Similar connectivity profiles in humans and monkeys used to generate a Theory of Mind

The ability to infer emotion or intention in others from their outward appearance and behavior, has been called a “Theory of Mind” (TOM). While cognitive scientists have debated whether animals other than humans possess a TOM, many animals (like monkeys) clearly react to facial expression or body movements. One area of the human brain that has received considerable attention in discussions of TOM, is the temporo-parietal junction (TPJ). If each half of the brain is viewed as a boxing glove, the TPA corresponds to the junction between the “thumb” and body of the glove. To explore whether the TPJ regions of humans and monkeys have similar “functional connectivity” profiles, a group of Oxford researchers turned to high resolution at-rest fMRI. The researchers generated correlation maps between each time series obtained for specific voxel regions of interest. Their results, just published in PNAS, show that the most similar TPJ connectivity profiles correspond to areas that process, among other things, faces and social stimuli within the temporal cortex.

When the brain first begins to develop in the womb, the cortex is basically a smooth sheet. The most noticeable topological feature in the cortex of all higher vertebrates, the lateral or Sylvian fissure, begins to take shape as an invagination in the side that proceeds from front to back. This fold, with the TPA at its apex, remains as the primary feature of the cortex even as it grows increasingly convoluted. It is little wonder that many of the most interesting mental phenomena, and malady, are often attributed to this region. Stimulation of this area has produced effects as widespread as out of body experiences, impostor syndromes, and even phantom body doubles with precise geometrically offsets to the primary body position.

It is a bit of a paradox perhaps, that many studies which look for uniform or predictable features in the brain have instead hit upon the very region where any such pigeonholing is most labile. In other words, when the brain folds, the TPA is precisely the region where the most scrunching happens, with the result the mature structure typically shows the most variance. In animals like cats and many monkeys, the cortical gyri and sulci, have virtually the same pattern in each individual. In humans however, attempts to assign names to specific folds of the TPA region is like playing a game of pin the tail on the donkey. For example, the Angular gyrus, Wernicke’s area, Supramarginal gyrus, and Inferior parietal area, can all be variously designated as part of the TPA.

Recent attempts to define a default mode network (DMN) using fMRI have included this same region. In theory, the DMN can be used to distinguish sleep from arousal. It was noted that neurons which project out of the cortex in this region have, in effect, more options open to them than those virtually anywhere else in the brain. For example, directly under the angular gyrus is the area known as the temporo-parietal fiber association area. It includes at least seven long range white matter superhighways. That is not to say TPA neurons have free reign to board any tract they choose, (especially those like the optic radiations whose foundations are strongly and quickly set by myelin), but certainly the wide variance in behavioral correlates of these cells has an anatomical basis.

The Oxford study used Macaques, a monkey which has been on a separate evolutionary path from humans for around 30 million years. They note that the superior temporal (STS) region of the Macaque contains face cells that have been found to be more responsive to social cues rather than to identity. The researchers included the STS in their MRI meta-analysis, and also incorporated information from the BrainMap database, a large repository of neuroimaging data. While it is encouraging to see big data being put to use, it is often difficult to follow exactly how the data is processed to yield the so-called “activation likelihood estimation maps for activity elicited by theory of mind paradigms and by face discrimination or processing.”

As various federal projects begin to assemble connectomes for the human brain, functional connectivity studies that use highly processed MRI data, will need to be made as simple and straightforward as possible if they are to be put to widespread use. MRI tractography is a related technology that can assign physical connectivity by performing a meta-analysis on diffusion tensor data. Using scans and connectomes to generate theories to explain some of the strange mental phenomena generated secondary to stroke or by various kinds of electromagnetic stimulation are the best approaches we have at the moment. New technologies generated by the BRAIN Initiative will hopefully allow a finer-grained exploration of theory of mind.

Study charts exercise for stroke patients’ brains

A new study has found that stroke patients’ brains show strong cortical motor activity when observing others performing physical tasks — a finding that offers new insight into stroke rehabilitation.

