Neuroscience

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Study reveals brain mechanism behind chronic pain’s sapping of motivation

Chronic pain is among the most abundant of all medical afflictions in the developed world. It differs from a short-term episode of pain not only in its duration, but also in triggering in its sufferers a psychic exhaustion best described by the question, “Why bother?”

A new study in mice, conducted by investigators at the Stanford University School of Medicine, has identified a set of changes in key parts of the brain that may explain chronic pain’s capacity to stifle motivation. The discovery could lead to entirely new classes of treatment for this damaging psychological consequence of chronic pain.

Many tens of millions of people in the United States suffer persistent pain due to diverse problems including migraines, arthritis, lower back pain, sports injuries, irritable bowel syndrome and shingles. For many of these conditions, there are no good treatments, and a crippling loss of mojo can result.

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“With chronic pain, your whole life changes in a way that doesn’t happen with acute pain,” said Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences and the study’s senior author. “Yet this absence of motivation caused by chronic pain, which can continue even when the pain is transiently relieved, has been largely ignored by medical science.”

A series of experiments in mice by Malenka and his colleagues, described in a study published Aug. 1 in Science, showed that persistent pain causes changes in a set of nerve cells in a deep-brain structure known to be important in reward-seeking behavior: the pursuit of goals likely to yield pleasurable results. Malenka’s lab has been studying this brain structure, the nucleus accumbens, for two decades.

“We showed that those brain changes don’t go away when you transiently relieve the mice’s pain,” Malenka said. The experiments also indicated that the mice’s diminished motivation to perform reward-generating tasks didn’t stem from their pain’s rendering them incapable of experiencing pleasure or from any accompanying physical impairment, he said.

How pain and reward interact

“This study is important — to my knowledge, the first to explain how pain and reward interact. It begins to get to an understanding of why it’s such a struggle for people undergoing chronic pain to get through the day,” said Howard Fields, MD, PhD, a professor of neurology at the University of California-San Francisco and founder of that school’s pain management center.

Fields, who did not participate in the Malenka group’s study but wrote an accompanying perspective piece published simultaneously in Science, described the psychological effect of chronic pain as “the clouding of the future. There’s no escape from it. You want it to end, but it doesn’t.” As a result, people become pessimistic and irritable, he said. “People come to expect the next day is going to wind up being painful. It just takes the edge off of life’s little pleasures — and big pleasures, for that matter.”

The experiments were spearheaded by the study’s first author, Neil Schwartz, PhD, a postdoctoral scholar in Malenka’s lab. “You can’t just ask a hungry mouse how motivated it is to pursue its heart’s desire,” Malenka said. “But there are ways of asking that mouse, ‘How hard are you willing to work for food?’”

Schwartz, Malenka and their associates looked at lab mice enduring chronic paw pain due either to persistent inflammation or to nerve damage. The mice also happened to be hungry. The scientists trained the mice to poke their noses into a hole to get a food pellet. At first, a single nose poke earned a pellet. But over time, the number of nose pokes required for a reward was increased. In essence, the researchers were asking these mice: How hard are you willing to work for food? Will you poke your nose into that hole once to satisfy your hunger? Ten times? Even 150 times?

Fading motivation

Within a week after the onset of chronic pain, the animals grew increasingly less likely to work hard for food than pain-free control animals were. The researchers next explored three possible explanations: Were the mice unable to work because their pain was too severe? Did something about being in pain cause them to not value the food reward as much? Or was their failure to seek food due simply to a lack of motivation? Additional tests showed that the mice had no movement problems. “Like other research groups, we found that they can scamper around just fine,” said Malenka. Also, when the mice were given free access to food, they ate just as much as the animals who weren’t in pain — so they still valued the food. But they were less willing to put in an effort to obtain food than mice who’d suffered no pain.

Moreover, the difference didn’t disappear even when the scientists relieved the mice’s pain with analgesics. “They were in demonstrably less pain, but they were still less willing to work,” Malenka said.

The Stanford scientists then focused on the nucleus accumbens, a brain structure known to be involved in computing the behavioral strategies that prompt us to seek or avoid things that can affect our survival. They found that chronic pain permanently changed certain connections to the nucleus accumbens, causing an enduring downshift in the excitation transmitted by them. Importantly, Malenka’s group showed that a particular brain chemical called galanin plays a critical role in this enduring suppression of nucleus accumbens excitability.

Galanin is a short signaling-protein snippet secreted by certain cells in various places in the brain. While its presence in the brain has been known for a good 60 years or so, galanin’s role is not well-defined and probably differs widely in different brain structures. There have been hints, though, that galanin activity might play a role in pain. For example, it’s been previously shown in animal models that galanin levels in the brain increase with the persistence of pain.

Possible therapies?

Schwartz, Malenka and their peers identified receptors for galanin on a set of nerve cells in the nucleus accumbens and demonstrated that disabling galanin’s signaling via this receptor prevented the long-term suppression of motivation seen in mice — and people — with chronic pain. This suggests that therapeutic compounds with similar effects could someday be developed, although they would have to be carefully targeted so as to not disrupt galanin signaling in other important brain circuits.

“There’s no reason to think this finding won’t generalize to people,” said Fields of UCSF. “Our brains have galanin, and a nucleus accumbens, just as mouse brains do. However, before jumping from mice to humans it would be wise to test other animal species. If the same things happen in a non-rodent species that happen in mice, then it’s probable they happen in humans, too.”

(Source: med.stanford.edu)

Filed under pain chronic pain motivation reward nucleus accumbens neuroscience science

