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

The primate amygdala in social perception – insights from electrophysiological recordings and stimulation

The role of the amygdala in emotion and social perception has been intensively investigated primarily through studies using functional magnetic resonance imaging (fMRI). Recently, this topic has been examined using single-unit recordings in both humans and monkeys, with a focus on face processing. The findings provide novel insights, including several surprises: amygdala neurons have very long response latencies, show highly nonlinear responses to whole faces, and can be exquisitely selective for very specific parts of faces such as the eyes. In humans, the responses of amygdala neurons correlate with internal states evoked by faces, rather than with their objective features. Current and future studies extend the investigations to psychiatric illnesses such as autism, in which atypical face processing is a hallmark of social dysfunction

Safety and Utility of Hybrid Depth Electrodes for Seizure Localization and Single-Unit Neuronal Recording

Background: Invasive electrode monitoring provides more precise localization of epileptogenic foci in patients with medically refractory epilepsy. The use of hybrid depth electrodes that include microwires for simultaneous single-neuron monitoring is becoming more widespread. Objective: To determine the safety and utility of hybrid depth electrodes for intracranial monitoring of medically refractory epilepsy. Methods: We reviewed the medical charts of 53 cases of medically refractory epilepsy operated on from 2006 to 2017, where both non-hybrid and hybrid microwire depth electrodes were used for intracranial monitoring. We assessed the localization accuracy and complications that arose to assess the relative safety and utility of hybrid depth electrodes compared with standard electrodes. Results: A total of 555 electrodes were implanted in 52 patients. The overall per-electrode complication rate was 2.3%, with a per-case complication rate of 20.8%. There were no infections or deaths. Serious or hemorrhagic complications occurred in 2 patients (0.4% per-electrode risk). Complications did not correlate with the use of any particular electrode type, and hybrids were equally as reliable as standard electrodes in localizing seizure onset zones. Conclusions: Hybrid depth electrodes appear to be as safe and effective as standard depth electrodes for intracranial monitoring and provide unique opportunities to study the human brain at single-neuron resolution

Encoding of target detection during visual search by single neurons in the human brain

Neurons in the primate medial temporal lobe (MTL) respond selectively to visual categories such as faces, contributing to how the brain represents stimulus meaning. However, it remains unknown whether MTL neurons continue to encode stimulus meaning when it changes flexibly as a function of variable task demands imposed by goal-directed behavior. While classically associated with long-term memory, recent lesion and neuroimaging studies show that the MTL also contributes critically to the online guidance of goal-directed behaviors such as visual search. Do such tasks modulate responses of neurons in the MTL, and if so, do their responses mirror bottom-up input from visual cortices or do they reflect more abstract goal-directed properties? To answer these questions, we performed concurrent recordings of eye movements and single neurons in the MTL and medial frontal cortex (MFC) in human neurosurgical patients performing a memory-guided visual search task. We identified a distinct population of target-selective neurons in both the MTL and MFC whose response signaled whether the currently fixated stimulus was a target or distractor. This target-selective response was invariant to visual category and predicted whether a target was detected or missed behaviorally during a given fixation. The response latencies, relative to fixation onset, of MFC target-selective neurons preceded those in the MTL by ∼200 ms, suggesting a frontal origin for the target signal. The human MTL thus represents not only fixed stimulus identity, but also task-specified stimulus relevance due to top-down goal relevance

Combined Phase-Rate Coding by Persistently Active Neurons as a Mechanism for Maintaining Multiple Items in Working Memory in Humans

Maintaining multiple items in working memory (WM) is central to human behavior. Persistently active neurons are thought to be a mechanism to maintain WMs, but it remains unclear how such activity is coordinated when multiple items are kept in memory. We show that memoranda-selective persistently active neurons in the human medial temporal lobe phase lock to ongoing slow-frequency (1–7 Hz) oscillations during WM maintenance. The properties of phase locking are dependent on memory content and load. During high memory loads, the phase of the oscillatory activity to which neurons phase lock provides information about memory content not available in the firing rate of the neurons. We provide a computational model that reveals that inhibitory-feedback-mediated competition between multiple persistently active neurons reproduces this phenomenon. This work reveals a mechanism for the active maintenance of multiple items in WM that relies on persistently active neurons whose activation is orchestrated by oscillatory activity

Combined Phase-Rate Coding by Persistently Active Neurons as a Mechanism for Maintaining Multiple Items in Working Memory in Humans

Maintaining multiple items in working memory (WM) is central to human behavior. Persistently active neurons are thought to be a mechanism to maintain WMs, but it remains unclear how such activity is coordinated when multiple items are kept in memory. We show that memoranda-selective persistently active neurons in the human medial temporal lobe phase lock to ongoing slow-frequency (1–7 Hz) oscillations during WM maintenance. The properties of phase locking are dependent on memory content and load. During high memory loads, the phase of the oscillatory activity to which neurons phase lock provides information about memory content not available in the firing rate of the neurons. We provide a computational model that reveals that inhibitory-feedback-mediated competition between multiple persistently active neurons reproduces this phenomenon. This work reveals a mechanism for the active maintenance of multiple items in WM that relies on persistently active neurons whose activation is orchestrated by oscillatory activity

Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform

Determining cell types is critical for understanding neural circuits but remains elusive in the living human brain. Current approaches discriminate units into putative cell classes using features of the extracellular action potential (EAP); in absence of ground truth data, this remains a problematic procedure. We find that EAPs in deep structures of the brain exhibit robust and systematic variability during the cardiac cycle. These cardiac-related features refine neural classification. We use these features to link bio-realistic models generated from in vitro human whole-cell recordings of morphologically classified neurons to in vivo recordings. We differentiate aspiny inhibitory and spiny excitatory human hippocampal neurons and, in a second stage, demonstrate that cardiac-motion features reveal two types of spiny neurons with distinct intrinsic electrophysiological properties and phase-locking characteristics to endogenous oscillations. This multi-modal approach markedly improves cell classification in humans, offers interpretable cell classes, and is applicable to other brain areas and species

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

Predicting Action Content On-Line and in Real Time before Action Onset - an Intracranial Human Study

The ability to predict action content from neural signals in real time before the action occurs has been long sought in the neuroscientific study of decision-making, agency and volition. On-line real-time (ORT) prediction is important for understanding the relation between neural correlates of decision-making and conscious, voluntary action as well as for brain-machine interfaces. Here, epilepsy patients, implantded with intracranial depth microelectodes or subdural grid electrodes for clinical purposes, participated in a "matching-pennies" game against an opponent. In each trial, subjects were given a 5 s countdown, after which they had to raise their left or right hand immediately as the "go" signal appeared on a computer screen. They won a fixed amount of money if they raised a different hand than their opponent and lost that amount otherwise. The question we here studied was the extent to which neural precursors of the subjects' decisions can be detected in intracranial local field potentials (LFP) prior to the onset of the action. We found that combinded low-frequency (0.1-5 Hz) LFP signals from 10 electrodes were predictive of the intended left-/right-hand movements before the onset of the go signal. Our ORT system predicted which hand the patient would raise 0.5 s before the go signal with 68% accuracy in two patients. Based on these results, we constructed an ORT system that tracked up to 30 electrodes simultaneously, and tested it on retrospective data from 7 patients. On average, we could predict the correct hand choice in 83% of the trials, which rose to 92% if we let the system drop 3/10 of the trials on which it was less confident. Out system demonstrates-for the first time-the feasibility of accurately predicting a binary action on single trials in real time for patients with intracranial recordings, well before the action occurs