Using functional magnetic resonance imaging (fMRI), a team of researchers from USC monitored the brains of 24 individuals — 12 who had suffered strokes and 12 age-matched people who had not — as they watched others performing actions made using the arm and hand that would be difficult for a person who can no longer use their arm due to stroke — actions such as lifting a pencil or flipping a card.

The researchers found that while the typical brain responded to the visual stimulus with activity in cortical motor regions that are generally activated when we watch others perform actions, in the stroke-affected brain, activity was strongest in these regions of the damaged hemisphere and strongest when stroke patients viewed actions they would have the most difficulty performing.

Activating regions near the damaged portion of the brain is like exercising it, building strength that can help it recover to a degree.

“Watching others perform physical tasks leads to activations in motor areas of the damaged hemisphere of the brain after stroke, which is exactly what we’re trying to do in therapy,” said Kathleen Garrison, lead author of a paper on the research. “If we can help drive plasticity in these brain regions, we may be able to help individuals with stroke recover more of the ability to move their arm and hand.”

Garrison, who completed the research while studying at USC and is currently a postdoctoral researcher at the Yale University School of Medicine, worked with Lisa Aziz-Zadeh of the USC Brain and Creativity Institute, based at the USC Dornsife College of Letters, Arts and Sciences, and the Division of Occupational Science and Occupational Therapy; Carolee Winstein, director of the Motor Behavior and Neurorehabilitation Laboratory in the Division of Biokinesiology and Physical Therapy; and former USC doctoral student Sook-Lei Liew and postdoctoral researcher Savio Wong.

Their research was posted online ahead of publication by the journal Stroke on June 6.

Using action-observation in stroke rehabilitation has shown promise in early studies, and this study is among the first to explain why it may be effective.

“It’s like you’re priming the pump,” Winstein said. “You’re getting these circuits engaged through the action-observation before they even attempt to move.”

The process is a kind of virtual exercise program for the brain that prepares you for the real exercise that includes the brain and body.

The study also offers support for expanding action-observation as a therapeutic technique, particularly for individuals who have been screened using fMRI and have shown a strong response to it.

“We could make videos of what patients will be doing in therapy and then have them watch it as homework,” Aziz-Zadeh said. “In some cases, it could pave the way for them to do better.”

New tasks become as simple as waving a hand with brain-computer interfaces

Small electrodes placed on or inside the brain allow patients to interact with computers or control robotic limbs simply by thinking about how to execute those actions. This technology could improve communication and daily life for a person who is paralyzed or has lost the ability to speak from a stroke or neurodegenerative disease.

Now, University of Washington researchers have demonstrated that when humans use this technology – called a brain-computer interface – the brain behaves much like it does when completing simple motor skills such as kicking a ball, typing or waving a hand. Learning to control a robotic arm or a prosthetic limb could become second nature for people who are paralyzed.

“What we’re seeing is that practice makes perfect with these tasks,” said Rajesh Rao, a UW professor of computer science and engineering and a senior researcher involved in the study. “There’s a lot of engagement of the brain’s cognitive resources at the very beginning, but as you get better at the task, those resources aren’t needed anymore and the brain is freed up.”

Rao and UW collaborators Jeffrey Ojemann, a professor of neurological surgery, and Jeremiah Wander, a doctoral student in bioengineering, published their results online June 10 in the Proceedings of the National Academy of Sciences.

In this study, seven people with severe epilepsy were hospitalized for a monitoring procedure that tries to identify where in the brain seizures originate. Physicians cut through the scalp, drilled into the skull and placed a thin sheet of electrodes directly on top of the brain. While they were watching for seizure signals, the researchers also conducted this study.

The patients were asked to move a mouse cursor on a computer screen by using only their thoughts to control the cursor’s movement. Electrodes on their brains picked up the signals directing the cursor to move, sending them to an amplifier and then a laptop to be analyzed. Within 40 milliseconds, the computer calculated the intentions transmitted through the signal and updated the movement of the cursor on the screen.

