Tech & Science

Gray Matter Anatomy

5.2_NW0418_BrainLabs_01
05/09/14
In the Magazine
A scarcity of brains for autopsies could be holding back neuroscience Mehau Kulyk/Science Source

As her brain betrayed her, Lea Shmoldas lost the ability to paint, knit, write or even control her bodily functions. But she never lost her mind. With it, she made one final decision before she died: She would donate her brain to science.

There is no cure for multiple system atrophy, a disorder with symptoms similar to those of Parkinson’s disease. It’s extremely rare, affecting about four out of every 100,000 people, according to a report in the journal Brain. There is also no clear cause. Her husband, John, assured Lea that they had made the right choice—that Lea’s brain could help solve these mysteries. “If they can help anybody else avoid the circumstances that we found ourselves in,” John told her, “then it’s the right thing to do.”

By mid-March, Lea, at age 65, could no longer swallow the yogurt that contained her crushed-up pills. She struggled to breathe, and as she lay in bed, John called their two children. She did not have long, he told them. Just after midnight, John awoke to turn Lea on her side. With one touch, he knew.

Within hours, the pickup service of the autopsy lab at the Neuropathology Laboratory at the University of California, Los Angeles, Medical Center arrived to pick up Lea’s body.

“It's remarkable how few brains we have to study for neurodevelopmental disorders like autism, for rare [central nervous system] disorders like DiGeorge syndrome or for control brain tissue, especially at young ages,” says Thomas R. Insel, director of the National Institute of Mental Health, which recently launched the Human NeuroBioBank to increase collection of brain tissue.

The rate of physical autopsies in the U.S. has plummeted by more than 50 percent over the past four decades—to around 5 percent, according to the Centers for Disease Control and Prevention. Hospitals used to be obligated to meet an autopsy quota of 20 percent, but now most bodies are not autopsied unless they are the subjects of investigations or if the patient explicitly asked for one.

Many patients think MRIs and CT scans can tell doctors enough about the body and brain, so there is no need to entertain unpleasant thoughts about having their remains cut up. In addition, neuroimaging scans and the rising popularity of “virtual autopsies” mean scientists can avoid cutting—nice for the patient and family. But some studies have shown that CT and MRI scans frequently miss common causes of sudden death, which are easily identifiable in normal autopsies.

Actual brain tissue can be used to probe deeper—to see gene expression and subareas of the brain implicated in disorders, says Michelle Freund, a project officer with the National Institute of Mental Health. That is why it is such “a very precious limited resource.”

According to Insel, physical brain banks will be critical to President Barack Obama’s BRAIN Initiative, a landmark national project, launched in 2013, bringing together leading researchers seeking to understand the brain’s wiring and how it gives rise to human behavior. The project is largely focused on neurotechnologies but will also involve working with human tissue, Insel says, likely focusing on cell classification, which can only be studied using postmortem tissue.

In March, the president proposed doubling federal funding for the BRAIN Initiative, from $100 million to $200 million. The federal push to unlock what Obama called the mystery behind the “3 pounds of matter that sits between our ears” comes at a crucial time for saw-and-scalpel researchers. The U.S. is facing a critical shortage of forensic pathologists, employing half as many as the 1,000 needed, according to a 2012 report from the Scientific Working Group for Medicolegal Death Investigation. Pay is low, and the job can take an emotional toll.

There remains a stigma attached to donating your brain to science. “Death is very difficult,” says Freund. “Especially if the death is unexpected, family members really don’t want people probing into a loved one’s body.” Even if deceased was preregistered to donate to science, the brain bank will step back if the family objects. “It’s not worth a fight,” she says.

5.2_NW0418_BrainLabs_05 This microscopic image of brain tissue shows changes in the brain due to Cerebral Amyloid Angiopathy. Courtesy of Division of Neuropathology, UCLA

Three days after her death, Lea’s body had been laid out beneath a white towel inside of UCLA’s Neuropathology Laboratory, coral-painted toenails peeking out and a green name tag on her right ankle.

A petite neuropathology fellow, Denise Ng, held the scalpel. Ng started her fellowship at UCLA, under the guidance of Harry Vinters, one of the world’s leading brain researchers, and one of two experts called upon in 2012 to determine the cause of death for Soviet leader Vladimir Lenin. Ng, 32, understands what it is like to lose a loved one to a degenerative brain disorder. Her grandfather had Alzheimer’s.

After pulling the towel off Lea’s face, revealing eyes still traced in blue liner, Ng parted Lea’s hair carefully. She took a thick white string and tied a half-ponytail. “Just in case they want to do an open casket,” Ng said through her surgical mask. “I try to hide all of the incisions.”

She began behind the right ear, cutting along the parted hairline, peeling skin and connective tissue from the skull, and used a saw to carve through bone from the forehead to the ears. With a tug, the dura mater was revealed: a cloth-like, artery-laced protective membrane. “Tough mother,” it means in Latin. Then, the thin pia mater: “soft mother.”

