Grid cells in the entorhinal cortex appear to represent spatial location via a triangular coordinate system. Such cells, which have been identified in rats, bats, and monkeys, are believed to support a wide range of spatial behaviors. By recording neuronal activity from neurosurgical patients performing a virtual-navigation task we identified cells exhibiting grid-like spiking patterns in the human brain, suggesting that humans and simpler animals rely on homologous spatial-coding schemes.

BACKGROUND The medial temporal structures, including the hippocampus and the entorhinal cortex, are critical for the ability to transform daily experience into lasting memories. We tested the hypothesis that deep-brain stimulation of the hippocampus or entorhinal cortex alters memory performance. METHODS We implanted intracranial depth electrodes in seven subjects to identify seizure-onset zones for subsequent epilepsy surgery. The subjects completed a spatial learning task during which they learned destinations within virtual environments. During half the learning trials, focal electrical stimulation was given below the threshold that elicits an afterdischarge (i.e., a neuronal discharge that occurs after termination of the stimulus). RESULTS Entorhinal stimulation applied while the subjects learned locations of landmarks enhanced their subsequent memory of these locations: the subjects reached these landmarks more quickly and by shorter routes, as compared with locations learned without stimulation. Entorhinal stimulation also resulted in a resetting of the phase of the theta rhythm, as shown on the hippocampal electroencephalogram. Direct hippocampal stimulation was not effective. In this small series, no adverse events associated with the procedure were observed. CONCLUSIONS Stimulation of the entorhinal region enhanced memory of spatial information when applied during learning. (Funded by the National Institutes of Health and the Dana Foundation.)

OBJECTIVE An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1–3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol. METHOD MRI scans of a single healthy adult human subject were acquired both at 3 Tesla and 7 Tesla. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities of their choice. The resulting set of 21 segmentations was analyzed in a common anatomical space to quantify similarity and identify areas of agreement. RESULTS The differences between the 21 protocols include the region within which segmentation is performed, the set of anatomical labels used, and the extents of specific anatomical labels. The greatest overall disagreement among the protocols is at the CA1/subiculum boundary, and disagreement across all structures is greatest in the anterior portion of the hippocampal formation relative to the body and tail. CONCLUSIONS The combined examination of the 21 protocols in the same dataset suggests possible strategies towards developing a harmonized subfield segmentation protocol and facilitates comparison between published studies.

Sleep deprivation (SD) is a major source of morbidity with widespread health effects including increased risks of hypertension, diabetes, obesity, heart attack, and stroke1. Moreover, SD brings about vehicle accidents and medical errors2–4, and is therefore an urgent topic of investigation. During SD, homeostatic and circadian processes interact to build up sleep pressure5 that results in slow behavioral performance (cognitive lapses) typically attributed to attentional thalamic and fronto-parietal circuits6–14, but the underlying mechanisms remain unclear3,15. Recently, it was found in human electroencephalogram (EEG)16,17 and in the local field potential (LFP) of non-human primates18 and rodents19 that during SD, regional ‘sleep-like’ slow/theta waves co-occur with impaired behavioral performance during wakefulness. Here we used intracranial electrodes to record single-neuron and LFP activities in human neurosurgical patients performing a face/non-face categorization psychomotor vigilance task (PVT)20–24 in multiple experimental sessions, including after full-night SD. We find that just before cognitive lapses, selective spiking responses of individual neurons in the medial temporal lobe (MTL) are attenuated, delayed, and lengthened. These ‘neuronal lapses’ are evident on a trial-by-trial basis comparing the slowest behavioral PVT reaction times to the fastest. Furthermore, during cognitive lapses LFPs exhibit a relative local increase in slow/theta activity that is correlated with degraded single-neuron responses and with baseline theta activity. Our results show that cognitive lapses involve local state-dependent changes in neuronal activity already in the MTL.

The advent of high-resolution magnetic resonance imaging (MRI) has enabled in vivo research in a variety of populations and diseases on the structure and function of hippocampal subfields and subdivisions of the parahippocampal gyrus. Due to the many extant and highly discrepant segmentation protocols, comparing results across studies is difficult. To overcome this barrier, the Hippocampal Subfields Group was formed as an international collaboration with the aim of developing a harmonized protocol for manual segmentation of hippocampal and parahippocampal subregions on high-resolution MRI. In this commentary we discuss the goals for this protocol and the associated key challenges involved in its development. These include differences among existing anatomical reference materials, striking the right balance between reliability of measurements and anatomical validity, and the development of a versatile protocol that can be adopted for the study of populations varying in age and health. The commentary outlines these key challenges, as well as the proposed solution of each, with concrete examples from our working plan. Finally, with two examples, we illustrate how the harmonized protocol, once completed, is expected to impact the field by producing measurements that are quantitatively comparable across labs and by facilitating the synthesis of findings across different studies.