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(Image caption: Positron-Emission-Tomography (PET) of a depressive patient without medication (left) with elevated monoamine-oxidase-A-levels (green, yellow, red) and after a six-week-treatment with the monoamine-oxidase-A-inhibitor moclobemid (right). Credit: © Sacher et al., 2011, J Psy Neurosci.) Monoamine oxidase A: biomarker for postpartum depression Many women suffer from baby blues after giving birth. Some even develop full-blown postpartum depression in the weeks that follow. Monoamine oxidase A, an enzyme responsible for the breakdown of neurotransmitters like dopamine and serotonin, plays an important role in this condition. In comparison to healthy women, women who experience postpartum depression present strongly elevated levels of the enzyme in their brains. This was discovered by a Canadian-German research team including Julia Sacher from the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig. Their findings could help in the prevention of postpartum depression and in the development of new drugs for its treatment. For most women, the birth of their baby is one of the most strenuous but also happiest days in their lives. However, joy and happiness are often followed by fatigue and exhaustion. The vast majority of women experience a temporary drop in mood for a few days after birth. These symptoms of “baby blues” are not an illness; however, in some cases they can represent early signs of an imminent episode of depression: in 13 percent of mothers, the emotional turmoil experienced after childbirth leads to the development of a full-blown postpartum depression. Postpartum depression is harmful not only to the mother, but also to the baby. It is difficult to treat this condition effectively, as its precise neurobiological causes have remained unidentified to date. The new study shows that postpartum depression is accompanied by strongly elevated monoamine oxidase A in the brain, particularly in the prefrontal cortex and in the anterior cingulate cortex. In women with postpartum depression, the values recorded were 21 percent higher than those of women who were not plagued by negative feelings after giving birth. Women who did not develop full-blown depression but found themselves crying more often than usual due to depressed mood also presented moderately elevated values. “Therefore, we should promote strategies that help to reduce monoamine oxidase A levels in the brain, and avoid everything that makes these values rise,” explains Sacher. Such factors include heavy smoking, alcohol consumption and chronic stress, for example when the mother feels neglected and abandoned by her partner and family. “My ultimate goal is to provide women and their families with very concrete lifestyle recommendations that will enable them to prevent postpartum depression,” explains the psychiatrist. A new generation of long-established drugs could also play an important role in the treatment of postpartum depression in future. Up to now, depressed mothers are mainly given drugs that increase the concentration of serotonin in the brain. However, because monoamine oxidase A breaks down not only serotonin but also other monoamines like dopamine and noradrenaline, a treatment that directly targets monoamine oxidase A could have a higher success rate, particularly in very serious cases: this alternative is provided by selective and reversible monoamine-oxidase- A inhibitors. “The first monoamine oxidase inhibitors often had severe side effects, for example hypertensive crises, which necessitated adherence to a strict diet,” explains Sacher. “However, the new selective and reversible drugs are better tolerated,” she adds. In the next stage of this research involving clinical trials, the scientists intend to test the effectiveness of these reversible monoamine oxidase A inhibitors in the treatment of postpartum depression. Because the measurement of this enzyme in the brain requires complex technology, it is not suitable for routine testing. Thus, the researchers are also looking for a peripheral marker of this enzyme that can be detected in saliva or blood. Four years ago, Julia Sacher and her colleagues at the Centre for Addiction and Mental Health CAMH in Toronto already succeeded in showing that, in the first week postpartum, the concentration of the enzyme monoamine oxidase A in the brain is on average 40 percent higher than in women who had not recently given birth. “The monoamine oxidase A values behave in the opposite way to oestrogen levels. When oestrogen levels drop acutely after childbirth, the concentration of monoamine oxidase A rises. This drastic change also influences serotonin levels, known as the happiness hormone,” explains Dr. Sacher. In most women, the values quickly return to normal. In others, they remain raised – and thereby promote the development of depression.

(Image caption: Positron-Emission-Tomography (PET) of a depressive patient without medication (left) with elevated monoamine-oxidase-A-levels (green, yellow, red) and after a six-week-treatment with the monoamine-oxidase-A-inhibitor moclobemid (right). Credit: © Sacher et al., 2011, J Psy Neurosci.)

Monoamine oxidase A: biomarker for postpartum depression

Many women suffer from baby blues after giving birth. Some even develop full-blown postpartum depression in the weeks that follow. Monoamine oxidase A, an enzyme responsible for the breakdown of neurotransmitters like dopamine and serotonin, plays an important role in this condition. In comparison to healthy women, women who experience postpartum depression present strongly elevated levels of the enzyme in their brains. This was discovered by a Canadian-German research team including Julia Sacher from the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig. Their findings could help in the prevention of postpartum depression and in the development of new drugs for its treatment.

For most women, the birth of their baby is one of the most strenuous but also happiest days in their lives. However, joy and happiness are often followed by fatigue and exhaustion. The vast majority of women experience a temporary drop in mood for a few days after birth. These symptoms of “baby blues” are not an illness; however, in some cases they can represent early signs of an imminent episode of depression: in 13 percent of mothers, the emotional turmoil experienced after childbirth leads to the development of a full-blown postpartum depression. Postpartum depression is harmful not only to the mother, but also to the baby. It is difficult to treat this condition effectively, as its precise neurobiological causes have remained unidentified to date.

The new study shows that postpartum depression is accompanied by strongly elevated monoamine oxidase A in the brain, particularly in the prefrontal cortex and in the anterior cingulate cortex. In women with postpartum depression, the values recorded were 21 percent higher than those of women who were not plagued by negative feelings after giving birth. Women who did not develop full-blown depression but found themselves crying more often than usual due to depressed mood also presented moderately elevated values.

“Therefore, we should promote strategies that help to reduce monoamine oxidase A levels in the brain, and avoid everything that makes these values rise,” explains Sacher. Such factors include heavy smoking, alcohol consumption and chronic stress, for example when the mother feels neglected and abandoned by her partner and family. “My ultimate goal is to provide women and their families with very concrete lifestyle recommendations that will enable them to prevent postpartum depression,” explains the psychiatrist.

A new generation of long-established drugs could also play an important role in the treatment of postpartum depression in future. Up to now, depressed mothers are mainly given drugs that increase the concentration of serotonin in the brain. However, because monoamine oxidase A breaks down not only serotonin but also other monoamines like dopamine and noradrenaline, a treatment that directly targets monoamine oxidase A could have a higher success rate, particularly in very serious cases: this alternative is provided by selective and reversible monoamine-oxidase- A inhibitors. “The first monoamine oxidase inhibitors often had severe side effects, for example hypertensive crises, which necessitated adherence to a strict diet,” explains Sacher. “However, the new selective and reversible drugs are better tolerated,” she adds. In the next stage of this research involving clinical trials, the scientists intend to test the effectiveness of these reversible monoamine oxidase A inhibitors in the treatment of postpartum depression.

Because the measurement of this enzyme in the brain requires complex technology, it is not suitable for routine testing. Thus, the researchers are also looking for a peripheral marker of this enzyme that can be detected in saliva or blood.

Four years ago, Julia Sacher and her colleagues at the Centre for Addiction and Mental Health CAMH in Toronto already succeeded in showing that, in the first week postpartum, the concentration of the enzyme monoamine oxidase A in the brain is on average 40 percent higher than in women who had not recently given birth. “The monoamine oxidase A values behave in the opposite way to oestrogen levels. When oestrogen levels drop acutely after childbirth, the concentration of monoamine oxidase A rises. This drastic change also influences serotonin levels, known as the happiness hormone,” explains Dr. Sacher. In most women, the values quickly return to normal. In others, they remain raised – and thereby promote the development of depression.

