Drug Resistant EpilepsyNCT05997758
Investigating Surprise Signals in the Anterior Insula
An observational study of Drug Resistant Epilepsy and Healthy, run by University Hospital, Geneva at 1 site in Switzerland.
Trial summary
The investigators propose a behavioral experiment with SEEG recording and stimulation, to both confirm the role of a brain region known as the anterior insula in identifying surprise, and disambiguate between competing principles behind adaptation: optimizing and satisficing. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Drug Resistant Epilepsy, Healthy
- What is being tested?
- SEEG stimulation and Adaptation task
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 50 participants
- Where
- 1 siteSwitzerland
- Study dates
- 15 Jan 2024to Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients who suffer from potentially surgically remediable drug-resistant focal epilepsy and require evaluation with intracranial stereo-EEG electrodes and have them implanted in the anterior insula hospitalized at the Hôpitaux Universitaires Genève.
Who may be able to join
- 18 years or older
- Fluent in French or English
- Patient who suffers from potentially surgically remediable drug-resistant focal epilepsy
- Patient who requires evaluation with intracranial stereo-EEG electrodes and has them implanted in the anterior insula
- Patient who is able and willing to provide informed consent
Who cannot join
- Severe concomitant psychiatric disease or major psychological distress
- Patients who have an implanted stimulation device (e.g. pacemaker, defibrillator, neurostimulator)
- Intellectual/neurological/psychiatric deficiencies* or inability to understand or follow the procedure
- Visual/motor deficiencies which could affect task performance
- The presence of seizures during routine clinical stimulation of insular electrodes
- Failure to complete the pre-experiment task training
- As determined by their clinical evaluation.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Service de Neurologie, Dpt des Neurosciences cliniques HUG
Geneva, 1205
Fabienne Picard, MD, +41 22.3725.258, Fabienne.Picard@hcuge.ch
About this study
Official title: Investigating Surprise Signals in the Anterior Insula in Epilepsy Patients With Stereoelectroencephalography Recording
The investigators propose a behavioral experiment with SEEG recording and stimulation, to both confirm the role of a brain region known as the anterior insula in identifying surprise, and disambiguate between competing principles behind adaptation: optimizing and satisficing. Optimizers continue to learn and adapt if performance can be improved, while satisficers are satisfied with a good enough performance and will cease adapting once that is reached.
To study surprise signals in the anterior insula, a brain structure where these signals have been very prominent, the investigators will employ an experiment with subjects who are under SEEG (stereoelectroencephalogram) recording, that is, recording from electrodes which have been surgically implanted in the brain. These recordings will be done as patients perform a task where they try to anticipate the movements of a target on a line in two different learning environments (conditions). The experimenters will then determine whether these signals reflect surprise relative to past engagement with the environment, or surprise that reveals that the agent no longer feels in control because uncertainty is not in line with the reference model. If evidence is consistent with the former, adaptation reflects traditional reinforcement and aims at optimizing behavior. If evidence instead is consistent with the latter, behavior is guided by a prior model (a reference model) and behavior is satisficing.
Read more
An fMRI study by d'Acremont and Bossaerts provides initial evidence that activation in the anterior insula supports the satisficing hypothesis, however it lacks the temporal granularity to completely rule out optimizing. In the current project, the investigators propose to use the higher time resolution of SEEG recordings to confirm these findings and reject the optimizing hypothesis.
Additionally, stimulations of the anterior insula during a subset of trials will be used to determine whether insular activation following surprise signals and preceding changes in behavior (learning) is merely correlational or in fact causal. Stimulation will allow us to determine to what extent the subjects' sense of control and subsequent behavior can be influenced in accordance with surprise-based modeling of behavior.
The cohort for this study will be patients with drug-resistant, focal epilepsy and who are hospitalized at the Hôpitaux Universitaires de Genève (HUG) for pre-surgical evaluation of their epilepsy using SEEG. The protocol will run in parallel with the patients' clinical procedures.
- Conditions
- Drug Resistant Epilepsy, Healthy
- Being tested
- SEEG stimulation, Adaptation task
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SEEG stimulationOther
Electrodes already implanted in patient's anterior insula will be stimulated below the patient-specific threshold at which a seizure was induced. This stimulations will coincide with certain trials in the adaptation task.
Adaptation taskBehavioural
Participants will perform a task that requires them to learn and correctly respond to outliers of two sorts; inconsequential outliers, which require no action, and outliers that are relevant to the course of stimuli and outcomes in future trials, requiring adaptive action.
| Study group | Role | What they receive |
|---|---|---|
| Patients | Patients who suffer from potentially surgically remediable drug-resistant focal epilepsy and who require evaluation with intracranial stereo-EEG electrodes and have them implanted in the anterior insula.
