Neuroscience › Cellular and Molecular Neuroscience

Neuroscience and Neural Engineering

Works Count: 62560

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This cluster of papers explores advancements in neural interface technology, focusing on neural stimulation, electrode arrays, neuroprostheses, retinal prosthesis, nanomaterials, chronic recording, brain tissue response to implants, biocompatible implants, and electrical stimulation. The research covers a wide range of topics related to the development and application of neural interfaces for both experimental and clinical purposes.

Keywords

Neural Stimulation; Electrode Arrays; Neuroprostheses; Retinal Prosthesis; Nanomaterials; Chronic Recording; Brain Tissue Response; Biocompatible Implants; Electrical Stimulation; Neuronal Networks

The Ionic Channels in Excitable Membranes

1975-01-01

R. D. Keynes

This chapter contains section titled: References Discussion References This chapter contains section titled: References Discussion References

Biophysics of Computation

1998-11-12

Christof Koch

Neural network research often builds on the fiction that neurons are simple linear threshold units, completely neglecting the highly dynamic and complex nature of synapses, dendrites, and voltage-dependent ionic currents. … Neural network research often builds on the fiction that neurons are simple linear threshold units, completely neglecting the highly dynamic and complex nature of synapses, dendrites, and voltage-dependent ionic currents. Biophysics of Computation: Information Processing in Single Neurons challenges this notion, using richly detailed experimental and theoretical findings from cellular biophysics to explain the repertoire of computational functions available to single neurons. The author shows how individual nerve cells can multiply, integrate, or delay synaptic inputs and how information can be encoded in the voltage across the membrane, in the intracellular calcium concentration, or in the timing of individual spikes. Key topics covered include the linear cable equation; cable theory as applied to passive dendritic trees and dendritic spines; chemical and electrical synapses and how to treat them from a computational point of view; nonlinear interactions of synaptic input in passive and active dendritic trees; the Hodgkin-Huxley model of action potential generation and propagation; phase space analysis; linking stochastic ionic channels to membrane-dependent currents; calcium and potassium currents and their role in information processing; the role of diffusion, buffering and binding of calcium, and other messenger systems in information processing and storage; short- and long-term models of synaptic plasticity; simplified models of single cells; stochastic aspects of neuronal firing; the nature of the neuronal code; and unconventional models of sub-cellular computation. Biophysics of Computation: Information Processing in Single Neurons serves as an ideal text for advanced undergraduate and graduate courses in cellular biophysics, computational neuroscience, and neural networks, and will appeal to students and professionals in neuroscience, electrical and computer engineering, and physics.

Electrophysiological properties of neocortical neurons in vitro

1982-12-01

Barry W. Connors , Michael J. Gutnick , D. A. Prince

1. Intracellular recordings were obtained from neurons of the guinea pig sensorimotor cortical slice maintained in vitro. Under control recording conditions input resistances, time constants, and spiking characteristics of slice … 1. Intracellular recordings were obtained from neurons of the guinea pig sensorimotor cortical slice maintained in vitro. Under control recording conditions input resistances, time constants, and spiking characteristics of slice neurons were well within the ranges reported by other investigators for neocortical neurons in situ. However, resting potentials (mean of -75 mV) and spike amplitudes (mean of 93.5 mV) were 10-25 mV greater than has been observed in intact preparations. 2. Current-voltage relationships obtained under current clamp revealed a spectrum of membrane-rectifying properties at potentials that were subthreshold for spike generation. Ionic and pharmacologic analyses suggest that subthreshold membrane behavior is dominated by voltage-sensitive, very slowly inactivating conductances to K+ and Na+. 3. Action potentials were predominantly Na+ dependent under normal conditions but when outward K+ currents were reduced pharmacologically, it was possible, in most cells, to evoke a non-Na+-dependent, tetrodotoxin-(TTX) insensitive spike, which was followed by a prominent depolarizing after-potential. Both of these events were blocked by the Ca2+ current antagonists, Co2+ and Mn2+. 4. A small population of neurons generated intrinsic, all-or-none burst potentials when depolarized with current pulses or by synaptic activation. These cells were located at a narrow range of depths comprising layer IV and the more superficial parts of layer V. 5. Spontaneous excitatory synaptic potentials appeared in all neurons. Spontaneous inhibitory events were visible in only about 10% of the cells, and in those cases apparently reversed polarity at a level slightly positive to resting potential. Stimulation of the surface of the slice at low intensities evoked robust and usually concurrent excitatory and inhibitory synaptic potentials. Unitary inhibitory postsynaptic potentials (IPSPs) reversed at levels positive to rest. Stronger stimulation produced a labile, long-duration, hyperpolarizing IPSP with a reversal potential 15-20 mV negative to the resting level. 6. Neocortical neurons in vitro retain the basic membrane and synaptic properties ascribed to them in situ. However, the array of passive and active membrane behavior observed in the slice suggests that cortical neurons may be differentiated by specific functional properties as well as by their extensive morphological diversity.

Mesocorticolimbic dopaminergic network: functional and regulatory roles

1991-01-01

Michel Le Moal , H. Simon

The control of firing pattern in nigral dopamine neurons: burst firing

1984-11-01

AA Grace , BS Bunney

In addition to firing in a single spiking mode, dopamine (DA) cells have been observed to fire in a bursting pattern with consecutive spikes in a burst displaying progressively decreasing … In addition to firing in a single spiking mode, dopamine (DA) cells have been observed to fire in a bursting pattern with consecutive spikes in a burst displaying progressively decreasing amplitude and increasing duration. In vivo intracellular recording demonstrated the bursts to typically ride on a depolarizing wave (5 to 15 mV amplitude). Although the burst-firing frequency of DA cells showed little correlation with the base line firing rate, increases in firing rate were usually associated with an increase in burst firing. Increases in burst firing could also be elicited by intracellular calcium injection and could be prevented by intracellular injection of EGTA, suggesting a calcium involvement in bursting. Blockade of potassium conductances with extracellular iontophoresis of barium or intracellular injection of tetraethylammonium bromide could also trigger an increased degree of burst firing in DA cells. These data suggest that the increased calcium influx accompanying an increased firing rate triggers burst firing, possibly by inactivating a potassium conductance. A switch from a single spiking mode to a burst-firing mode may be important in modulating striatal DA release, as shown for burst firing in other preparations.

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Calcium release from the sarcoplasmic reticulum

1977-01-01

Makoto Endo

Branching dendritic trees and motoneuron membrane resistivity

1959-11-01

Wilfrid Rall

Single-channel currents recorded from membrane of denervated frog muscle fibres

1976-04-01

Erwin Neher , Bert Sakmann

Voltage Dependent Charge Movement in Skeletal Muscle: a Possible Step in Excitation–Contraction Coupling

1973-03-01

Martin F. Schneider , W K Chandler

Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia.

1977-01-01

Jens Astrup , L. Symon , Neil M. Branston +1 more

As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm … As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as well as evoked potential were made in the baboon neocortex. Reductions in blood flow were obtained by occlusion of the middle cerebral artery and depression beyond the ischemic threshold of electrical function achieved by a reduction of systemic blood pressure which, in the ischemic zones, changed local cerebral blood flow proportionally. Abolition of evoked response could not be explained by depolarization by release of intracellular K+, nor was it critically dependent on cortical pH. However, the massive release of intracellular K+ was by itself critically dependent on cortical blood flow and occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive. That neurons can survive for some time in this state of lethargy is evidenced by the observations that an increase in rCBF, if sufficient, can restore evoked potential and normalize extracellular K+ activity as well as pH.

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CHEMOAFFINITY IN THE ORDERLY GROWTH OF NERVE FIBER PATTERNS AND CONNECTIONS

1963-10-01

R. W. Sperry

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Stimulation of the cerebral cortex in the intact human subject

1980-05-01

P A Merton , Helen Morton

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A quantitative description of membrane current and its application to conduction and excitation in nerve

1952-08-28

A. L. Hodgkin , A. F. Huxley

The role of calcium in neuromuscular facilitation

1968-03-01

B. Katz , Ricardo Miledi

1. The hypothesis is put forward that a residue of the ;active calcium' which enters the terminal axon membrane during the nerve impulse is responsible for short-term facilitation.2. This suggestion … 1. The hypothesis is put forward that a residue of the ;active calcium' which enters the terminal axon membrane during the nerve impulse is responsible for short-term facilitation.2. This suggestion has been tested on the myoneural junction by varying the local calcium concentration so that during the first of two nerve impulses [Ca](o) is either much lower than, or raised to a level approaching that, during the second impulse. Facilitation is much larger in the latter case, which is in accordance with the ;calcium hypothesis'.3. A short pulse of depolarization focally applied to the junction is followed by a brief period of very intense facilitation. This can be seen in the tetrodotoxin-treated preparation, e.g. by lengthening the depolarization from 1 to 2 msec which can cause a more than fifty-fold increase in transmitter release. This large ;early facilitation' (which presumably occurs also during the course of a normal action potential) is discussed in relation to the ;calcium hypothesis'.