And then to Lea’s brain, 86 billion neurons, 1,230 grams of tissue.

As Lea’s condition worsened over the years, John kept taking her to the doctor for a series of neurological scans, but none provided enough information to pinpoint an exact cause. Now that scientists could actually handle Lea’s brain, they were hoping to figure out once and for all why it failed her.

Ng poked a needle around, looking for the cerebrospinal fluid, which cushions the brain. Once removed, the fluid would be added to UCLA’s collection, available as a resource to researchers for testing. She poked again. “When the needle gives, you know you’re in the right spot,” she said.

Another poke, and still no fluid. She called Audley Broadey over to help.

Broadey is an autopsy technician who spends most of his days in an office with Jimi Hendrix pictures on the wall, waiting for the day’s dissections. At 69, he has been working as an autopsy tech for UCLA’s corpses for 27 years, so he’s a virtuoso in human anatomy. “It’s still interesting to me after all these years,” he says. “The body, once you open it up, tells a whole story. It’s an open book of how you lived your life.” Broadey picked up the needle. With a prick, he filled the 20-milliliter syringe.

Leaning over Lea’s brain, Ng snipped small segments, to be frozen without any tainting from chemicals for dementia studies. “I’m taking sections of the hippocampus,” she said. It’s an area important to neurological disorders such as Alzheimer’s. Then she took some pieces from the right and left temporal sections. Then sections of the midbrain, known to be involved in Parkinson’s disease.

With blue-gloved hands, she removed Lea’s brain and weighed it. So far she could see no obvious abnormalities.

The rest of Lea’s brain would be fixed in formalin and paraformaldehyde, awaiting dissection. Meanwhile, an embalmer would be hard at work making over her body.

Before she died, Lea worried that having an autopsy would mean there could not be an open casket at her funeral. But that, as pathologists point out, is a myth that prevents many people from deciding to donate their bodies to science. Five days after Ng removed Lea’s brain, the family held a viewing. John thought his wife looked beautiful in the white gown she had picked out herself two years earlier. She wore a Cleopatra-style necklace and a diamond barrel ring, with her Louis Vuitton handbag, fur coat and sparkly shoes arranged next to the casket.

5.2_NW0418_BrainLabs_06 Microscopic image of brain tissue shows changes from Cortical Dysplasia. Courtesy of Division of Neuropathology, UCLA

A month later, Ng removed Lea’s brain from the toxic chemicals; it had set into a tofu-like texture. She washed it thoroughly.  

In a room next to the autopsy lab, filled with high-rise bleachers, Ng sliced Lea’s brain in half across the coronal plane, or crown. She continued to slice, separating it into various parts and placing the pieces into trays, as doctors and medical students looked on. They come every Tuesday: dissection day.

Behind Ng, a screen displayed radiology images of Lea’s brain taken in 2008, showing the pons (“bridge” in Latin), a part of the brainstem that serves as a communications hub linking both hemispheres and the spinal cord. Fibers around the pons send messages to the cerebellum, helping plan muscle movement. The pons commonly appears diminished in patients with multiple system atrophy. It is also affected in people who are drunk and having a hard time walking, Ng explained. The screen changed. Digital images from 2010 showed that Lea’s pons had shrunk significantly two years later.

With the pons in hand, Ng noted the fibers that had degenerated or died away. She examined the loca coeruleus, or "dark blue spot,” the area of the pons that plays a role in processing sensory information like sight, sound, smell, touch, and taste. She told her rapt audience it looked pale.

It is too early to tell what kind of contribution Lea’s brain could make to the field, Ng said, but there is infinite potential for brains like hers to lead to new discoveries. That’s why the remaining parts of her brain would be stored in the UCLA bank, which receives about 40 to 50 dementia brains a year, all available for research that might one day lead to a root cause or cure for multiple system atrophy.

But sometimes, discoveries happen much faster. In a recent breakthrough paper in the journal Science, researchers from the Salk Institute and the University of Virginia reported that they had studied DNA taken from brain cells and found that many neurons had mutations. Before this discovery, scientists believed all cells in a single brain shared the same DNA. The findings blew the field of brain study wide open. Could these mutations be responsible for differences in personality? Could this be the reason why some people are mentally gifted and others are mentally ill? The study, Insel says, “reminds us that there is no substitute for studying the brain.”

The medical students (who came only to witness the initial slicing) left, and Ng went back to Lea’s brain. She slivered micro-thin parts of the pons that would be embedded in wax so she could examine them more closely under a microscope. Her hands moving steadily with precision, she worked beneath a colorful wall mural that read, “Hic locus est ubi mors gaudet succurrere vitae.”

“This is the place where death delights in helping life.”

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