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New Technology Enables More Sensitive Detection of Neural Activity
Far-reaching Potential for Seizure Detection

HIGH-RESOLUTION, FLEXIBLE, ACTIVE ELECTRODE ARRAY with 360 amplified and multiplexed electrodes. The electrode array is ultrathin and fl exible, allowing close contact with the brain and high-resolution recordings of seizures.

The technology to record the electrical circuitry of the brain — from an individual cell to an orchestra of neuronal players — has not changed substantially in four decades. Scientists have been placing electrodes in the brain to record the behavior of neurons but the discoveries are constrained by the technology. Each electrode needs to be threaded to a wire and scientists can only obtain a high-resolution snapshot if they confine the electrodes to a small space.

Now, a team of neuroscientists and engineers has designed a technology that may enable the next generation of scientists to see and hear things that they never have before.

Jonathan Viventi, PhD, assistant professor of electrical engineering at Polytechnic Institute and assistant professor of neuroscience at the Center for Neural Science at New York University, and his colleagues reported in the Nov. 13 online edition of Nature Neuroscience that they built a device that allows them to sample 360 electrodes within a square centimeter, with only 39 wires — offering a resolution that is 400 times what is currently available.

The current technology offers one electrode per square centimeter and is tasked with measuring from about 12 million neurons. “This is a huge distance in neuroscience,” said Dr. Viventi, who added that they are now testing a 1024 electrode array that would require 65 wires. This technology allows better access to the information available from the brain, he said.

DR. BRIAN LITT: “This technology allows us to look at large areas of brain at the same time. This resolution has not been possible before now.”

Scientists said that the device would be a major advance for conditions like epilepsy where brain recordings are often necessary to identify the locus of a seizure. Also, a growing number of patients are undergoing surgery to implant stimulating electrodes on the surface of the brain to disrupt the electrical circuits at the start of a seizure.

The standard technology samples every 10 millimeters in the target tissue and each measurement point will require a wire that goes to an electrical pacemaker-like device. It is now known that seizure activity is on a scale that is less than one millimeter. “We have been a hundred times off,” said Dr. Viventi.

The device, described in the new paper, integrates ultrathin and flexible silicon nano-membrane transistors into the electrode array.

“This is a very different device,” said Dr. Viventi. “It is a powered circuit.”

The array is built on flexible plastic sheets like cellophane. Every contact has its own amplifier and multiplexed circuitry. The research team reduced the thickness of the arrays to allow it to bend into the deep fissures and sulci of brain tissue.

The scientists record at one-half millimeter. The 360-channel active electrode array was tested over a large region of brain tissue, around 10 x 9 millimeters. High-resolution mapping is generally done on a small region of 4 x 4 millimeters. They reduced the number of wires nine-fold.

“We hope this will allow doctors to better understand the electrical patterns of a seizure,” said Dr. Viventi. The researchers said that the device can be scaled to 80 x 80 millimeters with 25,600 channels.

To test the device, the investigators recorded spatial properties of cat brain activity, normally and under the constraint of a seizure. In looking at the activity during seizure onset, they discovered that the electrical activity of the neurons created a spiral wave across the brain. “It looks like a pattern that moves around during the seizure that is similar to how cells behave during a cardiac arrhythmia,” said Dr. Viventi. “We have never seen this before in an animal model. This discovery will help us understand the mechanisms that trigger a seizure.”

DR. JONATHAN VIVENTI: “We hope this will allow doctors to better understand the electrical patterns of a seizure.”

“Seizure control may be analogous to the control of cardiac rhythms,” Dr. Viventi and his colleagues wrote in the paper. “If spiral waves are observed in the human cortex the clinical implications will be profound.”

The spiraling pattern had been documented in brain slices in a petri dish but this was the first time that scientists could identify such activity in a living organism, said Brian Litt, MD, associate professor of neurology and engineering, and senior author of the study. He said that he was surprised to see that the seizures seem to be coming from tiny islands of brain, “more like a cloud of pepper than a golf ball.”

The potential goes well beyond epilepsy. The team is now looking at brain interface devices that could potentially be used to help blind people see and deaf people hear. They are now testing the electrode array to identify finer maps of the auditory and visual cortices to develop more sensitive brain interfaces.

Dr. Litt said that the high resolution could mean that they could one day stimulate the pattern of the auditory cortex that “we could play the sound right onto the brain.” They are collaborating with scientists and engineers to develop cortical prostheses.

“The technology is helping us identify new areas of the auditory and visual system,” said Dr. Viventi.

In the Nature Neuroscience paper, the scientists also reported on the behavior of sleep spindles, short bursts of electrical activity that were thought to occur throughout large areas of the brain during sleep and under anesthesia. The arrays provided quite a different picture: the spindles don't move at all.

“You see them like a blink of light and then they disappear,” said Dr. Viventi.

“This technology allows us to look at large areas of brain at the same time,” said Dr. Litt. “This resolution has not been possible before now.”

The researchers are now conducting safety studies to move the technology into the clinic. They contend that the materials will be safer than the penetrating microelectrode arrays used today that can cause hemorrhage and inflammation.

They are also working on the next generation of the device that could record brain signals, recognize the abnormal pattern and deliver an electrical charge to stop the activity and prevent a seizure.

AN ILLUSTRATION OF HOW a thumbnail-sized, ultra-thin sensor would fit in the brain, allowing high-resolution recording of seizures.

EXPERTS COMMENT

“This is a big advance,” said Story Landis, PhD, director of the NINDS, which helped fund the study. “This technology will give us a much more accurate way of tracing irregular activity in the brain. The standard microelectrodes in the brain are too far apart and not sufficiently sensitive.”

What's more, she added, “the flexibility of the arrays allows scientists to record deep down into the sulci.”

Orrin Devinsky, MD, director of the Epilepsy Center at New York University (NYU) and professor of neurology at NYU Langone School of Medicine, agrees. “This study suggests a new and exciting methodology to use electrodes that can get into regions previously not explored by standard electrodes.”

He added: “Electrical recordings to localize seizure onset has been limited by our technology and access to areas. The study tells us more about seizure onsets in parts of the cerebral cortex that are buried (for example, in sulci). In many patients, we have extensive coverage but never seem to find the focus or seizure onset. It may be that there isn't one — that seizures start from wide areas of the cortex simultaneously. But in many cases, seizures probably do arise locally and we simply don't have electrodes over the onset zone. These electrodes may help solve some of these problems, which could be the difference between success and failure.”

REFERENCE:

• Viventi J, Kim DH, Litt B, et al. Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo. Nat Neurosci 2011; E-pub 2011 Nov 13.