Brain implants: Restoring memory with a microchip

William Gibson’s popular science fiction tale “Johnny Mnemonic” foresaw sensitive information being carried by microchips in the brain by 2021. A team of American neuroscientists could be making this fantasy world a reality.

Their motivation is different but the outcome would be somewhat similar. Hailed as one of 2013’s top ten technological breakthroughs by MIT, the work by the University of Southern California, North Carolina’s Wake Forest University and other partners has actually spanned a decade.

But the U.S.-wide team now thinks that it will see a memory device being implanted in a small number of human volunteers within two years and available to patients in five to 10 years. They can’t quite contain their excitement.

"I never thought I’d see this in my lifetime," said Ted Berger, professor of biomedical engineering at the University of Southern California in Los Angeles. "I might not benefit from it myself but my kids will."

Rob Hampson, associate professor of physiology and pharmacology at Wake Forest University, agrees. “We keep pushing forward, every time I put an estimate on it, it gets shorter and shorter.”

The scientists — who bring varied skills to the table, including mathematical modeling and psychiatry — believe they have cracked how long-term memories are made, stored and retrieved and how to replicate this process in brains that are damaged, particularly by stroke or localized injury.

Berger said they record a memory being made, in an undamaged area of the brain, then use that data to predict what a damaged area “downstream” should be doing. Electrodes are then used to stimulate the damaged area to replicate the action of the undamaged cells.

They concentrate on the hippocampus — part of the cerebral cortex which sits deep in the brain — where short-term memories become long-term ones. Berger has looked at how electrical signals travel through neurons there to form those long-term memories and has used his expertise in mathematical modeling to mimic these movements using electronics.

Hampson, whose university has done much of the animal studies, adds: “We support and reinforce the signal in the hippocampus but we are moving forward with the idea that if you can study enough of the inputs and outputs to replace the function of the hippocampus, you can bypass the hippocampus.”

The team’s experiments on rats and monkeys have shown that certain brain functions can be replaced with signals via electrodes. You would think that the work of then creating an implant for people and getting such a thing approved would be a Herculean task, but think again.

For 15 years, people have been having brain implants to provide deep brain stimulation to treat epilepsy and Parkinson’s disease — a reported 80,000 people have now had such devices placed in their brains. So many of the hurdles have already been overcome — particularly the “yuck factor” and the fear factor.

"It’s now commonly accepted that humans will have electrodes put in them — it’s done for epilepsy, deep brain stimulation, (that has made it) easier for investigative research, it’s much more acceptable now than five to 10 years ago," Hampson says.

Much of the work that remains now is in shrinking down the electronics.

"Right now it’s not a device, it’s a fair amount of equipment,"Hampson says. "We’re probably looking at devices in the five to 10 year range for human patients."

The ultimate goal in memory research would be to treat Alzheimer’s Disease but unlike in stroke or localized brain injury, Alzheimer’s tends to affect many parts of the brain, especially in its later stages, making these implants a less likely option any time soon.

Berger foresees a future, however, where drugs and implants could be used together to treat early dementia. Drugs could be used to enhance the action of cells that surround the most damaged areas, and the team’s memory implant could be used to replace a lot of the lost cells in the center of the damaged area. “I think the best strategy is going to involve both drugs and devices,” he says.

Unfortunately, the team found that its method can’t help patients with advanced dementia.

"When looking at a patient with mild memory loss, there’s probably enough residual signal to work with, but not when there’s significant memory loss," Hampson said.

Constantine Lyketsos, professor of psychiatry and behavioral sciences at John Hopkins Medicine in Baltimore which is trialing a deep brain stimulator implant for Alzheimer’s patients was a little skeptical of the other team’s claims.

"The brain has a lot of redundancy, it can function pretty well if loses one or two parts. But memory involves circuits diffusely dispersed throughout the brain so it’s hard to envision." However, he added that it was more likely to be successful in helping victims of stroke or localized brain injury as indeed its makers are aiming to do.

The UK’s Alzheimer’s Society is cautiously optimistic.

