Posts tagged neuroimaging
Articles and news from the latest research reports.
Do Patients in a Vegetative State Recognize Loved Ones?
TAU researchers find unresponsive patients’ brains may recognize photographs of their family and friends
Patients in a vegetative state are awake, breathe on their own, and seem to go in and out of sleep. But they do not respond to what is happening around them and exhibit no signs of conscious awareness. With communication impossible, friends and family are left wondering if the patients even know they are there.
Now, using functional magnetic resonance imaging (fMRI), Dr. Haggai Sharon and Dr. Yotam Pasternak of Tel Aviv University’s Functional Brain Center and Sackler Faculty of Medicine and the Tel Aviv Sourasky Medical Center have shown that the brains of patients in a vegetative state emotionally react to photographs of people they know personally as though they recognize them.
"We showed that patients in a vegetative state can react differently to different stimuli in the environment depending on their emotional value," said Dr. Sharon. "It’s not a generic thing; it’s personal and autobiographical. We engaged the person, the individual, inside the patient."
The findings, published in PLOS ONE, deepen our understanding of the vegetative state and may offer hope for better care and the development of novel treatments. Researchers from TAU’s School of Psychological Sciences, Department of Neurology, and Sagol School of Neuroscience and the Loewenstein Hospital in Ranaana contributed to the research.
Talking to the brain
For many years, patients in a vegetative state were believed to have no awareness of self or environment. But in recent years, doctors have made use of fMRI to examine brain activity in such patients. They have found that some patients in a vegetative state can perform complex cognitive tasks on command, like imagining a physical activity such as playing tennis, or, in one case, even answering yes-or-no questions. But these cases are rare and don’t provide any indication as to whether patients are having personal emotional experiences in such a state.
To gain insight into “what it feels like to be in a vegetative state,” the researchers worked with four patients in a persistent (defined as “month-long”) or permanent (persisting for more than three months) vegetative state. They showed them photographs of people they did and did not personally know, then gauged the patients’ reactions using fMRI, which measures blood flow in the brain to detect areas of neurological activity in real time. In response to all the photographs, a region specific to facial recognition was activated in the patients’ brains, indicating that their brains had correctly identified that they were looking at faces.
But in response to the photographs of close family members and friends, brain regions involved in emotional significance and autobiographical information were also activated in the patients’ brains. In other words, the patients reacted with activations of brain centers involved in processing emotion, as though they knew the people in the photographs. The results suggest patients in a vegetative state can register and categorize complex visual information and connect it to memories – a groundbreaking finding.
The ghost in the machine
However, the researchers could not be sure if the patients were conscious of their emotions or just reacting spontaneously. So they then verbally asked the patients to imagine their parents’ faces. Surprisingly, one patient, a 60-year-old kindergarten teacher who was hit by a car while crossing the street, exhibited complex brain activity in the face- and emotion-specific brain regions, identical to brain activity seen in healthy people. The researchers say her response is the strongest evidence yet that vegetative-state patients can be “emotionally aware.” A second patient, a 23-year-old woman, exhibited activity just in the emotion-specific brain regions. (Significantly, both patients woke up within two months of the tests. They did not remember being in a vegetative state.)
"This experiment, a first of its kind, demonstrates that some vegetative patients may not only possess emotional awareness of the environment but also experience emotional awareness driven by internal processes, such as images," said Dr. Sharon.
Research focused on the “emotional awareness” of patients in a vegetative state is only a few years old. The researchers hope their work will eventually contribute to improved care and treatment. They have also begun working with patients in a minimally conscious state to better understand how regions of the brain interact in response to familiar cues. Emotions, they say, could help unlock the secrets of consciousness.
(Source: aftau.org)
Brain structure shows affinity with numbers
The structure of the brain shows the way in which we process numbers. People either do this spatially or non-spatially. A study by Florian Krause from the Donders Institute in Nijmegen shows for the first time that these individual differences have a structural basis in the brain. The Journal of Cognitive Neuroscience published the results in an early access version of the article.
People who process numbers spatially do this using an imaginary horizontal line along which the numbers are arranged from low to high, left to right. A non-spatial representation is also possible, by comparing numbers to other magnitudes such as force or luminosity.
