Issue No. 88 BNA Bulletin Spring 2020 THE VOICE OF BRITISH NEUROSCIENCE TODAY Curious for answers The neurobiology of curiosity Painful truths The of pain

PLUS: Neuropixels Neurofeedback for pain FENS 2020 11-15 July 2020 | Glasgow, UK

Organised by the Federation of European Neuroscience Societies (FENS) Hosted by the British Neuroscience Association (BNA)

DATES & DEADLINES 20 April 2020: Final deadline for submission of Forum events 23 June 2020: Deadline for late registration

Where European neuroscience meets the world

REGISTER NOW REGISTRATION OPEN 20 plenary and special lectures 56 parallel symposia 3,500 abstracts The FENS Forum is Europe’s premier neuroscience meeting. It covers all domains in modern neuroscience, from basic to translational research. For further information, please visit www.fens.org/2020 and follow us on social media #FENS2020

www.fens.org/2020 Contents

Issue No. 88 BNA Bulletin Spring 2020 BNA Bulletin THE VOICE OF BRITISH NEUROSCIENCE TODAY Editor: Curious for answers Ian Jones, Jinja Publishing Ltd The neurobiology of curiosity Design and production: Painful truths The genetics of pain Jag Matharu, News Research PLUS: Thin Air Productions Ltd Neuropixels Neurofeedback for pain FENS 2020 Advertising in the BNA Bulletin: Contact the BNA office 05 24 ([email protected]) for advertising Message from David Bennett: rates and submission criteria. the President and The genetics of pain Copyright: © The British Neuroscience Association. Chief Executive Extracts may be reproduced only with permission of the BNA. John Tenniel’s illustration 26 from The Nursery ‘Alice’ (1889), ISSN: 1475-8679 06–08 Matteo Carandini: a shortened version of Alice’s Neuroscience news Neuropixels and Adventures in Wonderland BNA Office adapted by Lewis Carroll for Anne Cooke distributed brain young children. Curiosity was University of Bristol function too much for young Alice. Dorothy Hodgkin Building See page 30 for more on the Whitson Street neuroscience of curiosity. Bristol BS1 3NY Image: WikiMedia Commons. Web: www.bna.org.uk Analysis 28 The British Neuroscience Aleksandra Association is a registered charity (1103852) and a Vučković: registered company (04307833) 09 Neurofeedback limited by guarantee. FENS 2020 control of chronic pain BNA Council and National Committee 10 BNA COUNCIL The BNA’s year 30 Annette Dolphin (UCL): President of pain Matthias Gruber: Rik Henson (Cambridge): President-Elect The neuroscience Stafford Lightman (Bristol): Immediate Past President of curiosity Zoe Kourtzi (Cambridge): Secretary 11 Catherine Harmer (Oxford): Treasurer Brain and Anthony Isles (Cardiff): Communications Neuroscience 32 Anne Lingford-Hughes (Imperial): Professional Liaison Advances Irene Tracey: Sarah Guthrie (Sussex) and Hugh Piggins (Bristol): A life in science Meetings Secretary Rosamund Langston (Dundee): Group Co-ordinator

Narender Ramnani (Royal Holloway, University of London): 12 Research Policy BNA Christmas Alan M Palmer, Kevin Cox, Manfred Berners: Symposium and Independent Trustees prize winners Et cetera NATIONAL COMMITTEE Crawford Winlove (Exeter): Education and Engagement Secretary 14-17 34 Elizabeth Coulthard: Membership Secretary and Out and About Undergraduate Neurology Advisor and postgraduate Natalie Doig (Oxford): Students and Early Careers Representative prize winners Emma Yhnell (Cardiff): Equal Opportunities and 18–23 Diversity Representative Bright Brains BNA EXECUTIVE Anne Cooke: Chief Executive Sophie Sykes-Jerrold: Development Director Alex Campbell: Head of Communications and Marketing Louise Tratt: Executive Officer Lydia Bown: BNA Outreach Ambassador Elena Toma: BNA Outreach Ambassador

www.bna.org.uk Spring 2020 BNA Bulletin 03 04 BNA Bulletin Spring 2020 www.bna.org.uk News

Message from the President and Chief Executive Manifesto launch Dear BNA Members We’ve had an incredible winter, despite the record rainfall! One of the highlights was the launch of our high-profile campaign, ‘Credibility in Neuroscience’, with an event at the House of Commons in late November. In front of a broad guest list of politicians, media, academics and members, we unveiled our manifesto – with the aim to raise awareness and enable all neuroscientists to stay informed about credibility. You can keep up to date with all things ‘InCredible’ at www.bnacredibility.org.uk. The BNA launched its ‘Credibility in Neuroscience’ We’ve also been working hard on advocacy. A recent example manifesto at an evening reception at the House of has been our contribution, via our Trustee for Research Policy, Commons on 25 November 2019, with guest speakers Narender Ramnani, to a POSTnote on brain–computer interfaces, including BNA Patron Lord Winston and Dorothy focusing on the underpinning technology, its applications, Bishop (Oxford) as well as BNA Chief Executive and the associated ethical and regulatory challenges. Anne Cooke. Of course, central to our campaigning work is making sure The vision of our manifesto is for neuroscience we properly represent your voice, as members. That’s why research to be as robust, reliable, replicable and it’s always a treat to speak to so many of you at our annual reproducible as possible. It is backed by three Christmas Symposium. The latest symposium, on pain, was a commitments: to support a shift in research particular success. Held at iconic at King’s College culture that is welcomed and desired by the whole London, the meeting included speakers from institutions across neuroscience research community; to equip all the UK and Europe, and featured on Radio 4’s All in the Mind. neuroscientists with the skills, knowledge, tools Looking forward, we’re currently in full throttle as host and processes they need to carry out credible society for FENS 2020 (11–15 July). We’re proud to be helping to neuroscientific research; and to change the landscape host ‘introductory courses’ on 10 July 2020. These accessible in which neuroscientists operate so that the introductions, delivered by internationally renowned researchers, influences that drive neuroscience research also will increase your knowledge and perhaps even stimulate a drive the most credible research. change in career direction. Plus, we’re also helping to stage Thanks to generous funding from the Gatsby a city-wide ‘Great Glasgow Brain Fest’ for the wider public. Charitable Foundation, we are developing a Don’t forget, as members you benefit from discounted significant programme of activities, promoting and registration rates. supporting credibility in neuroscience research over Another date for your diary: 14 May 2020. At Eli Lilly’s Research the next ten years. Further information about our Centre in Surrey, we’ll be hosting ‘New treatments for pain’, manifesto, planned activities and credibility more a meeting bringing together the commercial, academic, and generally can be found on our dedicated new not-for-profit sectors. The aim is to share current knowledge, website (www.bnacredibility.org.uk). identify future directions, and enable collaboration, providing delegates with practical ways to accelerate their own work. See our website for full details. Today in As you can see, there’s a lot going on! Our members remain at the heart of our work, so do get in touch if there’s anything Parliament we can help you with. It’s only by strengthening and growing our very special, collaborative and innovative neuroscience In October 2019, the BNA was accepted as a member community that we can continue to advance neuroscience of the Parliamentary and Scientific Committee in the UK and beyond. (P&SC). Established in 1939, this committee is a key interface between scientists and parliamentarians, and will provide valuable opportunities for the BNA to inform discussion and decision-making in both the House of Commons and the House of Lords on issues related to neuroscience. The BNA will be represented on the P&SC by Narender Ramnani, Trustee for Research Policy. Annette Dolphin Anne Cooke President Chief Executive www.bna.org.uk Spring 2020 BNA Bulletin 05 News

supported by the Gatsby Charitable further information. Never the Foundation and Wellcome, which aims to This initiative is a key part of our bridge the gap between clinical psychiatry commitment to enabling greater twain and neuroscience. Bristol delegates sharing of information and growing the had the opportunity to hear about the connection between associate members In November 2019, the BNA and the latest ground-breaking research and and scientists. If you have a question Sainsbury–Wellcome Centre at UCL its implications for understanding and you would like answered, send it to teamed up to organise a lunchtime treating psychiatric conditions, as well [email protected]. event on the implications of the as to network with scientific and clinical Research Excellence Framework (REF) colleagues. See bit.ly/2H1Y2LC for more for reproducibility. ‘Never the twain details of the Integrating Neuroscience Brain Fest shall meet’ featured presentations from Project. open science advocate Marcus Munafo As well as a rich menu of scientific goodies, (Bristol), BNA President-Elect Rik Henson the BNA’s Host Society Committee is (Cambridge) and Helena Mills, Head of Brain teasers planning a full programme of public events REF Policy at Research England. BNA associate members can now take – under the banner of the ‘Great Glasgow advantage of an enhanced version of Brain Fest’. The main event will be held the ‘Ask a Scientist’ service. Associate on the weekend before FENS, 4–5 July, Neuro Nets members can submit queries to the BNA at Glasgow Science Centre. Full details office, which identifies a suitable expert of the programme will be announced In October 2019, the BNA took part in able to answer it. As well as responses later in the spring. one of the first regional neuroscience being sent to the original questioner, they update days – ‘Neuro Nets’ – in Bristol. will now also be included in the e-bulletin The events are being run across the UK as sent to all associate members, along with part of the Royal College of Psychiatrists’ the name of the scientist who answered Integrating Neuroscience Project, the question and any other relevant

Local News and Events

Sheffield success holding research days. More information of advanced imaging and use of virtual Congratulations to the Sheffield Institute about the Centre can be found at reality in research. for Translational Neuroscience (SITraN), bit.ly/2S57mV4. which has been awarded the Queen’s Brain Bee Anniversary Prize for innovation in UCL Neuro Day Cardiff’s Neuroscience and Mental Health neuroscience. The prize recognises The 11th UCL Neuroscience Symposium Research Institute hosted the annual outstanding work by UK higher education will be held at the ULC Institute of Wales Brain Bee competition in December institutions demonstrating quality and Education on 26 June 2020. As well as 2019. Sixth-form science students from innovation in their research, and this presentations from across UCL, keynote six schools came together to compete and award reflects Sheffield’s great success addresses will be delivered by Vanessa test their knowledge of neuroscience in in research designed to improve care of Ruta (Rockefeller University, New York) lab challenges, written exam questions people with neurodegenerative conditions and Philip McGuire (KCL). and a team neuro-challenge. Three female such as Parkinson’s disease and motor students from Cathedral School took neuron disease. SITraN, which celebrates CNS2020 home first, second and third prizes, and its 10th anniversary in 2020, is part of The 2020 Cambridge Neuroscience Cathedral School claimed the Wales Brain the University of Sheffield’s newly Seminar (CNS2020) will take place on Bee shield for the second year running. launched Neuroscience Institute. 15 April 2020. The meeting, to be held at Robinson College, will feature speakers Edinburgh neuro-day UCLAN research day from across the many departments The 2020 Edinburgh Neuroscience Day The University of Central Lancashire in Cambridge involved in neuroscience took place on 11 March 2020. The Annual (UCLAN) Research Centre for Brain and research as well as external speakers. Distinguished Lecture 2020 was delivered Behaviour held its first research day in by Robin Ali (UCL). December 2019. The Centre was founded Oxford outreach in August 2019 and has been supporting Neuroscience researchers across Oxford neuroscience research by awarding small made major contributions to the IF Oxford research grants, organising monthly Science and Ideas Festival in October seminars by external speakers and 2019. Events included a demonstration

06 BNA Bulletin Spring 2020 www.bna.org.uk News

Blavatnik BPS award Edinburgh award Francesca Happé (KCL) has been awarded award the British Psychological Society’s (BPS’s) Presidents’ Award for 2019. Charles ffrench-Constant received Happé has made major contributions to Edinburgh’s 2019 Chancellor’s Award for the understanding of the neurocognitive Research Excellence. Reflecting the great basis of social impairments in autism. strength of Edinburgh neuroscience, the The 2019 BPS Lifetime Achievement previous year’s Chancellor’s Award went Award went to Susan Michie (UCL). to Richard Morris.

Tim Behrens. Mental health Gontijo Award Tim Behrens (Oxford) has received a Blavatnik Award for Young Scientists, Elaine Fox (Oxford) has been appointed Laura Ferraiuolo (Sheffield) was the selected by the Blavatnik Family the national Mental Health Impact and winner of the 2019 Paulo Gontijo Award, Foundation and the New York Academy Engagement Coordinator by UK Research in recognition of her work on glial cells and of Sciences. The awards are the largest and Innovation, the umbrella body of motor neuron disease. Established in 2007, unrestricted cash prizes available to the UK Research Councils. She will play the Paulo Gontijo Award recognises early- scientists under the age of 42. Professor a key role in promoting the coordination career researchers working on the causes Behrens receives a laureateship worth of collaborative and multidisciplinary and treatments of motor neuron disease. £75,000 in the life sciences category. research in mental health. The 2020 laureates and finalists were honoured at a ceremony in London on Epilepsy award 4 March 2020 and presented their research RCPE award at a public symposium the following day. Angela Vincent (Oxford) received the Sarah Tabrizi (UCL) has been awarded the Research Recognition Award, Clinical Alexander Morison Medal by the Royal Science, at the 2019 annual meeting of SfN appointee College of Physicians of Edinburgh (RCPE). the American Epilepsy Society. Professor Her co-head of department, Nick Fox, Vincent, who shared the award with Jane Haley (Edinburgh) has been received the same recognition the previous J Dalmau, has made major contributions appointed to the Society for Neuroscience’s year. Professor Tabrizi has made landmark to epilepsy research and treatment, and (SfN’s) Neuroscience Training Committee. contributions to the understanding and was the BNA Outstanding Contribution Dr Haley is the only non-US member of treatment of Huntington’s disease. to Neuroscience award winner in 2015. the 16-strong committee, which oversees the implementation of SfN’s higher education and training strategy. Her three- Graham year term began at the 2019 SfN annual meeting in Chicago. Bull Prize Sarosh Irani (Oxford) has been awarded Nature award the Royal College of Physicians’ Graham Bull Prize in Clinical Science/Goulstonian Tom Baden (Sussex) is the inaugural Lectureship for his work in autoimmune winner of the Nature Research Awards neurology. Angela Vincent. for Driving Global Impact. Established in partnership with Tencent, the Awards recognise early-career researchers whose Synaptome Mike Berridge work has made, or has the potential to make, a positive impact on society. funding The BNA was saddened to hear of As well as his groundbreaking research on the death of Sir FRS vision (see BNA Bulletin 81, Autumn 2017), Seth Grant (Edinburgh) has been awarded in February 2019. Professor Berridge Professor Baden has also been involved in £1.3m by Wellcome to continue his work carried out pioneering research on signal initiatives to use tools such as 3D printing mapping the molecular composition of transduction, particularly on inositol to produce affordable lab equipment. the synapse across the brain. trisphosphate signalling and its links to intracellular calcium release. www.bna.org.uk Spring 2020 BNA Bulletin 07 News

