Spatial Scene Recognition Memory in Epilepsy Surgery

Investigations of Spatial Recognition Memory to Improve Cognitive Outcomes in Epilepsy Surgery

This study investigates the anatomical and physiological basis of spatial scene recognition memory in patients with temporal lobe epilepsy and temporal lobe lesions. Standard neuropsychological tests are insensitive to important memory deficits experienced by patients, particularly in spatial/scene memory, recollective experience, and familiarity processing. Using a validated virtual tour paradigm, the study examines how familiarity-based recognition and recall of spatial scenes relate to specific brain structures. In Aim I, a large cohort of patients with varied temporal lobe lesions at Emory University undergoes the virtual tour task with voxel-based lesion-symptom mapping to localize necessary brain regions. In Aim II, scalp event-related potentials and eye tracking in healthy participants at UC Davis characterize the temporal dynamics and lateralization of scene recognition. In Aim III, intracranial EEG recordings (including local field potentials and single-unit activity) in epilepsy surgery patients at UC Davis determine the precise network dynamics underlying spatial scene familiarity and recall. The long-term goal is to improve the prediction and prevention of cognitive morbidity from epilepsy surgery by providing a more complete model of spatial recognition memory circuits.

Study Overview

• Status: Recruiting
• Conditions: Memory Disorders; Focal Epilepsy; Temporal Lobe Epilepsy; Epilepsy, Temporal Lobe; Epilepsy Intractable; Memory Deficits; Spatial Perception; Memory Dysfunction; Epilepsy Surgery; Medically Refractory Epilepsy; Memory Disorder, Spatial; Epilepsy Comorbidities
• Intervention / Treatment: Behavioral: Virtual Tour Recognition Memory Task; Diagnostic test: MRI Neuroimaging and Neuropsychological Assessment (Aim I); Device: Intracranial EEG Recording with Research Electrodes (Aim III only)

Detailed Description

Recognition memory can be divided into familiarity (a sense that something has been encountered before) and recollection (identification or elaborative recall). Patients with temporal lobe epilepsy often report subjective memory difficulties that are not captured by conventional neuropsychological tests, which lack assessments of true episodic and scene memory. This study uses a virtual tour paradigm that objectively separates familiarity-based recognition from recall for spatial scenes. The central hypothesis is that spatial scene recognition memory critically involves the convergence of dorsal and ventral visual streams in the inferior parietal lobule and parahippocampal gyrus, with familiarity-based recognition involving neocortical structures and recall involving the parahippocampal gyrus, entorhinal cortices, and hippocampus. The study employs three complementary approaches: (1) lesion-symptom mapping in ~310 surgical patients and 150 controls, (2) scalp ERP and eye-tracking in 80 healthy participants, and (3) intracranial electrophysiology (LFP and single-unit recordings) in ~80 patients undergoing stereoelectroencephalography (SEEG) for clinical seizure localization. Research electrodes (FDA-approved Dixi micro-macro or Behnke-Fried with tetrode components) are placed at clinically determined locations to additionally capture single-neuron activity. This study was classified as a Basic Experimental Studies in Humans (BESH) mechanism; it does not evaluate a health-related clinical outcome but uses clinical populations and FDA-approved research electrodes to study basic neuroscience questions about memory.

• Study Type: Interventional
• Enrollment (Estimated): 620
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nigel P Pedersen, MD; Phone Number: 916-734-3251; Email: nppedersen@health.ucdavis.edu

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • Recruiting
      • UC Davis Medical Center
      • Contact: Nigel P Pedersen, MD; Phone Number: 916-734-3251; Email: nppedersen@health.ucdavis.edu
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital
      • Contact: Daniel L Drane, PhD; Phone Number: 404-727-2844; Email: ddrane@emory.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18 years or older
• For Aims I and III: Diagnosis of focal epilepsy or temporal lobe lesion; patients undergoing evaluation for or having undergone epilepsy surgery
• For Aim II: Healthy adult participants
• Full-Scale IQ ≥ 70
• English proficiency sufficient to understand and complete the task
• For Aim I: Enrolled in or eligible for Emory University epilepsy surgery research registry
• For Aim III: Undergoing clinically indicated stereoelectroencephalography (SEEG) at UC Davis Medical Center
• Able to provide informed consent (or for Aim I retrospective component, prior consent in Emory registry)

Exclusion Criteria:

• Full-Scale IQ < 70
• Inability to provide informed consent
• For Aim III: Age > 55 years
• For Aim II: History of neurological or psychiatric disorder (as applicable per study protocol)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aim I: Lesion-Symptom Mapping; Patients with temporal lobe lesions (n≈310) and healthy controls (n≈150) at Emory University. Retrospective cohort with existing surgical lesions plus prospectively enrolled new surgical patients (~60 over 5 years). Intervention(s): Behavioral: Virtual Tour Recognition Memory Task; Diagnostic: MRI neuroimaging and neuropsychological assessment	Behavioral: Virtual Tour Recognition Memory Task; Participants are passively navigated through virtual tour scenes (5-second video clips) during a study phase and are asked to generate descriptive names for each scene. During the test phase, they view novel, spatially similar (same configuration, different objects), or identical scenes and rate familiarity, indicate old/new judgments, report déjà vu sensations, and attempt to recall scene names. The task consists of two study-test blocks. This is a cognitive/behavioral assessment, not a therapeutic intervention.; Diagnostic test: MRI Neuroimaging and Neuropsychological Assessment (Aim I); Pre- and post-surgical structural MRI (T1-weighted, diffusion-weighted imaging, resting-state fMRI) obtained as part of the clinical epilepsy surgery evaluation at Emory University. Extensive neuropsychological battery administered pre- and post-operatively (6 months and 1 year) including Wechsler memory scales, Rey-Osterrieth Complex Figure, confrontation naming, and additional measures.
Experimental: Aim II: Scalp ERP Study; Healthy participants (n=80) recruited from UC Davis campus community. Intervention: Behavioral: Virtual Tour Recognition Memory Task (still-image version) during Scalp EEG/ERP recording and eye tracking	Behavioral: Virtual Tour Recognition Memory Task; Participants are passively navigated through virtual tour scenes (5-second video clips) during a study phase and are asked to generate descriptive names for each scene. During the test phase, they view novel, spatially similar (same configuration, different objects), or identical scenes and rate familiarity, indicate old/new judgments, report déjà vu sensations, and attempt to recall scene names. The task consists of two study-test blocks. This is a cognitive/behavioral assessment, not a therapeutic intervention.
Experimental: Aim III: Intracranial EEG; Patients with epilepsy undergoing clinically indicated SEEG (n≈80) at UC Davis Medical Center. Behavioral Intervention: Virtual Tour Recognition Memory Task; Other Intervention: Intracranial EEG recording via clinically placed electrodes, a minority of which have research microelectrodes (FDA-approved Dixi micro-macro or Behnke-Fried Ad-Tech electrodes)	Behavioral: Virtual Tour Recognition Memory Task; Participants are passively navigated through virtual tour scenes (5-second video clips) during a study phase and are asked to generate descriptive names for each scene. During the test phase, they view novel, spatially similar (same configuration, different objects), or identical scenes and rate familiarity, indicate old/new judgments, report déjà vu sensations, and attempt to recall scene names. The task consists of two study-test blocks. This is a cognitive/behavioral assessment, not a therapeutic intervention.; Device: Intracranial EEG Recording with Research Electrodes (Aim III only); Patients undergoing clinically indicated stereoelectroencephalography (SEEG) for seizure localization have electrodes implanted at locations determined solely by clinical need. In a subset of patients, FDA-approved research electrodes (Dixi micro-macro electrodes or Behnke-Fried As-Tech electrodes with tetrode components) substitute standard clinical electrodes at the same clinically determined locations. These electrodes have the same geometry as clinical electrodes and are FDA-approved. The tetrode component enables single-neuron recording for research purposes and adds no additional risk. Electrode placement is not altered by study participation. Local field potentials (LFP) and, where available, single-unit data are recorded during the virtual tour task and resting state.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scene familiarity discrimination accuracy	Rate of correct familiarity judgments for spatially similar test scenes versus novel scenes (recognition without identification/RWI effect), measured as the proportion of "familiar" responses to configurally matched scenes minus false alarm rate to novel scenes.	From enrollment until the end of eight weeks, during which time testing is scheduled (Aim II), or during the hospitalization for invasive EEG studies (Aim III). Participants in Aim I can undergo repeat testing (six months, one year, etc.)
Scene recall accuracy	Proportion of test scenes for which participants correctly recall the name or identifying details of the corresponding study scene (verified recall), separately for identical repeat scenes and configurally similar scenes.	From enrollment until the end of eight weeks, during which time testing is scheduled (Aim II), or during the hospitalization for invasive EEG studies (Aim III). Participants in Aim I can undergo repeat testing (six months, one year, etc.)
Lesion-symptom correlation for familiarity and recall (Aim I)	Voxel-based lesion-symptom mapping (VBLSM) correlating surgical lesion volumes in temporal lobe subregions (temporopolar, perirhinal, entorhinal, parahippocampal, hippocampal) with familiarity and recall behavioral scores.	Testing is scheduled within eight weeks of enrollment for all patients, with repeat testing at six and 12 months after surgery for those enrolled pre-operatively
ERP amplitude and latency associated with familiarity and recall (Aim II)	Amplitude and latency of event-related potential components (FN400, late positive component) in specified scalp regions (e.g., LAS, RAS, LPS, RPS) as a function of scene familiarity and recall conditions.	During EEG recording session
Intracranial theta and gamma power and connectivity during familiarity judgments (Aim III)	Theta (3-7 Hz) and gamma-band (30-150 Hz) event-related synchronization/desynchronization in parahippocampal, perirhinal, entorhinal, and hippocampal contacts during familiarity versus recall conditions, plus functional connectivity measures (imaginary coherence, phase-amplitude coupling).	During intracranial EEG monitoring (typically 1-2 weeks hospital stay)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Déjà vu report rate	Proportion of test trials in which participants report a feeling of déjà vu, analyzed by scene condition (similar, repeat, novel).	During testing sessions with the virtual tour
Vividness of Visual Imagery Questionnaire, Second Edition (VVIQ-2) scores (Aim I)	Self-reported vividness of visual imagery correlated with lesion location and recognition memory performance. The VVIQ-2 is a 32-item self-report questionnaire in which each item is rated on a scale from 1 (no image at all) to 5 (perfectly clear and vivid). Total scores range from 32 to 160. Higher scores indicate more vivid visual imagery.	During testing session
Hyperfamiliarity commission errors	Rate of false positive familiarity judgments for novel scenes (false alarms), as a measure of hyperfamiliarity.	During testing session
Neuropsychological test performance (Aim I)	Standard neuropsychological battery scores (Wechsler Memory Scale, Rey-Osterrieth Complex Figure, confrontation naming, etc.) correlated with virtual tour performance and lesion characteristics.	Pre-surgery and 6 months / 1 year post-surgery
Single-unit firing rate (subset of patients in Aim III)	Mean firing rate (spikes per second) of individual neurons recorded from parahippocampal and perirhinal cortex during familiarity versus recall conditions, in patients with tetrode/microelectrode recordings.	During intracranial EEG monitoring
Single-unit stimulus selectivity (subset of patients in Aim III)	Selectivity index (area under the receiver operating characteristic curve) quantifying the discriminability of familiar versus novel scene conditions in individual neurons recorded from parahippocampal and perirhinal cortex, in patients with tetrode/microelectrode recordings.	During intracranial EEG monitoring