Different grey matter volumes
Florian Krause identified this predisposition to spatial or non-spatial number processing in MRI scans of test subjects. He discovered differences in grey matter volume, which contains the cell bodies of nerve cells, in two specific locations. Spatially oriented brains have an above-average grey matter volume in the right precuneus, a small area of the brain associated with processing visual-spatial information. Non-spatially oriented brains have more grey matter in the left angular gyrus, an area associated with semantic and conceptual processing.
Spatial numbers
For a long time, scientists thought that everyone processed numbers predominantly in a spatial way. Krause demonstrates that this is not the case. In his own words: ‘Our current study stresses the importance of non-spatial number representations. This is important since researchers in the field tend to focus mainly on spatial representations. Personally, I think that numbers are understood in terms of our body experiences. We use information about size in real life to understand number size in our heads.’
Classifying numbers
The thirty people taking part in the study were put into an MRI scanner and were shown numbers between 1 and 9 (except 5). In two consecutive judgement tasks, they had to classify the presented digits as odd or even. Both tasks differed only in the required response: in the spatial task subjects had to click with their index finger or middle finger to classify the digits, and in the non-spatial task they applied either a small or a large force on a pressure sensor with their thumb. Both tests were carried out using the right hand. Importantly, participants coupled the spatial response as well as the force response to the size of the presented number, as they responded faster with a left or soft press for small numbers and with a right or hard press for large numbers. Krause worked out those couplings for each subject, and compared the scores with the information from their brain scan.
Potential benefits for teaching maths
At present, maths is largely taught on the basis of a spatial number processing. ‘People with a non-spatial representation of numbers would probably benefit from a different approach to maths teaching’, says Krause. ‘It is possible to let pupils experience the size of numbers in a non-spatial way. This could involve expressing numbers with your body while doing simple arithmetics, for example.’ Krause is planning several new studies to explore the scientific basis of methods like these in more detail.
Study Raises Questions about Longstanding Forensic Identification Technique
Forensic experts have long used the shape of a person’s skull to make positive identifications of human remains. But those findings may now be called into question, since a new study from North Carolina State University shows that there is not enough variation in skull shapes to make a positive ID.
“In a lot of cases, murder victims or the victims of disasters are from lower socioeconomic backgrounds and don’t have extensive dental records we can use to make a match,” says Dr. Ann Ross, a forensic expert and professor of anthropology at NC State who is senior author of a paper on the new study. “But those people may have been in car accidents or other incidents that led them to have their skulls X-rayed in emergency rooms or elsewhere. And those skull X-rays have often been used to make IDs. I’ve done it myself.
“But now we’ve tried to validate this technique, and our research shows that the shape of the skull isn’t enough to make a positive ID,” Ross says.
At issue is the “cranial vault outline,” not the “face” of the skull. The cranial vault outline is the profile of the skull when viewed from the side, running from just above the bridge of the nose to the point where the skull and neck meet.
For the study, the researchers surveyed 106 members of the American Academy of Forensic Sciences. Survey participants were asked to evaluate 14 antemortem X-rays and five postmortem X-rays. Participants were then asked to match the 5 postmortem X-rays with the appropriate antemortem X-ray, effectively establishing a positive ID.
But the researchers found that only 47 percent of the participants made accurate identifications on all five skulls. Participants who have Ph.D.s did slightly better, with 56 percent of them getting all five correct. (The test has been made available here so that anyone can take it.)
“This doesn’t mean that cranial vault outlines aren’t useful,” says Ashley Maxwell, lead author of the paper and a former graduate student at NC State. “For example, outlines can be valuable if teeth or other features are missing or have been destroyed. But it does mean that cranial vault outlines shouldn’t be given too much weight.
“The more characteristics we can take into account, such as facial features and cranial vault outlines, the more accurate we can be,” Maxwell says.
Recurring memory traces boost long-lasting memories
While the human brain is in a resting state, patterns of neuronal activity which are associated to specific memories may spontaneously reappear. Such recurrences contribute to memory consolidation – i.e. to the stabilization of memory contents. Scientists of the DZNE and the University of Bonn are reporting these findings in the current issue of The Journal of Neuroscience. The researchers headed by Nikolai Axmacher performed a memory test on a series of persons while monitoring their brain activity by functional magnetic resonance imaging (fMRI). The experimental setup comprised several resting states including a nap inside a neuroimaging scanner. The study indicates that resting periods can generally promote memory performance.
