Brain Function Study for Epilepsy
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Dartmouth-Hitchcock Medical Center
Disqualifiers: Stroke, Dementia, Psychosis, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This study will enroll patients with epilepsy who are being evaluated for epilepsy surgery and have electrodes implanted in the brain and/or have electrodes on the scalp. Additionally, this study will recruit normal and online controls (participants who do not have epilepsy). Participants will be asked to participate in 1 to 2 (30-90 minutes) daily sessions designed to test aspects of human cognition such as memory, speech, language, feeling, movement, attention, sound perception, and emotions. Generally, this will involve working on a computer, looking at pictures or watching videos, and answering questions. Additionally, participants may be asked to be hooked up to additional equipment such as eye tracker, electrical stimulator, heart rate monitor, sweat monitor or other non-invasive equipment. The overall aim of this study is to use human intracranial electrophysiology (the recording of the electrical activity of the human brain) to study localization and function of the human brain.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.
What data supports the effectiveness of this treatment for epilepsy?
Research shows that Vagus Nerve Stimulation (VNS) can improve working memory and attention in patients with epilepsy, as well as enhance cognitive functions like alertness and arousal. These findings suggest that VNS may have beneficial effects on brain function in epilepsy beyond just reducing seizures.
12345Is vagus nerve stimulation (VNS) safe for humans?
Vagus nerve stimulation (VNS) is generally considered safe for humans, as it is an accepted treatment for epilepsy and depression. Studies have shown that while VNS can affect memory and reaction times, these effects are reversible and not significant in clinical settings.
12456How does vagus nerve stimulation differ from other treatments for epilepsy?
Vagus nerve stimulation (VNS) is unique because it involves electrical stimulation of the vagus nerve to help control seizures, unlike traditional drug treatments. It not only reduces seizure frequency but also has potential cognitive benefits, such as improving working memory and affecting emotional reactivity, which are not typically associated with standard epilepsy medications.
12789Eligibility Criteria
This trial is for adults with refractory epilepsy who are undergoing clinical intracranial EEG recording as part of their evaluation for epilepsy surgery. It also includes healthy individuals and online participants without epilepsy to serve as controls.Inclusion Criteria
I am 18 years or older and may need a scalp EEG.
I am 18 years or older and may have an intracranial EEG.
I am 18 years or older and do not have the condition being studied.
+3 more
Exclusion Criteria
Patients with Scalp EEG must not be able to provide informed consent for any reason
Normal Controls must be determined not to be appropriate normal control for the study population
Patients with Intracranial EEG must not be able to provide informed consent for any reason
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants engage in daily sessions designed to test aspects of human cognition such as memory, speech, language, feeling, movement, attention, sound perception, and emotions, with continuous recording of brain activity using intracranial and scalp EEG.
2 weeks
1-2 daily sessions (30-90 minutes each)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests various aspects of human cognition in patients with electrodes implanted in the brain or on the scalp, using tasks related to memory, speech, emotions, etc., often involving computers and additional non-invasive monitoring equipment.
4Treatment groups
Experimental Treatment
Active Control
Group I: Scalp EEG (electrodes are placed on a participant's scalp)Experimental Treatment8 Interventions
Patients with non-invasive scalp electrodes who are admitted to the hospital for clinical reasons will be asked to participate in various study tasks with the recording of their EEG (recording of brain waves via electrodes attached to a participant's scalp) during these tasks.
Group II: Invasive EEG (electrodes are implanted in a participant's brain)Experimental Treatment9 Interventions
Patients with intracranial electrodes (electrodes are implanted in a participant's brain) undergoing pre-surgical evaluation for clinical reasons will be asked to participate in various study tasks with the recording of intracranial EEG (recording of brain waves via electrodes implanted in a participant's brain) during these tasks.
Group III: Normal ControlsActive Control7 Interventions
Normal controls will be recruited from family members of patients, from advertisements, or from online tools. There will be no EEG recordings obtained from these participants.
Group IV: Online ControlsActive Control7 Interventions
Certain control subjects will be recruited through Amazon Mechanical Turk. These participants will be given their task on the online platform using Qualtric survey function. The task design will be identical to normal controls who are recruited in-person, with the exception of identifiers. There will be no EEG recordings obtained from these participants.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Dartmouth-Hitchcock Medical CenterLebanon, NH
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Who Is Running the Clinical Trial?
