How Far Should Brain Researchers Go?

Recent advances in neuroscience enable us to manipulate the workings of the brain and intervene to treat some neurological disorders. How far should researchers go in their quest to understand this complex organ and improve people’s quality of life, and to what extent should they be responsible for making sure that others do not misuse their findings? Researchers addressed such dilemmas during the William Safire Seminar on Neuroethics at the 9^th FENS Forum of Neuroscience held in Milan, Italy, earlier this month.

Vincent Walsh, a professor of cognitive neuroscience at University College London, discussed the use of non-invasive brain stimulation techniques such as transcranial direct current stimulation. Studies published in the past few years purport to show that these techniques can enhance a variety of brain functions, such as memory, numeracy, and language learning. Furthermore, cheap DIY brain stimulation devices are now available commercially, making it possible for anyone to attempt to boost their brain function.

Walsh questioned the reliability of the findings. “We’re at a stage where the quality control [of these studies] has become very poor,” he said. “There are some very bold claims, but there isn’t a single significant replication between laboratories. One of the most highly cited papers in the field comes from my own laboratory, and I’ve twice failed to replicate it myself.”

He also pointed out that the enhancement effects seen under laboratory conditions are unlikely to transfer to our daily lives. “The enhancement effects seen in the laboratory are significant and meaningful, [but] there are no significant demonstrations of them in real-world situations.”

“We are no longer in control of what stories the general public hear about our data,” he added. “They can decide which papers are worth listening to before any scientific consensus has been reached, so we have a duty to be much more measured in the claims we make.”

Walsh thinks that brain stimulation should not be used to enhance performance in sports, education, or other realms. “You don’t get good at anything with a short-term fix, but with years of training and judgment. If we allow [cognitive enhancement] into education then we lose the whole idea of what education is about.”

Clinical neuropsychologist Barbara Sahakian of the University of Cambridge, who chaired the seminar, said that enhancement may be desirable in certain situations.  “We may want to enhance military personnel in a war situation, or doctors who are working late at night, in order to make sure they remain awake and alert.”

Itzhak Fried, a professor of neurosurgery and psychiatry at the University of California, Los Angeles, discussed the ethics of performing experiments on people with epilepsy during brain surgery. Most epileptic patients respond well to anticonvulsant drugs, but in the minority who do not, surgery is performed as a last resort. Using a technique pioneered by Wilder Penfield in the 1930s, surgeons can use electrodes to identify and remove the brain tissue producing the seizures while the patient is fully conscious.

After placing the electrodes onto the brain surface, the surgeon has to wait, sometimes for many days, for the patient to have a seizure. This provides the rare opportunity to study the brain directly, and Fried, who also directs UCLA’s Adult Epilepsy Surgery Program, is one of the pioneers of taking single cell recordings from human brain cells under these conditions.

“We are very privileged [to be able to do this], but it raises serious ethical issues,” said Fried. Surgery is perfectly justified, he explained, but performing experiments is not-while it may provide some insight into how the brain works, it is of no benefit whatsoever to the patient.

All members of Fried’s neurosurgery program are required to examine and adhere to the Belmont Report, which was published in 1979, and which sets out ethical principles and guidelines for the protection of study participants. The three principles outlined in the report are:

1. Respect: In all cases, researchers must protect patients’ autonomy, treat them with the utmost courtesy and respect, and only enrol them in such studies after informed consent;
2. Beneficence: Researchers must maximise the benefits of their experiments, while at the same time avoiding at all costs causing harm to the participants; and,
3. Justice: Researchers must ensure that their experiments are designed well and that their procedures are safe, non-exploitative, and administered fairly.

“We prolong the operative time and we may cause patient discomfort and injury to the brain tissue, so we have a special responsibility to do good science and ask good questions,” says Fried, “but this is a very delicate and unique situation, and there are no obvious answers to these ethical questions.”

Petra Huppi, director of the Division of Child Development and Growth at the University of Geneva, uses magnetic resonance imaging to understand developmental brain disorders, particularly in pre-term infants, who are at far higher risk of such disorders than are full-term infants.

The number of pre-term infants born each year is rising in most countries, and although improvements in medicine have led to improved outcomes and better quality of life for many, those treating them still face difficult ethical questions. “Pediatricians are committed to promoting childrens’ health, treating their illnesses, and saving their lives,” said Huppi, “but sometimes we are forced to wrestle with dreadful choices.”

Should they, for example, save a very premature infant’s life, despite the possibility that the child will develop severe neurological impairments? “It’s our professional responsibility to face these difficult questions,” said Huppi. “How can we honour these responsibilities, and how can imaging technologies help us in taking them up?”

Head ultrasound is an imaging technique that can reveal signs of brain haemorrhage in pre-term infants. Following its introduction in the 1970s, withdrawal of life support was recommended for pre-terms whose ultrasound scans showed signs of brain hemorrhage, and during the 1980s and 90s, care was withdrawn from between 35% and 80% of such infants.

“We were playing God,” says Huppi. “We now know that head ultrasound only has a positive predictive value of 48%, and that a large number of babies with head ultrasound abnormalities have normal outcomes.” Furthermore, the brain is far more resilient than we once thought it was, and can often compensate for damage via its structural and functional plasticity, especially with early medical and social interventions.

Methods such as diffusion tensor imaging can now be used to visualise brain connectivity in pre-term infants, and to track the changes in connectivity that occur as a result of interventions. They can therefore provide more accurate prognoses for pre-term infants than traditional ultrasound.

“We’ve convincingly shown that the brain is plastic using these imaging methodologies, and we can better evaluate the environmental factors that can help us shape brain development,” said Huppi. “When we intervene with an enriched care program we can have a positive effect on brain development and cognitive performance, and these effects last up to school age.”

“The early years have the highest yield for effects on cognitive development, and enriched environments in the first years of life can greatly improve the cognitive capacities of pre-term infants,” she added. “We’d really like to get to the point when the quality of life for pre-term infants is the same for others.”

Writer Moheb Costandi sits on the Board of Directors of the International Neuroethics Society.