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Nat Commun ; 12(1): 4839, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376673


The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.

Potenciais de Ação/fisiologia , Epilepsia/fisiopatologia , Aprendizagem/fisiologia , Neurônios/fisiologia , Ritmo Teta/fisiologia , Adolescente , Adulto , Epilepsia/diagnóstico , Feminino , Hipocampo/citologia , Hipocampo/fisiologia , Humanos , Masculino , Modelos Neurológicos , Neurônios/citologia , Estimulação Luminosa/métodos , Lobo Temporal/citologia , Lobo Temporal/fisiologia , Adulto Jovem
J Neurosci ; 41(31): 6714-6725, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34183446


An indispensable feature of episodic memory is our ability to temporally piece together different elements of an experience into a coherent memory. Hippocampal time cells-neurons that represent temporal information-may play a critical role in this process. Although these cells have been repeatedly found in rodents, it is still unclear to what extent similar temporal selectivity exists in the human hippocampus. Here, we show that temporal context modulates the firing activity of human hippocampal neurons during structured temporal experiences. We recorded neuronal activity in the human brain while patients of either sex learned predictable sequences of pictures. We report that human time cells fire at successive moments in this task. Furthermore, time cells also signaled inherently changing temporal contexts during empty 10 s gap periods between trials while participants waited for the task to resume. Finally, population activity allowed for decoding temporal epoch identity, both during sequence learning and during the gap periods. These findings suggest that human hippocampal neurons could play an essential role in temporally organizing distinct moments of an experience in episodic memory.SIGNIFICANCE STATEMENT Episodic memory refers to our ability to remember the what, where, and when of a past experience. Representing time is an important component of this form of memory. Here, we show that neurons in the human hippocampus represent temporal information. This temporal signature was observed both when participants were actively engaged in a memory task, as well as during 10-s-long gaps when they were asked to wait before performing the task. Furthermore, the activity of the population of hippocampal cells allowed for decoding one temporal epoch from another. These results suggest a robust representation of time in the human hippocampus.

J Neurosci Methods ; 286: 38-55, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28512008


BACKGROUND: Primate neurobiologists use chronically implanted devices such as pedestals for head stabilization and chambers to gain access to the brain and study its activity. Such implants are skull-mounted, and made from a hard, durable material, such as titanium. NEW METHOD: Here, we present a low-cost method of creating customized 3D-printed cranial implants that are tailored to the anatomy of individual animals. We performed pre-surgical computed tomography (CT) and magnetic resonance (MR) scans to generate three-dimensional (3D) models of the skull and brain. We then used 3D modelling software to design implantable head posts, chambers, and a pedestal anchorage base, as well as craniotomy guides to aid us during surgery. Prototypes were made from plastic or resin, while implants were 3D-printed in titanium. The implants underwent post-processing and received a coating of osteocompatible material to promote bone integration. RESULTS: Their tailored fit greatly facilitated surgical implantation, and eliminated the gap between the implant and the bone. To date, our implants remain robust and well-integrated with the skull. COMPARISON WITH EXISTING METHOD(S): Commercial-off-the-shelf solutions typically come with a uniform, flat base, preventing them from sitting flush against the curved surface of the skull. This leaves gaps for fluid and tissue ingress, increasing the risk of microbial infection and tissue inflammation, as well as implant loss. CONCLUSIONS: The use of 3D printing technology enabled us to quickly and affordably create unique, complex designs, avoiding the constraints levied by traditional production methods, thereby boosting experimental success and improving the wellbeing of the animals.

Encéfalo/diagnóstico por imagem , Cabeça/diagnóstico por imagem , Cabeça/cirurgia , Modelos Anatômicos , Impressão Tridimensional , Próteses e Implantes , Animais , Vasos Sanguíneos/diagnóstico por imagem , Encéfalo/cirurgia , Mapeamento Encefálico , Imageamento Tridimensional , Macaca mulatta , Masculino , Impressão Tridimensional/instrumentação , Tomografia Computadorizada por Raios X
PLoS Biol ; 14(3): e1002420, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27015604


Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

Córtex Visual/fisiologia , Percepção Visual/fisiologia , Potenciais de Ação , Adulto , Animais , Atenção/fisiologia , Feminino , Humanos , Macaca , Imageamento por Ressonância Magnética