News in Brief Neuroscience@Nottingham Chicken stress Tom Smulders (Newcastle) is leading The annual Neuroscience@Nottingham Research and Poster Day took place on 15 January a €3.9m European initiative, funded 2020, attended by neuroscientists from across various departments in Nottingham and by the EU Marie Curie Fund, exploring other institutions. The event kicked off with a workshop on ‘Multi-disciplinary approaches how stress affects the chicken brain. to treating anxiety disorders’, which brought together research in rat models of fear and The ChickenStress European Training anxiety (Carl Stevenson, Nottingham) with clinical research (Naomi Fineberg, University Network is bringing together 20 partners of Hertfordshire; Catherine Harmer, Oxford), as well as with experience of clinical in academia and industry to explore treatment practice (Fineberg; Stephen Regel, Nottingham). the impact of the rearing environment This was followed by the poster session, where around 30 posters were presented and other factors on behaviour and on research ranging from molecular and cellular to cognitive, computational and clinical brain function, with the ultimate goal neuroscience. Two postgraduate poster prizes were awarded to Samantha Harrison of improving animal welfare. (‘Using fNIRS to assess cortical responses to auditory and visual speech in a paediatric population’) and Sara Goncalves (‘MIA-induced osteoarthritis-like knee pain impacts BAP meeting on cognitive function in Lister hooded rats’). The summer meeting of the British The guest speaker Catherine Harmer (Oxford) gave a lecture on ‘How do Association for Psychopharmacology will antidepressant drugs work?’. The lecture was preceded by brief presentations highlighting take place in London on 19–22 July 2020. key neuroscience-related initiatives at Nottingham, including the Research Beacon for Precision Imaging and the Interdisciplinary Research Clusters on Technological BNS meeting Innovations in Health and Wellbeing, and on Improving Health and Wellbeing in The spring 2020 meeting of the British Contemporary Society. The event was supported by the BBSRC and the BNA. Neuropsychological Society will take place on 22–23 April 2020 at the Clinical Neurosciences Centre, Queen Square, New funding London. The Elizabeth Warrington Prize Lecture will be delivered by Muireann Peter Kind, Adrian Bird and colleagues in Edinburgh have been awarded £12m funding Irish (University of Sydney). from the Simons Foundation, extended funding for the Simons Initiative for the Developing Brain from 2022 to 2025. Developing brain The Wolfson Foundation has made a £10m award to support a new Wolfson Centre The Academy of Medical Sciences for Young People’s Mental Health at Cardiff. The Centre, to be led by Frances Rice and has published a summary of a two- Stephan Collishaw, will be a dedicated interdisciplinary research centre focusing on day interdisciplinary workshop on reducing anxiety and depression in young people. ‘The developing brain in health and The author J K Rowling has donated a further £15.3m to Edinburgh to support disease’. A PDF can be downloaded research on ‘the invisible disabilities’ experienced by people with multiple sclerosis, at bit.ly/2w0yQD3. such as cognitive impairment and pain. The investment will support new facilities and research at Edinburgh’s Anne Rowling Regenerative Neurology Clinic. Recruitment A US$7m grant from the Alzheimer’s Association in the USA will allow UCL Mental health research charity MQ researchers to investigate the influence of genetics, health and lifestyle on dementia has launched a new digital platform, risk across the life course in 500 members of the 1946 British birth cohort. Participate, to address the challenge of Researchers from Edinburgh (Claire Durrant) and UCL (Cara Croft and Christy Hung) recruitment in mental health research. have received £1.5m fellowship funding from Sir Jackie Stewart’s Race Against Dementia The website (https://participate. charity, working in partnership with Alzheimer’s Research UK. As well as research mqmentalhealth.org) enables potential funding, the initiative provides with opportunities for support from innovation participants to discover ongoing research experts at Dyson Technology and Formula 1 motorsport. projects and what they involve. European Research Council Consolidator Grants have been awarded to Tiago Branco (UCL; Circuit and cellular mechanisms for computing spatial vectors to shelter during escape), Pleasantine Mill (Edinburgh; Molecular principles of mammalian axonemal dynein assembly), Jean-Baptiste Pingault (UCL; From parental risk to child mental illness: a genetically informed investigation of intergenerational risk pathways) and Nathalie Rochefort (Edinburgh; Envisioning the reward: Neuronal circuits for goal- directed learning).

08 BNA Bulletin Spring 2020 www.bna.org.uk Analysis FENS 2020 – The countdown begins Registration for the 2020 FENS Forum, the European neuroscience event of the year, is now open.

With the FENS Forum coming to the UK for the first time since 2000, the BNA is proud to be the host society of FENS Forum 2020. We have had a hands-on role in developing the exciting and stimulating programme – as well as an unrivalled line up of plenary speakers (see Box), FENS Forum 2020 will feature 56 parallel symposia and more than 3500 abstracts, as well as associated mini-conferences, technical workshops, a grand debate, multiple opportunities for networking, and public events.

Masterclasses and receive up to €1000 in support costs, or a Forum networking event. Satellite The BNA and the Gatsby Charitable thanks to the Young Investigator Training meetings are independent but related Foundation are sponsoring a range of Programme (YITP). scientific events scheduled for before or introductory masterclasses in topical areas Organised by the Host Society after the FENS Forum, while networking of neuroscience, which will be held on Committee and the BNA, and funded events are held in the evening during the Friday 10 July 2020, the day before the by the International Brain Research Forum. The closing date for proposals start of the FENS Forum. Organisation (IBRO), the scheme will is 20 April 2020. The courses are being delivered by enable early-career researchers to internationally renowned researchers and undertake a short, focused research Plenary lectures build from a broad and easy-to-understand project, to build their technical skills • Eve Marder (USA): Differential introduction to the latest cutting-edge and provide networking opportunities. resilience to perturbation of circuits research. The courses are being held at More than 30 UK-based researchers with similar performance (Fred Kavli various centres across Glasgow: across all areas of neuroscience Opening Lecture). • Improving mental health and psychiatric have offered to host a visit and have • Erin Schuman (Germany): disorders: complementary preclinical and developed mini-projects (see https:// Local protein synthesis in neurons. clinical research: University of Strathclyde forum2020.fens.org/young-investigator- • Sheena Josselyn (Canada): • Credibility of neuroscience: increasing programme/ for details). The amygdala and memory: the transparency and reliability of modern- Recalling the past, imaging the future. day neuroscience: University of Strathclyde Workshops, mini-conferences • Rosa Cossart (France): • The microbiome and the gut–brain and events How development scaffolds adult axis: What is it and why is it important? A range of specialist workshops will take hippocampal dynamics. University of Strathclyde place as part of the meeting. These focus • Andreas Meyer-Lindenberg • Manipulating neuronal activity using on optogenetics, large-scale monitoring (Germany): Neural mechanisms of chemo- and optogenetics: University of of neural activity, technologies for environmental risk for psychiatric Glasgow studying glial cells, Drosophila whole disorders (Presidential Lecture) • Glial cells: Identities, functions brain connectomics, negotiation skills • Rui Costa (USA): Discovering, and roles in brain health and disease: and career advice. reinforcing and refining actions. Glasgow Caledonian University In addition, eight mini-conferences • Sonia Garel (France): Early cortical For full details and registration will be held on Saturday 11 July 2020. wiring and neuroimmune interactions information, see https://forum2020.fens. These will cover areas such as behavioural (ERA-NET Neuron Lecture) org/introductory-courses/ neuroscience, cognitive impairment, • Jan Born (Germany): Sleep’s role in human brain imaging, neuroeconomics, memory consolidation (Tianqiao and Young Investigator translational neuroscience, sleep, nicotine Chrissy Chen Institute Lecture). Training Programme and brain development, and a Cajal Club • Karl Deisseroth (USA): New approaches Thirty lucky early-career researchers from event. to studying intact brain structure around the world will have the opportunity If you would like to get involved in and function (Hertie Foundation to spend 2–3 weeks before the FENS the FENS Forum, there is still time to Closing Lecture). Forum in a leading UK neuroscience lab, submit proposals for a satellite meeting www.bna.org.uk Spring 2020 BNA Bulletin 09 Analysis Pain: Friend and foe Pain, the BNA’s theme for 2020, is both a medical challenge and a scientific conundrum.

The experience of acute pain might not NOWHERE IS THE PHRASE ‘ALL IN simple correlation between brain activity be pleasant but it serves a vital function, THE MIND’ LESS HELPFUL THAN and perception of pain. As a result, warning us of tissue damage and helping IN PAIN – THE EXPERIENCE OF psychological factors and brain states can us to learn things to avoid. But when pain PAIN AND ALL THE FACTORS THAT have a major impact on the experience persists after initial injuries have healed MODULATE IT EMERGE FROM THE of pain. Nowhere is the phrase ‘all in then it can have a devastating impact INTERPLAY BETWEEN NEURONS. the mind’ less helpful than in pain – on quality of life. the experience of pain and all the factors Although the full extent of chronic pain to the deaths of more than 130 people that modulate it emerge from the is difficult to judge precisely, it is without every day from overdoses in 2016 and 2017. interplay between neurons. question a major medical challenge Added to this complexity is the and a source of misery for millions (see A scientific conundrum experience of pain unrelated to tissue Box). Chronic pain is associated with As well as being a medical challenge, injury – grief, heartbreak and other forms a wide range of conditions, including pain is a complex phenomenon that is of mental anguish. The relationship cancers, diabetes (diabetic neuropathy), only partially understood. Notably, pain between ‘mental’ and ‘physical’ pain is nerve injury, migraine, degenerating can be studied at many different levels. also beginning to be teased apart. conditions such as multiple sclerosis, Central to pain are the sensory neurons Pain is therefore an ideal theme for the and musculoskeletal conditions such that detect tissue damage, nociceptors. BNA for 2020. It is scientifically fascinating as rheumatoid arthritis. Much is now known about the ion channels and of great socioeconomic significance. In terms of pain control, acute pain and other signalling molecules that The year kicked off with a pain-related can usually be managed effectively. generate pain signals. These molecules are BNA Christmas Symposium – stay tuned Over-the-counter medicines such as also important targets for the development for news of more events and initiatives aspirin, ibuprofen and paracetamol enable of pharmacological interventions. during the year. us to deal with everyday aches and pains. As well as the molecular properties Stronger analgesics are available to of ion channels, researchers are also The impact of pain clinicians managing more severe pain. studying the activities of nociceptors and • Chronic pain affects between one-third Chronic pain, by contrast, presents of the neural pathways that convey pain and one-half of the UK population. a more formidable medical challenge. sensory to the brain via the spinal cord. • Almost half of people with chronic Some effective drugs do exist but they Brain imaging studies have revealed much pain have a diagnosis of depression do not work for everyone and it is difficult about the networks of brain activity and two-thirds are unable to work to predict which drug a patient is likely associated with pain. outside the home. to respond to. Furthermore, the risk of But pain is much more than just • In 2016, £537m was spent on dependency is a major issue with some signal and response. Descending pathways analgesic prescriptions, with at least an treatments – witness the opioids epidemic can have a significant modulating impact additional 50% cost incurred from the in the USA; an estimated 10 million on pain signalling to the brain at the prescription of other drug classes such as Americans are misusing opioids, leading level of the spinal cord. And there is no antidepressants and antiepileptic drugs. • The economic impact of pain is high due to absenteeism, poor productivity and people with pain leaving the workforce. In the UK, the annual productivity cost of back pain is estimated to be between £5bn and £10.7bn. • Painful conditions such as arthritis and back pain account for one-third of all claims for disability benefits in the UK. • An EU-wide survey in 2017 found that 95 million people across Europe live with chronic pain and the total economic impact of chronic pain was estimated to be as high as €300bn. Wellcome Images

The pain of gout, coloured etching, 1835, after J Gillray, 1799.

10 BNA Bulletin Spring 2020 www.bna.org.uk Analysis Indexing ahoy Brain and Neuroscience Advances has passed the key PubMed Central assessment – paving the way to full indexing in 2020.