Structure and Function of Voltage-Sensitive Ion Channels

1988-10-07

William A. Catterall

Voltage-sensitive ion channels mediate action potentials in electrically excitable cells and play important roles in signal transduction in other cell types. In the past several years, their protein components have … Voltage-sensitive ion channels mediate action potentials in electrically excitable cells and play important roles in signal transduction in other cell types. In the past several years, their protein components have been identified, isolated, and restored to functional form in the purified state. Na + and Ca 2+ channels consist of a principal transmembrane subunit, which forms the ion-conducting pore and is expressed with a variable number of associated subunits in different cell types. The principal subunits of voltage-sensitive Na + , Ca 2+ , and K + channels are homologous members of a gene family. Models relating the primary structures of these principal subunits to their functional properties have been proposed, and experimental results have begun to define a functional map of these proteins. Coordinated application of biochemical, biophysical, and molecular genetic methods should lead to a clear understanding of the molecular basis of electrical excitability.

Self-Organized Formation of Polarized Cortical Tissues from ESCs and Its Active Manipulation by Extrinsic Signals

2008-11-01

Mototsugu Eiraku , Kiichi Watanabe , Mami Matsuo‐Takasaki +7 more

Impulses and Physiological States in Theoretical Models of Nerve Membrane

1961-07-01

Richard Fitzhugh

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Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches

1981-08-01

Owen P. Hamill , Alain Marty , Erwin Neher +2 more

A permanent change in brain function resulting from daily electrical stimulation

1969-11-01

Graham V. Goddard , Dan McIntyre , Curtis K. Leech

Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain.

1954-01-01

John Olds , Peter Milner

The action of calcium on the electrical properties of squid axons

1957-07-11

B. Frankenhaeuser , A. L. Hodgkin

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to … Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

A microfluidic culture platform for CNS axonal injury, regeneration and transport

2005-07-21

Anne Marion Taylor , Mathew Blurton‐Jones , Seog Woo Rhee +3 more

Electrophysiological properties of guinea‐pig thalamic neurones: an in vitro study.

1984-04-01

Henrik Jahnsen , R. Llinás

The electroresponsive properties of guinea‐pig thalamic neurones were studied using an in vitro slice preparation. A total of 650 cells were recorded intracellularly comprising all regions of the thalamus; of … The electroresponsive properties of guinea‐pig thalamic neurones were studied using an in vitro slice preparation. A total of 650 cells were recorded intracellularly comprising all regions of the thalamus; of these 229 fulfilled our criterion for recording stability and were used as the data base for this report. The resting membrane potential for thirty‐four representative neurones which were analysed in detail was ‐64 +/‐ 5 mV (mean +/‐ S.D.), input resistance 42 +/‐ 18 M omega, and action potential amplitude 80 +/‐ 7 mV. Intracellular staining with horseradish peroxidase and Lucifer Yellow revealed that the recorded cells had different morphology. In some their axonal trajectory characterized them as thalamo‐cortical relay cells. Two main types of neuronal firing were observed. From a membrane potential negative to ‐60 mV, anti‐ or orthodromic and direct activation generated a single burst of spikes, consisting of a low‐threshold spike (l.t.s.) of low amplitude and a set of fast superimposed spikes. Tonic repetitive firing was observed if the neurones were activated from a more positive membrane potential; this was a constant finding in all but two of the cells which fulfilled the stability criteria. The l.t.s. response was totally inactivated at membrane potentials positive to ‐55 mV. As the membrane was hyperpolarized from this level the amplitude of the l.t.s. increased and became fully developed at potentials negative to ‐70 mV. This increase is due to a de‐inactivation of the ionic conductance generating this response. After activation the l.t.s. showed refractoriness for approximately 170 ms. Deinactivation of l.t.s. is a voltage‐ and time‐dependent process; full de‐inactivation after a step hyperpolarization to maximal l.t.s. amplitude (‐75 to ‐80 mV) requires 150‐180 ms. Membrane depolarization positive to ‐55 mV generated sudden sustained depolarizing 'plateau potentials', capable of supporting repetitive firing (each action potential being followed by a marked after‐hyperpolarization, a.h.p.). The a.h.p. and the plateau potential controlled the voltage trajectory during the interspike interval and, with the fast spike, constitute a functional state where the thalamic neurone displayed oscillatory properties. Frequency‐current (f‐I) plots from different initial levels of membrane potential were obtained by the application of square current pulses of long duration (2s). From resting membrane potential and from hyperpolarized levels a rather stereotyped onset firing rate was observed due to the presence of the l.t.s.(ABSTRACT TRUNCATED AT 400 WORDS)

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Voltage oscillations in the barnacle giant muscle fiber

1981-07-01

Catherine E. Morris , Harold Lecar

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A second-generation current conveyor and its applications

1970-02-01

A.S. Sedra , K.C. Smith

Which elements are excited in electrical stimulation of mammalian central nervous system: A review

1975-11-01

James B. Ranck

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An Active Pulse Transmission Line Simulating Nerve Axon

1962-10-01

J. Nagumo , S. Arimoto , S. Yoshizawa

To electronically simulate an animal nerve axon, the authors made an active pulse transmission line using tunnel diodes. The equation of propagation for this line is the same as that … To electronically simulate an animal nerve axon, the authors made an active pulse transmission line using tunnel diodes. The equation of propagation for this line is the same as that for a simplified model of nerve membrane treated elsewhere. This line shapes the signal waveform during transmission, that is, there being a specific pulse-like waveform peculiar to this line, smaller signals are amplified, larger ones are attenuated, narrower ones are widened and those which are wider are shrunk, all approaching the above-mentioned specific waveform. In addition, this line has a certain threshold value in respect to the signal height, and signals smaller than the threshold or noise are eliminated in the course of transmission. Because of the above-mentioned shaping action and the existence of a threshold, this line makes possible highly reliable pulse transmission, and will be useful for various kinds of information-processing systems.

Low access resistance perforated patch recordings using amphotericin B

1991-03-01

James L. Rae , Kim Cooper , Peter Gates +1 more

Cholinergic and inhibitory synapses in a pathway from motor‐axon collaterals to motoneurones

1954-12-30

J. C. Eccles , P. Fatt , K. Koketsu

Electronic dura mater for long-term multimodal neural interfaces

2015-01-09

Ivan R. Minev , Pavel Musienko , Arthur Hirsch +7 more

The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and … The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and elasticity of dura mater, the protective membrane of the brain and spinal cord. The electronic dura mater, which we call e-dura, embeds interconnects, electrodes, and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. The soft implants extracted cortical states in freely behaving animals for brain-machine interface and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury.

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Stimulation of neurite outgrowth using an electrically conducting polymer

1997-08-19

Christine E. Schmidt , Venkatram R. Shastri , Joseph P. Vacanti +1 more

Damage to peripheral nerves often cannot be repaired by the juxtaposition of the severed nerve ends. Surgeons have typically used autologous nerve grafts, which have several drawbacks including the need … Damage to peripheral nerves often cannot be repaired by the juxtaposition of the severed nerve ends. Surgeons have typically used autologous nerve grafts, which have several drawbacks including the need for multiple surgical procedures and loss of function at the donor site. As an alternative, the use of nerve guidance channels to bridge the gap between severed nerve ends is being explored. In this paper, the electrically conductive polymer—oxidized polypyrrole (PP)—has been evaluated for use as a substrate to enhance nerve cell interactions in culture as a first step toward potentially using such polymers to stimulate in vivo nerve regeneration. Image analysis demonstrates that PC-12 cells and primary chicken sciatic nerve explants attached and extended neurites equally well on both PP films and tissue culture polystyrene in the absence of electrical stimulation. In contrast, PC-12 cells interacted poorly with indium tin oxide (ITO), poly( l -lactic acid) (PLA), and poly(lactic acid-co-glycolic acid) surfaces. However, PC-12 cells cultured on PP films and subjected to an electrical stimulus through the film showed a significant increase in neurite lengths compared with ones that were not subjected to electrical stimulation through the film and tissue culture polystyrene controls. The median neurite length for PC-12 cells grown on PP and subjected to an electrical stimulus was 18.14 μm ( n = 5643) compared with 9.5 μm ( n = 4440) for controls. Furthermore, animal implantation studies reveal that PP invokes little adverse tissue response compared with poly(lactic acid-co-glycolic acid).

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Autoimmune Response to Acetylcholine Receptor

1973-05-25

Jim Patrick , Jon Lindstrom

Injection of rabbits with acetylcholine receptor highly purified from the electric organ of Electrophorus electricus emulsified in complete Freund's adjuvant resulted in the production of precipitating antibody to acetylcholine receptor. … Injection of rabbits with acetylcholine receptor highly purified from the electric organ of Electrophorus electricus emulsified in complete Freund's adjuvant resulted in the production of precipitating antibody to acetylcholine receptor. After the second injection of antigen, the animals developed the flaccid paralysis and abnormal electromyographs characteristic of neuromuscular blockade. Treatment with the anticholinesterases edrophonium or neostigmine dramatically alleviated the paralysis and the fatigue seen in electromyography.

