Parallel and distributed encoding of speech across human auditory cortex.

Speech perception is thought to rely on a cortical feedforward serial transformation of acoustic into linguistic representations. Using intracranial recordings across the entire human auditory cortex, electrocortical stimulation, and surgical ablation, we show that cortical processing across areas is not consistent with a serial hierarchical organization. Instead, response latency and receptive field analyses demonstrate parallel and distinct information processing in the primary and nonprimary auditory cortices. This functional dissociation was also observed where stimulation of the primary auditory cortex evokes auditory hallucination but does not distort or interfere with speech perception. Opposite effects were observed during stimulation of nonprimary cortex in superior temporal gyrus. Ablation of the primary auditory cortex does not affect speech perception. These results establish a distributed functional organization of parallel information processing throughout the human auditory cortex and demonstrate an essential independent role for nonprimary auditory cortex in speech processing.

Dynamic Stimulation of Visual Cortex Produces Form Vision in Sighted and Blind Humans.

A visual cortical prosthesis (VCP) has long been proposed as a strategy for restoring useful vision to the blind, under the assumption that visual percepts of small spots of light produced with electrical stimulation of visual cortex (phosphenes) will combine into coherent percepts of visual forms, like pixels on a video screen. We tested an alternative strategy in which shapes were traced on the surface of visual cortex by stimulating electrodes in dynamic sequence. In both sighted and blind participants, dynamic stimulation enabled accurate recognition of letter shapes predicted by the brain's spatial map of the visual world. Forms were presented and recognized rapidly by blind participants, up to 86 forms per minute. These findings demonstrate that a brain prosthetic can produce coherent percepts of visual forms.

Extracellular DNA Promotes Efficient Extracellular Electron Transfer by Pyocyanin in Pseudomonas aeruginosa Biofilms.

Redox cycling of extracellular electron shuttles can enable the metabolic activity of subpopulations within multicellular bacterial biofilms that lack direct access to electron acceptors or donors. How these shuttles catalyze extracellular electron transfer (EET) within biofilms without being lost to the environment has been a long-standing question. Here, we show that phenazines mediate efficient EET through interactions with extracellular DNA (eDNA) in Pseudomonas aeruginosa biofilms. Retention of pyocyanin (PYO) and phenazine carboxamide in the biofilm matrix is facilitated by eDNA binding. In vitro, different phenazines can exchange electrons in the presence or absence of DNA and can participate directly in redox reactions through DNA. In vivo, biofilm eDNA can also support rapid electron transfer between redox active intercalators. Together, these results establish that PYO:eDNA interactions support an efficient redox cycle with rapid EET that is faster than the rate of PYO loss from the biofilm.

Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields.

We report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice.

A three-dimensional liquid diode for soft, integrated permeable electronics.

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.

Capturing carbon dioxide from air with charged-sorbents.

Emissions reduction and greenhouse gas removal from the atmosphere are both necessary to achieve net-zero emissions and limit climate change1. There is thus a need for improved sorbents for the capture of carbon dioxide from the atmosphere, a process known as direct air capture. In particular, low-cost materials that can be regenerated at low temperatures would overcome the limitations of current technologies. In this work, we introduce a new class of designer sorbent materials known as 'charged-sorbents'. These materials are prepared through a battery-like charging process that accumulates ions in the pores of low-cost activated carbons, with the inserted ions then serving as sites for carbon dioxide adsorption. We use our charging process to accumulate reactive hydroxide ions in the pores of a carbon electrode, and find that the resulting sorbent material can rapidly capture carbon dioxide from ambient air by means of (bi)carbonate formation. Unlike traditional bulk carbonates, charged-sorbent regeneration can be achieved at low temperatures (90-100 °C) and the sorbent's conductive nature permits direct Joule heating regeneration2,3 using renewable electricity. Given their highly tailorable pore environments and low cost, we anticipate that charged-sorbents will find numerous potential applications in chemical separations, catalysis and beyond.

Large-scale single-neuron speech sound encoding across the depth of human cortex.

Understanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays1-3 to record from 685 neurons across cortical layers at nine sites in a high-level auditory region that is critical for speech, the superior temporal gyrus4,5, while participants listened to spoken sentences. Single neurons encoded a wide range of speech sound cues, including features of consonants and vowels, relative vocal pitch, onsets, amplitude envelope and sequence statistics. Neurons at each cross-laminar recording exhibited dominant tuning to a primary speech feature while also containing a substantial proportion of neurons that encoded other features contributing to heterogeneous selectivity. Spatially, neurons at similar cortical depths tended to encode similar speech features. Activity across all cortical layers was predictive of high-frequency field potentials (electrocorticography), providing a neuronal origin for macroelectrode recordings from the cortical surface. Together, these results establish single-neuron tuning across the cortical laminae as an important dimension of speech encoding in human superior temporal gyrus.

