Links to external sources may no longer work as intended. The content may not represent the latest thinking in this area or the Society’s current position on the topic.
Interpreting BOLD: a dialogue between cognitive and cellular neuroscience
Theo Murphy international scientific meeting organised by Dr Anusha Mishra, Professor David Attwell FRS, Dr Zebulun Kurth-Nelson, Dr Catherine N. Hall and Dr Clare Howarth
Cognitive neuroscientists use BOLD signals to non-invasively study brain activity, although the neurophysiological underpinnings of these signals are poorly understood. By bringing together scientists using BOLD/fMRI as a tool with those studying the underlying neurovascular coupling mechanisms, the aim of this meeting was to create a novel dialogue to understand how BOLD relates to brain activity and inform future neurovascular and cognitive research.
Download the meeting programme
Audio recordings of the talks will be made available on this page shortly.
Enquiries: please contact Kavli.Events@royalsociety.org
Organisers
Schedule
Chair
Professor David Attwell FRS, University College London, UK
Professor David Attwell FRS, University College London, UK
David Attwell studied physics as an undergraduate in Oxford, and then did a PhD working on nerve and muscle with Julian Jack. After a post-doc in Berkeley working on the retina with Frank Werblin, he came to UCL as a Lecturer and is now Jodrell Professor of Physiology. His research has covered synaptic transmission and information processing in the CNS, the properties of glial cells, glutamate uptake and how it reverses and releases glutamate in ischaemia, the energy supply to the brain and its regulation at the capillary level by pericytes, and the cellular basis of BOLD imaging. He is a Fellow of the Royal Society and of the Academy of Medical Sciences.
| 09:10 - 09:40 |
Uses, misuses, new uses and fundamental limitations of MRI in cognitive science
When BOLD contrast was discovered in the early 1990s, it provoked an explosion of interest in exploring human cognition using brain mapping techniques based on MRI. Standards for data acquisition and analysis were rapidly put in place, in order to assist comparison of results across laboratories. Recently, MRI data acquisition capabilities have improved dramatically, inviting a rethink of strategies for relating functional brain activity at the systems level with its neuronal substrates and functional connections. This presentation will review the following questions: a) What can structural and functional BOLD MRI reveal about human cognition that other techniques cannot provide? b) In which areas of cognitive science has fMRI made major contributions? c) What are the implicit assumptions underlying now-popular analysis techniques, and what are the flaws in these assumptions? d) Can MRI-based myeloarchitectural parcellation of the cortex and high resolution fMRI methodology make these assumptions unnecessary? e) Are there other ways of analyzing MRI/fMRI data that provide deeper insight? f) Will cortical layer-specific fMRI enable questions of causality to be addressed, and what are the best candidate techniques for such acquisitions? g) What are the likely fundamental limitations of all MRI and fMRI methods? 
Professor Robert Turner, Max Planck Institute for Human Cognitive and Brain Sciences, Germany
Professor Robert Turner, Max Planck Institute for Human Cognitive and Brain Sciences, GermanyRobert Turner played a key role in the invention of actively shielded gradient coils used widely in MRI, in the development of diffusion weighted imaging of the human brain, which allows assessment of brain connectivity and evaluation of stroke damage, and in the discovery of functional MRI by measurement of the effects of blood oxygenation changes. As a Max-Planck Institute Director in Leipzig, Germany, he has been engaged in the discovery of native cortical anatomical maps of individual living human brains using ultra-high field MRI. He started his academic career as a physicist, studying maths and physics at Cornell University until 1968, and completed his doctorate in physics at Simon Fraser University, Vancouver. After three years as a post-doctoral physicist at the Cavendish Laboratory, Cambridge, he broadened his horizons by studying social anthropology at University College London. During the period of ethnographic fieldwork that followed, he encountered MRI, which had been recently invented, and realized that this technique could provide insight into basic aspects of human nature, via maps of human brain organization. Returning to physics as a lecturer at Nottingham University in 1984, he built his own MRI scanner in 1984, designed and built gradient coils for MRI, and assisted the Nobel Prize winning Sir Peter Mansfield in developing ultra-fast MRI techniques. As a Visiting Scientist at NIH between 1988 and 1994, he pioneered functional magnetic resonance imaging (fMRI) and diffusion weighted imaging. This led to his appointment as Wellcome Principal Research Fellow and Professor in Imaging Physics at the Institute of Neurology in London, where he established fMRI as a tool for cognitive neuroscience. |
|
|---|---|---|
| 09:50 - 10:20 |
Neurovascular coupling: when its reliability as a marker of neuronal activity gets challenged