Researchers found that when patients started the task, a lot of brain activity was centered in the prefrontal cortex, an area associated with learning a new skill. But after often as little as 10 minutes, frontal brain activity lessened, and the brain signals transitioned to patterns similar to those seen during more automatic actions.

“Now we have a brain marker that shows a patient has actually learned a task,” Ojemann said. “Once the signal has turned off, you can assume the person has learned it.”

While researchers have demonstrated success in using brain-computer interfaces in monkeys and humans, this is the first study that clearly maps the neurological signals throughout the brain. The researchers were surprised at how many parts of the brain were involved.

“We now have a larger-scale view of what’s happening in the brain of a subject as he or she is learning a task,” Rao said. “The surprising result is that even though only a very localized population of cells is used in the brain-computer interface, the brain recruits many other areas that aren’t directly involved to get the job done.”

Several types of brain-computer interfaces are being developed and tested. The least invasive is a device placed on a person’s head that can detect weak electrical signatures of brain activity. Basic commercial gaming products are on the market, but this technology isn’t very reliable yet because signals from eye blinking and other muscle movements interfere too much.

A more invasive alternative is to surgically place electrodes inside the brain tissue itself to record the activity of individual neurons. Researchers at Brown University and the University of Pittsburgh have demonstrated this in humans as patients, unable to move their arms or legs, have learned to control robotic arms using the signal directly from their brain.

The UW team tested electrodes on the surface of the brain, underneath the skull. This allows researchers to record brain signals at higher frequencies and with less interference than measurements from the scalp. A future wireless device could be built to remain inside a person’s head for a longer time to be able to control computer cursors or robotic limbs at home.

“This is one push as to how we can improve the devices and make them more useful to people,” Wander said. “If we have an understanding of how someone learns to use these devices, we can build them to respond accordingly.”

The research team, along with the National Science Foundation’s Engineering Research Center for Sensorimotor Neural Engineering headquartered at the UW, will continue developing these technologies.

Video Gamers Really Do See More

Hours spent at the video gaming console not only train a player’s hands to work the buttons on the controller, they probably also train the brain to make better and faster use of visual input, according to Duke University researchers.

"Gamers see the world differently," said Greg Appelbaum, an assistant professor of psychiatry in the Duke School of Medicine. "They are able to extract more information from a visual scene."

It can be difficult to find non-gamers among college students these days, but from among a pool of subjects participating in a much larger study in Stephen Mitroff’s Visual Cognition Lab at Duke, the researchers found 125 participants who were either non-gamers or very intensive gamers. 

Each participant was run though a visual sensory memory task that flashed a circular arrangement of eight letters for just one-tenth of a second. After a delay ranging from 13 milliseconds to 2.5 seconds, an arrow appeared, pointing to one spot on the circle where a letter had been. Participants were asked to identify which letter had been in that spot.

At every time interval, intensive players of action video games outperformed non-gamers in recalling the letter.

Earlier research by others has found that gamers are quicker at responding to visual stimuli and can track more items than non-gamers. When playing a game, especially one of the “first-person shooters,” a gamer makes “probabilistic inferences” about what he’s seeing — good guy or bad guy, moving left or moving right — as rapidly as he can. 

Appelbaum said that with time and experience, the gamer apparently gets better at doing this. “They need less information to arrive at a probabilistic conclusion, and they do it faster.” 

Both groups experienced a rapid decay in memory of what the letters had been, but the gamers outperformed the non-gamers at every time interval. 

The visual system sifts information out from what the eyes are seeing, and data that isn’t used decays quite rapidly, Appelbaum said. Gamers discard the unused stuff just about as fast as everyone else, but they appear to be starting with more information to begin with.

The researchers examined three possible reasons for the gamers’ apparently superior ability to make probabilistic inferences. Either they see better, they retain visual memory longer or they’ve improved their decision-making. 

