In a bright surgical theatre in central London, neurosurgeon Ahmed Toma makes an incision on the side of a woman’s head. Then, he bores a small hole into her skull, revealing a glimpse of the pink, pulsating brain beneath. Even the unconscious brain can learn — and predict what you’ll say next Toma is preparing to implant a shunt to drain excess cerebrospinal fluid — a routine treatment for a condition called normal pressure hydrocephalus, in which fluid builds up inside the skull.
His patient at the National Hospital for Neurology and Neurosurgery (NHNN) has also agreed to take part in an experiment: one that involves briefly placing a centimetre-long probe, thinner than a human hair, into her brain. Called Neuropixels, this probe is designed to record the electrical activity of hundreds of neurons at once. As Toma and a team of researchers carefully insert the probe into the patient’s brain, Mihaly Kollo, a research scientist at the Francis Crick Institute in London, stands nearby, monitoring a multicoloured array of outputs from the probe’s recording sites in real time.
After controlling for electrical noise from the operating table and other surgical equipment, Kollo plays an audio sequence of repeating terms — ‘blind spot’, ‘parking spot, ‘piggy bank’ and so on — to examine how the brain represents the transitions between stimuli, and how they are influenced by frequency and familiarity. As the words ring through the theatre, some trigger brain perturbations that sweep across the waveforms representing the probe’s output — a clear sign that it is picking up activity. Scientists have long conducted experiments during neurosurgery, which offers a rare opportunity to access a living (and often awake) human brain.
But Neuropixels probes might provide researchers with the sharpest view of the organ yet. Since their debut in 2017, Neuropixels have transformed how neuroscientists do electrophysiology experiments in animals, allowing them to record electrical activity from hundreds, sometimes even tens of thousands, of neurons at once. Over the past year, at the NHNN, which is part of the University College London Hospitals, Kollo and his colleagues have been collaborating with neurosurgeons such as Toma to take Neuropixels recordings in people.
Medicine Nobel awarded for brain ‘switch’ that controls neurons with light There are other ways of surveying single-cell activity in large populations of neurons, such as calcium imaging, which tracks the movement of calcium ions that occurs each time a neuron fires. But these techniques can be too slow to capture the action potentials in certain neurons, or require genetically encoded sensors, limiting their use in some organisms and precluding it in humans. For people, researchers have relied mostly on devices that sit on the surface of the brain and measure population-level activity, such as high-density electrocorticography.
There have also long been tools that can make a relatively small number of recordings at the single-cell level, such as the Utah array — a tiny device studded with miniature needles that penetrate about a millimetre into the brain and that has 96 recording channels. Pierre Bourdillon, a neurosurgeon at the Adolphe de Rothschild Foundation Hospital in Paris, likens the technological leap for human neuroscience enabled by Neuropixels to the difference between trying to decipher conversations from a single microphone at a busy intersection and listening in on those same discussions using individual microphones attached to the speakers’ collars. Now we’re just starting to see the first teams using this kind of technology in humans.” A short walk from the NHNN, at the hospital-turned-research institute known as the Cruciform Building at University College London, neuroscientist Matteo Carandini is applying the most cutting-edge version of Neuropixels technology in organisms with much smaller brains.
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