NeurOn Topic: Learning and Teaching

Professor Charlene Gamaldo is a Professor of Neurology and Anesthesia Critical Care at Johns Hopkins. She is also the Medical Director of the Johns Hopkins Center for Sleep & Wellness at Howard County General Hospital and the Vice-Chair of the Faculty Development. She completed her BSc studies at the University of Virginia and her medical degree at The George Washington University School of Medicine with an internship at the Greater Baltimore Medical Center. She completed her neurology residency at the University of North Carolina Hospital before joining Johns Hopkins. In 2017, she was nominated for the Board of Directors of the American Academy of Neurology.

 

Martha Cottam) What are the most significant challenges you have faced as a sleep researcher?

Two primary issues. First, sleep research (when I first started) could be quite expensive and resource-intense as it primarily called for a sleep lab facility and various levels of trained technicians to carry our comprehensive physiologic studies. This makes the ability to even start a career with pilot data more difficult for young investigators unless heavily supported and funded. This also makes the adaptation of these investigative approaches more challenging if you want to be inclusive of a diversity of programs, institutions, communities and even countries with a variable degree of resources. The innovation of ambulatory methods to monitor and study sleep is a welcomed opportunity to close this gap. These various devices, approaches and methods are coming out at a fast and furious pace. Time and due diligence are still required to validate these various methods against gold standard sleep procedures and across various settings and subjects. It will be critical to maintaining the integrity of the discipline, both clinically and investigative. Secondly, the factors that impact sleep physiology include a complex interplay of neuro-bio-psycho-social-cultural factors, which makes it fascinating to study, but also challenging to consider all of these factors in developing a solid research design.

 

Lucy Bedwell) Do you think habitual poor sleep hygiene practices can be successfully remedied? And what are the challenges of overcoming these to improve sleep quality? 

Sleep hygiene is always a good idea to adopt but rarely serves as the sole answer to addressing sleep quality issues. In fact, in research design protocols testing out Cognitive-Behavioural-Treatment Interventions for Insomnia (CBT-I), now widely viewed as a gold and first-line strategy for treating insomnia, sleep hygiene is accepted as an appropriate placebo arm to test against the intervention approach. CBT-I is an approach that typically includes a varying combination of 7 different behavioural and cognitive approaches to address sleep that are calibrated based on the personal needs and perspectives of the patient. This is where the challenge comes: it really does require a very deliberative, intentional and somewhat long-term commitment to your sleep health analogous to the focus and commitment needed to have sustainable changes with weight loss.

 

Alice Farquharson) Which other chronic disease your work on HIV and sleep loss may be applicable to?

I was very interested in looking at the relationship between sleep quality amongst individuals living with HIV, namely because of the neurocognitive sequelae that became more notable once we turned the corner with therapies that allowed management of the virus in a manner more tantamount to a chronic condition. Despite evidence of undetectable viral load, individuals living with HIV experienced a greater degree of sleep complaints along with other neurological conditions such as cognitive loss, depression, anxiety, even neuropathy. I was intrigued since many of these conditions had also been associated with poor sleep in the general population and those suffering from other medical and neurological symptoms. For this reason, it was great to adapt my model of characterizing the presence and potential inter-relationship of sleep in other neurological, medical and community cohorts, including Parkinson’s Disease, Opiate Use Disorder, Paediatric Cancer survivors, Marijuana Withdrawal, Underserved Communities.

 

Nan Fletcher-Lloyd) What is your opinion on the use of meditation to improve restfulness before sleep? 

I love it and think it is a great idea if the patient embraces the technique. I see meditation as in the realm of the relaxation arm that is 1 of the approaches for CBT-I. The key to executing these various approaches and the likelihood of their success is the authentic buy-in of both the provider and patients. If one or both do not embrace the approach, then it is less likely to be effective.

 

Bethany Goh) What was it that initially drew you to the field of sleep medicine? 

I was drawn to Sleep as a discipline because I really saw it as an indispensable part of preventative and integrative health care. Sleep medicine typifies personalized medicine, where optimal care must involve all factors of the patient as a person. In thinking about sleep medicine, I’m often inspired by the words of Sir William Osler, who said, “The good physician treats the disease; the great physician treats the patient who has the disease.”

 

Marcelina Wojewska) What do you hope to learn and discover in the field of sleep medicine in the future? 

Sleep can serve as another model for understanding personalized and precision methods of care. Just consider all the factors that influence a person being a good or bad sleeper? I’m inspired by new techniques to further our understanding of the complexity of the relationship to subsequently adopt these approaches with greater precision and accuracy in both diagnosis and management.

 

Lucy Bedwell) What do you see in the future of sleep research? 

Increasing AI application in the understanding of sleep, whether related to developing diagnostic biomarkers, genomics to assist with precision therapeutics, signal analysis of various physiologic signals like EEG, heart variability, arterial tone at the laboratory level and eventually at the consumer wearable level.

 

Bethany Goh) Do you have any advice for BIPOC women entering science and medicine?

Innovation and adaptability have clearly been linked with diversity of thought and perspective. To truly realize this benefit, diversity must come with inclusion and placing a high value in providing a supportive environment for diverse voices to be heard. My advice to BIPOC women entering science and medicine is to consider evidence supporting a track record of demonstrable strides towards diversity and inclusion when choosing programs for your training and career. Once there, try to do your best to surround yourself with a mosaic team of peers, advisors and sponsors who embrace this perspective. Hence, you have a fertile environment not only for you to thrive, but for your team and the scientific community as a whole to thrive as well.

 

Bethany Goh) Have you seen diversity and inclusion in medicine evolve over your career? 

Yes, I have seen greater attention on actionable policies, plans and long-term strategies to address diversity and inclusion in the last year. This also comes with shedding light on the past to understand contextually how historical positions and policies in medicine and in society have had a sustained impact on where we are today. There has certainly been a great deal more magnification on this relationship. The key, however, is the importance of maintaining this focus and keeping up the momentum since the historical factors that got us here did not happen overnight and, as such, the work to achieve a more inclusive environment will not either. It will take sustained resources, time, effort, passion, and emphasis on this being an unwavering priority for everyone in medicine and something we all value as servants of health.

Read Interview with Professor Charlene Gamaldo: ‘Diversity must come with inclusion and placing a high value in providing a supportive environment for diverse voices to be heard’ in full

Professor Ruth Arnon is a leading Israeli biochemist and the Paul Ehrlich Professor of Immunology at the Weizmann Institute of Science. She is also the co-chair of the UK-Israel Science Council, a former Secretary-General of the International Union of Immunological Sciences and former President of the European Federation of Immunological Societies. Among her numerous accolades, she won the Robert Koch Prize in Medical Sciences (1979), the Chevalier de l’Ordre de la Légion d’Honneur (1994), the Rothschild Prize in Life Sciences (1998), and she was recognised as the first female President of the Israel Academy of Sciences and Humanities (2010).

 

Philipp Klocke) Looking back, what would you tell your younger self about the professional choices you made over your career?

I would tell her that she has chosen wisely. Looking back, I have enjoyed the road I have taken. It brought me satisfaction and, until today, I enjoy going to the lab.  It seems I have made the right choice.

 

Philipp Klocke) What is your approach to promoting scientific research among young people/adolescents?

My approach is to arouse their curiosity so that they will be interested in science.

 

Phoebe Liddell) How has the research environment changed for women during your career?

Personally, I have never felt any discrimination due to being a woman. However, in general, it’s possible that men were promoted at a faster pace than women. Today, it seems that there is an effort to avoid such discrimination.

 

Tianze Lin) Could you please comment briefly on Israeli scientific research, such as main strengths, weaknesses, challenges in the future? I am also interested in women’s participation in science (and dedicated strategies to promote that).

In Israel, there is a great effort to promote science and technology. Over 4% of the GDP is devoted to this. Women certainly participate in this effort both in academia and in high-tech and bio-tec companies. Quite a few women play a significant role – as Professors in Universities as CEO’s of companies, etc.

 

All members) How can we give women more access to high-level positions in research?

Just pay more attention to the progress they make in their research, give them a chance to write scientific papers and present at national and international conferences.

 

Nicole Kocurova) What do you think was the most groundbreaking scientific finding you contributed to during your research career?

The most groundbreaking scientific finding was producing a synthetic polymer that inhibits the animal model for multiple sclerosis, which led to the development of Copaxone.

 

Nicole Kocurova) How does the research environment compare in different countries and institutions that you were/are affiliated with?

Nowadays, in Europe, the USA, Canada and Australia, the environment is excellent. I am not familiar with the situation in other countries.

 

Phoebe Liddell) What do you think could improve international collaboration in science research?

More exchange programmes for students and young scientists at the beginning of their career would be helpful. Also, grants that support collaboration between scientists from different countries will promote teamwork.

 

Federico Licini) What are the advantages and disadvantages of working in academia compared to working in the pharmaceutical industry?

In academia, you have more freedom to follow your curiosity. In industry, you probably have a higher salary and have a chance to develop practical products, whether medical or industrial.

 

Federico Licini) How do you effectively balance your time to be part of multiple advisory boards for relevant scientific institutes while also conducting your research?

I manage.

 

Ruby Lathey) As a leading scientist who has roles in multiple fields of research and positions in both academia and industry, what are your opinions on communication between various sectors of science and how this can be improved?

I am an enthusiastic supporter of communication. It can be achieved by holding joint conferences and by the industry providing grants and support to scientists in academia and, thus, attract them to be interested in projects that are of mutual interests.

 

Nicole) Where do you think research is heading in your research field?

