The Neuropixels 1.0 NHP probe is for much longer than current high-density recording probes, offering recording entry to a lot of the mind of a rhesus macaque or different massive animal. Credit score: Trautmann et al.
To map the mammalian mind and its varied capabilities with rising precision, neuroscientists depend on high-resolution imaging strategies and different superior experimental instruments. These embody high-density silicon probes, needle-like gadgets integrating a number of electrodes that may be inserted into mind tissue to select up voltage modifications related to the firing of neurons.
These gadgets have up to now principally been used to watch and research the exercise of neurons within the rodent mind. Nonetheless, they proved much less efficient when finding out the brains of non-human primates (NHPs), akin to macaques, which extra carefully resemble the human mind.
Researchers at Columbia College Medical Middle and Columbia College not too long ago demonstrated the potential of Neuropixels 1.0 NHP, a extra scalable probe developed by IMEC, for gathering brain-wide and high-resolution neural recordings in macaques and different NHPs.
Their challenge resulted in a paper revealed in Nature Neuroscience.
“Our paper was inspired by a fundamental need in the neuroscience community to overcome the limitations of existing neural recording technologies in NHPs,” Eric M. Trautmann, first writer of the paper, informed Medical Xpress.
“The original Neuropixels 1.0 probe, while transformative for rodent models, had limited functionality in NHPs due to its 10-mm length, which restricted access to superficial brain targets, and a thin shank (24 µm) that made insertion through the primate dura mater difficult. Other existing linear arrays are limited in channel count, and surface arrays like the Utah array or floating microwire arrays were confined to superficial cortex and fixed depths.”
Trautmann and his colleagues had been searching for a probe that might permit them to precisely and reliably report neural exercise within the brains of NHPs and different massive animals. They wished this gadget to additionally reliably report the exercise of huge populations of neurons with single-neuron and single-spike decision, or in different phrases, isolate the exercise of single neurons and detect particular person motion potentials.
“The new recording electrode developed by IMEC is fabricated as a 54-mm-long monolithic piece of silicon that integrates both the shank and the base electronics,” defined Trautmann.
“The probe features a significantly longer, wider, and thicker shank (45 mm long, 125 µm wide, and 90 µm thick) compared to the original Neuropixels 1.0 probe.”
The probe examined by the authors has a complete of 4,416 recording websites (i.e., pixels) distributed alongside the complete size of its 45-mm shank and grouped into 11.5 “banks” of 384 channels every. Notably, experimenters can even choose one in all these “banks” to gather simultaneous recordings throughout 384 websites, through a swap positioned below each website.
“The probe utilizes the same low-noise readout channels with programmable gain and 10-bit resolution on a 130-nm Silicon-on-Insulator CMOS platform as the Neuropixels 1.0,” mentioned Trautmann.
“The tip of the shank is mechanically ground to a 25° bevel angle on the side plane, creating a sharpened tip along both axes to facilitate insertion and minimize tissue damage.”
The brand new Neuropixels gadget affords neuroscientists deeper entry into buildings all through the mind of huge animals, which can’t be accessed by shorter high-density probes. Furthermore, its 90 µm thickness and sharper shank permit it to successfully penetrate the powerful membrane masking the primate mind and spinal twine, referred to as the primate dura mater.
“Further advantages of our approach include its scalability and high channel count, or in other words, the ability to programmably select 384 channels from over 4,400 sites and collect simultaneous multi-area recording from thousands of neurons,” mentioned Trautmann.
“This feature allows experimenters to decouple the process of optimizing a recording location from probe positioning, facilitating surveys of neural activity along the entire probe length without physical movement.”
Because the newly developed probe is bigger than the person reticules (i.e., masks) generally used to manufacture gadgets through photolithographic strategies, its builders needed to devise approaches to allow its dependable realization. These included a “stitching” technique to exactly align options alongside the probe throughout a number of steps, in addition to stress compensation layers that stop it from bending.
“Internal metal wires were widened and spaced to minimize resistance, thermal noise, and crosstalk,” defined Trautmann. “Another advantage of our probe is its high spatial resolution. The dense recording sites facilitate high-quality, automated spike sorting and enable continuous tracking of neurons even with drifting motion between the probe and tissue.”
