xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05997758</url>
    </required_header>
    <id_info>
      <org_study_id>2022-02041</org_study_id>
      <nct_id>NCT05997758</nct_id>
    </id_info>
    <brief_title>Investigating Surprise Signals in the Anterior Insula</brief_title>
    <official_title>Investigating Surprise Signals in the Anterior Insula in Epilepsy Patients With Stereoelectroencephalography Recording</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Geneva</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Geneva, Switzerland</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University Hospital, Geneva</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The investigators propose a behavioral experiment with SEEG recording and stimulation, to&#xD;
        both confirm the role of a brain region known as the anterior insula in identifying surprise,&#xD;
        and disambiguate between competing principles behind adaptation: optimizing and satisficing.&#xD;
        Optimizers continue to learn and adapt if performance can be improved, while satisficers are&#xD;
        satisfied with a good enough performance and will cease adapting once that is reached.&#xD;
  &#xD;
        To study surprise signals in the anterior insula, a brain structure where these signals have&#xD;
        been very prominent, the investigators will employ an experiment with subjects who are under&#xD;
        SEEG (stereoelectroencephalogram) recording, that is, recording from electrodes which have&#xD;
        been surgically implanted in the brain. These recordings will be done as patients perform a&#xD;
        task where they try to anticipate the movements of a target on a line in two different&#xD;
        learning environments (conditions). The experimenters will then determine whether these&#xD;
        signals reflect surprise relative to past engagement with the environment, or surprise that&#xD;
        reveals that the agent no longer feels in control because uncertainty is not in line with the&#xD;
        reference model. If evidence is consistent with the former, adaptation reflects traditional&#xD;
        reinforcement and aims at optimizing behavior. If evidence instead is consistent with the&#xD;
        latter, behavior is guided by a prior model (a reference model) and behavior is satisficing.&#xD;
  &#xD;
        An fMRI study by d'Acremont and Bossaerts provides initial evidence that activation in the&#xD;
        anterior insula supports the satisficing hypothesis, however it lacks the temporal&#xD;
        granularity to completely rule out optimizing. In the current project, the investigators&#xD;
        propose to use the higher time resolution of SEEG recordings to confirm these findings and&#xD;
        reject the optimizing hypothesis.&#xD;
  &#xD;
        Additionally, stimulations of the anterior insula during a subset of trials will be used to&#xD;
        determine whether insular activation following surprise signals and preceding changes in&#xD;
        behavior (learning) is merely correlational or in fact causal. Stimulation will allow us to&#xD;
        determine to what extent the subjects' sense of control and subsequent behavior can be&#xD;
        influenced in accordance with surprise-based modeling of behavior.&#xD;
  &#xD;
        The cohort for this study will be patients with drug-resistant, focal epilepsy and who are&#xD;
        hospitalized at the Hôpitaux Universitaires de Genève (HUG) for pre-surgical evaluation of&#xD;
        their epilepsy using SEEG. The protocol will run in parallel with the patients' clinical&#xD;
        procedures.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">July 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Cross-Sectional</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Bias adjustment -- non-stimulation trials (behavioral, numerical)</measure>
      <time_frame>Up to 2500 ms after stimuli presentation. All data collected during eight 5-minute sessions on the same day</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Bias adjustment -- stimulation trials (behavioral, numerical)</measure>
      <time_frame>Up to 2500 ms after stimuli presentation. All data collected during four 5-minute sessions on the same day</time_frame>
      <description>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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SEEG-ERP--non-stimulation trials</measure>
      <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</time_frame>
      <description>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).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SEEG-TF--non-stimulation trials</measure>
      <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</time_frame>
      <description>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.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Reaction time (numerical)</measure>
      <time_frame>Up to 2500 ms after stimuli presentation. All data collected during 8 5-minute sessions on the same day</time_frame>
      <description>Comparison of subjects' response times to stimuli</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Drug Resistant Epilepsy</condition>
    <condition>Healthy</condition>
    <arm_group>
      <arm_group_label>Patients</arm_group_label>
      <description>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.&#xD;
  N = 10</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Subclinical</arm_group_label>