I hope that a universal flu vaccine will be developed in the not too far future.

 

Philipp Klocke) Do you think the BioNTech mRNA vaccine for future MS therapeutics is a potential success story?

I am not sure. It has as yet not been approached.

 

All members) Having worked on the influenza vaccine, what are your views on the current Covid-19 vaccination situation?

Developing an effective vaccine for COVID-19 in a record time of less than six months is an unbelievable achievement. Hopefully, it will help the world overcome the pandemic.

 

Picture credit: Weizmann Institute of Science

Read Interview with Professor Ruth Arnon: ‘Pay more attention to the progress women make in their research’ in full

Dr Martina Di Simplicio is a Clinical Senior Lecturer in Psychiatry working at the Centre for Psychiatry, Imperial College London. She investigates the cognitive and neural bases of mental imagery-focused emotion regulation treatment in bipolar disorder and self-harm. Before joining the UK, she trained in medicine and psychiatry at the University of Siena, Italy. She completed her PhD at the University of Oxford, where she trained in cognitive behavioural therapy at the Oxford Cognitive Therapy Centre, and specialised on mental imagery-based techniques. She then worked as a Career Development Fellow at the MRC Cognition and Brain Sciences Unit and as a Research Associate at Jesus College in Cambridge.

 

Nan Fletcher-Lloyd) In terms of women in science, do you have anyone you would consider being an inspiration to you? Who are they and why?

Since I was a teenager, my hero was Professor Rita Levi-Montalcini, the Italian neuroscientist and Nobel Laureate. I guess she was the only woman scientist with an international profile that we would know of at that time. Moreover, her personal history as a young Jewish girl left on me this impression of dedication, resilience and stamina that makes anything feels achievable if you have a real passion for studying. I also loved that she was old, full of wrinkles and beautiful; a different kind of woman to what you would see every day on a magazine. I recommend the comic book with her story if you don’t know her. I once happened to be in a hotel in Siena, my hometown, where she stayed. I saw her from a distance, but I was too shy to approach her. I still regret that.

 

Nan Fletcher-Lloyd) During your career, what would you consider to be your most important achievement, and why?

Do you want the job interview answer or the real-life answer? Jokes aside, so far it has been developing a new intervention that targets self-harm in young people. We are at the early stages of treatment development, so there’s a lot of work to do, from testing efficacy to unpacking mechanisms etc., but our initial data are promising. Importantly, every time I present it to a clinical team or young people, the feedback I receive is that it could fill a gap in clinical need, which is the motivation to keep working on it.

 

Nan Fletcher-Lloyd) What do you find to be the most interesting aspect(s) about your field of work?

I am drawn to cognitive neuroscience because the gap between performance on a cognitive task and translation into clinical psychiatry is *relatively* small. Thus, my research can simultaneously observe phenomenology (i.e., try to get into the subjective perspective of what patients are experiencing) and dissect it into cognitive dimensions. As a field, we claim that if we get it right, by training or manipulating certain cognitive functions (e.g., attention to specific stimuli or working memory), we can revert the psychopathology, but we still have to prove it. This is a great challenge to work towards.

 

Melendez, Sylvana) Could you elaborate more on your work about future episodic stimulation and the clinical benefits of this research?

Episodic future simulation happens in your mind (and body) when you imagine a specific detailed future scenario. Think of one specific activity or event that you’ve missed out on due to Covid-19, and then visualise in your mind as vividly as you can how the first time will be when you will be able to meet that friend again, travel to that particular place, see a relative who is shielding. While you imagine this, you may catch yourself smiling, getting teary or feel your heart racing. This kind of future mental imagery can become dysfunctional, for instance, if someone can’t stop vividly imagining terrible future scenarios, which generate high anxiety. Similarly, one can train the adaptive use of future simulation to enhance motivation towards rewarding activities. For example, to help overcome anhedonia (a core symptom of depression), or to engage in helpful behaviours as an alternative to self-harm. In my lab, we are testing which specific components of cognitive processes can be modified by future simulation and what makes future simulation work therapeutically to improve mood or behaviour. For example, is it about the duration, about how much you repeat it, about the ability to engage somatic areas of the brain and elicit change in the sympathetic/parasympathetic system? I am also interested in translating this into digital tools so that people could use an app to practice future mental imagery.

 

Philipp Klocke) A career in science naturally involves setbacks and failures – what keeps you motivated and on track?

Probably that I remain really passionate and interested in my area of research, whenever I have to start writing or re-writing a grant application, the process of setting hypotheses and designing experiments is fun and makes me overcome the fatigue or disappointment from previous failures. The other important aspect is a good peer network of colleagues with whom you can bounce off ideas and get open, direct and merciless, but constructive, feedback. That kind of contact is more difficult over Zoom or Teams, and it is probably what I am starting to miss due to the pandemic.

 

Alessia Marrocu) Working in the field of mental health and psychiatry, have you found it to be led predominantly by men or women? Stereotypically, it seems that the mental health field attracts more women, and I wondered if you have experienced this to be true or otherwise.

You are right. There are more women undergraduate psychology students, mental health nurses and, probably, the same goes for psychiatry trainees, because, compared to other medical specialities, it has the reputation of a better work-life balance. However, you have to look at the top of the pyramid: as in other sciences, professors in psychology and psychiatry remain predominantly white men. The good news is that things are changing – our Division of Psychiatry led by Prof Anne Lingford-Hughes is definitely a good example. The critical point is looking at how many women get into a postdoc or their first independent research position compared to their male colleagues.

 

Lucy Bedwell) In addition to experiencing sexism in academia, women are commonly perceived to experience increased ageism in comparison to male colleagues. Have you observed any differences in the way younger and older female colleagues are treated and have navigated the world of academia?

Sadly, yes. It’s unspoken, often subtle and non-verbal behaviour, but, to some people, you will always be “a young girl” …probably until you are a professor nearing retirement, and they may not even be aware they are doing this. I think it’s a broader cultural aspect that means that women are still raised to be “nice girls” and it becomes an ingrained mechanism that shifts not just men’s but women’s own behaviour. I definitely catch myself reverting to that position when I am in meetings with more senior people, predominantly men. I quite like being informal (which might be associated with young age), but since I noticed that all my male consultant colleagues wear a suit, I always wear a blazer in the clinic or whenever I have an important meeting. The flip side of the coin is that women who are very assertive and direct can be more easily labelled as “angry”, particularly if they are from a BAME background. I am hopeful though that, as we talk more and more openly about this, things will continue improving for your generation. I am also curious about whether academia more equally led by women will become less hierarchical.

 

Melendez, Sylvana) Which advice would you give to women in sciences who are just starting their career?

First, build resilience mechanisms and a support team… your own “fan club” of other women (and men too) that is a safe space to lick your wounds after another grant rejection and who will boost your confidence ahead of an interview. And not just academics: my most useful interview preparation was a mock with two friends who work in industry. This will help you “market” yourself a bit better while remaining true to your values, as women are still known to be (as a general rule with its own limitations) more self-critical than men.

Second, make sure you say “No, Thank you” as much as yes, as not all offers are opportunities, but can be distractors, and other colleagues can take on that additional responsibility too.

Third, if you are striving for an ambitious career, make sure your partner is ready to have an equal share of domestic and childcare responsibilities.

Read Interview with Dr Martina Di Simplicio: ‘Build resilience mechanisms and a support team’ in full

The Brain Prize is one of the most important awards in neuroscience. Awarded by the Lundbeck Foundation, it is worth approximately 1,3 million €. Professor Huda Y. Zoghbi and Prof. Sir Adrian Bird were awarded the 2020 Brain Prize for their ‘groundbreaking work to map and understand epigenetic regulation of the brain and for identifying the gene that causes Rett syndrome’, as stated by the Brain Prize motivation. Professor Huda Y. Zoghbi is an Investigator at the Howard Hughes Medical Institute, a Professor at the Baylor College of Medicine and the Director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. Among her numerous accolades, she has also won the Gruber Prize in Neuroscience in 2011, the Dickson Prize and the Pearl Meister Greengard Prize in 2013, the Shaw Prize in Life Science and Medicine in 2016, the Canada Gairdner International Award and the Breakthrough Prize in Life Sciences in 2017.

 

Elton Yeung) How does it feel to be awarded the Brain Prize? How will this impact your future plans?

It was a big surprise and it felt surreal as I had no idea this prize is given to scientists outside Europe or to molecular mechanisms of disease. As the news sank in, I started reflecting about the meaning of the prize and I realized it is a tribute to my patients and trainees, the ones that inspired me and the ones that trusted me. This prize will help us push forward on some challenging fronts to bring new ways to help treat people with Rett.

 

Rebecca Womersley) Learning about the scientific journey that led to your discoveries was incredibly inspiring. What would you say was your biggest inspiration through your research on Rett syndrome?

 Hands down the biggest inspiration came from people affected by Rett syndrome. Watching them struggle with all that this disease brings on and live with it, day after day and year after year, is what inspired and continues to inspire me to try harder to come up with solutions.

 

Kitty Murphy) Winning the Brain Prize is a great motivator and inspiration for women in STEM. What are the key moments that have led to this success?

First and foremost, encountering my first and then my second patient with Rett syndrome. Once I saw them, I could not take them out of my mind and wanted to help. Other key moments include meeting Ruthie Amir, who trusted me and was willing to work on Rett. Then there were the long days, months, and years of patience and perseverance as we systematically went through genes on the X chromosome, till we found the culprit—that was a most exciting moment.