Changes in neuronal activity are spatially and temporally coupled to concurrent changes in cerebral blood flow (CBF), a process known as neurovascular coupling (NVC) that forms the basis of several brain imaging techniques. Yet, it is unclear how reliable this coupling remains during altered brain states and, particularly, under pathological conditions. Using the whisker-to-barrel pathway, a well-established model of NVC, we tested whether the coupling between neuronal activity and CBF would be affected by changes in brain states induced by varying the levels of acetylcholine (ACh), a potent modulator of sensory processing. Under acute increases in ACh tone, whisker-evoked hemodynamic responses and neuronal signals (LFPs and band-limited power) were potentiated despite no change in the extent and identity of the neuronal network recruited within the activated barrel. Inversely, chronic ACh deprivation compacted the activated barrel and reduced both sensory-evoked hemodynamic and neuronal responses. Our findings indicate that hemodynamic signals dependably reflect changes in the activity of the neural circuit underlying sensory processing under states of enhanced ACh neurotransmission and in conditions of a cholinergic deprived network as seen in Alzheimer’s disease. 
Professor Edith Hamel, Montreal Neurological Institute, McGill University, Canada
Professor Edith Hamel, Montreal Neurological Institute, McGill University, CanadaDr Edith Hamel is director of the Laboratory of Cerebrovascular Research at the Montreal Neurological Institute, McGill University, Montréal, Canada. Her research focuses on neuro-glio-vascular interactions that assure a proper blood supply to activated brain areas, a phenomenon known as ‘neurovascular coupling’. These interactions are at the basis of several brain imaging techniques that use hemodynamic signals to map changes in brain activity under physiological and pathological conditions. An important aspect of her research is dedicated to the understanding of how specific neuronal populations sculpt changes in neuronal activity in response to specific stimuli and how these changes are communicated to blood vessels. Another aspect of Dr Hamel’s research aims at understanding the impact of cerebrovascular alterations on cognitive failure in Alzheimer’s disease and vascular dementia. Dr Hamel has published over 135 peer-reviewed journal articles, and she is currently President of the International Society of Cerebral Blood Flow and Metabolism. |
|
| 11:00 - 11:30 |
Vasomotion: a link from ultra-slow neuronal activity to blood oxygenation
The blood-oxygenation-level-dependent (BOLD) fMRI signal is a central technology of modern cognitive neuroscience. An intriguing issue is that ultra-slow variations (~ 0.1 Hz) in the oxygenation of brain tissue appear to be mirrored across conjugate brain areas in the two hemispheres. This is referred to as ‘resting-state’ BOLD fMRI and this finding has been inverted in many studies of human cognition, so that ultra-slow co-fluctuations are interpreted as ‘function connections’. Yet the mechanism to support this interpretation remains to be discovered. Here we address this relation in awake mice through measurements of neuronal activity, tissue oxygenation, and conventional and ultra-large field two-photon imaging of vascular dynamics. We provide evidence that arteriole vasomotion can link ongoing, coordinated neuronal activity with ultra-slow oscillations in blood oxygenation. This result may justify inferring neuronal connections from synchronous ultra-slow vasodynamics between different brain areas. 
Professor David Kleinfeld, University of California, San Diego, USA
Professor David Kleinfeld, University of California, San Diego, USADavid Kleinfeld is a Distinguished Professor of Physics and of Neurobiology (courtesy) and currently holds the Endowed Chair in Experimental Biophysics. He trained in experimental physics with George Feher, then shifted his research efforts to the study of networks within nervous systems while a Member of Technical Staff at AT&T Bell Laboratories. His ongoing programs address the basis of exploration and active sensation within brainstem circuits and the relation of vascular architecture and vasodynamics to the control of blood flow within cortex. These two programs are synergistic and further involve the development of tools for neurological data acquisition and analysis. David is committed to the education of young neuroscientists. Beyond training protégés that have gone on to faculty positions at research universities, he has co-directed and/or lectured at postgraduate summer schools at Cold Spring Harbor Laboratory, Laval University, and the Marine Biological Laboratory for over two decades. |
|
| 11:40 - 12:10 |
Model-based approaches that connect BOLD imaging and dopaminergic transmission in humans
Using a simple sequential decision task we provide new data showing a cross cohort relationship between BOLD responses during the decision task and sub-second electrochemical estimates of dopamine and serotonin from the dorsal striatum. Not surprisingly the relationship among these three separate measures is not simple even allowing for the possibility that some features of the signaling are unique to the state of the subjects’ brains (i.e. Parkinson’s Disease or Essential Tremors). Dopamine and serotonin appear to correlate with error signals for experienced rewards and one form of counterfactual signals (what might have been gained or loss had the choice been different). Moreover, fluctuations in these two transmitters prospectively encode a subject’s strategy on their next choice (stay or shift) with dopamine carrying this information following a positive prediction error and serotonin carrying it following a negative prediction error. We speculate about the connection between the measured BOLD response and the measured neuromodulator response; however the results do suggest more complexity than is latent is models built solely around the BOLD response. 
