Finding the Seat of Human Consciousness

Philosophers have long struggled to define human consciousness. Now, a team of researchers led by neurologists at Beth Israel Deaconess Medical Center (BIDMC) has pinpointed the regions of the brain that may play a role maintaining it. Their findings, which have already garnered multiple awards from the American Academy of Neurology, were published today in that society's journal, Neurology.

"For the first time, we have found a connection between the brainstem region involved in arousal and regions involved in awareness, two prerequisites for consciousness," said Michael D. Fox, MD, PhD, Director of the Laboratory for Brain Network Imaging and Modulation and the Associate Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC. "A lot of pieces of evidence all came together to point to this network playing a role in human consciousness." 

Classical neurology holds that arousal and awareness are two critical components of consciousness. Arousal is likely regulated by the brainstem - the portion of the brain, contiguous with the spinal cord, that is responsible for the sleep/wake cycle and cardiac and respiratory rates. Awareness, another critical component of consciousness, has long been thought to reside somewhere in the cortex, the outer layer of the brain responsible for many of its higher functions.

The researchers analyzed 36 patients with brainstem lesions, of which 12 led to coma and 24 did not. Mapping the injuries revealed that a small "coma-specific" area of the brainstem - the rostral dorsolateral pontine tegmentum - was significantly associated with coma. Ten out of the 12 coma-inducing brainstem lesions involved this area, while just one of the 24 control lesions did.

Armed with that information, Fox and colleagues, including lead author David Fischer, MD, then a medical student at Harvard Medical School, used a wiring diagram of the healthy human brain - based on a large, shared data set called the Human Connectome - to identify which other parts of the brain were connected to these coma-causing lesions. Their analysis revealed two areas in the cortex of the brain that were significantly connected to the coma-specific region of the brainstem. One sat in the left, ventral, anterior insula (AI), the other in the pregenual anterior cingulate cortex (pACC). Both regions have been implicated previously in arousal and awareness.

A connectome is a comprehensive map of neural connections in the brain, and may be thought of as its "wiring diagram". More broadly, a connectome would include the mapping of all neural connections within an organism's nervous system.


"We now have a great map of how the brain is wired up in the Human Connectome," said Fox, who is also an Assistant Professor of Neurology at Harvard Medical School. "We can look at not just the location of lesions, but also their connectivity. Over the past year, researchers in my lab have used this approach to understand visual and auditory hallucinations, impaired speech, and movement disorders. A collaborative team of neuroscientists and physicians had the insight and unique expertise needed to apply this approach to consciousness."

The team included co-lead author, Aaron Boes, MD, PhD, and co-senior author, Joel Geerling, MD, PhD, both formerly of BIDMC and now of University of Iowa Carver College of Medicine.

Finally, the team investigated whether this brainstem-cortex network was functioning in another subset of patients with disorders of consciousness, including coma. Using a special type of MRI scan, the scientists found that their newly identified "consciousness network" was disrupted in patients with impaired consciousness. The findings - bolstered by data from rodent studies - suggest the network between the brainstem and these two cortical regions plays a role maintaining human consciousness.

"The added value of thinking about coma as a network disorder is it presents possible targets for therapy, such as using brain stimulation to augment recovery," Boes said.

A next step, Fox notes, may be to investigate other data sets in which patients lost consciousness to find out if the same, different or overlapping neural networks are involved.

"This is most relevant if we can use these networks as a target for brain stimulation for people with disorders of consciousness," said Fox. "If we zero in on the regions and network involved, can we someday wake someone up who is in a persistent vegetative state? That's the ultimate question."

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Tea Drinkers Live Longer

Four Green Teas in White Bowls Credit: A Girl With Tea / Wikimedia Commons
Drinking tea at least three times a week is linked with a longer and healthier life, according to a study published today in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC). "Habitual tea consumption is associated with lower risks of cardiovascular disease and all-cause death," said first author Dr. Xinyan Wang, Chinese Academy of Medical Sciences, Beijing, China. "The favorable health effects are the most robust for green tea and for long-term habitual tea drinkers." The analysis included 100,902 participants of the China-PAR project with no history of heart attack, stroke, or cancer. Participants were classified into two groups: habitual tea drinkers (three or more times a week) and never or non-habitual tea drinkers (less than three times a week) and followed-up for a median of 7.3 years. Habitual tea consumption was associated with more healthy years of life and longer life expectancy. For example, the analyses estimated that 50-year-old habitual tea drinkers would develop coronary heart disease and stroke 1.41 years later and live 1.26 years longer than those who never or seldom drank tea. Compared with never or non-habitual tea drinkers, habitual tea consumers had a 20% lower risk of incident heart disease and stroke, 22% lower risk of fatal heart disease and stroke, and 15% decreased risk of all-cause death. 