Filed under monoamine oxidase A postpartum depression neurotransmitters prefrontal cortex neuroscience science

106 notes

(Image credit: The insular cortex of an autism mouse model is already so strongly activated by a single sensory modality (here a sound), that it is unable to perform its role in integrating information from multiple sources. Credit: © MPI of Neurobiology / Gogolla) Insular cortex alterations in mouse models of autism The insular cortex is an integral “hub”, combining sensory, emotional and cognitive content. Not surprisingly, alterations in insular structure and function have been reported in many psychiatric disorders, such as anxiety disorders, depression, addiction and autism spectrum disorders (ASD). Scientists from Harvard University and the Max-Planck Institute of Neurobiology in Martinsried now describe consistent alterations in integrative processing of the insular cortex across autism mouse models of diverse etiologies. In particular, the delicate balance between excitation and inhibition in the autistic brains was disturbed, but could be pharmacologically re-adjusted. The results could help the development of novel diagnostic and therapeutic strategies. Autism is a neurodevelopmental disorder characterized by impaired social interaction, verbal and non-verbal communication, and by restricted and repetitive behaviors. Diagnosis is solely based on behavioral analysis as biological markers and neurological underpinnings remain unknown. This makes the development of novel therapeutic strategies extremely difficult.  As the cellular basis of autism spectrum disorders cannot be addressed in human patients, scientists have developed a number of mouse models for the disease. Similar to humans, mice are social animals and communicate through species-specific vocalizations. The mouse models harbor all diagnostic hallmark criteria of autism, such as repetitive, stereotypic behaviors and deficits in social interactions and communication. Nadine Gogolla and her colleagues in the laboratory of Takao Hensch at Harvard University have now searched for common neural circuit alterations in mouse models of autism. They concentrated on the insular cortex, a brain structure that contributes to social, emotional and cognitive functions. ‘We wanted to know whether we can detect differences in the way the insular cortex processes information in healthy or autism-like mice’, says Nadine Gogolla, who was recently appointed Leader of a Research Group at the Max Planck Institute of Neurobiology. As the researchers now report, the insular cortex of healthy mice integrates stimuli from different sensory modalities and reacts more strongly when two different stimuli are presented concomitantly (e.g. a sound and a touch). ‘We recognize a rose more easily when we smell and see it rather than when we just see or smell it’ says Nadine Gogolla. This capacity of combining sensory stimuli was consistently affected in all autism models the researchers looked at. Interestingly, often one sense alone elicited such a strong response that adding a second modality did not add further information. This is very reminiscent of the sensory hyper-responsiveness experienced by many autistic patients. The scientist further discovered that the insular cortex of adult autism-model mice resembled the activation patterns observed in very young control mice. ‘It seemed as if the insular cortex of the autism-models did not mature properly after birth’, says Gogolla. For proper brain function, excitation and inhibition have to be in equilibrium. In the now identified part of the insular cortex, the scientists found that this equilibrium was disturbed. In one of the mouse models, inhibitory contacts between nerve cells were strongly reduced. To test the influence of this reduction on sensory processing, the researchers gave mice the drug Diazepam, which is also known under the trade name Valium, to boost inhibitory transmission in the brain. Indeed, this treatment transiently rescued the capacity of the insular cortex to combine stimuli of different sensory modalities. The balance between excitation and inhibition in the brain is established after birth. The scientists thus treated young animals over several days with Diazepam. This treatment was efficient in reestablishing the insular cortex capacity for sensory integration permanently, even in adult mice that did not received any further treatment. Interestingly, also the stereotypic grooming of the animals was significantly reduced. All autism models investigated showed alterations in inhibitory molecules. However, the alterations were very diverse. While in some models certain molecules were reduced, the opposite was true in another model. These results suggest that the disequilibrium between excitation and inhibition may be an important factor in the neuropathology of autism. However, future therapies will need to be carefully tailored to each particular subgroup of autism. For instance, an artificial boost of inhibition through a drug like Diazepam in healthy mice can throw the delicate equilibrium off and create changes in the insular cortex similar to those seen in the autism models. Whether a therapeutic strategy aimed on keeping the brain’s equilibrium between excitation and inhibition could be useful and if so, how to test the individuals’ status of the excitation/inhibition balance and how to implement individually tailored treatments, would need to be established through further studies and pre-clinical tests.

(Image credit: The insular cortex of an autism mouse model is already so strongly activated by a single sensory modality (here a sound), that it is unable to perform its role in integrating information from multiple sources. Credit: © MPI of Neurobiology / Gogolla)

Insular cortex alterations in mouse models of autism

The insular cortex is an integral “hub”, combining sensory, emotional and cognitive content. Not surprisingly, alterations in insular structure and function have been reported in many psychiatric disorders, such as anxiety disorders, depression, addiction and autism spectrum disorders (ASD). Scientists from Harvard University and the Max-Planck Institute of Neurobiology in Martinsried now describe consistent alterations in integrative processing of the insular cortex across autism mouse models of diverse etiologies. In particular, the delicate balance between excitation and inhibition in the autistic brains was disturbed, but could be pharmacologically re-adjusted. The results could help the development of novel diagnostic and therapeutic strategies.

Autism is a neurodevelopmental disorder characterized by impaired social interaction, verbal and non-verbal communication, and by restricted and repetitive behaviors. Diagnosis is solely based on behavioral analysis as biological markers and neurological underpinnings remain unknown. This makes the development of novel therapeutic strategies extremely difficult. 

As the cellular basis of autism spectrum disorders cannot be addressed in human patients, scientists have developed a number of mouse models for the disease. Similar to humans, mice are social animals and communicate through species-specific vocalizations. The mouse models harbor all diagnostic hallmark criteria of autism, such as repetitive, stereotypic behaviors and deficits in social interactions and communication.

Nadine Gogolla and her colleagues in the laboratory of Takao Hensch at Harvard University have now searched for common neural circuit alterations in mouse models of autism. They concentrated on the insular cortex, a brain structure that contributes to social, emotional and cognitive functions. ‘We wanted to know whether we can detect differences in the way the insular cortex processes information in healthy or autism-like mice’, says Nadine Gogolla, who was recently appointed Leader of a Research Group at the Max Planck Institute of Neurobiology.

