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New Research Vistas
The research mission of the new BHI is based on the following 5 Mind Body Medicine hypotheses:
- The human psychosocial environment is emulated and experienced in the biology of the brain and thus mind and body form a unity.
- Psychosocial stress leads to cellular oxidative stress.
- Severe oxidative stress leads to selective disease vulnerability based on genetic vulnerabilities.
- Disease vulnerability can be gauged with the use of a Mind Body Medicine Equation: Stress Factors/ Resiliency Components = Selective Disease Vulnerability.
- Stress reduction through the use of relaxation response (RR) and resiliency strengthening through cognitive skills training, social support and prosocial behavior, optimism and belief and spirituality, and nutrition and exercise will reduce disease vulnerability and enhance health.
These Mind Body Medicine hypotheses guide the work of our 3 BHI Core Research Programs:
- Human Clinical
- Mind Body Neuroimaging
- Animal Behavioral Neuroscience
1. Human Clinical Research
The Human Clinical Research is under the direction of John Denninger, MD, PhD. He is assisted by Elyse Park, PhD, Chief of the Behavioral Health Section, and a team that includes Jonathan Lerner, PhD and Christina Psaros, PhD who are both research psychologists. There are four research coordinators—Megan Foret, MA; Mariola Milik, MS; Victoria Lepoutre, MS and Nicole Hasheminejad, BS. Consultants include Jeff Dusek, PhD; Patricia Hibbert, MD, PhD; William Stason, MD, MPH, Randall Zusman, MD, John Levine, MD, PhD, Jeff Huffman, MD, Elizabeth Hoge, MD, and Lobsang Rapgay, PhD.
Recent findings include:
- The covariance of diminished oxygen consumption with exhaled nitric oxide in those achieving RR.
- An 8 week RR training was successful in reducing systolic hypertension to the point that anti-hypertensive medication could be reduced in elderly subjects with this difficult to treat disorder.
- Our cardiac rehabilitation program was proven in a CMS supported study to reduce several cardiac risk factors.
Ongoing research includes:
- studies of the effect of mind body programs in cardiac wellness and rehabilitation;
- hypertension (looking at endothelial functioning) and pre-hypertension;
- epilepsy;
- inflammatory bowel syndrome and irritable bowel syndrome;
- temporal mandibular disorder and other oral pain syndromes;
- depression in a community populations in collaboration with the MGH Community Health Program;
- post traumatic stress disorder; child and adolescent ADHD and adverse childhood events in collaboration with the St Francis Hospital Center of Hartford, CT;
- adaptation to chronic mental illnesses in collaboration with Peer Support groups in Massachusetts, Michigan and Georgia.
- We are also pursuing programs in China directed at helping earthquake victims and in India addressing their new hypertension epidemic, both of which will include research components if actualized.
Mindful of the fact that certain settings are breeding grounds for high stress and attendant health consequences, we are committed to special research programs to improve health and enhance performance in schools, in the workplace and in the military. Marilyn Wilcher and Dr Elyse Park, building on successful past Institute research in diverse contexts ranging from South Central Los Angeles to Harvard University, have begun research studies at the Needham High School and in the Fenway School. Collaboration with the American Research Institute on an educational grant submission is anticipated. With funding from the Blackburn Foundation, we are focusing on employee health at the NStar Company, to look specifically at the impact of our Lighten Up Training Program on weight loss. BHI is also a research collaborator with the MGH Human Resources Department in their “Be Fit” Employee health program. Future projects include a collaboration with the Samueli Institute on training and research to address the clinical needs of returning soldiers with trauma spectrum disorders. We have visited the Brooke Army Medical Center and have been invited to propose a research program to help their staff avoid “compassion fatigue”.
An essential aspect of this Core Program is our Genomic, Epigenetic and Proteomic Program in collaboration with Tuvea Libermann, PhD and his Genetics Lab at BIDMC and the Broad Institute. In a recent ground breaking study published in the journal PLOSOne, our team was able to show that novice subjects after 8 weeks of RR training showed blood gene activation profiles consistent with reduced oxidative stress and reduced pro-inflammation. This pattern was in the same direction, although not as robust, as the gene expression profile of another cohort of long term users of a variety of meditative techniques. We are now embarking on a new generation of blood gene expression and methylation studies of all our subjects. Proteomic studies will then follow. We hope to be able to begin uncovering the causal links that explain the mind (stress, relaxation and resiliency)- body (clinical phenotypes) effects that we see in our clinical studies.
