Technology for neuroengineering

This Review highlights technological advances in exoskeleton technology from the past two decades, and challenges and opportunities in the exoskeleton-assisted rehabilitation of gait.

Systemically administered piezoelectric nanoparticles producing nitric oxide and generating direct current under high-intensity focused ultrasound can be used to stimulate deep tissue in the brain, as shown in a mouse model of Parkinson’s disease.

Transmembrane water-efflux rate is a sensitive biomarker of the expression of aquaporin-4, and can be measured via conventional dynamic-contrast-enhanced magnetic resonance imaging, as shown in animals and in patients with gliomas.

Closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates.

Two variants of the adeno-associated virus serotype 9 engineered to display specific cell-penetrating peptides on the capsid show enhanced transduction of cells of the central nervous system in small and large animals.

Optimized ultraflexible electrode arrays enable months-long electrophysiological recordings of several thousand neurons at densities of up to 1,000 neural units per cubic millimetre.

Bioresorbable silicon-based optoelectronic thin films can selectively excite or inhibit neural activities, as shown in mice with exposed sciatic nerves and somatosensory cortices.

A stretchable neuromorphic ‘nerve’ restores coordinated and smooth motions in the legs of mice with neurological motor disorders, enabling the animals to kick a ball, walk or run.

An endovascular wireless and battery-free millimetric implant enables the stimulation of peripheral nerves that are difficult to reach via traditional surgeries.

Deep-brain stimulation in freely behaving mice can be achieved via wide-field near-infrared illumination and stereotactically injected photothermal transducers activating neurons ectopically expressing a temperature-sensitive cation channel.

This Review discusses the most promising gene therapies, cell therapies and retinal prostheses for the treatment of retinal degeneration, as well as upcoming technologies for enhancing vision restoration.

This Review describes the current optogenetics toolkit, and discusses its preclinical and translational applicability.

An organic electrolytic photocapacitor transducing deep-red light into electrical signals and implanted within a thin cuff around the sciatic nerve of rats allows for wireless electrical stimulation of the nerve for over 100 days.

The integration of scalable and modular hardware and software for the remote operation of programmable miniaturized wireless networks allows for the study of the behaviour of large groups of rodents.

A generative model that learns mappings between hand kinematics and the associated neural spike trains can be rapidly adapted to new sessions or participants by using limited additional neural data.

Closed-loop electrical stimulation of the internal capsule of participants undergoing intracranial epilepsy monitoring improved the participants’ performance on a cognitive conflict task, and performance could be decoded from electrode activity.

A soft and lightweight neuroprosthetic hand that offers simultaneous myoelectric control and tactile feedback outperformed a conventional rigid neuroprosthetic hand in speed and dexterity.

A closed-loop brain–machine interface modulates sensory-affective experiences in real time in freely behaving rats by coupling neural codes for nociception directly with therapeutic cortical stimulation.

This Perspective argues that technologies for the neural interfacing of robotic devices with the body that have been clinically tested in humans should be leveraged toward the creation of a new generation of high-performance bionic limbs.

This Review Article discusses progress in the development of miniaturized and ultralightweight devices for neuroengineering that are wireless, battery-free and fully implantable.

A neuroprosthetic interface comprising a muscle actuator coupled to a natively pedicled skin flap in a cuff-like architecture elicits graded contact and vibratory afferent signals analogous to those elicited by mechanical stimulation of intact skin.

Input–output models can predict multiregional brain network dynamics in response to temporally varying patterns of ongoing direct electrical stimulation, with variabilities in prediction accuracy explained by at-rest functional connectivity.

This Review discusses non-invasive and invasive technologies for conveying artificial sensory feedback through bionic hands.

Two clinically relevant subtypes of post-traumatic stress disorder and major depressive disorder have been identified via machine learning analyses of functional connectivity patterns in resting-state electroencephalography.

Analyses of data from intracortical brain–computer interfaces implanted in rhesus macaques and in a human suggest that the circuit design parameters of current recording interfaces can be relaxed considerably without loss of performance.

Post-mortem histopathological data can be used to classify neuropathologies into six transdiagnostic clusters, and patient membership to these clusters can be predicted from cognitive scores, genotype and protein levels in cerebrospinal fluid.

The 300–1,000 Hz band of spiking activity, dominated by local single-unit spikes, can enhance the decoding performance of neural interfaces.

Neural activity residing in a low-dimensional space that reflects specific correlation patterns among neurons can be used to maintain the performance of brain–computer interfaces in the presence of recording instabilities.

A wireless and battery-free 1.7-mm³ neural stimulator implanted onto the sciatic nerve of rats allows for repeatable stimulation across a range of physiological responses.

A reconfigurable nanophotonic silicon probe, implanted in anaesthetized mice, that switches multiple optical beams in less than 20 μs enables the optical stimulation of multineuron spike patterns in the brain at sub-millisecond precision.

A near-infrared-light-sensitive photovoltaic subretinal prosthesis triggers behavioural responses in awake macaques, even two years after device implantation.

An intraneural electrode array placed in the optic nerve can selectively activate optic-nerve fibres in rabbits.

Bioresorbable photonic devices for the spectroscopic characterization of tissues and biofluids can continuously monitor cerebral temperature, oxygenation and neural activity in the brains of freely moving mice before they are fully resorbed.

Smartphone-controlled soft optofluidic probes with replaceable plug-like drug cartridges enable chronic in vivo pharmacology and optogenetics for the selective wireless manipulation of brain circuits in rodents.

Analyses of interregional neural networks from electrocorticography data from a large database of individuals with medication-resistant epilepsy highlight the structural, geometric and genetic factors that shape network organization.

