Neuroscience's Future Includes Medical Advances and Ethical Quandaries

Advances in neuroscience are changing our understanding of the brain and opening doors to potential treatment of previously intractable disorders, but they also are posing tough ethical questions such as whether it is ever permissible (or possible) to alter memories, enhance cognition, or read a mind.

More broadly, these research advances are raising questions that could encroach on traditional concepts of free will and personal responsibility, according to speakers at the annual meeting of the International Neuroethics Society — held 13-14 Nov. at the AAAS building in Washington, D.C.

AAAS CEO Alan I. Leshner, who moderated a session on the future of neuroscience research and ethical implications, said that scientists must anticipate questions from the public on what their research means for concepts of "the self" and "the soul."

"When you say the mind is the product of a series of physical, chemical events" people get anxious, said Leshner, a physiological psychologist by training and a former director of the National Institute on Drug Abuse. "As we look into the future, we need to be prepared for a much wider array of ethics and values issues than most of us in neuroscience have thought about in the past."

Scientists alone are not going to be able to control the use of new developments in the neurosciences. Thomas Insel, director of the National Institute of Mental Health (NIMH), noted how frequently neuroimaging and other techniques are being "used, and often misused, by lots of other people."

Courts have seen a surge in the number of defendants arguing that their brains were to blame for their crimes and relying on questionable brain scans and other unproven neuroscience, experts say. In some cases, such evidence has helped to reduce defendants' sentences.

Some days, Insel said, it seems that neuroscience "is used by everybody except mental health providers, which I think really tells you something — that judges now are learning about neuroimaging, psychiatrists not so much, and social workers, who are the main providers for mental health care in the United States, not at all."

George Koob, director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), said he doesn't have any pat answer to the "my brain made me do it" defense. There is some evidence, he said, that neurons in certain command centers of the brain are firing even before a person becomes consciously aware of making a choice.

The basal ganglia, a group of interconnected brain areas located deep in the cerebral cortex, help establish routine behavior patterns, Koob said. "That system makes selections all the time and establishes, ultimately in a hierarchical way, the habits that we engage in."

Research suggests that "moments before you are aware of what you going to do next, a time in which you subjectively have complete freedom to behave however you please, your brain has already determined what you are going to do," Koob said.

Research also has shown that drug addiction is a disease tied to dysfunction in the brain's reward pathways and centers for impulse control and executive function. "Are there times when my brain really did make me do it?" Koob asked. "I don't necessarily have an answer to that." But rather than discussing a fuzzy concept of free will, he said, it may be more appropriate to ask whether a person is capable of self-control or what Koob calls "self-regulation."

A part of the brain that controls self-regulation, Koob said, is the ventral medial region of the prefrontal cortex (located at the front of the brain, just behind the forehead). Researchers are finding that region can be damaged or compromised in alcoholics and other substance abusers as well as in persons with post-traumatic stress disorder (PTSD). It also is not fully developed in the adolescent brain, and that can lead to impulsive, risky behavior and inappropriate decision making.

NIDA, NIAAA and several other NIH agencies are planning a decade-long longitudinal study of children and their risks of becoming substance abusers as adolescents. Ethics will be a part of the conversation. If the study suggests that some children are at increased risk, what obligations do researchers have to inform them and their parents and pursue preventive measures?

When it comes brain disorders generally, Insel said, it is crucial to identify people at risk before symptoms emerge. "Once you have symptoms emerging, you are in the eighth or ninth inning," he said. "And you've got to get there in the first or second or third inning if you want to really be able to win the game."

Yet there is a public reluctance regarding efforts to find early markers for potential disorders. "When you identify symptoms early in heart disease and cancer," Insel said, "it's considered exciting and heroic and people are cheering."

But when researchers use cognitive testing and imaging methods to try to find warning signs of brain disorders such as autism or schizophrenia in children and adolescents, "People get really anxious," Insel said. Researchers and medical professionals must weigh the risks of labeling a child prematurely with the potential benefits of preventive intervention, he said.

Insel also addressed the gap between the thousands of research papers by neuroscientists and their impact in the real world. He worries that the field will continue to explode while "people with brain disorders who you will see on the streets of Washington, covered up in blankets because they are homeless, are not going to be any better off. And that, I think, is an ethical problem that we have to figure out."

Animal research has made some tantalizing discoveries, he said, but that is not being translated into treatments and cures for human patients. "It's amazing to think of what we can do if you're a mouse with MS or Alzheimer's, or a mouse with ALS, or a mouse with autism," Insel said. "We can fix you." But despite, for example, the very real advances in understanding the genomics and biology of a rare, autism-related disorder called Phelan-McDermid syndrome, effective treatment remains elusive and parents with affected children tell Insel: "Hey, I don't have forever here and this is not a mouse. Help me."

As Insel put it, they are asking: Where is the deliverable? "That's what keeps me up at night," he said. "It's worrying that we are doing more and more sophisticated science that is not turning into more and more impactful care for people who have brain disorders."

Still, the promise of neuroscience is real. Geoffrey Ling, director of the biological technologies office at the Pentagon's Defense Advanced Research Projects Agency (DARPA), said that new tools and imaging methods are allowing scientists to understand the human brain as never before.

"The next 10 or 20 years are going to be revolutionary," Ling said. "I deeply believe that."

He cited the remarkable advances, funded by DARPA and others, in use of prosthetics that can be manipulated by thought alone. Jan Scheuermann, a woman paralyzed from the neck down, is able to use a robot arm to grasp objects. Microelectrode arrays implanted in her brain cells connect to electronic circuitry that controls movement of the prosthetic arm. Ling said her skills have greatly improved since she first received the brain implant in early 2012. She recently used a direct interface from her brain to a flight simulator for the F-35 Joint Strike Fighter, Ling said, and was able to "fly" the craft in level flight.

"She was able to have that level of control," Ling said. "That shows the power of direct interface with assistive devices."

Ling also predicted the development of more sophisticated imaging devices that will allow even better insight on the inner workings of the brain and the central nervous system. He noted that the best tool available today, the magnetic resonance imaging device or MRI, has been around since the 1980s. A variant, the functional MRI or fMRI, was developed in the 1990s. New imaging tools that provide more physiologically relevant data are on the horizon, Ling said.

He also noted progress toward a potential diagnostic tool for Alzheimer's disease. Researchers at Georgetown University and six other institutions announced earlier this year that a new blood test has been developed that can predict with 90 percent accuracy if a healthy person will develop mild cognitive impairment (MCI) or Alzheimer's disease within three years.

The ethical dilemma is obvious, however. Ling said patients may be told: "You have mild cognitive changes, but in three years' time you are guaranteed to have grade 2 or grade 3 Alzheimer's disease." And there is nothing yet that clinicians can do for you. "Is that ethical to tell the patient that," Ling asked. Or is it ethical to tell patients they carry the dominant gene for Huntington's disease, a devastating neurological disorder that strikes by age 40? Ling is confident advances in treatment in the coming decades will ease such dilemmas.

While he urged a dose of humility, noting that scientists still know "Much less about the brain than we know about the heart, the kidney, the liver, the lung," Insel said clinicians must provide care that is aligned with what is known today. "That is the moral mandate — bridging the gap between what we know from research and what we do in practice for those with brain disorders," he said.