How does the olfactory apparatus of vertebrates detect and discriminate thousands of odors? Our approach to elucidating the mechanisms of olfactory discrimination involves the characterization of odorant receptors and the neural pathways that they activate. We are also interested in the developmental mechanisms responsible for specifying odorant receptor expression in olfactory neurons and the pathfinding of these cells’ axons to their appropriate targets. Finally, our lab is developing DNA microarray technologies to elucidate genome-wide patterns of gene expression in the nervous system.
This is a timely topic since there are some important football games today and it’s almost the superbowl. Last year the NFL donated $30million to the NIH for brain research on the impacts of football. Very necessary since a) there’s a lot of evidence linking brain injury to football and b) the league has been under scrutiny lately because of this. However, it seems as though the NFL may be trying to influence the type of research being conducted. ESPN reports:
Three of the NFL’s top health and safety officers confronted the National Institutes of Health last June after the NIH selected a Boston University researcher to lead a major study on football and brain disease, Outside the Lines has learned.
The new information contradicts denials by the NFL and a foundation it partners with that the league had any involvement or input in the fate of a $16 million study to find methods to diagnose — in living patients — chronic traumatic encephalopathy, a brain disease found in dozens of deceased NFL players.
Outside the Lines reported in December that the NFL, which in 2012 promised an “unrestricted” $30 million gift to the NIH for brain research, backed out of funding the new study over concerns about the lead researcher, Boston University’s Dr. Robert Stern, who has been critical of the league. In the story, a senior NIH official said that the NFL retained veto power over projects it might fund with its donation, and it effectively used that power in the Stern study. Almost immediately, NFL spokesman Brian McCarthy deemed the report “inaccurate.” The league and the foundation both said the league’s overall donation comes with no strings attached.
But Dr. Walter Koroshetz, director of the National Institute for Neurological Disorders and Stroke, told Outside the Lines this week that the NFL raised several concerns about Stern’s selection during a June conference call that included Jeff Miller, the NFL’s senior vice president for health and safety; Dr. Richard Ellenbogen, co-chairman of the Head, Neck and Spine Committee; and Dr. Mitch Berger, chairman of the sub-committee on the long-term effects of brain and spine injury.
The NFL alleged that the review process that led to Stern’s selection was marred by conflicts of interest, Koroshetz said. In addition, league officials charged that Stern was biased because he had filed an affidavit opposing the settlement of a lawsuit in which thousands of former players accused the NFL of hiding the link between football and brain damage.
And now, weak, short of breath, my once-firm muscles melted away by cancer, I find my thoughts, increasingly, not on the supernatural or spiritual, but on what is meant by living a good and worthwhile life — achieving a sense of peace within oneself. I find my thoughts drifting to the Sabbath, the day of rest, the seventh day of the week, and perhaps the seventh day of one’s life as well, when one can feel that one’s work is done, and one may, in good conscience, rest.
Science Of Sadness And Joy: ‘Inside Out’ Gets Childhood Emotions Right
JUNE 13, 2015
Joy (left, voiced by Amy Poehler) and Sadness (voiced by Phyllis Smith) catch a ride on the Train of Thought in Pixar’s Inside Out. The movie opens in theaters nationwide June 19.
Hollywood’s version of science often asks us to believe that dinosaurs can be cloned from ancient DNA (they can’t), or that the next ice age could develop in just a few days (it couldn’t).
But Pixar’s filmInside Out is an animated fantasy that remains remarkably true to what scientists have learned about the mind, emotion and memory.
The film is about an 11-year-old girl named Riley who moves from her happy home in Minnesota to the West Coast, where she has no friends and pizza is made with broccoli. Much of the film is spent inside Riley’s mind, which features a control center manned by five personified emotions: Joy, Sadness, Fear, Anger and Disgust.
“I think they really nailed it,” says Dacher Keltner, a professor of psychology at the University of California, Berkeley who worked as a consultant to the filmmakers.