Water-responsive supercontractile polymer films for bioelectronic interfaces.

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics interfaces, however, cannot be standardized, because tissues are soft1-3 and have arbitrary shapes and sizes4-6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10-12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.

Complex molecule synthesis by electrocatalytic decarboxylative cross-coupling.

Modern retrosynthetic analysis in organic chemistry is based on the principle of polar relationships between functional groups to guide the design of synthetic routes1. This method, termed polar retrosynthetic analysis, assigns partial positive (electrophilic) or negative (nucleophilic) charges to constituent functional groups in complex molecules followed by disconnecting bonds between opposing charges2-4. Although this approach forms the basis of undergraduate curriculum in organic chemistry5 and strategic applications of most synthetic methods6, the implementation often requires a long list of ancillary considerations to mitigate chemoselectivity and oxidation state issues involving protecting groups and precise reaction choreography3,4,7. Here we report a radical-based Ni/Ag-electrocatalytic cross-coupling of substituted carboxylic acids, thereby enabling an intuitive and modular approach to accessing complex molecular architectures. This new method relies on a key silver additive that forms an active Ag nanoparticle-coated electrode surface8,9 in situ along with carefully chosen ligands that modulate the reactivity of Ni. Through judicious choice of conditions and ligands, the cross-couplings can be rendered highly diastereoselective. To demonstrate the simplifying power of these reactions, concise syntheses of 14 natural products and two medicinally relevant molecules were completed.

Perovskite solar cells based on screen-printed thin films.

One potential advantage of perovskite solar cells (PSCs) is the ability to solution process the precursors and deposit films from solution1,2. At present, spin coating, blade coating, spray coating, inkjet printing and slot-die printing have been investigated to deposit hybrid perovskite thin films3-6. Here we expand the range of deposition methods to include screen-printing, enabled by a stable and viscosity-adjustable (40-44,000 cP) perovskite ink made from a methylammonium acetate ionic liquid solvent. We demonstrate control over perovskite thin-film thickness (from about 120 nm to about 1,200 nm), area (from 0.5 × 0.5 cm2 to 5 × 5 cm2) and patterning on different substrates. Printing rates in excess of 20 cm s-1 and close to 100% ink use were achieved. Using this deposition method in ambient air and regardless of humidity, we obtained the best efficiencies of 20.52% (0.05 cm2) and 18.12% (1 cm2) compared with 20.13% and 12.52%, respectively, for the spin-coated thin films in normal devices with thermally evaporated metal electrodes. Most notably, fully screen-printing devices with a single machine in ambient air have been successfully explored. The corresponding photovoltaic cells exhibit high efficiencies of 14.98%, 13.53% and 11.80% on 0.05-cm2, 1.00-cm2 and 16.37-cm2 (small-module) areas, respectively, along with 96.75% of the initial efficiency retained over 300 h of operation at maximum power point.

Direct imaging of single-molecule electrochemical reactions in solution.

Chemical reactions tend to be conceptualized in terms of individual molecules transforming into products, but are usually observed in experiments that probe the average behaviour of the ensemble. Single-molecule methods move beyond ensemble averages and reveal the statistical distribution of reaction positions, pathways and dynamics1-3. This has been shown with optical traps and scanning probe microscopy manipulating and observing individual reactions at defined locations with high spatial resolution4,5, and with modern optical methods using ultrasensitive photodetectors3,6,7 that enable high-throughput single-molecule measurements. However, effective probing of single-molecule solution chemistry remains challenging. Here we demonstrate optical imaging of single-molecule electrochemical reactions7 in aqueous solution and its use for super-resolution microscopy. The method utilizes a chemiluminescent reaction involving a ruthenium complex electrochemically generated at an electrode8, which ensures minimal background signal. This allows us to directly capture single photons of the electrochemiluminescence of individual reactions, and to develop super-resolved electrochemiluminescence microscopy for imaging the adhesion dynamics of live cells with high spatiotemporal resolution. We anticipate that our method will advance the fundamental understanding of electrochemical reactions and prove useful for bioassays and cell-imaging applications.

High-frequency and intrinsically stretchable polymer diodes.

Skin-like intrinsically stretchable soft electronic devices are essential to realize next-generation remote and preventative medicine for advanced personal healthcare1-4. The recent development of intrinsically stretchable conductors and semiconductors has enabled highly mechanically robust and skin-conformable electronic circuits or optoelectronic devices2,5-10. However, their operating frequencies have been limited to less than 100 hertz, which is much lower than that required for many applications. Here we report intrinsically stretchable diodes-based on stretchable organic and nanomaterials-capable of operating at a frequency as high as 13.56 megahertz. This operating frequency is high enough for the wireless operation of soft sensors and electrochromic display pixels using radiofrequency identification in which the base-carrier frequency is 6.78 megahertz or 13.56 megahertz. This was achieved through a combination of rational material design and device engineering. Specifically, we developed a stretchable anode, cathode, semiconductor and current collector that can satisfy the strict requirements for high-frequency operation. Finally, we show the operational feasibility of our diode by integrating it with a stretchable sensor, electrochromic display pixel and antenna to realize a stretchable wireless tag. This work is an important step towards enabling enhanced functionalities and capabilities for skin-like wearable electronics.

