Spatial Scene Recognition Memory in Epilepsy Surgery

Official title

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

Overview

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

• 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 therape
• 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 te
• 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.

Primary outcome measures

• Scene familiarity discrimination accuracy [Time frame: 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 [Time frame: 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) [Time frame: 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) [Time frame: During EEG recording session]
• Intracranial theta and gamma power and connectivity during familiarity judgments (Aim III) [Time frame: During intracranial EEG monitoring (typically 1-2 weeks hospital stay)]

Secondary outcome measures (6)

• Déjà vu report rate [Time frame: During testing sessions with the virtual tour]
• Vividness of Visual Imagery Questionnaire, Second Edition (VVIQ-2) scores (Aim I) [Time frame: During testing session]
• Hyperfamiliarity commission errors [Time frame: During testing session]
• Neuropsychological test performance (Aim I) [Time frame: Pre-surgery and 6 months / 1 year post-surgery]
• Single-unit firing rate (subset of patients in Aim III) [Time frame: During intracranial EEG monitoring]
• Single-unit stimulus selectivity (subset of patients in Aim III) [Time frame: During intracranial EEG monitoring]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 2 centers

• UC Davis Medical Center — Sacramento
• Emory University Hospital — Atlanta

Identifiers

NCT: NCT07580183 · 2347891

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