Overview[edit]

There are many techniques available to record brain activity—including electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI)—but these do not allow for single-neuron resolution.^[6] Neurons are the basic functional units in the brain; they transmit information through the body using electrical signals called action potentials. Currently, single-unit recordings provide the most precise recordings from a single neuron. A single unit is defined as a single, firing neuron whose spike potentials are distinctly isolated by a recording microelectrode.^[3]

The ability to record signals from neurons is centered around the electric current flow through the neuron. As an action potential propagates through the cell, the electric current flows in and out of the soma and axons at excitable membrane regions. This current creates a measurable, changing voltage potential within (and outside) the cell. This allows for two basic types of single-unit recordings. Intracellular single-unit recordings occur within the neuron and measure the voltage change (with respect to time) across the membrane during action potentials. This outputs as a trace with information on membrane resting potential, postsynaptic potentials and spikes through the soma (or axon). Alternatively, when the microelectrode is close to the cell surface extracellular recordings measure the voltage change (with respect to time) outside the cell, giving only spike information.^[7] Different types of microelectrodes can be used for single-unit recordings; they are typically high-impedance, fine-tipped and conductive. Fine tips allow for easy penetration without extensive damage to the cell, but they also correlate with high impedance. Additionally, electrical and/or ionic conductivity allow for recordings from both non-polarizable and polarizable electrodes.^[8] The two primary classes of electrodes are glass micropipettes and metal electrodes. Electrolyte-filled glass micropipettes are mainly used for intracellular single-unit recordings; metal electrodes (commonly made of stainless steel, platinum, tungsten or iridium) and used for both types of recordings.^[3]

Single-unit recordings have provided tools to explore the brain and apply this knowledge to current technologies. Cognitive scientists have used single-unit recordings in the brains of animals and humans to study behaviors and functions. Electrodes can also be inserted into the brain of epileptic patients to determine the position of epileptic foci.^[6] More recently, single-unit recordings have been used in brain machine interfaces (BMI). BMIs record brain signals and decode an intended response, which then controls the movement of an external device (such as a computer cursor or prosthetic limb).^[5]

1790s: The first evidence of electrical activity in the nervous system was observed by in the 1790s with his studies on dissected frogs. He discovered that you can induce a dead frog leg to twitch with a spark.^[9]

Luigi Galvani

1888: , a Spanish neuroscientist, revolutionized neuroscience with his neuron theory, describing the structure of the nervous system and presence of basic functional units— neurons. He won the Nobel Prize in Physiology or Medicine for this work in 1906.^[10]

Santiago Ramón y Cajal

1928: One of the earliest accounts of being able to record from the nervous system was by in his 1928 publication "The Basis of Sensation". In this, he describes his recordings of electrical discharges in single nerve fibers using a Lippmann electrometer. He won the Nobel Prize in 1932 for his work revealing the function of neurons.^[11]

Edgar Adrian

1940: Renshaw, Forbes & Morrison performed original studies recording discharge of in the hippocampus using glass microelectrodes in cats.^[12]

pyramidal cells

1950: Woldring and Dirken report the ability to obtain spike activity from the surface of the with platinum wires.^[13]

cerebral cortex

1952: Li and Jasper applied the Renshaw, Forbes, & Morrison method to study electrical activity in the cerebral cortex of a cat. Hodgkin–Huxley model was revealed, where they used a squid giant axon to determine the exact mechanism of action potentials.^[15]

[14]

1953: microelectrodes developed for recording.^[16]

Iridium

1957: used intracellular single-unit recording to study synaptic mechanisms in motoneurons (for which he won the Nobel Prize in 1963).

John Eccles

1958: microelectrodes developed for recording.^[17]

Stainless steel

1959: Studies by and Torsten Wiesel. They used single neuron recordings to map the visual cortex in unanesthesized, unrestrained cats using tungsten electrodes. This work won them the Nobel Prize in 1981 for information processing in the visual system.

David H. Hubel

1960: Glass-insulated platinum microelectrodes developed for recording.

[18]

1967: The first record of multi-electrode arrays for recording was published by Marg and Adams. They applied this method to record many units at a single time in a single patient for diagnostic and therapeutic brain surgery.

[19]

1978: Schmidt et al. implanted chronic recording micro-cortical electrodes into the cortex of monkeys and showed that they could teach them to control neuronal firing rates, a key step to the possibility of recording neuronal signals and using them for BMIs.

[20]

1981: Kruger and Bach assemble 30 individual microelectrodes in a 5x6 configuration and implant the electrodes for simultaneous recording of multiple units.

[21]

1992: Development of the "Utah Intracortical Electrode Array (UIEA), a which can access the columnar structure of the cerebral cortex for neurophysiological or neuroprosthetic applications".^[22]^[23]

multiple-electrode array

1994: The Michigan array, a silicon planar electrode with multiple recording sites, was developed. NeuroNexus, a private neurotechnology company, is formed based on this technology.

[24]

1998: A key breakthrough for BMIs was achieved by Kennedy and Bakay with development of . In patients with amyotrophic lateral sclerosis (ALS), a neurological condition affecting the ability to control voluntary movement, they were able to successfully record action potentials using microelectrode arrays to control a computer cursor.^[25]

neurotrophic electrodes

2016: co-founded and invested $100 million for Neuralink, which aims to develop ultra-high bandwidth BMIs. In 2019, he and Neuralink published their work followed by a live-stream press conference.^[26]

Elon Musk

The ability to record from single units started with the discovery that the nervous system has electrical properties. Since then, single unit recordings have become an important method for understanding mechanisms and functions of the nervous system. Over the years, single unit recording continued to provide insight on topographical mapping of the cortex. Eventual development of microelectrode arrays allowed recording from multiple units at a time.

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Barlow H. B. (1972). . Perception. 1 (4): 371–394. doi:10.1068/p010371. PMID 4377168. S2CID 17487970.

"Single units and sensation: A neuron doctrine for perceptual psychology?"

BeMent S. L.; Wise K. D.; et al. (1986). "Solid-State Electrodes for Multichannel Multiplexed Intracortical Neuronal Recording". IEEE Transactions on Biomedical Engineering. 33 (2): 230–241. :10.1109/tbme.1986.325895. PMID 3957372. S2CID 26878763.

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Kennedy P. R.; Bakay R. A. E. (1997). "Activity of single action potentials in monkey motor cortex during long-term task learning". Brain Research. 760 (1–2): 251–254. :10.1016/s0006-8993(97)00051-6. PMID 9237542. S2CID 20139805.

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Lewicki M. S. (1998). "A review of methods for spike sorting: the detection and classification of neural action potentials". Network: Computation in Neural Systems. 9 (4): R53–78. :10.1088/0954-898x_9_4_001. PMID 10221571.

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Schiller P. H.; Stryker M. (1972). "Single-unit recording and stimulation in superior colliculus of the alert rhesus monkey". Journal of Neurophysiology. 35 (6): 915–924. :10.1152/jn.1972.35.6.915. PMID 4631839. S2CID 18323877.

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