Looking at these results, Applebaum said, it appears that prolonged memory retention isn’t the reason. But the other two factors might both be in play — it is possible that the gamers see more immediately, and they are better able make better correct decisions from the information they have available.

To get at this question, the researchers will need more data from brainwaves and MRI imagery to see where the brains of gamers have been trained to perform differently on visual tasks.

Loyola surgeon using electrical stimulation to speed recovery in Bell’s palsy patients

A Loyola University Medical Center surgeon is using electrical stimulation as part of an advanced surgical technique to treat Bell’s palsy. Bell’s palsy is a condition that causes paralysis on one side of a patient’s face.

During surgery, Dr. John Leonetti stimulates the patient’s damaged facial nerve with an electric current, helping to jump-start the nerve in an effort to restore improved facial movement more quickly.

Leonetti said some patients who have received electrical stimulation have seen muscle movement return to their face after one or two months — rather than the four-to-six months it typically takes for movement to return following surgery.

A virus triggered Bell’s palsy in Audrey Rex, 15, of Lemont, Ill. Her right eye could not close and her smile was lopsided, making her feel self-conscious. She had to drink from a straw, and eating was frustrating - she would accidently bite her bottom lip when it got stuck on her teeth.

She was treated with steroids, but after six weeks, there were no improvements. So Audrey’s mother did further research and made an appointment with Leonetti, and he recommended surgery with electrical stimulation, followed by physical therapy. Today, Audrey’s appearance has returned to normal, and she has regained nearly all of the facial muscle movements she had lost.

“I feel very blessed that we were referred to Dr. Leonetti,” said Deborah Rex, Audrey’s mother.

Bell’s palsy is classified as an idiopathic disorder, meaning its cause is not definitely known. However, most physicians believe Bell’s palsy is caused by a viral-induced swelling of the facial nerve within its bony covering. Symptoms include paralysis on one side of the face; inability to close one eye; drooling; dryness of the eye; impaired taste; and a complete inability to express emotion on one side of the face. 

Bell’s palsy occurs when the nerve that controls muscles on one side of the face becomes swollen, inflamed or compressed. The nerve runs through a narrow, bony canal called the Fallopian canal. Following a viral infection, the nerve swells inside the canal, restricting the flow of blood and oxygen to nerve cells.

Most cases can be successfully treated with oral steroids, and 85 percent of patients experience good recovery within a month. But if symptoms persist for longer than a month, the patient may need surgery, Leonetti said. If surgery is delayed for longer than three months, the nerve damage from Bell’s palsy can be permanent. Thus, the optimal window for surgery is between one and three months after onset of symptoms.

The surgery is called microscopic decompression of the facial nerve. The surgeon removes the bony covering of the facial nerve, then slits open the outer covering of the nerve. This gives the nerve room to swell. In addition to this standard procedure, Leonetti uses an electric stimulator to send a current through the nerve. This jump starts the nerve to speed its recovery.

Decompression of the facial nerve is an established technique for treating Bell’s palsy, and electric stimulation is an established technique used in other surgeries involving the nerve. “We are combining two standard treatments to create an exceptional treatment,” Leonetti said.

Following surgery, Audrey worked with Loyola physical therapist Lisa Burkman, who used a mirror and biofeedback to teach Audrey individualized exercises of her mouth, eye, forehead, cheek and chin. Leonetti said Audrey’s case illustrates that the road back from Bell’s palsy is a multidisciplinary effort that involves the surgeon, physical therapist and patient.

Researchers Provide the First Comprehensive and Prospective Characterization of a Genetic Subtype of Autism

In the first prospective study of its kind, Seaver Autism Center researchers at the Icahn School of Medicine at Mount Sinai provide new evidence of the severity of intellectual, motor, and speech impairments in a subtype of autism called Phelan-McDermid Syndrome (PMS). The data are published online in the June 11 issue of the journal Molecular Autism.