 

Elton Yeung) Back to the days when you started raising awareness and advocating for the Rett’s syndrome (or other works), what was the most challenging step/setback and what was your strategy for tackling them?

Some of the challenges stemmed from the fact that I was young, just getting trained in molecular genetics, and hence it was very hard to have a voice that anyone would pay attention to. The other big challenge is the fact that the disease is sporadic and people had a hard time believing a sporadic disease could be genetically determined. Of course, today, we know this is very common. The only way I was able to overcome these challenges is by ignoring them and doing the work.

 

Rebecca Womersley) What would you say was the most challenging time in your career so far? How did you overcome these challenges?

The first was leaving my Alma mater, the American University of Beirut during the Lebanese civil war and being stuck in the USA and unable to return. I was fortunate to be accepted at Meharry Medical College, where I was able to finish medical school. The second challenging time was encountering children with neurological problems during my residency and feeling helpless in that I did not know the causes of their diseases and could not help in a meaningful way. This, of course, led to the third challenge which is switching from being a well-trained clinician to one who wants to do basic research but without a relevant experience—the transition was not easy and was truly humbling.

 

Kitty Murphy) What do you think was the greatest challenge female scientists faced when you began your career? How has this changed with time? 

To me, the greatest challenge as a female scientist was that I did not have around me role models of other female scientists who were successfully running a lab and trying to raise two babies. I did not know if I am making the right decision working, if my kids will be OK, how to balance things, and so on. I created my own world and dedicated my time to family and work. This was the best decision. Today women with and without children are key in the research workforce and are excellent role models for younger women. I share my stories with new working mothers so that they feel no guilt, as for years I lived with worry and guilt, until I discovered my kids turned out great. I thank my awesome husband, who was/is my main source of support and a wonderful dad.

 

Rebecca Womersley) Have you seen a positive change in the representation of female scientists in neurogenetics over your research career? Do you have advice for young women starting their research career in neurogenomics? 

Absolutely. I am embarrassed to say I was the lone female in that field when I started, but today there are so many wonderful, accomplished female scientists, in genetics, neuroscience, and neurogenetics. It is the most wonderful and exciting field as it uses genetics to solve some of the hardest disorders afflicting humanity.

 

Elton Yeung) What would be your advice for people trying to advocate for underrepresented and underfunded issues?

Please do not give up. This is so important. We will never be successful and safe as a society unless we attend to all issues and all people. This is an issue I am passionate about, as well. It is so important, thank you for dedicating your efforts to it.

 

Elton Yeung) How do you balance between personal life, research and medicine? Additionally, what would be your advice physician-scientist to-be?

To me, balance is living life doing what you think is important and dedicating the time to do it right. I am very organized and try to plan. When kids were little I was extremely disciplined about maximizing my work and productivity when in the lab (no breaks and no wasting of time), so I can go home and spend quality time with them, eat together, and put them to bed. I often had to go back to work after they slept, but at least I was with them when they needed me. I also made time for my husband, and we always did something special one weekend night. That said, there was no room for anything else in my life, exercise and other activities, came about much later… I was all about family and work until the kids went to college. Then I had more time to add exercise into my daily routine, and including travel in my working routine. As for a physician-scientist career, it is a most rewarding career, but please be prepared to dedicate 80% of your time to research and 20% to clinical work. This balance is critical.

 

Kitty Murphy) If you were to start your career over again in the present day, what areas of research would excite you as a career path? 

If I were starting today, I would do a double major in biology and math, and then specialize in tackling the genetics of mental illness. Psychiatry today is where neurology was a couple of decades ago, and we need to do so much work to solve these diseases that represent the largest burden on people, families, and society. I would hope a background in math would help invoke smart ways to tackle the complicated genetics of these disorders.

 

Rebecca Womersley) Which direction would you like to give to your research in the next ten years? 

I am hoping we can bring effective therapies to people with Rett syndrome and MECP2 duplications and come up with smart interventions that can prevent adult neurodegenerative diseases, like Alzheimer and Parkinson from ever developing.

 

Photography credit: Mr. Paul V. Kuntz

Read Interview with Professor Huda Zoghbi: ‘We will never be successful and safe as a society unless we attend to all issues and all people’ in full

Professor Carla J. Shatz is the first woman who received a PhD in Neurobiology from Harvard and the first woman who become Head of the Department of Neurobiology in the same university. She made breakthrough discoveries about the cellular and molecular basis of early cerebral development. Past President of the Society for Neuroscience, she is Fellow of the Royal Society, an elected member of the American Academy of Arts and Sciences, and of the National Academy of Sciences. Her long list of achievements includes also the Gerard Prize, the Gruber Prize, the Champalimaud Foundation Vision Award and the Kavli Prize in Neuroscience. Last, but certainly not list, here you can find the names of some among the neuroscientists she mentored during her career.

 

Alina Bondarenko) After completing your undergraduate studies, were you determined to pursue a career in neuroscience or were you considering other directions as well? Which options did you have at that time?

My undergraduate degree was in Chemistry. By my junior year of university, I realized that, although I loved Chemistry, it would not engage me over a lifetime. This realization propelled me directly into the newly born field of neuroscience. In 1968, on the advice of my undergraduate chemistry tutor Frank Westheimer, I reached out to two young faculty members of the newly formed (1966) Department of Neurobiology at Harvard Medical School: David Hubel and Torsten Wiesel. I spent my senior undergraduate year with them in tutorial and lab experience and was enraptured forever by studies of visual system function and development. Upon graduating (Harvard 1969; there was only one other woman chemistry major in my class), I was awarded a Marshall Scholarship to study for 2 years at University College, London. This wonderful honor happened because, unbeknown to me, the Dean of Students nominated me. It was quite unexpected since very few women were selected as Marshall Scholars (and women were not eligible for Rhodes Scholarships in those days). I received an M.Phil. in Physiology in 1971. The experience at UCL was formative and crucially educational- as a chemistry major at Harvard, I had never taken a single course in biology or physiology and so had a lot of catching up to do.

Living in London was exciting and wonderful, but I was anxious to return to the US. The question, though, was: how should I continue my career training? Should I apply to medical school or to graduate school? At the time women were admitted to Medical School, though in small numbers. Two of my uncles were clinical neurologists and both urged me to go to medical school. But several years earlier, Sonia- my paternal grandmother- had a devastating stroke. Not enough was known about the brain and even these two caring physicians could do nothing for Sonia except put her in a wheelchair and consign her to a nursing home. So, my decision was made: Go to graduate school, conduct research and make discoveries that might someday be relevant to help Grandma. When I made this decision, both of my uncles told me that I had made a “fatal career error” by deciding to do a Ph.D. rather than an M.D. When I received the Ph.D. in Neurobiology from Harvard Medical School in 1976, I was the first woman to do so. I felt welcomed and appreciated by Hubel and Wiesel, though at the time I expect that they and the Department were conducting their own “experiment” to see if a woman could succeed. Happily, the experiment proved successful. And eventually one of those neurologist uncles actually took me out to lunch and applauded my decision!

 

Kofoworola Agunbiade) You are the first woman who received a PhD in neurobiology from Harvard. Could you please give us one example of a situation where you had to be more vocal and assertive than your male colleagues?

As a Ph.D. student, I’m not sure that I ever had to be MORE vocal or assertive than my male colleagues. The environment in the Department of Neurobiology was remarkably supportive. However, please understand that I have always had a forceful personality and I think this trait has been both a strength and a weakness. As a child, my family engaged in many lively intellectual discussions and “arguments” around the dinner table and this family experience prepared me well as a Ph.D. student to hold my own in a scientific discussion (though it was definitely arduous dinner experiences for boyfriends and husband). Perhaps this early training even prepared me too well: Women are not necessarily rewarded or respected for being assertive. A challenge throughout my career has been to achieve a delicate balance on the tightrope between being overly assertive, as opposed to too compliant, since in both cases you end up being ignored. For example, I am not alone in having the experience of gently making a comment at a meeting that is promptly ignored, just to hear the exact same comment being applauded as a great idea when made again by a male colleague a few minutes later. This still happens to me, though these days I don’t hesitate to point it out.

 

Kofoworola Agunbiade) What was it like to work with Nobel Laureates David Hubel and Torsten Wiesel? How did they ‘shape’ you as a scientist?

The discoveries of Hubel and Wiesel of the columnar organization of circuits in primary visual cortex of animals with binocular vision, which resulted in the Nobel Prize in Physiology or Medicine in 1981, revealed brain circuits of almost crystalline- like perfection. Every day as a Ph.D. student I watched the beauty of visual system organization unfold before my eyes. I thought, “all research must be like this”, with major discoveries rolling off the press constantly! Of course, when I started my own lab, I realized that was not true, but from David and Torsten I learned the joy of research, the importance of articulating and presenting results clearly, and the thrill of going scientifically where few have ventured before. I can’t emphasize this point about venturing into the unknown enough- they described their own experiments as a voyage of discovery. If you view your research as an adventure, you don’t tire easily when difficulties are encountered because difficulties are part and parcel of any good adventure. Hubel and Wiesel were real people- we also played tennis together, ate dinner in lab together when experiments were running over night, went on ski trips and so on. From them I learned that the lab is also a home and your colleagues are your scientific family. Hubel and Wiesel have both been wonderful mentors and scientific parents ever since. But note that I did not have any “Womentors”, since at that time all faculty members in the Neurobiology Department at Harvard Medical School were men.

 

Alina Bondarenko) Have you ever felt that you, or your work, was treated differently because you were a woman, particularly at the early stages of your career?