Dartmouth-Hitchcock Medical CenterLead Sponsor
Dartmouth CollegeCollaborator
Brown UniversityCollaborator
References
Vagus nerve stimulation improves working memory performance. [2018]Vagus nerve stimulation (VNS) is used for treating refractory epilepsy and major depression. While the impact of this treatment on seizures has been established, its impact on human cognition remains equivocal. The goal of this study is to elucidate the immediate effects of vagus nerve stimulation on attention, cognition, and emotional reactivity in patients with epilepsy. Twenty patients (12 male and 8 female; 45 ± 13 years old) treated with VNS due to refractory epilepsy participated in the study. Subjects performed a computer-based test of executive functions embedded with emotional distractors while their brain activity was recorded with electroencephalography. Subjects' cognitive performance, early visual event-related potential N1, and frontal alpha asymmetry were studied when cyclic vagus nerve stimulation was on and when it was off. We found that vagus nerve stimulation improved working memory performance as seen in reduced errors on a subtask that relied on working memory, odds ratio (OR) = 0.63 (95% confidence interval, CI [0.47, 0.85]) and increased N1 amplitude, F(1, 15) = 10.17, p = .006. In addition, vagus nerve stimulation resulted in longer reaction time, F(1, 16) = 8.23, p = .019, and greater frontal alpha asymmetry, F(1, 16) = 11.79, p = .003, in response to threat-related distractors. This is the first study to show immediate improvement in working memory performance in humans with clinically relevant vagus nerve stimulation. Furthermore, vagus nerve stimulation had immediate effects on emotional reactivity evidenced in behavior and brain physiology.
Memory alterations during acute high-intensity vagus nerve stimulation. [2019]Left cervical vagus nerve stimulation (VNS) is an accepted add-on treatment for pharmacoresistant epilepsy. However, it also allows the investigation of the effects of peripheral nerve stimulation on central nervous functions. The impact of 4.5 min high intensity VNS (>1 mA) on material-specific memory and decision times was evaluated in an experimental 'box car' design in 11 patients with pharmacoresistant epilepsy. Results indicate reversible deterioration of figural but not verbal memory and a trend of accelerated decision times during VNS. Thus, further support of cognitive effects of VNS is provided. There are indications of a major projection of VNS to activating brain structures of and the right hemisphere. Significant cognitive side effects in clinical application are unlikely because of the reversibility of the effect and differences between experimental and therapeutic stimulation conditions. However, since the effectors and the direction of the cognitive effects of VNS seem to depend strongly on stimulation conditions, we recommend future experimental research covering a larger range of stimulation conditions.
Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. [2022]Vagus nerve stimulation (VNS) is an established treatment method for therapy-refractory epilepsy and, in Europe, for treatment-resistant depression also. Clinical and experimental investigations have also shown positive effects of VNS on cognition in epilepsy and depression. The purpose of the present pilot study was to investigate the effect of VNS on cognition in patients with Alzheimer's disease.
Transcutaneous Auricular Vagus Nerve Stimulation Facilitates Cortical Arousal and Alertness. [2023]Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising noninvasive technique with potential beneficial effects on human emotion and cognition, including cortical arousal and alertness. However, it remains unclear how taVNS could improve cortical arousal and alertness, which are crucial for consciousness and daily task performance. Here, we aimed to estimate the modulatory effect of taVNS on cortical arousal and alertness and to reveal its underlying neural mechanisms. Sixty subjects were recruited and randomly assigned to either the taVNS group (receiving taVNS for 20 min) or the control group (receiving taVNS for 30 s). The effects of taVNS were evaluated behaviorally using a cue-target pattern task, and neurologically using a resting-state electroencephalogram (EEG). We found that taVNS facilitated the reaction time for the targets requiring right-hand responses and attenuated high-frequency alpha oscillations under the close-eye resting state. Importantly, taVNS-modulated alpha oscillations were positively correlated with the facilitated target detection performance, i.e., reduced reaction time. Furthermore, microstate analysis of the resting-state EEG when the eyes were closed illustrated that taVNS reduced the mean duration of microstate C, which has been proven to be associated with alertness. Altogether, this work provided novel evidence suggesting that taVNS could be an enhancer of both cortical arousal and alertness.
