Posts Tagged ‘brain’

Dr. Lewis L. Judd led the National Institute of Mental Health from 1988 to 1990. (National Library of Medicine)

By Emily Langer

Lewis L. Judd, a nationally known psychiatrist who helped turn the focus of his profession from psychoanalysis to neuroscience, an approach that sought to destigmatize mental illness by treating it as cancer, heart disease or any other medical problem, died Dec. 16 in La Jolla, Calif. He was 88.

The cause was cardiac arrest, said his wife, Pat Judd.

For decades, psychiatrists were schooled in the theories of Sigmund Freud, the founder of psychoanalysis, who posited that mental disturbances could be treated through dialogue with a therapist. Practitioners sought to interpret their patients’ dreams, giving little attention to the physical functioning of the brain or the chemicals that regulate it.

Dr. Judd agreed, he once told the Associated Press, that a physician must look at patients as a “whole individual,” with all their “worries, concerns, aspirations and needs,” and not resort to simply “popping a pill in their mouth.” But he found the long-prevailing psychoanalytic approach too limiting to explain or treat afflictions such as depression, bipolar disorder, severe anxiety and schizophrenia — “these serious mental disorders that have defied our understanding for centuries,” he once told the Chicago Tribune.

Instead, he advocated a biological approach, starting at the molecular level of the brain. As director of the National Institute of Mental Health in Bethesda, Md. — a post he held from 1988 to 1990, during a hiatus from his decades-long chairmanship of the psychiatry department at the University of California at San Diego — he helped launch a federal research initiative known as the “Decade of the Brain.”

“He was obsessed with educating the public and the profession . . . that mental illnesses were biological illnesses, that schizophrenia and depression were diseases of the brain,” Alan I. Leshner, Dr. Judd’s deputy at NIMH and later chief executive of the American Association for the Advancement of Science, said in an interview. “At the time, that was a heretical thought.”

Today, the biological component of many mental illnesses is widely accepted. When Dr. Judd led NIMH, it was not; he once cited a survey in which 71 percent of respondents said mental illness was a result of personal weakness and a third attributed it to sinful behavior. Poor parenting was another common alleged culprit.

Dr. Judd argued that the biological approach to psychiatry held the promise not only of deepening understanding of the body’s most complex organ but of improving lives: If mental disorders could be shown to be a result of brain chemistry or of physical dysfunction, patients might feel less stigmatized and therefore more willing to seek treatment.

“We look at the homeless and feel that if they only got their act together, they could lift themselves up,” Dr. Judd told the Los Angeles Times in 1988, discussing the prevalence of mental illness among homeless people. “We would never believe that about someone who has cancer or some other physical disease.”

As head of NIMH, which is an arm of the National Institutes of Health and the chief federal agency for research on mental illness, Dr. Judd oversaw more than $500 million in research money. He described the Decade of the Brain — a designation conferred by Congress and President George H.W. Bush — as a “research plan designed to bring a precise and detailed understanding of all the elements of brain function within our own lifetimes.”

During his tenure at NIMH, scientists for the first time successfully grew brain tissue in a laboratory. Dr. Judd was among those scientists who touted the potential of medical imaging, such as MRIs and PET scans, to reveal the inner workings of the brain and the potential causes of diseases such as schizophrenia.

Almost 30 years after the Decade of the Brain began, much about the organ remains elusive. Leshner credited the initiative with helping bring attention to the importance of brain research as well as inspiring the Brain Initiative, a public-private research effort advanced by the Obama administration.

“The brain is really the last frontier for scientists,” Dr. Judd said.

Lewis Lund Judd was born in Los Angeles on Feb. 10, 1930. His father was an obstetrician-gynecologist, and his mother was a homemaker. Dr. Judd’s brother, Howard Judd, also became an OB/GYN and a noted researcher in women’s health at the University of California at Los Angeles.

Dr. Judd received a bachelor’s degree in psychology from the University of Utah in 1954 and a medical degree from UCLA in 1958. In the early years of his career, he served in the Air Force as a base psychiatrist.