The year began with a bang for Brain and “THIS IS AN EXCITING AND Neuroscience Advances with the news that IMPORTANT MILESTONE FOR THE the journal had passed PubMed Central’s JOURNAL AND TESTAMENT TO scientific assessment. To safeguard THE EXTRAORDINARY EFFORTS the quality of PubMed Central, the US OF THE EDITORS AND STAFF AT National Library of Medicine undertakes a SAGE. I’M VERY GRATEFUL FOR comprehensive assessment of the scientific THE UNSTINTING SUPPORT I’VE rigor of journals applying to be indexed HAD THROUGHOUT FROM THE fascinating insight into the development and included in PubMed Central. This is the BNA OFFICE AND COUNCIL.” of our understanding of GABA, critical step in the application process for Jeff Dalley, Editor-in-Chief, from its discovery as ‘factor I’ in indexing – a short technical evaluation is Brain and Neuroscience Advances crustaceans to its current position as now in progress which should present few one of the most critical neurotransmitters issues for Brain and Neuroscience Advances’ to SAGE Journals for their efforts in controlling human brain function. publishers, SAGE Journals. shepherding Brain and Neuroscience If you would like to contribute to We therefore anticipate that final Advances through the PubMed Central Special Collections, or if there is an area approval will be secured in spring 2020. submission process. of neuroscience you think would benefit As well as including all new articles, Special collections from a Special Collection and would like to PubMed Central will also retrospectively A stimulating set of papers will shortly be involved in its development, then get index all content back to 2017. This will be published in the Special Collection on in touch with the Brain and Neuroscience ensure greater visibility of articles and neuroinflammation, overseen by Lead Advances Editor-in-Chief, Jeff Dalley provide a major fillip to the journal. Guest Editor Kerrie Thomas (Cardiff) ([email protected]). The positive opinion from PubMed and Guest Editors Paul Morgan and Central is testament to the unceasing Jeremy Hall (Cardiff). Glasgow bound labours of Editor-in-Chief Jeff Dalley and A further Special Collection is being Brain and Neuroscience Advances will also his team of Senior Editors, Editorial Board developed on fast-acting antidepressants have a presence at FENS 2020 in Glasgow Members, and all the researchers involved such as ketamine and its derivatives. in July. Professor Dalley will be taking part in the published content of Brain and This Special Collection is being overseen in a Special Interest Event at lunchtime on Neuroscience Advances. We are incredibly by Guest Editors Catherine Harmer Sunday 12 July, ‘How society-owned journals grateful to everyone who has devoted (Oxford) and Mitul Mehta (KCL). handle your paper’, alongside editors from time to making Brain and Neuroscience Another article has also been added to Neuroscience, the Journal of Neuroscience, Advances a success, including researchers the Special Collection celebrating 50 years and the European Journal of Neuroscience. who have submitted papers for publication of British neuroscience. Trevor Smart in early volumes. We are also grateful and Anne Stephenson (UCL) provide a Newly published Claudia Metzler-Baddeley (Cardiff) and colleagues have published novel in vivo neuroimaging evidence for distinct microstructural properties of pre-commissural and post-commissural fibers in the fornix, a key structure in the hippocampal complex (see Figure). It what seems like the blink of an eye, we are already onto Brain and Neuroscience Advances volume 4. All content is freely available at https://journals.sagepub.com/home/ bna and full details on how to submit a manuscript can be found at https://journals.sagepub.com/author- instructions/BNA. Projections from the rat hippocampal formation (from Mathiasen et al.). www.bna.org.uk Spring 2020 BNA Bulletin 11 Analysis Pain gain Though focused on pain, the BNA Christmas Symposium was a festive pleasure.

PAIN IS A COMPLEX Laurie in House – kidnapping a patient PHENOMENON, TRIGGERED BY and forcing him to undergo mirror box NOCICEPTORS IN THE PERIPHERY therapy – Tamar Makin (UCL) focused on DETECTING TISSUE DAMAGE BUT the perplexing challenge of phantom limb CHARACTERISED BY COMPLEX pain. People who undergo amputations PATTERNS OF PROCESSING IN commonly maintain the perception of the THE BRAIN WHICH GIVE RISE lost limb, which often feels painful. This TO THE SUBJECTIVE EXPERIENCE has traditionally been thought to reflect OF PAIN. loss of inputs from the amputated limb to the somatosensory cortex, followed by The BNA Christmas Symposium attracted a nociceptor-specific HCN channel, ‘invasion’ of surrounding areas into what more participants than ever to its new HCN2, that may be a ‘pacemaker of were that limb’s cortical areas. The mirror venue at Bush House on the Strand, pain’. Ivabradine, an HCN antagonist, has box treatment is designed to reverse this formally the home of the BBC World analgesic properties, but lowers heart process. However, Dr Makin’s work has Service but now occupied by KCL. As is rate alarmingly. His group has developed revealed that somatosensory cortical now traditional, the Symposium provided a compound that is specific for HCN2 and areas appeared to be preserved to a much an opportunity to introduce the BNA’s has shown great promise in pre-clinical greater degree than previously thought. theme for the coming year, pain. models. Rights to the compound were Rarely, people are born without the Irene Tracey (Oxford), the brains sold to Merck for US$340m. ability to sense pain. As David Bennett behind the programme, provided a brief Bridget Lumb (Bristol) focused on pointed out, such people are often seen introduction to the field, and raised descending pathways, which have the as curiosities – as illustrated by the some of the points due to be discussed capacity to modulate pain signals from ‘human pincushion’, Edward Gibson, who by Joanna Bourke (Birkbeck) who was the periphery. With Richard Apps, she has in the 1920s would insert needles into unfortunately unable to attend. Pain is been exploring interactions between the his face in the cause of entertainment. a complex phenomenon, triggered by periaqueductal grey and the cerebellum, Mutations in several are now known nociceptors in the periphery detecting in a more systems-wide perspective that to cause insensitivity to pain, such as tissue damage but characterised by integrates motor responses to painful PRDM12 and Nav1.7, and generally disrupt complex patterns of processing in the stimuli. the function of nociceptors (although brain which give rise to the subjective Lesley Colvin (Dundee) brought a mutations in a FAAH pseudogene experience of pain. As well as neural clinician’s view of pain. Chronic pain is influence pain perception by altering signalling, this experience is also common – affecting 18% of people in endocannabinoid production). As well as influenced by sociocultural factors – Scotland – and difficult to treat. Although providing insights in to the mechanisms including religious interpretations of most patients will respond to a treatment, of pain signalling, identification of suffering and the supposedly character- it is currently difficult to predict in advance such genes also provides leads for drug enhancing properties of physical adversity. which option would be most appropriate. development. Professor Tracey distinguished acute Dr Colvin pointed to the current difficulties Ulrike Bingel (Essen) discussed the pain, which helps us to detect and avoid in assessment; better methods would help remarkable power of the placebo effect threats to health, from chronic pain – to identify those at risk of chronic pain to modulate pain. Key to its success, she pain that persists after initial injury. and help to stratify treatments. Dr Colvin suggested, were expectancy and beliefs While we all think nothing of a popping also discussed the challenge of long-term and conditioning/learning, emphasising a paracetamol, chronic pain is notoriously use of opioids, a major health crisis in the the key importance of context and the difficult to treat. USA. Prescribing of opioids has begun patient–practitioner interaction. Although However, Peter McNaughton (KCL) to decline in Scotland, but unfortunately lying to patients is ethically questionable, described promising work that may use of illegal opioids has increased in a deeper understanding of how placebo lead to a new treatment option. Chronic response, as has use of other treatments effects work could inform approaches for neuropathic pain reflects repetitive firing such as gabapentinoids, which have been maximising the likelihood of treatment in nociceptors after nerve damage. HCN responsible for an increasing number responses. Remarkable, though, even ion channels play a key role in controlling of deaths. ‘open label’ placebo studies have shown firing rate in cardiac muscle cells, and Beginning with an unconventional statistically significant positive effects. Professor McNaughton has identified approach to treatment adopted by Hugh Keith Phillips (Eli Lilly) noted that

12 BNA Bulletin Spring 2020 www.bna.org.uk Analysis

pain was a challenging area for drug pain pathway. often not seen as a particularly pleasant development, with a very high failure rate. Switching to pleasure, Siri Leknes experience (often the reverse) – although Important ways forward could include (Oslo) provided a thought-provoking eliminating pain is very blissful. Professor greater focus on patient-based target presentation on opioids. She noted that Leknes suggested that the effects of selection, patient stratification, and their effects were more complex than opioids were very variable, with only a validation of biomarkers for assessing often assumed. Work with agonists and proportion of users likely to progress to treatment effects and ensuring that antagonists suggests that they have addiction and users representing a very treatments actually engage with targeted some impact on reward responsiveness, distinct group. biological systems in the ways envisaged. reduce pain and stress (particularly cortisol Continuing the theme of illicit He described a range of biomarkers being levels) but have little or no impact on drugs, Val Curran (UCL) discussed latest developed for different points in the mood. Perhaps surprisingly, agonists are findings on cannabis. She pointed out that cannabis contains more than 140 PRIZE-WINNERS cannabinoid compounds, although The Christmas Symposium as also the time when the annual BNA awards most attention has focused on Δ9- are handed out. This year’s eminently deserving winners were: tetrahydrocannabinol (THC, which generates the cannabis high) and cannabidiol (CBD). THC and CBD are the yin and the yang of cannabis, the former being associated with most of its ill- effects and the latter being protective and possibly even therapeutically useful. Unfortunately, use of high-THC versions of cannabis such as skunk is increasing. Evidence of CBD’s role in pain relief is less clear – while US medical authorities are relatively positive, attitudes in the UK are more ambivalent. The meeting finished with a wide- ranging discussion touching upon the challenges of the placebo effect for drug Outstanding Contribution Public Engagement of development, whether the placebo effect to Neuroscience 2019: Neuroscience 2019: could be harnessed in clinical practice, and Steve McMahon Dean Burnett whether industry pessimism about drug Professor McMahon is Sherrington Dean Burnett is a neuroscientist, development for pain was justified. The Professor of Physiology at KCL and lecturer, author, blogger, podcaster, importance of individual differences was directs the Pain pundit, science communicator, stressed – in laboratory animals as well Consortium. He has long been one comedian and numerous other things, as people. The speakers also contributed of the world’s leading researchers depending (he says) on who’s asking to a special edition of BBC Radio 4's All in studying the molecular mechanisms and what they need. Previous a lecturer the Mind, presented by Claudia Hammond. of pain and nurturing the next at Cardiff, Dr Burnett is currently a full- Finally, three game students bravely generation of UK pain researchers. time author. His ‘Brain Flapping’ column took part in a test of the placebo effect, appeared in from 2012 to being fooled into thinking that an Postgraduate award 2019: 2018 and his book The Idiot Brain was affordable white wine was an expensive James Phillips published by Guardian Faber Publishing. red – a perfect segue to unblinded wine (Cambridge; see page 34). tasting at the post-symposium reception.

Undergraduate award 2019: Pia Siegele (Edinburgh; see page 34) www.bna.org.uk Spring 2020 BNA Bulletin 13 Analysis Out and about Notable events and people in the BNA world.

Speakers at the formal launch of the BNA’s credibility manifesto at the House of Commons included Lord Winston and Dorothy Bishop.

The BNA team had a strong presence at Carl Stevenson, Catherine Harmer and Harry Devito made good use of his last the Bristol ‘Neuro Nets’ meeting aiming Stephen Regel discuss anxiety at the half-term, producing this rather splendid to strengthen connections between the Neuroscience@Nottingham Day 2020. model of a nerve cell. It looks good enough neuroscience and psychiatry communities. to eat.

14 BNA Bulletin Spring 2020 www.bna.org.uk Analysis Out and about

The Seventh Cambridge Neuroscience Symposium, Artificial and Biological Cognition (ABC2019), attracted a large and engaged audience (and two selfie-taking BNA staffers…).

‘ David Marr: 50 years on’ was an ABC2019 satellite meeting marking the seminal contributions of David Marr to neuroscientific thought. Cambridge Neuroscience coordinator Dervila Glynn (below left, centre) is shown with the meeting speakers.

www.bna.org.uk Spring 2020 BNA Bulletin 15 Analysis Out and about

Chas Bountra (far left), Pro-Vice-Chancellor, Innovation, represented Oxford Jane Haley (Edinburgh Neuroscience Scientific Coordinator at the official signature ceremony for the European University of Brain and and BNA Local Group Rep) was presented with an MBE Technology, NeurotechEU bid led by Tansu Celikel at Radboud University on by HRH The Princess Royal at Buckingham Palace on 24 January 2020. The ceremony also included a panel discussion with the 29 January 2020. Coincidentally, Princess Anne also rectors of the eight founding universities which was chaired by Kia Nobre, presided at Jane’s UCL graduation ceremony in 1987. Chair of the Oxford Neuroscience Strategy Committee.

Neil Harrison (Cardiff) delivered the Hodge Centre for Neuropsychiatric Immunology’s annual Public Lecture, ‘Inflammation and depression: Too much of a good thing?’, to a sell-out crowd on 21 November 2019.

Getting to know your BNA

this programme. Lydia and I deliver Why did you apply for Name: Elena Toma neuroscience outreach sessions in schools a placement at the BNA? Job title: BNA Outreach Ambassador and I am currently working on my own The BNA is a fantastic organisation that Joined the BNA: September 2019 modules – Drugs & Addiction and Speech & really emphasises the importance of raising Language. I am very excited to be delivering awareness of neuroscience and how it is outreach sessions in schools and collecting relevant to everyone. I really wanted the Role in a nutshell data to determine the effectiveness of chance to be a part of this and dedicate My main role is working on the BNA’s the programme! My role also involves my year in industry to helping in public new education programme, consisting keeping the website updated with jobs, engagement and promoting neuroscience of neuroscience materials to provide events and news articles, as well as helping research. neuroscientists with ‘tool-kits’ to support at internal and external events and with outreach. My main project is to evaluate other admin and communication tasks.

16 BNA Bulletin Spring 2020 www.bna.org.uk Analysis

schools because I think raising awareness and enthusiasm of neuroscience in young people is really important. It’s so rewarding to see young students engage, get excited and ask lots of interesting questions about neuroscience and what it’s like to study neuroscience at university. Plus the executive team here at the BNA are very welcoming and supportive – being a part of the team has been one of the best things about this placement year.