I still feel that way. For a while, I thought that this feeling would disappear with success and age, but experience has proven otherwise. Being resilient is really helpful. Having good friends with whom to share your feelings and frustrations is crucial.

 

Alina Bondarenko) Which ‘leadership’ advice would you give to someone who feels like an outsider?

When I was a student, women were outsiders. Now, happily there is a good representation of women in neuroscience Ph.D. Programs, but not among the professoriate. Women are still forging paths to achieve balance between family and work. And so are men. This is an important time socially, when many men have partners who also have very high- powered jobs and so the challenge of creating a life that can encompass both work and family persists. Being “outside” is not only about gender and diversity. It can also be about being on the periphery of your own research field because you are forging a new scientific path or direction. My advice (which I try to take but not always successfully) is to have compassion and persistence. With compassion comes new ideas for creating a supportive environment based on your own experience. From this work, change can come but only with persistence.

 

Nadhrah Izmi) You are also the first woman to become Head of the Neurobiology Department at Harvard: what are the achievements you are most proud of?

I am most proud of the achievements of the junior faculty who were hired during my ChairWomanship (2000-2007). All of them are now very successful and all have received tenure: Lisa Goodrich, Bernardo Sabatini, Rachel Wilson, Chenghua Gu. Prior to my time as Chair, the basic science departments at Harvard Medical School had not granted tenure to junior faculty, who were generally expected to move on. This situation created both a gender gap and also an age gap between junior and senior faculty because the same great men who were there when I was a Ph.D. student were still on the faculty 25+ years later. The newly hired young scientists created a fresh environment of excitement and scientific novelty, and also most wonderfully all also managed to start families! They themselves achieved this success; I only helped by providing adequate resources and trying to create a positive and supportive environment in which they were expected succeed.

 

Faissal Sharif) It seems like students around the world are being taught with your explanation of the Hebbian theory ‘Cells that fire together, wire together’. What was the origin of that phrase? Did you expect that it would catch on?

It amuses me that the phrase is frequently attributed to Donald Hebb. In fact, I coined that phrase and used it often in lectures and seminars beginning in about 1989-1990, when my lab discovered the existence of spontaneously generated waves of activity in the developing retina (Meister et al, Science 1991; Shatz, Scientific American 1992). The phrase helps to explain how spontaneous neural activity during visual system development can drive synapse remodeling, resulting in highly ordered connections between eye and brain in which nearest neighbor relationships are preserved. The 2 key requirements for ‘Cells that fire together, wire together’ are 1) that groups of closely neighboring retinal ganglion cells (RGCs: the output neurons of the eye) are synchronously active, and 2) that there are Hebbian-based synaptic mechanisms similar to LTP (for strengthening) or LTD (for weakening out of synch inputs) at developing retinogeniculate synapses. It took us a number of additional years to prove that these endogenous patterns of retinal waves are relayed by the RGCs to their target LGN neurons in thalamus and drive Hebbian mechanisms of synaptic plasticity.

I’ve always been interested in the “nature vs nurture” question: That is, the question of how much connectivity is hard wired versus how much is tuned up by sensory experience driven by neural activity. When I set up my own lab at Stanford as an Assistant Professor, it occurred to me that by studying the development of connections between the retinal ganglion cells and their target LGN neurons it might be possible to address this question. The connections from eye to LGN are a developmental biologist’s dream because they are relatively accessible and highly stereotyped: In adult, retinal ganglion cells from each eye form connections with LGN neurons in separate but adjacent eye-specific layers. Prior to work from my lab, it had been generally assumed that the LGN layers had to be hard wired because they form prior to birth, well before the rods and cones function and before visual experience.

In the visual system of binocular mammals, this eye-specific segregation of RGCs is not present at the beginning of development. We showed that the eye-specific layers emerge as RGC axons remodel by pruning away sets of inappropriately located synapses and by growing and strengthening correctly located ones. We also found that these early synapses are functional and that the pruning process, which occurs long before vision, requires neural activity. Blocking action potential activity prevented eye-specific segregation. This observation surprised many at first but provided important evidence against the argument that connections are entirely hard-wired. On the other hand, blocking action potential activity did not alter the targeting of RGC axons to the LGN or the initial formation of the retinotopic map, both of which we know now are dependent on hard-wired molecular guidance cues, underscoring the dynamic interplay between “nature and nurture”.

The biggest surprise of all came when our lab discovered that the type of neural activity needed for LGN layer formation is generated spontaneously by the RGCs in the form of highly correlated “waves” of firing that sweep across the retina. This discovery was completely unexpected and happened at Stanford during a wonderful collaboration between Rachel Wong, at the time a postdoc in my lab and now a Professor at University of Washington, and Markus Meister, a postdoc in Denis Baylor’s lab and now a professor at Cal Tech. We used what was then a novel method of multielectrode recording to monitor simultaneously the neural activity of well over 50 retinal ganglion cells and found, incredibly, that even in the dark and prior to vision, neighboring RGCs in the eye fire action potentials synchronously. Subsequently, my lab showed that this synchronous activity is relayed to LGN neurons. These discoveries in the late 1980’s and 1990’s made me think about how Hebb synapses might function in developing systems, and I coined the phrase, “cells that fire together wire together” to help explain and teach the concept to students and audiences.

 

Nadhrah Izmi) Looking backwards, what advice would you give to your 20-something-year-old self?  

I would have told myself to check my fertility status! When I left home at age 16 to go to college, I had no idea what I might become. If you had asked me then to predict my future, I would have said that the one certainty is that I would be married with children. It is incredible to me that my life has turned out so differently. Back then, there were no role models to lead the way. I married, but waited until my scientific career was fully established and I had received tenure before embarking on creating a family, only to learn that it was too late to have children. I was an “experiment” in early in vitro fertilization techniques, which were unsuccessful despite many attempts. Nowadays there are so many options – and my advice to my 20-something year old self is to have a fertility evaluation and take appropriate steps. Though I don’t have biological offspring, there is still a silver lining. Over the years, I have been truly privileged to have incredible students and postdocs in the lab; these are my scientific children, and now even grandchildren (google Carla J. Shatz Family Tree – Neurotree). Without them, none of the discoveries would have happened. These extraordinary people- many now colleagues and friends- are not only talented and creative, but they have also had the courage to join me on the scientific journey, which has often ventured into unknown and controversial territory. There is no adequate way to express my gratitude to them.

Read Interview with Professor Carla Shatz: ‘When I received the PhD in Neurobiology from Harvard Medical School in 1976, I was the first woman to do so’ in full

Professor Fiona Watt is a leading British scientist in the field of Regenerative Medicine and the Executive chair of the MRC. She obtained her Bachelor of Arts and her Master’s Degree from the University of Cambridge and her PhD from the University of Oxford. After a two-year postdoc at the MIT, she came back to the UK to open her own lab at the Kennedy Institute of Rheumatology. Then, she moved to the Cancer Research UK, London Research Institute, and taught at the University of Cambridge, where she was also Deputy Director of the Wellcome Trust Centre for Stem Cell Research and of Cancer Research UK, Cambridge Research Institute. She then joined King’s College London, where she is currently directing the Centre for Stem Cells & Regenerative Medicine. Fellow of the Royal Society (since 2003), she has been the first woman president of the International Society of Stem Cell Research (2008).

 

Rebecca Womersley) What piece of advice would you have liked to receive at the beginning of your scientific career? 

That the people you meet early in your career are likely to pop up again for the rest of it.

 

Rebecca Womersley) Who are your role models, both within and outside of science, which have helped you ‘shaping’ your career? 

I would like to pay tribute to Brigid Hogan – she has not only been a great scientific role model but also a true friend and ally.

 

Elton Yeung) In 2008 you became the first woman President of the International Society of Stem Cell Research (ISSCR): have you ever experienced any significant challenges or setbacks in that role? 

No – the stem cell field has always attracted talented female researchers.

 

Matthew Brace) In 2018 you were appointed as the Executive Chair of the MRC: what attracted you to this role and what are your key goals for the coming years? 

The MRC is over 100 years old and yet its mission has remained constant – to improve human health through world-class research. Who wouldn’t want to lead such a wonderful organisation? I am very keen to support individual clinical and non-clinical scientists, to foster collaboration and translation, and to ensure that no-one is denied access to the infrastructure required to pursue their research.

 

Elton Yeung) Which specific traits of yours contributed to your success as a successful leader? 

Growing up, I only ever wanted to be a scientist. I’m adventurous and I tend to say ‘yes’ rather than ‘no’. And which skills and attributes are crucial for a successful leadership? I believe that it is important to listen to others, to have clarity of vision and to be compassionate.

 

Elton Yeung) How holding remarkable leadership roles have changed you as a human being? 

I have some sleepless nights and quite a few enemies.

 

Matthew Brace) How do you divide your time between the MRC and the Centre for Stem Cells and Regenerative Medicine at King’s College London, which you lead? 

I’m on secondment at the MRC for 80% of my time. That means I have one day a week at King’s and can hold weekly group meetings as well as catching up with everyone in my lab. I’m lucky that it only takes 25 minutes to walk between my office at the MRC and my lab. I can therefore fit lab time round MRC meetings and I don’t have to stick rigidly to one particular day of the week for King’s.

 

Matthew Brace) Stem cell research has advanced significantly over the past 20 years. What do you hope will be better understood in the next 20 years? 

I really hope that cell and gene therapies will continue to progress into clinical applications.

 

Rebecca Womersley) Many people assume there is a clearly defined boundary between arts and sciences: do you think so? Which role does creativity play in your work? 

I think scientists have much more in common – intellectually – with artists than with doctors, who are really craftsmen and women. Scientists need to have the time and space to be creative.