Green tea, Credit: MASA / Wikimedia Commons

The potential influence of changes in tea drinking behavior were analysed in a subset of 14,081 participants with assessments at two time points. The average duration between the two surveys was 8.2 years, and the median follow-up after the second survey was 5.3 years. Habitual tea drinkers who maintained their habit in both surveys had a 39% lower risk of incident heart disease and stroke, 56% lower risk of fatal heart disease and stroke, and 29% decreased risk of all-cause death compared to consistent never or non-habitual tea drinkers. Senior author Dr. Dongfeng Gu, Chinese Academy of Medical Sciences, said: "The protective effects of tea were most pronounced among the consistent habitual tea drinking group. Mechanism studies have suggested that the main bioactive compounds in tea, namely polyphenols, are not stored in the body long-term. Thus, frequent tea intake over an extended period may be necessary for the cardioprotective effect." In a subanalysis by type of tea, drinking green tea was linked with approximately 25% lower risks for incident heart disease and stroke, fatal heart disease and stroke, and all-cause death. However, no significant associations were observed for black tea. Dr. Gu noted that a preference for green tea is unique to East Asia. "In our study population, 49% of habitual tea drinkers consumed green tea most frequently, while only 8% preferred black tea. The small proportion of habitual black tea drinkers might make it more difficult to observe robust associations, but our findings hint at a differential effect between tea types." Two factors may be at play. First, green tea is a rich source of polyphenols which protect against cardiovascular disease and its risk factors including high blood pressure and dyslipidaemia. Black tea is fully fermented and during this process polyphenols are oxidised into pigments and may lose their antioxidant effects. Second, black tea is often served with milk, which previous research has shown may counteract the favourable health effects of tea on vascular function. Gender-specific analyses showed that the protective effects of habitual tea consumption were pronounced and robust across different outcomes for men, but only modest for women. Dr. Wang said: "One reason might be that 48% of men were habitual tea consumers compared to just 20% of women. Secondly, women had much lower incidence of, and mortality from, heart disease and stroke. These differences made it more likely to find statistically significant results among men." She added: "The China-PAR project is ongoing, and with more person-years of follow-up among women the associations may become more pronounced." The authors concluded that randomized trials are warranted to confirm the findings and provide evidence for dietary guidelines and lifestyle recommendations. Funding: Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2017-I2M-1-004); National Key R&D Program of China (2017YFC0211700 and 2018YFC1311703).
  • Contacts and sources: The European Society of Cardiology
  • Publication: Tea consumption and the risk of atherosclerotic cardiovascular disease and all-cause mortality: The China-PAR project. Wang X, Liu F, Li J, et al. . Eur J Prev Cardiol. 2019. doi:10.1177/2047487319894685.
  • 2China-PAR: Prediction for ASCVD Risk in China project Source: https://www.ineffableisland.com:
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India's first vaccine candidate Covaxin's Phase-3 trials begin


Vaccine maker Bharat Biotech has announced that it has commenced Phase-3 trials of Covaxin, India's first indigenous vaccine for COVID-19.

The Phase-3 trials, which involve 26,000 volunteers across India, are being conducted in partnership with the Indian Council of Medical Research (ICMR).

This is India's first Phase-3 efficacy study for a COVID-19 vaccine, and the largest Phase-3 efficacy trial ever conducted in India, the Hyderabad-based company said.

Trial volunteers will receive two intramuscular injections approximately 28 days apart. Participants will be randomly assigned to receive Covaxin or a placebo. The trial is double blinded, such that the investigators, the participants and the company will not be aware of who is assigned to which group.

The trials are being conducted at 22 institutes in India including the All India Institute of Medical Sciences (AIIMS), the Guru Tegh Bahadur Hospital (both New Delhi), the Aligarh Muslim University, the Grant Government Medical College and Sir J.J. Group of Hospitals, Lokmanya Tilak Municipal General Hospital and Medical College (Sion Hospital) (all three Mumbai), the ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, the Directorate of Public Health and Preventive Medicine, Chennai and King George Hospital, Vizag.

Participating volunteers, who undergo vaccination in the Phase-3 trials, will be monitored to detect occurrence of COVID-19.

Covaxin has been evaluated in about 1,000 subjects in Phase-1 and Phase-2 clinical trials, with promising safety and immunogenicity data. Volunteers who wish to participate in this trial should be adults over 18 years of age.

Covaxin by Bharat Biotech is developed in collaboration with the ICMR - National Institute of Virology (NIV). This indigenous, inactivated vaccine is developed and manufactured in Bharat Biotech's BSL-3 (Bio-Safety Level 3) bio containment facility.

Covaxin is a highly purified and inactivated vaccine, manufactured in a vero cell manufacturing platform with an excellent safety track record of more than 300 million doses supplied.

"The development and clinical evaluation of Covaxin marks a significant milestone for vaccinology in India, for a novel vaccine. It is important for Indian companies to innovate and develop indigenous vaccines, especially during a pandemic. Covaxin has garnered interest from several countries worldwide for supplies and introduction," said Suchitra Ella, Joint Managing Director of Bharat Biotech Source: https://southasiamonitor.org/
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