Professor Read Montague, Virginia Tech Carilion Research Institute, USA and University College London, UK
Professor Read Montague, Virginia Tech Carilion Research Institute, USA and University College London, UKRead Montague holds a Principal Research Fellowship from the Wellcome Trust and is a principal at the Wellcome Trust Centre for Neuroimaging. He is a professor of physics at Virginia Tech Carilion Research Institute where he is also founding director of the Computational Psychiatry Unit and Human Neuroimaging Lab. Montague's work lies at the intersection of computational neuroscience and neuroimaging, and in recent years has focused on imaging brain function during active social exchange. Montague is broadly interested in the detailed neurobiology of social behaviour with a particular emphasis on the role of neuromodulatory systems that deliver dopamine and serotonin throughout the brain. His laboratory uses theoretical, computational, and experimental approaches to these issues. In particular, the group now employs novel approaches to functional neuroimaging, new biomarkers for mental disease, spectroscopy, real-time voltammetry, and computational simulations. Montague also directs the Roanoke Brain Study, a project aimed at understanding decision-making through the lifespan and its relationship to brain development, function, and disease. Work in the laboratory is supported by the National Institutes of Health, National Science Foundation, The Kane Family Foundation, Autism Speaks, The MacArthur Foundation, The Dana Foundation, and The Wellcome Trust. |
| 13:30 - 14:00 |
Multimodal investigation of the neurovascular unit following focal cerebral ischemia
In recent years, the state of the peri-infarct zone, a meta-stable region of at-risk brain tissue that surrounds the permanently damaged necrotic core, has been identified as a major determinant of functional outcome post stroke. We used BOLD, arterial spin labelling and intra-cortical array electrophysiology to identify the changes in the neurovascular unit in an endothelin-1 rat model of focal cortical ischemia. Two days following ischemic insult, peri-lesional tissue exhibited heightened resting perfusion and increased vascular reactivity to hypercapnia. These hemodynamic alterations were accompanied by changes in phase-amplitude coupling of the neurons. The synchronization of amplitudes of faster rhythms with the phase of slower rhythms was altered in the perilesional tissue, indicating pathophysiological functioning of the neuronal network surrounding the necrosis. These distinct changes in the vascular vs. neuronal reactivity make BOLD fMRI responses particularly hard to interpret and necessitate multi-modal experiments to independently assess the evolution of changes in the respective cellular populations over the course ischemic injury progression. 
