Posts tagged neuroimaging
Posts tagged neuroimaging
After capturing the first brain images of two alert, unrestrained dogs last year, researchers at Emory University have confirmed their methods and results by replicating them in an experiment involving 13 dogs.
The research, published by the Public Library of Science One (PLOS One), showed that most of the dogs had a positive response in the caudate region of the brain when given a hand signal indicating they would receive a food treat, as compared to a different hand signal for “no treat.”
“Our experiment last year was really a proof of concept, demonstrating that dogs could be trained to undergo successful functional Magnetic Resonance Imaging (fMRI),” says the lead researcher Gregory Berns, director of Emory’s Center for Neuropolicy. “Now we’ve shown that the initial study wasn’t a fluke: Canine fMRI is reliable and can be done with minimal stress to the dogs. We have laid the foundation for exploring the neural biology and cognitive processes of man’s best, and oldest, friend.”
Co-authors of the paper include Andrew Brooks, a post-doctoral fellow at the Center for Neuropolicy, and Mark Spivak, a dog trainer and the owner of Comprehensive Pet Therapy.
Both the initial experiment and the more recent one involved training the dogs to acclimatize to an fMRI machine. The task requires dogs to cooperatively enter the small enclosure of the fMRI scanner and remain completely motionless despite the noise and vibration of the machine.
Only those dogs that willingly cooperated were involved in the experiments. The canine subjects were given harmless fMRI brain scans while they watched a human giving hand signals that the dogs had been trained to understand. One signal indicated that the dog would receive a hot dog for a treat. The other hand signal meant that the dog would not receive a hot dog.
The most recent experiment involved the original two dogs, plus 11 additional ones, of varying breeds. Eight out of the 13 showed the positive caudate response for the hand signal indicating they were going to receive a hot dog.
The caudate sits above the brain stem in mammals and has the highest concentration of dopamine receptors, which are implicated in motivation and pleasure, among other neurological processes.
“We know that in humans, the caudate region is associated with decision-making, motivation and processing emotions,” Berns says.
As a point of reference, the researchers compared the results to a similar experiment Berns had led 10 years previously involving humans, in which the subjects pressed a button when a light appeared, to get a squirt of fruit juice.
Eleven of 17 humans involved in that experiment showed a positive response in the caudate region that was similar to the positive response of the dogs. “Our findings suggest that the caudate region of the canine brain behaves similarly to the caudate of the human brain, under similar circumstances,” Berns says.
Six of the dogs involved in the experiment had been specially bred and trained to assist disabled people as companion animals, and two of the dogs (including one of the service dogs) had worked as therapy dogs, used to help alleviate stress in people in hospitals or nursing homes. All of the service/therapy dogs showed a greater level of positive caudate activation for the hot dog signal, compared to the other dogs.
“We don’t know if the service dogs and therapy dogs showed this difference because of genetics, or because of the environment in which they were raised, but we hope to find out in future experiments,” Berns says. “This may be the first hint of how the brains of dogs with different temperaments and personalities differ.”
He adds: “I don’t think it was because they liked hot dogs more. I saw no evidence of that. None of the dogs turned down the hot dogs.”
One limitation of the experiments is the small number of subjects and the selectivity of the dogs involved, since only certain dogs can be trained to do the experiments, Berns says.
“We’re expanding our cohort to include more dogs and more breeds,” Berns says. “As the dogs get more accustomed to the process, we can conduct more complicated experiments.”
Plans call for comparing how the canine brain responds to hand signals coming from the dog’s owner, a stranger and a computer. Another experiment already under way is looking at the neural response of dogs when they are exposed to scents of members of their households, both humans and other dogs, and unfamiliar humans and dogs.
“Ultimately, our goal is to map out canine cognitive processes,” says Berns, who recently published a book entitled “How Dogs Love Us: A Neuroscientist and His Adopted Dog Decode the Canine Brain.”
Even in an increasingly technical era, the role of dogs has not diminished, Berns says. In addition to being popular pets, he notes that dogs are important in the U.S. military, in search-and-rescue missions, as assistants for the disabled and as therapeutic stress relievers for hospital patients and others.
“Dogs have been a part of human society for longer than any other animal,” Berns says. He cites a genetic analysis recently published in Science suggesting that the domestication of dogs goes back 18,000 to 32,000 years, preceding the development of agriculture some 10,000 years ago.
