User:Pmcmenamin3/Neurotrophic electrode

The Neurotrophic electrode is an intracortical device designed to read the electrical signals that the brain uses to process information. It consists of a small, hollow glass cone attached to several electrically conductive gold wires. The term "neurotrophic" means "relating to the nutrition and maintenance of nerve tissue" and the device gets its name from the fact that it is coated with Matrigel and Nerve growth factor to encourage the expansion of neurites through its tip. It was invented by neurologist Dr. Philip Kennedy and was successfully implanted for the first time in a human patient in 1996 by neurosurgeon Roy Bakay.

Motivation for Development
Victims of Locked-in syndrome are cognitively intact and aware of their surroundings, but cannot move or communicate due to near complete paralysis of voluntary muscles. In early attempts to return some degree of control to these patients, researchers used cortical signals obtained with Electroencephalography to drive a mouse cursor. However, EEG lacks the speed and precision that can be obtained by using a direct cortical interface.

Patients with other motor diseases, such as ALS and cerebral palsy, as well as those who have suffered a severe stroke or spinal cord injury, also stand to benefit from implanted electrodes. Cortical signals can be used to control robotic limbs, so as the technology improves and the risks of the procedure are reduced, direct interfacing may even provide assistance for amputees.

Design Development
When Dr. Kennedy was designing the electrode, he knew he needed a device that would be wireless, biologically compatible, and capable of chronic implantation. Initial studies with Rhesus monkeys and rats demonstrated that the Neurotrophic electrode was capable of chronic implantation for as long as 14 months (human trials would later establish even greater robustness). This longevity was invaluable for the studies because while the monkeys were being trained at a task, neurons that were initially silent began firing as the task was learned, a phenomenon that would not have been observable if the electrode was not capable of long term implantation.

Glass Cone
The glass cone is only 1-2 mm long, and as mentioned above, it is filled with trophic factors in order to encourage axons and dendrites to grow and extend through its hollow body. When the neurites reach the other end, they rejoin with the neuropil on that side, which anchors the glass cone in place. As a result, stable and robust long-term recording is attainable. The cone sits with its tip near layer five of the cortex, among corticospinal tract cell bodies, and is inserted at an angle of 45 degrees from the surface, about 5 or 6 mm deep.

Gold wires
Three or four gold wires are glued to the inside of the glass cone and protrude out the back. They record the electrical activity of the axons that have grown through the cone, and are insulated with Teflon. The wires are coiled so as to relieve strain since they are embedded in the cortex on one end and attached to the amplifiers, which are fixed to the inside of the skull, on the other. Two wires are plugged into each amplifier to provide differential signalling.

Wireless Transmitter
One of the greatest strengths of the Neurotrophic electrode is its wireless capability, because without transdermal wiring, the risk of infection is significantly reduced. As neural signals are collected by the electrodes, they travel up the gold wires and through the cranium, where they are passed on to the differential amplifiers. The amplified signals are sent through a switch to a transmitter, where they are converted to FM signals and broadcast with an antenna. The amplifiers and the transmitters are powered by a 1 MHz induction signal that is rectified and filtered. The antenna, amplifiers, analog switches, and FM transmitters are all contained in a standard surface mount printed circuit board that sits just under the scalp. The whole ensemble is coated in protective gels, Parylene, Elvax, and Silastic, to make it biocompatible and to protect the electronics from fluids.

Data Acquisition System
On the outside of the patient's scalp rests the corresponding induction coil and an antenna that sends the FM signal to the receiver. These devices are temporarily held in place with a water-soluble paste. The receiver demodulates the signal and sends it to the computer for spike sorting and data recording.

Assembly
Most of the Neurotrophic electrode is made by hand. The gold wires are cut to the correct length, coiled on a hand wound mandrill, and then bent to an angle of 45 degrees just above the cone in order to limit the implantation depth. One more bend in the opposite direction is added where the wires pass through the skull. The tips are stripped of their Teflon coating, and the ones farthest from the cone are soldered and then sealed with dental acrylic to a component connector. The glass cone is made by heating and pulling a "thin walled borosilicate microfilament glass rod" to a point and then that point is clipped with a forceps. The other end is not a straight cut, but rather is carved at an angle to provide a shelf onto which the gold wires can be attached. Then, the wires are placed on the shelf, and a methylmethacrylate gel glue is applied in several coats, with care taken to avoid covering the conductive tips. Lastly, the device is sterilized using glutaraldehyde gas at a low temperature and aerated.

Computer Cursor Control
Dr. Kennedy's first patient, MH, died 76 days after implantation due to her underlying illness, but his second patient, Johnny Ray, was able to learn how to control a computer cursor with the device. Three distinct neural signals from the electrode were correlated with cursor movement along the x-axis, along the y-axis, and a "select" function, respectively. Movement in a given direction was triggered by an increase in neuron firing rate on the associated channel. Initially, bi-directional cursor control on each axis was enabled, but this arrangement proved to be difficult for the patient to manage, so researchers limited movement to one direction, and enabled screen wrapping.