Co‐operative action of calcium ions in transmitter release at the neuromuscular junction

1967-11-01

F. A. Dodge , R Rahamimoff

1. The quantitative dependence of transmitter release on external calcium concentration has been studied at the frog neuromuscular junction, using intracellular recording and taking the amplitude of the end‐plate potential … 1. The quantitative dependence of transmitter release on external calcium concentration has been studied at the frog neuromuscular junction, using intracellular recording and taking the amplitude of the end‐plate potential (e.p.p.) as an index of the number of packets released. 2. The relation between [Ca] and the e.p.p. is highly non‐linear. The initial part of this relation on double logarithmic co‐ordinates gives a straight line with a slope of nearly four (mean 3·78 ± 0·2 S.D. in 28 experiments). Addition of a constant amount of Mg reduces the e.p.p. without altering the slope of the log e.p.p./log Ca relation. 3. The slope of this logarithmic relation diminishes as [Ca] is raised towards the normal level. 4. The results are explained quantitatively on the hypothesis that Ca ions combine with a specific site X on the nerve terminal forming CaX, and that the number of packets of acetylcholine released is proportional to the fourth power of [CaX]. 5. The analysis suggests that a co‐operative action of about four calcium ions is necessary for the release of each quantal packet of transmitter by the nerve impulse.

Surgery in the Rat during Electrical Analgesia Induced by Focal Brain Stimulation

1969-04-25

David V. Reynolds

Chronic monopolar electrodes were implanted in the region of the midbrain central gray in eight rats. In three rats, continuous 60 cycle-per-second sine-wave stimulation resulted in an electrical analgesia defined … Chronic monopolar electrodes were implanted in the region of the midbrain central gray in eight rats. In three rats, continuous 60 cycle-per-second sine-wave stimulation resulted in an electrical analgesia defined by the elimination of responses to aversive stimulation while general motor responsiveness was retained. Exploratory laparotomy was carried out in these animals during continuous brain stimulation without the use of chemical anesthetics. Following surgery, brain stimulation was terminated, and responses to aversive stimuli returned. Electrodes effective in inducing electrical analgesia at the lowest currents were located at the dorsolateral perimeter of the midbrain central gray. It was concluded that focal brain stimulation in this region can induce analgesia in the absence of diffusely applied "whole brain" stimulation.

Intracellular and extracellular electrophysiology of nigral dopaminergic neurons—1. Identification and characterization

1983-10-01

Anthony A. Grace , B.S. Bunney

Scalp electrode impedance, infection risk, and EEG data quality

2001-03-01

Thomas C. Ferrée , Phan Luu , Gerald S. Russell +1 more

Voltage clamp studies of a transient outward membrane current in gastropod neural somata

1971-02-01

John A. Connor , Charles F. Stevens

1. Outward directed membrane currents have been studied in voltage clamp experiments on isolated neural somata of the marine gastropod Anisodoris.2. Stepping the membrane potential from a hyperpolarized level to … 1. Outward directed membrane currents have been studied in voltage clamp experiments on isolated neural somata of the marine gastropod Anisodoris.2. Stepping the membrane potential from a hyperpolarized level to a value in the neighbourhood of resting potential (-35 to -50 mV at 5 degrees C) results in an outward current transient, I(A), which is apparently carried by potassium ions.3. The peak amplitude of I(A) is dependent upon both the holding voltage level and the test step voltage while the time courses of development and decay are independent of, or only slightly dependent on, these parameters.4. The developing and decaying phases of I(A) are approximated by exponentials, leading to time constants for development of 10-25 msec and for decay of 220-600 msec over the aggregate of cells studied (data at 5 degrees C). Q(10) for the processes is approximately 3.5. It is concluded that the transport mechanism for I(A) is at least operationally distinct from the mechanism underlying delayed outward current, I(K).

Neural Stimulation and Recording Electrodes

2008-04-22

Stuart F. Cogan

Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An … Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An understanding of the electrochemical mechanisms underlying the behavior of neural stimulation and recording electrodes is important for the development of chronically implanted devices, particularly those employing large numbers of microelectrodes. For stimulation, materials that support charge injection by capacitive and faradaic mechanisms are available. These include titanium nitride, platinum, and iridium oxide, each with certain advantages and limitations. The use of charge-balanced waveforms and maximum electrochemical potential excursions as criteria for reversible charge injection with these electrode materials are described and critiqued. Techniques for characterizing electrochemical properties relevant to stimulation and recording are described with examples of differences in the in vitro and in vivo response of electrodes.

Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo

2011-11-13

Jonathan Viventi , Dae‐Hyeong Kim , Leif Vigeland +7 more

Response of brain tissue to chronically implanted neural electrodes

2005-09-28

Vadim S. Polikov , Patrick A. Tresco , W.M. Reichert

An analysis of the end‐plate potential recorded with an intra‐cellular electrode

1951-11-28

P. Fatt , B. Katz

Somatosensory cortical map changes following digit amputation in adult monkeys

1984-04-20

Michael M. Merzenich , Randall J. Nelson , Michael P. Stryker +3 more

Abstract The cortical representations of the hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2–8 months after surgical amputation of digit 3, … Abstract The cortical representations of the hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2–8 months after surgical amputation of digit 3, or of both digits 2 and 3. Digital nerves were tied to prevent their regeneration within the amputation stump. Successive maps were derived in several monkeys to determine the nature of changes in map organization in the same individuals over time. In all monkeys studied, the representations of adjacent digits and palmar surfaces expanded topographically to occupy most or all of the cortical territories formerly representing the amputated digit(s). With the expansion of the representations of these surrounding skin surfaces (1) there were severalfold increases in their magnification and (2) roughly corresponding decreases in receptive field areas. Thus, with increases in magnification, surrounding skin surfaces were represented in correspondingly finer grain, implying that the rule relating receptive field overlap to separation in distance across the cortex (see Sur et al., '80) was dynamically maintained as receptive fields progressively decreased in size. These studies also revealed that: (1) the discontinuities between the representations of the digits underwent significant translocations (usually by hundreds of microns) after amputation, and sharp new discontinuous boundaries formed where usually separated, expanded digital representations (e.g., of digits 1 and 4) approached each other in the reorganizing map, implying that these map discontinuities are normally dynamically maintained. (2) Changes in receptive field sizes with expansion of representations of surrounding skin surfaces into the deprived cortical zone had a spatial distribution and time course similar to changes in sensory acuity on the stumps of human amputees. This suggests that experience‐dependent map changes result in changes in sensory capabilities. (3) The major topographic changes were limited to a cortical zone 500–700 μm on either side of the initial boundaries of the representation of the amputated digits. More distant regions did not appear to reorganize (i.e., were not occupied by inputs from surrounding skin surfaces) even many months after amputation. (4) The representations of some skin surfaces moved in entirety to locations within the former territories of representation of amputated digits in every monkey studied. In man, no mislocation errors or perceptual distortions result from stimulation of surfaces surrounding a digital amputation. This constitutes further evidence that any given skin surface can be represented by many alternative functional maps at different times of life in these cortical fields (Merzenich et al., '83b). These studies further demonstrate that basic features of somatosensory cortical maps (receptive field sizes, cortical sites of representation of given skin surfaces, representational discontinuities, and probably submodality column boundaries) are dynamically maintained. They suggest that cortical skin surface maps are alterable by experience in adults, and that experience‐dependent map changes reflect and possibly account for concomitant changes in tactual abilities. Finally, these results bear implications for mechanisms underlying these cortical map dynamics.

Inactivation of the sodium channel. I. Sodium current experiments.

1977-11-01

Francisco Bezanilla , Clay M. Armstrong

Gating current (Ig) has been studied in relation to inactivation of Na channels. No component of Ig has the time course of inactivation; apparently little or no charge movement is … Gating current (Ig) has been studied in relation to inactivation of Na channels. No component of Ig has the time course of inactivation; apparently little or no charge movement is associated with this step. Inactivation nonetheless affects Ig by immobilizing about two-thirds of gating charge. Immobilization can be followed by measuring ON charge movement during a pulse and comparing it to OFF charge after the pulse. The OFF:ON ratio is near 1 for a pulse so short that no inactivation occurs, and the ratio drops to about one-third with a time course that parallels inactivation. Other correlations between inactivation and immobilization are that: (a) they have the same voltage dependence; (b) charge movement recovers with the time coures of recovery from inactivation. We interpret this to mean that the immobilized charge returns slowly to "off" position with the time course of recovery from inactivation, and that the small current generated is lost in base-line noise. At -150 mV recover is very rapid, and the immobilized charge forms a distinct slow component of current as it returns to off position. After destruction of inactivation by pronase, there is no immobilization of charge. A model is presented in which inactivation gains its voltage dependence by coupling to the activation gate.

