Tag: wellness

Open-label placebo injection demonstrates ‘modest’ benefit in chronic back pain

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Key takeaways:

  • A non-deceptive placebo injection reduced chronic back pain with effect size similar to typical treatments.
  • Secondary outcome benefits and brain changes lasted up to 1 year.

A single saline injection, openly prescribed as a placebo, yielded approximately 1 month of chronic back pain improvement, along with longer-term benefits in depression and sleep, according to data published in JAMA Network Open.

“We have known that placebos can be powerful pain relievers, but it has been unclear how to use them ethically, without patient deception,” Yoni K. Ashar, PhD, assistant professor at the University of Colorado Anschutz Medical Campus, told Healio. “This spurred the development of the ‘open label,’ non-deceptive placebo treatment, which we studied here.”

To investigate the long-term efficacy of open label placebo in chronic back pain, Ashar and colleagues recruited 101 adults (mean age, 40.4 years) with moderate chronic back pain from the Boulder, Colorado, area between November 2017 and August 2018, with a follow-up at 1 year.

Trial participants were randomly assigned to either continue their usual care alone or to also receive a single, open label lumbar saline injection, along with information about how the placebo effect can lead to pain relief. The primary outcome was average pain over the last week 1 month after treatment, measured using a scale of 0 to 10. Secondary outcomes also assessed pain interference, depression, anxiety, anger and sleep quality.

At 1 month, those who received placebo injections reported greater reductions in chronic back pain than the usual care group (relative reduction, 0.61; Hedges g = 0.45; 95% CI, –0.89 to 0.04), according to the researchers.

By 1 year post-treatment, the between-group difference in pain relief was reduced to insignificance. However, after 1 month, other significant benefits were seen in depression, anger, anxiety and sleep disruption, with “medium sized” effect sizes ranging from 0.3 to 0.5 (P < .03 for all).

The researchers also compared neuroimaging between the groups. Functional MRI scans were taken as participants performed both an “evoked” back pain procedure, which used an inflating balloon to cause back distention and pain, and a “spontaneous” pain procedure, where patients rated their pain once per minute over the course of an 8-minute scan.

Overall, the neuroimaging showed “altered brain responses to evoked back pain and altered functional connectivity during spontaneous pain consistent with engagement of descending modulatory pain pathways,” Ashar and colleagues wrote.

The researchers described the placebo injection’s pain relief benefit as “modest in magnitude” but clinically significant and comparable with the effect sizes of typical treatments such as NSAIDs, but with fewer adverse events.

“These findings speak to the power of healing rituals, even when we know they are healing rituals,” Ashar said. “Although we view this study as more mechanistic and conceptually provocative than as clinically applicable, it suggests that providers may be able to ethically prescribe a placebo for their patients one day, without deception. In addition, the duration of benefits on secondary outcomes and the observed brain changes were surprising, considering how brief and minimalist the intervention was.”

https://www.healio.com/news/rheumatology/20241022/openlabel-placebo-injection-demonstrates-modest-benefit-in-chronic-back-pain?utm_source=selligent&utm_medium=email&utm_campaign=news

Your Brain Divides the Day Into “Chapters” Based on Priorities

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Summary: New research shows that the brain divides the day into “chapters” based on what a person focuses on. These mental boundaries aren’t solely prompted by changes in surroundings but also by internal goals and priorities. In experiments using audio narratives, participants’ brains organized events differently depending on whether they focused on specific details.

This study suggests that how we experience and remember events is influenced by both context and what matters most to us at the time.

Key Facts:

  • The brain forms new “chapters” based on attention and personal goals, not just environment.
  • MRI scans showed that people segmented stories differently depending on their focus.
  • The research may help explain how expectations influence memory formation.

Source: Columbia University

The moment a person steps off the street and into a restaurant—to take just one example—the brain mentally starts a new “chapter” of the day, a change that causes a big shift in brain activity. Shifts like this happen all day long, as people encounter new environments, like going out for lunch, attending their kid’s soccer game, or settling in for a night of watching TV.

But what determines how the brain divides the day into individual events that we can understand and remember separately?  

That’s what a new paper in the journal Current Biology aimed to find out. 

The research team, led by Christopher Baldassano, an associate professor of Psychology, and Alexandra De Soares, then a member of his lab, turned up interesting results.

The researchers wanted to better understand what prompts the brain to form a boundary around the events we encounter, effectively registering it as a new “chapter” in the day.

One possibility is that new chapters are entirely caused by big changes in a person’s surroundings, like how walking into a restaurant takes them from outdoors to indoors.

Another possibility, however, is that the new chapters are prompted by internal scripts that our brain writes based on past experience, and that even big environmental changes might be ignored by our brain if they are not related to our current priorities and goals.

To test their hypothesis, researchers developed a set of 16 audio narratives, each about three to four minutes long. Each narrative took place in one of four locations (a restaurant, an airport, a grocery store, and a lecture hall) and dealt with one of four social situations (a breakup, a proposal, a business deal, and a meet cute).

The researchers found that the way the brain divides up an experience into individual events depends on what a person currently cares about and is paying attention to.

When listening to a story about a marriage proposal at a restaurant, for example, subjects’ prefrontal cortex would usually be organizing the story into events related to the proposal, leading up (hopefully) to the final “yes.”

But the researchers found that they could force the prefrontal cortex to organize the story in a different way if they instead asked study participants to focus on the events related to the dinner orders of the couple. For study participants who were told to focus on these details, moments like ordering dishes became critical new chapters in the story.

“We wanted to challenge the theory that the sudden shifts in brain activity when we start a new chapter of our day are only being caused by sudden shifts in the world—that the brain isn’t really ‘doing’ anything interesting when it creates new chapters, it’s just responding passively to a change in sensory inputs,” Baldassano said.