"Finding ways to combat symptoms caused by changes in the brain is an ongoing battle for researchers. An implant like this one is an interesting avenue to explore," said Doug Brown, director of research and development.

Hampson says the team’s breakthrough is “like the difference between a cane, to help you walk, and a prosthetic limb — it’s two different approaches.”

It will still take time for many people to accept their findings and their claims, he says, but they don’t expect to have a shortage of volunteers stepping forward to try their implant — the project is partly funded by the U.S. military which is looking for help with battlefield injuries.

There are U.S. soldiers coming back from operations with brain trauma and a neurologist at DARPA (the Defense Advanced Research Projects Agency) is asking “what can you do for my boys?” Hampson says.

"That’s what it’s all about."

Laughter perception networks in brain different for mocking, joyful or ticklish laughter

A laugh may signal mockery, humor, joy or simply be a response to tickling, but each kind of laughter conveys a wealth of auditory and social information. These different kinds of laughter also spark different connections within the “laughter perception network” in the human brain depending on their context, according to research published May 8 in the open access journal PLOS ONE by Dirk Wildgruber and colleagues from the University of Tuebingen, Germany.

Laughter in animals is a form of social bonding based on a primordial reflex to tickling, but human laughter has come a long way from these playful roots. Though many people laugh when they’re tickled, ‘social laughter’ in humans can be used to communicate happiness, taunts or other conscious messages to peers. Here, researchers studied participants’ neural responses as they listened to three kinds of laughter: joy, taunt and tickling.

"Laughing at someone and laughing with someone leads to different social consequences," says Wildgruber. "Specific cerebral connectivity patterns during perception of these different types of laughter presumably reflect modulation of attentional mechanisms and processing resources.

The researchers found that brain regions sensitive to processing more complex social information were activated when people heard joyous or taunting laughter, but not when they heard the ‘tickling laughter’. However, ‘tickling laughter’ is more complex than the other types at the acoustic level, and consequently activated brain regions sensitive to this higher degree of acoustic complexity. These dynamic changes activated and connected different regions depending on the kind of laughter participants heard. Patterns of brain connectivity can impact cognitive function in health and disease. Though some previous research has examined how speech can influence these patterns, this study is among the first few to examine non-verbal vocal cues like laughter.

(Image: Bigstock)

Five “sudden symptoms” of stroke: Recognizing these could save a life - even a young life

Stroke is the fourth-leading cause of death in the United States. Each year an estimated 795,000 people in this country experience a stroke.* That’s approximately the equivalent of every man, woman and child living in Anaheim and Long Beach combined. But did you know that stroke is also the No. 1 cause of adult disability?

Even more surprising, stroke is no longer a disease only of the elderly. Nearly 20 percent of strokes occur in people younger than age 55, and over the past decade, the average age at stroke occurrence has dropped from 71 to 69.

"The good news," says Patrick D. Lyden, MD, chair of Neurology and director of the Stroke Program at Cedars-Sinai Medical Center, "is that quickly recognizing the signs of stroke and seeking immediate medical care from stroke specialists can minimize the effects of the disease or even save a life. And just as important as knowing the symptoms is the knowledge that regardless of an individual’s age, those symptoms need to be treated as the emergency that they are."

• Sudden numbness or weakness of the face, arm or leg on one side of the body.

• Sudden confusion, trouble speaking or understanding.

• Sudden trouble seeing on one side.

• Sudden, severe difficulty walking, dizziness, loss of balance or coordination.

• Sudden, severe headache with no known cause.

It is important to emphasize the words “sudden” and “severe” and the number “one.” Any of these symptoms can occur in a mild, fleeting way and not be worrisome, but if any one of them comes on suddenly and is quite severe, it could signal the onset of a stroke, which increasingly is described as a “brain attack,” because like a heart attack, a stroke requires immediate action to improve the odds against disability and death.

Time is brain

The National Stroke Association estimates that two-thirds of stroke survivors have some disability.