Mutation or deletion of a gene known as SHANK3 is one of the more common single-gene causes of autism spectrum disorders and is critical to the development of PMS, a  severe type of autism. To date, clinicians have relied on case studies and retrospective reviews of medical records to understand  the features of this disorder and how the clinical presentation relates to the extent of the genetic changes in the SHANK3 region. In the first systematic and comprehensive prospective trial, researchers led by Alex Kolevzon, MD, Clinical Director of the Seaver Autism Center, under the direction of Joseph Buxbaum, PhD, Director of the Seaver Autism Center, enrolled 32 participants with SHANK3 deletions to comprehensively assess their clinical symptoms and examine how the size of the SHANK3 deletion correlated to those symptoms.

“Previous studies have not utilized prospective assessments to understand Phelan-McDermid Syndrome, and the prevalence of autism spectrum disorder has never been examined using gold-standard instruments” said Dr. Kolevzon. “There is no established standard for assessing  this type of autism, and our study provides important guidance in developing such a standard.”

Of the 32 patients enrolled, 84 percent met criteria for an autism spectrum disorder. Seventy-seven percent of patients exhibited severe to profound intellectual disability, with 19 percent using some form of verbal communication. Other common features included low muscle tone, gait disturbance, and seizures. The researchers also found that patients who had larger SHANK3 deletions had more severe disease.

“Our findings provide additional evidence of the significant impairment associated with SHANK3 deficiency,” said Dr. Kolevzon. “Also, knowing how large the deletion of the  SHANK3 gene is may have important implications for medical monitoring and individualizing treatment plans. Results  also provide much-needed guidance in developing a standardized methodology for evaluating the features of this disorder.”

Many of the patients who participated in this study were next enrolled in a clinical trial at Mount Sinai evaluating Insulin-Like Growth Factor-1 (IGF-1), a  commercially available compound for growth deficiency that is known to promote nerve cell survival as well as synaptic maturation and plasticity.  The primary aim of the study is to target core features of PMS, including social withdrawal and language impairment, which will be measured using both behavioral and objective assessments. The clinical studies with IGF-1 were supported by studies in a genetically modified mouse with a mutation in SHANK3. These studies, carried out by Dr. Ozlem Bozdagi of the Seaver Autism Center, carefully examined brain function in the mice when SHANK3 was mutated, and provided preclinical evidence for a beneficial effect of IGF-1. These studies were reported the April 27th issue of Molecular Autism (1, 2).

“The Seaver Autism Center has the unique capacity to evaluate autism spectrum disorders on both the molecular level and the clinical level,” said Dr. Buxbaum. “This capability puts us in a unique position to see the entire picture—the connection between genetics and behavior in these disorders—and to develop new treatments and better tailor existing ones for these children.”

Hope for Spinal Cord Injuries

Laura Wong has coaxed damaged nerve cells to grow and send messages to the brain again

“An ailment not to be treated,” read the prescription for a spinal cord injury on an Egyptian papyrus in 1,700 B.C. Not much has changed in the intervening millennia. Despite decades of research, modern medicine has made little headway in its quest to reverse damage to the central nervous system.

That is not to say, however, that there isn’t a glimmer of hope. Laura Wong, an M.D./Ph.D. student in Professor Eric Frank’s molecular physiology lab at the Sackler School, has been able to coax damaged nerve cells known as sensory neurons to regenerate, growing as much as 10 times longer than previously documented. What’s more, the new neurons make organized connections with their counterparts inside the spinal cord and brain stem, ensuring information from the outside world paints an accurate picture inside the brain.

“All the regeneration in the world isn’t going to make any difference if they don’t reconnect. You’re still not going to get any function,” says Wong, who has worked since 2010 in Frank’s lab, which is trying to develop therapies for spinal cord injuries.

