This Special Music Helped Preemie Babies’ Brains Develop
Listening to music helped preterm babies' brains develop, according to the results of a new Swiss study.
Move over, Baby Einstein: New research from Switzerland shows that listening to soothing music in the first weeks of life helps encourage brain development in preterm babies.
For the study, the scientists recruited a harpist and a new-age musician to compose three pieces of music.
The Lowdown
Children who are born prematurely, between 24 and 32 weeks of pregnancy, are far more likely to survive today than they used to be—but because their brains are less developed at birth, they're still at high risk for learning difficulties and emotional disorders later in life.
Researchers in Geneva thought that the unfamiliar and stressful noises in neonatal intensive care units might be partially responsible. After all, a hospital ward filled with alarms, other infants crying, and adults bustling in and out is far more disruptive than the quiet in-utero environment the babies are used to. They decided to test whether listening to pleasant music could have a positive, counterbalancing effect on the babies' brain development.
Led by Dr. Petra Hüppi at the University of Geneva, the scientists recruited Swiss harpist and new-age musician Andreas Vollenweider (who has collaborated with the likes of Carly Simon, Bryan Adams, and Bobby McFerrin). Vollenweider developed three pieces of music specifically for the NICU babies, which were played for them five times per week. Each track was used for specific purposes: To help the baby wake up; to stimulate a baby who was already awake; and to help the baby fall back asleep.
When they reached an age equivalent to a full-term baby, the infants underwent an MRI. The researchers focused on connections within the salience network, which determines how relevant information is, and then processes and acts on it—crucial components of healthy social behavior and emotional regulation. The neural networks of preemies who had listened to Vollenweider's pieces were stronger than preterm babies who had not received the intervention, and were instead much more similar to full-term babies.
Next Up
The first infants in the study are now 6 years old—the age when cognitive problems usually become diagnosable. Researchers plan to follow up with more cognitive and socio-emotional assessments, to determine whether the effects of the music intervention have lasted.
The first infants in the study are now 6 years old—the age when cognitive problems usually become diagnosable.
The scientists note in their paper that, while they saw strong results in the babies' primary auditory cortex and thalamus connections—suggesting that they had developed an ability to recognize and respond to familiar music—there was less reaction in the regions responsible for socioemotional processing. They hypothesize that more time spent listening to music during a NICU stay could improve those connections as well; but another study would be needed to know for sure.
Open Questions
Because this initial study had a fairly small sample size (only 20 preterm infants underwent the musical intervention, with another 19 studied as a control group), and they all listened to the same music for the same amount of time, it's still undetermined whether variations in the type and frequency of music would make a difference. Are Vollenweider's harps, bells, and punji the runaway favorite, or would other styles of music help, too? (Would "Baby Shark" help … or hurt?) There's also a chance that other types of repetitive sounds, like parents speaking or singing to their children, might have similar effects.
But the biggest question is still the one that the scientists plan to tackle next: Whether the intervention lasts as the children grow up. If it does, that's great news for any family with a preemie — and for the baby-sized headphone industry.
The Friday Five: Scientists treated this girl's disease before she was born
In this week's Friday Five, scientists treated this girl's rare diseases in utero. Plus, how to lift weights in half the time, electric shocks help people regain the ability to walk, meditation is found to work as well as medication, and much more.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five:
- Kids treated for diseases before they're born
- How to lift weights in half the time
- Electric shocks help people regain the ability to walk
- Meditation just as good as medication?
- These foods could pump up your motivation
Tapping into the Power of the Placebo Effect
When Wayne Jonas was in medical school 40 years ago, doctors would write out a prescription for placebos, spelling it out backwards in capital letters, O-B-E-C-A-L-P. The pharmacist would fill the prescription with a sugar pill, recalls Jonas, now director of integrative health programs at the Samueli Foundation. It fulfilled the patient's desire for the doctor to do something when perhaps no drug could help, and the sugar pills did no harm.
Today, that deception is seen as unethical. But time and time again, studies have shown that placebos can have real benefits. Now, researchers are trying to untangle the mysteries of placebo effect in an effort to better treat patients.
The use of placebos took off in the post-WWII period, when randomized controlled clinical trials became the gold standard for medical research. One group in a study would be treated with a placebo, a supposedly inert pill or procedure that would not affect normal healing and recovery, while another group in the study would receive an "active" component, most commonly a pill under investigation. Presumably, the group receiving the active treatment would have a better response and the difference from the placebo group would represent the efficacy of the drug being tested. That was the basis for drug approval by the U.S. Food and Drug Administration.
"Placebo responses were marginalized," says Ted Kaptchuk, director of the Program in Placebo Studies & Therapeutic Encounters at Harvard Medical School. "Doctors were taught they have to overcome it when they were thinking about using an effective drug."
But that began to change around the turn of the 21st century. The National Institutes of Health held a series of meetings to set a research agenda and fund studies to answer some basic questions, led by Jonas who was in charge of the office of alternative medicine at the time. "People spontaneously get better all the time," says Kaptchuk. The crucial question was, is the placebo effect real? Is it more than just spontaneous healing?
Brain mechanisms
A turning point came in 2001 in a paper in Science that showed physical evidence of the placebo effect. It used positron emission tomography (PET) scans to measure release patterns of dopamine — a chemical messenger involved in how we feel pleasure — in the brains of patients with Parkinson's disease. Surprisingly, the placebo activated the same patterns that were activated by Parkinson's drugs, such as levodopa. It proved the placebo effect was real; now the search was on to better understand and control it.