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THE PLASTIC HUMAN BRAIN CORTEX

2005-07-15

Álvaro Pascual‐Leone , Amir Amedi , Felipe Fregni +1 more

Plasticity is an intrinsic property of the human brain and represents evolution's invention to enable the nervous system to escape the restrictions of its own genome and thus adapt to … Plasticity is an intrinsic property of the human brain and represents evolution's invention to enable the nervous system to escape the restrictions of its own genome and thus adapt to environmental pressures, physiologic changes, and experiences. Dynamic shifts in the strength of preexisting connections across distributed neural networks, changes in task-related cortico-cortical and cortico-subcortical coherence and modifications of the mapping between behavior and neural activity take place in response to changes in afferent input or efferent demand. Such rapid, ongoing changes may be followed by the establishment of new connections through dendritic growth and arborization. However, they harbor the danger that the evolving pattern of neural activation may in itself lead to abnormal behavior. Plasticity is the mechanism for development and learning, as much as a cause of pathology. The challenge we face is to learn enough about the mechanisms of plasticity to modulate them to achieve the best behavioral outcome for a given subject.

Ionic Blockage of Sodium Channels in Nerve

1973-06-01

Ann M. Woodhull

Increasing the hydrogen ion concentration of the bathing medium reversibly depresses the sodium permeability of voltage-clamped frog nerves. The depression depends on membrane voltage: changing from pH 7 to pH … Increasing the hydrogen ion concentration of the bathing medium reversibly depresses the sodium permeability of voltage-clamped frog nerves. The depression depends on membrane voltage: changing from pH 7 to pH 5 causes a 60% reduction in sodium permeability at +20 mV, but only a 20% reduction at +180 mV. This voltage-dependent block of sodium channels by hydrogen ions is explained by assuming that hydrogen ions enter the open sodium channel and bind there, preventing sodium ion passage. The voltage dependence arises because the binding site is assumed to lie far enough across the membrane for bound ions to be affected by part of the potential difference across the membrane. Equations are derived for the general case where the blocking ion enters the channel from either side of the membrane. For H(+) ion blockage, a simpler model, in which H(+) enters the channel only from the bathing medium, is found to be sufficient. The dissociation constant of H(+) ions from the channel site, 3.9 x 10(-6) M (pK(a) 5.4), is like that of a carboxylic acid. From the voltage dependence of the block, this acid site is about one-quarter of the way across the membrane potential from the outside. In addition to blocking as described by the model, hydrogen ions also shift the responses of sodium channel "gates" to voltage, probably by altering the surface potential of the nerve. Evidence for voltage-dependent blockage by calcium ions is also presented.

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Electrical stimulation of excitable tissue: design of efficacious and safe protocols

2005-01-04

Daniel R. Merrill , Marom Bikson , John G. R. Jefferys

Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics

2010-04-18

Dae‐Hyeong Kim , Jonathan Viventi , Jason J. Amsden +7 more

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Fully integrated silicon probes for high-density recording of neural activity

2017-11-07

James J. Jun , Nicholas A. Steinmetz , Joshua H. Siegle +7 more

Ion Channels/Excitable Membranes

2011-08-24

PART I Classical biophysics of the squid giant axon The superfamily of voltage-gated channels Voltage-gated calcium channels Potassium channels and chloride channels Ligand-gated channels of fast chemical synapses Modulation, slow … PART I Classical biophysics of the squid giant axon The superfamily of voltage-gated channels Voltage-gated calcium channels Potassium channels and chloride channels Ligand-gated channels of fast chemical synapses Modulation, slow synaptic action, and second messengers Sensory transduction and excitable cells Calcium dynamics, epithelial transport, and intercellular coupling PART II Elementary properties of ions in solution Elementary properties of pores Counting channels Structure of channel proteins Selective permeability: Independence Selective permeability: Saturation and binding Classical mechanisms of block Structure-function studies of permeation and block Gating mechanisms: Kinetic thinking Gating: Voltage sensing and inactivation Modification of gating in voltage-sensitive channels Cell biology and channels Evolution and origins

Calcium Channel

1981-03-01

Susumu Hagiwara , L Byerly

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, … The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More

Rolipram and Electrical Stimulation Synergistically Promote Neuronal Differentiation of Adipose-derived Stromal Cells: an in Vitro Study

2025-06-25

Milad Rahimzadegan , Alireza Soltani Khaboushan , Somayeh Niknazar +4 more | Stem Cell Reviews and Reports

Abstract This study investigates gold-decorated polycaprolactone/chitosan nanofibers as conductive scaffolds for promoting neuronal differentiation of adipose-derived mesenchymal stromal cells (ADSCs) harvested from the dorsal interscapular region of Wistar rats under … Abstract This study investigates gold-decorated polycaprolactone/chitosan nanofibers as conductive scaffolds for promoting neuronal differentiation of adipose-derived mesenchymal stromal cells (ADSCs) harvested from the dorsal interscapular region of Wistar rats under electrical stimulation (ES) with optimal rolipram concentrations. The scaffold was fabricated through electrospinning and in situ synthesis of gold nanoparticles (AuNPs). Morphology and AuNPs distribution were evaluated using a Field Emission Scanning Electron Microscope (FE-SEM) and energy dispersive X-ray spectroscopy (EDX). Rolipram, known to increase neuronal cyclic adenosine monophosphate (cAMP) activity and reduce inflammation, was loaded into the scaffolds using alginate hydrogel. The scaffolds were subjected to a release study and tests for ADSC proliferation and differentiation into neuron-like cells. Immunostaining of β-Tubulin III and MAP2 was used to assess the effect of ES, alone and in combination with rolipram, on the efficacy of neuronal differentiation of ADSCs. The distribution of AuNPs was uniform within the scaffolds with an electrical conductivity of 0.12 S.cm −1 . Rolipram significantly improved the development of neurons from ADSCs, and this effect was more prominent at higher concentrations (1 and 5 µM). The study revealed that using an electrical density of 100 mV/mm, in combination with 5 µM rolipram and conductive scaffolds, led to a significant increase in the percentage of MAP2 and β-Tubulin III positive cells and the neuronal differentiation of ADSCs, with further elevation of cAMP levels compared to using 5 µM rolipram without ES. We found that combining rolipram and electrical stimulation at optimized doses and voltages can enhance nerve regeneration applications. Graphical Abstract

Towards a high efficiency implantable electric simulator for programmable biomedical stimulations

2025-06-25

Hany Shaker , Kasem Khalil , Mohamed Abbas +1 more | Computers & Electrical Engineering

Long-Term Multiparameter Sensing Integrated On-Chip Ultrasound for Epileptic Neuron Modulation

2025-06-24

Yongxu Ju , Xiao Wang , Yang Liu +2 more | ACS Sensors

Ultrasound neuromodulation holds great potential for treating neurological disorders. However, the molecular mechanisms underlying its effects remain unclear. There is a lack of systematic safety evaluation and standardized quantification of … Ultrasound neuromodulation holds great potential for treating neurological disorders. However, the molecular mechanisms underlying its effects remain unclear. There is a lack of systematic safety evaluation and standardized quantification of therapeutic outcomes. To address these challenges, this study integrates on-chip ultrasound with multiparameter cellular monitoring to quantitatively assess the therapeutic effects of various ultrasound parameters on neurological diseases from both electrophysiological and metabolic perspectives. Long-term monitoring is employed for a comprehensive evaluation of ultrasound safety. Notably, the combination of high-resolution, synchronous signal monitoring and biochemical indicators provides a deeper and more thorough understanding of the molecular mechanisms involved in ultrasound neuromodulation. Furthermore, using an on-chip epileptic neuron model, it is demonstrated that epileptic neurons exhibit high-frequency firing and synchronized oscillations in excitability, temperature, intracellular calcium, and mitochondrial calcium concentrations. The application of on-chip ultrasound effectively suppresses epileptiform discharges in neurons and inhibits both these oscillations and neuronal bursting events. When tuning with acoustic enhancer sodium valproate-loaded nanobubbles, the antiepileptic therapy effect can be significantly enhanced by maintaining mitochondrial calcium homeostasis. By integrating multiparameter long-term monitoring with on-chip ultrasound, this study presents an advanced approach for investigating the mechanisms of ultrasound neuromodulation, facilitating standardized evaluation and long-term safety assessment.

