Activity of human hippocampal and amygdala neurons during retrieval of declarative memories

Episodic memories allow us to remember not only that we have seen an item before but also where and when we have seen it (context). Sometimes, we can confidently report that we have seen something (familiarity) but cannot recollect where or when it was seen. Thus, the two components of episodic recall, familiarity and recollection, can be behaviorally dissociated. It is not clear, however, whether these two components of memory are represented separately by distinct brain structures or different populations of neurons in a single anatomical structure. Here, we report that the spiking activity of single neurons in the human hippocampus and amygdala [the medial temporal lobe (MTL)] contain information about both components of memory. We analyzed a class of neurons that changed its firing rate to the second presentation of a previously novel stimulus. We found that the neuronal activity evoked by the presentation of a familiar stimulus (during retrieval) distinguishes stimuli that will be successfully recollected from stimuli that will not be recollected. Importantly, the ability to predict whether a stimulus is familiar is not influenced by whether the stimulus will later be recollected. We thus conclude that human MTL neurons contain information about both components of memory. These data support a continuous strength of memory model of MTL function: the stronger the neuronal response, the better the memory

Single-trial learning of novel stimuli by individual neurons of the human hippocampus-amygdala complex

The ability to distinguish novel from familiar stimuli allows nervous systems to rapidly encode significant events following even a single exposure to a stimulus. This detection of novelty is necessary for many types of learning. Neurons in the medial temporal lobe (MTL) are critically involved in the acquisition of long-term declarative memories. During a learning task, we recorded from individual MTL neurons in vivo using microwire electrodes implanted in human epilepsy surgery patients. We report here the discovery of two classes of neurons in the hippocampus and amygdala that exhibit single-trial learning: novelty and familiarity detectors, which show a selective increase in firing for new and old stimuli, respectively. The neurons retain memory for the stimulus for 24 hr. Thus, neurons in the MTL contain information sufficient for reliable novelty-familiarity discrimination and also show rapid plasticity as a result of single-trial learning

Long-term (10 years) prognostic value of a normal thallium-201 myocardial exercise scintigraphy in patients with coronary artery disease documented by angiography

In order to assess the prognostic significance of normal exercise thallium-210 myocardial scintigraphy in patients with documented coronary artery disease, we studied the incidence of cardiac death and non-fatal myocardial infarction in 69 symptomatic patients without prior Q wave myocardial infarction, who demonstrated one or more significant coronary lesions (stenosis ≤70%) on an angiogram performed within 3 months of scintigraphy (Group 1). These patients were compared to a second group of 136 patients with an abnormal exercise scintigram, defined by the presence of reversible defect(s) and angiographically proven coronary artery disease (Group 2), and to a third group of 102 patients with normal exercise scintigraphy without significant coronary lesions (stenosis ≥30%) or with normal coronary angiography (Group 3). In contrast to coronary lesions observed in Group 2, patients in Group I presented more frequently with single- vessel disease (83% vs 35%, P>0·0001) and with more distal lesions (55% vs 23%, P>0·0001). Over a mean follow-up period of 8·6 years, one fatal and eight non-fatal cases of myocardial infarction were observed in Group 1. The majority of patients in Group 1 were treated medically: only 24 (35%) underwent myocardial revascularization, usually by coronary angioplasty. There was no significant difference in the incidence of combined major cardiac events (cardiac death, non-fatal myocardial infarction) in patients with normal exercise scintigraphy, with or without documented coronary artery disease (Groups 1 and 3), while the incidence was higher in Group 2. However, while the mortality remained very low in Group 1, the incidence of non-fatal myocardial infraction was not different from that of Group 2, where most patients underwent revascularization procedures. In conclusion, patients with coronary artery disease and a normal exercise thallium-201 myocardial scintigram usually have mild coronary lesions (single-vessel disease, distal location) and good long-term prognosis, with a low incidence of cardiac deat

Human memory strength is predicted by theta-frequency phase-locking of single neurons

Learning from novel experiences is a major task of the central nervous system. In mammals, the medial temporal lobe is crucial for this rapid form of learning. The modification of synapses and neuronal circuits through plasticity is thought to underlie memory formation. The induction of synaptic plasticity is favoured by coordinated action-potential timing across populations of neurons. Such coordinated activity of neural populations can give rise to oscillations of different frequencies, recorded in local field potentials. Brain oscillations in the theta frequency range (3–8 Hz) are often associated with the favourable induction of synaptic plasticity as well as behavioural memory. Here we report the activity of single neurons recorded together with the local field potential in humans engaged in a learning task. We show that successful memory formation in humans is predicted by a tight coordination of spike timing with the local theta oscillation. More stereotyped spiking predicts better memory, as indicated by higher retrieval confidence reported by subjects. These findings provide a link between the known modulation of theta oscillations by many memory-modulating behaviours and circuit mechanisms of plasticity

A NWB-based dataset and processing pipeline of human single-neuron activity during a declarative memory task

