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Neurons in hippocampus, entorhinal cortex, and neocortex tend to fall into separate clusters based on firing rate, burst fraction, and spike width. Scatterplots of spike width, firing rate averaged over a session, and burst fraction (fraction of ISIs 20 ms), are shown for units from several inferior temporal structures. Plots show all possible pairwise combinations of these 3 variables. Average firing rate and burst fraction are plotted using a logarithmic scale. Each point represents 1 unit. Only units that were considered to be well isolated were used for these plots. A-C: data from monkey 1, showing units recorded from CA1, CA3/DG, or neocortical areas, in different colors. Note that data from different hippocampal subfields tend to fall into the same cluster, which (with some exceptions) is rather distinct from cluster for neocortical cells. D-F: combined data from all 3 monkeys used in this study, showing units recorded from hippocampus, neocortex, and entorhinal cortex, in different colors. All entorhinal data came from posterior areas EC or ELC from monkey 2; other regions had contributions from all 3 monkeys. Neocortical data came from areas IP, TE, TF, and TL. Plots indicate that points from each brain area cluster differently. Hippocampal cells in particular are characterized by low firing rates, bursty spike trains, and relatively broad spike waveforms.
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Neural unit activity and EEGs were recorded from inferior temporal regions of three rhesus macaques chronically implanted with "hyperdrives" holding 12 individually movable tetrodes. Recordings were made from each monkey over a period of approximately 3 mo, while the electrodes were moved by small increments through the hippocampus and neighboring...
Citations
... Using spectral methods, their characteristics are shown to vary along the long (septotemporal) CA1 axis within animals 15 and most notably with phylogenetic distance across species, e.g., when measured in rodents vs human and non-human primates 11,16,17 . Furthermore, in diseases affecting hippocampal function, such as Temporal Lobe Epilepsy (TLE), pathological forms of ripples have been reported [18][19][20][21] , as well as along aging 22,23 . ...
... The filter was not re-trained. with the literature 16,17 , macaque SWRs had lower frequencies and higher power as compared to mouse ripples (Fig. 6c). ...
... When applied to data from the macaque anterior hippocampus, we found that models trained with LFP signals from the dorsal hippocampus of mice can perform relatively well, especially considering established differences in frequency and in LFP shape in monkeys and human 10,16,17 . After retraining, their operation improved significantly, reaching the inter-experts' performance levels at 0.7 30 . ...
The study of sharp-wave ripples has advanced our understanding of memory function, and their alteration in neurological conditions such as epilepsy is considered a biomarker of dysfunction. Sharp-wave ripples exhibit diverse waveforms and properties that cannot be fully characterized by spectral methods alone. Here, we describe a toolbox of machine-learning models for automatic detection and analysis of these events. The machine-learning architectures, which resulted from a crowdsourced hackathon, are able to capture a wealth of ripple features recorded in the dorsal hippocampus of mice across awake and sleep conditions. When applied to data from the macaque hippocampus, these models are able to generalize detection and reveal shared properties across species. We hereby provide a user-friendly open-source toolbox for model use and extension, which can help to accelerate and standardize analysis of sharp-wave ripples, lowering the threshold for its adoption in biomedical applications.
... [1][2][3][4][5][6] Comparatively, however, low-frequency oscillations during virtual navigation in humans are of lower frequency and less continuous, 19 leading to the suggestion that theta oscillations may be of lower frequency in humans than rodents, 28 possibly differ in anterior versus posterior hippocampus based on self-motion, 27 or are simply harder to observe. 37 One factor that might contribute to the differences between humans and rats in terms of theta oscillations during navigation is that most rodent studies involve navigation with the full range of body-based cues (i.e., head rotations and walking cues) although human patient studies typically involve navigation in virtual reality. One experiment that directly contrasted virtual with real-world ambulation, however, reported only modest increases in frequency and oscillatory prevalence 9 during real-world navigation (see also Aghajan et al. 8 ). ...
