Evidence supporting deep brain stimulation of the medial septum in the treatment of temporal lobe epilepsy

Cole, Eric R.; Grogan, Dayton; Laxpati, Nealen G.; Fernandez, Alejandra M.; Skelton, Henry; Isbaine, Faiçal; Gutekunst, Claire‐Anne; Gross, Robert E.

doi:10.1111/epi.17326

Cited by 24 publications

(17 citation statements)

References 168 publications

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“…Low-frequency stimulation (1 or 10 Hz) of the fornix in a single patient during stereo EEG decreased excitability, while high-frequency stimulation (50 Hz) increased excitability and led to a clinical seizure [24]. The medial septum has outputs to the hippocampus, where disruption of physiologic theta frequency activity has been observed in epilepsy, and its restoration is associated with seizure reduction [25 ▪ ]. Continuous medial septum stimulation in mouse epilepsy models was noted to be more effective than intermittent stimulation [26].…”

Section: Stimulation Targetsmentioning

confidence: 99%

Emerging approaches in neurostimulation for epilepsy

Lundstrom

Osman

Starnes

et al. 2023

Current Opinion in Neurology

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Purpose of reviewNeurostimulation is a quickly growing treatment approach for epilepsy patients. We summarize recent approaches to provide a perspective on the future of neurostimulation.Recent findingsInvasive stimulation for treatment of focal epilepsy includes vagus nerve stimulation, responsive neurostimulation of the cortex and deep brain stimulation of the anterior nucleus of the thalamus. A wide range of other targets have been considered, including centromedian, central lateral and pulvinar thalamic nuclei; medial septum, nucleus accumbens, subthalamic nucleus, cerebellum, fornicodorsocommissure and piriform cortex. Stimulation for generalized onset seizures and mixed epilepsies as well as increased efforts focusing on paediatric populations have emerged. Hardware with more permanently implanted lead options and sensing capabilities is emerging. A wider variety of programming approaches than typically used may improve patient outcomes. Finally, noninvasive brain stimulation with its favourable risk profile offers the potential to treat increasingly diverse epilepsy patients.SummaryNeurostimulation for the treatment of epilepsy is surprisingly varied. Flexibility and reversibility of neurostimulation allows for rapid innovation. There remains a continued need for excitability biomarkers to guide treatment and innovation. Neurostimulation, a part of bioelectronic medicine, offers distinctive benefits as well as unique challenges.

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Section: Stimulation Targetsmentioning

confidence: 99%

Emerging approaches in neurostimulation for epilepsy

Lundstrom

Osman

Starnes

et al. 2023

Current Opinion in Neurology

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show abstract

“…The former observation is particularly surprising given that the medial septum is known to be a predominant driver of the hippocampal theta rhythm. 10, 11 Taken together, these results contradict common conventions in translational neuromodulation studies. For example, a study investigating electrical stimulation in the medial septum as a treatment for epilepsy might choose theta-frequency or theta-burst stimulation based on literature showing that hippocampal theta rhythms are seizure-resistant, then measure its effect on seizure frequency compared to sham stimulation (based on a mechanistic hypothesis of entraining hippocampal theta rhythms).…”

Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

“…10 In addition, a better understanding of how various parameters of medial septum stimulation can control hippocampal oscillations could improve its therapeutic potential as a treatment for epilepsy. 11 In this study, we test five different classes of optogenetic stimulation waveforms in the medial septum, comprehensively sweep their parameters, and measure their effects on hippocampal activity. First, we characterize the effects of varying the stimulation waveform on single biomarkers with well-characterized roles in hippocampal functiontheta power and low gamma powerand find significant but modest differences between the effects of different temporal waveforms on individual frequency bands.…”

Section: Introductionmentioning

confidence: 99%

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Irregular optogenetic stimulation waveforms can induce naturalistic patterns of hippocampal spectral activity