“Most neuroscience studies on animals are conducted to serve as models for human disease and brain functions,” Berns says. “We’re not studying canine cognition to serve as a model for humans, but what we learn about the dog brain may also help us understand more about how our own brains evolved.”
Using a novel stroke rehabilitation device that converts an individual’s thoughts to electrical impulses to move upper extremities, stroke patients reported improvements in their motor function and ability to perform activities of daily living. Results of the study were presented today at the annual meeting of the Radiological Society of North America (RSNA).
"Each year, nearly 800,000 people suffer a new or recurrent stroke in the United States, and 50 percent of those have some degree of upper extremity disability," said Vivek Prabhakaran, M.D., Ph.D., director of functional neuroimaging in radiology at the University of Wisconsin-Madison. "Rehabilitation sessions with our device allow patients to achieve an additional level of recovery and a higher quality of life."
Dr. Prabhakaran, along with co-principal investigator Justin Williams, Ph.D., and a multidisciplinary team, built the new rehabilitation device by pairing a functional electrical stimulation (FES) system, which is currently used to help stroke patients recover limb function, and a brain control interface (BCI), which provides a direct communication pathway between the brain and this peripheral stimulation device.
In an FES system, electrical currents are used to activate nerves in paralyzed extremities. Using a computer and an electrode cap placed on the head, the new BCI-FES device (called the Closed-Loop Neural Activity-Triggered Stroke Rehabilitation Device) interprets electrical impulses from the brain and transmits the information to the FES.
"FES is a passive technique in that the electrical impulses move the patients’ extremities for them," Dr. Prabhakaran said. "When a patient using our device is asked to imagine or attempt to move his or her hand, the BCI translates that brain activity to a signal that triggers the FES. Our system adds an active component to the rehabilitation by linking brain activity to the peripheral stimulation device, which gives the patients direct control over their movement."
The Wisconsin team conducted a small clinical trial of their rehabilitation device, enlisting eight patients with one hand affected by stroke. The patients were also able to serve as a control group by using their normal, unaffected hand. Patients in the study represented a wide range of stroke severity and amount of time elapsed since the stroke occurred. Despite having received standard rehabilitative care, the patients had varying degrees of residual motor deficits in their upper extremities. Each underwent nine to 15 rehabilitation sessions of two to three hours with the new device over a period of three to six weeks.
The patients also underwent functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) before, at the mid-point of, at the end of, and one month following the rehabilitation period. fMRI is able to show which areas of the brain are activated while the patient performs a task, and DTI reveals the integrity of fibers within the white matter that connects the brain’s functional areas.
Patients who suffered a stroke of moderate severity realized the greatest improvements to motor function following the rehabilitation sessions. Patients diagnosed with mild and severe strokes reported improved ability to complete activities of daily living following rehabilitation.
Dr. Prabhakaran said the results captured throughout the rehabilitation process—specifically the ratio of hemispheric involvement of motor areas—related well to the behavioral changes observed in patients. A comparison of pre-rehabilitation and post-rehabilitation fMRI results revealed reorganization in the regions of the brain responsible for motor function. DTI results over the course of the rehabilitation period revealed a gradual strengthening of the integrity of the fiber tracts.
"Our hope is that this device not only shortens rehabilitation time for stroke patients, but also that it brings a higher level of recovery than is achievable with the current standard of care," Dr. Prabhakaran said. "We believe brain imaging will be helpful in both planning and tracking a stroke patient’s therapy, as well as learning more about neuroplastic changes during recovery."
Scientists have discovered that playing computer games can bring players’ emotional responses and brain activity into unison.
By measuring the activity of facial muscles and imaging the brain while gaming, the group found out that people go through similar emotions and display matching brainwaves. The study of Helsinki Institute for Information Technology HIIT researchers is now published in PLOS ONE.
– It’s well known that people who communicate face-to-face will start to imitate each other. People adopt each other’s poses and gestures, much like infectious yawning. What is less known is that the very physiology of interacting people shows a type of mimicry – which we call synchrony or linkage, explains Michiel Sovijärvi-Spapé.