Decades of work in rodents suggest that movement is a powerful driver of hippocampal low-frequency ‘‘theta’’ oscillations. Puzzlingly, such movement-related theta increases in primates are less sustained and of lower frequency, leading to questions about their functional relevance. Verbal memory encoding and retrieval lead to robust increases in low-frequency oscillations in humans, and one possibility is that memory might be a stronger driver of hippocampal theta oscillations in humans than navigation. Here, neurosurgical patients navigated routes and then immediately mentally simulated the same routes while undergoing intra- cranial recordings. We found that mentally simulating the same route that was just navigated elicited oscil- lations that were of greater power, higher frequency, and longer duration than those involving navigation. Our findings suggest that memory is a more potent driver of human hippocampal theta oscillations than naviga- tion, supporting models of internally generated theta oscillations in the human hippocampus.
... In rodents, hippocampal SWRs are pronounced during offline states (23,24), but they occur during awake states in humans (25), as well as nonhuman primates during visual search and goal-directed visual exploration, termed exploratory SWRs (26,27). Hippocampal SWR occurrence of monkeys is increased when the subject's gaze is focused near a target object during search or when patients observe familiar pictures of scenes or faces (5,26,28). ...
Sharp-wave ripples (SWRs) are highly synchronous neuronal activity events. They have been predominantly observed in the hippocampus during offline states such as pause in exploration, slow-wave sleep, and quiescent wakefulness. SWRs have been linked to memory consolidation, spatial navigation, and spatial decision-making. Recently, SWRs have been reported during visual search, a form of remote spatial exploration, in macaque hippocampus. However, the association between SWRs and multiple forms of awake conscious and goal-directed behavior is unknown. We report that ripple activity occurs in macaque visual areas V1 and V4 during focused spatial attention. The occurrence of ripples is modulated by stimulus characteristics, increased by attention toward the receptive field, and by the size of the attentional focus. During attention cued to the receptive field, the monkey's reaction time in detecting behaviorally relevant events was reduced by ripples. These results show that ripple activity is not limited to hippocampal activity during offline states, rather they occur in the neocortex during active attentive states and vigilance behaviors.
... Despite the major differences in their spatial codes between primates and rodents, the firing statistics of hippocampal neurons appear to be consistent [96,104,105]. The firing rate distributions show a log-normal pattern, with the majority firing at a very low rate. ...
The hippocampus has been extensively implicated in spatial navigation in rodents and more recently in bats. Numerous studies have revealed that various kinds of spatial information are encoded across hippocampal regions. In contrast, investigations of spatial behavioral correlates in the primate hippocampus are scarce and have been mostly limited to head-restrained subjects during virtual navigation. However, recent advances made in freely-moving primates suggest marked differences in spatial representations from rodents, albeit some similarities. Here, we review empirical studies examining the neural correlates of spatial navigation in the primate (including human) hippocampus at the levels of local field potentials and single units. The lower frequency theta oscillations are often intermittent. Single neuron responses are highly mixed and task-dependent. We also discuss neuronal selectivity in the eye and head coordinates. Finally, we propose that future studies should focus on investigating both intrinsic and extrinsic population activity and examining spatial coding properties in large-scale hippocampal-neocortical networks across tasks.
... Similarly, SPW-Rs in macaque monkeys occur during rest periods between tasks and grooming 97,98 . As in rodents, ripples are present in and near the CA1 pyramidal layer but not in other layers 98 . ...
... Similarly, SPW-Rs in macaque monkeys occur during rest periods between tasks and grooming 97,98 . As in rodents, ripples are present in and near the CA1 pyramidal layer but not in other layers 98 . The oscillation frequency of ripples in primates is slower (110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125) Hz) than in rodents. ...
... oriens. Increased power of slow-wave activity during these quiescent periods correlates with bouts of SPW-Rs events especially with eye closure 98 . Thus, SPW-Rs in rodents and monkeys share physiological and behavioral characteristics. ...
Decades of rodent research have established the role of hippocampal sharp wave ripples (SPW-Rs) in consolidating and guiding experience. More recently, intracranial recordings in humans have suggested their role in episodic and semantic memory. Yet, common standards for recording, detection, and reporting do not exist. Here, we outline the methodological challenges involved in detecting ripple events and offer practical recommendations to improve separation from other high-frequency oscillations. We argue that shared experimental, detection, and reporting standards will provide a solid foundation for future translational discovery.
... and nonhuman primates (2,3) have identified bursts of highfrequency oscillatory activity, known as ripples, in the hippocampus and surrounding medial temporal lobe (MTL) regions. These ripples reflect the coordinated activity of large neuronal ensembles in the hippocampus (4) and cortex (5). ...