“Our research found that isn’t the case: The brain is, in fact, actively organizing our life experiences into chunks that are meaningful to us.”

The researchers measured where the brain created new chapters both by looking at MRI scans of the brain to identify fresh brain activity, and, in a separate group of participants, by asking them to press a button to indicate when they thought a new part of the story had begun.

They found that the brain divided stories into separate chapters depending on the perspective they were told to be attuned to—and it didn’t just apply to the proposal-in-a-restaurant scenario: A person hearing a story about a breakup in an airport could, if prompted to pay attention to details of the airport experience, register new chapters as they went through security and arrived at their gate.

Meanwhile, a person who heard a story about a person closing a business deal while grocery shopping could be prompted to register either the new steps of the business deal as new chapters, or to be attuned primarily to the phases of grocery shopping instead.

The details that the study participants were prompted to pay attention to influenced what their brain perceived as a new chapter in the story.

Moving forward, the researchers hope to investigate the impact that expectations have on long-term memory. As part of this study, the researchers also asked each participant to tell them everything they remembered about each story.

They are still in the process of analyzing the data to understand how the perspective they were asked to adopt while listening to the story changes the way they remember it. More broadly, this study is part of an ongoing effort in the field to build a comprehensive theory about how real-life experiences are divided up into event memories.

The results indicate that prior knowledge and expectations are a key ingredient in how this cognitive system works.

Baldassano described the work as a passion project.

“Tracking activity patterns in the brain over time is a big challenge that requires using complex analysis tools,” he said: “Using meaningful stories and mathematical models to discover something new about cognition is exactly the kind of unconventional research in my lab that I am most proud of and excited about.”

About this neuroscience research news

Author: Christopher Shea
Source: Columbia University

Your Brain Divides the Day Into “Chapters” Based on Priorities

More severe OSA linked to premature aging in adults

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A heightened oxygen desaturation index was significantly linked to epigenetic age acceleration determined via two epigenetic clocks, according to a presentation at the American Thoracic Society International Conference.

“OSA severity is associated with positive epigenetic age acceleration or premature aging,” Ilia Ostrovski, respirology fellow from University of British Columbia, said during his presentation. “We also conclude that the association between obstructive sleep apnea and positive epigenetic age acceleration is better demonstrated by second generation epigenetic clocks likely due to their calibration with physiologic outcomes rather than chronological age.”

In a large, cross-sectional study, Ostrovski and colleagues evaluated epigenetic age, a biologic age biomarker, of 1,254 adults (mean age, 53 years; 43% women) from the 2016 to 2019 Canadian Sleep and Circadian Network biobank who underwent sleep testing to find out if OSA severity is linked to premature aging, or epigenetic age acceleration.

Researchers utilized blood samples to extract DNA and four validated epigenetic clocks to find epigenetic age estimations.

“Levels of DNA methylation at certain sites in the genome are associated with chronological age; thus, epigenetic or biological age can be predicted exploiting this feature of the DNA methylome,” Ostrovski and colleagues wrote in the study abstract.

Ostrovski noted during his presentation that first generation clocks (Horvath pan-tissue and Hannum) are calibrated to chronologic age, whereas second generation clocks (PhenoAge and GrimAge) are calibrated to physiologic outcomes and mortality.

“It’s becoming increasingly recognized that these [second generation clocks] capture age-related decline better than first generation clocks,” he said.

The total cohort included 325 controls (median age, 54 years; 54% women; median BMI, 28 kg/m2) and 929 individuals with OSA.

Of those with OSA, most had severe OSA (n = 387; median age, 56 years; 34% women; median BMI, 37 kg/m2), followed by moderate OSA (n = 297; median age, 56 years; 36% women; median BMI, 33 kg/m2) and mild OSA (n = 245; median age, 58 years; 51% women; median BMI, 31 kg/m2).

Baseline characteristics with a greater proportion of those with severe or moderate OSA vs. those with mild OSA or controls included current smoking status (14% vs. 12% vs. 9% vs. 7.4%), diabetes (28% vs. 18% vs. 17% vs. 9.3%), hypertension (51% vs. 55% vs. 42% vs. 32%) and cardiovascular disease (14% vs. 15% vs. 13% vs. 9%).

The proportion of individuals with alcohol use disorder was similar among controls, those with mild OSA and those with moderate OSA (63% vs. 62% vs. 63%) but lower among those with severe OSA (52%).

Further, median oxygen desaturation index (ODI) at baseline increased as OSA became more severe, starting at two desaturation episodes per hour in the control group and escalating to 10 episodes per hour in the mild OSA group, 21 episodes per hour in the moderate group and 50 episodes per hour in the severe group.

To find the relationship between epigenetic age acceleration and ODI for each clock, researchers used linear regression adjusted for blood cell type proportions, age, sex, ethnicity, smoking, alcohol use, BMI, chip ID and chip position/row.

Using the GrimAge clock, each rise in ODI by 10 corresponded to epigenetic age acceleration of 0.16 years (P = .004). The same increase in ODI was also linked to epigenetic age acceleration of 0.11 years in the PhenoAge clock (P = .039).

No significant relationship was found between the two factors when using each of the first-generation clocks, and Ostrovski highlighted that the link became nonsignificant after factoring in BMI.

“We feel that future work should prioritize prospective evaluation of the impact of OSA severity on aging-related outcomes and also determine whether treatment of OSA reverses its effect on epigenetic age acceleration,” Ostrovski said.

Reference:

https://www.healio.com/news/pulmonology/20240612/more-severe-osa-linked-to-premature-aging-in-adults?utm_source=selligent&utm_medium=email&utm_campaign=news