"Clot-busting" drugs make it possible in some cases to stop a stroke in progress and even reverse damage. But the crucial element is time. If given within three hours of onset, the drugs improve outcomes by about 30 percent.

Not every hospital or stroke center has the facilities, staff or resources to provide complete care for every stroke patient, but many hospitals and health authorities are collaborating to establish regional stroke-treatment networks to be sure that even the most complex cases are rapidly transferred to a center with the needed level of care.

(Image: National Stroke Association)

New methods to explore astrocyte effects on brain function

A study in The Journal of General Physiology [1, 2] presents new methods to evaluate how astrocytes contribute to brain function, paving the way for future exploration of these important brain cells at unprecedented levels of detail.

Astrocytes—the most abundant cell type in the human brain—play crucial roles in brain physiology, which may include modulating synaptic activity and regulating local blood flow. Existing research tools can be used to monitor calcium signals associated with interactions between astrocytes and neurons or blood vessels. Until now, however, astrocytic calcium signals have been investigated mainly in their somata (cell bodies) and large processes, rather than in distal fine processes close to neuronal synapses or the endfeet that surround blood vessels. Previous studies have also mainly investigated immature specimens rather than mature brain cells.

Now, a team of California researchers provides detailed methods to visualize calcium signals throughout entire astrocytes in hippocampal slices from adult mice. The team observed numerous spontaneous localized calcium signals throughout the entire astrocyte, including the branchlets and endfeet. Their results indicated that calcium signals in endfeet were independent of those in somata and occurred more frequently. In addition to the specific findings, their methods can be used in future studies to advance our understanding of the physiology of astrocytes and their interactions with neurons and the microvasculature of the brain.

Νeuroscientists use statistical model to draft fantasy teams of neurons

This past weekend teams from the National Football League used statistics like height, weight and speed to draft the best college players, and in a few weeks, armchair enthusiasts will use similar measures to select players for their own fantasy football teams. Neuroscientists at Carnegie Mellon University are taking a similar approach to compile “dream teams” of neurons using a statistics-based method that can evaluate the fitness of individual neurons.

After assembling the teams, a computer simulation pitted the groups of neurons against one another in a playoff-style format to find out which population was the best. Researchers analyzed the winning teams to see what types of neurons made the most successful squads.

The results were published in the early online edition of the Proceedings of the National Academy of Sciences the week of April 29.

"We wanted to know what team of neurons would be most likely to perform best in response to a variety of stimuli," said Nathan Urban, the Dr. Frederick A. Schwertz Distinguished Professor of Life Sciences and head of the Department of Biological Sciences at Carnegie Mellon.

The human brain contains more than 100 billion neurons that work together in smaller groups to complete certain tasks like processing an odor, or seeing a color. Previous work by Urban’s lab found that no two neurons are exactly alike and that diverse teams of neurons were better able to determine a stimulus than teams of similar neurons.

"The next step in our work was to figure out how to assemble the best possible population of neurons in order to complete a task," said Urban, who is also a member of the joint Carnegie Mellon/University of Pittsburgh Center for the Neural Basis of Cognition (CNBC).

However, using existing methods, scouting for the best team of neurons was a seemingly daunting task. It would be impossible for scientists to determine how each of the billions of neurons in the brain would individually respond to a multitude of stimuli. Urban and Shreejoy Tripathy, the article’s lead author and graduate student in the CNBC’s Program in Neural Computation, solved this problem using a statistical modeling approach, known as generalized linear models (GLMs), to analyze the cell-to-cell variability. Urban and Tripathy found that by applying this approach they were able to accurately reproduce the behavior of individual neurons in a computer, allowing them to gather statistics on each single cell.

Then, much like in fantasy football, the computer model used the statistics to put together thousands of teams of neurons. The teams competed against one another in a computer simulation to see which were able to most accurately recreate a stimulus delivered to the team of neurons. In the end researchers identified a small set of teams that they could study to see what characteristics made those populations successful.

They found that the winning teams of neurons were diverse but not as diverse as they would be if they were selected at random from the general population of neurons. The most successful sets contained a heterogeneous group of neurons that were flexible and able to respond well to a variety of stimuli.