Effect of Vagus Nerve Stimulation on Attention and Working Memory in Neuropsychiatric Disorders: A Systematic Review. [2022]It has been suggested that vagus nerve stimulation (VNS) may enhance attention and working memory. The neuromodulator effects of VNS are thought to activate the release of neurotransmitters involving cognition and to promote neuronal plasticity. Therefore, VNS has been studied for its effects on attention and working memory impairment in neuropsychiatric disorders.
Concurrent brain-responsive and vagus nerve stimulation for treatment of drug-resistant focal epilepsy. [2022]Clinical trials of a brain-responsive neurostimulator, RNS® System (RNS), excluded patients with a vagus nerve stimulator, VNS® System (VNS). The goal of this study was to evaluate seizure outcomes and safety of concurrent RNS and VNS stimulation in adults with drug-resistant focal-onset seizures.
Vagus nerve stimulation outcome prediction: from simple parameters to advanced models. [2022]Since its approval as an adjunct treatment for refractory partial epilepsy, the positive effects of vagus nerve stimulation (VNS) on seizure frequency and severity have been supported by many studies. Seizure reduction of more than 50 % can be expected in at least 50 % of patients. However, a complete post-VNS seizure freedom is rarely achieved and 25 % of patients do not benefit from VNS. Our study provides an overview of the potential predictors of VNS response, from the most simple and basic data to sophisticated EEG processing studies and functional imaging studying brain connectivity. The data support better outcomes in younger patients with early VNS implantation, in patients with posttraumatic epilepsy or tuberous sclerosis, and in patients without bilateral interictal epileptiform discharges. The variability of heart activity has also been studied with some promising results. Because the generally accepted hypothesis of the VNS mechanism is the modulation of synaptic activity in multiple cortical and subcortical regions of the brain, the studies of brain response to external stimulation and/or of brain connectivity were used for models predicting the effect of VNS in individual patients. Although the predictive value of these models is high, the required special equipment and sophisticated mathematical tools limit their routine use (Ref. 58). Keywords: epilepsy, vagus nerve stimulation, response predictor, EEG.
Electrocorticography Analysis in Patients With Dual Neurostimulators Supports Desynchronization as a Mechanism of Action for Acute Vagal Nerve Stimulator Stimulation. [2023]Both vagal nerve stimulation (VNS) and responsive neurostimulation (RNS System) are treatment options for medically refractory focal epilepsy. The mechanism of action of both devices remains poorly understood. Limited prior evidence suggests that acute VNS stimulation may reduce epileptiform activity and cause EEG desynchronization on electrocorticography (ECoG). Our study aims to isolate effects of VNS on ECoG as recorded by RNS System in patients who have both devices, by comparing ECoG samples with and without acute VNS stimulation.
Symptomatic responses elicited by electrical stimulation of the cingulate cortex: Study of a cohort of epileptic patients and literature review. [2023]Our understanding of cingulate cortex function is limited. As a method for locating the epileptogenic zone, direct electrical cortical stimulation (ECS) provides an opportunity to understand the functional localization of the cingulate cortex. This study aimed to learn more about the function of the cingulate cortex by analyzing a large body of data from our center and by reviewing existing literature on cortical mapping. We retrospectively analyzed the ECS data of 124 patients with drug-resistant epilepsy who had undergone electrode implantation in the cingulate cortex. The standard stimulation parameters included a biphasic pulse and bipolar stimulation at 50 Hz. Furthermore, we reviewed existing studies on cingulate responses elicited by the ECS and compared them with our results. A total of 329 responses were evoked in 276 contacts using ECS. Of these, 196 were physiological functional responses, which included sensory, affective, autonomic, language, visual, vestibular, and motor responses, along with a few other sensations. Sensory, motor, vestibular, and visual responses were concentrated in the cingulate sulcus visual area (CSv). Furthermore, 133 epilepsy-related responses were evoked, most of which were concentrated in the ventral cingulate cortex. No responses were evoked by 498 contacts. Furthermore, the comparison of our ECS results with those reported in 11 comprehensive reviews revealed that the cingulate cortex is involved in complicated functions. The cingulate cortex is involved in sensory, affective, autonomic, language, visual, vestibular, and motor functions. The CSv is an integrating node of sensory, motor, vestibular, and visual systems.