Sunday, October 19, 2008
Neuroscience Research Updates for October
Some fascinating brand new studies in the land of neuroscience recently. Check out the 3 studies and write ups below from our friends at PhysOrg.com
Scientists restore movement to paralyzed limbs through artificial brain-muscle connections
Researchers in a study funded by the National Institutes of Health have demonstrated for the first time that a direct artificial connection from the brain to muscles can restore voluntary movement in monkeys whose arms have been temporarily anesthetized. The results may have promising implications for the quarter of a million Americans affected by spinal cord injuries and thousands of others with paralyzing neurological diseases, although clinical applications are years away.
"This study demonstrates a novel approach to restoring movement through neuroprosthetic devices, one that would link a person's brain to the activation of individual muscles in a paralyzed limb to produce natural control and movements," said Joseph Pancrazio, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS).
The research was conducted by Eberhard E. Fetz, Ph.D., professor of physiology and biophysics at the University of Washington in Seattle and an NINDS Javits awardee; Chet T. Moritz, Ph.D., a post-doctoral fellow funded by NINDS; and Steve I. Perlmutter, Ph.D., research associate professor. The results appear in the online Oct. 15 issue of Nature. The study was performed at the Washington National Primate Research Center, which is funded by NIH's National Center for Research Resources.
In the study, the researchers trained monkeys to control the activity of single nerve cells in the motor cortex, an area of the brain that controls voluntary movements. Neuronal activity was detected using a type of brain-computer interface. In this case, electrodes implanted in the motor cortex were connected via external circuitry to a computer. The neural activity led to movements of a cursor, as monkeys played a target practice game.
After each monkey mastered control of the cursor, the researchers temporarily paralyzed the monkey's wrist muscles using a local anesthetic to block nerve conduction. Next, the researchers converted the activity in the monkey's brain to electrical stimulation delivered to the paralyzed wrist muscles. The monkeys continued to play the target practice game—only now cursor movements were driven by actual wrist movements—demonstrating that they had regained the ability to control the otherwise paralyzed wrist.
The group's approach is one of several lines of current neuroprosthetic research. Some investigators are using brain-computer interfaces to record signals from multiple neurons and convert those signals to control a robotic limb. Other researchers have delivered artificial stimulation directly to paralyzed arm muscles in order to drive arm movement—a technique called functional electrical stimulation (FES). The Fetz study is the first to combine a brain-computer interface with real-time control of FES.
"A robotic arm would be better for someone whose physical arm has been lost or if the muscles have atrophied, but if you have an arm whose muscles can be stimulated, a person can learn to reactivate them with this technology," says Dr. Fetz.
Until now, brain-computer interfaces were designed to decode the activity of neurons known to be associated with movement of specific body parts. Here, the researchers discovered that any motor cortex cell, regardless of whether it had been previously associated with wrist movement, was capable of stimulating muscle activity. This finding greatly expands the potential number of neurons that could control signals for brain-computer interfaces and also illustrates the flexibility of the motor cortex.
"The cells don't have to have a preordained role in the movement. We can create a direct link between the cell and the motor output that the user can learn to control and optimize over time," says Dr. Fetz.
Dr. Fetz and his colleagues found that the monkeys' control over neuronal activity—and the resulting control over stimulation of their wrist muscles—improved significantly with practice. Practice time was limited by the duration of the nerve block. Comparing the monkeys' performance during an initial two-minute practice and a two-minute peak performance period, the scientists found the monkeys successfully hit the target three times more frequently and with less error during the peak performance. In the future, greater control could be gained by using implanted circuits to create long-lasting artificial connections, allowing more time for learning and optimizing control, Dr. Fetz says.
The researchers also found that the monkeys could achieve independent control of both the wrist flexor and extensor muscles.
"An important next step will be to increase the number of direct connections between cortical cells and muscles to control coordinated activation of muscles," says Dr. Fetz.
If researchers are able to establish a connection between the motor cortex and sites in the spinal cord below the injury, people with spinal injuries may be able to achieve coordinated movements.
Clinical applications are still probably at least a decade away, according to Dr. Fetz. Better methods for recording cortical neurons and for controlling multiple muscles must be developed, along with implantable circuitry that could be used reliably and safely, he says.
Source: National Institute of Neurological Disorders and Stroke
If you liked this article, check out this one Army Funds "Synthetic Telepathy" Research from Wired Magazine
Experiments support alternative theory of information processing in the cortex
Neurons in the sound-processing part of the brain's cortex are experts at timing. With remarkable precision, they fire electrochemical pulses or "spikes" in sync with the cues they receive from other neurons, even when these cues are separated by very small time intervals.
A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL), studying this phenomenon in rats, has demonstrated that "spike timing" in cortical neurons can influence behavior even at minuscule time intervals, more precise than previously imagined. Experiments focusing on the auditory cortex revealed that animals in the midst of decision-making have the ability to distinguish incoming signals separated by as little as three milliseconds.
Probing the relation of neuronal firing rates and behavior
The finding, published ahead of print October 12 in the online edition of Nature Neuroscience, adds to the current understanding of how neuronal activity in the brain's cortex modulates behavior. According to the standard model of cortical activity, behavior is thought to be determined by the rate of spiking -- the number of spikes occurring within a given interval. The CSHL team, led by Professor Anthony Zador, Ph.D., wanted to determine whether spike timing had any impact on decision-making and measure the shortest decision-driving interval between spikes.
