Deep Brain Stimulation for Epilepsy

Nagel, Sean J.; Najm, Imad

doi:10.1111/j.1525-1403.2009.00239.x

Cited by 37 publications

(18 citation statements)

References 92 publications

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“…Seizure control by periodic electrical stimulation is a promising avenue for the treatment of refractory epilepsies [1], [2]. Experimental studies have investigated a variety of electrical stimulation protocols, observing seizure suppression both in humans [3]–[6] and in non-human animal or in vitro models of epilepsy [7], [8].…”

Section: Introductionmentioning

confidence: 99%

Controlling Seizure-Like Events by Perturbing Ion Concentration Dynamics with Periodic Stimulation

2013

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We investigate the effects of adding periodic stimulation to a generic, conductance-based neuron model that includes ion concentration dynamics of sodium and potassium. Under conditions of high extracellular potassium, the model exhibits repeating, spontaneous, seizure-like bursting events associated with slow modulation of the ion concentrations local to the neuron. We show that for a range of parameter values, depolarizing and hyperpolarizing periodic stimulation pulses (including frequencies lower than 4 Hz) can stop the spontaneous bursting by interacting with the ion concentration dynamics. Stimulation can also control the magnitude of evoked responses to modeled physiological inputs. We develop an understanding of the nonlinear dynamics of this system by a timescale separation procedure that identifies effective nullclines in the ion concentration parameter space. Our results suggest that the manipulation of ion concentration dynamics via external or endogenous stimulation may play an important role in neuronal excitability, seizure dynamics, and control.

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Section: Introductionmentioning

confidence: 99%

Controlling Seizure-Like Events by Perturbing Ion Concentration Dynamics with Periodic Stimulation

2013

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“…It is thought that DBS disrupts or inhibits epileptiform activity in epileptogenic thalamocortical networks (Lega, Halpern, Jaggi, & Baltuch, 2010; Lim et al, 2008). By targeting crucial nodes in the epileptogenic network, such as ANT with its wide limbic and cortical connections, regions involved in sustaining, propagating, or triggering epileptic activity could be inhibited (Nagel & Najm, 2009; Zumsteg, Lozano, & Wennberg, 2006). …”

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confidence: 99%

Immediate effects of deep brain stimulation of anterior thalamic nuclei on executive functions and emotion–attention interaction in humans

Hartikainen

Sun

Polvivaara

et al. 2014

Journal of Clinical and Experimental Neuropsychology

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BackgroundDeep brain stimulation (DBS) of anterior thalamic nuclei (ANT) is a novel promising therapeutic method for treating refractory epilepsy. Despite reports of subjective memory impairments and mood disturbances in patients with ANT-DBS, little is known of its effects on cognitive and affective processes.HypothesisThe anterior thalamus has connections to prefrontal and limbic networks important for cognitive control and emotional reactivity. More specifically, anterior cingulate cortex (ACC), linked with ANT, has been assigned roles related to response inhibition and attention allocation to threat. Thus, we hypothesized ANT-DBS to influence executive functions, particularly response inhibition, and modulate emotional reactivity to threat.MethodTwelve patients having undergone ANT-DBS for intractable epilepsy participated in the study. Patients performed a computer-based executive reaction time (RT) test—that is, a go/ no-go visual discrimination task with threat-related emotional distractors and rule switching, while the DBS was switched ON (5/5 mA constant current) and OFF every few minutes.ResultsANT-DBS increased the amount of commission errors—that is, errors where subjects failed to withhold from responding. Furthermore, ANT-DBS slowed RTs in context of threat-related distractors. When stimulation was turned off, threat-related distractors had no distinct effect on RTs.ConclusionWe found immediate objective effects of ANT-DBS on human cognitive control and emotion-attention interaction. We suggest that ANT-DBS compromised response inhibition and enhanced attention allocation to threat due to altered functioning of neural networks that involve the DBS-target, ANT, and the regions connected to it such as ACC. The results highlight the need to consider affective and cognitive side-effects in addition to the therapeutic effect when adjusting stimulation parameters. Furthermore, this study introduces a novel window into cognitive and affective processes by modulating the associative and limbic networks with direct stimulation of key nodes in the thalamus.

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“…Targets proposed for stimulation have included the anterior nucleus of the thalamus (ANT), the centromedian nucleus of the thalamus (CMT), the subthalamic nucleus, and the hippocampus 21. Much of this work has been performed in rodent models and has provided valuable insight into the pathogenesis of seizures.…”

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confidence: 99%

Placement of Deep Brain Electrodes in the Dog Using the Brainsight Frameless Stereotactic System: A Pilot Feasibility Study

Long

Frey

Freestone

et al. 2013

Veterinary Internal Medicne

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BackgroundDeep brain stimulation (DBS) together with concurrent EEG recording has shown promise in the treatment of epilepsy. A novel device is capable of combining these 2 functions and may prove valuable in the treatment of epilepsy in dogs. However, stereotactic implantation of electrodes in dogs has not yet been evaluated.ObjectiveTo evaluate the feasibility and safety of implanting stimulating and recording electrodes in the brain of normal dogs using the Brainsight system and to evaluate the function of a novel DBS and recording device.AnimalsFour male intact Greyhounds, confirmed to be normal by clinical and neurologic examinations and hematology and biochemistry testing.Methods MRI imaging of the brain was performed after attachment of fiducial markers. MRI scans were used to calculate trajectories for electrode placement in the thalamus and hippocampus, which was performed via burr hole craniotomy. Postoperative CT scanning was performed to evaluate electrode location and accuracy of placement was calculated. Serial neurologic examinations were performed to evaluate neurologic deficits and EEG recordings obtained to evaluate the effects of stimulation.ResultsElectrodes were successfully placed in 3 of 4 dogs with a mean accuracy of 4.6 ± 1.5 mm. EEG recordings showed evoked potentials in response to stimulation with a circadian variation in time‐to‐maximal amplitude. No neurologic deficits were seen in any dog.Conclusions and Clinical ImportanceStereotactic placement of electrodes is safe and feasible in the dog. The development of a novel device capable of providing simultaneous neurostimulation and EEG recording potentially represents a major advance in the treatment of epilepsy.

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Deep Brain Stimulation for Epilepsy

Cited by 37 publications

References 92 publications

Controlling Seizure-Like Events by Perturbing Ion Concentration Dynamics with Periodic Stimulation

Controlling Seizure-Like Events by Perturbing Ion Concentration Dynamics with Periodic Stimulation

Immediate effects of deep brain stimulation of anterior thalamic nuclei on executive functions and emotion–attention interaction in humans

Placement of Deep Brain Electrodes in the Dog Using the Brainsight Frameless Stereotactic System: A Pilot Feasibility Study

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