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But the biggest findings in this field may well come from tinier brains.
In a review published 30 March in Molecular Psychiatry, a group of Australian researchersargues thatflies, bees, worms and fish have much to offer psychiatric research.
Even the most primitive nervous systems share some important features with ours. Synapses in the worm Caenorhabditis elegans, for instance, relay chemical messages using the same neurotransmitters we do. The layout of various brain regions in humans and zebrafish is also remarkably similar.
Obviously, these organisms don’t display behavioral hallmarks of psychiatric diseases — imagine measuring the social anxiety of an autistic worm, or hallucinations in a schizophrenic fish. Still, they do show some explicit behaviors that could be informative.
For example, honeybees are dependent on the social structure of their hive; when they are deprived of those interactions, their brain does not wire properly and their memory declines.
These models offer two major advantages over rodents. First, their biology is simpler. C. elegans has just 302 neurons — compared with 4 million in a mouse or 100 billion in a human — and scientists have already worked out the position, shape and connectivity of each one.
Second, they allow for faster, more efficient experimental manipulations. For example, the fruit fly carries roughly 75 percent of all known human disease genes, but because of its 10-day generation time, its genome is infinitely easier to tinker with. Likewise, because zebrafish embryos are transparent, scientists can quickly see structural effects of specific genetic changes.
Some autism researchers have already taken advantage of these model systems. In February, researchers reported that honeybee brains surge with the autism-linked neurexin and neuroligin proteins during learning. Other groups have shown that FMRP, the protein missing in fragile X, controls sleep behaviors in fruit flies.
The reviewers urge scientists to do more “species hopping” — synthesizing findings from many organisms of varying complexity.
Back in March, I wrote about a high-profile criminal case that was the first to use functional magnetic resonance imaging (fMRI). The defendant was a man who raped and murdered several women. His lawyers used the brain scanning technology to argue that their client is a psychopath, and therefore not deserving of the death penalty. It didn’t work.
Now, it looks like another hyped application of fMRI — lie detection — may also have its first day in court, depending on what one judge decides. As ScienceInsider reports:
The defendant in the case is a psychiatrist named Lorne Semrau, who is accused of defrauding Medicare and Medicaid. As reported last week by Wired Science, Semrau claims he had no intention to do so and has retained the services of Cephos, a Massachusetts-based company that sells fMRI-based lie-detection services, to help establish that he is telling the truth. Court documents indicate that Semrau’s lawyer introduced a motion for Cephos CEO Steven Laken to testify as an expert witness on his behalf.
Today [May 13], Judge Tu Pham will hear testimony for and against the inclusion of the fMRI evidence in what’s known as a Daubert hearing, which takes its name from a 1995 Supreme Court case that established guidelines for the admissibility of expert testimony in federal cases. These include factors such as the error rates associated with a given technology, whether it is supported by published research, and whether it is accepted by the scientific community.
No one knows what causes the condition, defined by the inability to recognize and interpret sounds. It appears in an estimated two to five percent of children, and is only beginning to get a bit of public attention.
Last week, speech pathologist Lois Kam Heymann published a book about APD called The Sound of Hope. The book has made a splash thanks to comedian Rosie O’Donnell, who wrote about her 10-year-old son’s struggle with the disorder in the book’s foreword.
APD is often misdiagnosed as autism. Children with either disorder share some overt symptoms — such as a sparse vocabulary, poor grades and trouble paying attention — and both conditions are characterized by difficulties in understanding abstract metaphors. The conversation delays in children with APD can sometimes lead to impaired social interactions and isolation reminiscent of autism.
At the same time, some people with autism report extreme sensitivities to sounds, and a growing number of researchers are taking a close look at auditory processing problems in autism.
For example, using brain imaging, Tim Roberts at Children’s Hospital of Philadelphia has found that the brains of children with autism respond to sounds a split second slower than do those of healthy children. And a few groups have identified distinctive sound patterns in the speech of children with autism.
There are obvious differences between APD and autism. Autism often includes problems in other sensory systems, including vision, touch and smell. Children with autism often have low intelligence quotients or mental retardation, whereas those with APD usually have normal intelligence.
So far, there’s also one promising overlap: children with either condition can be helped by speech therapy and intensive behavioral intervention.
We’re making rapid strides in understanding the brain, but we still know little about what genetic or molecular problems cause mental illnesses.
There hasn’t been a new schizophrenia drug in 50 years, or a depression drug in 20. Nor are there any drugs to improve the hallmark symptoms of autism.
This “frustrating lack of progress” has prompted several big names in psychiatry and genetics — including Nobel Laureates Eric Kandel and Jim Watson — to call for a 10-year international scheme that would combine the latest in genetics and animal research to combat psychiatric diseases.
In the past few years, research on these diseases has revolved around genetic association studies: researchers compare the genes of those with a given disorder with healthy controls and try to pinpoint candidate genes that they then study in mouse models.
But that approach hasn’t really worked because behavior — and behavioral illness — is more often the result of several different genetic mutations, epigenetic changes and brain lesions acting together.
Writing in the March 26 issue of Science, these experts argue that psychiatric research should instead integrate whole-genome sequencing — which doesn’t rely on preconceived notions about which genes or chromosomal regions are important — with more sophisticated studies of specific brain circuits, in which all genetic snags converge.
The grand plan comes with a grander price tag, however: $200 million a year over the next decade. But compare that with income lost to mental illness in the U.S. alone each year: at least $200 billion.