Depending on one’s mood and activity different regions are active in the human brain. Perceptions and thoughts also influence this condition and this results in a pattern of neuronal activity which is linked to the experienced situation. When it is recalled, similar patterns, which are slumbering in the brain, are reactivated. How this happens, is still largely unknown.
The prevalent theory of memory formation assumes that memories are stored in a gradual manner. At first, the brain stores new information only temporarily. For memories to remain in the long term, a further step is required. „We call it consolidation“, Dr. Nikolai Axmacher explains, who is a researcher at the Department of Epileptology of the University of Bonn and at the Bonn site of the DZNE. “We do not know exactly how this happens. However, studies suggest that a process we call reactivation is of importance. When this occurs, the brain replays activity patterns associated with a particular memory. In principle, this is a familiar concept. It is a fact that things that are actively repeated and practiced are better memorized. However, we assume that a reactivation of memory contents may also happen spontaneously without there being an external trigger.”
A memory test inside the scanner
Axmacher and his team tested this hypothesis in an experiment that involved ten healthy participants with an average age of 24 years. They were shown a series of pictures, which displayed – among other things – frogs, trees, airplanes and people. Each of these pictures was associated with a white square as a label at a different location. The subjects were asked to memorize the position of the square. At the end of the experiment all images were shown again, but this time without the label. The study participants were then asked to indicate with a mouse cursor where the missing mark was originally located. Memory performance was measured as the distance between the correct and the indicated position.
“This is an associative task. Visual and spatial perceptions have to be linked together”, the researcher explains. “Such tasks involve several brain regions. These include the visual cortex and the hippocampus, which takes part in many memory processes.”
Brain activity was recorded by fMRI during the entire experiment, which lasted several hours and included resting periods and a nap inside the neuroimaging scanner.
Recurrent brain patterns increased the accuracy
For data processing a pattern recognition algorithm was trained to look for similarities between neuronal patterns observed during initial encoding and patterns appearing at later occasions. “This method is complex, but quite effective”, Axmacher says. “Analysis showed that neuronal activity associated with images that were shown initially did reappear during subsequent resting periods and in the sleeping phase.”
Memory performance correlated with the replay of neuronal activity patterns. “The more frequently a pattern had reappeared, the more accurate test participants could label the corresponding image”, Axmacher summarizes the findings. “These results support our assumption that neural patterns can spontaneously reappear and that they promote the formation of long-lasting memory contents. There was already evidence for this from animal studies. Our experiment shows that this phenomenon also happens in humans.”
Memory performance benefits from resting periods
The study indicates that resting periods can generally foster memory performance. “Though, our data did not show whether sleeping had a particular effect. This may be due to the experimental setup, which only allowed for a comparatively short nap”, Axmacher reckons. “By contrast, night sleep is considered to be beneficial for the consolidation of memory contents. But it usually takes many hours and includes multiple transitions between different stages of sleep. However, other studies suggest that even short naps may positively affect memory consolidation.”
An objective look at memory contents
It is up to speculation whether the recurring brain patterns triggered conscious memories or whether they remained below the threshold of perception. “I think it is reasonable to assume that during resting periods the test participants let their mind wander and that they recalled images they had just seen before. But this is a matter of subjective perception of the test participants. That’s something we did not look at because it is not essential for our investigation“, Axmacher says. “The strength of our approach lies rather in the fact that we look at memory contents from the outside, in an objective manner. And that we can evaluate them by pattern recognition. This opens ways to many questions of research. For example, brain patterns that reoccur spontaneously are also of interest in the context of experimental dream research.”
(Source: dzne.de)
Multi-dog study points to canine brain’s reward center
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.”
Novel Rehabilitation Device Improves Motor Skills after Stroke
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."
Playing computer games makes brains feel and think alike
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.
Researchers map brain areas vital to understanding language
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.”
Brain Still Injured from Concussion After Symptoms Fade
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.