Epilepsy Comorbidities, Epilepsy Intractable, Epilepsy Surgery, Epilepsy, Temporal Lobe, Focal Epilepsy, Medically Refractory Epilepsy, Memory Deficits, Memory Disorders, Memory Disorder, Spatial, Memory Dysfunction, Spatial Perception, Temporal Lobe Epilepsy
Conditions
Keywords
spatial memory, recognition memory, familiarity, recollection, neural circuits of memory, phenomenology of memory, scene memory, virtual tour, epilepsy surgery, SEEG, stereo-electroencephalography, lesion-symptom mapping, network-symptom mapping, cognitive electrophysiology, event-related potentials, intracranial EEG, iEEG, parahippocampal gyrus, perirhinal cortex, hippocampus, tetrodes, deja vu, neuropsychology, consciousness
Brief summary
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.
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.
Interventions
BEHAVIORALVirtual 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.
DEVICEIntracranial 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.
DIAGNOSTIC_TESTMRI 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.
Sponsors
University of California, Davis
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Note: Under the NIH clinical trial definition used at the time of submission (2024-2025), this study is classified as a clinical trial because participants are prospectively assigned to interventions (cognitive testing paradigms; in Aim III, research electrode recordings). However, the primary purpose is basic science - understanding the neural basis of memory - not evaluating a clinical/health outcome.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Scene familiarity discrimination accuracy | 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.) | 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. |
| Scene recall accuracy | 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.) | 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. |
| Lesion-symptom correlation for familiarity and recall (Aim I) | 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 | 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. |
| ERP amplitude and latency associated with familiarity and recall (Aim II) | During EEG recording session | 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. |
| Intracranial theta and gamma power and connectivity during familiarity judgments (Aim III) | During intracranial EEG monitoring (typically 1-2 weeks hospital stay) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Déjà vu report rate | During testing sessions with the virtual tour | Proportion of test trials in which participants report a feeling of déjà vu, analyzed by scene condition (similar, repeat, novel). |
| Vividness of Visual Imagery Questionnaire, Second Edition (VVIQ-2) scores (Aim I) | During testing session | 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. |
| Hyperfamiliarity commission errors | During testing session | Rate of false positive familiarity judgments for novel scenes (false alarms), as a measure of hyperfamiliarity. |
| Neuropsychological test performance (Aim I) | Pre-surgery and 6 months / 1 year post-surgery | Standard neuropsychological battery scores (Wechsler Memory Scale, Rey-Osterrieth Complex Figure, confrontation naming, etc.) correlated with virtual tour performance and lesion characteristics. |
| Single-unit firing rate (subset of patients in Aim III) | During intracranial EEG monitoring | 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. |
| Single-unit stimulus selectivity (subset of patients in Aim III) | During intracranial EEG monitoring | 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. |
Countries
United States
Contacts
CONTACTNigel P Pedersen, MD
Outcome results
None listed