Contributions of primate prefrontal cortex and medial temporal lobe to temporal-order memory

Abstract

Neuropsychological and neurophysiological studies have emphasized the role of the prefrontal cortex (PFC) in maintaining information about the temporal order of events or items for upcoming actions. However, the medial temporal lobe (MTL) has also been considered critical to bind individual events or items to their temporal context in episodic memory. Here we characterize the contributions of these brain areas by comparing single-unit activity in the dorsal and ventral regions of macaque lateral PFC (d-PFC and v-PFC) with activity in MTL areas including the hippocampus (HPC), entorhinal cortex, and perirhinal cortex (PRC) as well as in area TE during the encoding phase of a temporal-order memory task. The v-PFC cells signaled specific items at particular time periods of the task. By contrast, MTL cortical cells signaled specific items across multiple time periods and discriminated the items between time periods by modulating their firing rates. Analysis of the temporal dynamics of these signals showed that the conjunctive signal of item and temporal-order information in PRC developed earlier than that seen in v-PFC. During the delay interval between the two cue stimuli, while v-PFC provided prominent stimulus-selective delay activity, MTL areas did not. Both regions of PFC and HPC exhibited an incremental timing signal that appeared to represent the continuous passage of time during the encoding phase. However, the incremental timing signal in HPC was more prominent than that observed in PFC. These results suggest that PFC and MTL contribute to the encoding of the integration of item and timing information in distinct ways.

The development of spatiotemporal organization of episodic memory in children and its disruption in Williams Syndrome

“…Interestingly, despite a clear and consistent deficit in spatio-temporal and episodic recall, the spared memory for sequences of objects in WS suggests a relative independence of object-related processes within the episodic system that might rely in part on connections with the prefrontal cortex (Naya et al, 2017). Additionally, this objectrelated success is consistent with spatial navigation studies that show better landmark use in WS compared with children similar in mental age (Lakusta et al, 2010).…”

A temporal record of the past with a spectrum of time constants in the monkey entorhinal cortex

“…The current results are consistent with previous findings in the monkey. A recent investigation of single-neuron activity across shorter timescales (within a ∼1 s delay) identified timevarying responses in the hippocampus, but not the entorhinal cortex 13 . However, in earlier work with longer trial durations, entorhinal neurons exhibited response dynamics across several seconds 45 .…”

“…Building on pioneering work demonstrating a spatial code in the hippocampus and entorhinal cortex 6,7 , recent research has shown that hippocampal representations also carry information about the time at which past events took place, suggesting that the MTL maintains a representation of spatiotemporal context in support of episodic memory [8][9][10] . Although a great deal is known about the temporal coding properties of neurons in the hippocampus, the temporal code in the entorhinal cortex, which provides the majority of the cortical input to the hippocampus is less understood, but see [11][12][13][14] .Hippocampal time cells provide a record of recent events including explicit information about when an event occurred. Analogous to hippocampal place cells that fire when an animal is in a circumscribed region of physical space 6, 15 , hippocampal time cells fire during a circumscribed period of time within unfilled delays 8,9,16 .…”

Hippocampal cells integrate past memory and present perception for the future

“…We also constructed individual brain atlases based on the electrophysiological properties around the tip of the electrode (e.g., grey matter, white matter, sulcus, lateral ventricle, and bottom of the brain). The recording sites were estimated by combining the individual MRI atlases and physiological atlases (45).…”