Dr Bojana Stefanovic, Sunnybrook Research Institute, Canada
Dr Bojana Stefanovic, Sunnybrook Research Institute, CanadaDr Stefanovic completed undergraduate training in Electrical Engineering at UBC and obtained a PhD in Biomedical Engineering from McGill, where she developed MRI pulse sequences for quantification of stimulation-elicited changes in cerebral hemodynamics in humans. During postdoctoral studies at NIH, she conducted imaging studies on neurovascular coupling in rodent and non-human primate models. In 2008, Dr Stefanovic joined Imaging Research at the Sunnybrook Health Sciences Centre and Medical Biophysics at the University of Toronto, where she has been an Associate Professor since 2014. Dr Stefanovic’s laboratory is focused on the development of in vivo high field MRI, two-photon fluorescence microscopy, and extracellular and intracellular recordings for tracking functional deficits in different cellular populations comprising the neurovascular unit over the course of neurodegeneration in transgenic rodent models of Alzheimer’s Disease and during chronic stage of recovery in rodent models of focal ischemia. |
|
|---|---|---|
| 14:10 - 14:40 |
Deep neural networks: a new framework for understanding how the brain works
Recent advances in neural network modelling have enabled major strides in computer vision and other artificial intelligence applications. Artificial neural networks are inspired by the brain and their computations could be implemented in biological neurons. Although designed with engineering goals, this technology provides the basis for tomorrow’s computational neuroscience. In order to test such models with massively multivariate brain-activity data, we can characterise the representational spaces in brains and models by matrices of representational dissimilarities among stimuli. Deep convolutional neural nets trained for visual object recognition have internal representational spaces remarkably similar to those of the human and monkey ventral visual pathway. Deep neural networks explain representations of novel images as reflected in both functional magnetic resonance imaging (fMRI) data and neuronal recordings. Current challenges include exploration of alternative neural net models consistent with typically limited neurophysiological data and statistical inference to adjudicate among them while taking into account how the measurement method samples neuronal activity patterns. For fMRI, we need to model how hundreds or thousands of voxels within an area reflect the representations in many millions of neurons. We are entering an exciting new era, in which we will be able to build neurobiologically faithful feedforward and recurrent computational models of how biological brains perform high-level feats of intelligence including vision. 
Dr Nikolaus Kriegeskorte, Medical Research Council, UK
Dr Nikolaus Kriegeskorte, Medical Research Council, UKNikolaus Kriegeskorte is a brain scientist who studies visual object recognition using functional magnetic resonance imaging, pattern-information analysis, and computational modelling. He is a Principal Investigator at the Medical Research Council's Cognition and Brain Sciences Unit in Cambridge, UK. With a background in psychology and computer science, he did his thesis research at the Frankfurt Max Planck Institute for Brain Research and Maastricht University, and worked as a postdoctoral fellow at the University of Minnesota and at the National Institutes of Mental Health. |
|
| 15:20 - 15:50 |
Imaging the mechanisms of cognition
Human imaging approaches have had great success in uncovering cognitive mechanisms associated with brain areas and gross neural signals. There is, however, a large gap between such studies and studies in animal models which make inferences at the level of cells and synapses. Recently human imaging work has led to techniques that have the potential to bridge this gap by making inferences at the mesoscopic scale of neural ensembles. I will present two such studies that use coarse brain imaging and interventional tools to try to make inferences about how cognitive associations are stored in synapses and in organised cellular activity. We think it is very important that the field moves towards being able to make such inferences in humans, because it would mean that mechanistic theories of complex cognitive processes and psychiatric conditions that are developed in animal models could be tested directly. 
Professor Tim Behrens, University of Oxford, UK
Professor Tim Behrens, University of Oxford, UKTim Behrens is interested in neural coding in the prefrontal cortex and how this relates to learning and choice. His work spans a number of techniques and species in an attempt to reconcile the precise measures and manipulations of activity that can be acquired invasively with the complex and well controlled behaviours that can be studied in humans. |
| 09:00 - 09:30 |
Cellular and molecular determinants of the hemodynamic response
The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use noninvasive technologies. This is in contrast to animal models where a rich, detailed view on the cellular level brain function has become available due to recent advances in microscopic optical imaging and genetics. Thus, a central challenge facing neuroscience today is leveraging these mechanistic insights from animal studies to accurately draw physiological inferences from human noninvasive signals. We will discuss a strategy of addressing this challenge by combining human and animal experiments and computational modeling with the endpoint goal to deliver a quantitative probe for neuronal activity of known cell types in human brain enabling a paradigm shift in human fMRI studies: from a simple mapping of fMRI signal change to the explicit estimation of the relative activity levels of specific neuronal cell types. 