Toward Crosstalk-free All-optical Interrogation of Neural Circuits

2025-06-24

Gang Yan , Guangnan Tian , Yifeng Fu +5 more

ABSTRACT All-optical interrogation, based on high-resolution two-photon stimulation and imaging, has emerged as a potentially transformative approach in neuroscience, allowing for the simultaneous precise manipulation and monitoring of neuronal activity … ABSTRACT All-optical interrogation, based on high-resolution two-photon stimulation and imaging, has emerged as a potentially transformative approach in neuroscience, allowing for the simultaneous precise manipulation and monitoring of neuronal activity across various model organisms. However, the unintended excitation of light-gated ion channels such as channelrhodopsin (ChR) during two-photon calcium imaging with genetically encoded calcium indicators (GECIs) introduces artifactual neuronal perturbation and contaminates neural activity measurements. In this study, we propose an active pixel power control (APPC) approach, which dynamically adjusts the imaging laser power at each scanning pixel, to address the challenge. We aim to achieve simultaneous two-photon optogenetic manipulation and calcium imaging with a single femtosecond laser, while minimizing the crosstalk between manipulation and imaging. To study this technology’s capabilities, we applied it to the larval zebrafish brain in vivo. Our results demonstrate that the APPC approach preserves GECI signal quality while suppressing optogenetic artifacts significantly. This enhances the accuracy of neural circuit dissection and advances the precision of all-optical interrogation, offering a robust framework for probing neural circuit dynamics and causality in vivo with high fidelity, potentially across various model organisms. Importantly, this technology can be seamlessly integrated with commonly used two-photon microscope systems in laboratories worldwide.

High-density Multielectrode Array Recordings of Retinal Waves Using An Electrophysiology Platform

2025-06-24

Rishikesh Kumar Gupta , Natalie M. Clark , Keith Yeager +2 more | Journal of Visualized Experiments

Closed-loop electrical stimulation prevents focal epilepsy progression and long-term memory impairment

2025-06-23

José Javier Ferrero , Ahnaf Rashik Hassan , Zelin Yu +7 more | Nature Neuroscience

Fabrication and Characterization of PEDOT:PSS‐Based Microstructured Electrodes for In Vitro Cell Culture

2025-06-23

Gema Lopez , Juncal A. Alonso-Cabrera , Carlos Marcuello +5 more | Advanced Materials Interfaces

Abstract Bioelectronics is an evolving field focused on creating efficient interfaces between electronic systems and biological environments, where electrodes are crucial for detecting, recording, and stimulating signals. While traditional fabrication … Abstract Bioelectronics is an evolving field focused on creating efficient interfaces between electronic systems and biological environments, where electrodes are crucial for detecting, recording, and stimulating signals. While traditional fabrication techniques offer high precision, they are costly and lack scalability. Vacuum soft lithography offers a scalable, time‐efficient alternative for manufacturing microstructured electrodes. When combined with poly(3,4‐ethylenedioxythiophene) poly(styrene sulfonate) (PEDOT:PSS), a conducting polymer known for its biocompatibility and stability, this approach presents a promising solution for advancing bioelectronic applications. This study demonstrates the successful application of vacuum soft lithography for fabricating PEDOT:PSS‐based microstructured electrodes. These PEDOT:PSS‐based microstructured electrodes are fabricated and characterized based on their morphology, mechanics, and electrochemical properties. The PEDOT:PSS mixture containing 2% (3‐glycidyloxypropyl)trimethoxysilane (GOPS) demonstrates optimal properties, achieving an excellent balance of reproducibility, conductivity, and mechanical integrity, with in vitro cytocompatibility confirmed through testing with the MDA‐MB‐231 breast cancer cell line. This approach offers significant advantages, including reduced costs and production times, making it a viable alternative to conventional methods. Future research will explore its use with other conducting materials for broader bioelectronic applications.

A Geometrically Transient Material for Bioelectronic Implants

2025-06-23

Selin Olenik , John D. Goodwin , Atharv Naik +7 more | bioRxiv (Cold Spring Harbor Laboratory)

The outstanding barrier properties of skin make it difficult to obtain reliable physiological information (especially chemical) without the use of implantable bioelectronic sensing devices to directly access the internal biology. … The outstanding barrier properties of skin make it difficult to obtain reliable physiological information (especially chemical) without the use of implantable bioelectronic sensing devices to directly access the internal biology. The clinical utility of bioelectronic implants however, hinges on a key geometrical optimization problem: devices must scale-down in size to reduce surgical invasiveness while also creating enough space to integrate electronics for wireless power delivery, data exchange, and electrical/electrochemical monitoring. Here, we present a minimally invasive bioelectronic implant with a transient geometry that can be inserted subcutaneously and measures important markers, such as pH, temperature, cardiac and respiratory activity, and levels of lithium, an important element for medical applications. To produce this new class of minimally invasive and foldable implantable sensors, we developed a fabrication method that works with highly flexible substrates to enable multiple-fold miniaturization during implantation. After implantation, the implant autonomously unfolds back to its planar form for continuous wireless operation. We demonstrate the key concepts concerning implantation, operation, and removal through extensive in vitro , ex vivo , and in vivo animal experiments. Our approach allows for robust multiplexed monitoring using quick and suture-free insertion procedures and may provide a unique advantage in the transition towards personalized health profiles.

Volume Control for a Cortical Network

2025-06-21

Runming Wang , Gene Y. Fridman | bioRxiv (Cold Spring Harbor Laboratory)

Excitability is a fundamental property of cortical networks, shaping their responses to input. Here, we use ionic direct current (iDC) to modulate excitability with sub-10-ms temporal resolution and submillimeter spatial … Excitability is a fundamental property of cortical networks, shaping their responses to input. Here, we use ionic direct current (iDC) to modulate excitability with sub-10-ms temporal resolution and submillimeter spatial precision across the cortical surface, greatly surpassing the capabilities of pharmacological tools. In anesthetized rats, we recorded laminar neural responses in the S1HL cortex to spontaneous delta oscillations and to foot stimulation with and without iDC delivered to the cortical surface. Cathodic iDC suppressed, and anodic iDC enhanced, evoked responses across recording sites. iDC shifted the spatiotemporal excitability pattern in a graded manner, paralleling the effects of weaker or stronger foot stimuli. A computational model reproduced these effects and implicated dendritic summation at the axon initial segment (AIS) as a key mechanism for bidirectional modulation. This approach enables precise, causal manipulation of cortical responsiveness in vivo and offers a platform for dissecting functional circuits and developing targeted neurotherapeutic interventions.

Human Stem Cell-Derived Neural Organoids for the Discovery of Antiseizure Agents

2025-06-20

Hamed Salmanzadeh , Robert F. Halliwell | Receptors

Background: The development of cerebral organoids created from human pluripotent stem cells in 3D culture may greatly improve the discovery of neuropsychiatric medicines. Methods: In the current study we differentiated … Background: The development of cerebral organoids created from human pluripotent stem cells in 3D culture may greatly improve the discovery of neuropsychiatric medicines. Methods: In the current study we differentiated neural organoids from a human pluripotent stem cell line in vitro, recorded the development of neurophysiological activity using multielectrode arrays (MEAs) and characterized the neuropharmacology of synaptic signaling over 8 months in vitro. In addition, we investigated the ability of these organoids to display epileptiform activity in response to a convulsant agent and the effects of antiseizure medicines to inhibit this abnormal activity. Results: Single and bursts of action potentials from individual neurons and network bursts were recorded on the MEA plates and significantly increased and became more complex from week 7 to week 30, consistent with neural network formation. Neural spiking was reduced by the Na channel blocker tetrodotoxin but increased by the inhibitor of KV7 potassium channels XE991, confirming the involvement of voltage-gated sodium and potassium channels in action potential activity. The GABA antagonists bicuculline and picrotoxin each increased the spike rate, consistent with inhibitory synaptic signaling. In contrast, the glutamate receptor antagonist kynurenic acid inhibited the spike rate, consistent with excitatory synaptic transmission in the organoids. The convulsant 4-aminopyridine increased spiking, bursts and synchronized firing, consistent with epileptiform activity in vitro. The anticonvulsants carbamazepine, ethosuximide and diazepam each inhibited this epileptiform neural activity. Conclusions: Together, our data demonstrate that neural organoids form inhibitory and excitatory synaptic circuits, generate epileptiform activity in response to a convulsant agent and detect the antiseizure properties of diverse antiepileptic drugs, supporting their value in drug discovery.

Human Cortical Organoids with a Novel SCN2A Variant Exhibit Hyperexcitability and Differential Responses to Anti-Seizure Compounds

2025-06-20

Yuling Yang , Yang Cai , Shuyang Wang +4 more | Neuroscience Bulletin

Topographical Patterning of Cell‐Repellent Interfaces for Immune‐Stealth Implantable Electronics via Multiphoton Ablation Lithography

2025-06-19

Hyunseon Seo , Gwan‐Jin Ko , Sangmin Song +7 more | PubMed

Abstract Stable and reliable operation of implantable electronics must ensure both high‐quality electrical performance and chronic biocompatibility. Here, immune‐stealth implantable electronics fabricated by multiphoton ablation lithography are introduced. The cell‐repellent … Abstract Stable and reliable operation of implantable electronics must ensure both high‐quality electrical performance and chronic biocompatibility. Here, immune‐stealth implantable electronics fabricated by multiphoton ablation lithography are introduced. The cell‐repellent interface, consisting of micro‐grooves and nano‐islands, can be created by laser‐assisted topography patterning on a thin film substrate. This patterned surface demonstrates a 20‐fold increase in cell‐repellent effectiveness against immune cells such as macrophages and fibroblasts due to disturbance of focal adhesion. Furthermore, the cell‐repellent interface can also be patterned on the sub‐micron electrode layer without compromising its electrical and electrochemical performance. When the electrocardiogram (ECG) sensor applying the cell‐repellent interface is implanted into a rat subcutaneous tissue, inflammation and fibrotic reactions are effectively suppressed for 6 weeks. Consequently, stable ECG readings with clear PQRST waveforms are obtained in real‐time for 4 weeks, suggesting its potential to enhance chronic biocompatibility of implantable electronics.