My Nature news feature about using brain scans in court went up yesterday, and the editors are keeping it in front of the pay wall (at least for now). So no reason not to go check it out (plus related podcast)!
The first comment on the piece (pasted below) is a doozy, and I’m curious about what others think about whether psychopathy should be an aggravating or a mitigating factor:
Read the rest of this entry »
The close-ups are so striking, they made the cover of the 11 January Journal of Cell Biology.
To capture this pretty picture, the researchers used a complex technique called electron cryotomography. They first froze rat brain cells in action at temperatures as low as -165 degrees Celsius, then looked at the cells at different angles using an electron microscope and, finally, reconstructed them in three dimensions on a computer.
There are other methods to look at synapses, but they require cells to be fixed in chemicals for a long time, which can distort the final product. Light microscopy, a much older and more popular technique, illuminates living cells, but only down to 400 nanometers.
Electron cryotomography seems to beat all of these: its flash-freezing preserves the cell’s structure, and its resolution is 5 nanometers — the size of a few dozen atoms.
The technique reveals the workings of some of the tiny protein filaments scattered across a synapse, whose role had been largely unknown before. One type of filament, dubbed ‘tethers’, anchors synaptic vesicles — the bubble-like structures that shuttle chemical messengers inside the cell — to the cell membrane. That way, when the cell receives the appropriate electric signal, the vesicles are in the right position to release the chemicals into the synapse.
Courtesy: U. of Washington Institute for Learning & Brain Sciences
In typical conversation, people speak at a rate of 250 milliseconds per syllable. So imagine how confusing it would be if you lagged behind — even if only by a fraction of a second.
That tiny delay may be what’s provoking the language problems in some children with autism.
Tim Roberts, a radiologist at the Children’s Hospital of Philadelphia, has been studying the phenomenon for the last decade. He uses magnetoencephalography, or MEG, the ‘hair dryer’ brain imaging method that uses magnetic fields to detect changes in brain activity on the order of 10 milliseconds or less.
Last week, his team reported that when listening to tones of different frequencies, children with autism give brain responses in their right hemispheres about 11 milliseconds slower than healthy controls do. In other, unpublished work, Roberts found a much longer delay — about 50 milliseconds — when children with the disorder process speech sounds, such as ‘ah’ or ‘ou’.
The average age of children in the study was 10 years. If the findings are similar in babies and toddlers with autism, Roberts says this lag measurement may be a reliable marker for diagnosing the disorder, even before other symptoms appear.
MEG would be particularly useful for young children because it’s non-invasive and doesn’t require them to perform a difficult task. On the downside, a MEG scan isn’t a realistic option for the majority of children with autism — there are only about 100 machines worldwide.
Meet ‘The Novack Experience’, a Philadelphia cover band of earnest rockers who, oh yeah, just happen to be doctors and medical students. The energetic lead is Dennis Novack, 63, an internist and an associate dean at Drexel University College of Medicine. All of the bands featured in the clip competed recently in a med school ‘battle of the bands’ concert, covered by The Scientist.
How do they find time to practice?? Here’s what members of one of the other bands, ‘Freaks of Nurture’, said:
Despite the intense pressure of PhD programs and demands of med school, the band members have found support for their music among their academic mentors. After hearing the band play, “the chair said I should spend more time on my music,” laughed [band leader Alec] Schmaier. Being known as the scientist or resident who plays in a band has its benefits, say band members. In the sea of medical school students, having a unique hobby allows you to stand out in the crowd, said singer Ehimare Akhabue. The dual identity can have other benefits, added bass player Rob Fenning. Rather than getting grilled on the difficult questions during med school interviews, questions invariably veer to what it’s like to play in a band, he said.
“The plan is to put me inside the fMRI scanner, apply burning heat, and see whether I can train myself to regulate my pain.”
That’s from reporter Erik Vance, who recently visited the lab of Stanford neurologist Sean Mackey. In a new feature for Nature, Vance describes Mackey’s research through the lens of being an actual participant (fair warning, this is uncomfortable to read):
Inside the coffin-sized tube of the fMRI machine, spasms in my back from its powerful magnet distract from the burning plate strapped again to my arm. On a screen above, I can see a squiggly line that represents the activity in a part of my anterior cingulate cortex. Mackey asks that I envision the heat as alternately searing and soothing. The aim is to master control of the line so that it (and thus my pain) goes up and down. As I switch between these visions the line on the screen twitches up and down.
It is surprisingly difficult. Willpower and meditation have little effect, and after two hours it is increasingly hard to make the stubborn little line move at all.
In this case, I think Vance’s first-person account is remarkably effective way to tell the story. Pain is fundamentally experiential, after all.
It seems like I’m hearing more and more about journalists who put themselves through odd or unpleasant situations for the sake of a story. Ted Conover became a guard at Sing Sing to find out what prison life is really like. Slate‘s Emily Yoffe, aka The Human Guinea Pig, has for six years written firsthand accounts, such as what it’s like to: be a daycare worker, a member of the Washington Nationals grounds crew, or compete in a matzo-ball eating competition.
As On the Media pointed out last year during an interview with Conover, this approach is usually extremely popular with readers. But when is going undercover unethical? Or worse — when does it become a gimmick?
Because these defects are seen during a critical period of learning, they could prevent developing brain cells from linking up to appropriate brain circuits, says lead investigator Carlos Portera-Cailliau, assistant professor of neurology and neurobiology at the University of California in Los Angeles. “This presumably has serious consequences for the ability of these mice to learn,” he says.