In the study, test participants play a computer game called Hedgewars, in which they manage their own team of animated hedgehogs and in turns shoot the opposing team with ballistic artillery. The goal is to destroy the opposing team’s hedgehogs. The research team varied the amount of competitiveness in the gaming situation: players teamed up against the computer and they were also pinned directly against each other.
The players were measured for facial muscle reactions with facial electromyography, or fEMG, and their brainwaves were measured with electroencephalography, EEG.
– Replicating previous studies, we found linkage in the fEMG: two players showed both similar emotions and similar brainwaves at similar times. We further observed a linkage also in the brainwaves with EEG, tells Sovijärvi-Spapé.
A striking discovery indicates further that the more competitive the gaming gets, the more in sync are the emotional responses of the players. The test subjects were to report emotions themselves, and negative emotions were associated with the linkage effect.
– Although counterintuitive, the discovered effect increases as a game becomes more competitive. And the more competitive it gets, the more the players’ positive emotions begin to reflect each other. All the while their experiences of negative emotions increase.
The results present promising upshots for further study.
– Feeling others’ emotions could be particularly beneficial in competitive settings: the linkage may enable one to better anticipate the actions of opponents.
Another interpretation suggested by the group is that the physical linkage of emotion may work to compensate a possibly faltering social bond while competing in a gaming setting.
– Since our participants were all friends before the game, we can speculate that the linkage is most prominent when a friendship is ‘threatened’ while competing against each other, ponders Sovijärvi-Spapé.
When reading text or listening to someone speak, we construct rich mental models that allow us to draw conclusions about other people, objects, actions, events, mental states and contexts. This ability to understand written or spoken language, called “discourse comprehension,” is a hallmark of the human mind and central to everyday social life. In a new study, researchers uncovered the brain mechanisms that underlie discourse comprehension.
The study appears in Brain: A Journal of Neurology.
With his team, study leader Aron Barbey, a professor of neuroscience, of psychology, and of speech and hearing science at the University of Illinois, previously had mapped general intelligence, emotional intelligence and a host of other high-level cognitive functions. Barbey is the director of the Decision Neuroscience Laboratory at the Beckman Institute for Advanced Science and Technology at Illinois.
To investigate the brain regions that underlie discourse comprehension, the researchers studied a group of 145 American male Vietnam War veterans who sustained penetrating head injuries during combat. Barbey said these shrapnel-induced injuries typically produced focal brain damage, unlike injuries caused by stroke or other neurological disorders that affect multiple regions. These focal injuries allowed the researchers to pinpoint the structures that are critically important to discourse comprehension.
“Neuropsychological patients with focal brain lesions provide a valuable opportunity to study how different brain structures contribute to discourse comprehension,” Barbey said.
A technique called voxel-based lesion-symptom mapping allowed the team to pool data from the veterans’ CT scans to create a collective, three-dimensional map of the cerebral cortex. They divided this composite brain into units called voxels (the three-dimensional counterparts of two-dimensional pixels). This allowed them to compare the discourse comprehension abilities of patients with damage to a particular voxel or cluster of voxels with those of patients without injuries to those brain regions.
The researchers identified a network of brain areas in the frontal and parietal cortex that are essential to discourse comprehension.
“Rather than engaging brain regions that are classically involved in language processing, our results indicate that discourse comprehension depends on an executive control network that helps integrate incoming language with prior knowledge and experience,” Barbey said. Executive control, also known as executive function, refers to the ability to plan, organize and regulate one’s behavior.
“The findings help us understand the neural foundations of discourse comprehension, and suggest that core elements of discourse processing emerge from a network of brain regions that support language processing and executive functions. The findings offer new insights into basic questions about the nature of discourse comprehension,” Barbey said, “and could offer new targets for clinical interventions to help patients with cognitive-communication disorders.
“Discourse comprehension is a hallmark of human social behavior,” Barbey said. “By studying the mechanisms that underlie these abilities, we’re able to advance our understanding of the remarkable cognitive and neural architecture from which language comprehension emerges.”
After a mild concussion, special brain scans show evidence of brain abnormalities four months later, when symptoms from the concussion have mostly dissipated, according to research published in the November 20, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“These results suggest that there are potentially two different modes of recovery for concussion, with the memory, thinking and behavioral symptoms improving more quickly than the physiological injuries in the brain,” said study author Andrew R. Mayer, PhD, of the Mind Research Network and University of New Mexico School of Medicine in Albuquerque.