Her findings, which she presented at the annual meeting of the Society for Neuroscience in 2011 and 2012, shed light on the complex processes behind nerve cell growth and regeneration. If those results can be replicated in patients, it could prevent certain types of nerve damage and improve quality of life for some.

Going the Distance

Unlike tissues such as skin and bone, the cells of the central nervous system in an adult are notoriously resistant to healing. Not only does the supply of natural growth stimulants decline as we age, but the body also produces chemicals that discourage nerve cells from regenerating. Worse, the scar tissue that starts to form immediately after a spinal cord injury also contains compounds that hinder nerve cell growth.

Researchers in Frank’s lab have been seeking ways to either stimulate growth or block the mechanisms that inhibit nerve cell growth—or both—since 2005. Wong’s predecessor in the lab, Pamela Harvey, a 2009 graduate of the Sackler School, tested a synthetic version of a nerve cell growth factor, called artemin, on crushed sensory neurons that relay information from the hands, arms and shoulders to the brain.

The damage mimics a common injury called Erb’s palsy, which can occur when a baby’s shoulder gets caught behind the mother’s pelvis during labor and delivery, creating undue strain on nerves in the newborn’s neck. Riders thrown head first off a motorcycle or snowmobile can suffer similar injuries.

“Anytime the shoulder goes one way and the head and neck go the other, that’s when you see these injuries,” Wong says.

In earlier experiments, Harvey and Frank found that treating with artemin did indeed stimulate the sensory nerve fibers to regenerate and grow back into the spinal cord over the course of about six weeks. In her follow-up experiments, Wong showed that artemin could induce those nerve fibers to grow the 3- to 4-centimeter distance from there up to the brainstem, where the brain and the spinal cord meet. That’s a little more than an inch—or roughly 10 times longer than any other researchers have been able to demonstrate with artemin or any other growth factor.

“A lot of other researchers just haven’t seen this length,” notes Wong, who saw the artemin-induced growth occur over a period of three to six months.

That’s important, because while axons only have to grow across microscopic distances in a developing embryo, they would have to bridge much wider gaps—depending on the site of the injury—to heal a neural injury in an adult, Wong says. Nerves that extend from the spine to the foot or toe can reach lengths of about 60 centimeters, she adds.

But Wong’s artemin-treated nerve fibers achieved more than unprecedented growth. They also reestablished connections with correct regions in the brain stem, just as Harvey had seen the nerve cells do in the spinal cord. That is, the axons essentially plugged themselves back in just as they were prior to the injury, and, like an old-fashioned telephone switchboard, they sent the right messages to the right parts of the brain.

That’s crucial because should the sensory nerves that relay pain signals become crossed, for example, it could result in a patient feeling phantom pain or the sensation of pain from something that shouldn’t cause discomfort at all.

“With some other growth-promoting compounds you get regeneration, but you see those axons growing kind of willy-nilly,” says Wong. “You can see where it would be just as detrimental to have things wired incorrectly as it would be to have things not wired at all.”

Just a Start

Artemin isn’t a panacea for spinal cord injuries, Wong and Frank stress. To work its cellular magic, the compound must be administered within a day or two, and the sooner the better. Also, artemin promotes growth only in sensory neurons—and so far, only in rats—which means such growth wouldn’t improve motor function for someone who had been paralyzed by a spinal cord injury, for example.

But if the findings, which Wong presented at the Society for Neuroscience meetings in 2011 and 2012, prove applicable to humans, restoring sensation alone could still improve quality of life, even for those living with paralysis. Giving these people the ability to sense heat, cold and pain could help them avoid other accidental injuries, says Frank.

Wong hopes her work with sensory neurons will help unlock the secrets to promoting regeneration of other, more obstinate types of neurons in the brainstem and spinal cord. While she demonstrated that the sensory nerves plugged themselves back into the spinal cord precisely where they should have, it’s not clear how they did that.

Frank speculates that chemical cues guided the cells back into place. Should researchers be able to identify those cues, they potentially could use that knowledge to spark regeneration of other classes of neurons, such as motor neurons.

