Abstracts

Rationale: Patients with medial temporal lobe (MTL) epilepsy commonly experience memory deficits. The exact circuit-level dysfunction leading to specific kinds of memory impairment remain unknown. Prior work has identified three different functional types of cells within the human MTL whose response is related to specific aspects of episodic memory: memory selective (MS) neurons (Rutishauser et al., 2015), visually selective (VS) neurons, and animal responsive (AR) (Mormann et al., 2011). We characterized the properties of MS, VS, and AR cells separately for neurons located within and outside the seizure onset zone (SOZ) to identify a neuronal correlate of impaired memory due to epilepsy.

Methods: A total of 1973 single neurons in the medial temporal lobes (MTL) were recorded from 62 patients who performed a visual recognition memory task with implanted hybrid depth electrodes. We compared the number and tuning strength of MS, VS, and AR neurons between the pathologic SOZ and the non-epileptic zone and correlated these electrophysiologic findings with the subjects’ memory task performance and neuropsychological scores.

Results: We detected 159 MS, 366 VS, and 298 AR neurons across all subjects. Behaviorally, subjects with a SOZ in the right MTL had impaired memory retrieval ability as demonstrated by a change in the shape of the ROC curve compared to those with a left MTL SOZ (zROC values of left vs. right, 95%CI = -1.06, -0.074; P = 0.021). Neuronally, while MS cells were present in both the SOZ and the non-SOZ, the responses of MS neurons located in the right MTL SOZ were impaired (effect size metric “ω2” quantifying neuronal selectivity, inside vs. outside SOZ; P = 0.0024) when subjects’ made high-confidence retrieval decisions. In contrast, the response of VS neurons, which signal categorical identity (a kind of semantic memory), were unaffected regardless of their location in the SOZ (ω2 inside vs. outside SOZ; P = 0.32). AR neurons, which are thought to have a unique role only in the amygdala, showed reduced responses only when located within the amygdala of the MTL SOZ (ω2 inside vs. outside SOZ; P = 0.048). In addition to our memory task, the visual reproduction subtest scores from the Wechsler Memory Scale were significantly lower only for right-sided SOZ patients compared to the normative distribution (P = 0.01).

Conclusions: Subjects with a right-sided MTL SOZs displayed impaired visual recognition memory. Here, we present the first evidence that these deficits can be mechanistically explained on a single neuron level. Only a specific subset of neurons involved in declarative memory were disrupted within the SOZ, whereas other cell types retain their properties even within the SOZ. This data shows that cell specific responses of selective neurons within the SOZ can be used to assess the causal effects of local circuit disruption by the SOZ. Our results establish a neural correlate of cognitive impairment that we predict can serve as a target and biomarker for future novel treatments to restore memory function in patients suffering from temporal lobe epilepsy.

Funding: Please list any funding that was received in support of this abstract.: Grant supported by the NIMH (R01MH110831) and NINDS (U01NS117839) to UR.