Synergistic material-microbe interface toward deeper anaerobic defluorination.

Per- and polyfluoroalkyl substances (PFAS), particularly the perfluorinated ones, are recalcitrant to biodegradation. By integrating an enrichment culture of reductive defluorination with biocompatible electrodes for the electrochemical process, a deeper defluorination of a C6-perfluorinated unsaturated PFAS was achieved compared to the biological or electrochemical system alone. Two synergies in the bioelectrochemical system were identified: i) The in-series microbial-electrochemical defluorination and ii) the electrochemically enabled microbial defluorination of intermediates. These synergies at the material-microbe interfaces surpassed the limitation of microbial defluorination and further turned the biotransformation end products into less fluorinated products, which could be less toxic and more biodegradable in the environment. This material-microbe hybrid system brings opportunities in the bioremediation of PFAS driven by renewable electricity and warrants future research on mechanistic understanding of defluorinating and electroactive microorganisms at the material-microbe interface for system optimizations.

Engineering bionanoreactor in bacteria for efficient hydrogen production.

Hydrogen production through water splitting is a vital strategy for renewable and sustainable clean energy. In this study, we developed an approach integrating nanomaterial engineering and synthetic biology to establish a bionanoreactor system for efficient hydrogen production. The periplasmic space (20 to 30 nm) of an electroactive bacterium, Shewanella oneidensis MR-1, was engineered to serve as a bionanoreactor to enhance the interaction between electrons and protons, catalyzed by hydrogenases for hydrogen generation. To optimize electron transfer, we used the microbially reduced graphene oxide (rGO) to coat the electrode, which improved the electron transfer from the electrode to the cells. Native MtrCAB protein complex on S. oneidensis and self-assembled iron sulfide (FeS) nanoparticles acted in tandem to facilitate electron transfer from an electrode to the periplasm. To enhance proton transport, S. oneidensis MR-1 was engineered to express Gloeobacter rhodopsin (GR) and the light-harvesting antenna canthaxanthin. This led to efficient proton pumping when exposed to light, resulting in a 35.6% increase in the rate of hydrogen production. The overexpression of native [FeFe]-hydrogenase further improved the hydrogen production rate by 56.8%. The bionanoreactor engineered in S. oneidensis MR-1 achieved a hydrogen yield of 80.4 µmol/mg protein/day with a Faraday efficiency of 80% at a potential of -0.75 V. This periplasmic bionanoreactor combines the strengths of both nanomaterial and biological components, providing an efficient approach for microbial electrosynthesis.

Third-order nanocircuit elements for neuromorphic engineering.

Current hardware approaches to biomimetic or neuromorphic artificial intelligence rely on elaborate transistor circuits to simulate biological functions. However, these can instead be more faithfully emulated by higher-order circuit elements that naturally express neuromorphic nonlinear dynamics1-4. Generating neuromorphic action potentials in a circuit element theoretically requires a minimum of third-order complexity (for example, three dynamical electrophysical processes)5, but there have been few examples of second-order neuromorphic elements, and no previous demonstration of any isolated third-order element6-8. Using both experiments and modelling, here we show how multiple electrophysical processes-including Mott transition dynamics-form a nanoscale third-order circuit element. We demonstrate simple transistorless networks of third-order elements that perform Boolean operations and find analogue solutions to a computationally hard graph-partitioning problem. This work paves a way towards very compact and densely functional neuromorphic computing primitives, and energy-efficient validation of neuroscientific models.

Spontaneous travelling cortical waves gate perception in behaving primates.

Perceptual sensitivity varies from moment to moment. One potential source of this variability is spontaneous fluctuations in cortical activity that can travel as waves1. Spontaneous travelling waves have been reported during anaesthesia2-7, but it is not known whether they have a role during waking perception. Here, using newly developed analytic techniques to characterize the moment-to-moment dynamics of noisy multielectrode data, we identify spontaneous waves of activity in the extrastriate visual cortex of awake, behaving marmosets (Callithrix jacchus). In monkeys trained to detect faint visual targets, the timing and position of spontaneous travelling waves before target onset predicted the magnitude of target-evoked activity and the likelihood of target detection. By contrast, spatially disorganized fluctuations of neural activity were much less predictive. These results reveal an important role for spontaneous travelling waves in sensory processing through the modulation of neural and perceptual sensitivity.