 

Elton Yeung) What would be your advice for women scientists who are about to start their journey in science? 

Go for it – it is much better to try and fail than never to try at all.

 

Matthew Brace) What is the most important advice you would give to a new PI on how to lead a lab?

Treat your team members with respect.

 

Rebecca Womersley) Looking backwards, which moment(s) are you particularly fond of and attached to? 

Over the years I have often taken my children to conferences. I will never forget my eldest telling me, after a conference reception, that I was ‘just a nerd magnet’.

Read Interview with Professor Fiona Watt: ‘It is much better to try and fail than never to try at all’ in full

 

Professor Marina Picciotto began her scientific career at Stanford University, where she received a B.S degree in biological sciences, and completed her PhD in Molecular Neurobiology at The Rockefeller University in New York City. She did a postdoc at the Pasteur Institute in Paris before joining Yale University in 1995, where she is currently the Charles B. G. Murphy Professor of Psychiatry and Professor in the Child Study Center. Among her many roles, she is also Deputy Chair for Basic Science Research within the Department of Psychiatry, Deputy Director of the Kavli Institute for Neuroscience and Editor-in-Chief of The Journal of Neuroscience. She won several prestigious awards, including the ‘Presidential Early Career Award for Scientists and Engineers’ (2000), the election to the National Academy of Medicine (2012) and as AAAS (American Association for the Advancement of Science) Fellow (2014), and the ‘Bernice Grafstein Award for Outstanding Mentorship’ from the Society for Neuroscience two weeks ago.

Does received a bachelor’s degree in Biology from the University of Sussex and is currently a MSc student in Translational Neuroscience at Imperial College London. The ever-changing world of science fascinates her, especially when it comes down to understanding the complexity of the human brain. To quote Francis Crick: ‘There is no scientific study more vital to man than the study of his own brain. Our entire view of the universe depends on it’.

Have you always known you wanted to do a PhD or was it something you decided as a Master student?

When I was an undergraduate, I worked in a laboratory, but thought I wanted to do a medical degree. By the end of my university degree, I knew I didn’t want to leave the lab, but only applied for graduate school after realizing late that I didn’t want to go to medical school or practice medicine. My graduate program did not offer a Masters degree.

Have you ever had to deal with the ‘imposter syndrome’, especially during the early stages of your career? 

I only started to have “imposter syndrome” once I got a faculty position. I always had doubts during training that my project would work out well or that I would be able to complete the experiments, but I was sure I was absolutely right to be there. When I became an assistant professor, I had many more doubts about whether I would be able to do what was needed to maintain a research program and continue to find out new things while supporting the work. While the doubts and anxiety about my abilities definitely got better as I became more senior, the internal dialogue about whether I should be doing what I’m doing and whether I have the abilities to do it is always there.

What would be your advice to neutralise the ‘imposter syndrome’?

I think most of us struggle with this and it is not something that should make us stop working as scientists if we continue to enjoy the work. I tell the internal voice that I will stop only when I decide it isn’t worth it to me or until someone actually makes me go home.

You have worked on nicotine and addiction. What is your stance on the use of e-cigarettes to help curb smoking addictions?

Anything that helps current smokers stop smoking is a huge public health boon. E-cigarettes are less harmful to addicted smokers than burned tobacco products. That said, the tobacco companies have taken advantage of this to market e-cigarettes to adolescents and non-tobacco users as perfectly safe. That is not true and neglects the fact that e-liquids contain a large number of chemicals that are being taken into the lungs, even though they aren’t “burned” and there is a large literature on the effects of nicotine on the developing brain. I don’t believe pregnant women or teenagers should vape nicotine.

Among the many roles you have, you are the editor-in-chief of The Journal of Neuroscience, Professor of Psychiatry at Yale University, PI of the Picciotto Lab and Deputy Director of the Kavli Institute for Neuroscience. How do you reconcile all these roles?

In some ways the roles are complementary. For example, I learn a tremendous amount about current neuroscience from my work at the Journal of Neuroscience and that improves the work in my own lab. I also get a lot of satisfaction from helping junior faculty succeed in their own work, my main role as Deputy Chair of the Department of Psychiatry, and that is a satisfaction that keeps me going in my academic career. Sometimes all the roles require my attention in a burst and it is challenging, but for the most part I am able to handle them by having people who help with many of the details and by learning what is most important for me to pay attention to, what is easy to get off my desk quickly, and how to delegate when I am not the right person to do something.

How do you achieve a good work/life balance?

Balance is probably a bad term that we have all adopted. What I think we should strive for is an understanding of our own values and needs that allow us to understand what we are willing to devote to each part of our lives. I have a pretty strict hierarchy of what is important to me, so my desire to be with my daughter and family on most evenings and weekends and also take care of them when they needed me most, allowed me to prioritize my time in a way that, for the most part, worked for me. My work is very important to me, so there is a baseline time commitment that I was also not willing to give up. My “balance” is almost certainly not the same as someone else’s. Determining what your own values are is essential to being able to find a work arrangement that is coherent with those values, and to spend the time with family that works with a partner or other family members.

What are your main tasks as editor-in-chief of The Journal of Neuroscience?

I have served in each of the editorial roles at The Journal of Neuroscience during my career, starting as an Associate Editor, then Reviewing and Senior Editor, and each has different demands. At The Journal of Neuroscience, Associate Editors are called on to serve as third reviewer and to step in when another reviewer is very late or disappears. Reviewing Editors invite reviewers and make the first decision on a manuscript they handle. Senior Editors make the final decision and calibrate the decisions across multiple Reviewing Editors. As a result, the Editor in Chief does not handle manuscript review personally. I will be called in if there is a difficult appeal or if there is any consideration of scientific or ethical misconduct. I also get to select the new editors when there is an opening on the editorial board, set Journal policies, write editorials to publicize our policies and communicate about best practices in experimental design or other issues important to the field, work with our Features Editor to select articles to highlight each week, communicate with Reviewing and Senior Editors to coordinate our editorial policies and decisions, work with our publisher (the Society for Neuroscience) to make sure that the Journal is operating appropriately, and most fun, work with our Features Editor and administrative staff to select the cover each week.

Pre-registration is something relatively new which some academic journals are starting to accept. How do you think this will affect the world of scientific research and publishing? 

Pre-registration is ideal for some types of studies where the experimental design is already clear. I think it will increase the reporting of negative findings, improve the power of pre-registered studies and overall increase the rigor of studies for which all the experiments can be predicted in advance. Pre-registration will not work for all types of studies, however. There are many things that are explored in basic science labs that cannot be predicted, and much of the work to come up with a new direction in this type of “discovery science” cannot be predicted. Science needs rigor, but it also needs unpredictability and exploration. Both need to co-exist and the limitations of each approach should be accepted. In the end, I believe that science relies most on replication and building on what was discovered. If a result is robust, it will be used by the next scientist to move the field forward. If not, it will ultimately be abandoned. There are ways to make sure that dead ends are abandoned more quickly, but we cannot avoid them completely.

How would you further support women in STEM within academia, in order to increase their presence?

Women are discouraged from STEM positions in academia at different points of their education and careers. In some fields such as mathematics, women face barriers early in their education when their abilities are still doubted by educators and maybe even family and other students. The public awareness campaigns that are currently encouraging entry into STEM fields can help with that, and teacher training, elimination of “weed out” courses for math and engineering, and changes in the format of early teaching may help in those fields. In other STEM fields, like biological sciences, there are equal numbers of students who enter, but the loss becomes greater at each stage of career development. At the postdoc level, we have to acknowledge that a handful of the most “prestigious” labs are often the source of candidates for subsequent academic positions. If funders of those large labs require equity in the trainees in those labs and if university search committees broaden their search beyond trainees from those labs, there will be a larger pool of diverse junior faculty members. At later stages of academic careers, our internal representation of what a “smart” person looks like and what a “leader” looks like also plays a very important role in who we select as chairs and deans. These types of unconscious biases are held by all of us, and the more that these biases can become acknowledged, the more we can broaden what we think a “leader” looks like, the more different types of leaders we will select. Finally, many individuals get discouraged after years of trying to change a system in which they feel they are either slighted or not recognized. An understanding that positive feedback and mentorship is essential throughout a career, not just during training, may help keep talented scientists in academic careers by making them understand that they are valued despite the obstacles or setbacks they continue to encounter.

Which changes would you like to see in the scientific landscape within the next 5-10 years?

I would like to see scientists continue their move to collaborate across disciplines and find ways to learn from others in fields as distant as possible from their own, both across scientific disciplines and between science and arts or other humanities. I would like to see a continued move by funding agencies to put aside a portion of their grants to very risky projects that may not work out and to find a way to communicate results of “failed” studies, rather than letting them disappear. Finally, as a neuroscientist, I hope to see a continued focus on integrating results across levels of observation (molecular, cellular, circuits, systems, behaviors, organisms) so that we can embrace the complexity of nervous systems and how they allow all of us with neurons to interact appropriately with our environments.

Read Interview with Professor Marina Picciotto: ‘Positive feedback and mentorship are essential throughout a career’ in full

Dr Magdalena Sastre is Reader in Molecular Neuroscience at Imperial College London. She graduated in Sciences and did her PhD in Biology and Health Sciences at the University of the Balearic Islands, Spain. She trained in Neuroscience in the USA (Cornell University and New York University) and in Germany (Universities of Munich, Bonn and Frankfurt). She is interested in the molecular mechanisms whereby inflammation impacts on aging-related neuronal degeneration. Her research is based on a multidisciplinary approach using molecular/cell biology, pharmacological, imaging and biochemical techniques.