He joined UC-San Diego in 1970 and became department chairman in 1977, helping grow his faculty into one of the most respected the country. He stepped down as chairman in 2013 and retired in 2015.

Dr. Judd’s first marriage, to Anne Nealy, ended in divorce. Survivors include his wife of 45 years, the former Patricia Hoffman, who is also a psychiatry professor at UC-San Diego, of La Jolla; three daughters from his first marriage, Allison Fee of Whidbey Island, Wash., Catherine Judd of Miami and Stephanie Judd of Chevy Chase, Md.; and four grandchildren.

Ever exploring the outer reaches of his field, Dr. Judd participated in a dialogue with the Dalai Lama in 1989 about life and the mind.

“Our model of mental health is mostly defined in terms of the absence of mental illness,” Dr. Judd told the New York Times, reflecting on the Tibetan Buddhist leader’s discussion of wisdom and compassion. “They may have more positive ones that might be worth our study.”


Patterns of gene expression unite the prairie vole Microtus ochrogaster with other monogamous species, including certain frogs, fish, and birds. YVA MOMATIUK AND JOHN EASTCOTT/MINDEN PICTURES

By Kelly Servick

In the animal world, monogamy has some clear perks. Living in pairs can give animals some stability and certainty in the constant struggle to reproduce and protect their young—which may be why it has evolved independently in various species. Now, an analysis of gene activity within the brains of frogs, rodents, fish, and birds suggests there may be a pattern common to monogamous creatures. Despite very different brain structures and evolutionary histories, these animals all seem to have developed monogamy by turning on and off some of the same sets of genes.

“It is quite surprising,” says Harvard University evolutionary biologist Hopi Hoekstra, who was not involved in the new work. “It suggests that there’s a sort of genomic strategy to becoming monogamous that evolution has repeatedly tapped into.”

Evolutionary biologists have proposed various benefits to so-called social monogamy, where mates pair up for at least a breeding season to care for their young and defend their territory. When potential mates are scarce or widely dispersed, for example, forming a single-pair bond can ensure they get to keep reproducing.

Neuroscientist Hans Hofmann and evolutionary biologist Rebecca Young at the University of Texas in Austin wanted to explore how the regulation of genes in the brain might have changed when a nonmonogamous species evolved to become monogamous. For example, the complex set of genes that underlie the ability to tolerate the presence of another member of one’s species presumably exists in nonmonogamous animals, but might be activated in different patterns to allow prolonged partnerships in monogamous ones.

“We wanted to be bold—and maybe a little bit crazy” in the new experiment, Hofmann says. Instead of doing a relatively straightforward genetic comparison between closely related species on either side of the monogamy divide, he and colleagues wanted to hunt down a gene activity signature associated with monogamy in males across a wide variety of species—frogs, mice, voles, birds, and fish. So in each of these groups, they selected two species, one monogamous and one nonmonogamous.

Rounding up the brains of those animals took an international team and years of effort. Hostile regional authorities and a complicated permitting system confronted the team in Romania as they tried to capture two types of a native songbird. Hofmann donned scuba gear and plunged into Africa’s Lake Tanganyika to chase finger-length cichlid fish into nets. Delicately debraining them while aboard a rocking boat, he says, was a struggle.

Back the lab, the researchers then grouped roughly comparable genes across all 10 species based on similarities in their sequences. For each of these cross-species gene groups, they measured activity based on how much the cells in the brain transcribed the DNA’s proteinmaking instructions into strands of RNA.

Among the monogamous animals, a pattern emerged. The researchers found certain sets of genes were more likely to be “turned up” or “turned down” in those creatures than in the nonmonogamous species. And they ruled out other reasons why these monogamous animals might have similar gene expression patterns, including similar environments or close evolutionary relationships.

Among the genes with increased activity in monogamous species were those involved in neural development, signaling between cells, learning, and memory, the researchers report online today in the Proceedings of the National Academy of Sciences. They speculate that genes that make the brain more adaptable—and better able to remember—might also help animals recognize their mates and find their presence rewarding.