A key part of the effect can be the beliefs, expectations, context, and "rituals" of the encounter between doctor and patient. Belief by the doctor and patient that the treatment would work, and the formalized practices of administering the treatment can all contribute to a positive outcome.
Conditioning can be another important component in generating a response, as Pavlov demonstrated more than a century ago in his experiments with dogs. They were trained with a bell prior to feeding such that they would begin to salivate in anticipation at the sound of a bell even with no food present.
Translating that to humans, studies with pain medications and sleeping aids showed that patients who had a positive response with a certain dose of those medications could have the same response if the doses was reduced and a dummy pill substituted, even to the point where there was no longer any active ingredient.
Researchers think placebo treatments can work particularly well in helping people deal with pain and psychological disorders.
Those types of studies troubled Kaptchuk because they often relied on deception; patients weren't told they were receiving a placebo, or at best there was a possibility that they might be randomized to receive a placebo. He believed the placebo effect could work even if patients were told upfront that they were going to receive a placebo. More than a dozen so call "open-label placebo" studies across numerous medical conditions, by Kaptchuk and others, have shown that you don't have to lie to patients for a placebo to work.
Jonas likes to tell the story of a patient who used methotrexate, a potent immunosuppressant, to control her rheumatoid arthritis. She was planning a long trip and didn't want to be bothered with the injections and monitoring required in using the drug, So she began to drink a powerful herbal extract of anise, a licorice flavor that she hated, prior to each injection. She reduced the amount of methotrexate over a period of months and finally stopped, but continued to drink the anise. That process had conditioned her body "to alter her immune function and her autoimmunity" as if she were taking the drug, much like Pavlov's dogs had been trained. She has not taken methotrexate for more than a year.
An intriguing paper published in May 2021 found that mild, non-invasive electric stimulation to the brain could not only boost the placebo effect on pain but also reduce the "nocebo" effect — when patients report a negative effect to a sham treatment. While the work is very preliminary, it may open the door to directly manipulating these responses.
Researchers think placebo treatments can work particularly well in helping people deal with pain and psychological disorders, areas where drugs often are of little help. Still, placebos aren't a cure and only a portion of patients experience a placebo effect.
Nocebo
If medicine were a soap opera, the nocebo would be the evil twin of the placebo. It's what happens when patients have adverse side effects because of the expectation that they will. It's commonly seem when patients claims to experience pain or gastric distress that can occur with a drug even when they've received a placebo. The side effects were either imagined or caused by something else.
"Up to 97% of reported pharmaceutical side effects are not caused by the drug itself but rather by nocebo effects and symptom misattribution," according to one 2019 paper.
One way to reduce a nocebo response is to simply not tell patients that specific side effects might occur. An example is a liver biopsy, in which a large-gauge needle is used to extract a tissue sample for examination. Those told ahead of time that they might experience some pain were more likely to report pain and greater pain than those who weren't offered this information.
Interestingly, a nocebo response plays out in the hippocampus, a part of the brain that is never activated in a placebo response. "I think what we are dealing with with nocebo is anxiety," says Kaptchuk, but he acknowledges that others disagree.
Distraction may be another way to minimize the nocebo effect. Pediatricians are using virtual reality (VR) to engage children and distract them during routine procedures such as blood draws and changing wound dressings, and burn patients of all ages have found relief with specially created VRs.
Treatment response
Jonas argues that what we commonly call the placebo effect is misnamed and leading us astray. "The fact is people heal and that inherent healing capacity is both powerful and influenced by mental, social, and contextual factors that are embedded in every medical encounter since the idea of treatment began," he wrote in a 2019 article in the journal Frontiers in Psychiatry. "Our understanding of healing and ability to enhance it will be accelerated if we stop using the term 'placebo response' and call it what it is—the meaning response, and its special application in medicine called the healing response."
He cites evidence that "only 15% to 20% of the healing of an individual or a population comes from health care. The rest—nearly 80%—comes from other factors rarely addressed in the health care system: behavioral and lifestyle choices that people make in their daily life."
To better align treatments and maximize their effectiveness, Jonas has created HOPE (Healing Oriented Practices & Environments) Note, "a patient-guided process designed to identify the patient's values and goals in their life and for healing." Essentially, it seeks to make clear to both doctor and patient what the patient's goals are in seeking treatment. In an extreme example of terminal cancer, some patients may choose to extend life despite the often brutal treatments, while others might prefer to optimize quality of life in the remaining time that they have. It builds on practices already taught in medical schools. Jonas believes doctors and patients can use tools like these to maximize the treatment response and achieve better outcomes.
Much of the medical profession has been resistant to these approaches. Part of that is simply tradition and limited data on their effectiveness, but another very real factor is the billing process for how they are reimbursed. Jonas says a new medical billing code added this year gives doctors another way to be compensated for the extra time and effort that a more holistic approach to medicine may initially require. Other moves away from fee-for-service payments to bundling and payment for outcomes, and the integrated care provided by the Veterans Affairs, Kaiser Permanente and other groups offer longer term hope for the future of approaches that might enhance the healing response.
This article was first published by Leaps.org on July 7, 2021.