Science

It’s Time to Get Cerebral About Trauma – a Neuroscientist Leads the Way

Bhatnagar Prize awardee Vidita Vaidya finds it fascinating how we develop such different ways of responding to trauma despite sharing an identical neurological architecture.

Vidita Vaidya. Credit: Nandita Jayaraj/TLoS

Vidita Vaidya. Credit: Nandita Jayaraj/TLoS

The Life of Science – Joy, sadness, fear, anger and disgust – these emotions were given lives and personalities of their own in last year’s Disney Pixar animation movie Inside Out (2015). These emotions resided in the mind of a young girl, and their emotions’ stories got us thinking about the circuits inside our brain. And Vidita Vaidya’s lab at the Tata Institute of Fundamental Research (TIFR), Mumbai, comes as close as possible to a real life Inside Out.

Centuries of investigations have given us a clear picture of how the brain coordinates movement, bodily functions and the mechanics of how we perceive sensations like pain and sight. However, the network of circuits that regulates emotional response is still an enigma, says Vaidya. “We have a reasonable understanding of the negative spectrum of emotions like fear and stress responses, but we don’t know much about the positive side. What regulates joy? Where is our sense of resilience? Optimism?” Vaidya asks. “And all of these are clearly regulated by our brain.” Her lab at TIFR is one of the few in India to explore these complex questions.

Vaidya concedes that we may never reach a time where we fully grasp the entire mechanical working of the brain – so dynamic is the organ – but the field is advancing at such a rapid pace that it is only a matter of time before we understand several more specific aspects. For example, “We [will] at least understand which brain circuits make us vulnerable or resilient to stress,” she says. “Often, even two individuals who are genetically identical may have very different emotional responses.” She explained that this is partly because they may have been exposed to different environments, and their circuits would have learnt different things.

Why won’t antidepressants work?

Similarly, we may soon understand why antidepressants take months to kick in, and sometimes don’t work at all. This is a serious issue around the world, Vaidya tells The Life of Science. “Imagine a doctor prescribing you medication and telling you [that you have] to wait for six weeks before knowing whether it will work. Unfortunately, that’s the reality currently. One-third of patients with severe clinical depression don’t respond to any drugs out there. The worst part is you cannot predict who’s going to be treatment-resistant till they become treatment-resistant.”

This happens because most such drugs work by elevating levels of neurotransmitters called norepinephrine and serotonin in the brain. Both these hormones have multiple receptors – of which we only want to target a few. Vaidya breaks it down: “You’re throwing a ball aiming for one of 10 sticks. Sure, it’ll hit the right stick, but in the process, the ball knocks down other sticks, too. So you will get the desired effect but you will get a bunch of other effects also. Now if some of the side-effects end up counteracting the desired one, it takes that much longer for the drug to work. This is what we discovered.”

All her laboratory experiments are conducted on mice and rats. While we can’t take for granted that things will work identically in humans, Vaidya says the rodents make for fairly good models despite their smaller brains as their neural circuits are fairly conserved across species in evolution. And, as she points out, not to mention all the mood-regulating drugs in the market today were originally tested on rodents. “Obviously, the ideal closest analog would be primates, but you can’t do these kinds of experiments on primates.”

Slices of mouse brains in Vidita Vaidya's lab at TIFR. Credit: Nandita Jayaraj/TLoS

Slices of mouse brains in Vidita Vaidya’s lab at TIFR. Credit: Nandita Jayaraj/TLoS

But how do you tell if a mouse is disgusted or sad or angry? You can’t, says Vaidya, but what you can do is monitor their behaviour after genetically altering one or more networks, or exposing them to environmental stress factors. “In their early life, their major interaction is with their mother. We can change the nature of that interaction, alter the mother’s care for the pup, etc.” For example, a mouse pup is put under a much higher level of maternal care than usual, or is deprived of the usual care from the mother, and the changes in behaviour are recorded.

When the wounds remain

These kinds of experiments are designed to probe into a particularly critical stage in life: the early window. In humans, this lasts from the time spent in the womb to up to about 12 years of age. “We have a strong feeling that that this initial period of time is critical in determining how your brain is going to be wired up for emotional responses [as an] adult,” says Vaidya. This is the time when a lot of neural connections get consolidated and others get eliminated based on which ones you use more often. “If you have a series of traumatic experiences in early life, it’s very likely they will leave consequences within your brain. We’re very interested in those consequences in particular, because they tend to be very long-lasting. This is not so with trauma in adults.”

Vaidya finds it fascinating how we all develop such unique circuitry, and, consequently, such different ways of responding to trauma despite sharing an identical neurological architecture. “It’s like this,” she explains. “In the beginning, an architect designs all the flats in a building identically. But after people start living in them, the homes will look extremely different because they bring in their own personal flavour. Similarly, genetically, our brains are designed on a blueprint, we all have prefrontal cortex in the same place, and yet in the micro details we vary.”

A study from her lab showed proof of this. “We showed that when you have traumatic events happen in the early window of life you actually show ageing-related effects two years down the road. The ability of the hippocampus [a part of the brain] to make new neurons drops abnormally in trauma. This tells us that if there is a traumatic early event, you may not see effects right away but there are effects down the road waiting for you.”