What do you get up to when you’re not being BNA Outreach What’s your dream job, and why? sessions in schools as a full-time job. Ambassadors? I’m not sure exactly what my dream job I am also considering roles such as a I love travelling, hiking and rock climbing, is yet, but I have had a lot of volunteering physician associate, as working within and generally being outdoors. I enjoy life experience working with many different a multidisciplinary team, and directly drawing and pottery too, which for me are types of people and that is something with patients, really appeals to me – the best ways to relax and unwind. I am I really enjoy. Through my placement, hopefully in a neurology unit. also a volunteer committee member for I have developed a passion for outreach the Bristol Hub Schools Plus programme, and science communication, so perhaps What’s the best thing about which trains and coordinates students as something along those lines. I would working at the BNA? volunteer tutors in schools with the aim love to be able to deliver outreach I love delivering neuroscience sessions in of tackling educational poverty.

engagement before, and being passionate What’s your dream job, and why? Name: Lydia Bown about engaging people in science, I was For a summer while I was at sixth-form Job title: BNA Outreach Ambassador really excited about getting involved in college I volunteered at the National Joined the BNA: September 2019 the work the BNA does to increase public Marine Aquarium in Plymouth and loved awareness of neuroscience research. It was it, especially giving talks to the public and Role in a nutshell also a great opportunity to have hands-on chatting to people of all ages about the Generally, helping where help is needed! experience of how a scientific society works; marine life in the aquarium. It would be There are regular admin jobs I do, as well to see all the behind-the-scenes work which amazing to have a job where I’m able to as posting on our social media channels goes into the BNA’s projects and enables engage people in science in a similar way, and website. I’m often involved in writing us to support and represent neuroscientists while being able to do some writing and creating various resources for the BNA, and neuroscience research. (which I’ve so enjoyed during my from writing an article for the website placement) and to use my creativity highlighting research published in the our What’s the best thing about on some interesting projects. journal, to putting together gift vouchers working at the BNA? for those who wish to give membership It’s been such a great experience to come What do you get up to when as a gift, or editing videos we’ve produced into a team of lovely and talented people, you’re not being BNA Outreach about neuroscience. One of my main roles to be able to work alongside them and Ambassadors? is to engage with our Associate Members to be given real responsibility and the I love a cycle ride in the countryside or a and grow the work we do for them, which opportunity to get stuck in to different long walk, especially in late spring and early has involved putting together the new projects. Being a small team, we work summer when the swallows and house Associate eBulletin each month. I also closely with each other and it’s brilliant martins are around, but at the moment I’m work closely with Elena on the BNA’s to see how the skills of different people having lots of fun going to salsa classes! education project. come together to achieve the great things the BNA does. It’s also rewarding and Why did you apply for exciting to be able to see one’s ideas and a placement at the BNA? suggestions being quickly talked through Having done some outreach and public and put into action. www.bna.org.uk Spring 2020 BNA Bulletin 17 Issue No. 14 Spring 2020

Welcome to the spring edition of our ‘Bright Bright Brains: A big thank you Brains’ Newsletter! This edition is very special As this is the final issue of ‘Bright Brains’ that because it is the last edition I will be editing Jayanthiny is editing as founding chief editor, as founding chief editor. ‘Bright Brains’ was we would like to take the opportunity to thank launched five years ago to give a voice to her and her team of editors and contributors, the BNA’s young members, and it has been for all their hard work putting together issues a pleasure and a privilege to be able to turn over the past few years. To date, ‘Bright Brains’ the vision of ‘Bright Brains’ into reality. has more than succeeded in its aim of giving Half a decade later, with a total of 112 a voice to early-career neuroscientists, with ever- print articles, 63 online articles produced by interesting, informative and entertaining articles. Editor-In-Chief 81 writers, 80 editors and 50 contributors, Early-career researchers and students remain Jayanthiny Kangatharan, PhD ‘Bright Brains’ has been successful in helping a key group for us at the BNA and we’ll continue young members become vocal about their to include a special section within the Bulletin Section Editors views. On behalf of the entire ‘Bright Brains’ to highlight material from young neuroscientists Jack Cooper, Jayanthiny team, I would like to thank the BNA for in future issues. We’re currently consulting on Kangatharan, PhD, Marco Travaglio making ‘Bright Brains’ a great success. the best way to achieve this, with content that The BNA has recognised the importance of will best reflect the interests and concerns of Editors its young members’ contributions to science researchers in the formative stages of their Stephanie Baker, PhD, Inês Barreiros, communication, and the role they play in careers. We’re aiming to have something new Francesco Berti, Deannah Blackely, positioning neuroscience as a science that Jeremy Chabros, Jack Cooper, and ready to go in the summer. leads to a better understanding of how Nerissa Culi, Aisha Islam, Jayanthiny In the meantime, thanks again to all the Kangatharan, PhD, Paulina Pokorska, we can improve lives. ‘Bright Brainers’ - your efforts have been Laura Riggall, Marco Travaglio Below are quotes on how ‘Bright Brains’ greatly appreciated. has made a difference to contributors, with Design & Production complete quotes available in our online section. Anne Cooke, BNA Chief Executive Joshua Au-Yeung, MBBS, Inês In this edition, our ‘Nuntia’ section reveals Barreiros, Jack Cooper, Bernardo how you can increase your motivation, and it Dias, Aisha Islam, Jayanthiny Kangatharan, PhD, Tiffany Quinn, explores the link between cognitive decline and “Editing the work of others is possibly more Ryan Stanyard, Marco Travaglio air pollution. Our ‘Socialia’ section highlights valuable to my development as a science the changes to neuroscience in the context communicator than my own writing, and gives of open science. Our ‘Varietas’ section shows me greater confidence when writing myself.” how volunteering can add another dimension Jack Cooper to our understanding of neurodegenerative diseases, and uncovers what kind of diet can “Contributing as an editor, I have enjoyed help you preserve normal brain function in old being updated on new and upcoming trends, age. It also tells you how neuroimaging can leading to stimulation of many thought- be used together with Bayesian optimisation, provoking discussions amongst my peers, and provides information on how fear alongside reviving the importance of both inhibition is mediated in the brain. ‘Numquid inter- and multidisciplinary perspectives.” sciebas...?’ illustrates how electrophysiological Aisha Islam methodologies can help network neuroscience develop new therapies, while ‘Quid novi?’ “In every submission, there is a value-adding evaluates the health effects of foods that process where we contribute to a product are high in nitrate. Finally, we sincerely hope that is always better than the original draft that you will have as much joy in reading our with the ultimate purpose of advancing final ‘Bright Brains’ newsletter as we had in the standards of our research community. producing it! Innovation starts here.” Marco Travaglio

Jayanthiny Kangatharan, “My editorial role with Bright Brains ‘Bright Brains’ newsletter coordinator undeniably helped me to become a more succinct scientist, something I'm immensely grateful for.” Ryan Stanyard

18 BNA Bulletin Spring 2020 www.bna.org.uk NUNTIA

they project to the nucleus accumbens the reward. Visualise the completion of a as well as to other ‘limbic’ regions such as project and embrace the perceived reward the hippocampus and to prefrontal cortex. from completing the task. Using real-time While the earliest experiments were brain-imaging techniques, neuroscientists thought to suggest that dopamine have found that reward information is regulates our ability to perceive pleasure processed in the prefrontal cortex and that Marco Travaglio and reward, it was not until recently this area interacts directly with the nucleus PhD student in Neuroscience, that this idea was overturned to show accumbens and VTA to trigger motivated that dopamine activity may actually be behaviour. What this means is that related to human motivation instead. anticipated reward can directly influence Recent experiments showed that animals your willingness to work by activating Neuroscience of motivation with lower levels of dopamine opt for the very key brain motivation centres. and how to improve it the low-value, easier-to-obtain reward But ultimately, while neuroscience whereas animals with higher levels of certainly helps to hack our biological What is motivation? It is an invigorating brain dopamine would show increased constraints, we should not forget that old- force that enables you to act, whether it motivation to work harder to obtain the school self-discipline and determination are is to get out of bed or to sign the much- high-value reward. Regarding where in two of the most powerful forces to boost awaited contract that will shape the rest the brain dopamine exerts its effects, your motivation. Much research is needed of your career. Dopamine has emerged as consensus revolves around the idea that to fully understand the complex biological a key neurotransmitter involved in almost high levels of dopamine in the nucleus mechanisms that generate and maintain every aspect of motivation. It conveys its accumbens will encourage you to tick every our willpower but, in the meantime, signal by passing from one neuron to the box of your to-do list whereas low levels passion and perseverance into whatever next through the ‘mesolimbic pathway’, will leave you sprawling in your bed. you are doing will probably get your otherwise known as a neuronal circuit that So what can we do to improve our dopamine flowing. The rest will follow. connects the middle of the brain (midbrain) motivation? Train your brain. Researchers The full article with references can be to its outermost region (cerebral cortex). suggest that our brain can be trained to found at: www.bna.org.uk/publications/ Dopaminergic neurons originate from the create the right dopamine environment bright-brains/bb-online/. ventral tegmental area (VTA), from where and one way to do this is by anticipating

2008 in Mexico City. Healthy children in hippocampal neuronal atrophy and Mexico City with no known risk factors upregulation of proinflammatory mediators for cognitive dysfunction exhibited are present in the brains of both highly hyperintense prefrontal white matter exposed humans and animals. These are all lesions and significant deficits in cognitive well-established hallmarks of Alzheimer’s tasks, compared with their clean-air disease. Most recently, a study carried out Rachel Jones counterparts. These results gained traction in London reported a positive exposure– Graduate student in Neuroscience, and inspired a range of subsequent studies response relationship between air pollution University of Leeds reporting similar findings. Adults exposed and incidence of Alzheimer’s disease to long-term high levels of air pollution diagnosis in adults with no recorded history tend to show significant deficits in verbal of dementia, unexplained by confounding Air pollution: a risk factor memory, attention and episodic memory factors. Our ageing population will for Alzheimer’s disease? compared to less exposed adults. The naturally result in increased financial and trend of results even suggested that each emotional burdens on society, stemming Environmental awareness surrounding 10 μg/m3 increment increase in particulate from age-related diseases including climate change has become an increasingly matter (PM, particles suspended in air Alzheimer’s disease. In a ‘two-birds-one- common topic of discussion among pollution) concentration that adults were stone’ approach, being mindful of our politicians, the media and general public exposed to was equivalent to cognitively environmental impact and reducing levels alike. Currently, the effects of air pollution ageing by approximately 2 years. of air pollution could help mitigate these on the central nervous system (CNS) Researchers consequently hypothesised burdens. Further research is imperative to are being investigated, in particular that long-term PM exposure could be a risk obtain concrete evidence of links between its involvement in the development of factor for the development of Alzheimer’s air pollution and Alzheimer’s disease, Alzheimer’s disease. disease. Incomplete knowledge of disease potentially influencing environmental policy One of the first examples of a link progression, plus the potential to modulate changes worldwide. between air pollution exposure and environmental risk factors (unlike genetic This article together with references cognitive decline, the primary characteristic risk factors), provided motivation to take can be found at: www.bna.org.uk/ of Alzheimer’s disease, was reported in research further. Abnormal Aβ deposition, publications/ bright-brains/bb-online/.

www.bna.org.uk Spring 2020 BNA Bulletin 19 SOCIALIA

To address this question, the Cortex has not been signed by all research Club – the Oxford University Neuroscience institutions, and a recent meta-analysis Society –organised a panel discussion showed that 40% of research universities in on open science and open access. We the USA and Canada explicitly mention that invited Elisa de Ranieri, editor at Nature journal impact factor can be used for tenure Communications, John Inglis, co-founder and promotion evaluations. Does this mean Marta Blanco Pozo of bioRxiv and medRxiv and executive that publishing in open access journals with PhD student in Neuroscience, director at Cold Spring Harbor Laboratory lower impact factors rather than renowned University of Oxford Press, Sally Rumsey, Head of Scholarly closed journals could jeopardise early career Communications and Research Data researchers’ futures or make it difficult Management at the Bodleian Library, and for more senior researchers to keep their The open access dilemma Mark Patterson, executive director of eLife. positions? We started by discussing how journals, All of the panellists agreed on the From making code and data available institutions and repositories are improving complexity of this issue. Moreover, a way to to publishing in open access journals, a the way research is being published and assess research quality aside from a journal’s great effort is currently being made to shared, how subscription fees are increasing impact factor has not been established yet. promote open science and to make research at a higher rate than university funds, and In brief, the research community needs to accessible to everyone. Major funding how universities and institutions could continue discussing these issues, and find bodies, including the Wellcome Trust, are support publishing in open access journals. new ways to address them. Initiatives such now updating their policies to align with Then, the focus of the debate shifted to as Plan S are certainly changing research ‘Plan S’, which is “an initiative to make full the impact that open access might have on publishing culture. However, the way this will and immediate Open Access to research researchers’ careers. affect researchers at different career levels publications a reality”. This means that Some institutions like Oxford have and institutions is still to be determined. from 2021, all scientific research findings signed the San Francisco Declaration on This article together with references can must be published in open access journals Research Assessment (DORA), which states be found at: www.bna.org.uk/publications/ or platforms. But do we know how this that the impact factor from journals should bright-brains/bb-online/. will affect both senior and early-career not be used to assess quality research or in researchers? the hiring process. However, this declaration

Far more commonly but less dramatically under way. The introduction of the open and undermining for the public, a paucity science and registered reports frameworks of published materials and data has is becoming lucrative to many stakeholders. contributed to what has been termed the These platforms are enabling researchers ‘replication crisis’. This term was popularised to critically review changes to methods and largely in the psychological literature but flag gaps in planned analyses. Alleviating Ryan Stanyard it is also relevant to neuroscience and the the focus from high-impact publishing in the PhD student in Neuroscience, KCL medical sciences. Neuroscientists have wake of the Research Excellence Framework endeavoured to provide better access to both and the archaic pyramid scheme in academic raw and processed data in addition to other advancement, this new approach provides research materials. Similarly, neuroscience better means of appraising bids for funding Open Science: has begun to introduce registered reports high-expenditure research projects and Changes to Neuroscience in line with new guidelines, a framework acknowledges the merit of peer scrutiny. common in international and multicentre Adjustment to new terms in this arena In recent years, both neuroscience and the protocols for imaging or genomic studies, may be daunting. There may be questions as psychological sciences have witnessed among others. Nonetheless, the transition to how early-career researchers will engage a call for a robust framework to provide to replicable science is not progressing with pre-published or pre-print materials or online materials that better enable scrutiny without difficulty. how they will convince principal investigators of research. This will help guard both the In 2019, a year in which the BNA Festival opposing the movement. Open science validity of financial investment in research of Neuroscience (Dublin) and the meeting of advocates for more transparent, supportive and mark a stand against publication bias the Organisation of Human Brain Mapping scrutiny of peer-reviewed literature prior and credibility inflation. Previous media (Rome) were celebrated, we have also to, during and following formal publication. scrutiny has ousted pioneers in psychology, seen papers exploring themes such as Ultimately, this gives more credibility to discredited for fabricating data, using neural oscillations in artificially re-perfused neuroscience research. convoluted methodologies to mask the porcine tissue gracing the likes of Nature. This article together with references can absence of true results and misleading Yet, equal strides in fundamental changes be found at: www.bna.org.uk/publications/ readers. to research and publication structure are bright-brains/bb-online/.