      <description>Healthy individuals who match the clinical population in age and level of education.&#xD;
  N = 40</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>SEEG stimulation</intervention_name>
      <description>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.</description>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Adaptation task</intervention_name>
      <description>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.</description>
      <arm_group_label>Patients</arm_group_label>
      <arm_group_label>Subclinical</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Patients who suffer from potentially surgically remediable drug-resistant focal epilepsy&#xD;
          and require evaluation with intracranial stereo-EEG electrodes and have them implanted in&#xD;
          the anterior insula hospitalized at the Hôpitaux Universitaires Genève.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18 years or older&#xD;
  &#xD;
            -  Fluent in French or English&#xD;
  &#xD;
            -  Patient who suffers from potentially surgically remediable drug-resistant focal&#xD;
               epilepsy&#xD;
  &#xD;
            -  Patient who requires evaluation with intracranial stereo-EEG electrodes and has them&#xD;
               implanted in the anterior insula&#xD;
  &#xD;
            -  Patient who is able and willing to provide informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Severe concomitant psychiatric disease or major psychological distress&#xD;
  &#xD;
            -  Patients who have an implanted stimulation device (e.g. pacemaker, defibrillator,&#xD;
               neurostimulator)&#xD;
  &#xD;
            -  Intellectual/neurological/psychiatric deficiencies* or inability to understand or&#xD;
               follow the procedure&#xD;
  &#xD;
            -  Visual/motor deficiencies which could affect task performance&#xD;
  &#xD;
            -  The presence of seizures during routine clinical stimulation of insular electrodes&#xD;
  &#xD;
            -  Failure to complete the pre-experiment task training&#xD;
  &#xD;
                 -  As determined by their clinical evaluation.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Fabienne Picard, MD</last_name>
      <phone>+41 22 372 5258</phone>
      <email>Fabienne.Picard@hcuge.ch</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Nina Sooter</last_name>
      <phone>+41 79 6791 949</phone>
      <email>nina.sooter@unige.ch</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Service de Neurologie, Dpt des Neurosciences cliniques HUG</name>
        <address>
          <city>Geneva</city>
          <zip>1205</zip>
          <country>Switzerland</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Switzerland</country>
    </location_countries>
    <reference>
      <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.</citation>
      <PMID>26850528</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 11, 2023</last_update_submitted>
    <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University Hospital, Geneva</investigator_affiliation>
      <investigator_full_name>Fabienne PICARD</investigator_full_name>
      <investigator_title>Prof</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Epilepsy</mesh_term>
      <mesh_term>Drug Resistant Epilepsy</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05997758
  org study id: 2022-02041
  nct id: NCT05997758
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  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.
  observational model: Case-Control
  time perspective: Cross-Sectional
  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
  description: 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.
  measure: 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
  description: 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.
  measure: 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
  description: 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).
  measure: 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
  description: 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.
  measure: Reaction time (numerical)
  time frame: Up to 2500 ms after stimuli presentation. All data collected during 8 5-minute sessions on the same day
  description: Comparison of subjects' response times to stimuli
  arm group label: Patients
  description: 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
  arm group label: Subclinical
  description: Healthy individuals who match the clinical population in age and level of education.
  N = 40
  intervention type: Other
  intervention name: SEEG stimulation
  description: 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.
  arm group label: Patients
  intervention type: Behavioral
  intervention name: Adaptation task
  description: 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.
  arm group label: Patients
  arm group label: Subclinical
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Fabienne Picard, MD
  phone: +41 22 372 5258
  email: Fabienne.Picard@hcuge.ch
  last name: Nina Sooter
  phone: +41 79 6791 949
  email: nina.sooter@unige.ch
  facility: 
  country: Switzerland
  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.
  PMID: 26850528
  responsible party type: Principal Investigator
  investigator affiliation: University Hospital, Geneva
  investigator full name: Fabienne PICARD
  investigator title: Prof
  mesh term: Epilepsy
  mesh term: Drug Resistant Epilepsy