Mayer further suggests that healing from concussions may be similar to other body ailments such as recovering from a burn. “During recovery, reported symptoms like pain are greatly reduced before the body is finished healing, when the tissue scabs. These finding may have important implications about when it is truly safe to resume physical activities that could produce a second concussion, potentially further injuring an already vulnerable brain.”
Mayer noted that standard brain scans such as CT or MRI would not pick up on these subtle changes in the brain. “Unfortunately, this can lead to the common misperception that any persistent symptoms are psychological.”
The study compared 50 people who had suffered a mild concussion to 50 healthy people of similar age and education. All the participants had tests of their memory and thinking skills and other symptoms such as anxiety and depression two weeks after the concussion, as well as brain scans. Four months after the concussion, 26 of the patients and 26 controls repeated the tests and scans.
The study found that two weeks after the injury the people who had concussions had more self-reported problems with memory and thinking skills, physical problems such as headaches and dizziness, and emotional problems such as depression and anxiety than people who had not had concussions. By four months after the injury, the symptoms were significantly reduced by up to 27 percent.
The people who had concussions also had evidence of abnormalities in the gray matter in the frontal cortex area of both sides of the brain, based on the diffusion tensor imaging scans. The increase equated to about 10 percent compared to the healthy people in the study. These abnormalities were still apparent four months after the concussion. In contrast, there was no evidence of cellular loss on scans.
Mayer said possible explanations for the brain abnormalities could be cytotoxic edema, which results from changes in where fluids are located in and around brain cells, or reactive gliosis, which is the change in glial cells’ shape in response to damage to the central nervous system.
George Melendez has been called a medical miracle. After a near drowning deprived his brain of oxygen, Melendez remained in a fitful, minimally conscious state until his mother, in 2002, decided to give him the sleep aid drug Ambien to quiet his moaning and writhing. The next thing she knew, her son was quietly looking at her and trying to talk. He has been using the drug ever since to maintain awareness, but no one could understand why Ambien led to such an awakening.
Now, a team of scientists led by Weill Cornell Medical College has discovered a signature of brain activity in Melendez and two other similarly “awakened” patients they say explain why he and others regain some consciousness after using Ambien or other drugs or treatments. The pattern of activity, reported Nov. 19 in the journal eLife, was identified by analyzing the common electroencephalography (EEG) test, which tracks brain waves.
"We found a surprisingly consistent picture of electrical activity in all three patients before they receive the drug. Most interesting is that their specific pattern of activity suggests a particular process occurring in the brain cells of the cerebral cortex and also supports the role of a crucial brain circuit," says the study’s senior investigator, Dr. Nicholas Schiff, the Jerold B. Katz Professor of Neurology and Neuroscience and professor of public health at Weill Cornell. "These findings may help predict other patients who might similarly harbor reserve capacity, whether they are able to respond to Ambien or other approaches." Dr. Schiff is also on the faculty of the Feil Family Brain and Mind Research Institute at Weill Cornell and is a neurologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
"We are focused on finding ways to identify patients who have a functional reserve of cognitive capacities that can be rescued and how to achieve this result," Dr. Schiff adds. "These findings give us a very important lead to follow, and we will now rigorously test their implications in other patients."
Although it is not precisely known how many Americans are diagnosed as severely brain injured with disorders of consciousness, by one estimate there are nearly 300,000 patients trapped in a minimally conscious state who may retain some awareness, according to Dr. Schiff.
Riding a Wave of Excitation
The three patients in the study suffered brain damage in different ways. One fell and the other had a brain aneurysm that led to multiple strokes. Melendez was in a car accident that led to his nearly drowning. All three patients — two men and a woman — become aware when Ambien was used, a rare response that has been documented in fewer than 15 brain-injured patients.
The research team, which included scientists from Memorial Sloan-Kettering Cancer Center, Boston University School of Medicine, and the University Hospital of Liège in Belgium, used EEG to measure electrical activity in the patients’ brains before and after they were given the drug.
Although each patient’s brain was damaged in different ways, all showed the same unique features of low frequency waves in their EEG readings. These low frequency oscillations are most prominent over the frontal cortex, a region strongly dependent for its activity on other brain structures, particularly the central thalamus and the striatum, which together support short-term memory, reward, motivation, attention, alertness and sleep, among other functions.