As the researchers now report, the insular cortex of healthy mice integrates stimuli from different sensory modalities and reacts more strongly when two different stimuli are presented concomitantly (e.g. a sound and a touch). ‘We recognize a rose more easily when we smell and see it rather than when we just see or smell it’ says Nadine Gogolla. This capacity of combining sensory stimuli was consistently affected in all autism models the researchers looked at. Interestingly, often one sense alone elicited such a strong response that adding a second modality did not add further information. This is very reminiscent of the sensory hyper-responsiveness experienced by many autistic patients. The scientist further discovered that the insular cortex of adult autism-model mice resembled the activation patterns observed in very young control mice. ‘It seemed as if the insular cortex of the autism-models did not mature properly after birth’, says Gogolla.

For proper brain function, excitation and inhibition have to be in equilibrium. In the now identified part of the insular cortex, the scientists found that this equilibrium was disturbed. In one of the mouse models, inhibitory contacts between nerve cells were strongly reduced.

To test the influence of this reduction on sensory processing, the researchers gave mice the drug Diazepam, which is also known under the trade name Valium, to boost inhibitory transmission in the brain. Indeed, this treatment transiently rescued the capacity of the insular cortex to combine stimuli of different sensory modalities. The balance between excitation and inhibition in the brain is established after birth. The scientists thus treated young animals over several days with Diazepam. This treatment was efficient in reestablishing the insular cortex capacity for sensory integration permanently, even in adult mice that did not received any further treatment. Interestingly, also the stereotypic grooming of the animals was significantly reduced.

All autism models investigated showed alterations in inhibitory molecules. However, the alterations were very diverse. While in some models certain molecules were reduced, the opposite was true in another model. These results suggest that the disequilibrium between excitation and inhibition may be an important factor in the neuropathology of autism. However, future therapies will need to be carefully tailored to each particular subgroup of autism. For instance, an artificial boost of inhibition through a drug like Diazepam in healthy mice can throw the delicate equilibrium off and create changes in the insular cortex similar to those seen in the autism models. Whether a therapeutic strategy aimed on keeping the brain’s equilibrium between excitation and inhibition could be useful and if so, how to test the individuals’ status of the excitation/inhibition balance and how to implement individually tailored treatments, would need to be established through further studies and pre-clinical tests.

Filed under insular cortex autism brain function diazepam animal model neuroscience science

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New Mapping Approach Lets Scientists Zoom In And Out As The Brain Processes Sound Researchers at Johns Hopkins have mapped the sound-processing part of the mouse brain in a way that keeps both the proverbial forest and the trees in view. Their imaging technique allows zooming in and out on views of brain activity within mice, and it enabled the team to watch brain cells light up as mice “called” to each other. The results, which represent a step toward better understanding how our own brains process language, appear online July 31 the journal Neuron. In the past, researchers often studied sound processing in various animal brains by poking tiny electrodes into the auditory cortex, the part of the brain that processes sound. They then played tones and observed the response of nearby neurons, laboriously repeating the process over a gridlike pattern to figure out where the active neurons were. The neurons seemed to be laid out in neatly organized bands, each responding to a different tone. More recently, a technique called two-photon microscopy has allowed researchers to focus in on minute slices of the live mouse brain, observing activity in unprecedented detail. This newer approach has suggested that the well-manicured arrangement of bands might be an illusion. But, says David Yue, M.D., Ph.D., a professor of biomedical engineering and neuroscience at the Johns Hopkins University School of Medicine, “You could lose your way within the zoomed-in views afforded by two-photon microscopy and not know exactly where you are in the brain.” Yue led the study along with Eric Young, Ph.D., also a professor of biomedical engineering and a researcher in Johns Hopkins’ Institute for Basic Biomedical Sciences. To get the bigger picture, John Issa, a graduate student in Yue’s lab, used a mouse genetically engineered to produce a molecule that glows green in the presence of calcium. Since calcium levels rise in neurons when they become active, neurons in the mouse’s auditory cortex glow green when activated by various sounds. Issa used a two-photon microscope to peer into the brains of live mice as they listened to sounds and saw which neurons lit up in response, piecing together a global map of a given mouse’s auditory cortex. “With these mice, we were able to both monitor the activity of individual populations of neurons and zoom out to see how those populations fit into a larger organizational picture,” he says. With these advances, Issa and the rest of the research team were able see the tidy tone bands identified in earlier electrode studies. In addition, the new imaging platform quickly revealed more sophisticated properties of the auditory cortex, particularly as mice listened to the chirps they use to communicate with each other. “Understanding how sound representation is organized in the brain is ultimately very important for better treating hearing deficits,” Yue says. “We hope that mouse experiments like this can provide a basis for figuring out how our own brains process language and, eventually, how to help people with cochlear implants and similar interventions hear better.” Yue notes that the same approach could also be used to understand other parts of the brain as they react to outside stimuli, such as the visual cortex and the parts of the brain responsible for processing stimuli from limbs.

New Mapping Approach Lets Scientists Zoom In And Out As The Brain Processes Sound

Researchers at Johns Hopkins have mapped the sound-processing part of the mouse brain in a way that keeps both the proverbial forest and the trees in view. Their imaging technique allows zooming in and out on views of brain activity within mice, and it enabled the team to watch brain cells light up as mice “called” to each other. The results, which represent a step toward better understanding how our own brains process language, appear online July 31 the journal Neuron.

In the past, researchers often studied sound processing in various animal brains by poking tiny electrodes into the auditory cortex, the part of the brain that processes sound. They then played tones and observed the response of nearby neurons, laboriously repeating the process over a gridlike pattern to figure out where the active neurons were. The neurons seemed to be laid out in neatly organized bands, each responding to a different tone. More recently, a technique called two-photon microscopy has allowed researchers to focus in on minute slices of the live mouse brain, observing activity in unprecedented detail. This newer approach has suggested that the well-manicured arrangement of bands might be an illusion. But, says David Yue, M.D., Ph.D., a professor of biomedical engineering and neuroscience at the Johns Hopkins University School of Medicine, “You could lose your way within the zoomed-in views afforded by two-photon microscopy and not know exactly where you are in the brain.” Yue led the study along with Eric Young, Ph.D., also a professor of biomedical engineering and a researcher in Johns Hopkins’ Institute for Basic Biomedical Sciences.