N = 10 Receives: Other: SEEG stimulation; Behavioral: Adaptation task | |
| Subclinical | Healthy individuals who match the clinical population in age and level of education.
N = 40 Receives: Behavioral: Adaptation task |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bias adjustment -- non-stimulation trials (behavioral, numerical)
Subjects' choices, measured as the degree of bias correction they employ (a numerical value typically between 0 and +/-3) during outlier trials and the trials immediately following them. These will be quantitatively compared between conditions using Bayes-optimal choices and choices as predicted by Model-Reference Based Adaptive Control.
Measured: Up to 2500 ms after stimuli presentation. All data collected during eight 5-minute sessions on the same day
Bias adjustment -- stimulation trials (behavioral, numerical)
Subjects' choices, measured as the degree of bias correction they employ (a numerical value typically between 0 and +/-3) during stimulation trials (both outlier and non-outlier trials). These will be quantitatively compared to choices on the same trial types without stimulation.
Measured: Up to 2500 ms after stimuli presentation. All data collected during four 5-minute sessions on the same day
SEEG-ERP--non-stimulation trials
Event-related potentials (ERPs) extracted from subjects' stereoelectroencephalographies from intercranial electrodes implanted in the anterior insulae. ERPs will be averaged across the time series and t-statistics will be computed for effect of condition (outlier type).
Measured: Up to 2500 ms after stimuli presentation. Averaged over all trials for each task condition. All data collected during 8 5-minute sessions on the same day
SEEG-TF--non-stimulation trials
The stereoelectroencephalographies from intercranial electrodes implanted in subjects' anterior insulae will be used for time frequency (TF) analyses. Time series components will be extracted for multiple frequencies and t-statistics of the effects of condition (outlier type) will be computed for each frequency.
Measured: Up to 2500 ms after stimuli presentation. Averaged over all trials for each task condition. All data collected during 8 5-minute sessions on the same day
Secondary outcomes (1)
Reaction time (numerical)
Comparison of subjects' response times to stimuli
Measured: Up to 2500 ms after stimuli presentation. All data collected during 8 5-minute sessions on the same day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2023
- Study start15 Jan 2024
- Primary completionJul 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug Resistant EpilepsyStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Collaborators
- University of Geneva, Switzerland
- Responsible party
- Principal investigator, Fabienne PICARD, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05997758
- Sponsor's protocol ID
- 2022-02041
- Status last verified
- May 2024
- First submitted
- 1 Jun 2023
- Last updated
- 8 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
d'Acremont M, Bossaerts P. Neural Mechanisms Behind Identification of Leptokurtic Noise and Adaptive Behavioral Response. Cereb Cortex. 2016 Apr;26(4):1818-1830. doi: 10.1093/cercor/bhw013. Epub 2016 Feb 4.
PubMed 26850528
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Surprise Signals in the Anterior Insula in Epilepsy Patients With Stereoelectroencephalography Recording
- ClinicalTrials.gov ID
- NCT05997758
- Acronym / sponsor ID
- 2022-02041
- Conditions
- Drug Resistant Epilepsy, Healthy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Collaborators
- University of Geneva, Switzerland
- Study start
- 15 Jan 2024 (actual)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 18 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose a behavioral experiment with SEEG recording and stimulation, to both confirm the role of a brain region known as the anterior insula in identifying surprise, and disambiguate between competing principles behind adaptation: optimizing and satisficing. Optimizers continue to learn and adapt if performance can be improved, while satisficers are satisfied with a good enough performance and will cease adapting once that is reached.
To study surprise signals in the anterior insula, a brain structure where these signals have been very prominent, the investigators will employ an experiment with subjects who are under SEEG (stereoelectroencephalogram) recording, that is, recording from electrodes which have been surgically implanted in the brain. These recordings will be done as patients perform a task where they try to anticipate the movements of a target on a line in two different learning environments (conditions). The experimenters will then determine whether these signals reflect surprise relative to past engagement with the environment, or surprise that reveals that the agent no longer feels in control because uncertainty is not in line with the reference model. If evidence is consistent with the former, adaptation reflects traditional reinforcement and aims at optimizing behavior. If evidence instead is consistent with the latter, behavior is guided by a prior model (a reference model) and behavior is satisficing.
An fMRI study by d'Acremont and Bossaerts provides initial evidence that activation in the anterior insula supports the satisficing hypothesis, however it lacks the temporal granularity to completely rule out optimizing. In the current project, the investigators propose to use the higher time resolution of SEEG recordings to confirm these findings and reject the optimizing hypothesis.
Additionally, stimulations of the anterior insula during a subset of trials will be used to determine whether insular activation following surprise signals and preceding changes in behavior (learning) is merely correlational or in fact causal. Stimulation will allow us to determine to what extent the subjects' sense of control and subsequent behavior can be influenced in accordance with surprise-based modeling of behavior.