In this setting of an idling brain, the investigators propose that Ambien works like any anesthesia drug, in that it briefly triggers a fast wave of excitation in brain cells before producing sleep — a phenomenon known as paradoxical excitation. Instead of going on to produce sedation and sleep, as it does in healthy people who use the drug, zolpidem further activates the brain after it’s affected the idling cells, allowing the patients to become more awake than at baseline. “What we think is happening in these patients is that the initial excitation produced by Ambien turns on a specific circuit. The drug creates the opportunity for the brain to effectively catch a ride on this initial wave of excitation, and turn itself back on,” Dr. Schiff says.
This proposed “mesocircuit” links the cortical regions of the brain to the central thalamus and striatum. Neurons in the central thalamus are highly connected to other parts of the brain, “so damage in one part of the brain or another will affect the thalamus, which is key to consciousness,” Dr. Schiff says. Neurons in the striatum “will only fire if there is a lot of electrical input coming to them quickly,” he says.
"We believe the switch that Ambien turns on is at the level of the joint connections between these three brain structures," Dr. Schiff says.
The pattern of brain activity seen in the EEG on Ambien was also the same in all the patients in the study. But the circuit turns off again when the effects of the drug diminish. Using the drug regularly at mealtimes, Melendez can speak fluently, and read and write simple phrases. His tremors and spasticity are significantly reduced on Ambien and he can use objects, such as a spoon, and is alert and can communicate. The first patient in the study can reliably move from minimally conscious to “the mid-range of what is called a confusional state — a more alert status, but not full consciousness,” Dr. Schiff says. “Use of Ambien offers a step in the right direction, but certainly not a cure.”
Different Ways to Kick-Start the Brain
The resting EEG pattern the researchers saw in the patients indicates they have a “recruitable reserve” of function in these critical brain areas that Ambien can harness to turn the brain on, even if only temporarily. “The idea is that hopefully we can screen other patients with EEG to find out if they also have such a reserve,” Dr. Schiff says.
And while some of these patients may not respond to Ambien — as the drug works at a very specific brain receptor and individuals can vary considerably in having enough of it in the key components of the proposed circuit — other drugs may target the same structures and potentially produce similar effects, he says. For example, two drugs (amantadine and L-Dopa) that provide extra dopamine, a brain chemical that fuels the part of the brain damaged in the study’s patients, have been shown to have similar effects on restoring function in patients with severe brain injuries, as has electrical brain stimulation of the central thalamus.
"Now that we have uncovered important insight into fundamental mechanisms underlying the dramatic and rare response of some severely brain-injured patients to Ambien, we hope to systematically explore ways to achieve such kick-starts in other patients — that is our goal," Dr. Schiff says.
A new blood biomarker correctly predicted which concussion victims went on to have white matter tract structural damage and persistent cognitive dysfunction following a mild traumatic brain injury (mTBI). Researchers in the Perelman School of Medicine at the University of Pennsylvania, in conjunction with colleagues at Baylor College of Medicine, found that the blood levels of a protein called calpain-cleaved αII-spectrin N-terminal fragment (SNTF) were twice as high in a subset of patients following a traumatic injury. If validated in larger studies, this blood test could identify concussion patients at increased risk for persistent cognitive dysfunction or further brain damage and disability if returning to sports or military activities.
More than 1.5 million children and adults suffer concussions each year in the United States, and hundreds of thousands of military personal endure these mild traumatic brain injuries worldwide. Current tests are not capable of determining the extent of the injury or whether the injured person will be among the 15-30 percent who experience significant, persistent cognitive deficits, such as processing speed, working memory and the ability to switch or balance multiple thoughts.
"New tests that are fast, simple, and reliable are badly needed to predict who may experience long-term effects from concussions, and as new treatments are developed in the future, to identify who should be eligible for clinical trials or early interventions," said lead author Robert Siman, PhD, research professor of Neurosurgery at Penn. "Measuring the blood levels of SNTF on the day of a brain injury may help to identify the subset of concussed patients who are at risk of persistent disability."