To get the bigger picture, John Issa, a graduate student in Yue’s lab, used a mouse genetically engineered to produce a molecule that glows green in the presence of calcium. Since calcium levels rise in neurons when they become active, neurons in the mouse’s auditory cortex glow green when activated by various sounds. Issa used a two-photon microscope to peer into the brains of live mice as they listened to sounds and saw which neurons lit up in response, piecing together a global map of a given mouse’s auditory cortex. “With these mice, we were able to both monitor the activity of individual populations of neurons and zoom out to see how those populations fit into a larger organizational picture,” he says.

With these advances, Issa and the rest of the research team were able see the tidy tone bands identified in earlier electrode studies. In addition, the new imaging platform quickly revealed more sophisticated properties of the auditory cortex, particularly as mice listened to the chirps they use to communicate with each other. “Understanding how sound representation is organized in the brain is ultimately very important for better treating hearing deficits,” Yue says. “We hope that mouse experiments like this can provide a basis for figuring out how our own brains process language and, eventually, how to help people with cochlear implants and similar interventions hear better.”

Yue notes that the same approach could also be used to understand other parts of the brain as they react to outside stimuli, such as the visual cortex and the parts of the brain responsible for processing stimuli from limbs.

Filed under sound processing brain activity auditory cortex hearing neuroscience science

241 notes

Noise-Induced Hearing Loss Alters Brain Responses to Speech Prolonged exposure to loud noise alters how the brain processes speech, potentially increasing the difficulty in distinguishing speech sounds, according to neuroscientists at The University of Texas at Dallas. In a paper published this week in Ear and Hearing, researchers demonstrated for the first time how noise-induced hearing loss affects the brain’s recognition of speech sounds. Noise-induced hearing loss (NIHL) reaches all corners of the population, affecting an estimated 15 percent of Americans between the ages of 20 and 69, according to the National Institute of Deafness and Other Communication Disorders (NIDCD). Exposure to intensely loud sounds leads to permanent damage of the hair cells, which act as sound receivers in the ear. Once damaged, the hair cells do not grow back, leading to NIHL. “As we have made machines and electronic devices more powerful, the potential to cause permanent damage has grown tremendously,” said Dr. Michael Kilgard, co-author and Margaret Fonde Jonsson Professor in the School of Behavioral and Brain Sciences. “Even the smaller MP3 players can reach volume levels that are highly damaging to the ear in a matter of minutes.” Before the study, scientists had not clearly understood the direct effects of NIHL on how the brain responds to speech. To simulate two types of noise trauma that clinical populations face, UT Dallas scientists exposed rats to moderate or intense levels of noise for an hour. One group heard a high-frequency noise at 115 decibels inducing moderate hearing loss, and a second group heard a low-frequency noise at 124 decibels causing severe hearing loss. For comparison, the American Speech-Language-Hearing Association lists the maximum output of an MP3 player or the sound of a chain saw at about 110 decibels and the siren on an emergency vehicle at 120 decibels. Regular exposure to sounds greater than 100 decibels for more than a minute at a time may lead to permanent hearing loss, according to the NIDCD. Researchers observed how the two types of hearing loss affected speech sound processing in the rats by recording the neuronal response in the auditory cortex a month after the noise exposure. The auditory cortex, one of the main areas that processes sounds in the brain, is organized on a scale, like a piano. Neurons at one end of the cortex respond to low-frequency sounds, while other neurons at the opposite end react to higher frequencies. In the group with severe hearing loss, less than one-third of the tested auditory cortex sites that normally respond to sound reacted to stimulation. In the sites that did respond, there were unusual patterns of activity. The neurons reacted slower, the sounds had to be louder and the neurons responded to frequency ranges narrower than normal. Additionally, the rats could not tell the speech sounds apart in a behavioral task they could successfully complete before the hearing loss. In the group with moderate hearing loss, the area of the cortex responding to sounds didn’t change, but the neurons’ reaction did. A larger area of the auditory cortex responded to low-frequency sounds. Neurons reacting to high frequencies needed more intense sound stimulation and responded slower than those in normal hearing animals. Despite these changes, the rats were still able to discriminate the speech sounds in a behavioral task. “Although the ear is critical to hearing, it is just the first step of many processing stages needed to hold a conversation,” Kilgard said. “We are beginning to understand how hearing damage alters the brain and makes it hard to process speech, especially in noisy environments.”

Noise-Induced Hearing Loss Alters Brain Responses to Speech

Prolonged exposure to loud noise alters how the brain processes speech, potentially increasing the difficulty in distinguishing speech sounds, according to neuroscientists at The University of Texas at Dallas.

In a paper published this week in Ear and Hearing, researchers demonstrated for the first time how noise-induced hearing loss affects the brain’s recognition of speech sounds.

Noise-induced hearing loss (NIHL) reaches all corners of the population, affecting an estimated 15 percent of Americans between the ages of 20 and 69, according to the National Institute of Deafness and Other Communication Disorders (NIDCD).

Exposure to intensely loud sounds leads to permanent damage of the hair cells, which act as sound receivers in the ear. Once damaged, the hair cells do not grow back, leading to NIHL.

“As we have made machines and electronic devices more powerful, the potential to cause permanent damage has grown tremendously,” said Dr. Michael Kilgard, co-author and Margaret Fonde Jonsson Professor in the School of Behavioral and Brain Sciences. “Even the smaller MP3 players can reach volume levels that are highly damaging to the ear in a matter of minutes.”

Before the study, scientists had not clearly understood the direct effects of NIHL on how the brain responds to speech.

To simulate two types of noise trauma that clinical populations face, UT Dallas scientists exposed rats to moderate or intense levels of noise for an hour. One group heard a high-frequency noise at 115 decibels inducing moderate hearing loss, and a second group heard a low-frequency noise at 124 decibels causing severe hearing loss.

For comparison, the American Speech-Language-Hearing Association lists the maximum output of an MP3 player or the sound of a chain saw at about 110 decibels and the siren on an emergency vehicle at 120 decibels. Regular exposure to sounds greater than 100 decibels for more than a minute at a time may lead to permanent hearing loss, according to the NIDCD.

Researchers observed how the two types of hearing loss affected speech sound processing in the rats by recording the neuronal response in the auditory cortex a month after the noise exposure. The auditory cortex, one of the main areas that processes sounds in the brain, is organized on a scale, like a piano. Neurons at one end of the cortex respond to low-frequency sounds, while other neurons at the opposite end react to higher frequencies.

In the group with severe hearing loss, less than one-third of the tested auditory cortex sites that normally respond to sound reacted to stimulation. In the sites that did respond, there were unusual patterns of activity. The neurons reacted slower, the sounds had to be louder and the neurons responded to frequency ranges narrower than normal. Additionally, the rats could not tell the speech sounds apart in a behavioral task they could successfully complete before the hearing loss.