Worried, yet hopeful

These findings have Vaidya worried: “I look at us as a country and we are a young country with a huge potential of youth,” she says. “But it seems to me that there are no-brainer things the country needs to do: nutrition, education and healthcare.”

She’s talking about the large population of under-15-year-olds – 372.4 million – who, without these basic amenities, are not well-equipped to deal with the trauma they may face, and end up bearing scars for the rest of their lives. “If we don’t fix this, it doesn’t matter what huge infrastructure development happens because the base of our pyramid cannot change their lives.”

Nevertheless, Vaidya is not bogged down by the realities her science confronts her with because the same science suggests that this situation need not be irreversible. “I have great faith in the brain as a plastic structure – it a has a great capacity for change. We can harness this for the generation of people who have been possibly nutritionally deprived or faced adversity,” she says. “I know my work is multiple steps removed from that in terms of application but in terms of fundamentals it gives us a handle of the circuits in the brain.”

India as a neuroscience destination

In spite of all the fuzziness (many of the phenomena she studies are difficult to define), Vaidya is very enthusiastic about neuroscience as a research option for young biologists. Even within India, Vaidya says there are several options today, rattling names off the top of her head: NCBS, IISc, NBRC (Gurgaon), IISER (Pune), IIT (Kanpur), and of course TIFR. But it depends on the area they want to research, she adds. “Some areas may be better studied abroad but the students need to come back. I hope they do. We need to build our tribe, it’s too small a community for such a large country.”

For Vaidya, who joined TIFR as a principal investigator when she was only 29, settling down in India was always the plan. She was able to do this earlier than most of her contemporaries probably because the brain caught her fancy early on. By the time she completed her bachelor’s degree in biochemistry at St. Xavier’s College in Mumbai, she more or less knew that’s what she wanted to study.

Having identified her broad area of interest at such an early stage enabled her to approach the next few years constructively. She completed her master’s degree and PhD at Yale University, and had two stints at labs in Stockholm and Oxford before she returned to her hometown, Mumbai, in 2000. She freely admits that there were challenges, as expected. She recalls the weeks of paperwork that she and fellow recent neuroscientist joinee Shubha Tole had to complete while setting up the institute’s first animal house and importing the transgenic mice.

None of this deterred her. “In India, there is an element of being the pioneer. There’s lots of jugaad [Hindi for ‘hacking’] involved and I liked that.” The best part for Vaidya is the inadvertent freedom: “It slows you down in certain ways but because you’re a little distant from the rest of the crew – you can do a meandered walk into an area, you don’t have to move with the mainstream. I find that these meandering walks sometimes takes you to the most exciting places!”

On being privileged and ‘manels

Vaidya counts herself among the tiny percentage of women who are privileged enough to not have been exposed to gender bias in their lives. Her mother, a doctor, was a living example of how it was possible for a career-woman to balance workloads. “My spouse and me divide the workload 50-50, whether it’s child or homecare. When that is not the case, it’s real tough. We’re not superhuman. I take it for granted but I don’t know if I could do what I do without this kind of support.”

On the institutional front, however, Vaidya acknowledges that much needs to be done to keep women in science. “Let’s say you organise a conference and you have only [male] speakers. Young graduate students watching this see ten men on the podium. You’re sending a message that you couldn’t find one woman, and then you say ‘Oh, but there just aren’t women so we couldn’t find them’. Well, then, there’s something wrong here,” remarks a visibly irritated Vaidya.

“You can’t use this meritocracy debate! Are you telling me we are incapable genetically? Clearly not. The brain is clearly capable of performing irrespective of gender. I think it’s reflective of the patriarchal society. It’s not true to think that science is not patriarchal because science is practised by people and people are conditioned that way.”

What Vaidya feels matters is being conscious of these problems and the willingness to listen and realise that there is a missing 50% of the population. “That’s bad for science. You’ve wiped out the possibility of having a representation from all communities or caste or gender or race.”


Watch Vidita Vaidya’s TEDx talk below:

Excerpt:

‘Outreach is a scientist’s moral responsibility’

“I think everyone should publish (research papers). I think results (of studies) should be accessible to the paying public since it’s their tax money that paid for it. Science should be accessible to them. I’m a big believer in open-access. Information should be available to the community, not owned by consortia. We need to examine these questions.

But dissemination through publication is not enough as they are accessed only by a small sub-community of other scientists, not to people who do not know the jargon. Talk to students, talk to kids, talk to older people – talk to people, period. I think outreach must be required of every single scientists who uses a taxpayer rupee. I do as much as I can – I always accept invitations to go give talks at schools, I attend Chai & Why sessions, Inspire camps. Outreach should be part and parcel of your process of doing science. If not, the danger is a widening gulf between the public and science. This is not good.”

This piece was originally published by The Life of Science. The Wire is happy to support this project by Aashima Dogra and Nandita Jayaraj, who are traveling across India to meet some fantastic women scientists.