20 BNA Bulletin Spring 2020 www.bna.org.uk VARIETAS

Alzheimer’s UK; she is going to shave off Mileha Soneji is a product designer who all her hair because the skydiving company has come up with some amazing tools to refused to let her do a jump! Sue has an help people with Parkinson’s disease. She amazing sense of humour, she enjoys her combined her design skills with her first- gym sessions and always gets involved hand experience of her uncle’s disease to with care home activities. She tells me create simple yet effective aids for people Tamsin Nicholson about the hazards of baking when you with Parkinson’s, such as a 3D printed Graduate student in Neuroscience, have multiple sclerosis and how cakes staircase to help people walk smoothly University of Glasgow have ended up on the walls and floor on flat surfaces. As a neuroscientist, after a spasm. She makes light of her you can set yourself up to innovate, too. disabilities, as someone who has accepted Combining your scientific knowledge with Why every neuroscientist them and learnt to live with it all. first-hand experience of the disease could should volunteer I have learnt a lot from my time with help you bring about simple innovations Sue. I have learnt about the power of that really do change lives. During my master’s, I developed an interest positivity, and that there is always so Translational research has become in neuroinflammation and chose to do my much more to a person than their disease. increasingly prominent in recent years, research project in a pre-clinical multiple But I have also come to appreciate what but translation is still something that a sclerosis lab. I loved my research and its it means to keep some independence lot of scientists struggle to achieve. By potential to help people. But it was years when your body begins to fail you. While volunteering, you can get that experience before I realised what I had been missing. a cure for multiple sclerosis would be to help you take something from bench A while later, I decided to volunteer in transformative, the little things can make to bedside and to make a real difference. a local care home. Here I met Sue: bubbly, a huge difference. Whether it is finding But even if you take that out of the friendly and fiercely independent. Only a way for Sue to complete her skydive, equation, ask yourself: how much can in her 60s, she is one of the youngest or to be able to eat peas without them you really understand a disease without residents and she acts like it. She tells rolling all over the floor, these small steps understanding the people who live with it? me about her fundraising plans for mean a lot.

cognitive decline. This pioneering work loss of brain cells, which can profoundly demonstrated that a large intake of mono- affect learning and memory. Complex unsaturated fatty acids, abundant in olive substances with important anti-oxidant oil, is protective against cognitive decline. properties such as olive oil, wine, nuts, Encouraged by these intriguing results, fruits and vegetables are present in high scientist Valls-Pedret and colleagues at concentrations in the Mediterranean diet, Marco Travaglio the Barcelona’s Institut d’Investigacions suggesting that these substances may PhD student in Neuroscience, Biomèdiques August Pi Sunyer embarked reduce oxidative processes in the brain, University of Cambridge on the first-of-its-kind clinical trial preserving normal brain function. looking at the association between a Nonetheless, while mounting research Mediterranean diet and cognitive function points to the beneficial effects of the Food for your brain: in older individuals. Results were striking. Mediterranean diet on brain health, more The Mediterranean diet After several years of data (and food) research is needed to prove its effects. crunching, researchers demonstrated that Most studies suggest a link between this Historians used to call it the ‘cradle of participants allocated the Mediterranean- diet and brain function but little is known civilisation’ but for many scientists today style diets display improved learning and about the mechanisms that drive its effects the real value of the Mediterranean basin memory whereas those allocated a normal on the brain. In addition, defining minimum does not lie in its contribution to history. diet show signs of cognitive decline. But quantities of recommended foods remains Accumulating evidence suggests that how does a Mediterranean diet exert its a priority. Researchers agree that there are feeding your brain with the plant-based effect on the brain? Most experts suggest lots of benefits and no known downside diet of the olive-growing Mediterranean that its mysterious effects could stem to following a healthy diet. However, while regions may reduce the risk of cognitive from the abundance of anti-oxidant agents adding olive oil and mixed nuts to your problems, effectively making you live that it provides. Oxidative stress is often diet may benefit your brain cells, using a longer and healthier life. In 1999, as cited as major cause of cell damage in excessive amounts will only make you part of a broader investigation into the several age-related brain conditions and gain weight. So… don’t go nuts! prevalence of several diseases in older is caused by the accumulation of toxic This article in full together with adults, researchers at the University of Bari compounds in the brain called free radicals. references can be found at: www.bna. discovered that individual elements of the With time, excessive accumulation of org.uk/publications/bright-brains/bb- Mediterranean diet are protective against free radicals can lead to the irreversible online/. www.bna.org.uk Spring 2020 BNA Bulletin 21 VARIETAS

to reduce phase-encoding steps during or have attention-deficit hyperactivity acquisition, and effectively reducing scan disorder) do not need to undergo less times). These technologies can be co- important scans and can complete either utilised alongside a Bayesian optimisation more relevant runs of a task/paradigm or approach; rather than scanning an finish early. Second, this approach means entire subject’s brain/‘volume’ according scanning can focus on tasks/areas of Ryan Stanyard to protocol, subjects are scanned at interest. Finally, in totality, this approach PhD student in Neuroscience, KCL increasing resolutions in sub-sampled would deliver lucrative cost savings. regions of interest or indeed the whole Given conventional imaging costs ~£400- brain. Next, this individual’s scan is 600 per hour, whether commercially, for compared in real-time against a database research or clinically, shorter scan times Bayesian optimisation of normative typically developing healthy could potentially deliver huge savings for controls, matching for resolution, age bodies such as the NHS. Conversely, scans In conventional structural and functional and other stratifiers of interest (e.g. sex, from conventional imaging are routinely MRI, image acquisition is led by disease severity), yielding a dynamic and anonymised (personal data are redacted) radiographers (or researchers in some flexible approach. By comparing in-scan and so can be used by other researchers to institutes). Subjects are scanned according subjects against normative populations bolster modelling normative distributions to study protocols, adjusting parameters for given tasks, the algorithm can derive if technical specifications match their own for the size of the subjects’ brain volumes. which tasks/areas an individual is most sampling strategy. A series of pre-planned scans are to be ‘different’ from relative to a normative This article together with references completed within a confined scanning sample, guiding subsequent acquisitions. can be found at: www.bna.org.uk/ window, which in many studies is typically This is useful for several reasons. First, publications/bright-brains/bb-online/. around 1 hour. Efficient acquisitions individuals with low tolerance for MRI (e.g. often employ parallel imaging techniques people with claustrophobia, who are hyper- (using spatial localisation techniques anxious or physically/mentally disabled

essential for understanding fear-related Thy1 neurons in the BLA blocked the disorders as it is the process upon which transmission of fear-related signals to exposure therapy is based. But how can we downstream areas, important in regulating target this extinction process? physiological and behavioural consequences Fear conditioning is a well-established following fear exposure, and revealed a technique, which helped identify the role of Thy1-expressing BLA neurons in Andreea Pantiru amygdala as a key structure of the brain fear circuitry. Behavioural analysis showed PhD student in Neuroscience, involved in the formation, consolidation and that optogenetic inhibition of BLA Thy1- University of Leeds extinction of fearful memories. This learning expressing neurons during fear conditioning/ paradigm represents the coupling of an extinction results in increased fear responses, event, the conditioned stimulus (CS), with an while chemogenetic activation of these Fighting to forget aversive event, the unconditioned stimulus neurons reduces fear-related behaviours in (US). Even one CS–UC pairing is sufficient mice, highlighting the importance of Thy1 Fear is an emotional experience deeply to elicit a fear response to CS alone. CS- neurons in extinction. ingrained in evolution to foster survival and dependent fear can be diminished through Overall, these studies emphasise the enable avoidance of potentially harmful subsequent repeated and unreinforced significant role that Thy1-expressing BLA conditions. However, fear may become re-exposure to the CS, which leads to fear neurons play in mediating fear inhibition and dysfunctional and result in anxiety and extinction. Enhancing fear extinction could provide insight into a new potential target trauma-related disorders, such as post- potentially ameliorate disorders, such as for fear disorders, such as PTSD. A better traumatic stress disorder (PTSD). Exposure PTSD, by inhibiting the intrusive recollection understanding of how fear is encoded will therapy is the main approach to combat of traumatic experiences. ultimately lead to efficient biologically driven PTSD, but 40% of patients fail to respond The basolateral nucleus of the amygdala approaches for treatment and prevention of to this therapy. Fear encoding is not fully (BLA) contains two electrophysiologically fear-related disorders. understood; therefore, development of distinct populations of neurons: one that This article together with references can better treatments requires an improved is activated during acquisition and one be found at: www.bna.org.uk/publications/ comprehension of how fear is processed activated during extinction of fear. Research bright-brains/bb-online/. in the brain. Fear extinction is a learning revealed that thymus cell antigen 1 (Thy1) mechanism, which manifests in a decline is distinctively expressed in extinction cells, in fear responses towards a stimulus that which mark a population of glutamatergic was previously eliciting fear. Extinction is neurons within the BLA. Activation of

22 BNA Bulletin Spring 2020 www.bna.org.uk VARIETAS NUMQUID SCIEBAS...?

neurodevelopment. The vast majority of interneurons and pyramidal cells. Loss-of- evidence in this field comes from non- function of Mecp2 leads to disrupted wiring invasive imaging studies, such as resting- of cortical circuits and defective network state fMRI or magnetoencephalography. activity. Using drugs that act preferentially However, although these methods enable on NMDA receptors with pathological evaluation of network topology and activity, subunit compositions points to a possible Jeremy Chabros they require time, resources and volunteers. way through which functional connectivity Medical student, Electrophysiological experimental could be protected. University of Cambridge methods, such as multi-array electrode As NMDA receptors play a pivotal role in (MAE) recordings, bridge the gap between synaptic plasticity, MAE studies can also help cellular and network neuroscience. In vitro to explore the nature of this mechanism. In search of a Rett recordings from human dissociated cortical Moreover, this approach can be used to syndrome treatment cultures are more ethical than animal study other disorders of the nervous system. studies, more closely resemble conditions Indeed, it is applicable wherever pathology is a childhood disorder that occur during human neurodevelopment, influences network topology or function. leading to cognitive and motor impairment. are more cost- and time-effective, and The inherent assumption, however, is It is the second most common cause of enable genetic and/or pharmacological that the changes occurring at the network severe intellectual disability worldwide. intervention. level in vitro can recapitulate the events Although it currently remains without The majority of Rett syndrome cases in vivo. Although this might only be true a cure, recent advances in network involve a mutation in the MECP2 . in certain situations, using such systems neuroscience might aid the emergence of Among its myriad of roles, the Mecp2 will, nonetheless, accelerate basic and novel therapeutic strategies. protein influences the switch between translational research in such cases. Network neuroscience has been the Glu2NB and Glu2NA NMDA receptor This article with references can be mainstay for elucidating how functional subunits, differentially affecting receptor found at: www.bna.org.uk/publications/ connections are established during deactivation kinetics in parvalbumin-positive bright-brains/bb-online/.

VARIETAS QUID NOVI? weight or evidence base. reduced blood pressure and decreased risk A diet that has a growing body of of ischaemic stroke and coronary artery evidence of health benefits is a high-nitrate disease. diet. Nitrates are a common constituent The beneficial vascular effects of dietary of our diets found in abundance in fruits nitrate in preventing and treating neuro- and vegetables, particularly in beetroot vascular disease are currently being explored. Joshua Au-Yeung, MBBS and green leafy vegetables. Dietary nitrate Bondonno et al. found that higher vegetable Academic Clinical in Clinical increases the systemic availability of nitric nitrate was associated with a decreased Pharmacology and Therapeutics, Guy’s oxide, which in turn regulates several carotid artery wall thickness and a 17% lower and St Thomas’ NHS Foundation Trust physiological processes that improve cardiac risk of stroke. Another study showed that a blood flow and exercise tolerance. high-nitrate diet improved cerebral perfusion Evidence of the beneficial effects of in frontal lobe white matter, critical areas Beetroot and the brain beetroot juice, which contains high amounts that degenerate in dementia. of nitrate, was first demonstrated in a Fad diets come in and out of fashion on In a culture of miracle cures and quick study by Webb et al., which showed that a weekly basis. So far, evidence suggests fixes, we are constantly bombarded with beetroot juice reduced blood pressure. that eating beetroots, or a diet high in nitrate sensationalist headlines of fad diets that Another study showed that beetroot juice content, can reduce your cardiovascular risk promise instant weight loss or nonsensical supplementation improved efficiency and improve exercise tolerance. However, health improvements. Having to weave and performance of athletes in cycling further high quality research needs to be through headlines, blogs and celebrity and marathon runners. Similarly, The conducted regarding whether beetroot is endorsements of a new cancer cure or Dietary Approaches to Stop Hypertension a viable treatment for stroke or dementia super-drug can make it difficult to know study showed that a ‘combination diet’ prevention. Until then, at the risk of sounding whether any of these claims bear any real high in fruit and green leafy vegetables sensationalist, there is no harm in grabbing a beetroot juice the next time you are out brunching with your friends. Answers to the crossword from Issue 13 – Autumn 2019 This article in full with references can be Horizontal 3: pTau; 4: MCI; 5: AD; 7: HDAC inhibitors; 8: PD; 9: GWA; 10: Lumbar puncture. found at: www.bna.org.uk/publications/ Vertical 1: Medial Amygdala; 2: Entorhinal cortex; 6: PTSD. bright-brains/bb-online/. www.bna.org.uk Spring 2020 BNA Bulletin 23 Research Pain – from molecules to minds Genetic approaches are revealing new targets for treatment of neuropathic pain.

