Brain Recording Techniques
The earliest brain recordings — electroencephalograms, or EEGs — used surface electrodes on the scalp to record ongoing brain potentials from large areas of the brain. Most of what researchers know about individual neuronal function (neurophysiology) began in about the middle of the 20th century with the invention and use of microelectrodes, which could sample the activity of single neurons, and oscilloscopes, which could display events lasting milliseconds or less.
As the following discussion shows, several advances have been made in the kinds of devices used to record the workings of the neurons.
Single extracellular microelectrodes
Extracellular microelectrodes are very thin, needlelike wires that are electrically insulated except at their very tip. The tips of these are on the order of the size of a neuron’s cell body (typically 20 micrometers across, depending on the neuronal type).
The electrode tip is inserted into the neural tissue until the tip happens to be near one particular cell, so that the voltage the microelectrode detects is almost entirely due to the action potential currents from the ion channels opening in that one nearby cell soma. These electrodes also sometimes record action potentials from nearby axons. Extracellular microelectrodes have also been used to stimulate neurons to fire by generating pulses of current through the electrode and shocking the neuron to fire artificially.
Microelectrode arrays are clusters of microelectrodes that sample up to hundreds of cells simultaneously. Some of these have been implanted in paralyzed humans so that, for example, when the person thought of making some movement in his brain and activated his motor neurons, the electronically detected signal could be used to bypass the damaged spinal cord and activate muscles directly by sending shocking pulses to them. These recordings have also been used to control computer cursors for communication.
Sharp intracellular electrodes
Intracellular recordings in mammalian neurons were first done with sharp intracellular microelectrodes, also called glass pipettes. These are glass tubes that are heated in the middle and then pulled apart so that the tube necks down and breaks in the middle. The tip at the break can have a diameter of less than one micrometer and still be hollow! These glass microelectrodes are sufficiently small compared to a 20-micrometer diameter cell that they can be inserted inside cells.
Intracellular electrodes inserted through the cell’s membrane allow researchers to sample the electrical activity inside the cell from its synaptic inputs. Sharp intracellular electrodes are filled with a conductive saline solution to make an electrical connection between their open tip inside the cell and electronic amplifiers and displays.
A chloride silver wire inside the micropipette connects the inside of the cell, through the saline solution in the pipette, to an electronic amplifier. Micropipettes yield more information about what’s going on inside the cell, but because they inevitably damage the cell from the penetration, they can’t be implanted permanently as would be needed for neural prostheses that would, for example, record motor cortex commands to artificially drive muscles in people who are paralyzed.
Patch-clamp microelectrodes are made like glass microelectrodes except that, instead of being inserted into the cell, they are placed against the cell membrane so that the glass makes a chemical bond, called a gigaseal, with the cell membrane.
In the intact membrane patch, the electrode can monitor currents passing through ion channels in the membrane within the gigaseal area.
In another configuration, the membrane within the gigaseal is ruptured by negative pressure, but the gigaseal along the perimeter of the pipette opening remains intact, so that, like a glass intracellular microelectrode, there is now electrical continuity between the interior of the cell through the saline solution in the pipette to the recording apparatus.
Optical imaging devices
Optical imaging advances in the late 20th century and the development of reporting dyes led to the use of optical recording techniques for monitoring neural activity. Here are the three main optical techniques for recording neural activity:
- Fluorescent dye-mediated monitoring of ionic concentration changes: This technique uses fluorescent dyes (dyes that absorb and then re-emit light) that change their fluorescence in response to the presence of ions like calcium, magnesium, or sodium. The most common dyes monitor calcium concentration, which is normally very low inside neurons but typically increases when the neuron is active due to calcium flux through cation channels that are not completely selective for sodium, and through voltage-dependent calcium channels that are sometimes common in neuronal dendritic trees as well as at the axon terminal. This means that activity within neural dendritic trees can sometimes be directly observed optically. Optical imaging also allows researchers to view the activity in multiple cells through a microscope. Fluorescent proteins can now be expressed in specific neuronal cells in specific parts of the brain by transgenetic techniques of DNA alteration in experimental animals.
- Fluorescent dye-mediated monitoring of membrane potential: Potentiometric dyes are dyes that bind neuronal cell membranes and change either their fluorescence or absorption of light in response to the level of depolarization of the membrane. The advantage of these dyes is that they give a direct reading of the electrical potential across the membrane so that membrane changes can be observed whether or not there happen to be ion channels there that flux calcium. On the other hand, the signal from these dyes is typically an order of magnitude less than that of calcium indicator dyes. These smaller signals are harder to detect.
- Intrinsic optical changes in excited neural tissue, such as light scattering: Intrinsic optical changes occur in neuronal tissue when cells are electrically active. The origin of these changes is unclear at the time of this writing but includes changes in light scattering due to transient cell swelling or rearrangement of intracellular organelle structures associated with electrical activation. One advantage of intrinsic optical techniques is that they require no dyes and are therefore less invasive. Intrinsic optical recordings similar to electroencephalograms (EEGs) are routinely carried out in humans using infrared light.