Dr Anna Devor, University of California, San Diego, USA
Dr Anna Devor, University of California, San Diego, USAAnna Devor holds two academic appointments as Associate Adjunct Professor in Neurosciences and Radiology at University of California San Diego (UCSD) and Instructor in Radiology at Massachusetts General Hospital (MGH, Harvard Medical School). Dr Devor has a broad base of knowledge in cellular and systems-level neuroscience. Her secondary expertise is development and refinement of microscopic optical technology for imaging of brain activity in live animals (in vivo). Dr Devor received her initial research training at the interface between experimental and computational neuroscience at Hebrew University of Jerusalem, Israel. Her PhD thesis focused on biophysical mechanisms of the membrane potential oscillations in a network of electrically coupled neurons. After completing her PhD in 2001, she went on to specialise in optical and MR-based imaging technology at Martinos Center for Biomedical Imaging at MGH before taking up an independent position as Instructor in Radiology at the same institution in 2004. In 2005, she accepted a second academic appointment at UCSD. The core of Dr Devor’s research program is focused on dissecting neuronal, glial and vascular mechanisms that underlie signals obtained with noninvasive brain imaging modalities such as fMRI. She has published extensively on imaging and recording of brain activity using 2-photon microscopy, voltage- and calcium-sensitive sensors, O2-sensitive phosphorescent probes, intrinsic optical contrasts and extracellular electrophysiological recordings. These microscopic measurements are integrated in a computational framework that allows prediction of macroscopic fMRI responses. Dr Devor also applies novel imaging technologies for in vivo investigation of mouse models of neurological disease and human stem cell-derived neurons transplanted in the mouse brain. |
|
|---|---|---|
| 09:40 - 10:10 |
Neural-metabolic coupling in the central visual pathway
Noninvasive neural imaging of the brain has become a primary neuroscience tool. Different techniques have been used but functional magnetic resonance imaging (fMRI) is currently the dominant procedure by which hemodynamic processes are monitored to infer properties of neural activity. A fundamental question concerns the functional relationship between the local hemodynamic changes that are measured and the implications for neuronal function. In a series of studies, we have measured an important metabolic parameter, tissue oxygen concentration, along with activated neural activity in the central visual pathway. Tissue oxygen changes are directly related to the blood oxygen level-dependent (BOLD) signal that is used in fMRI. We have employed a sensor that provides simultaneous co-localized measurements of oxygen concentration and neural activity from single cells to characteristics of the oxygen response including spatial, temporal and scaling parameters. We have also investigated changes in oxygen concentration with single cell, multiple unit, and local field potential activity. Finally, we have used specialized sensors to measure neurometabolic coupling between neural activity, glucose, and lactate in activated visual cortex. Findings of these studies will be described. 
Professor Ralph Freeman, University of California, Berkeley, USA
Professor Ralph Freeman, University of California, Berkeley, USAProfessor Freeman completed a PhD in Biophysics at the University of California, Berkeley and then began a faculty position there as Assistant Professor. He remained to become Full Professor associated with Vision Science, Optometry, Bioengineering, Biophysics and the Helen Wills Neuroscience Institute. He has held various fellowships and awards and is an elected Fellow of the American Association for the Advancement of Science, has been a visiting research scientist at the University of Cambridge, has given various invited lectures at worldwide institutions including a Plenary Lecture at the Society for Neuroscience. He has served as an advisor to journals, agencies, and organisations. He has published extensively on research covering topics that focus on organisation and function of the central visual pathway with an emphasis on binocular vision. His recent work is concerned with the neural and metabolic factors involved in non-invasive neural imaging. |
|
| 11:00 - 11:30 |
A BOLD look at the brain's intrinsic activity
Initially regarded as ‘noise’, spontaneous (intrinsic) activity accounts for a large portion of the brain’s metabolic cost. Moreover, it is now widely known that infra-slow (< 0.1 Hz) spontaneous activity, measured using resting state functional magnetic resonance imaging (rs-fMRI) of the blood oxygen level dependent (BOLD) signal, is spatially correlated within resting state networks (RSNs). However, despite these advances, the temporal organisation of spontaneous BOLD fluctuations among RNSs has remained elusive. By studying temporal lags in the resting state BOLD signal, we have recently shown spontaneous BOLD fluctuations consist of remarkably reproducible patterns of whole-brain propagation. Embedded in these propagation patterns are ‘motifs’ which, in turn, give rise to RSNs. Additionally, propagation patterns are markedly altered as a function of state, whether physiological or pathological. Thus, a deeper understanding of the temporal organisation of the BOLD signal may yield insights into the roles spontaneous activity plays in brain function. 