Zador's group designed an experiment in which rats were trained to behaviorally distinguish between two sounds. When placed in a cage with two water outlets, the rats were trained to turn either to the left or to the right waterspout depending on the sound. The sounds were then replaced by electrical impulses delivered directly to two spatially separated groups of neurons in the auditory cortex. The animals were then re-trained so that simultaneous stimulation of both groups of neurons spurred the animal toward the left waterspout, whereas sequential stimulation of the neuron bundles led the animal to the right waterspout. The rats consistently homed to the right waterspout until the timing between the two sequential stimuli narrowed to below 3 milliseconds. "This suggests that the cortex is capable of 'reading out' very precise nuances in spike timing to drive behavior," says Zador.
Deciphering the "Neural Code"
The group's discovery helps make the case for an alternate theory of how the brain processes information. Neuroscientists have made vast leaps in understanding how neurons communicate with each other in the brain. But they are still in the dark about what the neuron-to-neuron message actually consists of and how it's processed. Known as the "neural code," this blueprint for the brain's information-processing language has proved to be much more elusive than language that is encoded in our genome, which was deciphered decades ago.
The prevailing theory behind the neural code is based on the observation that neurons spike faster when they are transmitting information. This supports a "rate" code model, which stipulates that information is contained within the spiking rate of the neuron. But the CSHL team's new data suggest that the neural code might actually be a "timing" code, where information is encoded within the precise pattern of spiking – something that can be deduced by examining how the spikes are distributed over time.
Zador explains the difference between the two possibilities by likening the brain to an office and neurons to the people working in the office. "If lots of people are talking within each department in a company, you might get a good idea of what's going on in the company by just measuring how loudly people are talking within a given department, which is what the classical 'rate' model predicts," he says.
But as Zador also observes, conversation is not just about loudness; it's also about the identity of the speakers, their speech patterns, etc. "Our results demonstrate directly that there is more to this 'office' than just how loudly people are talking, and motivate us to try to figure out what that extra dimension is," he says. He and his CSHL team will continue to probe for the answers as their work on this and related mysteries about neural communication continues.
Citation: "Millisecond-scale differences in neural activity in auditory cortex can drive decisions" appeared October 12, 2008 as an advance online publication in Nature Neuroscience. The complete citation is: Yang Yang, Michael R DeWeese, Gonzalo Otazu, Anthony M Zador. The paper is available online at http://www.nature.com/neuro/journal/vaop/ncurrent/scriptbs/nn.2211.html
Source: Cold Spring Harbor Laboratory
Emotion and scent create lasting memories -- even in a sleeping brain
When French memoirist Marcel Proust dipped a pastry into his tea, the distinctive scent it produced suddenly opened the flood gates of his memory.
In a series of experiments with sleeping mice, researchers at the Duke University Medical Center have shown that the part of the brain that processes scents is indeed a key part of forming long-term memories, especially involving other individuals.
"We can all relate to the experience of walking into a room and smelling something that sparks a vivid, emotional memory about a family member from years or even decades ago," says Stephen Shea, Ph.D., the lead author of the study published in The Journal of Neuroscience. "This research sought to understand that phenomenon on a cellular level."
The researchers examined how strong memories are formed by creating new memories in the minds of mice while under sedation and monitoring their response to a memory-inducing stimulus afterwards, when they were awake.
"Our work is unique because it allows us to examine the cellular make-up of a memory, evaluate how the neurons change when a memory is formed and learn how that memory affects behavior," Shea adds.
The researchers created memories by stimulating the release of noradrenaline, a chemical present in the body during strong emotional events ranging from excitement to fear.
Previous studies have established a link between noradrenaline and the formation of enduring memories, especially during intense social events such as mating and childbirth. In mice and humans, the presence of noradrenaline also creates changes in the odor processing center of the brain, called the olfactory bulb.
"When an animal forms a strong memory about another, it is reliant on odor cues and noradrenaline. Both need to be present at the same time in order for the memory to be formed," Shea says. "Long-term memories created under these conditions often result in a permanent change in behavior."
The Duke team administered anesthesia to a mouse and stimulated the release of noradrenaline with an electrode while wafting the scent of either food or the urine of another mouse under the nose.
"We wanted to see if these two elements – noradrenaline and odor – present at the same time were the key ingredients needed in the recipe for creation of memory – this is a concept that had not been directly tested before this study," Shea says. "In essence, we recreated the chemical reaction that would occur when the mouse experiences a social event, such as giving birth," Shea says.
Researchers knew they could observe brain activity in more detail when the mouse was under anesthesia. If awake, the mouse would be forming memories from the surrounding environment. "When the animal is asleep, you can watch neurons in the brain rewire to store a memory and once awake see what the mouse learned even though it was asleep when the memory was created."
What they saw was an approximate 40 percent reduction in neuron activation after triggering the noradrenaline release – suggesting that a memory of the odor had been formed.
A day later, after the mouse was awake, the team observed changes in behavior in response to the scents, showing that they remembered the smells from when they were asleep.
"This work may have implications for furthering our understanding of how long-lasting memories are formed that are important to social bonding," says Richard Mooney, Ph.D., co-author and associate professor of neurobiology.
Source: Duke University