In a study published yesterday in Frontiers in Neurology, Penn and Baylor researchers evaluated blood samples and diffusion tensor images from a subgroup of 38 participants in a larger study of mTBI with ages ranging from 15 to 25 years old. 17 had sustained a head injury caused by blunt trauma, acceleration or deceleration forces, 13 had an orthopaedic injury, and 8 were healthy, uninjured, demographically matched controls.
In taking neuropsychological and cognitive tests over the course of three months, results within the mTBI group varied considerably, with some patients performing as well as the healthy controls throughout, while others showed impairment initially that resolved by three months, and a third group with cognitive dysfunction persisting through three months. The nine patients who had abnormally high levels of SNTF (7 mTBI and 2 orthopaedic patients) also had significant white matter damage apparent in radiological imaging.
"The blood test identified SNTF in some of the orthopaedic injury patients as well, suggesting that these injuries could also lead to abnormalities in the brain, such as a concussion, that may have been overlooked with existing tests," said Douglas Smith, MD, director of the Penn Center for Brain Injury and Repair and professor of Neurosurgery. "SNTF as a marker is consistent with our earlier research showing that calcium is dumped into neurons following a traumatic brain injury, as SNTF is a marker for neurodegeneration driven by calcium overload."
The blood test given on the day of the mild traumatic brain injury showed 100 percent sensitivity to predict concussions leading to persisting cognitive problems, and 75 percent specificity to correctly rule out those without functionally harmful concussions. If validated in larger studies, a blood test measuring levels of SNTF could be helpful in diagnosing and predicting risk of long term consequences of concussion. The Penn and Baylor researchers hope to determine the robustness of these findings with a second larger study, and determine the best time after concussion to measure SNTF in the blood in order to predict persistent brain dysfunction. The team also wants to evaluate their blood test for identifying when repetitive concussions begin to cause brain damage and persistent disability.
A research team at Worcester Polytechnic Institute (WPI) and The Rockefeller University in New York has developed a novel system to image brain activity in multiple awake and unconstrained worms. The technology, which makes it possible to study the genetics and neural circuitry associated with animal behavior, can also be used as a high-throughput screening tool for drug development targeting autism, anxiety, depression, schizophrenia, and other brain disorders.
Image: Neurons in the worms (marked by arrows) glow as the animals sense attractive odors.
The team details their technology and early results in the paper “High-throughput imaging of neuronal activity in Caenorhabditis elegans,” published on-line in advance of print by the journal Proceedings of the National Academy of Sciences.
"One of our major objectives is to understand the neural signals that direct behavior—how sensory information is processed through a network of neurons leading to specific decisions and responses," said Dirk Albrecht, PhD, assistant professor of biomedical engineering at WPI and senior author of the paper. Albrecht led the research team both at WPI and at Rockefeller, where he served previously as a postdoctoral researcher in the lab of Cori Bargmann, PhD, a Howard Hughes Medical Institute Investigator and a co-author of the new paper.
To study neuronal activity, Albrecht’s lab uses the tiny worm Caenorhabditis elegans (C. elegans), a nematode found in many environments around the world. A typical adult C. elegans is just 1 millimeter long and has 969 cells, of which 302 are neurons. Despite its small size, the worm is a complex organism able to do all of the things animals must do to survive. It can move, eat, mate, and process environmental cues that help it forage for food or react to threats. As a bonus for researchers, C.elegans is transparent. By using various imaging technologies, including optical microscopes, one can literally see into the worm and watch physiological processes in real time.
Numerous studies have been done by “worm labs” around the world exploring various neurological processes in C. elegans. These have typically been done using one worm at a time, with the animal’s body fixed in place on a slide. In their new paper, Albrecht’s team details how they imaged, recorded, and analyzed specific neurons in multiple animals as they wormed their way around a custom-designed microfluidic array, called an arena, where they were exposed to favorable or hostile sensory cues.
Specifically, the team engineered a strain of worms with neurons near the head that would glow when they sensed food odors. In experiments involving up to 23 worms at a time, Albrecht’s team infused pulses of attractive or repulsive odors into the arena and watched how the worms reacted. In general, the worms moved towards the positive odors and away from the negative odors, but the behaviors did not always follow this pattern. “We were able to show that the sensory neurons responded to the odors similarly in all the animals, but their behavioral responses differed significantly,” Albrecht said. “These animals are genetically identical, and they were raised together in the same environment, so where do their different choices come from?”