Mr Anish Mitra, Washington University, USA
Mr Anish Mitra, Washington University, USAAnish Mitra studied mathematics as an undergraduate at Stanford University. He subsequently obtained his master’s degree in biophysics, also at Stanford, and spent time at Google X developing neutrally-inspired machine learning algorithms. Anish is presently in the MD/PhD program at Washington University School of Medicine in St. Louis, where he is pursuing his PhD in the laboratory of Dr Marcus Raichle. Together with Dr Raichle, Anish is investigating the temporal structure of resting state activity using the spontaneous BOLD signal. He has recently found that the resting state BOLD signal is composed of multiple, reproducible patterns of propagation, and the preserved features of these propagation patterns give rise to resting state networks. |
|
| 11:40 - 12:10 |
Modeling the microvascular origin of BOLD fMRI from first principles
The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. We present a new method that uses oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and that predicts the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences. Finally, this method is used to validate and optimize the Calibrated fMRI approach used to recover the cerebral metabolic rate of oxygen CMRO2 in human studies. 
Dr Louis Gagnon, Laval University, Canada
Dr Louis Gagnon, Laval University, CanadaDr Gagnon was trained in Engineering Physics at Ecole Polytechnique Montreal and in Particle Physics at the TRIUMF accelerator in Vancouver. He completed his Master’s degree in 2008 in the laboratory of Professor Frédéric Lesage in Montreal, working on time-resolved spectroscopy, diffuse correlation spectroscopy and multimodal optical-fMRI fusion techniques. He then received his PhD in Medical Physics from the Harvard-MIT Division of Health Sciences and Technology in 2013. His thesis was completed in the laboratory of Professor David Boas at the Massachusetts General Hospital. There, he worked on Near-Infrared Spectroscopy including state-space modeling, multi-distance methods, motion correction and NIRS-fMRI fusion. He then switched his focus to two-photon microscopy and optical coherence tomography. He used these techniques to reconstruct microvascular blood flow and he developed a computational framework to predict macroscopic BOLD signals from those microscopic measurements of cortical physiology. Since the fall of 2013, he has been enrolled at Laval University in Canada to complete his MD training. His current research focuses on multi-scale modeling of brain imaging techniques. |
| 13:30 - 14:00 |
The role of the vascular endothelium in functional neurovascular coupling and the BOLD signal
Understanding the cellular mechanisms of neurovascular coupling should lead to improved understanding of the spatiotemporal properties of the BOLD response, the dependence of the response on neural activity, and the sensitivities of neurovascular coupling to different disease states. Here, we describe the previously overlooked importance of the vascular endothelium as route for the conduction of vasodilation during functional hyperemia. Dependence of the response on an endothelial pathway introduces new interpretations of earlier pharmacological results, explains mismatches in timing between astrocyte responses and vasodilation at the level of diving arterioles, introduces the possibility of multiple mechanisms with slow and fast components contributing to the non-linearities of the BOLD response, and introduces new explanations for the effects of drugs and disease states on brain function and cognitive decline. Through high-speed imaging of both neural activity and hemodynamics across the cortices of the awake, behaving mouse brain, we are exploring the broad consequences of endothelial involvement in neurovascular coupling, in stimulus-evoked and resting state conditions, during longitudinal disease progression, under different pharmacological conditions, and during early post-natal development. These results are important for both understanding how neurovascular coupling can influence brain health, and for improving interpretation of the BOLD signal in health and disease. 
Professor Elizabeth Hillman, Columbia University, USA
Professor Elizabeth Hillman, Columbia University, USADr Elizabeth Hillman is Associate Professor of Biomedical Engineering and Radiology and a member of the Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science at Columbia University. Dr Hillman received her undergraduate training in Physics and PhD in Medical Physics and Bioengineering at University College London. She was a post-doctoral fellow and then junior faculty at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital / Harvard Medical School before joining Columbia University in 2006. Dr Hillman’s research program focuses on understanding the mechanisms of functional neurovascular coupling in the brain. Her lab also specializes in the design and development of novel optical imaging and microscopy techniques for capturing structure and function in the living brain. |
|
|---|---|---|
| 14:10 - 14:40 |
Spatial limits of imaging human brain function and connectivity: whole brain to cortical columns and layers
In the last two and a half decades, magnetic resonance methods aimed at imaging neuronal activity have transformed our ability to study the human brain, going from early experiments demonstrating relatively course functional images in the visual cortex to functional mapping with laminar differentiation of neuronal ensembles that perform elementary computations. This development relied on an extensive set of experiments that examined the mechanisms underpinning the functional imaging signals, tackling questions about the spatial specificity of the neurovascular coupling and the connection between hemodynamic and metabolic consequences of neuronal activity and the perturbations on MR detected signals. These studies, conducted on animal models as well as in humans, have provided a rigorous, albeit as of yet incomplete, understanding of the mechanisms underlying the functional mapping signals that reflect neuronal activity, leading to the use of ever increasing magnetic fields to gain accuracy and resolution and to new imaging and image reconstruction methods to map functional activity at the level of cortical columns and layers, and connectivity with ever increasing spatial and temporal resolution. 