“There is hope—not proof—that even in humans these guidance molecules will persist into adulthood,” says Frank. “That means if we are able to get neurons to regenerate in patients, we might be able to make them go back to the right place. These experiments suggest we have some reason to believe it may work.”

High Sugar Intake Linked to Low Dopamine Release in Insulin Resistant Patients

PET study led by Stony Brook Professor indicates that overeating and weight gain contributing to onset of diabetes could be related to a deficit in reward circuits in the brain

Using positron emission tomography (PET) imaging of the brain, researchers have identified a sweet spot that operates in a disorderly way when simple sugars are introduced to people with insulin resistance, a precursor to type 2 diabetes. For those who have the metabolic syndrome, a sugar drink resulted in a lower-than-normal release of the chemical dopamine in a major pleasure center of the brain. This chemical response may be indicative of a deficient reward system, which could potentially be setting the stage for insulin resistance. This research could revolutionize the medical community’s understanding of how food-reward signaling contributes to obesity, according to a study presented at the Society of Nuclear Medicine and Molecular Imaging’s 2013 Annual Meeting.

"Insulin resistance is a significant contributor to obesity and diabetes," said Gene-Jack Wang, MD, lead author of the study and Professor of Radiology at Stony Brook University and researcher at the U.S. Department of Energy’s Brookhaven National Laboratory in Upton, N.Y. "A better understanding of the cerebral mechanisms underlying abnormal eating behaviors with insulin resistance would help in the development of interventions to counteract the deterioration caused by overeating and subsequent obesity. We suggest that insulin resistance and its association with less dopamine release in a central brain reward region might promote overeating to compensate for this deficit."

An estimated one-third of Americans are obese, according to the U.S. Centers for Disease Control and Prevention. The American Diabetes Association estimates that about 26 million Americans are living with diabetes and another 79 million are thought to be prediabetic, including those with insulin resistance.

The tendency to overeat may be caused by a complex biochemical relationship, as evidenced by preliminary research with rodents. Dr. Wang’s research marks the first clinical study of its kind with human subjects.

"Animal studies indicated that increased insulin resistance precedes the lack of control associated with pathological overeating," said Wang. "They also showed that sugar ingestion releases dopamine in brain regions associated with reward. However, the central mechanism that contributes to insulin resistance, pathological eating and weight gain is unknown."

He continued, “In this study we were able to confirm an abnormal dopamine response to glucose ingestion in the nucleus accumbens, where much of the brain’s reward circuitry is located. This may be the link we have been looking for between insulin resistance and obesity. To test this, we gave a glucose drink to an insulin-sensitive control group and an insulin-resistant group of individuals and we compared the release of dopamine in the brain reward center using PET.”

In this study, a total of 19 participants-including 11 healthy controls and eight insulin-resistant subjects-consumed a glucose drink and, on a separate day, an artificially sweetened drink containing sucralose. After each drink, PET imaging with C-11 raclopride-which binds to dopamine receptors-was performed. Researchers mapped lit-up areas of the brain and then gauged striatal dopamine receptor availability (which is inversely related to the amount of natural dopamine present in the brain). These results were matched with an evaluation in which patients were asked to document their eating behavior to assess any abnormal patterns in their day-to-day lives. Results showed agreement in receptor availability between insulin-resistant and healthy controls after ingestion of sucralose. However, after patients drank the sugary glucose, those who were insulin-resistant and had signs of disorderly eating were found to have remarkably lower natural dopamine release in response to glucose ingestion when compared with the insulin-sensitive control subjects.

"This study could help develop interventions, i.e., medication and lifestyle modification, for early-stage insulin-resistant subjects to counteract the deterioration that leads to obesity and/or diabetes," said Wang. "The findings set a path for future clinical studies using molecular imaging methods to assess the link of peripheral hormones with brain neurotransmitter systems and their association with eating behaviors."