Modulation of excitability by continuous low- and high-frequency stimulation in fully hippocampal kindled rats

Cordeiro, Joacir Graciolli; Somerlik, K. H.; Cordeiro, Karina Kohn; Aertsen, Ad; Araújo, João Cândido; Schulze‐Bonhage, Andreas

doi:10.1016/j.eplepsyres.2013.08.014

Cited by 9 publications

(4 citation statements)

References 36 publications

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“…Hence, a review of the literature shows that LFS applied to structures in the temporal lobe, such as hippocampus, amygdala, and thalamus, seems to be efficiently antiepileptogenic (for review see Han et al, 2014). In fact, application of the technique to animals during kindling results in several antiepileptogenic effects: increase in threshold for evoking afterdischarges (AD; Ullal et al, 1989;Weiss et al, 1998;Cordeiro et al, 2013), decrease in AD duration (Velisek et al, 2002;Goodman et al, 2005;Wu et al, 2008), decrease in number of seizures (Goodman et. al, 2005;Wu et al, 2008;Liu et al, 2013), decrease in severity of seizures (Weiss et al, 1998;Velisek et al, 2002), and many others.…”

Section: Electrical Stimulation Of the Nervous System As A Therapeuticmentioning

confidence: 99%

The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation

Cota

Drabowski

Oliveira

et al. 2016

J of Neuroscience Research

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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.

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Section: Electrical Stimulation Of the Nervous System As A Therapeuticmentioning

confidence: 99%

The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation

Cota

Drabowski

Oliveira

et al. 2016

J of Neuroscience Research

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“…Still, many questions remain about how best to harness the putative neuromodulatory effects of RNS. These effects likely depend on the stimulation parameters that are employed [ 9 , 10 ], but aside from experience-based practice, there are virtually no objective methods for selecting these parameters rationally. For example, based on experience during clinical trials, charge density is often increased empirically to enhance therapeutic response, but a definitive correlation between charge density and seizure frequency has not been shown [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Evidence of state-dependence in the effectiveness of responsive neurostimulation for seizure modulation

et al. 2021

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Background: An implanted device for brain-responsive neurostimulation (RNS ® System) is approved as an effective treatment to reduce seizures in adults with medically-refractory focal epilepsy. Clinical trials of the RNS System demonstrate population-level reduction in average seizure frequency, but therapeutic response is highly variable. Hypothesis: Recent evidence links seizures to cyclical fluctuations in underlying risk. We tested the hypothesis that effectiveness of responsive neurostimulation varies based on current state within cyclical risk fluctuations. Methods: We analyzed retrospective data from 25 adults with medically-refractory focal epilepsy implanted with the RNS System. Chronic electrocorticography was used to record electrographic seizures, and hidden Markov models decoded seizures into fluctuations in underlying risk. State-dependent associations of RNS System stimulation parameters with changes in risk were estimated. Results: Higher charge density was associated with improved outcomes, both for remaining in a low seizure risk state and for transitioning from a high to a low seizure risk state. The effect of stimulation frequency depended on initial seizure risk state: when starting in a low risk state, higher stimulation frequencies were associated with remaining in a low risk state, but when starting in a high risk state, lower stimulation frequencies were associated with transition to a low risk state. Findings were consistent across bipolar and monopolar stimulation configurations. Conclusion: The impact of RNS on seizure frequency exhibits state-dependence, such that stimulation parameters which are effective in one seizure risk state may not be effective in another. These findings represent conceptual advances in understanding the therapeutic mechanism of RNS, and directly inform current practices of RNS tuning and the development of next-generation neurostimulation systems.

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“…Previous research has shown that the efficacy of neurostimulation could be increased by carefully designing the temporal pattern of stimulation pulses. Frequency of stimulation (Chkhenkeli and Chkhenkeli, 1997;Cordeiro et al, 2013), periodicity (Wyckhuys et al, 2010;Buffel et al, 2014), and, in the case of multiple electrodes, synchronicity (Good et al, 2009;Nelson et al, 2011;Van Nieuwenhuyse et al, 2014) have all been shown to influence the success of neurostimulation. Furthermore, many have argued that stimulation must be custom tailored to the unique seizure topology and dynamics of each particular patient (Holt and Netoff, 2014;Mina et al, 2013;Taylor et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Designing Patient-Specific Optimal Neurostimulation Patterns for Seizure Suppression

et al. 2018

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Neurostimulation is a promising therapy for abating epileptic seizures. However, it is extremely difficult to identify optimal stimulation patterns experimentally. In this study, human recordings are used to develop a functional 24 neuron network statistical model of hippocampal connectivity and dynamics. Spontaneous seizure-like activity is induced in silico in this reconstructed neuronal network. The network is then used as a testbed to design and validate a wide range of neurostimulation patterns. Commonly used periodic trains were not able to permanently abate seizures at any frequency. A simulated annealing global optimization algorithm was then used to identify an optimal stimulation pattern, which successfully abated 92% of seizures. Finally, in a fully responsive, or closed-loop, neurostimulation paradigm, the optimal stimulation successfully prevented the network from entering the seizure state. We propose that the framework presented here for algorithmically identifying patient-specific neurostimulation patterns can greatly increase the efficacy of neurostimulation devices for seizures.

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Modulation of excitability by continuous low- and high-frequency stimulation in fully hippocampal kindled rats

Cited by 9 publications

References 36 publications

The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation

The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation

Evidence of state-dependence in the effectiveness of responsive neurostimulation for seizure modulation

Designing Patient-Specific Optimal Neurostimulation Patterns for Seizure Suppression

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