title: The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation.
abstract: 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 mesiotemporal epileptogenic areas, the amygdala included, as a means to treat medically refractory epilepsy. Regular high-frequency stimulation (HFS) commonly has anticonvulsant 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 anticonvulsant effect seems to vary at random among studies. As an alternative, studies by our group on the development and investigation of temporally unstructured electrical stimulation applied to the amygdala have shown that nonperiodic stimulation (NPS), which is a nonstandard form of LFS, is capable of suppressing both acute and chronic spontaneous seizures. We hypothesize two noncompetitive mechanisms for the therapeutic role of amygdala in NPS, 1) a direct desynchronization of epileptic circuitry in the forebrain and brainstem and 2) an indirect desynchronization/inhibition through nucleus accumbens activation. We conclude by reintroducing the idea that hypersynchronism, rather than hyperexcitability, may be the key for epileptic phenomena and epilepsy treatment.
authors.affiliation: Laboratório Interdisciplinar de Neuroengenharia e Neurociências, Departamento de Engenharia Elétrica (DEPEL), Universidade Federal de São João Del-Rei, São João Del-Rei, Minas Gerais, Brazil.
authors.forename: Vinícius Rosa
authors.initials: VR
authors.lastname: Cota
authors.affiliation: Laboratório Interdisciplinar de Neuroengenharia e Neurociências, Departamento de Engenharia Elétrica (DEPEL), Universidade Federal de São João Del-Rei, São João Del-Rei, Minas Gerais, Brazil.
authors.forename: Bruna Marcela Bacellar
authors.initials: BM
authors.lastname: Drabowski
authors.affiliation: Laboratório Interdisciplinar de Neuroengenharia e Neurociências, Departamento de Engenharia Elétrica (DEPEL), Universidade Federal de São João Del-Rei, São João Del-Rei, Minas Gerais, Brazil.
authors.forename: Jasiara Carla
authors.initials: JC
authors.lastname: de Oliveira
authors.affiliation: Núcleo de Neurociências, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Márcio Flávio Dutra
authors.initials: MF
authors.lastname: Moraes
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation / Q000379:methods*; D004827:Epilepsy / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D058117:Neural Prostheses
keywords: basolateral amygdala; electrical stimulation; epilepsy; epileptogenesis; hypersynchronism; ictogenesis; neural network; seizure suppression; temporal pattern