Cole

Eggers

Weiß

et al. 2022

Preprint

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Introduction: Brain stimulation is a fundamental and effective therapy for neurological diseases including Parkinsons disease, essential tremor, and epilepsy. One key challenge in delivering effective brain stimulation is identifying the stimulation parameters, such as the amplitude, frequency, contact configuration, and pulse width, that induce an optimal change in symptoms, behavior, or neural activity. Most clinical and translational studies use constant frequency pulses of stimulation, but stimulation with irregular pulse patterns or non-pulsatile waveforms might induce unique changes in neural activity that could enable better therapeutic responses. Here, we comprehensively evaluate several optogenetic stimulation waveforms, report their differing effects on hippocampal spectral activity, and compare these induced effects to activity recorded during natural behavior. Methods: Sprague Dawley rats were prepared for panneuronal excitatory optogenetic stimulation of the medial septum (hSyn ChR2) and 16-channel microelectrode recording in CA1 and CA3 layers of the hippocampus. We performed grid and random sampling of the parameters comprising several stimulation waveforms, including standard pulse, nested pulse, sinusoid, double sinusoid, and Poisson pulse waveforms. Results: We comprehensively report the effects of changing stimulation parameters in these parameter spaces on two key biomarkers of hippocampal function, theta and gamma power. Similarly, robust excitation of hippocampal gamma power was observed across all waveforms, whereas no set of stimulation parameters was sufficient to consistently increase power in the theta band beyond baseline levels of activity (despite the prominent role of the medial septum in pacing hippocampal theta oscillations). Using a manifold learning algorithm to compare high dimensional neural activity, we show that irregular stimulation patterns produce differing effects with respect to multi-band patterns of activity and can induce activity patterns that more closely resemble activity recorded during natural behavior than conventional parameters. Conclusion: Our counter intuitive findings, that stimulation of the medial septum ubiquitously does not increase hippocampal theta power, and that different waveforms have similar effects on single power bands, contradict recent trends in brain stimulation research, necessitating greater caution and fewer mechanistic assumptions as to how a given stimulation target or waveform will modulate a neurophysiological biomarker of disease. We also reveal that irregular stimulation patterns can have biomimetic utility, promoting their exploration in medical applications where inducing a particular activity pattern can have therapeutic benefit. Last, we demonstrate a scalable data driven analysis strategy that can make the discovery of such physiologically informed temporal stimulation patterns more empirically tractable in translational settings.

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“…We use previously published data from an investigation of medial septum optogenetic stimulation and hippocampal electrophysiological recording in rats [6,11]. The data was collected while a rat transitioned from anesthesia (2-3% isoflurane) to awake behavior.…”

Section: A Experimental Design and Data Collectionmentioning

confidence: 99%

Adaptive Bayesian Optimization for State-Dependent Brain Stimulation

Dabiri

Cole

Gross

2023

Preprint

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Brain stimulation has become an important treatment option for a variety of neurological and psychiatric diseases. A key challenge in improving brain stimulation is selecting the optimal set of stimulation parameters for each patient, as parameter spaces are too large for brute-force search and their induced effects can exhibit complex subject-specific behavior. To achieve greatest effectiveness, stimulation parameters may additionally need to be adjusted based on an underlying neural state, which may be unknown, unmeasurable, or challenging to quantify a priori. In this study, we first develop a simulation of a state-dependent brain stimulation experiment using rodent optogenetic stimulation data. We then use this simulation to demonstrate and evaluate two implementations of an adaptive Bayesian optimization algorithm that can model a dynamically changing response to stimulation parameters without requiring knowledge of the underlying neural state. We show that, while standard Bayesian optimization converges and overfits to a single optimal set of stimulation parameters, adaptive Bayesian optimization can continue to update and explore as the neural state is changing and can provide more accurate optimal parameter estimation when the optimal stimulation parameters shift. These results suggest that learning algorithms such as adaptive Bayesian optimization can successfully find optimal state-dependent stimulation parameters, even when brain sensing and decoding technologies are insufficient to track the relevant neural state.

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Evidence supporting deep brain stimulation of the medial septum in the treatment of temporal lobe epilepsy

Cited by 24 publications

References 168 publications

Emerging approaches in neurostimulation for epilepsy

Emerging approaches in neurostimulation for epilepsy

Irregular optogenetic stimulation waveforms can induce naturalistic patterns of hippocampal spectral activity

Adaptive Bayesian Optimization for State-Dependent Brain Stimulation

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