Catriona completed her undergraduate degree in Neuroscience at the University of Glasgow where she investigated the auto-immune disease Guillain-Barré syndrome. Throughout her MRes in Experimental Neuroscience at Imperial College London, she has since moved towards a computational neuroscience approach, from her first project focussing on cell death in Multiple Sclerosis, to her subsequent projects in attentional control in Huntington’s disease and metastable cognitive states in Autism spectrum disorder.

What drew you to scientific research?

During my Biology degree we were allowed to work in labs during our free time and I ran small projects in different fields; I did a small project on Botanics, another on Limnology, which is the study of inland aquatic ecosystems,and did my masters on the Physiology of obesity. However, my interest in Neuroscience grew during the last year of my degree, when I learnt that mental disorders have a biological basis; this was a big driver for my PhD, which was on the role of noradrenergic signalling in the brain of suicide victims and I found this research very exciting.

Your research is focused on molecular and cellular aspects of neurodegeneration: what is your favourite aspect of a job in research?

There are many aspects that I like, starting by designing a project (a new idea), performing the experiments, teaching future researchers, attending conferences, meeting new people and publishing the results, so reaching the research community around the World. I have met so many interesting people thanks to science that are now my friends, it is great to still get in touch with those colleagues!

What is the most exciting research currently going on in your area of research, both within and outside of your lab?

In the last few years, the interest for the role on Neuroinflammation in the field of neurodegeneration, and in particular Alzheimer’s disease (AD), has grown significantly. We have been working in this area for many years. In particular, now we have several papers in preparation, analysing the role of astrocytes in Alzheimer’s disease, using different approaches from animal models to potential therapies in humans.

In your opinion, how important is the public awareness and education of scientific advances in a world where misinformation can spread uncontrollably? 

It is really important. I think that public engagement activities are essential to educate people and to help understanding our work. Unfortunately, a lot of information in the internet and newspapers are “fake news” and they spread very quickly.

What role can scientific researchers play in the stimulation and moderation of accurate and meaningful discussion between the science community and the public?

As I said above, it is important to give talks to the general public and to students, participate in documentaries, open the labs (we do that once a year) and other types of activities. We always receive very good feedback from the public attending our events and they then become more aware on how they can also contribute to science, by for instance, donating their brains for research (when they die, of course)!

Have you observed a positive change in the employment of women in more senior roles in academic research in the recent years?

Unfortunately, I haven’t seen a big change. The percentage of women in senior roles at the university is quite low. We are not taken very seriously and often are offered positions in teaching roles and responsibilities rather than research, although most of the PhD student and postdocs in our department are women.

Donna Strickland, the third female to earn the Nobel Prize in Physics (2018) said that she was surprised by the focus on her gender, and that she sees herself as a scientist, rather than a woman in science. Do you believe the emphasis on gender in media coverage of scientific accolades is beneficial in the quest for equality across STEM subjects?

It is clear that women need more support, because there is undoubtedly a bias regarding prizes and reaching senior positions in Academia. I do not want that women are offered positions based on a certain number, but I believe that there are great women scientists that have been obviated and forgotten. In part it is our fault, because we tend to be more humbled than men are.

Do you have anyone who is particularly inspiring for you? Within or outside of science?

One of the most inspiring scientists for me has been Marie Curie, for her dedication. Another great scientist that I admire is Santiago Ramón y Cajal, the funder of modern Neuroscience. Science is not only great ideas, but hard work!

In what direction do you hope to take your lab over the next few years?

We will continue exploring the role of Neuroinflammation in Alzheimer’s disease, trying also to find potential new treatments for this devastating disease.

If you had to pick any other research area to study, what would it be?

It would have to be in the field of arts and history.

Read Interview with Dr Magdalena Sastre: ‘Inspired by Marie Curie and Santiago Ramón y Cajal’ in full

Alexandra did her undergraduate in Molecular Biotechnology at the Technical University of Munich and worked on a project related to familial ALS during the MSc in Translational Neuroscience at Imperial College London. She has started her PhD at the Max-Planck-Institute of Neurobiology in Munich.

‘What was once thought can never be unthought’is one of the most famous quotes from ‘The Physicists’ written by Friedrich Dürrenmatt. Published in 1963, it treatises the responsibility of science. Even though its historical background is the Cold War, the topic of science responsibility towards society is still extremely relevant nowadays. At the crossroads between science and society, the word ‘responsibility’includes a plethora of different aspects, from the application of scientific findings to the correctness and the reproducibility of scientific research, and beyond. Here we will briefly discuss the case of neuroimaging in a legal context, reproducibility and prevention of misconduct.

When neuroimaging enters the court

Neuroimaging findings have been recently used for dangerousness assessments in criminal trials as part of the psychiatric testimony (Gkotsi and Gasser, 2016). Neuroimaging is a term that includes different methods to visualise the structure of the brain or its responses to tasks. A widely used imaging neuroimaging technique is fMRI, which relates neuronal activity, either within a task or a resting state, to neuronal networks by measuring the change in oxygen in the blood. These changes (known as BOLD, an acronym for blood oxygen dependent contrast) are supposed to reflect changes in neuronal activity in the areas they occur.

However, fMRI still has some limitations. One of them is its limited temporal resolution (Ugurbil, 2016). Another one is linked to the fact that the measurement of neuronal activity is indirect, as it relies on changes in the blood supply of certain areas. For this reason, imaging data should be used very carefully, especially since, at first glance, they might look like ‘objective criteria’ to determine a person’s dangerousness (Gkotsi and Gasser, 2016). As easy explanations are tempting in times with rising public fears, Gkotsi and Gasserwarn about an ‘instrumentalisation of neuroscience in the interest of public safety’.

In addition to this, trying to relate features of dangerousness, like violence, to a single biological cause is a ‘simplistic falsity’ as it negotiates the social influences on an individual (Pustilnik, 2008). On top of that, the legal and social definition of what is seen as a violent behavior itself changed over time, making explanations of dangerousness even more complex. With our brains being extremely interconnected, it is not possible to relate something which is as complicated on different levels as violence only to a single brain region (Pustilnik, 2008). Even if certain brain regions like the prefrontal cortex, which is the anterior part of the brain, relate to ‘social control’, they are also linked to ‘problem solving’ or ‘pain processing’,and they are always integrated in a wider network (Onget al., 2018). Moreover, functional-anatomical correlations does not inform us about causality (Pustilnik, 2008).

Furthermore, this would also lead to the danger of stigmatisation of people with neurological or psychiatric disorders (Gkotsi and Gasser, 2016). For example, schizophrenia could be related to an ‘absence/diminishment of criminal responsibility’ in a systematic review (Tsimplouliset al., 2018). However, the same review states that ‘many individuals with schizophrenia do not meet the legal criteria for an insanity plea’. This serves as a reminder for a careful approach to every individual case since a psychiatric condition per seis not a factor for committing. Stigmatisation has negative effects: a large-scale study showed that, independently from the symptoms, only the diagnosis of schizophrenia lead to the diagnosed person being described as more ‘aggressive’, ‘dangerous’and less ‘trustworthy’(Imhoff, 2016). Moreover, the diagnosis of a risk of developing schizophrenia was related to stigmatisation, although more information about the actual risk of developing the psychosis could reduce the stigma (Yanget al., 2013).

Reproducibility and prevention of misconduct

Science needs to be reliable and reproducible. In 2016, a Naturesurvey conducted among more than 1500 researchers showed that more than 70% of them were unable to reproduce their own or another person’s findings (Baker, 2016). This does not necessarily mean that science is facing a crisis (Fanelli, 2018), keeping in mind that reproducibility issues can help to develop the state of knowledge by detecting hidden variables (Redishet al., 2018). Still several researchers appeal to take actions to ensure responsibility when possible. Those include publishing of methods in more detail as well as publishing negative results in conditions not used for the final experiment that gave the expected results, as this would also help other scientists (Drucker, 2016). Another suggestion would be to introduce a‘reproducibility index’for senior researchers as an easy way to show how many of their findings have been reproduced by another group (Drucker, 2016). Moreover, other scientists suggested that it should be easier to publish retractions while distinguishing between scientific misconduct and the recognition of being wrong due to later experiments (Flier, 2017). It was also pointed out that the peer-reviewing process should be publicly available for the benefit of  the whole community as other scientists could potentially profit from the suggestions made within this process (Flier, 2017). In addition, work of reviewers would be acknowledged while professional conflicts would be made obvious. During this process, it should be made sure that strict reviewers are not made target of harassment of disappointed authors(Flier, 2017).

To maintain responsible science, prevention of misconduct is another essential aspect. Another Naturesurvey conducted on more than 3,200 scientists found out that ‘slightly more than half of non-PIs said they had often or occasionally felt pressured to produce a particular result in the past year’(van Noorden, 2018), and‘Group and authority pressure’was one of the pitfalls named for research misconduct (Gunsalus and Robinson, 2018). More training was advocate to sensibilise young scientist on the theme of research misconduct and assessing the research climate in the lab as a further possible tools preventing this issue (Gunsalus and Robinson, 2018).

Conclusions

Overall, raising awareness of these problems in scientific research is the first step towards a more responsible scientific and social environment. Together with the suggestions made by different scientific groups, including more scientific training and critical reflection of their own research, everyone can contribute to this goal.

In ‘21 points to the Physicists’, Dürrenmatt stated that ‘the content of physics is the concern of physicists, its effect the concern of all men.’ As this is not only true for physics but for scientific research as a whole, responsibility should be a key characteristic of science.