The movie does a really good job of portraying what it’s like to be 11, Keltner says. “It zeroes in on one of the most poignant times in an individual’s life, which is the transition to the preteen and early teen years, where kids — and, I think, in particular girls — start to really powerfully feel the loss of childhood,” he says.
As the filmmakers were working, they would fire off emails to Keltner and to Paul Ekman, a pioneer in the study of emotions. The process helped create a movie that’s true to the underlying science when it shows things like how emotions tend to color Riley’s perception of the world.
“When you are in a fearful state, everything is imbued with threat and uncertainty and peril,” Keltner says. And when Riley is sad, he says, even her happy memories take on a bluish hue.
The filmmakers get a lot of other scientific details right. Inside Riley’s head, you see memories get locked in during sleep, experiences transformed into abstractions, and guards protecting the subconscious.
There are a few departures from the scientific norm. Long-term memories are portrayed as immutable snow globes, though scientists know these memories actually tend to change over time. And Riley gets five basic emotions instead of the six often described in textbooks. (“Surprise,” apparently, didn’t make the cut.)
Also disgust is present in a pretty mild form — the reaction a child has to eating broccoli. The film plays down a more powerful version of disgust, “like if you suddenly eat a piece of food and it has a worm in it, or it’s rotting, Keltner says.
One of the film’s high points, though, is its depiction of sadness, Keltner says. In many books and movies for kids, he says, sadness is dismissed as a negative emotion with no important role.
In Inside Out, star-shaped Joy gets more screen time. But when the emotions are in danger of getting lost in the endless corridors of long-term memory, it is Sadness, downcast and shaped like a blue teardrop, who emerges as an unlikely heroine.
For kids, Keltner says, that makes “a nice statement about how important sadness is to our understanding of who we are.”
Alzheimer’s disease is the most common form of dementia in older adults. At the moment there is no cure, but many clinicians feel that the earlier one is diagnosed, the better the possibilities are for treatment or slowing the disease.
But developing treatments or prevention approaches for Alzheimer’s disease is difficult. There is no biomarker (for example a blood test) or definitive medical test for it and there is no set age where people develop memory impairments and dementia.
Indeed, people can develop Alzheimer’s disease as young as 30 or well into old age. This is a real challenge for diagnosing Alzheimer’s in its early stages.
But in people with Down syndrome there is an age-dependent progression of changes associated with Alzheimer’s disease. This makes it much easier to map when and what kinds of changes happen in the brain in the early stages of the disease.
If we can understand how and when changes in the brain start to happen in people with Down syndrome, that could help us find ways to slow or prevent Alzheimer’s disease in this vulnerable group and for others with Alzheimer’s.
Adults with Down syndrome may provide insights for Alzheimer’s
The lifespan of people with Down syndrome has dramatically improved from 25 years in 1983 to over 60 years today although some minority groups still have lower lifespans.
Although many people with Down syndrome remain healthy as they get older, most are vulnerable to the development of Alzheimer’s disease.
Virtually all people with Down syndrome over 40 years old develop Alzheimer’s disease. It is estimated that over 70% in their 60’s and older also have dementia. This is a much higher rate than people without Down syndrome.
An image of beta-amyloid plaques in a 67-year-old patient with Down syndrome Elizabeth Head, Author provided
Over 95% of people with Down syndrome have a full extra copy of chromosome 21. There are two other causes of Down syndrome that include partial trisomy 21 where only a piece of chromosome 21 and associated genes are triplicated. The third type of Down syndrome is called mosaicism, where not all of the cells in the body have a fully extra copy of chromosome 21.
The gene for amyloid precursor protein, which is thought to be important for Alzheimer’s disease, is located on chromosome 21.
This amyloid precursor protein is cut into smaller pieces and the smaller protein, called beta-amyloid, is toxic to the cells in our brain or neurons. It collects into structures called beta-amyloid plaques, which are a hallmark of Alzheimer’s in all people. The plaques make it hard for neurons to communicate.