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: Emory University

Publications and helpful links

Helpful Links

• NIH Reporter Project Description

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: neuropsychology; event-related potentials; consciousness; hippocampus; SEEG; epilepsy surgery; spatial memory; familiarity; intracranial EEG; stereo-electroencephalography; recognition memory; recollection; neural circuits of memory; phenomenology of memory; scene memory; virtual tour; lesion-symptom mapping; network-symptom mapping; cognitive electrophysiology; iEEG; parahippocampal gyrus; perirhinal cortex; tetrodes; deja vu
• Additional Relevant MeSH Terms: Epileptic Syndromes; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurobehavioral Manifestations; Epilepsy; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Spatial Behavior; Drug Resistant Epilepsy; Memory Disorders; Epilepsies, Partial; Epilepsy, Temporal Lobe; Orientation, Spatial
• Other Study ID Numbers: 2347891

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified behavioral data, EEG/ERP data, and intracranial electrophysiology data will be shared via OpenNeuro and Emory Dataverse upon reasonable request. Identifiable data will remain at collection sites.
• IPD Sharing Time Frame: Data will be made available by the end of the performance period or upon publication.
• IPD Sharing Access Criteria: De-identified data will be freely available. Requests prior to publication will be by discussion with the PI. A data use agreement may be required for certain datasets.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No