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Khazali, M. F.

Publications and source records attributed to Khazali, M. F..

6 recordsLinked to original sources

Scalable hardware and software for high-density, multi-regional electrophysiology in non-human primates

Understanding how distributed neural circuits generate complex behaviors requires long-duration recordings from populations of individual neurons across multiple brain regions. High-density Neuropixels probes have revolutionized rodent systems neuroscience. Extending these capabilities to non-human primates (NHPs) for chronic, multi-regional recordings requires compact, implantable microdrive hardware and reliable automated spike-sorting software. NHPs provide access to complex and flexible behaviors that are difficult to study in other model systems. Extending the Neuropixels revolution to NHPs therefore depends on integrating hardware and software for long-duration, multi-regional recordings. Here, we present a scalable hardware-software platform co-designed for high-density neural data acquisition and reliable single-unit identification in NHPs. The Multi-regional Implantable NeuroDrive (MIND) is a lightweight, implantable microdrive that provides stable recordings from multiple independently positioned Neuropixels probes and is designed to support chronic, ambulatory, head-free recordings. We paired MIND with UnitAssay, an automated post-sorting curation framework that identifies and curates characteristic spike-sorting errors with minimal computational cost. Together, MIND and UnitAssay provide an integrated platform for implanted, multi-regional recordings in NHPs performing complex and naturalistic behaviors. We tested MIND and UnitAssay across parietal, prefrontal, and motor cortices in rhesus macaques performing reaching and eye-movement tasks. MIND enabled stable multi-probe recordings across cortical regions and durations. UnitAssay enabled automated curation of large-scale spike-sorting output and improved reliable single-unit identification relative to Kilosort 4 labels and standard SpikeInterface quality control. Together, MIND and UnitAssay provide a scalable solution for high-density, multi-regional, long-duration electrophysiology in NHPs.

neuroscience↗

The human hippocampus retroactively binds experiences across time

Creating memories requires linking events across seconds and minutes, but canonical mechanisms of associative plasticity operate over much shorter timescales. This poses a fundamental problem: how can the brain bind information that arrives at different times? Computational model and animal studies implicate the hippocampus in associating events across time, but when the hippocampus becomes engaged and how it interacts with representations of preceding events are unknown. Here we show, using intracranial recordings in humans forming image-word associations across a ~2-s temporal gap, that hippocampal high-frequency activity predicts later memory when the second event arrives, but not during the initial image or intervening delay. At this moment, neurons tuned to the preceding image reinstate stimulus-specific firing despite its sensory absence. Across trials, hippocampal high-frequency activity was selectively coupled to this reinstatement during successful encoding and increased before spiking of image-tuned neurons. These findings reveal a retroactive mode of hippocampal binding, whereby representations of preceding events are recruited when new information arrives. This mechanism provides a neural solution for binding experiences across the temporal discontinuities that characterize everyday life.

neuroscience↗

Beyond Rate: Hippocampal Phase Codes for Space and Memory

Place cells and concept neurons are defined by a rise in firing rate at a particular location or for a particular person or object. Neurons without such a rise remain unlabeled, although they keep firing during the task. Such neurons could still carry information in the timing of their spikes. Hippocampal theta provides a reference for this timing. We therefore asked whether the theta phase of a neuron's spikes depends on location or on the viewed image, even when its firing rate does not. We analysed hippocampal neurons in humans navigating a virtual city, rats running on a linear track, and humans viewing images of anima ls, faces, and places. In both navigation datasets, more neurons than expected by chance fired at a consistent theta phase at particular locations. This phase tuning remained after we excluded neurons whose firing rate depended on location. In human navigation, the spike phases of these remaining neurons improved location decoding beyond the firing rates of all neurons. More phase-tuned neurons than expected by chance also fired at progressively earlier theta phases as participants passed each neuron's preferred location. This pattern resembles phase precession, which classically occurs as an animal crosses the firing-rate field of a place cell. The neurons that showed it had no firing-rate field, so their phase shift was anchored to the location defined by phase tuning alone. During image viewing, more neurons than expected by chance changed the theta phase of their spikes after a particular image appeared. This effect remained after we removed, for each neuron, the images that changed its firing rate. Spike phases alone also predicted the image category above chance. Theta-relative spike timing therefore carries in formation about location and images that firing rate alone misses. We propose that weak input changes when a neuron fires with in the theta cycle, whereas strong input also raises its firing rate.

neuroscience↗

A preserved neural code for temporal order between memory formation and recall in the human medial temporal lobe

Temporal memory enables us to remember the temporal order of events happening in our life. The human medial temporal lobe (MTL) appears to contain neural representations supporting temporal memory formation, but the cellular mechanisms that preserve temporal order information for recall are largely unknown. Here, we examined whether human MTL neuronal activity represents the temporal position of events during memory formation and recall, using invasive single and multi-unit recordings in human epilepsy patients (n = 19). Participants freely navigated a virtual environment in order to explore and remember locations and temporal positions of objects. During each exploration period, they sequentially encountered two or three different objects, placed in different locations. This allowed us to examine single- and multi-unit neuronal firing rates (FR) as a function of the temporal position the objects were presented in. We found that a significant number of multi-units and single-units in various MTL regions including the hippocampus showed selectivity to the temporal position of objects during the exploration period. During recall, patients were asked to indicate which one of two objects from the same trial was found latter. Neural firing rates during recall showed a selectivity supporting recall of temporal positions. Interestingly, most of the selective single-units that stayed selective during encoding and recall preserved their temporal position preference. Our results thus suggest that neuronal activity in the human MTL contains a preserved neural code for temporal order in memory formation and recall.

neuroscience↗

Nonhuman primates exploit the prior assumption that the visual world is vertical

When human subjects tilt their heads in dark surroundings, the noisiness of vestibular information impedes precise reports on objects orientation with respect to earths vertical axis. This difficulty is mitigated if a vertical visual background is available. Tilted visual backgrounds induce feelings of head tilt in subjects who are in fact upright. This is often explained as a result of the brain resorting to the prior assumption that natural visual backgrounds are vertical. Here, we tested whether monkeys show comparable perceptual mechanisms. To this end we trained two monkeys to align a visual arrow to a vertical reference line that had variable luminance across trials, while including a large, clearly visible background square whose orientation changed from trial to trial. On around 20% of all trials, the vertical reference line was left out to measure the subjective visual vertical (SVV). When the frame was upright, the monkeys SVV was aligned with the gravitational vertical. In accordance with the perceptual reports of humans, however, when the frame was tilted, it induced an illusion of head tilt as indicated by a bias in SVV towards the frame orientation. Thus all primates exploit the prior assumption that the visual world is vertical.

neuroscience↗

V1 neurons encode the perceptual compensation of false torsion arising from Listings law

We try to deploy the retinal fovea to optimally scrutinize an object of interest by directing our eyes to it. Horizontal and vertical components of these fixation eye movements are determined by the objects location. However, fixation eye movements also involve a torsional component, which according to Listings law is fully determined by the 2D eye position acquired. According to Von Helmholtz knowledge of the torsion provided by this law alleviates the perceptual interpretation of the image tilt that changes with fixation, a view supported by psychophysical experiments he pioneered. We address the question where and how Listings law is implemented in the visual system and we show that neurons in monkey area V1 use knowledge of torsion to compensate the image tilt associated with specific eye positions as set by Listings law.

neuroscience↗