It makes sense that genes involved in brain development and function would underlie a complex behavior like monogamy, says behavioral neuroscientist Claudio Mello of Oregon Health & Science University in Portland. But because the researchers didn’t dissect out specific brain regions and analyze their RNA production independently, they can’t describe the finely tuned patterns of gene expression in areas that are key to reproductive behavior. “It seems to me unlikely that by themselves these genes will be able to ‘explain’ this behavior,” he says.

“The fact that they got any common genes at all is interesting,” adds Lisa Stubbs, a developmental geneticist at the University of Illinois in Urbana. “It is a superb data set and an expert analysis,” she says, “[but] the authors have not actually uncovered many important biological insights into monogamy.”

The study did turn up a curious outlier. Some of the genes with decreased expression in most of the monogamous species showed increased expression in one of them—the poison dart frog Ranitomeya imitator. Young notes that in this species’s evolutionary history, fathers cared for the young before cooperative parenting evolved. As a result, these frogs may have had a different evolutionary starting point than other animals in the study, later tapping into different genes to become monogamous.

Hoekstra, who has studied the genetics of monogamy in mice, sees “a lot of exciting next steps.” There are likely mutations in other regions of DNA that regulate the expression of the genes this study identified. But it will take more work to show a causal relationship between any particular genetic sequence and monogamous behavior.

People also often opt for monogamy, albeit for a complicated set of social and cultural reasons. So, do we share the gene activity signature common to monogamous birds, fish, and frogs? “We don’t know that,” says Hofmann, but “we certainly would speculate that the kind of gene expression patterns … might [show up] in humans as well.”

Ghrelin, the hormone that makes you hungry, also makes food, and food smells, irresistibly appealing. Karen Hopkin reports.

By Karen Hopkin

‘Tis the season…for overeating! But it’s not just your lack of willpower or the omnipresent holiday treats. No, you can lay some of the blame on ghrelin. Because a new study shows that ghrelin, the hormone that makes you hungry, also makes food…and food smells…irresistibly appealing. The finding appears in the journal Cell Reports. [Jung Eun Han et al, Ghrelin Enhances Food Odor Conditioning in Healthy Humans: An fMRI Study]

Ghrelin is produced in the stomach, and its levels rise before your habitual mealtimes and after you haven’t eaten for an extended period. So the hormone reminds you to put something in your belly. Injecting rats with ghrelin encourages them to eat…and people who receive a dose of ghrelin grab extra helpings from the buffet.

But how does the hormone induce overindulgence? To find out, researchers at McGill University trained volunteers to associate random images with the smell of food. For example, every time they saw a tree, they might get a whiff of freshly baked bread. At the same time, some of the subjects received ghrelin; others got only saline.

The volunteers were then ushered into an fMRI machine, where the researchers watched their brains to see which parts got turned on by different images.

Seems that in subjects under the influence of ghrelin, the brain region involved in pleasure and reward lit up only when volunteers viewed the images they associated with food aromas. Their brain pleasure centers were disinterested in images that had not been paired with food smells.

Also, when participants were then asked to rate the pleasantness of the images, the ones who’d been exposed to ghrelin gave higher grades to the food-associated pictures than did folks who got no ghrelin.


By Bahar Gholipour

A 49-year-old man in Brazil survived a stroke but underwent a strange personality change afterward — he developed “pathological generosity,” according to a report of his case.

His willingness to give liberally to others – including people he barely knew — dramatically changed his life. He would spend his money on children he met on the street, buying them soda, candies and junk food, his wife told the doctors. Mr. A, as the man is called in the case report, became unable to manage his financial life, or resume his job as a department manager within a large corporation.

The stroke apparently left Mr. A with “excessive and persistent generosity,” the researchers, led by Dr. Leonardo Fontenelle from the Federal University of Rio de Janeiro.

“Stroke can cause a whole variety of neuropsychological and behavioral changes,” said Dr. Larry Goldstein, neurologist and director of the Stroke Center at Duke University, who wasn’t involved with the case. “Although the observation of personality change is not that unusual, this particular one is apparently novel,” he told LiveScience.

Very often, a behavior change after a stroke depends on the extent of injury and the location of the injury in the brain, Goldstein said.