In people without Down syndrome there are normally two copies of this gene. In people with Down syndrome there are three copies of the gene because of the extra copy of chromosome 21. That means from an early age people with Down syndrome are making more of the beta-amyloid protein.
Beta-amyloid plaques are consistently observed in the brains of those with Down syndrome in their 30s, but they have also been reported in people eight- to 15 years old.
How does the brain change in people with Down syndrome as they get older?
Neurofibrillary tangles. Elizabeth Head, Author provided
The second feature of Alzheimer’s disease is neurofibrillary tangles. These are made up of a protein called tau that builds up inside of neurons in the brain and prevents them from functioning properly.
For people without Down syndrome, these neurofibrillary tangles can start to develop anywhere from age 30 to over 100 years. But for people with Down syndrome these tangles do not start to accumulate until they are over 40 years old. This is another example of how it may be easier to understand Alzheimer’s disease in people with Down syndrome because we know the ages at which neurofibrillary tangles begin.
Cerebrovascular pathology. Elizabeth Head, Author provided
When we learn more about when these changes happen, we can also start to think about ways to prevent or reverse them.
What does dementia look like in people with Down syndrome?
Many people are aware of the early warning signs of Alzheimer’s disease and that the loss of short-term memory is one of the key features.
For people with Down syndrome the evidence suggests similar changes may also happen in cognition and behavior as in the development of Alzheimer’s disease. Memory and thinking changes also appear in dementia with Down syndrome, but are more difficult to observe because of the nature of the intellectual disability.
But other changes, like social withdrawal, mood changes (including anxiety and depression), aggressive behavior, lack of interest in usual activities, change in sleep pattern and irritability, are easier to detect in Down syndrome. Similar changes also happen in people without Down syndrome who develop dementia in the moderate to severe stages of the disease.
What changes can we see in the brain by imaging?
The brains of people with Down syndrome have some differences compared to people of a similar age without Down syndrome. For example, in people in their 40s, the hippocampus of someone with Down syndrome may already show signs of atrophy (getting smaller) signaling early Alzheimer’s disease, a change we do not usually see in people without Down syndrome.
Our research group has been studying the connections between different brain structures by measuring white matter integrity – which is how well the long axons, the threadlike parts of neurons that connect to other neurons, are functioning. We do this by measuring how water molecules move along axons in people with Down syndrome.
We have found that the frontal lobes in people with Down syndrome may become increasingly disconnected from other parts of the brain. Similar changes in the white matter connections happen in Alzheimer’s disease in general.
In our study we see these changes in people in their late 30s, when we typically do not see these changes at all in people without Down syndrome.
If we can understand the predictive value of these images then we can determine what age is best to intervene and prevent the development of Alzheimer’s disease not only in Down syndrome but also in the general population.
Not everyone with Down syndrome develops Alzheimer’s disease
Some older adults with Down syndrome never develop dementia despite a genetic vulnerability to the disease. Because of this, we may get some fascinating new leads on ways to promote healthy brain aging in people with Down syndrome that may also be translated to the larger population.
Following people with Down syndrome as they age will provide exciting new approaches to promote brain health in this vulnerable group of individuals. To facilitate aging studies in Down syndrome, the National Institutes of Child Health and Development has taken the initiative to launch a Down Syndrome Registry that will help connect families with researchers and resources – and hopefully benefit people with Down syndrome by identifying ways to enrich their development and reduce risk of disease.
Oliver Sacks is a rare soul-reader among us, a golden heart that beats in resonance with an enlightened intellect and a refinement of feeling that finds the humanity cloistered in the deepest recesses of a damaged life. The stories he tells are the stories of his patients, but also his own; he knows and tells us, beautifully, how each experience touches and transforms his own, how each tale he narrates becomes part of his own narrative, his own life story. In this, and in writings such as Uncle Tungsten or Altered States, his New Yorker essay on hallucinatory drugs, we learn that to Oliver life is a grand experiment of the human condition, an experiment that can only bear fruit if we have the courage to engage fully with it. Oliver is the bravest man I know.