Your brain tells if a placebo can treat pain
The placebo
effect, a fake treatment with real therapeutic outcomes often confounds
the merit of successful drug trials. This questionable clinical
response is often attributed to the psychological expectation of a
positive outcome. This response translates to release of warm and fuzzy
neurotransmitters like dopamine and endorphins in cortical structures
responsible for moods, emotions, and awareness. Even knowing that you
are getting a placebo does not change the outcome specifically for
migraine pain treatment as shown by researchers in 2014.
The placebo was 50% as effective as the real drug in reducing the pain
and this result was attributed to the positive effect of ritual pill
taking in general.
But is it beyond just positive thinking? What happens in the brain that leads to the placebo effect?
These
questions drove the researchers to investigate placebo effects in clinical settings.
Their recent publication identified
specific psychological factors, anatomical features and functional
connectivity between selective regions that could predispose a subset of
patients response to placebo.
This study expands on the previously identified predictors based on brain functional connectivity for the treatment of pain and
addresses the inherent variability of cortical activity before and
after treatment. To that end, they also cross-validated an algorithm
that successfully predicted the response magnitude to placebo pain
treatment.
After
screening 129 chronic back pain patients and excluding all subjects
that did not meet the study requirements, a total of 63 patients divided
into 3 groups of 20, were studied to compare responses between the no
treatment group to randomized placebo treatment group. In the 6 visits
that spread over 8 weeks, the placebo response was tracked through
psychological questionnaires and neuroimaging scans (MRI: Magnetic
Resonance Imaging and DTI: Diffusion tensor imaging). Additionally, an
interactive phone application, specifically designed for the study was
also used to track the patient’s pain over time rather than just during
their visits.
Three
characterization approaches were used to understand the predisposed
response to placebo administration. Firstly, pain scores received via
the smartphone app showed the analgesic effects of placebo when compared
to no treatment patient cohort. Moreover, the pain reduced further in
the responders over time reaching a stable value for both treatment and
washout periods. Second, anatomical characteristics including
subcortical limbic volume asymmetry, sensorimotor cortical thickness,
and functional coupling of prefrontal regions, anterior cingulate and
periaqueductal gray were the natural traits that were selectively
present in the placebo effect observed population. However, studying the
brain structures that are associated with the emotional state, chronic
pain and placebo response in healthy individual risk factors like the
amygdala, hippocampus and nucleus accumbens did not reveal anything.
Lastly, 15 psychological questionnaires with 38 subscales revealed that
subjects with interoceptive awareness and openness were predisposed to
the placebo effect.
The
observed psychological traits and functional connectivity patterns
prior to placebo treatment when put through machine learning also
predicted the magnitude of the placebo effect independently. A nested
leave-one-out cross-validation method was used to predict each patient
response using independent training samples. The training was done with
one data set at a time. The classifier was first trained with the
questionnaire data and then the functional connectivity maps were fed
through. An interesting observation made was that prediction accuracy
did not differ significantly when trained with questionnaires alone vs
in combination with brain maps.
The
systematic study design and execution with novel cross-validated
predictive analysis sheds light on understanding and preparing for the
complex placebo effect in the perspective of chronic pain treatment.
Moreover, the authors also suggest that the questionnaire based easy
pre-study patient survey might be enough to predict the positive placebo
response population.
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Labels: amygdala, anatomical features, Brain, functional connectivity, hippocampus, interoceptive awareness, knows, neuroimaging scans, openness, placebo, psychological factors, selective regions, treat pain
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