 

 

References

Baker, M (2016): 1,500 scientists lift the lid on reproducibility. Nature 533 (7604), 452–454.

Drucker, DJ (2016): Never Waste a Good Crisis. Confronting Reproducibility in Translational Research. Cell metabolism 24 (3), 348–360.

Dürrenmatt, F (1963): The physicists. A play in 2 acts.

Fanelli, D (2018): Opinion. Is science really facing a reproducibility crisis, and do we need it to? Proceedings of the National Academy of Sciences of the United States of America 115 (11), 2628–2631.

Flier, JS (2017): Irreproducibility of published bioscience research. Diagnosis, pathogenesis and therapy. Molecular metabolism 6 (1), 2–9.

Gkotsi, GM; Gasser, J (2016): Neuroscience in forensic psychiatry. From responsibility to dangerousness. Ethical and legal implications of using neuroscience for dangerousness assessments. International journal of law and psychiatry 46, 58–67.

Gunsalus, CK; Robinson, AD (2018): Nine pitfalls of research misconduct. Nature 557 (7705), 297–299.

Imhoff, R (2016): Zeroing in on the Effect of the Schizophrenia Label on Stigmatizing Attitudes. A Large-scale Study. Schizophrenia bulletin 42 (2), 456–463.

Ong, W-Y; Stohler, CS; Herr, DR (2018): Role of the Prefrontal Cortex in Pain Processing. Molecular neurobiology.

Pustilnik, AC (2008): Violence on the brain: a critique of neuroscience in criminal law. Harvard Law School Faculty Scholarship Series.Paper 14

Redish, AD; Kummerfeld, E; Morris, RL; Love, AC (2018): Opinion. Reproducibility failures are essential to scientific inquiry. Proceedings of the National Academy of Sciences of the United States of America 115 (20), 5042–5046.

Tsimploulis, G; Niveau, G; Eytan, A; Giannakopoulos, P; Sentissi, O (2018): Schizophrenia and Criminal Responsibility. A Systematic Review. The Journal of nervous and mental disease 206 (5), 370–377.

Ugurbil, K (2016): What is feasible with imaging human brain function and connectivity using functional magnetic resonance imaging. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 371 (1705).

van Noorden, R (2018): Some hard numbers on science’s leadership problems. Nature 557 (7705), 294–296.

Yang, LH; Anglin, DM; Wonpat-Borja, AJ; Opler, MG; Greenspoon, M; Corcoran, CM (2013): Public stigma associated with psychosis risk syndrome in a college population. Implications for peer intervention. Psychiatric services (Washington, D.C.) 64 (3), 284–288.

 

Picture credits: Wellcome Collection (picture by Gabriel González-Escamilla)

Read A brief reflection on (neuro)science and social responsibility in full

Ines has completed a research project in computational neuroscience, focusing on learning impairments in Parkinson’s disease. Her previous research experience during her BSc included studies on rodent models of ADHD (University of Manchester) and Alzheimer’s disease (Institute for Functional Genomics, Montpellier, France). Her interest in writing about HIV stems from the fact that she was born and grew up in Mozambique, a country where HIV/AIDS continues to be a significant health threat, affecting over 10% of the population and where over 800,000 people live with HIV on ART.

On the 5^th of June 1981, the cases of 5 patients infected with what would later come to be known as the human immunodeficiency virus (HIV) were reported for the first time in Los Angeles, USA (CDC, 1981). In the years that followed, the virus rapidly spread across the globe, with a peak of new infections (3.5 million) recorded in 1997 (Roser and Ritchie, 2018). By 2016, there were approximately 36.7 million people living with HIV worldwide (UNAIDS, 2017).

The human immunodeficiency virus is transmitted through contact with bodily fluids. Although sexual transmission is the most common form, HIV can also be passed on through contact with infected blood or by vertical transmission. The latter refers to the case of mothers transmitting the virus to their children during pregnancy, childbirth or breastfeeding (Levy, 1993; Roser and Ritchie, 2018).

HIV belongs to a subgroup of viruses called lentiviruses. The term lentivirus comes from the Latin lentus, which means slow, owing to its long incubation period in the infected organism before any overt manifestation of disease is detectable (Haase,1986). Due to this defining characteristic, HIV infection is initially asymptomatic, but if left untreated, it may have notable negative effects and eventually lead to death (Moir et al., 2011). Although the viral infection in itself is not usually the direct cause of death, HIV suppresses the immune system, making patients particularly vulnerable to certain cancers and other infections, while being unable to naturally fight them. This state of immunosuppression and the spectrum of potentially fatal symptoms that accompany it are collectively termed Acquired Immune Deficiency Syndrome (AIDS) (Levy, 1993; Weiss, 1993; Naif, 2013). Over 70% of HIV infection cases have been reported in sub-Saharan Africa, where, to date, AIDS ranks as one of the major causes of death among adults (Roser and Ritchie, 2018).

Where the virus meets the brain

There is currently no vaccine or cure for HIV infection. Nonetheless, the last 37 years have seen major advances in the understanding of its pathophysiology as well as the wide range of clinical manifestations it may have. Among them, several neurological complications have been identified (Saloner and Cysique, 2017, Grant et al., 1987). These complications can be broadly categorised into two classes: primary and secondary. Primary complications arise as a direct effect of HIV replication in central nervous system cells; the most notable example being HIV-associated neurocognitive disorder (HAND). Secondary complications, however, result from the previously mentioned opportunistic infections that occur when patients are immunosuppressed (Kolson, 2017).

Evidence suggests that HIV enters the central nervous system within the first few weeks post-infection, an early stage in the course of the disease (Abidin et al., 2018). As the virus replicates, it may trigger a cascade of events at the molecular level that lead to chronic inflammation in the brain (Kolson, 2017). Consequently, the central nervous system may undergo primary damage that is only detected much later, when patients present with neuropsychological symptoms (Ellis et al., 2007, Abidin et al., 2018).

One of the most severe forms of cognitive impairment observed among patients is HIV-associated dementia (HAD) (Saylor et al., 2016, Grant et al., 1987, Ellis et al., 1997). In the early years of the AIDS epidemic, this was a common feature of a patient’s clinical presentation and was often fatal. This would go on to be so until the development of antiretroviral drugs in the mid 1990s (Saylor et al., 2016).

The impact of ART

Since the introduction of antiretroviral therapy (ART), there has been a major shift in  prognoses for patients living with HIV as well as in the manifestation of the virus in the brain. Briefly, antiretroviral drugs are a group of pharmacological agents that target different parts of the HIV life cycle. ART is not capable of eradicating the virus, but it is able to inhibit its replication, thus, reducing or entirely preventing immunosuppression (Ellis et al., 2007). In the present day, an HIV-positive diagnosis in areas where ART is readily available no longer necessarily translates to an imminent death or even to the development of AIDS (McArthur et al., 2003). Instead, HIV infection can become a chronic condition that allows patients to have close to normal life expectancies, especially when treatment is started early (Wandeler et al., 2016, Saylor et al., 2016). With regard to the brain, in patient populations undergoing ART, the incidence of severe neurocognitive problems such as HAD and that of secondary neurological complications has been shown to decrease drastically (Saylor et al., 2016).

Nevertheless, there are limitations to the therapeutic effect of ART. A neurologically relevant example of this is the finding that the blood brain barrier (BBB) restricts the entry of certain antiretroviral drugs into the central nervous system (Langford et al., 2006). The blood brain barrier separates neurons from circulating blood. Its permeability is highly selective, allowing for tight control of the material that is exchanged across it (Zlokovic, 2008). However, it has been hypothesized that by hindering the penetrance of certain antiretroviral drugs, the BBB allows the activity of HIV to partially persist in the brain (Ellis et al., 2007). In accordance with this hypothesis, over 50% of the HIV-positive population is estimated to be susceptible to HIV-associated neurocognitive disorders; though these are often milder forms of HAND than those observed pre-ART (Abidin et al., 2018, Chakradhar, 2018). However, it can also be hypothesised that independent of ART penetrance, such cognitive problems may be long-term sequelae of primary insults (Ellis et al., 2007).

Furthermore, the consequences of long-term administration of ART are currently not fully understood and it has been suggested that it could also play a role in neuronal damage (Kolson, 2017). Nevertheless, whatever the exact causes may be, mild forms of HAND are undeniably common among patients and can be detrimental to their quality of life (Saylor et al., 2016; Abidin et al., 2018). With the expanding availability of ART, the importance of addressing such issues has gained increased recognition given that  HIV positivity has become a long-term status for many of those affected (Wing, 2016; Chakradhar, 2018).

The aftermath of survival: from development to ageing 

The fact that ART allows HIV-positive individuals to live much longer than they could in the beginning of the AIDS epidemic has set several new neuroscience research challenges as there are still many gaps in the understanding of the long-term effects of HIV infection (Wing, 2016).

On one end of the age spectrum, there are increasing survival rates among children and adolescents who initiated ART soon after vertical transmission, creating a window of opportunity to investigate the role of HIV infection in the developing brain (Li et al., 2018, de Martino et al., 2000). Further, this group constitutes a new population of individuals, many of whom are now adults, who have been on ART for their entire lives.

On the other end, with the continuous (though decreasing) occurrence of new HIV infections and a reduction in deaths due to AIDS (UNAIDS, 2017), there is a growing HIV-positive population that is ageing (Wing, 2016). In fact, a study based on people living with HIV in the Netherlands projected that by 2030, almost 75% of this population would be composed of people aged 50 or older (Smit et al., 2015). This raises interest in the interaction between HIV infection and ageing-associated neurocognitive processes.