Bidirectional mechanisms and emerging strategies for implantable bioelectronic interfaces

2025-06-19

Zineng Yan , Weihang Gao , Yuyu Duan +4 more | Bioactive Materials

A Dynamic Spike Sorter for Multiscale Nanoelectrode Array Recordings

2025-06-18

Shivani Shukla , C. A. Walsh , Shashank Bansal +6 more | Advanced Materials Interfaces

Abstract High‐throughput, intracellular electrophysiology is crucial for advancing the understanding of neuronal processing and network dynamics. Nanoelectrode arrays (NEA) offer a promising approach by directly capturing intracellular signals across sub‐neuronal … Abstract High‐throughput, intracellular electrophysiology is crucial for advancing the understanding of neuronal processing and network dynamics. Nanoelectrode arrays (NEA) offer a promising approach by directly capturing intracellular signals across sub‐neuronal compartments, including action potentials, postsynaptic potentials, and low‐frequency membrane fluctuations. However, the complexity of NEA datasets, characterized by multiscale events of varying amplitude and duration, demands novel analytical strategies. In this work, a dynamic spike sorting pipeline is introduced and designed to isolate, extract, and sort these diverse electrical signals within a landscape of spontaneous electrical behavior. It is obtained estimates of signal attenuation and distortion using a bespoke biophysical circuit simulation designed to match the specific nanoelectrode interface. Based on these observations, bounds are set for filtering and extracting multiscale waveforms, and validated their isolation using pharmacological data. Finally, it is shown that multiscale analysis of spontaneous electrical recordings reveals interrelationships between high frequency events such as action potentials, and low frequency membrane potential fluctuations which may inform models of neuronal network excitability. Advanced sorting algorithms tailored for nanoelectrode array recordings are essential for unlocking the full potential of next generation, high throughput neuroelectronic devices and achieving a deeper understanding of neuronal dynamics.

Three-dimensional Printing of High-Performance Hydrogel Bioelectronic Implants

2025-06-18

Yuan Yao , Jianhua Luo , Yue Hui +7 more | Research Square (Research Square)

<title>Abstract</title> Implantable hydrogel bioelectronics are promising candidates for seamlessly bridging biological systems with intelligent devices. However, sustaining stable communication between hydrogel electronics and biological systems in complex physiological environments remains … <title>Abstract</title> Implantable hydrogel bioelectronics are promising candidates for seamlessly bridging biological systems with intelligent devices. However, sustaining stable communication between hydrogel electronics and biological systems in complex physiological environments remains a critical challenge, primarily due to the swelling-induced degradation of mechanical properties of hydrogel encapsulation and reduced electrical performance of the conductive networks. To address this, we developed a micelle-assembly approach to synthesize soft and highly stretchable hydrogels with swelling-resistant performance. Moreover, these hydrogels show alleviated foreign body reactions during long-term implantation, serving as valuable implant materials. Through embedded 3D printing technology, we engineered ultrasoft (~ 40 kPa) and stretchable (over 1,000%) hydrogel electronics with unprecedented conductivity retention in aqueous environment – conductivity over 9,000 S cm-1 post-printing and 4,000 S cm-1 even after swollen. We further printed three different types of invasive implants, including brain-computer interfaces, implantable wirelessly-powered optoelectronics and sciatic nerve stimulators. These devices can either perceive physiological signals or receive electronic orders and respond accordingly with extraordinary robustness and longevity in vivo. We believe that such technological advances hold great promise for the development of human-computer interfaces.

Transparent transfer-free multilayer graphene microelectrodes enable high quality recordings in brain slices

2025-06-18

Nerea Alvarez de Eulate , Christos Pavlou , Gonzalo León González +4 more | bioRxiv (Cold Spring Harbor Laboratory)

Abstract Resolving the underlying mechanisms of complex brain functions and associated disorders remains a major challenge in neuroscience, largely due to the difficulty in mapping large-scale neural network dynamics with … Abstract Resolving the underlying mechanisms of complex brain functions and associated disorders remains a major challenge in neuroscience, largely due to the difficulty in mapping large-scale neural network dynamics with high temporal and spatial resolution. Multimodal neural platforms that integrate optical and electrical modalities offer a promising approach that surpasses resolution limits. Over the last decade, transparent graphene microelectrodes have been proposed as highly suitable multimodal neural interfaces. However, their fabrication commonly relies on the manual transfer process of pre-grown graphene sheets which introduces reliability and scalability issues. In this study, multilayer graphene microelectrode arrays (MEAs) with electrode sizes as small as 10-50 µm in diameter, are fabricated using a transfer-free process on a transparent substrate for in vitro multimodal platforms. Through acute experiments using cerebellar brain slices, their ability to detect spontaneous extracellular spiking activity from neural cells, with a high signal-to-noise ratio up to 30-40 dB, is demonstrated. The recorded signal quality is found to be more limited by the electrode-tissue coupling than the MEA technology itself. Overall, this study shows the potential of transfer-free multilayer graphene MEAs to interface with neural tissue, which paves the way to advance neuroscientific research through the next-generation of multimodal neural interfaces.

Two-photon fiberscope with a proactive optoelectrical commutator for rotational resistance–free imaging in freely behaving rodents

2025-06-18

Yuehan Liu , Jing Zhang , D.-S. Guo +6 more | Neurophotonics

The recently developed two-photon (2P) fiberscope offers attractive opportunities in neuroscience by enabling high-resolution neural imaging in freely behaving rodents. However, like other miniature 2P devices, it involves a tether … The recently developed two-photon (2P) fiberscope offers attractive opportunities in neuroscience by enabling high-resolution neural imaging in freely behaving rodents. However, like other miniature 2P devices, it involves a tether (for fiber and scanner drive wires), which inevitably limits the animal's movement, especially its rotation. We aim to develop a platform for 2P fiberscopes (and other tethered miniature devices), enabling rotational resistance-free neuroimaging in freely rotating/walking rodents. We introduced a proactive optoelectrical commutator (pOEC) capable of real-time sensing and compensation for a tiny torque buildup in the tether (with a preselected threshold), preemptively eliminating the rotational resistance when the mouse physically rotates the fiberscope. Experimental results demonstrated that the pOEC effectively compensates for torque buildup in the fiberscope, thereby maintaining stable 2P imaging performance. In addition, the system minimizes the rotational resistance imposed by the head-mounted tether, enabling near-zero rotational burden during 2P neural imaging in freely behaving mice. Investigations of neural activity further revealed that a considerable proportion of motor cortex neurons exhibited statistically significant changes in their firing patterns when the mouse was restricted by tether-induced rotational resistance or completely immobilized via head fixation. The results indicated that rotational restriction induced visible impacts on neuronal activities. Our platform offers a promising opportunity for studying dynamic neural circuit functions under nearly natural conditions with minimized impacts by the rotational restriction.

A scalable 3D packaging technique for brain organoid arrays toward high-capacity bioprocessors

2025-06-17

Jeong Hee Kim , Minseok Kim , Keun‐Tae Kim +5 more | Biosensors and Bioelectronics

PID neural network-based multi-channel feedback closed-loop control for deep brain stimulation

2025-06-17

Bin Deng , Guohang Xiu , Weitong Liu +2 more | Biomedical Signal Processing and Control

Alleviation of Neuroinflammation on Electrode Interface by Biomimetic Electrical Microenvironment Modulation Based on Collagen/Polypyrrole Composite Film

2025-06-17

Chengwei Wu , Xiyue Duan , Xuzhao He +6 more | Colloids and Surfaces B Biointerfaces

Highly reconfigurable neuron-mimicking conductive networks through nanophase structure engineering

2025-06-17

Jiajun Fu , Wei Zhong , Haojie Zhao +5 more | Research Square (Research Square)

<title>Abstract</title> Bionic electronics are designed to bridge the gap between biological realms and conventional electronics by imitating the mechanical performance and versatile functionalities of biological tissue. However, it remains a … <title>Abstract</title> Bionic electronics are designed to bridge the gap between biological realms and conventional electronics by imitating the mechanical performance and versatile functionalities of biological tissue. However, it remains a great challenge to replicate the high dynamics and reconfigurability of living tissues at the hardware level without compromising electrical performance, spatial resolutions, and structural integrity. This issue is mainly rooted in the inherent conflict between excellent electrical performance and dynamic properties, in which the former requires electrical active components to have an intimate electrical connection at the molecular level while the latter nevertheless necessitates weak and responsive intermolecular interaction. To address this problem, a novel methodology of reversible nanophase regulation is proposed, inspired by the well-known ion-specific effect discovered in biological systems. As an exemplary model, physically crosslinked conductive networks are prepared with conducting polymers and polyvinyl alcohol as building blocks. With the benefits of the dynamic response to specific ions, the conductive network can successfully integrate multiple, traditionally contradictory properties—combining outstanding electrical/mechanical performance with excellent reconfigurability features such as micro-patternability and erasability of conductive pathways, in-situ wet solderability with good spatial resolution, and closed-loop recyclability. At last, the methodology proposed here showed good generality and could be extended to other material systems, promising to inspire the design of novel reconfigurable bionic devices for the integration of biological tissue and electronics in a diverse range of applications including human-machine interactions, neural tissue engineering, and degradable bioelectronics.