Neuropathic pain, persistent pain triggered “WE’VE GOT A LOT MORE At a glance by damage to somatosensory neurons, TARGETS AND A LOT MORE • Chronic pain linked to nerve damage is common, debilitating and difficult to UNDERSTANDING OF HOW (neuropathic pain) is common and treat. As well as running a peripheral DYSFUNCTIONAL NEURAL often hard to treat. neuropathy clinic in Oxford, David Bennett CIRCUITS LEAD TO CHRONIC is investigating the genetic and other PAIN, WHICH WE HOPE WILL • Identification of genes causing factors contributing to neuropathic pain – TRANSLATE INTO NOVEL inherited pain disorders has revealed work that could lead to more targeted THERAPIES.” key proteins involved in chronic pain and effective treatments. and new targets for drug development. Inspired by modules on pain in his insensitivity or extreme sensitivity to • Major initiatives are underway to intercalated BSc, Professor Bennett pain has revealed key components of pain deeply phenotype and stratify patients secured a Wellcome Trust scholarship systems, including the Nav1.7 voltage- to support more personalised treatment. to work with legendary pain researchers gated ion channel (product of the SCN9 Pat Wall and Steve McMahon. By chance, gene). Mutations in Nav1.7 alter its ion he had the opportunity to stand in for transporting properties and the electrical the latter on a placement at Genentech in excitability of pain-sensing neurons may not be obvious how a variant is San Francisco. Bitten by the research bug, (nociceptors), in some cases leading to contributing to susceptibility to pain. on his return, he enrolled on a PhD with hyperexcitability and chronic pain. Whatever their source, genetic leads John Priestley and Professor McMahon. Notably, several Mendelian pain disorders can be followed up in functional studies. Unusually, therefore, he embarked on have been tracked to abnormalities in ion Abnormal ion channels, for example, can a PhD – on the role of neurotrophic factors channels. Nociceptor hyperexcitability be expressed in cultured cells and their in pain – before he had even started his may therefore be a common feature of properties explored. Mutations can be clinical training. He went on to finish his neuropathic pain, although Professor ‘knocked in’ to create animal models. clinical training and served his time as Bennett suspects that it is unlikely to be But a particularly powerful technique now a junior doctor. “But I’d enjoyed research a single entity: “There are going to be is to generate induced pluripotent stem so much I’d always wanted to come back many pathophysiological drivers.” cells from patients and differentiate them to do more pain research.” Mendelian disorders with extreme into somatosensory neurons in culture A Wellcome Trust fellowship enabled phenotypes are very rare and may not for functional studies. him to complete his clinical training and necessarily be relevant to more common set up his own lab at King’s College pain conditions. The past decade or so Clinical understanding Hospital. Shortly after becoming a has seen explosive growth in genome- As the GWAS studies illustrate, the consultant, he moved to Oxford in 2012. wide association studies (GWAS), which diversity of neuropathic pain presents a Although challenging, he is convinced scan entire genomes to identify genetic major challenge – for clinical practice as that combining clinical work and research variants that are more common in patients well as research. Although some effective is an advantage. “I’m seeing people with than in controls and may therefore be drugs are available, they do not work for difficult neuropathic pain week in week involved in disease. all patients: “When sitting with a patient out. A lot of the research questions I try However, the impact of GWAS in pain in front of us, we don’t really know what to answer derive from clinical issues that has been limited. “It’s been difficult to would be the most appropriate drug for I’ve seen and as much as possible I want apply to pain, partly because you need that patient.” to take the research back into the clinic. quite large well-phenotyped cohorts,” The answer lies in more intensive There’s a lot of cross-fertilisation between says Professor Bennett. “We’re only phenotyping. In the landmark DOLORisk the two and that’s where I try to position just starting to see those results come study, for example, Professor Bennett and myself, to work at that translational through now.” Furthermore, identification colleagues are following a cohort of 10,000 boundary.” of genetic associations is often only the people from across Europe at risk of beginning of the story. “They’re often neuropathic pain. Notably, data collection The genetics of pain in regions of the genome that have spans a wide range of neural, biological, Over time, Professor Bennett has come regulatory functions,” points out Professor demographic and psychosocial factors. to specialise in the genetics of pain. Bennett. They may therefore not affect “Then you can begin to piece together Identifying the abnormal genes that the structure or function of a protein how one relates to the other.” cause inherited conditions involving either but where and when it is made, and it The longitudinal cohort approach

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Wellcome Images

side effects.” It is possible to block pain signals, for example using the anaesthetic lidocaine. However, lidocaine is not a practical treatment – it has to be applied locally as it shuts down all neural activity. Single gene studies have enabled some patients to be treated with drugs targeting their abnormal ion channels. More generally, they have revealed potential targets for drug development, and recent work has revealed signalling components specific to nociceptors: “If we could find a means of selectively silencing nociceptors, then that would be extremely helpful in terms of treating neuropathic pain.” Although some drugs for neuropathic pain are in clinical trials, it has been a challenging area for drug development, with a depressingly high failure rate. Professor Bennett is hopeful that recent work may help to overcome the perception that neuropathic pain is too ‘hard’: “We’ve got a lot more targets and a lot more understanding of how dysfunctional neural circuits lead to chronic pain, which we hope will translate into novel therapies.” Professor Bennett therefore remains upbeat, and doesn’t regret the extra Chronic pain, tormenting devils: Coloured etching by J Cawse, 1809, after G M Woodward. effort that combining clinical training and research has required: “It was a challenge, can reveal factors associated with the either facilitate or sometimes suppress no doubt about it. There were times when emergence of neuropathic pain. Although information at the level of the spinal cord.” I thought life would be simpler if I was data collection is ongoing, insights are As well as DOLORisk, Professor doing one or the other, but I have to say already emerging. Interestingly, points Bennett is also working with UK Biobank, I always enjoyed integrating the two out Professor Bennett, “Psychology has a whose 500,000 participants are providing and it was worth it in the end.” massive modulatory role.” Patients with detailed medical data, lifestyle information susceptibility to depression, anxiety, or and biological samples, undertaking more Calvo M et al. The genetics of neuropathic pain from prone to catastrophising are more likely to extensive phenotyping of people with model organisms to clinical application. Neuron. 2019;104(4):637–653. develop neuropathic pain. or at risk of neuropathic pain. Such work McDermott LA et al. Defining the functional role of NaV1.7 This could lead to unhelpful could reveal biomarkers enabling those at in human nociception. Neuron. 2019;101(5):905-919.e8. suggestions that their problems are ‘all particular risk of neuropathic pain to be Pascal MMV et al. DOLORisk: study protocol for a multi- centre observational study to understand the risk factors in their mind’. But, points out Professor identified and supporting stratification of and determinants of neuropathic pain. Wellcome Open Res. Bennett, that’s exactly what pain is patients, so clinicians can tailor treatments 2019;3:63. anyway – the experience of pain reflects to individual patients: “That’s something Themistocleous AC et al. Using stratified medicine to central brain activity even if nerve that we could deliver in the short term.” understand, diagnose, and treat neuropathic pain. Pain. 2018;159 Suppl 1:S31–S42. damage is peripheral. Moreover, he adds, In the longer term, new treatments Cregg R et al. Mexiletine as a treatment for primary “The brain doesn’t passively receive the are urgently needed: “Of course, what erythromelalgia: normalization of biophysical properties of signals coming into it; there’s also a top- we would like is new analgesic drugs mutant L858F NaV 1.7 sodium channels. Br J Pharmacol. 2014;171(19):4455–63. down pain modulatory circuit that can that are more effective and have fewer www.bna.org.uk Spring 2020 BNA Bulletin 25 Research Hundreds and thousands Neuropixels technology is enabling recordings to be made from tens of thousands of neurons – revealing a surprising picture of brain activity.

Recording from electrodes has been the ultraclean nanofabrication facility in This support enabled imec to develop mainstay of neurophysiology for decades. Europe. It has a strong research and version 1.0 of the Neuropixels probe, and As the technology has improved, the development focus and had already also to sell it at cost price. Affordability number of neurons from which recordings developed innovative solutions for was a key goal, and Neuropixels can be made has gradually increased. the ATLAS collaboration at CERN. technology can be adopted by labs even Now, an international research consortium imec were keen to help: “They said with modest funding. Importantly, very including Matteo Carandini (UCL) has they could build a new probe that instead little additional technology is required: developed new tools that look set to of having just a few sites of recording “Once you have them, you barely need revolutionise the field. on the shank that is inserted in the brain, a lab,” says Professor Carandini. “What Professor Carandini highlights the it would be way thinner and have 1000 comes out of them is already digital and key role played by Tim Harris, a Howard recording sites.” could be plugged into a laptop. It’s a big Hughes Medical Institute (HHMI) senior Although technically feasible, the democratiser of neurophysiology.” fellow at HHMI’s Janelia Farm Research development costs would be high given The second key development has Campus: “He realised that the kind of that the anticipated market is specialised been new software tools to manage the electrodes that laboratories were using and relatively small. Professor Harris streams of data generated by Neuropixels round the world to record from the therefore put together an international probes. With hundreds of detectors, each brain were based on 1980s technology.” consortium, which was able to secure neuron’s activity is likely to be picked up In other fields, technology had come on funding from sources including the HHMI, by five to six electrodes. The distinctive in leaps and bounds: “The technology the Allen Institute for Brain Science in properties of each neuron’s outputs, we carry on our mobile phones is way Seattle and Wellcome (via UCL). however, provide a way to match signal to way way superior.” originating neuron – spike sorting – and Professor Harris made contact with “I HAD TO LEARN LOTS OF to locate the position of active neurons. a not-for-profit semiconductor company NAMES OF BRAIN REGIONS THAT Software tools have been built that in Belgium, imec, which has the only I DIDN’T EVEN KNOW EXISTED.” automatically achieve spike sorting almost in real time: “That has made it possible for imec lots of labs to use them – without this it would have been really hard.”

Scientific insights Following the development of version 1 of the Neuropixels probes, the first papers resulting from their application were published in 2019. Karl Deisseroth and colleagues recorded from 20,000 neurons in studies of the signals underlying thirst. And Professor Carandini, his colleague Ken Harris at UCL and their international collaborators published a paper in Nature describing the results of visual processing studies recording from 30,000 neurons. “These are crazy numbers,” points out Professor Carandini. “My PhD thesis was about 50 neurons.” Professor Carandini’s particular interest is in decision-making informed by vision. The new technology has had a transformative impact on his work. Previously, researchers would specifically A first-generation Neuropixels probe. target their areas of interest: “Now instead

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you put these electrodes in and you record from a lot of brain regions you might not think you’re interested in because they happen to be along the path. And then you analyse the data and you realise very often there are very interesting signals in parts of the brain that you didn’t think you were interested in.” Importantly, this approach has provided a radically different view of brain function: “We discovered that the signals underlying decision-making are much more distributed across the brain than we thought.” Neuroscience textbooks The tip of the Neuropixels probe. perpetuate the idea that functions in the brain are neatly parcelled into different “WE DISCOVERED THAT THE from UCL – Ken Harris, Michael Häusser, regions. This may well be misleading, SIGNALS UNDERLYING DECISION- Sonja Hofer, Peter Latham and Tom Mrsic- says Professor Carandini: “They give the MAKING ARE MUCH MORE Flogel – have joined a global consortium, impression that there’s a fantastic division DISTRIBUTED ACROSS THE the International Brain Laboratory, to of labour. The division in brain regions, at BRAIN THAN WE THOUGHT.” systematically address brain function least in the mouse, it’s strongly supported using Neuropixels technology. Consortium by genetics and anatomy, but it’s not very Carandini is leading a team developing members are standardising behavioural well supported by physiology or activity, version 2.0, which will be lighter, smaller, techniques and parcelling out regions of in that there seem to be neurons have four shanks rather than one, and the brain to study, much like the Human distributed around the brain that seem will be more amenable to long-term Genome Project distributed chromosome to do things that are very similar even implantation so data can be recorded to different labs for sequencing. This though they are in different regions.” for weeks or months at a time. avoids duplication of efforts and This revelation was apparent in Other groups are exploring the greatly enhances the amount of data both the pioneering Neuropixels papers: potential for use in primates or humans, available. With data freely available, “Both of them indicate that things are although their small size, perfect for a new generation of neuroinformatics much more distributed than one would rodents, is a drawback when it comes researchers may never generate data have thought.” to species with larger brains. themselves but just work on the One consequence, says Professor There is also scope to increase mountains of data freely accessible Carandini, is that he has suddenly had recording capacity still further. “The limits in global databases. to become acquainted with some of the are due to the widths of the wires,” says All these efforts reflect a collaborative quieter backwaters of the brain, like the Professor Carandini. Neuropixels wires approach that has seen competitors join zona incerta: “I had to learn lots of names are 190 nm wide, but those in mobile forces to advance the field cooperatively: of brain regions that I didn’t even know phones go down to 6 nm – but at a cost: “It’s been a big success of open science,” existed.” “Your mobile phone gets very hot.” says Professor Carandini. Furthermore, the signals in these At the moment, the product specification unexpected locations do not appear to for Neuropixels probes is for a maximum Steinmetz NA, Koch C, Harris KD, Carandini M. Challenges be just noise or coincidental: “The signals increase of 1°C to avoid overheating the and opportunities for large-scale electrophysiology with Neuropixels probes. Curr Opin Neurobiol. 2018;50:92–100. are way cleaner and more repeatable brain. But there is little if any basis for Allen WE et al. Thirst regulates motivated behavior through than anything I’ve ever seen.” this threshold: “We don’t know yet how modulation of brainwide neural population dynamics. Science. much we can warm up the brain. This 2019;364(6437):253. Steinmetz NA, Zatka-Haas P, Carandini M, Harris KD. The future specification could be too conservative – Distributed coding of choice, action and engagement across With Neuropixels being picked up by we don’t know.” the mouse brain. Nature. 2019;576(7786):266–273. more than 200 labs, work has begun on Alongside this development work, the successors to version 1.0. Professor Professor Carandini and several colleagues www.bna.org.uk Spring 2020 BNA Bulletin 27 Research Non-trivial pursuit A deeper understanding of the neurobiology of curiosity could have important implications for areas such as education.