We are very aware of the need for us to develop electronic portals to deliver our “train the trainers” and clinical programs on-line to the large population in need of mind body interventions. We are committed to this effort and have started this process with a study funded by the Partners Connected Health Center looking at the acceptability and effectiveness of RR training delivered in the virtual world of Second Life.
2. Mind Body Neuroimaging
Mind Body Neuroimaging Research is under the direction of Allan George Bush, MD, MMSc, a neuroimager renowned for his functional MRI work on the paralimbic cortex. This area of the brain is most important for the purposes of mind body research because modern stress is often the result of conflicted decision-making in the face of dissonant cognitive and emotional signals that converge on the anterior cingulate, which is charged with the response selection function. Another part of the paralimbic cortex, the insula, is engaged in modulating the messages of stress between the viscera and the brain. Dr. Bush is researching brain activation changes with subjects who are challenged with response selection using the Bush Multi-system Interference Task pre- and post- 8 weeks of RR training. Given his ADHD neuroimaging expertise, he plans to study the brain activation patterns of adults with ADHD pre and post our mind body intervention to determine whether this adjunctive approach might benefit them. In an exciting future project, fMRI will be utilized to investigate how subjects make prosocial altruistic decisions and if our interventions, which have been shown to increase spiritual growth, can enhance that capacity.
Sara Lazar, PhD, another neuroimager working in this core area at BHI, was the lead investigator in 2 reports on the neuroimaging of meditation that have appeared in the journal Neuroreport. One was the first fMRI study done on meditators and showed that the reward and motivation areas of the brain were activated. The second study showed that the right insular cortex and the right prefrontal cortex were thickened in experienced meditators suggesting a practice effect on important brain structures. Currently at BHI, in an NIH funded project, Dr Lazar is collaborating with the UMass Center for Mindfulness Based Stress Reduction to compare the brain activation patterns produced by RR with the brain activation produced by mindfulness based stress reduction.
3. Animal Behavioral Neuroscience
Animal Behavioral Research, located at the Shriners Burn Institute, is under the direction of John Levine, MD, PhD, a child psychiatrist and research psychologist, assisted by a post-doctoral molecular biologist Monica Casali, PhD and a research assistant, Antonia Vitalo, BS. This research provides a rat model of stress and resiliency, making the mind body medicine equation more accessible to our manipulations.
In this project, rats are stressed through the use of isolation rearing and are compared to a group rearing in a resilient condition. In our studies rats subjected to isolation stress become hyperactive in open field testing, show immediate early gene (IEG) expression changes in hippocampus, amygdala and medial prefrontal cortex, and poor wound healing when compared to group reared rats. When isolated rats are provided with enriching Nestlets—soft cardboard squares that stimulate nest building behavior—their behavior pattern, brain IEG expression and wound healing move closer to the patterns expressed by group reared resilient rats. We believe that Nestlets can be considered as a RR and resiliency enhancement intervention. Our next generation of studies in collaboration with Dr Mohammed Milad and his lab will look at fear conditioning as another behavioral phenotype. We will also typify the changes further with biomarkers and neuroimaging. By doing so we will understand more deeply why increased stress and diminished resiliency increase vulnerability to disease, in this case poor wound healing, and why providing a stress reducing, resiliency building intervention can improve the equation.
Our unique comparative advantage as an Institute devoted to mind body medicine is our cross fertilizing core research infrastructure as described above. This integrated tripartite structure allows us to pursue the kind of interdisciplinary research that may uncover basic secrets about the mind body unity. In our human model, we will learn how clinical phenotypes are changed by our clinical mind body interventions and will learn how this occurs through the use of biomarkers and psychometrics, as well as blood gene expression profiles and methylation patterns and brain activation patterns. At the same time using our animal model, we will learn how behavioral phenotypes can be changed by our behavioral interventions and uncover the underlying mechanisms using biomarkers as well as blood gene expression profiles and methylation patterns and brain activation patterns. By matching these biological signatures in these 2 models we can be more assured that our findings about mind body causal links are evolutionarily grounded and constitutionally accurate. But moreover, by studying brain biomarkers and genomic and epigenetic fingerprints in our rats and correlating these brain based biological maps that are not accessible in humans, not only with our other animal data, but also with our human data, we stand the chance of cracking the code of the mind body unity.
If achievable, the potential benefit of such knowledge for the health of individuals and communities would be enormous.
While humbled by this daunting research mission, we nevertheless feel the time is right to pursue it given the generous support of our benefactor and the strength of the overall research enterprise which MGH provides.
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| For more information, contact the research department at 617.643.6047 or by email
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