Clinical trial NCT05997758: Investigating Surprise Signals in the Anterior Insula
Official title: Investigating Surprise Signals in the Anterior Insula in Epilepsy Patients With Stereoelectroencephalography Recording
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Drug Resistant Epilepsy
Healthy
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: University of Geneva, Switzerland
First posted: 2023-08-18
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Bias adjustment -- non-stimulation trials (behavioral, numerical)
timeFrame: Up to 2500 ms after stimuli presentation. All data collected during eight 5-minute sessions on the same day
measure: Bias adjustment -- stimulation trials (behavioral, numerical)
timeFrame: Up to 2500 ms after stimuli presentation. All data collected during four 5-minute sessions on the same day
measure: SEEG-ERP--non-stimulation trials
timeFrame: 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
measure: SEEG-TF--non-stimulation trials
timeFrame: 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:
measure: Reaction time (numerical)
timeFrame: Up to 2500 ms after stimuli presentation. All data collected during 8 5-minute sessions on the same day
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Service de Neurologie, Dpt des Neurosciences cliniques HUG
Study officials:
References:
citation: 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.