Covalent Binding of Dexamethasone to Polyimide Improves Biocompatibility of Neural Implantable Devices

2025-06-17

Giulia Turrin , Jose Crugeiras , Chiara Bisquoli +7 more | Advanced Healthcare Materials

Abstract Neural implants are widely used in prosthetic applications to interact with the peripheral nervous system, but their long‐term functionality is compromised by foreign body reactions (FBR). Thanks to its … Abstract Neural implants are widely used in prosthetic applications to interact with the peripheral nervous system, but their long‐term functionality is compromised by foreign body reactions (FBR). Thanks to its high biocompatibility, polyimide poly (biphenyl dianhydride)‐ p ‐phenylenediamine (BPDA‐PDA) represents a suitable material to fabricate ultrathin and ultra‐flexible neural implants. This study explores the surface functionalization of BPDA‐PDA, the electrically inert component of the neural implant. The novelty of this approach relies on the fact that dexamethasone (DEX covalently bound to BPDA‐PDA, enabling its sustained release over a period of at least 9 weeks. In vitro assays demonstrate that this strategy reduce the production of pro‐inflammatory markers in macrophages. In addition, the biocompatibility of the functionalized material has been ensured by evaluating the viability of dorsal root ganglia (DRG) neurons. Furthermore, in vivo implantation of DEX functionalized BPDA‐PDA substrates shows a significant reduction in inflammatory cell infiltration and fibrotic capsule thickness formed around the devices. These findings suggest that local release of DEX from the electrically inactive scaffold of neural implants may enhance their long‐term stability and performance by mitigating the FBR.

Magnetic‐Driven Torque‐Induced Electrical Stimulation for Millisecond‐Scale Wireless Neuromodulation

2025-06-16

Chao‐Chun Cheng , Li‐Ling Chen , Guan‐Jhong Tseng +3 more | Advanced Healthcare Materials

Abstract Wireless neuromodulation using nanoparticles, offering minimally invasive alternatives to conventional deep brain stimulation (DBS) while reducing the risks associated with hardware implants, has gained significant traction over the past … Abstract Wireless neuromodulation using nanoparticles, offering minimally invasive alternatives to conventional deep brain stimulation (DBS) while reducing the risks associated with hardware implants, has gained significant traction over the past decade. Nevertheless, ensuring millisecond‐scale wireless DBS for the precise temporal control of neuronal activity remains challenging. This study reports magnetic‐driven torque‐induced electrical stimulation (MagTIES), a torque‐based magnetoelectric neuromodulation method. By utilizing magnetic nanodiscs to generate torque under alternating magnetic fields (AMFs), the MagTIES induces a piezoelectric effect in piezoelectric nanoparticles, thereby overcoming the limitations of traditional magnetostriction‐based systems. With an AMF (50 mT at ≈10 Hz), the proposed approach triggers neuronal activity both in vitro and in vivo, specifically in the deep brain region of the amygdala, within milliseconds. Furthermore, MagTIES enables the fine‐tuning of amygdala brain oscillations through the precise modulation of the AMF frequency. By combining high spatial and temporal precision with minimal invasiveness, MagTIES provides an innovative approach for advancing neuroscience research with potential applications in understanding neural circuits and developing innovative therapies.

High-Efficiency, Low-Power, Fully Integrated Neural Electrical Stimulation Circuit

2025-06-16

Yujiao Wang , Jiahao Cheong , Cheng Liu | Applied Sciences

This paper presents a highly efficient, low-power, fully integrated neural stimulation circuit implemented using solely low-voltage devices. The circuit primarily consists of a high-voltage-generation circuit, an output driver circuit, and … This paper presents a highly efficient, low-power, fully integrated neural stimulation circuit implemented using solely low-voltage devices. The circuit primarily consists of a high-voltage-generation circuit, an output driver circuit, and a constant-current source, designed and simulated using a 180 nm low-voltage CMOS process. The high-voltage-generation circuit utilizes a negative-voltage-generation module together with a series–parallel capacitor charge pump circuit, which effectively reduces the number of charge pump stages by three, and saves 29% of the area compared to a conventional charge pump circuit. A bootstrap clock generation circuit was utilized to generate the control signal to ensure that all transistors work within their voltage limit. To realize the high-voltage output driver circuit using low-voltage devices, a stacked transistor structure with deep N-well (DNW) devices was utilized. The four different output voltage levels from the high-voltage-generation circuit were utilized to generate a different voltage domain of control signals and bias voltage for the stacked transistors, making sure that all transistors work within their voltage limit. Simulation results show that the high-voltage-generation circuit can generate an output of up to 12.69 V from a 1.65 V low input voltage, with a maximum output current of 1 mA, achieving 74.9% efficiency. The overall efficiency of the neural stimulation circuit, including the high-voltage-generation circuit, output driver circuit and constant-current source, reaches 74% under the voltage-controlled stimulation (VCS) mode and 59.5% under the current-controlled stimulation (CCS) mode, whereas the standby static power consumption is as low as 66 pW.

Cortical Stimulation-Based Transcriptome Shifts on Parkinson’s Disease Animal Model

2025-06-16

Johyeon Nam , Hongseong Shin , Chaeyeon You +4 more | ASN NEURO

Parkinson's disease is the second most prevalent neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons. Significant improvements in gait balance, particularly in step length and velocity, were … Parkinson's disease is the second most prevalent neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons. Significant improvements in gait balance, particularly in step length and velocity, were observed with less invasive wireless cortical stimulation. Transcriptome sequencing was performed to demonstrate the cellular mechanism, specifically targeting the primary motor cortex, where stimulation was applied. Our findings indicated that 38 differentially expressed genes (DEGs), initially downregulated following Parkinson's disease induction, were subsequently restored to normal levels after cortical stimulation. These 38 DEGs are potential targets for the treatment of motor disorders in Parkinson's disease. These genes are implicated in crucial processes, such as astrocyte-mediated blood vessel development and microglia-mediated phagocytosis of damaged motor neurons, suggesting their significant roles in improving behavioral disorders. Moreover, these biomarkers not only facilitate the rapid and accurate diagnosis of Parkinson's disease but also assist in precision medicine approaches.

Transcending pre-processing of physiological fluids and device-to-device variability in nanosheet networks for point of care (PoC) immunosensors

2025-06-16

P. Mukherjee , Rohit Thakur , S. Sen +2 more | Applied Materials Today

Food seeking suppression by environmental enrichment accompanies cell type- and circuit-specific prelimbic cortical modulation

2025-06-15

Kate Z. Peters , Romarua Agbude , Oliver G. Steele +2 more | bioRxiv (Cold Spring Harbor Laboratory)

Cues such as fast-food advertisements associated with food can provoke food cravings which may lead to unhealthy overeating. To effectively control such cravings, we need to better understand the factors … Cues such as fast-food advertisements associated with food can provoke food cravings which may lead to unhealthy overeating. To effectively control such cravings, we need to better understand the factors that reduce food cue reactivity and reveal corresponding anti-craving brain mechanisms. We previously reported that access to environmental enrichment (EE) that provides cognitive and physical stimulation in mice reduced cue-evoked sucrose seeking and prelimbic cortex (PL) neuronal reactivity. To date, the phenotype of PL neurons that undergo EE-induced adaptations has not been fully elucidated. Therefore, we used brain slice electrophysiology to investigate how EE modulated intrinsic excitability in the general population of PL interneurons and pyramidal cells. Additionally, we used retrograde tracing and the neuronal activity marker Fos to investigate how EE modulated cue-evoked recruitment of pyramidal cells projecting to the paraventricular nucleus of the thalamus (PVT) and nucleus accumbens core (NAc). Before the cue-evoked sucrose seeking test, EE enhanced the general, baseline excitability of inhibitory interneurons, but not pyramidal cells, thereby promoting inhibitory overdrive. During cue-evoked sucrose seeking, EE suppressed recruitment of PVT-, but not NAc-projecting, neurons thereby selectively promoting corticothalamic, but not corticoaccumbens, excitatory underdrive. Collectively, we further illuminate EE's anti-food seeking actions whereby EE promotes both cell type-specific (inhibitory interneuron overdrive) and circuit-specific (excitatory corticothalamic underdrive) neuroadaptations in the PL.