... ripple rate ∼ num recalls + (num recalls|participant) + (num recalls|participant : session), [3] where num recalls is the number of total recalls by the participant from the list the trial came from, ripple rate is the rate in the bin −600 to −100 ms, and the other factors are random effects for participant and session nested in participant, as in Eq. 1. The null hypothesis is no difference between number of recalls per list and change in ripple rate. ...
High-frequency oscillatory events, termed ripples, represent synchrony of neural activity in the brain. Recent evidence suggests that medial temporal lobe (MTL) ripples support memory retrieval. However, it is unclear if ripples signal the reinstatement of episodic memories. Analyzing electrophysiological MTL recordings from 245 neurosurgical participants performing episodic recall tasks, we find that the rate of hippocampal ripples rises just prior to the free recall of recently formed memories. This prerecall ripple effect (PRE) is stronger in the CA1 and CA3/dentate gyrus (CA3/DG) subfields of the hippocampus than the neighboring MTL regions entorhinal and parahippocampal cortex. PRE is also stronger prior to the retrieval of temporally and semantically clustered, as compared with unclustered, recalls, indicating the involvement of ripples in contextual reinstatement, which is a hallmark of episodic memory.
... While most studies based on data from rodents argue that hippocampal SWRs are pronounced during offline states (20,21), they occur during awake states in humans (22), as well as non-human primates during visual search and goal-directed visual exploration. These SWRs are termed exploratory SWRs (23,24). ...
Sharp-wave ripples (SWRs) are highly synchronous neuronal activity events. They have been predominantly observed in the hippocampus during offline states such as pause in exploration, slow-wave sleep and quiescent wakefulness. SWRs have been linked to memory consolidation, spatial navigation, and spatial decision-making. Recently, SWRs have been reported during visual search, a form of remote spatial exploration, in macaque hippocampus. However, the association between SWRs and multiple forms of awake conscious and goal-directed behavior is unknown. We report that ripple activity occurs in macaque visual areas V1 and V4 during focused spatial attention. The frequency of ripples is modulated by characteristics of the stimuli, by spatial attention directed toward a receptive field, and by the size of the attentional focus. Critically, the monkeys reaction times in detecting behaviorally relevant stimulus changes was affected on trials with SWRs. These results show that ripple activity is not limited to hippocampal activity during offline states, rather they occur in the neocortex during active attentive states and vigilance behaviors.
... Consistent with previous studies (Barnes et al., 1990;Skaggs et al., 2007), the activity of HF neurons was in general sparse, and the firing rates showed log-normal distributions, with SUB neurons showing the least sparsity (p < 0.001, Kruskal-Wallis test) ( Figure 3A). Individual HF neurons exhibited tuning to diverse spatial variables, including horizontal position, head height, linear speed, azimuth head direction, head tilt, headfacing location (where the head points, a 3D variable), egocentric boundary (relative position and direction to the arena boundary), and head angular velocity ( Figures 3B, 3C, S2, and S4G). ...
The hippocampal formation is linked to spatial navigation, but there is little corroboration from freely moving primates with concurrent monitoring of head and gaze stances. We recorded neural activity across hippocampal regions in rhesus macaques during free foraging in an open environment while tracking their head and eye. Theta activity was intermittently present at movement onset and modulated by saccades. Many neurons were phase-locked to theta, with few showing phase precession. Most neurons encoded a mixture of spatial variables beyond place and grid tuning. Spatial representations were dominated by facing location and allocentric direction, mostly in head, rather than gaze, coordinates. Importantly, eye movements strongly modulated neural activity in all regions. These findings reveal that the macaque hippocampal formation represents three-dimensional (3D) space using a multiplexed code, with head orientation and eye movement properties being dominant during free exploration.
... Using these criteria, we found that the HPC has a larger proportion of putative principal neurons firing bursts than the LPFC. This is in line with previous studies in the HPC that have reported an abundance of burst firing in HPC principal cells across species (Bliss & Collingridge, 1993;Lisman, 1997;Skaggs et al., 2007;Xu et al., 2012). It also agrees with studies in the LPFC reporting that information decoded during short-term memory and attention tasks is maximized when using time windows of 400ms or longer (Backen et al., 2018;Leavitt et al., 2017;Tremblay, Pieper, Sachs, & Martinez-Trujillo, 2015). ...