In addition to watching the head neurons light up as they picked up odor cues, the new system can trace signaling through “interneurons.” These are pathways that connect external sensors to the rest of the network (the “worm brain”) and send signals to muscle cells that adjust the worm’s movement based on the cues. Numerous brain disorders in people are believed to arise when neural networks malfunction. In some cases the malfunction is dramatic overreaction to a routine stimulus, while in others it is a lack of appropriate reactions to important cues. Since C. elegans and humans share many of the same genes, discovering genetic causes for differing neuronal responses in worms could be applicable to human physiology. Experimental compounds designed to modulate the action of nerve cells and neuronal networks could be tested first on worms using Albrecht’s new system. The compounds would be infused in the worm arena, along with other stimuli, and the reaction of the worms’ nervous systems could be imaged and analyzed.
"The basis of our work is to combine biomedical engineering and neuroscience to answer some of these fundamental questions and hopefully gain insight that would be beneficial for understanding and eventually treating human disorders," Albrecht said.
University of Arizona doctoral degree candidate Jay Sanguinetti has authored a new study, published online in the journal Psychological Science, that indicates that the brain processes and understands visual input that we may never consciously perceive.
The finding challenges currently accepted models about how the brain processes visual information.
A doctoral candidate in the UA’s Department of Psychology in the College of Science, Sanguinetti showed study participants a series of black silhouettes, some of which contained meaningful, real-world objects hidden in the white spaces on the outsides.
Saguinetti worked with his adviser Mary Peterson, a professor of psychology and director of the UA’s Cognitive Science Program, and with John Allen, a UA Distinguished Professor of psychology, cognitive science and neuroscience, to monitor subjects’ brainwaves with an electroencephalogram, or EEG, while they viewed the objects.
"We were asking the question of whether the brain was processing the meaning of the objects that are on the outside of these silhouettes," Sanguinetti said. "The specific question was, ‘Does the brain process those hidden shapes to the level of meaning, even when the subject doesn’t consciously see them?"
The answer, Sanguinetti’s data indicates, is yes.
Study participants’ brainwaves indicated that even if a person never consciously recognized the shapes on the outside of the image, their brains still processed those shapes to the level of understanding their meaning.
"There’s a brain signature for meaningful processing," Sanguinetti said. A peak in the averaged brainwaves called N400 indicates that the brain has recognized an object and associated it with a particular meaning.
"It happens about 400 milliseconds after the image is shown, less than a half a second," said Peterson. "As one looks at brainwaves, they’re undulating above a baseline axis and below that axis. The negative ones below the axis are called N and positive ones above the axis are called P, so N400 means it’s a negative waveform that happens approximately 400 milliseconds after the image is shown."
The presence of the N400 peak indicates that subjects’ brains recognize the meaning of the shapes on the outside of the figure.
"The participants in our experiments don’t see those shapes on the outside; nonetheless, the brain signature tells us that they have processed the meaning of those shapes," said Peterson. "But the brain rejects them as interpretations, and if it rejects the shapes from conscious perception, then you won’t have any awareness of them."
"We also have novel silhouettes as experimental controls," Sanguinetti said. "These are novel black shapes in the middle and nothing meaningful on the outside."
The N400 waveform does not appear on the EEG of subjects when they are seeing truly novel silhouettes, without images of any real-world objects, indicating that the brain does not recognize a meaningful object in the image.
"This is huge," Peterson said. "We have neural evidence that the brain is processing the shape and its meaning of the hidden images in the silhouettes we showed to participants in our study."
The finding leads to the question of why the brain would process the meaning of a shape when a person is ultimately not going to perceive it, Sanguinetti said.
"The traditional opinion in vision research is that this would be wasteful in terms of resources," he explained. "If you’re not going to ultimately see the object on the outside why would the brain waste all these processing resources and process that image up to the level of meaning?"
"Many, many theorists assume that because it takes a lot of energy for brain processing, that the brain is only going to spend time processing what you’re ultimately going to perceive," added Peterson. "But in fact the brain is deciding what you’re going to perceive, and it’s processing all of the information and then it’s determining what’s the best interpretation."
"This is a window into what the brain is doing all the time," Peterson said. "It’s always sifting through a variety of possibilities and finding the best interpretation for what’s out there. And the best interpretation may vary with the situation."