In comparison with current applied sciences, the Neuropixels 1.0 NHP probe can be less expensive. It may thus dramatically decrease the associated fee related to the recording of neurons, with a complete system value ranging between US$7,000 and US$15,000.
“We demonstrated the probe’s potential through four example experiments in macaques, addressing diverse neuroscience questions,” mentioned Traumann.
“We confirmed large-scale surveys of retinotopic group throughout a number of extrastriate visible cortical areas, recording hundreds of neurons concurrently and illustrating the orderly shift of receptive fields throughout cortical depths.
“We also collected stable, large-scale recordings during motor behaviors in superficial and deep structures (e.g., primary motor cortex, premotor cortex, globus pallidus interna, supplementary motor area), demonstrating the capture of diverse temporal patterns and improved force prediction with more neurons.”
Utilizing the brand new probe, the researchers may additionally report exercise in an space of the NHP mind that’s usually troublesome to entry (i.e, deep inferotemporal cortex face patches), all whereas the animals had been taking a look at photos of faces. Throughout a single knowledge assortment session, they had been in a position to detect lots of of neurons that appeared to contribute to the popularity of faces, which might have beforehand taken years.
“We also demonstrated the probe’s utility for studying single-trial correlates of decision-making, showing how LIP and superior colliculus (SC) neuron populations track accumulated evidence and exhibit distinct dynamics only observable through high-yield single-trial analyses,” mentioned Trautmann.
“The high density also facilitated measuring spike-spike correlations between neuron pairs, which is indicative of synaptic connections or shared input, enabling mapping of putative connections across cortical laminae and between regions.”
This current research may quickly open new invaluable potentialities for neuroscience analysis involving massive animals. By overcoming varied extensively reported engineering challenges, the brand new probe developed at IMEC was discovered to reliably report the exercise of neurons throughout the brains of non-human primates.
“We successfully surmounted significant engineering challenges related to fabricating large-scale silicon probes that exceed standard photolithographic reticle sizes through methods like stitching and by designing for mechanical strength and flexibility (stress compensation layers) for the long shank,” mentioned Trautmann.
“This technology enables new classes of experiments previously deemed impractical or impossible. This includes detailed electrophysiological mapping of brain areas at single-neuron and single-spike resolution, measuring spike-spike correlations between cells, and conducting simultaneous brain-wide recordings at an unprecedented scale.”
Sooner or later, the Neuropixels 1.0 NHP probe may very well be deployed in different laboratories worldwide, lowering the efforts, sources and prices at present related to finding out the brains of huge animals. It may additionally allow extra superior and complicated neuroscience experiments involving NHP, which may result in new thrilling discoveries.
“Our probe facilitates a more comprehensive and unbiased mapping of neural activity across multiple brain regions and depths, which is essential for understanding the coordinated action of large neuronal populations involved in sensory, motor, and cognitive operations,” mentioned Traumann.
“It could also allow researchers to perform single-trial analyses of neural activity at high resolution, which is particularly critical for studying cognitive functions, where brain processes can vary across task repetitions.”
If used to map neural circuits, the Neuropixels 1.0 NHP probe may quickly additionally assist to higher perceive how anatomical circuits within the brains of huge mammals carry out particular computations. Whereas the present model of the gadget is primarily optimized to carry out acute recordings, IMEC is at present engaged on additional bettering its capabilities.
“As part of our next studies, we plan to develop new hardware and test semi-chronic (multiple days or weeks) implantation,” added Trautmann.
“This will require new implant designs and is currently an untested but conceivable capability with appropriate insertion methods and hardware. Moreover, we are working on developing probes with intracortical microstimulation (ICMS) capabilities, which is not yet possible. However, the current generation of probes can be used to record alongside stimulation via a separate electrode.”
Written for you by our writer Ingrid Fadelli, edited by Gaby Clark, and fact-checked and reviewed by Robert Egan—this text is the results of cautious human work. We depend on readers such as you to maintain impartial science journalism alive.
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Extra info:
Eric M. Trautmann et al, Giant-scale high-density brain-wide neural recording in nonhuman primates, Nature Neuroscience (2025). DOI: 10.1038/s41593-025-01976-5.
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