In 2016, Turner and colleagues reported the first case of an individual with both HIV and Alzheimer’s disease, the most common cause of dementia (Turner et al, 2016). As more and more of these cases appear, it is important to find the means to distinguish between Alzheimer’s and HAND symptoms as well as to identify any links that may exist between them (Chakradhar, 2018). In recent years, it has often been debated whether HIV infection might accelerate ageing (Chakradhar, 2018, Deeks et al., 2013). Given, that age is the strongest risk factor for Alzheimer’s disease, this could be a potential link to HIV. Furthermore, a study in neurons derived from mice found that ART may contribute to the deposition of the protein, amyloid beta, a hallmark of Alzheimer’s disease pathology (Giunta et al., 2011). Taken together, these ideas build a case for the possibility of interactions between age, HIV and ART.

Future prospects: where to look for clues?  

One of the main aims for the future of neuro-HIV research is to find differences, be they anatomical, functional or molecular, between healthy and HIV-positive individuals that might help detect and/or predict the occurrence of neurological problems at early stages (Clifford, 2017). Such characteristic traits of pathological processes are known as biomarkers. The use of tools to visualise the brain in vivo (neuroimaging) has been an increasingly popular approach to solving this problem. For example, a few recent studies have applied neuroimaging techniques to the investigation of anatomical and functional changes in the brains of young people infected with HIV (Ackermann et al., 2016, Randall et al., 2017, Toich et al., 2017). Others have looked into characteristics that may distinguish the effects of the virus from processes associated to ageing or non-HIV-related neurodegeneration (Zhang et al., 2016, Cole et al., 2017). Further, a study by Wiesman et al,. (2018) specifically investigated potential imaging-based biomarkers of HAND. These studies have highlighted specific alterations in grey matter volume, white matter integrity and network connectivity. In time, such findings may begin to shape an HIV-specific neurocognitive profile. Ideally, this will improve prognosis for patients and help define new therapeutic approaches that might improve the quality of life of those living with HIV.

 

 

References

Abidin AZ, Dsouza AM, Nagarajan MB, Wang L, Qiu X, Schifitto G and Wismuller A (2018) Alteration of brain network topology in HIV-associated neurocognitive disorder: A novel functional connectivity perspective. Neuroimage: Clinical 17:768-777.

Ackermann C, Andronikou S, Saleh MG, Laughton B, Alhamud AA, van der Kouwe A, Kidd M, Cotton MF and Meintjes EM (2016) Early antiretroviral therapy in HIV-infected children is associated with diffuse white matter structural abnormality and corpus callosum sparing. American Journal of Neuroradiology 37(12):2363-9.

CDC (1981) Pneumocystis Pneumonia — Los Angeles. Morbidity and Mortality Weekly Report 30:250-2.

Chakradhar S (2018) A tale of two diseases: Aging HIV patients inspire a closer look at Alzheimer’s disease. Nature Medicine 24(4):376.

Clifford DB (2017) HIV Associated Neurocognitive Disorder. Current Opinion in Infectious Diseases 30(1):117-22.

Cole JH, Underwood J, Caan MW, De Francesco D, van Zoest RA, Leech R, Wit FW, Portegies P, Geurtsen GJ, Schmand BA, Schim van der Loeff MF, Franceschi C, Sabin CA, Majoie CB, Winston A, Reiss P and Sharp DJ (2017) Increased brain-predicted aging in treated HIV disease. Neurology 88(14):1349-1357.

de Martino M, Tovo PA, Balducci M, Galli L, Gabiano C, Rezza G and Pezzotti P (2000) Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. The Journal of the American Medical Association 284(2): 190-7.

Deeks SG, Lewin SR and Havlir DV (2013) The end of AIDS: HIV infection as a chronic disease. The Lancet  382(9903):1525-33.

Ellis R, Langford D and Masliah E (2007) HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nature Reviews Neuroscience 8(1):33.

Ellis RJ, Deutsch R, Heaton RK, Marcotte TD, McCutchan JA, Nelson JA, Abramson I, Thal LJ, Atkinson JH, Wallace MR and Grant I (1997) Neurocognitive impairment is an independent risk factor for death in HIV infection. Archives of Neurology 54(4):416-24.

Giunta B, Ehrhart J, Obregon DF, Lam L, Le L, Jin J, Fernandez F, Tan J and Shytle RD (2011) Antiretroviral medications disrupt microglial phagocytosis of beta-amyloid and increase its production by neurons: implications for HIV-associated neurocognitive disorders. Molecular Brain, 4(1):23.

Grant I, Atkinson JH, Hesselink JR, Kennedy CJ, Richman DD, Spector SA and McCutchan JA (1987) Evidence for early central nervous system involvement in the acquired immunodeficiency syndrome (AIDS) and other human immunodeficiency virus (HIV) infections. Annals of Internal Medicine 107(6):828-36.

Haase AT (1986) Pathogenesis of lentivirus infections. Nature 322(6075):130.

Kolson D (2017) Neurologic Complications in Persons with HIV Infection in the Era of Antiretroviral Therapy. Topics in Antiviral Medicine 25(3): 97-101.

Langford D, Marquie-Beck J, de Almeida S, Lazzaretto D, Letendre S, Grant I, McCutchan JA, Masliah E and Ellis RJ (2006) Relationship of antiretroviral treatment to postmortem brain tissue viral load in human immunodeficiency virus-infected patients. Journal of Neurovirology 12(2): 100-7.

Levy JA (1993) Pathogenesis of human immunodeficiency virus infection Microbiological Reviews 57(1):183-289.

Li J, Gao L, Wen Z, Zhang J, Wang P, Tu N, Lei H, Lin F, Gui XE and Wu G (2018) Structural Covariance of Gray Matter Volume in HIV Vertically Infected Adolescents. Scientific Reports 8(1):1182.

McArthur JC, Haughey N, Gartner S, Conant K, Pardo C, Nath A and Sacktor N (2003) Human immunodeficiency virus-associated dementia: an evolving disease. Journal of Neurovirology 9(2):205-21.

Moir S, Chun TW and Fauci AS (2011) Pathogenic mechanisms of HIV disease. Annual Review of Pathology 6:223-48.

Naif HM (2013) Pathogenesis of HIV Infection. Infectious Disease Reports 5(Suppl 1):e6.

Randall SR, Warton CMR, Holmes MJ, Cotton MF, Laughton B, van der Kouwe AJW and Meintjes EM (2017) Larger Subcortical Gray Matter Structures and Smaller Corpora Callosa at Age 5 Years in HIV Infected Children on Early ART. Frontiers in Neuroanatomy 11:95.

Roser M and Ritchie H (2018) HIV/AIDS OurWorldInData.org. Available at: https://ourworldindata.org/hiv-aids(Accessed: 22/05/2018).

Saloner R and Cysique LA (2017) HIV-Associated Neurocognitive Disorders: A Global Perspective. Journal of the International Neuropsychological Society 9:860-9.

Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M, Mankowski JL, Brown A, Volsky DJ and McArthur JC (2016) HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment. Nature Reviews Neurology 12(4):234.

Smit M, Brinkman K, Geerlings S, Smit C, Thyagarajan K, Sighem A, de Wolf F and Hallett TB (2015) Future challenges for clinical care of an ageing population infected with HIV: a modelling study. The Lancet Infectious Diseases 15(7):810-8.

Toich JTF, Taylor PA, Holmes MJ, Gohel S, Cotton MF, Dobbels E, Laughton B, Little F, van der Kouwe AJW, Biswal B and Meintjes EM (2017) Functional Connectivity Alterations between Networks and Associations with Infant Immune Health within Networks in HIV Infected Children on Early Treatment: A Study at 7 Years. Frontiers in Human Neuroscience 11:635.

Turner RS, Chadwick M, Horton WA, Simon GL, Jiang X and Esposito G (2016) An individual with human immunodeficiency virus, dementia, and central nervous system amyloid deposition. Alzheimer’s & Dementia 4:1-5.

UNAIDS (2017) UNAIDS DATA 2017. Available at: http://www.unaids.org/en/resources/documents/2017/2017_data_book(Accessed: 20/05/2017).

Wandeler G, Johnson LF and Egger M(2016) Trends in life expectancy of HIV-positive adults on ART across the globe: comparisons with general population. Current Opinion in HIV and AIDS 11(5):492-500.

Weiss RA (1993) How does HIV cause AIDS?. Science 260(5112):1273-9.

Wiesman AI, O’Neill J, Mills MS, Robertson KR, Fox HS, Swindells S and Wilson TW (2018) Aberrant occipital dynamics differentiate HIV-infected patients with and without cognitive impairment. Brain 141(6):1678-1690.

Wing EJ (2016) HIV and aging. International Journal of Infectious Diseases 53:61-68.

World Economic Forum (2018) HIV/AIDS is no longer the leading cause of death in Africa. Available at: https://www.weforum.org/agenda/2017/08/hiv-aids-is-no-longer-the-leading-cause-of-death-in-africa (Accessed:27/05/2018).

Zhang Y, Kwon D, Esmaeili-Firidouni P, Pfefferbaum A, Sullivan EV, Javitz H, Valcour V and Pohl KM (2016) Extracting patterns of morphometry distinguishing HIV associated neurodegeneration from mild cognitive impairment via group cardinality constrained classification. Human Brain Mapping 37(12):4523-4538.

Zlokovic BV (2008) The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders. Neuron 57(2):178-201.

Read The HIV-positive Brain in the ART Age in full