Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy

Koubeissi, Mohamad Z.; Joshi, Sumit; Eid, Alexandra; Emami, Mehrdad; Jaafar, Nadim; Syed, Tanvir U.; Foreman, Perry J.; Sheth, Anumeha; Amdur, Richard L.; Nasif, Mei Bou; Puente, Antonio N.; Aly, Radwa; Chen, Hai; Becker, Andrew; Gholipour, Taha; Makke, Yamane; Elmashad, Ahmed; Gagnon, Linda; Durand, Dominique M.; Gaillard, William D.; Shields, Donald C.

doi:10.1016/j.yebeh.2022.108667

Cited by 17 publications

(15 citation statements)

References 34 publications

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“…5,16 A concern regarding the use of LFS is the possibility of seizure exacerbation. However, there is evidence suggesting potential benefit from LFS in mesial temporal epilepsy, 17 similar to most patients in this study. LFS during invasive epilepsy monitoring has been used for seizure induction to facilitate epileptogenic zone identification, although higher frequencies (e.g., 50 Hz) have been noted to induce seizures more readily.…”

Section: Discussionsupporting

confidence: 76%

Responsive neurostimulation with low‐frequency stimulation

et al. 2022

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Deep brain stimulation and responsive neurostimulation (RNS) use highfrequency stimulation (HFS) per the pivotal trials and manufacturerrecommended therapy protocols. However, not all patients respond to HFS. In this retrospective case series, 10 patients implanted with the RNS System were programmed with low-frequency stimulation (LFS) to treat their seizures; nine of these patients were previously treated with HFS (100 Hz or greater). LFS was defined as frequency < 10 Hz. Burst duration was increased to at least 1000 ms. With HFS, patients had a median seizure reduction (MSR) of 13% (interquartile range[IQR] = −67 to 54) after a median of 19 months (IQR = 8-49). In contrast, LFS was associated with a 67% MSR (IQR = 13-95) when compared to HFS and 76% MSR (IQR = 43-91) when compared to baseline prior to implantation. Charge delivered per hour and pulses per day were not significantly different between HFS and LFS, although time stimulated per day was longer for LFS (228 min) than for HFS (7 min). There were no LFS-specific adverse effects reported by any of the patients. LFS could represent an alternative, effective method for delivering stimulation in focal drug-resistant epilepsy patients treated with the RNS System.

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Section: Discussionsupporting

confidence: 76%

Responsive neurostimulation with low‐frequency stimulation

et al. 2022

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“…Studies on DBS and RNS ® therapies reported variable outcomes on cognition (for review see 10,29,30 ) including depression and memory impairment 74,75 , which might be related to HFS interfering with ongoing brain activity 76,77 . Studies on LFS, reporting stable verbal memory scores with no psychiatric complications, suggest that LFS might be a safer treatment option for pharmacoresistant patients 22,23 . However, little is known about whether hippocampal LFS affects navigation and memory.…”

Section: Hippocampal Lfs Alleviates Deficits In Long-term Memory Recallmentioning

confidence: 99%

“…Especially for MTLE patients with HS, HFS has low effectiveness 14,18,19 , presumably due to extensive neuronal loss, reactive gliosis, and the resulting change in electrical resistance in the sclerotic hippocampus 20,21 . In contrast, hippocampal low-frequency stimulation (LFS) at 5 Hz reduced seizure activity remarkably in small clinical cohort studies, including MTLE patients with HS [22][23][24] . Additionally, recent findings demonstrated that LFS (10 min on/off) at 1 Hz in the epileptic focus decreased cortical excitability in pharmacoresistant epilepsy patients 25 .…”

Section: Introductionmentioning

confidence: 99%

“…In this regard, conflicting results were reported for HFS and RNS, likely due to variations in stimulation target, protocol, and the cognitive test applied (for review see 10,29,30 ). However, little is known about LFS-related cognitive effects 22,23 . For a systematic assessment of the LFS-related impact on seizure reduction and hippocampus-dependent cognitive functions, studies in translational animal models are crucial.…”

Section: Introductionmentioning

confidence: 99%

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On-demand low-frequency stimulation for seizure control: efficacy and behavioral implications

Paschen

Kleis

Vieira

et al. 2023

Preprint

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Mesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy in adults, is often refractory to medication and associated with hippocampal sclerosis. Deep brain stimulation represents an alternative treatment option for drug-resistant patients who are ineligible for resective brain surgery. In clinical practice, closed-loop stimulation at high frequencies is applied to interrupt ongoing seizures, yet with a high incidence of false detections, the drawback of delayed seizure-suppressive intervention and limited success in sclerotic tissue. More recently, hippocampal low-frequency stimulation (LFS) has been shown to reduce excitability in clinical settings and prevent seizures in experimental MTLE when applied continuously. However, as the hippocampus is important for navigation and memory, it would be beneficial to stimulate it only on-demand to reduce its exposure to LFS pulses, and to investigate LFS-related effects on cognition. Using the intrahippocampal kainate mouse model, which recapitulates the key features of MTLE, we developed an on-demand LFS setup and investigated its effects on spontaneous seizure activity and hippocampal function. Specifically, our online detection algorithm monitored epileptiform activity in hippocampal local field potential recordings and identified short epileptiform bursts preceding focal seizure clusters, triggering hippocampal LFS to stabilize the network state. In addition, we investigated the acute influence of LFS on behavioral performance, including anxiety-like behavior in the light-dark box test, spatial and non-spatial memory in the object location memory and novel object recognition test, as well as spatial navigation and long-term memory in the Barnes maze. Compared to open-loop stimulation protocols, on-demand LFS was more efficient in preventing focal seizure clusters, as the strong anti-epileptic effect was achieved with a reduced stimulation load. In behavioral tests, chronically epileptic mice were as mobile as healthy controls but showed increased anxiety, an altered spatial learning strategy and impaired memory performance. Most importantly, our experiments ruled out deleterious effects of hippocampal LFS on cognition and even showed alleviation of deficits in long-term memory recall. Taken together, our findings may provide a promising alternative to current therapies, overcoming some of their major limitations, and inspire further investigation of LFS for seizure control in MTLE.

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“…The hippocampal formation has a well-characterized functional network, where in general, CA3 neurons project to the CA1 region, and output via the subiculum. Anti-seizure effects have been found with stimulation at each of these regions 27,28,[28][29][30][31][32] as well as at hippocampal white-matter commissures 33,34,18 . Therapeutic effects have also been seen with stimulation of extra-hippocampal structures, including the anterior nucleus of the thalamus 7 and medial septum 35,36 .…”

Section: Introductionmentioning

confidence: 99%

Spatial and Amplitude Dynamics of Neurostimulation: Insights from the Acute Intrahippocampal Kainate Seizure Mouse Model

Foutz

Rensing

Han

et al. 2023

Preprint

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Objective: Neurostimulation is an emerging treatment for patients with medically refractory epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model. Methods: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of temporal lobe epilepsy. We evaluated combinations of six anatomic targets and three stimulus amplitudes. Results: We found that the spike-suppressive effects of high-frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 microamp stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation. Significance: These findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti-seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy.

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Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy

Cited by 17 publications

References 34 publications

Responsive neurostimulation with low‐frequency stimulation

Responsive neurostimulation with low‐frequency stimulation

On-demand low-frequency stimulation for seizure control: efficacy and behavioral implications

Spatial and Amplitude Dynamics of Neurostimulation: Insights from the Acute Intrahippocampal Kainate Seizure Mouse Model

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