Values encoded in orbitofrontal cortex are causally related to economic choices.

In the eighteenth century, Daniel Bernoulli, Adam Smith and Jeremy Bentham proposed that economic choices rely on the computation and comparison of subjective values1. This hypothesis continues to inform modern economic theory2 and research in behavioural economics3, but behavioural measures are ultimately not sufficient to verify the proposal4. Consistent with the hypothesis, when agents make choices, neurons in the orbitofrontal cortex (OFC) encode the subjective value of offered and chosen goods5. Value-encoding cells integrate multiple dimensions6-9, variability in the activity of each cell group correlates with variability in choices10,11 and the population dynamics suggests the formation of a decision12. However, it is unclear whether these neural processes are causally related to choices. More generally, the evidence linking economic choices to value signals in the brain13-15 remains correlational16. Here we show that neuronal activity in the OFC is causal to economic choices. We conducted two experiments using electrical stimulation in rhesus monkeys (Macaca mulatta). Low-current stimulation increased the subjective value of individual offers and thus predictably biased choices. Conversely, high-current stimulation disrupted both the computation and the comparison of subjective values, and thus increased choice variability. These results demonstrate a causal chain linking subjective values encoded in OFC to valuation and choice.

Doping-induced assembly interface for noninvasive in vivo local and systemic immunomodulation.

Peripheral neural interfaces, potent in modulating local and systemic immune responses for disease treatment, face significant challenges due to the peripheral nerves' broad distribution in tissues like the fascia, periosteum, and skin. The incongruity between static electronic components and the dynamic, complex organization of the peripheral nervous system often leads to interface failure, stalling circuit research and clinical applications. To overcome these, we developed a self-assembling, tissue-adaptive electrode composed of a single-component cocktail nanosheet colloid, including dopants, conducting polymers, stabilizers, and an MXene catalyst. Delivered via a jet injector to designated nerve terminals, this assembly utilizes reactive oxygen species to catalytically dope poly (3,4-ethylenedioxythiophene), enhancing π-π interactions between nanosheets, and yielding a conductive, biodegradable interface. This interface effectively regulates local immune activity and promotes sensory and motor nerve functional restoration in nerve-injured mice, while engaging the vagal-adrenal axis in freely moving mice, eliciting catecholamine neurotransmitter release, and suppressing systemic cytokine storms. This innovative strategy specifically targets nerve substructures, bolstering local and systemic immune modulation, and paving the way for the development of self-adaptive dynamic neural interfaces.

Human Hippocampal Ripples Signal Encoding of Episodic Memories.

Direct human brain recordings have confirmed the presence of high-frequency oscillatory events, termed ripples, during awake behavior. While many prior studies have focused on medial temporal lobe (MTL) ripples during memory retrieval, here we investigate ripples during memory encoding. Specifically, we ask whether ripples during encoding predict whether and how memories are subsequently recalled. Detecting ripples from MTL electrodes implanted in 116 neurosurgical participants (n = 61 male) performing a verbal episodic memory task, we find that encoding ripples do not distinguish recalled from not recalled items in any MTL region, even as high-frequency activity during encoding predicts recall in these same regions. Instead, hippocampal ripples increase during encoding of items that subsequently lead to recall of temporally and semantically associated items during retrieval, a phenomenon known as clustering. This subsequent clustering effect arises specifically when hippocampal ripples co-occur during encoding and retrieval, suggesting that ripples mediate both encoding and reinstatement of episodic memories.

Direct Electron Transfer-Type Oxidoreductases for Biomedical Applications.

Among the various types of enzyme-based biosensors, sensors utilizing enzymes capable of direct electron transfer (DET) are recognized as the most ideal. However, only a limited number of redox enzymes are capable of DET with electrodes, that is, dehydrogenases harboring a subunit or domain that functions specifically to accept electrons from the redox cofactor of the catalytic site and transfer the electrons to the external electron acceptor. Such subunits or domains act as built-in mediators for electron transfer between enzymes and electrodes; consequently, such enzymes enable direct electron transfer to electrodes and are designated as DET-type enzymes. DET-type enzymes fall into several categories, including redox cofactors of catalytic reactions, built-in mediators for DET with electrodes and by their protein hierarchic structures, DET-type oxidoreductases with oligomeric structures harboring electron transfer subunits, and monomeric DET-type oxidoreductases harboring electron transfer domains. In this review, we cover the science of DET-type oxidoreductases and their biomedical applications. First, we introduce the structural biology and current understanding of DET-type enzyme reactions. Next, we describe recent technological developments based on DET-type enzymes for biomedical applications, such as biosensors and biochemical energy harvesting for self-powered medical devices. Finally, after discussing how to further engineer and create DET-type enzymes, we address the future prospects for DET-type enzymes in biomedical engineering.