Nikoslogothetiscouldhavebeena

NEWS FEATURE NATURE|Vol 437|13 October 2005 The maestro of minds

With a mathematician’s logic and the perfectionism of a concert pianist, Nikos Logothetis is making waves in cognitive neuroscience — and putting the German town of Tübingen on the scientific map. Alison Abbottpays him a visit.

ikos Logothetis could have been a professional musician: as a student, he used to play the piano in Greek Nbars to earn his tuition fees. And his undergraduate training in mathematics nearly took him into physics. But his bedside reading in those formative years eventually led him to biology, for which neuroscientists can count themselves lucky. Today, Logothetis is at the top of his field. His experimental rigour commands widespread respect, and he is churning out a stream of red- MAX PLANCK INST. FOR BIOLOGICAL CYBERNETICS BIOLOGICAL FOR INST. PLANCK MAX hot papers. More importantly, his meticulous experiments have advanced the brain-imaging technique of functional magnetic resonance imaging (fMRI) as a respectable scientific tool. Logothetis seems both pleased and slightly embarrassed by such accolades. During our The expanding Max Planck Institute for Biological Cybernetics in Tübingen is luring top neuroscientists. interview, he frets about seeming conceited as we discuss his achievements. Such are the trou- States for 12 years. He first worked at the Mass- known as BOLD, is a measure of changes in bles of a bone fide polymath. Logothetis speaks achusetts Institute of Technology (MIT) in oxygen levels in the brain, caused by varia- six languages, and studied music for seven years Cambridge, Massachusetts, as a postdoctoral tions in blood flow. But until Logothetis at the Athens Conservatory in Greece. But fellow and later as a research scientist, and entered the fray, nobody had confirmed that music was always a companion, not a profes- then joined the faculty of the Division of Neu- these fluctuations actually correlate with sion. His first love was mathematics. Yet after roscience at Baylor College of Medicine in neuronal activity. completing a degree in the subject from the Houston, Texas. University of Athens in 1977, Logothetis was Logothetis’s main research focus has always Head hunting unsure about how to apply his training. been visual perception — understanding what In 2001, after painstaking studies in which he First, he toyed with the idea of going into goes on in our brains when we perceive and compared traditional electrophysiological physics, but worried that the certainties of recognize objects. During his early career, recordings in anaesthetized monkeys with ‘hard science’ would prove insufficiently chal- Logothetis worked mostly by recording the fMRI scans, Logothetis and his colleagues lenging. Then, soon after graduating, he fell activity of single neurons using sensitive elec- finally pinned down the neural correlate of under the spell of a book on his bedside table: trodes; he still uses such techniques for a major the BOLD signal. This turned out to be ‘local Chance and Necessityby Jacques Monod, the part of his work. But during the 1990s, Logo- field potentials’ — not the firing of individual French molecular geneticist who shared the thetis became increasingly involved in fMRI. cells, but the more slowly varying electrical 1965 Nobel prize in medicine for his work on This variant of MRI was then becoming a fash- activity of groups of cells as they receive and the genetic regulation of enzyme synthesis. ionable research tool, but was also acquiring a integrate information1. The paper was imme- Logothetis was particularly struck by Monod’s degree of notoriety. Some scientists were mak- diately hailed as a tour de forceof experimen- chapter on molecular cybernetics, which ing exaggerated claims for its ability to locate tal dexterity and data analysis2, and in 2003 introduced him to the concept of systems the precise anatomical locations of particular was the most highly cited study in biology, control in biology. “That chapter was a true cognitive processes. apart from a handful of genome papers. revelation for me and decisive in starting my Logothetis has no patience with such lack of By the time his landmark paper was pub- biology studies,” Logothetis says. rigour. He admits to having an “obsessive– lished, Logothetis had been back in Europe for compulsive attention to detail”, and soon several years. In the mid-1990s, he had been in Universal talent gained a reputation for careful and elegant hot demand, and was vigorously pursued by Although Logothetis had previously dismissed fMRI studies. The brain is a very accommo- Germany’s Max Planck Society, which installed biology as being “too descriptive and soft”, he dating structure,” he warns. “It will let you him as director of the Max Planck Institute for immediately embarked on a second under- generate a mass of data and interpret them to Biological Cybernetics in Tübingen. There, he graduate degree in the subject at the support your idea.” The key, he says, is strict was given the best available facilities, including Aristotle University of Thessaloniki. There, he quality of methodology and keeping the ears high-magnetic-field-strength fMRI machines, was introduced to neurobiology, which became resolutely plugged against the siren song of and state-of-the-art facilities for caring for his professional obsession only at the very end over-interpretation. experimental primates. of the course. More fundamentally, Logothetis was But happy as he was to be back in Europe, it After rushing through a PhD in neuro- frustrated that no one had fully tested the wasn’t long before Logothetis started to feel science at the Ludwig–Maximilians University underlying assumption behind fMRI. In oppressed by the isolation of Tübingen — a in Munich, Logothetis moved to the United most fMRI studies, the main signal recorded, smallish provincial town away from major