learning: “It’s actually about your interest, At a glance your curiosity, which shapes what you • Curiosity reflects the internal learn and what information you seek motivation to seek out new information. in daily life.” • A curious brain state enhances An emerging field learning and memory consolidation. Despite its importance to human behaviour, • The Prediction, Appraisal, Curiosity curiosity remains surprisingly under- and Exploration (PACE) model provides studied, in neuroscience at least. In part, a framework to guide the neuroscientific this may reflect a degree of uncertainty study of curiosity. about what it actually is: “We don’t really have an agreed definition of curiosity,” admits Dr Gruber. Psychology has a longer history of “WE TRIED TO BRING ALL THESE exploring curiosity, mostly focused on THEORIES OF CURIOSITY THAT ‘trait curiosity’ – curiosity as a permanent ARE OUT THERE IN PSYCHOLOGY personality characteristic. However, TOGETHER TO MAP IT ONTO Dr Gruber is more interested in ‘state BRAIN SYSTEMS.” curiosity’ – temporary changes in the brain indicative of someone being curious appears in the external environment, about something. generating sensory impacts that do not Dr Gruber’s work has principally focused match expectations. This perspective on exploring how state curiosity affects highlights the importance of structures brain activity and its impact on learning such as the hippocampus, known to have and memory. The most commonly used a role as a kind of novelty detector. method to elicit curiosity is through trivia Internally, information may arise that Overwhelmed by curiosity: Alice through the looking glass. questions, which to varying degrees is incompatible with existing concepts, trigger an interest among participants leading to cognitive conflict. This kind Following his undergraduate studies in to discover the answer. of situation is associated with activity Germany, Matthias Gruber (a Sir Henry in the anterior cingulate cortex (ACC). Dale Fellow at Cardiff funded by Wellcome Reducing uncertainty However, activation of these systems and the Royal Society) moved to UCL for One advantage of working in the field of does not automatically trigger a state of his PhD on learning and memory. Rather learning and memory, suggests Dr Gruber, curiosity: “We think there is a mechanism than the traditional approach of examining is that much is already known about in between, a prefrontal mechanism, that brain changes associated with learning the neural pathways involved, including is evaluating or appraising information and and memory, he wondered whether the those that enhance learning. In addition, then it leads to curiosity,” says Dr Gruber. brain’s initial state had any impact on past work in psychology has generated The involvement of the prefrontal subsequent learning. “And we found out a rich literature on curiosity. Against cortex is critical in determining the it actually does.” this backdrop and drawing on his own response to prediction errors. On the one The key finding was that motivation findings, Dr Gruber has developed the first hand, it can drive actions to find out more to learn enhanced learning and memory neuroscientific model of curiosity: “We tried to resolve uncertainty. “Or it could be the recall. However, motivating participants in to bring all these theories of curiosity that complete opposite – something that’s research studies usually means providing are out there in psychology together to very novel, something that eliciting lots opportunities for them to gain financial map it onto brain systems.” of internal cognitive conflict, could also rewards. During his postdoc at the The PACE (prediction, appraisal, lead to anxiety.” University of California Davis, Dr Gruber curiosity and exploration) model is rooted If the prefrontal cortex points us in began to wonder how realistic these in the classic principle of the prediction the direction of discovery, dopaminergic paradigms were. He realised that intrinsic error. A prediction error can arise when pathways are then engaged. “Then interests were strong motivators for something unexpected, new or unusual basically people are more active to seek out

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But perhaps the greatest impact could be in education: “That’s what excites me the most,” says Dr Gruber. Young people today face an uncertain future and the possibility of jobs yet to be invented. It is not clear what skills and knowledge they will need. “We need to help them to become lifelong learners, raise them to be curious citizens with active learning skills with excitement about learning and embrace this new A simplified version of the PACE model of curiosity. Adapted from Gruber and Ranganath, 2019. era where you continuously learn about new things and educate yourself.” information,” says Dr Gruber. In addition, Dr Gruber is trying to tease apart brain While much of his past research strong inputs into the hippocampus lead activity shared by attention and curiosity has been on young adults, he has also to enhanced memory encoding. and unique to each. begun to explore the impact of curiosity on learning and memory in children and Total recall What’s the point? adolescents. Early findings suggest that One of the most striking of Dr Gruber’s A bigger question is why we are curious while curiosity promotes learning and findings is that curiosity also enhances anyway. “That’s the key thing about memory in both groups, surprise at the learning of incidental information – a kind curiosity – there’s no immediate benefit answers gives a further boost to memory of spillover effect of an enhanced learning of it.” Acquiring mountains of knowledge only in adolescents. He has also begun state. For example, if participants are might make someone a whizz at Trivial to investigate curiosity and memory shown incidental faces while undertaking Pursuit, but it also absorbs the brain’s within virtual reality environments the trivia question test, their memory for precious resources. From an evolutionary and in computer games. those faces is greater when their curiosity perspective, curiosity may have provided Dr Gruber has come a long was since has been piqued: “We were really surprised a selective advantage: “Just knowing your his days as a postdoc when he had to by that,” says Dr Gruber. “We thought it environment better might help you in the win over his initially sceptical supervisor. was risky and probably wouldn’t work. long run.” However, as any cat will testify, The challenge was even greater as his And then it did work.” curiosity can be a dangerous thing, so initial pilot studies flopped. “It took some A reviewer of their paper was also balancing pressures would have acted time to convince him it was an area worth sceptical, and suggested that they check to keep curiosity in check. studying,” says Dr Gruber. “But I thought, the results by testing memory a day later. These arguments apply to trait ‘this is such an important topic, it's “We thought, this will never work out. curiosity, but the underpinnings of completely understudied, I need to find We ran the experiment, and the results state curiosity remain equally unclear: a way to study it’. That’s really what were very clear.” Memory for faces “We assume it’s a good thing – it’s a kept me going.” presented during high-curiosity states good thing for learning and memory, was still significantly greater a day later. but we don’t really know why. It’s very Gruber MJ, Ranganath C. How curiosity enhances This result was important, as it implied early days in the research field still.” hippocampus-dependent memory: The Prediction, Appraisal, Curiosity, and Exploration (PACE) framework. that memory consolidation as well as Dr Gruber sees several potential Trends Cogn Sci. 2019;23(12):1014–1025. encoding is enhanced by curiosity. This implications of research on curiosity. Gruber MJ et al. Post-learning hippocampal dynamics may distinguish curiosity from another Several conditions are associated with promote preferential retention of rewarding events. Neuron. 2016;89(5):1110–20. well-studied phenomenon, attention. abnormalities in dopaminergic systems, Gruber MJ, Gelman BD, Ranganath C. States of curiosity “We definitely think curiosity is related such as depression and apathy, which modulate hippocampus-dependent learning via the to attention: curiosity enhances attention could have implications for curiosity. dopaminergic circuit. Neuron. 2014;84(2):486–96. during encoding. But it must be more In addition, stimulating curiosity could be than attention, because it enhances a way to enhance learning and memory memory consolidation processes as well.” recall in those with memory impairments, In ongoing functional imaging studies, such as people with Alzheimer’s disease. www.bna.org.uk Spring 2020 BNA Bulletin 29 Research Positive feedback Neurofeedback could provide a way to improve management of chronic pain.

Nerve injury can have a devastating At a glance impact, leading to major disabilities • Chronic neuropathic pain is associated and paraplegia. On top of that, patients with abnormal activation of the with nerve damage are at significant sensorimotor cortex. risk of chronic neuropathic pain. With a background in engineering, Aleksandra • Through neurofeedback, patients Vučković is exploring whether can learn to modulate abnormal cortical technological solutions – specially, activity. EEG-based neurofeedback – could help • Reduced activity of the sensorimotor patients better control their pain. cortex is associated with clinically Based in the School of Engineering in significant pain relief. Glasgow, Dr Vučković has been working with clinicians Matthew Fraser and Mariel • EEG signals can also identify patients Purcell at Queen Elizabeth National with spinal injuries who are risk of Spinal Injuries Unit in Glasgow on brain– chronic neuropathic pain. computer interfaces to aid rehabilitation. The University of Glasgow has funded a Learning to use the neurofeedback equipment. dedicated research space within the Spinal Injuries Unit, the Scottish Centre for of EEG brain activity and, through Initial results were highly promising. Innovation in Spinal Cord Injury, in which practice, learn how to modulate brain Six out of seven patients in the pilot researchers from different universities in activity, receiving real-time feedback study experienced statistically significant the west of Scotland work together. through the visualisations. Neurofeedback reduction in pain, and four patients This work had focused her attention is showing promise in several treatment reported clinically relevant reduction on activation of the motor cortex. areas, including epilepsy and anxiety. in pain (>30%) which lasted at least a However, during her PhD in Aalborg, Having secured MRC funding, month after treatment. These figures Denmark, she had work alongside a large Dr Vučković travelled to London to gain are comparable with the results of pain group, and was aware that pain was training in neurofeedback techniques. pharmacological treatments. also associated with abnormalities in As an engineer, she was able to save The Inspire Foundation was cortical activation that could be detected money by building her own equipment sufficiently impressed with the findings by EEG. and, with her PhD student, set about that it funded a project to develop a set- Functional imaging studies have trialling the technique on patients up usable by patients and caregivers in demonstrated that chronic pain is in Glasgow. their own homes. An initial usability study associated with increased activation of Neurofeedback is not an instant found that 15 out of 20 participants were the sensorimotor cortex. Dr Vučković was fix, but Dr Vučković was fortunate that able to use the neurofeedback equipment able to show that EEG could also detect her study group included people with a and 12 out of the remaining 15 were able this abnormal brain activation: “When medical background, teachers and others to modulate their brain activation. Pain we ask people to imagine movement, keen to try something new to control reduction was statistically significant in we see that people who are about to their pain: “We had very motivated 12 participants and clinically relevant in develop pain or are in pain have much first participants, we were very lucky eight. Nine participants reported a high strong activity in motor cortex.” Notably, with that.” level of satisfaction with the intervention. activation patterns differed between Drawing on the earlier study, The mechanistic basis of paraplegic patients with and without participants were shown coloured bars neurofeedback interventions is poorly pain, suggesting they were related to sensitive to activity in the alpha, beta understood. Participants are taught pain rather than disability. and theta frequency ranges, those most to relax, but relaxation alone does not The reason for the study was her associated with pain. The alpha band was seem to be sufficient to modulate brain interest in using EEG signatures of pain as given greatest prominence, as it appears activity. Dr Vučković is co-supervising the basis of a neurofeedback intervention. to be the one most strongly linked to pain. a PhD student who is investigating In such approaches, participants are The size and colour of the bars shifted the psychological factors affecting the presented with visual representations in line with EEG recordings. success of the technique and patients’

30 BNA Bulletin Spring 2020 www.bna.org.uk Research

SIX OUT OF SEVEN PATIENTS IN THE PILOT STUDY EXPERIENCED STATISTICALLY SIGNIFICANT REDUCTION IN PAIN, AND FOUR PATIENTS REPORTED CLINICALLY RELEVANT REDUCTION IN PAIN (>30%) WHICH LASTED AT LEAST A MONTH AFTER TREATMENT.

The views of participants Adrian Wressell/Wellcome Images ends up on a wheelchair, they’re so overwhelmed they can’t really focus “THIS TRAINING IS LONGER on pain on top of that.” THAN I WOULD DO MY Dr Vučković has now begun a larger RELAXATION AND IT HAS AN study to explore early signatures of pain, IMMEDIATE EFFECT IN TERMS recruiting patients from both Glasgow OF LOWERING PAIN. WHAT IS and the National Spinal Injuries Centre at NEW FOR ME IS THAT THERE IS Stoke Mandeville. A key aim is to develop SOME RESIDUAL EFFECT THAT a tool that will help clinicians assess LASTS THREE TO FOUR DAYS patients and identify those at risk of FOLLOWING TRAINING WHERE chronic pain. “Ultimately what I would like THE PAIN LEVEL IS LOWER AND to make is something that doctors can DIFFERENT TO WHAT I WOULD easily use in neurology departments with NORMALLY EXPERIENCE”. ” existing 19-channel devices that they have in hospitals.” “SPASMS AT WORK HAVE She is also keen to secure funding DIMINISHED GREATLY. AND I Spinal injuries can lead to pain as well as loss of movement. for a larger randomised controlled trial MEAN GREATLY. AND I’VE ONLY of neurofeedback in spinal injury patients. JUST CLICKED THAT IT’S SINCE Predicting pain But she is also interested in exploring I’VE STARTED USING THIS [BCI- A further area of interest for Dr Vučković the potential of neurofeedback in other NFB] THAT WHEN I PUT THE is the evolution over time of changes groups of patients experiencing chronic HEADPHONES ON AT WORK, in the brain and the experience of pain. pain where EEG abnormalities have been THE SPASMS DIMINISH”. To this end, she established a cohort of observed, such as multiple sclerosis and new spinal injury patients. “We looked post-stroke patients. “ANOTHER THING I ALSO GOT at people early after injury, before they Neurofeedback has some way to go OUT OF THE RESEARCH IS JUST develop pain, and for 6 months follow up.” before it becomes a routine treatment for BEING IN CHARGE OF THE PAIN. By comparing signals from patients pain. But Dr Vučković has found it highly PRIOR TO THIS THE PAIN CAME who went on to develop pain from those rewarding to receive positive feedback AND IT WAS THERE AND who did not, Dr Vučković was able to from patients. “Me and my students are I COULDN’T DO MUCH ABOUT IT. discern brain activation signatures that so really happy when we find that it works AFTER THE RESEARCH I FELT were predictive of the development for somebody.” I COULD CONTROL THE PAIN. of neuropathic pain. Using a machine I WAS IN CONTROL AND THE learning approach, she has developed a Vuckovic A et al. Dynamic oscillatory signatures of PAIN DOESN’T HAVE TO BE classifier that can detect those at highest central neuropathic pain in spinal cord injury. J Pain. 2014;15(6):645–55. IN CHARGE OF YOU, YOU CAN risk of developing chronic pain. Hassan MA et al. The mechanism of neurofeedback PUSH THE PAIN BACK.” This raises the possibility that training for treatment of central neuropathic pain in neurofeedback could be used paraplegia: a pilot study. BMC Neurol. 2015;15:200. Al-Taleb MKH et al. Home used, patient self-managed, preventively, to block the development brain-computer interface for the management of central of pain. However, Dr Vučković has neuropathic pain post spinal cord injury: usability study. found that people soon after injury, J Neuroeng Rehabil. 2019;16(1):128. mentalising strategies. It appears that when not affected by neuropathic pain, Vučković A et al. EEG Correlates of Self-Managed Neurofeedback Treatment of Central Neuropathic Pain many participants focus on pleasant are generally not motivated to use in Chronic Spinal Cord Injury. Front Neurosci. 2019;13:762. episodic memories. Personality traits neurofeedback. In part, this reflects a Vučković A et al. Electroencephalographic Predictors of may also be important – the technique limited understanding of the nature of Neuropathic Pain in Subacute Spinal Cord Injury. J Pain. 2018;19(11):1256.e1-1256.e17. appears to be more effective in those neuropathic pain – most patients see Vučković A et al. Prediction of central neuropathic pain in who have the strongest sense that they pain as an acute affliction that can be spinal cord injury based on EEG classifier. Clin Neurophysiol. have agency over their lives. Indeed, a controlled by drugs and will fade when 2018;129(8):1605–1617. commonly stated benefit mentioned injuries heal. In addition, patients may by participants is that they now have a suddenly be facing a dramatic change greater sense of control over their pain. in their circumstances: “If somebody www.bna.org.uk Spring 2020 BNA Bulletin 31 Research Right place, right time Irene Tracey has run a functional neuroimaging unit, a university department and an Oxford college. Highly successful by any measure, her career has not followed any grand plan but has been based on being curious, loving science, people and seizing opportunities as they present themselves.