The computer receiving the neural signals was installed with software that either displayed a row of icons or a graphical keyboard on the monitor screen. Each icon represented an expression such as "Hello" or "I'm uncomfortable" and when one was selected, the corresponding phrase was output as speech. The patient was encouraged to attempt various tasks, such as moving the cursor to specific locations, improving his accuracy, and eventually, spelling words with the keyboard. Johnny Ray showed improvement across trials in each of the tasks he was given, with occasional lapses when he became tired.

Speech Synthesis
Computer cursor control is not the only way in which the Neurotrophic electrode has been implemented, however. Neural signals elicited from one of Dr. Kennedy's patients have also been used to formulate vowel sounds using a speech synthesizer in real time. The electronics setup was very similar to that used for the cursor, with the addition of a post-receiver neural decoder, and of course, the synthesizer itself. A pre-surgery fMRI scan indicated locations of high activity in the patient's brain while he was performing a picture naming task. The researchers were able to get good signals from the neurons in the area of the motor cortex associated with the movement of speech articulators, and decided to implant the electrode in that area.

As it turned out, neuron firing patterns in the implanted region corresponded to the trajectories of the intended formant frequencies. In other words, as the patient formulated a pair of vowel sounds in his mind, the spiking pattern shifted to represent the direction in which the frequencies were changing. In order to get audio output, the researchers used the decoder to convert the spike pattern back into formant frequencies for the synthesizer. When the patient was given real time audio feedback, his performance improved significantly across sessions, from an average hit rate of 45% on the first trial to 70% on the last. The average delay from neural firing to synthesizer output was 50 ms, which is approximately the same as the delay for a intact biological pathway.

Plasticity
Johnny Ray's condition was caused by a brainstem stroke, which left him with some capacity for minor facial movement. While he was undergoing training with the computer cursor, parts of his face would move, indicating that there was a correlation between those motor muscle commands and the neural signals he was using to operate the device. However, five months after the implantation, he stopped moving during activation of the signals, and when asked what he was thinking about to move the cursor, he replied "NOTHING." This event demonstrated that plasticity was occurring and indicated that his brain had incorporated the device as an extension of his body.

Comparison to other recording methods
There are many different ways to elicit the intentions of a disabled patient, but depending on the nature of his or her impairment, one method may be more appropriate than all others. Some distinctions are indicated below.

Augmentative and Alternative Communication
Augmentative and Alternative Communication, or AAC is a

Non-invasive brain computer interfacing
EEG/TMS
 * SNR
 * Resolution

Invasive brain computer interfacing
Local Field Potentials

The Neurotrophic electrode is inherently a single-unit device, that is, it reads the action potentials of individual neural units. In one experiment, however, Dr. Kennedy attempted to determine whether local field potentials could produce the same results with the computer cursor. He ran a series of tests with Johnny Ray and one other patient, TT, using implanted amplifiers with a 1000x gain followed by an external amplifier with a 10x gain, and then set a voltage threshold to determine pulse outputs. These outputs were used to either move a cursor or flex the index finger of a computer-generated graphical representation of a hand. The results demonstrated that LFPs are indeed capable of controlling assistive technology devices, suggesting that less invasive techniques can be used to restore functionality to locked-in patients. However, the study did not address the degree of control possible with LFPs or make a formal comparison between LFPs and single unit activity.

Utah Array Michigan Array ECoG

Activation Delay
The neurotrophic electrode is not active immediately after implantation due to the fact that the axons must grow into the cone before the device can pick up electrical signals. Studies have shown that tissue growth is largely complete as early as one month after the procedure, but take as many as four months to stabilize.

Surgery Risks
The risks involved with the implantation are those that are usually associated with brain surgery, namely, the possibility of bleeding, infection, seizures, stroke, and brain damage. Until the technology advances to the point that these risks are considerably reduced, the procedure will be reserved for extreme or experimental cases.

Device Failure
When Johnny Ray was implanted in 1998, one of the Neurotrophic electrodes started providing an intermittent signal after it had become anchored in the neuropil, and as a result, Dr. Kennedy was forced to rely on the remaining devices. Therefore, even if there is no complication from surgery, there is still a possibility that the electronics will fail. In addition, while the implants themselves are encased in the skull and are therefore relatively safe from physical damage, the electronics on the outside of the skull are vulnerable. Two of Dr. Kennedy's patients accidentally caused damage during spasms, but in both cases, only the external devices needed to be replaced.

Neuroprosthetics
At the time of this writing, Dr. Kennedy is working on the speech synthesis application of the electrode, but has plans to expand its uses to many different areas, one of which is restoring movement with neuroprosthetics.

Silent Speech
Silent speech is "speech processing in the absence of an intelligible acoustic signal" to be used either as an aid for the speech-handicapped or to communicate in areas with required silence or high background noise. One of the proposed future uses of the Neurotrophic electrode, and brain computer interfaces in general, is to enable silent speech by decoding the "speaker's" neural signals and transmitting the audio output to headphones worn by the intended receiver. The standard advantages and disadvantages of invasive versus non-invasive interfaces still apply. However, for this particular application, the Neurotrophic electrode has an advantage in that its has already been shown to be effective for restoring communication to disabled patients.