amostra consistiu de 45 sujeitos randomizados em 3 grupos de 15 sujeitos cada: grupo controle (submetido a 24 blocos de estimulação com intensidade de corrente zero), grupo 1 (24 blocos) e grupo 2 (36 blocos). A assimetria entre os pares de eletrodos F3-F4, C3-C4 e P3-P4 foi analisada ao longo dos grupos através de uma Anova. Os resultados apontaram para uma interação grupo x eletrodo e uma tendência de diminuição da assimetria inter-hemisférica após a eletroestimulação.
Fiep Bulletin on Line, 2010
Base de dados : LILACS. Pesquisa : 546539 [Identificador único]. Referências encontradas : 1 [ref... more Base de dados : LILACS. Pesquisa : 546539 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos relacionados. Id: 546539. ...
Many patients with epilepsy do not obtain proper control of their seizures through conventional t... more Many patients with epilepsy do not obtain proper control of their seizures through conventional treatment. We review aspects of the pathophysiology underlying epileptic phenomena, with a special interest in the role of the amygdala, stressing the importance of hypersynchronism in both ictogenesis and epileptogenesis. We then review experimental studies on electrical stimulation of mesio-temporal epileptogenic areas, the amygdala included, as a means to treat medically refractory epilepsy. Regular high-frequency stimulation (HFS) commonly has anticon-vulsant effects and sparse antiepileptogenic properties. On the other hand, HFS is related to acute and long-term increases in excitability related to direct neuronal activation , long-term potentiation, and kindling, raising concerns regarding its safety and jeopardizing in-depth understanding of its mechanisms. In turn, the safer regular low-frequency stimulation (LFS) has a robust antiepileptogenic effect, but its pro-or anticonvulsan...
Electrical stimulation applied to the basolateral amygdala in the pentylenetetrazole animal model... more Electrical stimulation applied to the basolateral amygdala in the pentylenetetrazole animal model of seizures may result in either a proconvulsant or an anticonvulsant effect depending on the interpulse intervals used: periodic or nonperiodic, respectively. We tested the effect of this electrical stimulation temporal coding on the spontaneous and recurrent behavioral seizures produced in the chronic phase of the pilocarpine animal model of temporal lobe epilepsy, an experimental protocol that better mimics the human condition. After 45 days of the pilocarpine-induced status epilepticus, male Wistar rats were submitted to a surgical procedure for the implantation of a bipolar electrical stimulation electrode in the right basolateral amygdala and were allowed to recover for seven days. The animals were then placed in a glass box, and their behaviors were recorded daily on DVD for 6 h for 4 consecutive days (control period). Spontaneous recurrent behavioral seizures when showed in animals were further recorded for an extra 4-day period (treatment period), under periodic or nonperiodic electrical stimulation. The number, duration, and severity of seizures (according to the modified Racine's scale) during treatment were compared with those during the control period. The nonperiodically stimulated group displayed a significantly reduced total number and duration of seizures. There was no difference between control and treatment periods for the periodically stimulated group. Results corroborate previous findings from our group showing that nonperiodic electrical stimulation has a robust anticonvulsant property. In addition, results from the pilocarpine animal model further strengthen nonperiodic electrical stimulation as a valid therapeutic approach in current medical practice. Our working hypothesis is that temporally unstructured electrical stimulation may wield its effect by desynchronizing neural networks involved in the ictogenic process.
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Papers by Jasiara Carla de Oliveira