A challenge for data sharing in systems neuroscience is the multitude of different data formats used. Neurodata Without Borders: Neurophysiology 2.0 (NWB:N) has emerged as a standardized data format for the storage of cellular-level data together with meta-data, stimulus information, and behavior. A key next step to facilitate NWB:N adoption is to provide easy to use processing pipelines to import/export data from/to NWB:N. Here, we present a NWB-formatted dataset of 1863 single neurons recorded from the medial temporal lobes of 59 human subjects undergoing intracranial monitoring while they performed a recognition memory task. We provide code to analyze and export/import stimuli, behavior, and electrophysiological recordings to/from NWB in both MATLAB and Python. The data files are NWB:N compliant, which affords interoperability between programming languages and operating systems. This combined data and code release is a case study for how to utilize NWB:N for human single-neuron recordings and enables easy re-use of this hard-to-obtain data for both teaching and research on the mechanisms of human memory

CHARACTERIZATION OF SPLENIC LYMPHOID CELLS IN FETAL AND NEWBORN MICE

In order to clarify the cellular events that precede the onset of immunological competence in the mouse, we have characterized and quantitated the lymphoid cells of the spleen as a function of age. Our results show that T cells and B cells both appeared in the spleens of Swiss-L mice as early as the 15th-16th day of gestation. Antigen-binding cells specific for each of three different antigens were also first detected during this same 24 h interval. The B cells and three varieties of antigen-binding cells increased in number rapidly and in parallel until about 1 wk after birth. The T cells, which were more numerous than B cells at first, increased in number somewhat more slowly. Coincident with the onset of response to antigen, there was a further increase in B cell numbers and a decrease in the T cell to B cell ratio. The capacity to respond to antigen by cellular proliferation and synthesis of antibody did not arise until about 2 wk after birth although there were no quantitative changes in the total numbers of T cells, B cells, and antigen-binding cells between 1 and 2 wk of age. Some qualitative change, such as the functional maturation of an antigen-reactive cell, may be required during this interval for the onset of this immunological response. Although the numbers of antigen-binding cells present in fetuses and young animals were smaller than in adults, we have as yet been unable to detect any restriction in the variety of specificities that can be expressed in fetuses, either in the kinds of antigens bound or in the range of avidities with which a single antigen is bound

Working Memory Load-related Theta Power Decreases in Dorsolateral Prefrontal Cortex Predict Individual Differences in Performance

Holding information in working memory (WM) is an active and effortful process that is accompanied by sustained load-dependent changes in oscillatory brain activity. These proportional power increases are often reported in EEG studies recording theta over frontal midline sites. Intracranial recordings, however, yield mixed results, depending on the brain area being recorded from. We recorded intracranial EEG with depth electrodes in 13 patients with epilepsy that were performing a Sternberg WM task. Here, we investigated patterns of theta power changes as a function of memory load during maintenance in three areas critical for WM: dorsolateral prefrontal cortex (DLPFC), dorsal ACC (dACC), and hippocampus. Theta frequency power in both hippocampus and dACC increased during maintenance. In contrast, theta frequency power in the DLPFC decreased during maintenance, and this decrease was proportional to memory load. Only the power decreases in DLPFC, but not the power increases in hippocampus and dACC, were predictive of behavior in a given trial. The extent of the load-related theta power decreases in the DLPFC in a given participant predicted a participant's RTs, revealing that DLPFC theta explains individual differences in WM ability between participants. Together, these data reveal a pattern of theta power decreases in the DLPFC that is predictive of behavior and that is opposite of that in other brain areas. This result suggests that theta band power changes serve different cognitive functions in different brain areas and specifically that theta power decreases in DLPFC have an important role in maintenance of information

Working Memory Load-related Theta Power Decreases in Dorsolateral Prefrontal Cortex Predict Individual Differences in Performance

Holding information in working memory (WM) is an active and effortful process that is accompanied by sustained load-dependent changes in oscillatory brain activity. These proportional power increases are often reported in EEG studies recording theta over frontal midline sites. Intracranial recordings, however, yield mixed results, depending on the brain area being recorded from. We recorded intracranial EEG with depth electrodes in 13 patients with epilepsy that were performing a Sternberg WM task. Here, we investigated patterns of theta power changes as a function of memory load during maintenance in three areas critical for WM: dorsolateral prefrontal cortex (DLPFC), dorsal ACC (dACC), and hippocampus. Theta frequency power in both hippocampus and dACC increased during maintenance. In contrast, theta frequency power in the DLPFC decreased during maintenance, and this decrease was proportional to memory load. Only the power decreases in DLPFC, but not the power increases in hippocampus and dACC, were predictive of behavior in a given trial. The extent of the load-related theta power decreases in the DLPFC in a given participant predicted a participant's RTs, revealing that DLPFC theta explains individual differences in WM ability between participants. Together, these data reveal a pattern of theta power decreases in the DLPFC that is predictive of behavior and that is opposite of that in other brain areas. This result suggests that theta band power changes serve different cognitive functions in different brain areas and specifically that theta power decreases in DLPFC have an important role in maintenance of information