Optoacoustic neuroimaging of mice expressing a genetically encoded calcium indicator allows for rapid, high-resolution, whole-brain 3D snapshots of neuronal calcium activity and haemodynamics.

Focal stimulation of cortical tissue from within a blood vessel via an electrode array mounted on a minimally invasive endovascular stent elicits responses from specific facial muscles and limbs in sheep.

Hydrogels made from decellularized human brain tissue facilitate the direct conversion of primary mouse embryonic fibroblasts into induced neuronal cells that lead to therapeutic outcomes after transplantation in an animal model of ischaemic stroke.

The combination of focused ultrasound and virally encoded receptors engineered to be activated by a designer drug enables, on intravenous administration of the drug, the non-invasive activation or inhibition of brain regions in mice, with cell-type and spatiotemporal specificity.

Viral transfection of a mixed nerve with two channelrhodopsins with spectrally distinct activation sensitivities enables, via two-colour stimulation of the nerve, optogenetic control over the activity of opposing muscle pairs in a rat hindlimb.

Gene editing of a single gene in the brain of an adult mouse model of fragile X syndrome, achieved via the intracranial injection of a nonviral Cas9 delivery vehicle, rescues mice from the exaggerated repetitive behaviours caused by the disease.

Intracellular, intercellular and extracellular silicon interfaces enable light-controlled non-genetic modulation of intracellular calcium dynamics, of cellular excitability, of neurotransmitter release from brain slices, and of brain activity in vivo.

Culturing conditions affect the transcriptomic profiles of induced neuronal cells, and 3D co-cultures of induced neuronal cells and astrocytic cells can be rapidly generated from the same pool of human embryonic stem cells.

Cells engineered to produce an analgesic in response to spearmint aroma and implanted in mouse models of chronic pain reduce the pain-associated behaviour after oral intake of spearmint essential oil with no adverse effects.

A computational approach that uses the statistics of movement to find a mapping between neural activity and motor variables decodes the intended movements of monkeys with performance comparable to that of supervised methods.

This Review discusses the role of glia as an effector of the performance and integration of devices implanted in the brain, and the implications of this for device development.

Ultrasound pulses controlling the release of an anaesthetic encapsulated in liposomes allow for the timing, intensity and duration of sciatic-nerve blocks in rats.

A man/machine interface based on the activity of spinal motor neurons reinnervating the muscles of a missing limb in amputees enables the generation of neural signals for potential prosthetic control.

Water exchange through the transmembrane channel aquaporin-4 can be measured by conventional dynamic-contrast-enhanced magnetic resonance imaging and is a sensitive biomarker of the proliferation of gliomas and their resistance to chemotherapy.

Comparisons of neural recordings across time, across subsets of neurons and across individuals requires the alignment of low-dimensional latent representations.

Robotic fingers and arms that augment the motor abilities of non-disabled individuals are increasingly feasible yet face neurocognitive barriers and hurdles in efferent motor control.

The dynamics of multiregional brain networks in response to temporally varying patterns of ongoing direct electrical stimulation can be predicted by modelling, with variabilities in prediction accuracy explained by at-rest functional connectivity.

Neuropathologies can be classified, on the basis of post-mortem histopathology and by using machine learning, into six transdiagnostic clusters associated with clinical phenotypes.

Wireless and leadless millimetre-scale implantable pulse generators, powered and controlled by ultrasonic links, enable the electrical stimulation of neural pathways in anaesthetized rats.

Needle-sized photonic devices that slowly dissolve in the body can spectroscopically characterize cerebral temperature, blood oxygenation and neural activity for weeks in unconstrained mice.

Smartphone-controlled optofluidic neural implants with replaceable and replenishable plug-like drug cartridges enable the selective wireless manipulation of brain circuits in rodents via chronic pharmacology and photostimulation.

The development of implantable electrode arrays that broadly and seamlessly integrate with brain tissue will require innovation that responsibly considers clinically relevant neuroethical concerns.

High-speed optoacoustic tomography can monitor the neural activity of a whole mouse brain, by using a genetically encoded calcium sensor originally developed for fluorescence microscopy.

Modelling diseases of the central and peripheral nervous systems and effectively treating neurological disorders via neuronal manipulation requires far better biomaterials and technology than are currently available.

A technique combining focused ultrasound for opening the blood–brain barrier and virally encoded engineered G-protein-coupled receptors for promoting the expression of a gene targeting excitatory neurons enables the non-invasive stimulation of specific brain regions and cell types in mice.

Design principles for the development of silicon biointerfaces enable the non-genetic, light-controlled modulation of intracellular Ca²⁺ dynamics, and of cellular excitability in vitro, in tissue slices and in mouse brains.

Polymer-coated gold nanoparticles carrying the CRISPR components for knocking out, in the striatum of adult mice with fragile X syndrome, a gene implied in the syndrome’s pathophysiology rescue the mice from the exaggerated repetitive behaviours characteristic of the syndrome’s phenotype.

Biopolymer matrices can modulate the transcriptomic profiles of stem-cell-derived neurons in 3D culture to make them resemble cells in specific brain regions, developmental stages and disease conditions.

Synthetic mammalian cells engineered to synthesize a painkiller in response to volatile spearmint reduce chronic pain in mice and do not seem to elicit adverse effects.

A method inspired by cryptography maps neural activity to limb movement without requiring the simultaneous collection of neural activity in the motor cortex and of the corresponding physical actions.

The ability to release an anaesthetic from liposomes by applying ultrasound opens up the possibility of managing localized pain on-demand.

High-frequency transcranial electric-field oscillations stimulate neural circuits in the deep brain.

Decoding the firing of individual spinal motor neurons enables the offline control of prosthetic limbs.

The increasing integration of wearable technologies with the human body raises neural and cognitive challenges and opportunities.