How stroke affects personality

A stroke occurs when a blood clot blocks the blood supply to the brain, or when a blood vessel in the brain bursts. Brain damage caused by low oxygen supply can lead to emotional changes, most commonly depression, but strokes have also been known to cause pathological laughing or crying, or neglect syndrome, in which people don’t recognize one side of their visual field.

In Mr. A’s case, the stroke was due to bleeding in the brain, related to his high blood pressure.

Understanding exactly what change in the brain was driving Mr. A’s excessive generosity is very interesting for scientists, especially because the condition is in many respects the opposite of disorders such as hoarding and sociopathy, the researchers said.

Doctors determined Mr. A’s stroke occurred in a subcortical region, (below the cerebral cortex, where higher-level thinking occurs), and the damage could have affected brain areas associated with regulating normal behaviors.

But knowing the location of a stroke doesn’t necessarily predict the behavioral change. The networking that happens in the brain means there are often effects in areas of the brain not right next to the injury, Goldstein said.

Studies have pointed to a couple of brain structures as being involved in acts of generosity, such as anonymously donating to charities. These brain structures include the brain’s reward system, the researchers said.

A life forever changed?

Mr. A’s pathological generosity may provide new insights into which brain areas affect “the delicate balance between altruism and egoism, which make up one of the pillars of ordinary social motivation and decision making,” the researchers said.

Other instances of excessive benevolent behavior have been seen in cases of people with mania, Parkinson’s disease treated by certain medications, and forms of dementia.

When doctors carried out a psychological evaluation of Mr. A, they didn’t find any evidence of manic symptoms or dementia. Mr. A. reported being depressed, forgetful and unable to pay attention. He also showed some behaviors that have been linked to damage in the frontal lobe of the brain, including lack of persistence and planning, and impaired judgment, according to the report.

A CT scan showed blood flow to several brain regions, including areas in the frontal lobe, was low. These regions, although far from the bleed focus, are connected with it by neural pathways. The damage in these pathways might have disrupted the interplay of neural systems that underpin key dimensions of personality, the researchers said.

Mr. A was put on medication to treat his depression. After two years, he said he felt cured, and stopped the depression treatment, but his pathological generosity was unchanged. He was aware of changes in his behavior. According to the researchers, he often claimed, “I saw death from up-close, now I want to be in high spirits.”

When doctors asked whether he intended to resume his former job, he replied that he had already worked enough, and that it was now time “to enjoy life, which is too short.”

This combined MR/PET image highlights areas of the brain in which patients with fibromyalgia were found to have increased glial activation, compared with unaffected control volunteers. Credit: Marco Loggia, PhD, Martinos Center for Biomedical Imaging, Massachusetts General Hospital).

A study by Massachusetts General Hospital (MGH) researchers – collaborating with a team at the Karolinska Institutet in Sweden – has documented for the first time widespread inflammation in the brains of patients with the poorly understood condition called fibromyalgia. Their report has been published online in the journal Brain, Behavior and Immunity.

“We don’t have good treatment options for fibromyalgia, so identifying a potential treatment target could lead to the development of innovative, more effective therapies,” says Marco Loggia, PhD, of the MGH-based Martinos Center for Biomedical Imaging, co-senior author of the report.

“And finding objective neurochemical changes in the brains of patients with fibromyalgia should help reduce the persistent stigma that many patients face, often being told their symptoms are imaginary and there’s nothing really wrong with them.”

Characterized by symptoms including chronic widespread pain, sleep problems, fatigue, and problems with thinking and memory, fibromyalgia affects around 4 million adults in the U.S., according to the Centers for Disease Control and Prevention.

Previous research from the Karolinska group led by Eva Kosek, MD, PhD, co-senior author of the current study, suggested a potential role for neuroinflammation in the condition – including elevated levels of inflammatory proteins in the cerebrospinal fluid – but no previous study has directly visualized neuroinflammation in fibromyalgia patients.