"You can’t have a football team made up of only linebackers. You need linebackers and tight ends, a quarterback and a kicker. But, the players can’t just be random people off of the street; they all need to be good athletes. And you need to draft for positions, not just the best player available. If your best player is a quarterback — you don’t take another quarterback with your first pick," Urban said. "It’s the same with neurons. To make the most effective grouping of neurons, you need a diverse bunch that also happens to be more robust and flexible than your average neuron."

Urban believes that GLMs can be used to further understand the importance of neuronal diversity. He plans to use the models to predict how alterations in the variability of neurons’ responses, which can be caused by learning or disease, impact function.

(Image courtesy: University of Iowa)

Thanks to Rare Alpine Bacteria, Researchers Identify One of Alcohol’s Key Gateways to the Brain

Thanks to a rare bacteria that grows only on rocks in the Swiss Alps, researchers at The University of Texas at Austin and the Pasteur Institute in France have been the first to identify how alcohol might affect key brain proteins.

It’s a major step on the road to eventually developing drugs that could disrupt the interaction between alcohol and the brain.

“Now that we’ve identified this key brain protein and understand its structure, it’s possible to imagine developing a drug that could block the binding site,” said Adron Harris, professor of biology and director of the Waggoner Center for Alcohol and Addiction at The University of Texas at Austin.

Harris and his former postdoctoral fellow Rebecca Howard, now an assistant professor at Skidmore College, are co-authors on the paper that was recently published in Nature Communications. It describes the structure of the brain protein, called a ligand-gated ion channel, that is a key enabler of many of the primary physiological and behavioral effects of alcohol.

Harris said that for some time there has been suggestive evidence that these ion channels are important binding sites for alcohol. Researchers couldn’t prove it, however, because they couldn’t crystallize the brain protein well enough, and therefore couldn’t use X-ray crystallography to determine the structure of the protein with and without alcohol present.

“For many of us in the alcohol field, this has been a Holy Grail, actually finding a binding site for alcohol on the brain proteins and showing it with X-ray crystallography,” said Harris. “But it hasn’t been possible because it is not possible to get a nice crystal.”

The breakthrough came when Marc Delarue and his colleagues at the Pasteur Institute sequenced the genome of cyanobacteria Gloeobacter violaceus. They noted a protein sequence on the bacteria that is remarkably similar to the sequence of a group of ligand-gated ion channels in the human brain. They were able to crystallize this protein. Harris saw the results and immediately got in touch.

“This is something you never would have found with any sort of logical approach,” he said. “You never would have guessed that this obscure bacterium would have something that looks like a brain protein in it. But the institute, because of Pasteur’s fascination with bacteria, has this huge collection of obscure bacteria, and over the last few years they’ve been sequencing the genomes, keeping an eye out for interesting properties.”

Harris and Howard asked their French colleagues to collaborate, got the cyanobacteria, changed one amino acid to make it sensitive to alcohol, and then crystallized both the original bacteria and the mutated one. They compared the two to see whether they could identify where the alcohol bound to the mutant. With further tests they confirmed that it was a meaningful site.

“Everything validated that the cavity in which the alcohol bound is important,” said Harris. “It doesn’t account for all the things that alcohol does, but it appears to be important for a lot of them, including some of the ‘rewarding’ effects and some of the negative, aversive effects.”

Going forward, Harris and his lab plan to use mice to observe how changes to the key protein affect behavior when the mice consume alcohol.

They’re also hoping to identify other important proteins from this family of ligand-gated ion channels. In the long term, he hopes to be involved in developing drugs that act on these proteins in ways that help people diminish or cease their drinking.

“So why do some people drink moderately and some excessively?” he said. “One reason lies in that the balance between the rewarding and the aversive effects, and that balance is different for different people, and it can change within an individual depending on their drinking patterns. Some of those effects are determined by the interactions of alcohol and these channels, so the hope is that we can alter the balance. Maybe we can diminish the reward or increase the aversive effects.”