In the group with moderate hearing loss, the area of the cortex responding to sounds didn’t change, but the neurons’ reaction did. A larger area of the auditory cortex responded to low-frequency sounds. Neurons reacting to high frequencies needed more intense sound stimulation and responded slower than those in normal hearing animals. Despite these changes, the rats were still able to discriminate the speech sounds in a behavioral task.

“Although the ear is critical to hearing, it is just the first step of many processing stages needed to hold a conversation,” Kilgard said. “We are beginning to understand how hearing damage alters the brain and makes it hard to process speech, especially in noisy environments.”

Filed under hearing loss auditory cortex hair cells speech sounds neuroscience science

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New research links anxiety to epilepsy-like seizures

New research by clinical psychologists from Arizona State University and the United Kingdom has revealed seizures that could be mistaken for epilepsy are linked to feelings of anxiety.

The team of researchers devised a new set of tests to determine whether there was a link between how people interpret and respond to anxiety, and incidences of psychogenic nonepileptic seizures (PNES).

Nicole Roberts, an associate professor in ASU’s New College of Interdisciplinary Arts and Sciences, collaborated with colleagues from the University of Lincoln, University of Nottingham and University of Sheffield in the United Kingdom. The team’s findings were published in the journal Epilepsy and Behavior.

The researchers used a series of questionnaires and computer tests to determine if a patient regularly avoids situations which might bring on anxiety.

These tests correctly predicted whether a patient had epilepsy or PNES – seizures that can be brought on by threatening situations, sensations, emotions, thoughts or memories – in 83 percent of study participants. Such seizures appear on the surface to be similar to epileptic fits, which are caused by abnormal brain activity.

“This research underscores the fact that PNES is a ‘real’ and disabling disorder with a potentially identifiable pathophysiology,” said Roberts, who directs New College’s Emotion, Culture, and Psychophysiology Laboratory, located on ASU’s West campus. “We need to continue to search for answers, not just in epilepsy clinics, but also in the realm of affective science and complex brain-behavior relationships.”

“PNES can be a very disabling condition, and it is important that we understand the triggers so that we provide the correct care and treatment,” said Lian Dimaro, a clinical psychologist based at Nottinghamshire Healthcare NHS Trust, who served as lead researcher for the study.

“This study was one of the first to bring modern psychological tools of investigation to this problem,” Dimaro said. “The findings support the idea that increasing a person’s tolerance of unpleasant emotions and reducing avoidant behavior may help with treatment, suggesting that patients could benefit from a range of therapies, including acceptance and commitment therapy to help reduce the frequency of seizures, although more research is needed in this area.”

Participants completed questionnaires to determine the level to which they suffered from anxiety, their awareness of their experiences and if they would avoid situations which would make them feel anxious.

They then completed a computer task which required rapid responses to true or false statements. This test was designed to gather data on immediate, or implicit, beliefs about anxiety. Participants also answered questions about common physical complaints that may have no medical explanation, also called somatic symptoms. These can include things like gastrointestinal problems, tiredness and back pain.

Results showed that those with PNES reported significantly more somatic symptoms than others in the study, as well as avoidance of situations which might make them anxious. The group with PNES also scored significantly higher on a measure of how aware they were of their anxiety compared with the control group.

The test subjects were 30 adults with PNES, 25 with epilepsy and 31 with no reported history of seizures who served as a nonclinical control group.

The researchers suggest that including tests to determine levels of anxiety and avoidance behavior may enable health professionals to make earlier diagnosis, and develop more effective intervention plans.

“Epileptic seizures are caused by abnormal electrical activity in the brain, while most PNES are thought to be a consequence of complex psychological processes that manifest in physical attacks,” said David Dawson, a research clinical psychologist from the University of Lincoln.

“It is believed that people suffering with PNES may have difficulty actively engaging with anxiety – a coping style known as experiential avoidance,” Dawson said. “We wanted to examine whether it was possible to make a clear link between seizure frequency and how people experience and manage anxiety. Our study is another step in understanding PNES, which could ultimately lead to better treatment and, therefore, patient outcomes in the future.”

Roberts, who received her doctorate in clinical psychology from the University of California, Berkeley, focuses her research on the study of emotion and on the cultural and biological forces that shape emotional responses. Examples include investigating how ethnicity and culture influence emotional displays and experiences; how the daily hassles of life, such as job stress and sleep deprivation, impact emotion regulation among individuals and couples; and how the emotion system breaks down in patients with psychopathology (such as PNES and post-traumatic stress disorder) or neurological dysfunction (such as epilepsy).

(Source: asunews.asu.edu)

Filed under anxiety psychogenic nonepileptic seizures seizures brain activity epilepsy neuroscience science

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New Mouse Model May Open Autism Treatment Research Avenues

The hallmark of an excellent researcher is an open mind. That flexibility and openness is what led Nina Schor, M.D., Ph.D., the William H. Eilinger Chair of Pediatrics at the University of Rochester, to follow a hunch about a brain receptor – resulting in a new mouse model that may give researchers a new avenue for testing drugs for autism. Nature Publishing Groups’ Translational Psychiatry published the study online today.

Schor had been studying p75 neurotrophin receptors in her long-standing neuroblastoma research, but she also knew that p75NTR is involved in the reaction to oxidative stress in the brain, which some research posits plays a role in the development of autism. The receptor is also prevalent in the developing brain and drops off as a child reaches 2 to 3 years old, which is when autism symptoms often begin to appear. P75NTR stays present in the typically developing cerebellum, hippocampus and basal forebrain, parts of the brain that are anatomically abnormal in autism.

“Science doesn’t always travel in a straight line,” Schor said. “Sometimes the importance of a scientific study in one field is what it unexpectedly tells us about another field.”

While other researchers are focused on the proteins found to be abnormal in patients with autism, Schor approached her investigation from the opposite direction. She thought about what characteristics a protein would have to have to be involved in processes thought to play a role in autism. “That list of characteristics looked suspiciously like those we had found to be associated with p75NTR.”

Then, Schor and her colleagues prevented mouse brains from making p75NTR in one autism-associated type of cell in the cerebellum. What they found was that not only does the mouse’s cerebellum resemble that of children with autism, but the mouse also behaves much like children with autism. They don’t engage in typical social behaviors of mice and instead, ignore stranger mice and lack curiosity about their surroundings. They also jump twice as much as typical mice, which is like a “stimming,” or self-stimulatory, behavior typical in children with autism.