Dual-drive integrated bionic finger inspired by human finger tendon-flesh tissue

2025-06-13

Zi‐Han Chen , Jiangbin Yin | Journal of Mechanisms and Robotics

Abstract The rising prevalence of human-machine interaction in industrial processes has led to increased interest in soft fingers, thanks to their superior safety and mechanical compliance. Human fingers, known for … Abstract The rising prevalence of human-machine interaction in industrial processes has led to increased interest in soft fingers, thanks to their superior safety and mechanical compliance. Human fingers, known for their exceptional grasping properties, serve as a significant inspiration in soft finger research. This study introduces a tendon–pneumatic-driven (TPD) soft finger, inspired by the tendon–flesh organization of human fingers. The TPD finger comprises a tendon-driven (TD) module and a pneumatic-driven (PD) module. The integration of these modules allows the TPD finger to achieve outstanding load-bearing capacity and high dexterity, all while maintaining significant mechanical compliance. To evaluate the TPD finger's performance, we first analyzed the coupling effect between the TD and PD modules under various driving strategies. We then demonstrated the TPD finger's capability to grasp a pencil lead (0.1 g, 0.7 mm) without damaging its structure, utilizing the drive compensation between the PD and TD modules. Additionally, the TPD gripper was employed to handle objects with fragile surfaces of various shapes and sizes. The results indicate that different gripping modes, combined with the coupling effect of varied actuation strategies, allow the TPD gripper to execute multiple grasping modes (pinch-up, pick-up, hold-up, torsion) effectively. Overall, the TPD gripper exhibits commendable performance in terms of compliance, load capacity, and flexibility.

Composite additive manufacturing for suspended microelectrode arrays: advancing oriented myocardial tissue culturing and electrophysiological sensing

2025-06-13

Mingcheng Xue , Wangzihan Zhang , Hang Jin +7 more | Biosensors and Bioelectronics

Revolutionizing neural regeneration with smart responsive materials: Current insights and future prospects

2025-06-13

Hongxia Gao , Huoyun Shen , X. Frank Zhang +7 more | Bioactive Materials

Implantable Microelectrodes for <i>In Vivo</i> Monitoring of Neurotransmitters

2025-06-13

Hiroya Abe , Chenzhong Li | Royal Society of Chemistry eBooks

Neurotransmitters have an important role in mediating information communication within the nervous systems. These chemical messengers facilitate the propagation of electrical signals across neural networks. Dysregulation or abnormality in neurotransmitter … Neurotransmitters have an important role in mediating information communication within the nervous systems. These chemical messengers facilitate the propagation of electrical signals across neural networks. Dysregulation or abnormality in neurotransmitter homeostasis probably causes neurodegenerative conditions such as Parkinson's disease and schizophrenia. Monitoring dynamic changes in the brain can provide insight into brain function and neurodegenerative diseases. Sophisticated structures can be fabricated with the development of micro- and nano-technologies. This chapter summarizes methods for evaluating neurotransmitters and fabricating implantable microdevices. For neurotransmitter evaluation methods, this chapter describes electrochemical methods, including amperometric and voltammetric methods, and electrical methods of field-effect transistors. The chapter also summarizes the use of materials such as silicon, carbon fiber, and polymer substrates.

Future Perspectives for Electrochemical Detection of Neurotransmitters

2025-06-13

K. S. Shalini Devi | Royal Society of Chemistry eBooks

The emerging wearable sensors in the health sector and advances in analytical devices to monitor neurological disorders using different nanomaterials have been discussed in the other chapters. This chapter covers … The emerging wearable sensors in the health sector and advances in analytical devices to monitor neurological disorders using different nanomaterials have been discussed in the other chapters. This chapter covers the focus of future research and discusses upcoming strategies, advantages, and limitations of existing devices using implantable electrodes for neurotransmitter detection. Electrochemical biosensors have been designed to detect several neurotransmitters (NTs) with excellent sensitivity and specificity. However, despite the advances achieved in this sector, there are still limitations and obstacles that must be addressed, such as improved interaction with clinical processes and biosensor performance. Furthermore, increasing sensitivity is critical, especially when detecting analytes with limited potential differences. Improving the signal-to-noise ratio and lowering detection limits continue to present problems. This chapter uses the overall information from the other chapters in the book to provide possible solutions to improve the future of continuous monitoring of NTs in humans.

Electrical Stimulation Modulates the Fate Decision of Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Subtypes

2025-06-12

Joseph P. Licata , Jonathan A. Gerstenhaber , Peter I. Lelkes | Stem Cells and Development

The differentiation of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into specific subtypes, including ventricular, atrial, conduction, and nodal, remains a significant challenge for in vitro disease modeling and regenerative medicine. … The differentiation of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into specific subtypes, including ventricular, atrial, conduction, and nodal, remains a significant challenge for in vitro disease modeling and regenerative medicine. While chemical approaches have been explored for subtype specification, these protocols often result in heterogeneous CM populations. In this study, we tested the hypothesis that differential electrical stimulation (ES) can guide/modulate the differentiation of subtype-specific CMs from hiPSCs. By varying stimulation parameters, such as frequency and onset of ES at different developmental time points, we demonstrate that ES alone promotes the differentiation of hiPSC into either ventricular or atrial CMs, without changing any chemical cues. Our results show that lower frequency stimulation earlier in development promotes atrial gene expression, while higher frequency ES later in development promotes ventricular differentiation. These findings were validated by gene expression analysis, immunostaining, and measurement of calcium signaling. This study highlights the potential of ES as a tunable tool for directing CM subtype specification, offering a promising strategy for the generation of pure populations of CM subtypes for use in precision medicine, disease modeling, and regenerative therapies.

A liability framework for high-risk neural devices

2025-06-12

Ari Rotenberg , Margot Gunning , Roland Nadler +2 more | Science

A no-fault compensation scheme may help balance innovation and patient protection. A no-fault compensation scheme may help balance innovation and patient protection.

The Goldilocks Paradox of Bioelectronics: Misreporting Piezoresistive Gauge Factor Is Obstructing Research Advancements

2025-06-12

Conor S. Boland | Advanced Materials

Abstract In the fable Goldilocks and The Three Bears, Goldilocks discerns between seemingly similar bowls of porridge using temperature. In the field of wearable bioelectronics, researchers do not have the … Abstract In the fable Goldilocks and The Three Bears, Goldilocks discerns between seemingly similar bowls of porridge using temperature. In the field of wearable bioelectronics, researchers do not have the same luxury of simple comparative analysis. Devices based on composite materials applying electrically conductive nanomaterial and polymer networks present a technology path towards an Internet of Things driven healthcare system. However, research progress has been obstructed by a lack of consistency with regards to the industry standard performance metric, the gauge factor ( G ). Paradoxically, studies cannot be compared, as no one study measures G the same. However, extrapolating the correct value for G , its intrinsic relationship between the signal linearity figure of merit outlines fieldwide performance limitations for devices, new metrics and materials selection criteria.

Human Peripheral Nerve-on-a-Chip on a Multiwell Microelectrode Array as a Scalable Preclinical Neurotoxicity Assay

2025-06-12

Corey M. Rountree , Tyler Rodriguez , C. Ethan Byrne +7 more | bioRxiv (Cold Spring Harbor Laboratory)

Abstract Reliable human-relevant models of peripheral nerve function remain a critical unmet need in preclinical drug development, particularly for predicting neurotoxicity and bridging the gap to clinical translation. Here, we … Abstract Reliable human-relevant models of peripheral nerve function remain a critical unmet need in preclinical drug development, particularly for predicting neurotoxicity and bridging the gap to clinical translation. Here, we introduce a next generation Nerve-on-a-Chip, PNS-3D organoids, as a novel human-cell-based 3D peripheral nerve microphysiological system (MPS) that recapitulates key functional and structural features of native nerves, including long-distance axonal outgrowth, physiological myelination, and clinically translational population level electrophysiology. The platform integrates iPSC-derived human sensory neurons and primary human Schwann cells within a spatially organized 3D environment, coupled to a custom embedded electrode array that enables high-content, longitudinal, and clinically translatable functional assessments. As a proof of concept, we evaluated the platform’s predictive power using vincristine, a chemotherapeutic agent known to cause chemotherapy-induced peripheral neuropathy (CIPN). PNS-3D organoids captured dose- and time-dependent deficits in nerve conduction velocity, compound action potential amplitude, and axonal degeneration, with IC₅₀ values in line with human clinical exposures— outperforming traditional 2D cultures and in vivo benchmarks. Transcriptomic and morphological analyses further revealed neuron-specific degeneration consistent with axonopathy. These results validate the platform as a human-relevant, clinically translation, and scalable solution, enabling mechanistic safety assessment and drug discovery for neurotoxic and neuroprotective therapeutics.

World first: brain implant lets man speak with expression ― and sing

2025-06-11

Miryam Naddaf | Nature