... It has been reported that a feature of HPC principal cells is they frequently fire in very rapid bursts, measured by ISIs below 20ms (Lisman, 1997;Skaggs et al., 2007), or even 6-8ms (Buzsáki, 2015;Ranck, 1973). This physiological burst can make up a significant proportion of all spikes, and a high burst fraction (fraction of all ISIs that are below 20ms) is a distinguishing feature of these HPC cells in primates (Skaggs et al., 2007) as well as rodents (Lisman, 1997). ...
... It has been reported that a feature of HPC principal cells is they frequently fire in very rapid bursts, measured by ISIs below 20ms (Lisman, 1997;Skaggs et al., 2007), or even 6-8ms (Buzsáki, 2015;Ranck, 1973). This physiological burst can make up a significant proportion of all spikes, and a high burst fraction (fraction of all ISIs that are below 20ms) is a distinguishing feature of these HPC cells in primates (Skaggs et al., 2007) as well as rodents (Lisman, 1997). The hippocampal spike burst has consistently proven intriguing to scientists (Kepecs, Wang, & Lisman, 2002;Lisman, 1997;Zeldenrust et al., 2018). ...
The primate hippocampus (HPC) and lateral prefrontal cortex (LPFC) are two brain structures deemed essential to long- and short-term memory functions respectively. Here we hypothesize that although both structures may encode similar information about the environment, the neural codes mediating neuronal communication in HPC and LPFC have differentially evolved to serve their corresponding memory functions. We used a virtual reality task in which animals navigated through a maze using a joystick and selected one of two targets in the arms of the maze according to a learned context-color rule. We found that neurons and neuronal populations in both regions encode similar information about the different task periods. Moreover, using statistical analyses and linear classifiers, we demonstrated that many HPC neurons concentrate spikes temporally into bursts, whereas most LPFC neurons sparsely distribute spikes over time. When integrating spike rates over short intervals, HPC neuronal ensembles reached maximum decoded information with fewer neurons than LPFC ensembles. We propose that HPC principal cells have evolved intrinsic properties that enable burst firing and temporal summation of synaptic potentials that ultimately facilitates synaptic plasticity and long-term memory formation. On the other hand, LPFC pyramidal cells have intrinsic properties that allow sparsely distributing spikes over time enabling encoding of short-term memories via persistent firing without necessarily triggering rapid changes in the synapses.
... To detect SWR, signals were band-pass filtered (100-300Hz), rectified and low-pass filtered (cut-off 20 Hz) [26]. We used a custom peak detection algorithm that detects peaks with SWR-specific features [27]. ...
Kindling is an electrical stimulation technique used to lower the threshold for epileptogenic activity in the brain. It can also be used as a tool to investigate electrophysiologic alterations that occur as a result of seizures. Epileptiform activity, like seizures and after-discharges (AD; evoked epileptiform activity), commonly cause memory impairment but rarely, can elicit vivid memory retrieval. We kindled the basolateral amygdala of a non-human primate (NHP) once weekly and had him perform a spatial memory task in a 3D virtual environment before, during and after kindling. AD were associated with an initial average performance increase of 46.6%. The enhancement which followed AD persisted up to 2 days. Memory task performance enhancement was accompanied by significant resetting of hippocampal theta oscillations and robust hippocampal potentiation as measured by field evoked potentials. However, neither lasted throughout the duration of performance enhancement. Sharp-wave ripples (SWR), a local field event that supports episodic memory, were generated more often throughout the period of enhancement. SWR rate increased from 14.38 SWR per min before kindling to 24.22 SWR per min after kindling on average. Our results show that kindling can be associated with improved memory. Memory function appears to depend on the particular induction circuit and the resultant excitation/inhibition ratio of the mesial temporal lobe network. Investigating the electrophysiologic underpinnings of this observed memory enhancement is an important step towards understanding the network alterations that occur after seizures and stimulation. Clinical Relevance-Our findings provide new insight into the effects of kindling stimulation in the primate brain. Kindling can cause increase MTL synchrony and the frequency of spontaneous seizures in a primate. This work highlights important considerations for therapeutic deep brain stimulation.