“Whether or not p75NTR turns out to be abnormal in children with autism,” Schor explained, “these studies still hold the promise of helping us explain the mechanisms behind the component behaviors of children with autism.

Schor plans to continue the research, focusing on more behavioral testing, finding evidence of whether children with autism have a p75NTR deficit in their cerebellum and starting pharmaceutical testing to see whether there is a drug that can replace the role p75NTR plays in that part of the brain.

“It’s a long way from a mouse model to a successful treatment in humans, but this is a good clue,” Schor said.

Filed under p75NTR autism cerebellum purkinje cells animal model neuroscience science

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Kids with Autism, Sensory Processing Disorders Show Brain Wiring Differences Researchers at UC San Francisco have found that children with sensory processing disorders have decreased structural brain connections in specific sensory regions different than those in autism, further establishing SPD as a clinically important neurodevelopmental disorder. The research, published in the journal PLOS ONE, is the first study to compare structural connectivity in the brains of children with an autism diagnosis versus those with an SPD diagnosis, and with a group of typically developing boys. This new research follows UCSF’s groundbreaking study published in 2013 that was the first to find that boys affected with SPD have quantifiable regional differences in brain structure when compared to typically developing boys. This work showed a biological basis for the disease but prompted the question of how these differences compared with other neurodevelopmental disorders. “With more than 1 percent of children in the U.S. diagnosed with an autism spectrum disorder, and reports of 5 to 16 percent of children having sensory processing difficulties, it’s essential we define the neural underpinnings of these conditions, and identify the areas they overlap and where they are very distinct,” said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF. SPD Gains Recognition as Distinct Condition SPD can be hard to pinpoint, as more than 90 percent of children with autism also are reported to have atypical sensory behaviors, and SPD has not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists. “One of the most striking new findings is that the children with SPD show even greater brain disconnection than the kids with a full autism diagnosis in some sensory-based tracts,” said Elysa Marco, MD, cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital San Francisco and the study’s corresponding author. “However, the children with autism, but not those with SPD, showed impairment in brain connections essential to the processing of facial emotion and memory.” Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with emotional regulation. Furthermore, a sound that is an irritant one day can be tolerated the next. The disease can be baffling for parents and has been a source of much controversy for clinicians who debate whether it constitutes its own disorder, according to the researchers. “These kids, however, often don’t get supportive services at school or in the community because SPD is not yet a recognized condition,” said Marco. “We are starting to catch up with what parents already knew; sensory challenges are real and can be measured both in the lab and the real world. Our next challenge is to find the reason why children have SPD and move these findings from the lab to the clinic.” Examining White Matter Tracts in the Brain In the study, researchers used an advanced form of MRI called diffusion tensor imaging (DTI), which measures the microscopic movement of water molecules within the brain in order to give information about the brain’s white matter tracts. The brain’s white matter forms the “wiring” that links different areas of the brain and is therefore essential for perceiving, thinking and action. DTI shows the direction of the white matter fibers and the integrity of the white matter, thereby mapping the structural connections between brain regions. The study examined the structural connectivity of specific white matter tracts in16 boys with SPD and 15 boys with autism between the ages of 8 and 12 and compared them with 23 typically developing boys of the same age range. The researchers found that both the SPD and autism groups showed decreased connectivity in multiple parieto-occipital tracts, the areas that handle basic sensory information in the back area of the brain. However, only the autism cohort showed impairment in the inferior fronto-occipital fasciculi (IFOF), inferior longitudinal fasciculi (ILF), fusiform-amygdala and the fusiform-hippocampus tracts – critical tracts for social-emotional processing.   “One of the classic features of autism is decreased eye-to-eye gaze, and the decreased ability to read facial emotions,” said Marco. “The impairment in this specific brain connectivity, not only differentiates the autism group from the SPD group but reflects the difficulties patients with autism have in the real world.  In our work, the more these regions are disconnected, the more challenge they are having with social skills.” Kids with isolated SPD showed less connectivity in the basic perception and integration tracts of the brain that serve as connections for the auditory, visual and somatosensory (tactile) systems involved in sensory processing. “If we can start by measuring a child’s brain connectivity and seeing how it is playing out in a child’s functional ability, we can then use that measure as a metric for success in our interventions and see if the connectivities are changing based on our clinical interventions,” said Marco. “Larger studies to replicate this early work are clearly needed but we are encouraged that DTI can be a powerful clinical and research tool for understanding the basis for sensory neurodevelopmental differences.”

Kids with Autism, Sensory Processing Disorders Show Brain Wiring Differences

Researchers at UC San Francisco have found that children with sensory processing disorders have decreased structural brain connections in specific sensory regions different than those in autism, further establishing SPD as a clinically important neurodevelopmental disorder.

The research, published in the journal PLOS ONE, is the first study to compare structural connectivity in the brains of children with an autism diagnosis versus those with an SPD diagnosis, and with a group of typically developing boys. This new research follows UCSF’s groundbreaking study published in 2013 that was the first to find that boys affected with SPD have quantifiable regional differences in brain structure when compared to typically developing boys. This work showed a biological basis for the disease but prompted the question of how these differences compared with other neurodevelopmental disorders.

“With more than 1 percent of children in the U.S. diagnosed with an autism spectrum disorder, and reports of 5 to 16 percent of children having sensory processing difficulties, it’s essential we define the neural underpinnings of these conditions, and identify the areas they overlap and where they are very distinct,” said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF.

SPD Gains Recognition as Distinct Condition

SPD can be hard to pinpoint, as more than 90 percent of children with autism also are reported to have atypical sensory behaviors, and SPD has not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.

“One of the most striking new findings is that the children with SPD show even greater brain disconnection than the kids with a full autism diagnosis in some sensory-based tracts,” said Elysa Marco, MD, cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital San Francisco and the study’s corresponding author. “However, the children with autism, but not those with SPD, showed impairment in brain connections essential to the processing of facial emotion and memory.”

Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with emotional regulation. Furthermore, a sound that is an irritant one day can be tolerated the next. The disease can be baffling for parents and has been a source of much controversy for clinicians who debate whether it constitutes its own disorder, according to the researchers.

“These kids, however, often don’t get supportive services at school or in the community because SPD is not yet a recognized condition,” said Marco. “We are starting to catch up with what parents already knew; sensory challenges are real and can be measured both in the lab and the real world. Our next challenge is to find the reason why children have SPD and move these findings from the lab to the clinic.”