Multi-talented: now a leader in the field of cognitive neuroscience, Nikos Logothetis studied music for seven years and could have been a concert pianist. intellectual centres. Then, in 1997, came an opened its new building in May last year. With Tübingen, he is developing a sophisticated offer to head the prestigious new McGovern 150 staff, the institute will work on conditions MRI contrast agent which changes its mag- Brain Research Institute at MIT, being set up such as Alzheimer’s disease. netic properties when it is exposed to calcium, with a donation of around US$350 million Safe in the knowledge that a critical mass of allowing the calcium to be visualized. This, he from the computer publishing magnate Pat neuroscientists are gathering around him, hopes, will provide a direct signal for the McGovern and his wife Lore Harp McGovern. Logothetis is now settled. He has expanded his fluxes of calcium ions that accompany the Extraordinary steps were taken to keep Logo- own department to more than 60 people and transmission of neural impulses. “If the mol- thetis in Germany. Hubert Markl, the president his head is a cauldron of plans. He is still not ecular signalling works, then maybe we would of the Max Planck Society at the time, worked convinced that we understand enough about not need to know so much about the BOLD hard to find a way to transfer Logothetis’s entire the neural events underlying fMRI recordings. signal,” he jokes. department to a larger city. Frankfurt, which The local field potentials that correlate with Meanwhile, Logothetis’s meticulous fMRI boasts a high level of neuroscience research the BOLD signal, for instance, are affected studies continue to make waves among neuro- activity, was front runner. by many different components of the brain’s scientists. In one recent paper3, he argued that electrical activity. “We must understand the the visual cortex does not reorganize itself fol- Done deal lowing damage to the retina. If Logothetis is Negotiations opened up, but regional politics “I prefer to work more like a postdoc right, he will have overturned a large body of blocked the efforts. So Markl vowed instead to than a research director.” literature which claims, using recordings from bring the mountain to Mohammed. A critical single neurons, that such reorganization does mass of high-level neuroscientists must be — Nikos Logothetis occur. Although the jury is still out, few who attracted to Tübingen, he declared. Markl are familiar with Logothetis’s work would bet aimed to recruit a leading technical expert in relation between the fMRI signal and all those against him being right. brain imaging, who could land Tübingen in components,” says Logothetis. Unlike many lab chiefs, Logothetis says he pole position in the race to develop the next Providing the answers will mean pushing will continue to deploy the hands-on skills that generation of fMRI machines. That person was the experimental envelope on all fronts. Logo- made his name. “I prefer to work more like a Kamil Ugurbil from the University of Min- thetis plans to use ‘tetrodes’ — electrodes with postdoc than a research director,” he says. nesota, who has now been appointed director four contact points — to follow in more detail “I like to do experiments myself.” Typically, of the Tübingen Institute’s new department for what is going on in several neurons simulta- he runs experiments in the mornings and high-field magnetic resonance. A €22-million neously. Those recordings will then be inte- crunches data until the small hours. Then it’s (US$27-million) building is currently being grated with studies in neuropharmacology, time for the maestro to wind down: if he’s built to accommodate Ugurbil’s team and three optical spectroscopy and molecular imaging. lucky, he fits in half an hour on his piano new fMRI machines. Making sense of the resulting data will before a short night’s sleep. ■ Meanwhile, the German Research Founda- push even Logothetis’s mathematical skills to Alison Abbott is Nature’s senior European tion (DFG), Germany’s main research grant- the limit. correspondent. ing agency, lobbied for a new neuroscience Logothetis is also using high-field fMRI institute planned by the charitable Hertie machines as spectrometers to record the lev- 1. Logothetis, N. K., Pauls, J., Augath, M., Trinath, T. & Oeltermann, A. Nature412,150–157 (2001). Foundation to be established in Tübingen. The els of individual neurotransmitters. And 2. Raichle, M. E. Nature412,128–130 (2001). Hertie Institute for Clinical Brain Research together with chemists at the University of 3. Smirnakis, S. M. et al. Nature435,300–307 (2005).