Having been evacuated during the war, “PAIN IS A HUGE TOPIC WHICH HAD EVERYTHING I LOVED. IT HAD Professor Tracey’s parents had little BASIC DISCOVERY SCIENCE, IT HAD ALL THIS CLINICAL RELEVANCE, educational opportunities themselves but IT WAS PHILOSOPHICAL – IT HAD EVERYTHING.” greatly valued education and encouraged learning: “It was an incredibly supportive – particularly one given by Professor home life,” she recalls. And, from her Sir George Radda on the emerging earliest years, she had the hallmarks of technology of in vivo magnetic resonance a future scientist: “I was always really spectroscopy (MRS): “I was like, ‘wow, I curious, and I was probably a bit of a pain need to do that’.” She realised it would growing up, constantly asking ‘why?’, give her an opportunity to use her physics ‘why?’, why?’.” Fortunately, she had five and maths expertise, applied to biological older siblings to pester. mechanisms. “I thought, ‘this is a win–win, Having been evacuated during the this is everything I love’.” war, Professor Tracey’s parents had little After a lab placement in her fourth educational opportunities themselves but year, she stayed in Oxford for a PhD, greatly valued education and encouraged again with George Radda (after a year out learning: “It was an incredibly supportive spent, among things, working in a Belgian home life,” she recalls. And, from her chocolate shop, travelling and playing earliest years, she had the hallmarks of hockey). To start with, she explored muscle a future scientist: “I was always really tissue in boys with Duchenne muscular Irene Tracey. curious, and I was probably a bit of a pain dystrophy. But the gene affected, growing up, constantly asking ‘why?’, dystrophin, is also normally expressed in the brain in action.” This was the birth of ‘why?’, why?’.” Fortunately, she had five the brain, and her supervisor was happy fMRI – and Professor Tracey wanted to be older siblings to pester. for her to change tack. A landmark paper right there at its dawn. She excelled at her local comprehensive followed and sparked an interest in Her work initially focused on changes school, and had a particular affinity for neuroscience: “I thought, the brain is a in the brains of people with HIV infections maths and physics: “It wasn’t that I was hell of a lot more interesting than skeletal and AIDS. But serendipity brought her bad at the others, it was just those I found muscle, I think I want to go into that.” to the field for which she is best known: effortless.” Notably, she suggests, skills in “Coffee room conversations led to a these areas were more widely beneficial: The birth of brain imaging chance meeting and a chat with the pain “There’s this natural overspill, everything It was fortuitous that the opportunity to clinic at Massachusetts General Hospital becomes much easier.” work with George Radda came as MRS and the struggles they have with trying Although specialising in the physical was being introduced into biology, and to understand pain – what is it, how do sciences at A-level and having a particular increasingly neuroscience. Timing was we know what is going behind the scenes, interest in astrophysics, the life sciences also perfect for her next move. In Harvard, the challenges of only having someone were still an option. Work experience researchers were combining Sherrington’s describe it.” convinced her that medical training was early ideas linking blood flow and brain Professor Tracey was intrigued: “This is not for her and her chemistry teacher activity and Radda’s magnetic resonance a huge topic which had everything I loved. introduced her to biochemistry: “I’d never work relating changes in relaxation times It had basic discovery science, it had all this even heard of it,” she says. of water (in plasma) to the oxygenation clinical relevance, it was philosophical – It Given her academic prowess and its state of blood – notably the change in ratio had everything.” outstanding reputation in biochemistry, of paramagnetic to diamagnetic iron within Oxford had also been making plans Oxford seemed a natural choice. Professor haemoglobin as it loses but then delivers to jump aboard the fMRI bandwagon, Tracey thrived in Oxford, yet a career in oxygen to feed active neurons: “All these and Professor Tracey had been identified science was far from certain. Nevertheless, ideas were known but this lab in Harvard as key to the future of its brain science exposure in lectures to leading scientists had put it all together and did the first research. With her mother being and their research was inspirational functional imaging experiments to look at diagnosed with Alzheimer’s disease, she

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returned to Oxford earlier than planned to “IT’S A PRIVILEGE TO BE ABLE TO DO WHAT WE DO. I DON’T SEE IT help support her family. As well as building AS A THING I HAVE TO COUNTERWEIGHT LIFE AGAINST... I HAVE THIS a highly successful research programme MIX OF THINGS I ENJOY DOING, AND AT DIFFERENT POINTS IN ONE’S in pain, she helped to establish the Oxford LIFE THIS COMPOSITE CHANGES.” Centre for Functional MRI of the Brain and became its second director, for ten years, because my husband was willing to and before taking on responsibility as Head of wanted to take on the lion’s share of the over-arching department, the Nuffield raising the kids.” Department of Clinical Neuroscience. With three children, Professor Tracey would manage the morning school run Learning to lead and her husband the evenings. Her elder Despite not having thought greatly about siblings also provided valuable support. The career advancement, Professor Tracey took secret, she suggests, is to be aware that to leadership like a duck to water. “You compromises and sacrifices would have to don’t seek it out, as an academic it gets be made: “I was very clear that I couldn’t thrust upon you,” she suggests. “We all do have it all, I absolutely didn’t have that our good citizenship in making the system expectation; I recognised that there would work because it’s self-governing. In that be sacrifices and compromises. You have to zeitgeist you need to step up and take on be honest with yourself about that.” some of these roles, whether it’s running Moreover, it is for individuals – and Running for pleasure (and charity). an imaging centre or a department.” families – to work out what is right for She adds that she was fortunate to them: “There’s not a template to follow. influential: “This isn't just about women, have incredibly supportive colleagues and Everybody has to decide what works for it’s also about men standing up and doing heads of department, men and women, them.” In her case, her husband took a things like my husband did. It sent a very encouraging her progress – people like Paul step back from his career: “Without him good message to his junior colleagues, who Matthews, Kay Davies, Angela Vincent and doing that, there was no way I could have similarly followed suit.” Chris Kennard. In turn, she aims to mentor taken on those extra leadership roles,” she In the autumn of 2019, Professor the younger generation, particularly female suggests. Tracey took up a new challenge, as Warden scientists. Leadership roles can seem Professor Tracey questions whether of Merton College – her alma mater. “The quite daunting, but she tries to encourage the notion of ‘work–life’ balance truly reason I’m doing it is because this is where women to give it a go: “You never quite applies in science: “It’s a privilege to be I came as an undergraduate and I stayed know whether you’re going to like it or able to do what we do. I don’t see it as on as a graduate. Because it was just so whether you’re going to be good at it.” thing I have to counterweight life against.” transformative for me, I want to give In Professor Tracey’s case, she Rather, she sees all the things she does, something back to somewhere that was discovered that she did have a flair for including ‘work’, as part of a mosaic or incredibly important in my life.” strategy and leadership: “And I really enjoy composite: “I have this mix of things I Again, timing was key: if she hadn’t it. I genuinely find it very rewarding to enjoy doing, and at different points in taken up the appointment in 2019 when a make things happen, to create physical one’s life this composite changes.” vacancy became available, it would be at buildings or cultures where I can see people She has also reluctantly come to least seven more years before the chance realise their full potential. That may sound realise that being a woman in a leadership would have come again. It was a big leap – clichéd or corny but that is honestly true: I position does matter. Sex may seem an she resigned a prestigious university chair just find that very fulfilling.” irrelevance when your aim is just to do a to take up a temporary appointment. So Which is not to say that things haven’t job as best you can, but seeing successful far she has no regrets and is loving the been challenging. In Boston, Professor women can be inspiring and establish new new role and, importantly, is being given Tracey married her fiancé from Oxford norms: “It doesn’t take many to change the time to continue her research. (Myles Allen, an atmospheric/climate the culture and to change the optics and Again, she is not worried or looking to physicist who joined her in Boston and to raise the bar of expectations so that far-out horizons: “This is what I want to do worked at MIT) and upon returning to women automatically assume ‘well, of now for this next phase. Who knows what Oxford they started a family. She was course I could go and become that because I’ll do afterwards, if anything – the one helping to care for a mother with dementia x, y and z did it’. And that does make a thing I have learnt is that opportunities and an ageing father. She is well aware difference.” unexpectedly arise, so I’m just going to see that her achievements relied significantly Moreover, she emphasises how this bit through and do the best I can and on family support: “I could only do that her husband’s actions have also been see what comes up.” www.bna.org.uk Spring 2020 BNA Bulletin 33 Et cetera

to integrate current knowledge on Q&A: Pia Siegele microglial signalling pathways relevant to Alzheimer’s disease. My diagram Pia Siegele (Edinburgh) was highlights the interconnectivity of these the winner of the BNA’s pathways and how important it is to Undergraduate Award 2019. consider this interconnectivity when trying to understand the disease and develop Q: What did you discover effective treatments. in your research? As part of my application for the BNA Q: What did you think when you undergraduate prize, I submitted two heard you’d won the BNA award? pieces of research. One was my honours I felt very honoured to have been awarded Annette Dolphin presents Pia Siegele with her award. dissertation in which I used whole-cell the BNA undergraduate prize! patch–clamp recordings to investigate 2020 – there are so many interesting and the connectivity of neurons within layers Q: What are you doing now? exciting possibilities! Wherever I end up, 2b and 3 in the lateral entorhinal cortex I am currently doing a Master’s in Cognitive I hope to make valuable contributions to (LEC), a brain region important for episodic Science within the School of Informatics our scientific community in the future. memory. My data provided new evidence at the . Throughout that the outputs and projection patterns my postgraduate studies, I hope to acquire Q: What do you enjoy doing of the two layers are not only distinct valuable advanced computational and outside science and medicine? from each other but also differ from mathematical skills to complement my I enjoy travelling, swimming, skiing and corresponding layers of the adjacent medial expertise in neuroscience. I am hoping to do hiking in my free time. When I am at home entorhinal cortex. Such morphological my master’s project on a topic that involves in Germany, I enjoy going on long walks studies will hopefully help us better interactions within neuronal networks. with my Icelandic sheepdog. I also very understand the structure of the LEC’s much appreciate good food and like neuronal circuitry and the computations Q: What are your to cook dishes from all over the world. carried out within it. long-term plans? The second project I submitted I haven’t made up my mind yet on what was a pathway diagram which aimed to do after I finish my master’s in August

a postdoc, and am also finishing a book Q&A: James Phillips I have been writing since the start of my thesis. It is kind of a neuroscience book, James Phillips (Cambridge) hub of the brain, the thalamus, using but also a bit broader than that, combining was the winner of the BNA’s genetic sequencing of its projections. some other areas of science/philosophy. Postgraduate Award 2019. We discovered that there are deep similarities in the organisational patterns Q: What are your of the pathways that get to visual, motor, long-term plans? prefrontal and other cortical areas from Fingers crossed to work as a researcher the thalamus. This provides support to at the interface of theory and experiment, the notion of a relatively ‘universal’ studying brains. The main next step is to function algorithm in thalamic systems, get the skillset needed to do a project with an architecture on which specialisations a higher theoretical/modelling component can then arise for each system. – I’ve mainly done analysis and experiments so far so it’s a gap to fill. Q: What did you think when you heard you’d won the BNA award? Q: What do you enjoy doing Annette Dolphin presents James Phillips with his award. I had to read the letter three times because outside science and medicine? it was surprising! But I felt very happy. I enjoy watching cricket, and also writing Q: What did you discover It came right after I preprinted a paper from (see above) and reading. But discussing, in your research? my thesis that the team had just finished, researching and then putting into action I did a few projects, but they centred on so it came at a good time. ideas/hypotheses is my main passion – how different brain areas interact. In one, science for me is a very social endeavour I started a project called thalamoSeq, Q: What are you doing now? and discussing it with others is not just which sought to understand the I’m currently teaching myself some important, but a central part of refining organisation of the central communication mathematics and theory to prepare for ideas and hypotheses.

34 BNA Bulletin Spring 2020 www.bna.org.uk Imperial College London, Exhibition Road Sunday 19th to Wednesday 22nd July Featuring a range of non-clinical and clinical presentations across a range of A Guest Lecture by Professor Val Curran neuropsychiatric conditions Cannabis: pleasures, pains & politics • Big data approaches to understanding Non-Clinical Session mental disorders and treatment response Are we getting closer to translatability in neuropsychiatric research? • Mapping impulsivity and compulsivity: Trainees’ Workshop phenotypes, cognitive markers, neural Funding and Fellowships domains and treatment A Public Lecture presented by Professor David Nutt • Enabling translational psychopharmacology New Horizons for obsessive-compulsive disorders: from lived experience to through preclinical MR technology novel interventions • What can computational analyses of brain PLUS bursaries, prizes and poster sessions imaging data tell us about mechanisms in Welcome Reception and Disco psychiatric disorders? Conference Dinner at the Royal Garden Hotel including • Social neuropeptides: Central oxytocin and presentation of the 2020 Prizes and Awards vasopressin pathways and translational For full details of the meeting go to implications www.bap.org.uk/BAP2020

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