Examining White Matter Tracts in the Brain

In the study, researchers used an advanced form of MRI called diffusion tensor imaging (DTI), which measures the microscopic movement of water molecules within the brain in order to give information about the brain’s white matter tracts. The brain’s white matter forms the “wiring” that links different areas of the brain and is therefore essential for perceiving, thinking and action. DTI shows the direction of the white matter fibers and the integrity of the white matter, thereby mapping the structural connections between brain regions.

The study examined the structural connectivity of specific white matter tracts in16 boys with SPD and 15 boys with autism between the ages of 8 and 12 and compared them with 23 typically developing boys of the same age range.

The researchers found that both the SPD and autism groups showed decreased connectivity in multiple parieto-occipital tracts, the areas that handle basic sensory information in the back area of the brain. However, only the autism cohort showed impairment in the inferior fronto-occipital fasciculi (IFOF), inferior longitudinal fasciculi (ILF), fusiform-amygdala and the fusiform-hippocampus tracts – critical tracts for social-emotional processing.  

“One of the classic features of autism is decreased eye-to-eye gaze, and the decreased ability to read facial emotions,” said Marco. “The impairment in this specific brain connectivity, not only differentiates the autism group from the SPD group but reflects the difficulties patients with autism have in the real world.  In our work, the more these regions are disconnected, the more challenge they are having with social skills.”

Kids with isolated SPD showed less connectivity in the basic perception and integration tracts of the brain that serve as connections for the auditory, visual and somatosensory (tactile) systems involved in sensory processing.

“If we can start by measuring a child’s brain connectivity and seeing how it is playing out in a child’s functional ability, we can then use that measure as a metric for success in our interventions and see if the connectivities are changing based on our clinical interventions,” said Marco. “Larger studies to replicate this early work are clearly needed but we are encouraged that DTI can be a powerful clinical and research tool for understanding the basis for sensory neurodevelopmental differences.”

Filed under autism sensory processing disorders white matter diffusion tensor imaging neuroscience science

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Striatal dopamine transporter binding correlates with body composition and visual attention bias for food cues in healthy young men

Research to be presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, describes a way that brain chemistry may make some people notice food more easily, which can tempt overeating even in people who are not overweight. Dopamine activity in the striatum, an area of the brain sensitive to food reward, was linked to how quickly men noticed a food picture hidden among neutral pictures. In turn, the men who quickly noticed food pictures also ate more.

From rodent research it is clear that dopamine action in the striatum motivates eating, and this goes awry in obesity. “We do know that in human obesity the striatal dopamine system is affected, but interesting enough we know little about the striatal dopamine system of young, healthy individuals and how it relates to the motivation to eat” says Susanne la Fleur from the Academic Medical Center in Amsterdam, who directed the study linking dopamine, attention to food, and eating.

Ordinarily the burst of dopamine during a rewarding activity is eventually stopped when it is re-absorbed into the cells it came from. That re-uptake process requires a brain chemical called “dopamine transporter” (DAT). Lower DAT means dopamine is reabsorbed more slowly, causing it to keep acting on the brain. The researchers scanned brains of healthy, non-obese young men to determine available DAT. The men completed a computerized visual attention task to see how quickly they could detect food pictures among neutral pictures. Subjects were also asked to report food intake during 7 days.

The researchers found that the men with lower DAT, which means higher dopamine activity, showed a stronger visual attention bias towards food, detecting food pictures more quickly. “We could speculate that in healthy humans dopamine does motivate eating, however although we did observe a correlation between striatal dopamine transporter binding and the visual attention bias for food; and between visual attention bias for food and actual food intake, we did not observe a correlation between striatal dopamine transporter binding and actual food intake. Thus, a factor in addition to dopamine must be involved in going from being motivated to actual eating”, la Fleur concluded.

(Source: eurekalert.org)

Filed under striatum dopamine dopamine transporter obesity visual attention neuroscience science

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Brain Response to Appetizing Food Cues Varies Among Obese People

People who have the most common genetic mutation linked to obesity respond differently to pictures of appetizing foods than overweight or obese people who do not have the genetic mutation, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).

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More than one-third of adults are obese. Obesity typically results from a combination of eating too much, getting too little physical activity and genetics. In particular, consumption of appetizing foods that are high in calories can lead to weight gain. Highly palatable foods such as chocolate trigger signals in the brain that give a feeling of pleasure and reward. These cravings can contribute to overeating. Reward signals are processed in specific areas of the brain, where sets of neurons release chemicals such as dopamine. However, very little is known about whether the reward centers of the brain work differently in some people who are overweight or obese.

The most common genetic cause of obesity involves mutations in the melanocortin 4 receptor (MC4R), which occur in about 1 percent of obese people and contribute to weight gain from an early age. The researchers compared three groups of people: eight people who were obese due to a problem in the MC4R gene, 10 people who were overweight or obese without the gene mutation and eight people who were normal weight. They performed functional Magnetic Resonance Imaging (fMRI) scans to look at how the reward centers in the brain were activated by pictures of appetizing food such as chocolate cake compared to bland food such as rice or broccoli and non-food items such as staplers.

“In our study, we found that people with the MC4R mutation responded in the same way as normal weight people, while the overweight people without the gene problem had a lower response,” said lead researcher Agatha van der Klaauw, MD, PhD, of the Wellcome Trust-MRC Institute of Metabolic Science at Addenbrooke’s Hospital in Cambridge, U.K. “In fact, the brain’s reward centers light up when people with the mutation and normal weight people viewed pictures of appetizing foods. But overweight people without the mutation did not have the same level of response.”

The scans revealed that obese people with the MC4R mutation had similar activity in the reward centers of the brain when shown a picture of a dessert like cake or chocolate as normal weight people. The researchers found that, in contrast, the reward centers were underactive in overweight and obese volunteers who did not have the gene mutation. This finding is intriguing as it shows a completely different response in two groups of people of the same age and weight.

“For the first time, we are seeing that the MC4R pathway is involved in the brain’s response to food cues and its underactivity in some overweight people,” van der Klaauw said. “Understanding this pathway may help in developing interventions to limit the overconsumption of highly palatable foods that can lead to weight gain.”

To address the obesity epidemic, the Cambridge team is continuing to study the pathways in the brain that coordinate the need to eat and the reward and pleasure of eating

(Source: endocrine.org)

Filed under obesity MC4R melanocortin gene mutations brain activity neuroscience science

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