A 2015 study by Loggia’s team used combined MR/PET scanning to document neuroinflammation – specifically activation of glial cells – in the brains of patients with chronic back pain. Hypothesizing that similar glial activation might be found in fibromyalgia patients as well, his team used the same PET radiopharmaceutical, which binds to the translocator protein (TSPO) that is overexpressed by activated glial cells, in their study enrolling 20 fibromyalgia patients and 14 control volunteers.

At the same time, Kosek’s team at Karolinska had enrolled a group of 11 patients and an equal number of control participants for a similar study with the TSPO-binding PET tracer. Since that radiopharmaceutical binds to two types of glial cells – microglia and astrocytes – they also imaged 11 patients, 6 who had the TSPO imaging and 5 others, and another 11 controls with a PET tracer that is thought to bind preferentially to astrocytes and not to microglia. At both centers, participants with fibromyalgia completed questionnaires to assess their symptoms. When the MGH team became aware of the similar investigation the Karolinska group had underway, the teams decided to combine their data into a single study.

The results from both centers found that glial activation in several regions of the brains of fibromyalgia patients was significantly greater than it was in control participants. Compared to the MGH team’s chronic back pain study, TSPO elevations were more widespread throughout the brain, which Loggia indicates corresponds to the more complex symptom patterns of fibromyalgia. TSPO levels in a structure called the cingulate gyrus – an area associated with emotional processing where neuroinflammation has been reported in patients with chronic fatigue syndrome – corresponded with patients reported levels of fatigue. The Karolinska team’s studies with the astrocyte-binding tracer found little difference between patients and controls, suggesting that microglia were primarily responsible for the increased neuro-inflammation in fibromyalgia patients.

“The activation of glial cells we observed in our studies releases inflammatory mediators that are thought to sensitize pain pathways and contribute to symptoms such as fatigue,” says Loggia, an assistant professor of Radiology at Harvard Medical School. “The ability to join forces with our colleagues at Karolinska was fantastic, because combining our data and seeing similar results at both sites gives confidence to the reliability of our results.”

This article has been republished from materials provided by Massachusetts General Hospital. Note: material may have been edited for length and content. For further information, please contact the cited source.

Albrecht, D. S., Forsberg, A., Sandström, A., Bergan, C., Kadetoff, D., Protsenko, E., . . . Loggia, M. L. (2018). Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation. Brain, Behavior, and Immunity. doi:10.1016/j.bbi.2018.09.018–8ZbNt7sDLF6bujB3qX9CeJA-hpSQwPHeSLoR5Ju1WYXA6SnOEepdO0o-J7qw_1aGB3nfwldpf30hV3pAvVi7SzJa8fw&_hsmi=68543465



The patient was a 25-year-old man who had been buried by an avalanche during a ski trip and endured 15 minutes without enough oxygen, a condition called hypoxia. After, he developed involuntary muscle jerks of his mouth when he tried to talk and his legs when he tried to walk—but his arms didn’t seem to have been affected. That changed weeks later, explain the authors, the patient’s team of doctors from the University of Munich in Germany. “He was in the rehabilitation clinic, and he was bored, so he started doing Sudokus,” says co-author and neurologist Dr. Berend Feddersen. When the right-handed patient tried to solve a Sudoku puzzle, he experienced quick muscular contractions—clonic seizures—of his left arm. The seizures stopped instantly when he stopped the game.

The authors explain it as a case of reflex epilepsy: seizures that can be triggered by external stimuli like playing games, reading, doing math, touching and bathing in warm water. For this patient, Sudoku, which involves ordering numbers one through nine in a square grid, was such a trigger. Reading, writing and even math alone didn’t have an effect. But visualization-spatial tasks, in which the patient sorted numbers in ascending order, did. “When he solves Sudoku, one of his strategies is to arrange the numbers in some 3D manner,” Feddersen says. “That’s very interesting, because when I do Sudoku, I just make trial and error.”

After analyzing his brain imaging data, the patient’s doctors concluded that the oxygen deprivation caused damage throughout the brain, especially to the U-fibres found all around the brain that contribute to inhibition. “When these kinds of neurons are dying, then you have not enough inhibition, so a loss of U-fibres leads to an overactivation,” Feddersen says. “For him, luckily it was this kind of Sudkoku thing which was the activation, and not another one he does in his daily life.” When the patient stopped solving Sudoku puzzles, the seizures stopped, too. “[He] has been seizure free for more than 5 years,” the study authors write.

