The ability to remember what happened where and when constitutes the basic fabric of our memories and who we are. Forming and recalling memories depends on detecting novelty, building associations to prior knowledge, and dynamically retrieving context-relevant information. Previous studies have scrutinized the neural machinery for individual components of recognition or associative memory under laboratory conditions, such as recalling elements from arbitrary lists of words or pictures. In this study, we implemented a well-known card-matching game that integrates multiple components of memory formation together in a naturalistic setting to investigate the dynamic neural processes underlying complex natural human memory. We recorded intracranial field potentials from 1,750 depth or subdural electrodes implanted in 20 patients with pharmacologically-intractable epilepsy while they were performing the task. We leveraged generalized linear models to simultaneously assess the relative contribution of neural responses to distinct task components. Neural activity in the gamma frequency band signaled novelty and graded degrees of familiarity, represented the strength and outcome of associative recall, and finally reflected visual feedback on a trial-by-trial basis. The large-scale data and models enable dissociating and at the same time dynamically tracing the different cognitive components during fast, complex, and natural human memory behaviors.

Introduction: In this report, we aim to describe the design for the randomized controlled trial of Stereotactic-electroencephalogram (EEG) guided Radiofrequency Thermocoagulation versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (STARTS). Mesial temporal lobe epilepsy (mTLE) is a classical subtype of temporal lobe epilepsy that often requires surgical intervention. Although anterior temporal lobectomy (ATL) remains the most popular treatment for mTLE, accumulating evidence has indicated that ATL can cause tetartanopia and memory impairments. Stereotactic EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) is a non-invasive alternative associated with lower seizure freedom but greater preservation of neurological function. In the present study, we aim to compare the safety and efficacy of SEEG-guided RF-TC and classical ATL in the treatment of mTLE. Methods and analysis: STARTS is a single-centre, two-arm, randomised controlled, parallel-group clinical trial. The study includes patients with typical mTLE over the age of 14 who have drug-resistant seizures for at least 2 years and have been determined via detailed evaluation to be surgical candidates prior to randomisation. The primary outcome measure is cognitive function at the 1-year follow-up after treatment. Seizure outcomes, visual field abnormalities after surgery, quality of life, ancillary outcomes, and adverse events will also be evaluated at 1-year follow-up as secondary outcomes. Disscussion: SEEG-guided RF-TC for mTLE remains a controversial seizure outcome but has the advantage for cognitive and visual filed protection. This is the first RCT studying cognitive outcomes and treatment results between SEEG-guided RF-TC and standard ATL for mTLE with hippocampal sclerosis. This study may provide a higher levels of clinical evidence for the treatment for mTLE. Trial registration: The STARTS protocol has been registered on the US National Institutes of Health (ClinicalTrials.gov): NCT03941613. The status of the STARTS was recruiting and the estimated study completion date was December 31, 2021.