The cohort for this study will be patients with drug-resistant, focal epilepsy and who are hospitalized at the Hôpitaux Universitaires de Genève (HUG) for pre-surgical evaluation of their epilepsy using SEEG. The protocol will run in parallel with the patients' clinical procedures.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Other: SEEG stimulation, Behavioral: Adaptation taskPatients who suffer from potentially surgically remediable drug-resistant focal epilepsy and who require evaluation with intracranial stereo-EEG electrodes and have them implanted in the anterior insula. N = 10 |
| Subclinical | – | Behavioral: Adaptation taskHealthy individuals who match the clinical population in age and level of education. N = 40 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who suffer from potentially surgically remediable drug-resistant focal epilepsy and require evaluation with intracranial stereo-EEG electrodes and have them implanted in the anterior insula hospitalized at the Hôpitaux Universitaires Genève.
Key inclusion criteria (5 listed)
- 18 years or older
- Fluent in French or English
- Patient who suffers from potentially surgically remediable drug-resistant focal epilepsy
- Patient who requires evaluation with intracranial stereo-EEG electrodes and has them implanted in the anterior insula
- Patient who is able and willing to provide informed consent
Key exclusion criteria (7 listed)
- Severe concomitant psychiatric disease or major psychological distress
- Patients who have an implanted stimulation device (e.g. pacemaker, defibrillator, neurostimulator)
- Intellectual/neurological/psychiatric deficiencies* or inability to understand or follow the procedure
- Visual/motor deficiencies which could affect task performance
- The presence of seizures during routine clinical stimulation of insular electrodes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SEEG stimulationElectrodes already implanted in patient's anterior insula will be stimulated below the patient-specific threshold at which a seizure was induced. This stimulations will coincide with certain trials in the adaptation task. | Other | Patients |
| Adaptation taskParticipants will perform a task that requires them to learn and correctly respond to outliers of two sorts; inconsequential outliers, which require no action, and outliers that are relevant to the course of stimuli and outcomes in future trials, requiring adaptive action. | Behavioural | Patients, Subclinical |
Primary outcome
Bias adjustment -- non-stimulation trials (behavioral, numerical)
Time frame: Up to 2500 ms after stimuli presentation. All data collected during eight 5-minute sessions on the same day
Subjects' choices, measured as the degree of bias correction they employ (a numerical value typically between 0 and +/-3) during outlier trials and the trials immediately following them. These will be quantitatively compared between conditions using Bayes-optimal choices and choices as predicted by Model-Reference Based Adaptive Control.
Bias adjustment -- stimulation trials (behavioral, numerical)
Time frame: Up to 2500 ms after stimuli presentation. All data collected during four 5-minute sessions on the same day
Subjects' choices, measured as the degree of bias correction they employ (a numerical value typically between 0 and +/-3) during stimulation trials (both outlier and non-outlier trials). These will be quantitatively compared to choices on the same trial types without stimulation.
SEEG-ERP--non-stimulation trials
Time frame: Up to 2500 ms after stimuli presentation. Averaged over all trials for each task condition. All data collected during 8 5-minute sessions on the same day
Event-related potentials (ERPs) extracted from subjects' stereoelectroencephalographies from intercranial electrodes implanted in the anterior insulae. ERPs will be averaged across the time series and t-statistics will be computed for effect of condition (outlier type).
SEEG-TF--non-stimulation trials
Time frame: Up to 2500 ms after stimuli presentation. Averaged over all trials for each task condition. All data collected during 8 5-minute sessions on the same day
The stereoelectroencephalographies from intercranial electrodes implanted in subjects' anterior insulae will be used for time frequency (TF) analyses. Time series components will be extracted for multiple frequencies and t-statistics of the effects of condition (outlier type) will be computed for each frequency.
1 secondary outcome
Reaction time (numerical)
Time frame: Up to 2500 ms after stimuli presentation. All data collected during 8 5-minute sessions on the same day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Background: PubMed 26850528d'Acremont M, Bossaerts P. Neural Mechanisms Behind Identification of Leptokurtic Noise and Adaptive Behavioral Response. Cereb Cortex. 2016 Apr;26(4):1818-1830. doi: 10.1093/cercor/bhw013. Epub 2016 Feb 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Drug Resistant Epilepsy and Healthy, run by University Hospital, Geneva at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fabienne Picard, MD (+41 22 372 5258, Fabienne.Picard@hcuge.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bias adjustment -- non-stimulation trials (behavioral, numerical) (time frame: Up to 2500 ms after stimuli presentation. All data collected during eight 5-minute sessions on the same day). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05997758, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024; AzTrials last refreshed its copy on 7 Nov 2026.