Greater activation of neurons on one side of the superior colliculus versus the other signals the detection of a relevant event. Credit: James Herman, Ph.D., National Eye Institute

by Aswini Kanneganti

Perceptual choice behavior, taking action based on the information received from the senses is often described by mathematical models. Although the associated neural activity was interpreted in 2007, translating the simulated evidence to the complex biological process has been challenging. Additionally, identifying the exact code and the behavioral changes to subtle changes in the neural code had proven to be difficult to test.

Researchers at the National Eye Institute (NEI) have investigated the neurons in the superior colliculus (SC) as they have activity related to target probability and comprise an activity map of the visual field. Previous work published by the same team showed that SC neuronal activity correlates with behavior in a covert color-change detection task. So, the scientists hypothesized that SC neuronal activity would be ideal to test decision outcome when a relevant or irrelevant perturbation occurs. The findings were published today in the journal Nature Neuroscience. NEI is part of the National Institutes of Health.

In their new study, Krauzlis, Herman, and colleagues used an “accumulator threshold model” to study how neuronal activity in the superior colliculus relates to behavior. This model assumes that the information builds up over time until it hits a certain threshold, after that a person or animal makes a decision. Because individual neurons can slowly build up information in this way, Herman and Krauzlis elected to use neuronal signals (instead of the experimental stimulus) as the input for their behavior-prediction model. Two non-human primates were tested for their behavioral responses and neuronal firing patterns in response to a covert color-change detection task. The monkeys were trained to release the joystick in response to subtle saturation changes at a relevant (cued) location and ignore changes at an irrelevant (uncued) foil location.

The findings support the notion that neurons in the SC are critical players in allowing us to detect visual objects and events. This structure doesn’t help us recognize what the specific object or event is; instead, it’s the part of the brain that decides something is there at all. By comparing brain activity recorded from the right and left superior colliculi at the same time, the researchers were able to predict whether an animal saw an event. The study provides evidence that, if the difference in neuronal activity between the two sides reached a specific threshold (e.g., neurons in the right superior colliculus fired more strongly than the left), the monkey would release the lever, confirming visualization of the event. To further confirm this finding, the researchers perturbed the neural activity on one side by either inhibiting on increasing the neural tone, and the behavioral responses were altered.

“While we’ve known for a long time that the superior colliculus is involved in perception, we really wanted to know exactly how this part of the brain controls the perceptual choice, and find a way to describe that mechanism with a mathematical model,” said James Herman, Ph.D., lead author of the study.

“The superior colliculus plays a foundational role in our ability to process and detect events,” said Richard Krauzlis, Ph.D., principal investigator in the Laboratory of Sensorimotor Research at NEI and senior author of the study. “This new work not only shows that a specific population of neurons directly cause behavior but also that a commonly used mathematical model can predict behavior based on these neurons.”

One reason for using the color change stimulus, Krauzlis said, was that the superior colliculus doesn’t itself process this information. Instead, other parts of the brain process the changing color and transmit that information to the superior colliculus for a decision to be made. In essence, this simple differential threshold of neuronal activity in the superior colliculus triggers the animal to report the presence of something in the visual field.

“It’s surprising to discover that despite the sophisticated visual machinery that we have in the cerebral cortex, these evolutionarily older structures are still critical for the visual perception that we’re used to,” said Herman.

“For this sort of task, where you’re not asked to say exactly what was the thing, but you’re just saying, did it happen, then this activity in the superior colliculus seems to be both necessary and sufficient,” said Krauzlis.

While the model accurately predicted behavior based on activity in the superior colliculus, the pattern of activation of neurons in the superior colliculus and the signal threshold itself was unique to each monkey, meaning that each monkey had its behavioral signal code.

For more information on how this neural code is decoded, watch the video by Marlene Behrmann, Professor at Carnegie Mellon University.