Our brains may have evolved to sift through the barrage of visual input in our eyes and identify those things that are most important for us to consciously perceive, such as a threat or resources such as food, Peterson suggested.
In the future, Peterson and Sanguinetti plan to look for the specific regions in the brain where the processing of meaning occurs.
"We’re trying to look at exactly what brain regions are involved," said Peterson. "The EEG tells us this processing is happening and it tells us when it’s happening, but it doesn’t tell us where it’s occurring in the brain."
"We want to look inside the brain to understand where and how this meaning is processed," said Peterson.
Images were shown to Sanguinetti’s study participants for only 170 milliseconds, yet their brains were able to complete the complex processes necessary to interpret the meaning of the hidden objects.
"There are a lot of processes that happen in the brain to help us interpret all the complexity that hits our eyeballs," Sanguinetti said. "The brain is able to process and interpret this information very quickly."
Sanguinetti’s study indicates that in our everyday life, as we walk down the street, for example, our brains may recognize many meaningful objects in the visual scene, but ultimately we are aware of only a handful of those objects.
The brain is working to provide us with the best, most useful possible interpretation of the visual world, Sanguinetti said, an interpretation that does not necessarily include all the information in the visual input.
When people appear comatose, how can we know their wishes?
A Michigan Technological University researcher says many non-communicative individuals may actually be able to express themselves better than is widely thought.
Syd Johnson, assistant professor of philosophy, has just published a paper in the American Journal of Bioethics: Neuroscience that argues that even patients with severe brain injuries could have more self-determination and empowerment. “New research with people using just their brains to communicate reveals that more of them might be able to make their own decisions,” she says.
Those decisions can literally be life and death, and the first question a caregiver should ask is “How do we determine if they are capable—as an ordinary person would be—of making these decisions?” Johnson asks.
She says because of their brain injuries, many have limited attention spans or movement/speech disorders that make it very difficult to communicate. “That’s why it’s important to find ways of assessing their wellbeing other than by asking them,” she says. “Being able to do that would open up the possibility of assessing quality of life even in those who have never been able to communicate, such as infants or people born with severe cognitive disabilities.”
And that leads to the tough questions, Johnson points out.
“Who makes the decision that someone desires, or not, to live in this state? Who makes the life assessment for people: to treat them or to allow them to die.”
The range of potential patients runs the gamut from grandparents to infants, Johnson says. Sometimes you can’t ask them, including those with cognitive disabilities, but sometimes you can.
She acknowledges the complexity of the issue, especially when decisions involve quality of life. “We assume they don’t want to live that way, but sometimes, are they okay?”
She uses the example of locked-in syndrome, where patients can blink “yes” or “no.” A majority says they are doing okay.
“So, then do we make a decision based on what we think it is like to be in that position?” Johnson says.
Many people adjust to this new way of life, she says, and it’s important for caregivers to get into their mind, to recognize what might be a foreign viewpoint for an able-bodied person.
“Then there are the misdiagnosed,” Johnson says. “As many as 40 percent could be conscious at some level, even in a permanent vegetative state. Even in a nursing home, it can be that no one is assessing them, and they might improve. Nobody is diagnosing anymore, and they are treated as if they are not ever going to get better.”
Researchers around the globe have begun to address these issues, and new evidence is coming in, thanks in part to fMRI: functional magnetic resonance imaging—a technique that directly measures the blood flow in the brain that can provide information on brain activity.
“Even EEGs [electroencephalograms, which measure electrical activity in the brain] can be used,” she says. “The patients can be asked questions and given two things to think about for answers: playing tennis for yes, walking around in their house for no. And different parts of their brain will light up. People can be conscious while appearing outwardly unconscious.”
The end-result could mean reassessing the quality of life, Johnson says. Some patients can be asked—the so-called “covertly aware” patients who are conscious but can communicate only with technological assistance.
“Just as importantly, we might be able to use technology to objectively measure aspects of quality of life even in patients who cannot communicate at all,” Johnson says.
The ethical issues loom.
“A person’s quality of life is inherently subjective, and the aim of quality of life assessment has always been to find ways to objectively measure that subjective state of being,” she says. “New technologies like fMRI might be able to provide a different kind of objective assessment of subjective wellbeing—by looking at brain activity—in those individuals who are unable to tell us how they’re doing.”