Professor Kâmil Uğurbil, University of Minnesota, USA
Professor Kâmil Uğurbil, University of Minnesota, USAKamil Ugurbil currently holds the McKnight Presidential Endowed Chair Professorship in Radiology, Neurosciences, and Medicine and is the Director of the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota. Professor Ugurbil was educated at Robert Academy, Istanbul (high school) and Columbia University, New York, N.Y. After completing his B.A. and Ph.D. degrees in physics, and chemical physics, respectively, at Columbia, he joined AT&T Bell Laboratories in 1977, and subsequently returned to Columbia as a faculty member in 1979. He moved to the University of Minnesota in 1982 where his research in magnetic resonance led to the evolution of his laboratory into an interdepartmental and interdisciplinary research centre, the CMRR. The work that introduced magnetic resonance imaging of neuronal activity in the human brain (known as fMRI) was accomplished independently and simultaneously in two laboratories, one of which was Ugurbil's in CMRR. Since then, his focus has been on development of methods and instrumentation capable of obtaining high resolution and high accuracy functional information in the human brain, targeting neuronal organizations at the level of cortical columns and layers; this body of work has culminated in unique accomplishments such as the first time imaging of orientation columns in the human primary visual cortex, as well as numerous new instrumentation and image acquisition approaches for functional and anatomical neuroimaging at very high magnetic fields. |
|
| 15:20 - 15:50 |
Functional MRI and the connectome
Functional MRI has many significant disadvantages as a source of information about nervous systems. It does not directly represent neuronal activity; it has coarse spatial and temporal resolution compared to the range of scales of space and time that brains subtend; it is not measured in SI units; experimental recordings are at least 80% noise; etc. Nonetheless, the patterns of between-regional correlation in slowly oscillating fMRI time series have turned out to be robustly replicable and not trivially explained. Graph theoretical models of human fMRI networks, derived from association matrices of pair-wise functional connectivity estimated for all possible pairs of ~300 regional nodes, demonstrate complex topology: small-worldness, hubs, modules, core/periphery, etc. These features are replicable and heritable. The topological and spatial or geometrical organization of fMRI networks is consistent with the theory that their formation is largely determined by the trade-off between a few competitive factors or conservation laws. Hypothetically, an economic trade-off between the biological cost and the topological value of network components could drive the formation of fMRI networks. To test the generality of this and other hypotheses generated by connectomic analysis of ‘resting state’ fMRI data, graph theoretical methods can be used to make comparable measurements in many other neuroscientific datasets. Meta-analysis of large scale libraries (N~1000 primary papers) of fMRI activation studies demonstrated that more expensive topological features (hubs, rich club) were associated with domain-general, ‘higher-order’ cognitive functions; and that high cost / high value network hubs were hotspots for structural brain deficits associated with many different brain disorders (including Alzheimer’s disease and schizophrenia). Many of the complex topological characteristics of large-scale human fMRI networks are qualitatively reproduced at the microscopic scale of functional networks derived from multi-electrode array recordings of growing neuronal cultures in vitro. The economical model of a trade-off between biological cost and topological value has been specifically re-affirmed by analysis of viral tract tracing data (~400 anterograde tracer injection experiments) on the anatomical connectivity of the mouse brain. We conclude that despite the well-known limitations of fMRI, it has emerged as almost uniquely capable of measuring the complex network organisation of human brain function in a way that is physically, neurobiologically, cognitively, and clinically meaningful. 
Professor Ed Bullmore, University of Cambridge, UK
Professor Ed Bullmore, University of Cambridge, UKEd Bullmore trained in clinical medicine at the University of Oxford and St Bartholomew’s Hospital in London, then worked as a Lecturer in Medicine at the University of Hong Kong, before specialist clinical training in psychiatry at St George’s Hospital, and then the Bethlem Royal & Maudsley Hospital, in London. His research career started in the early 1990s as a Wellcome Trust (Advanced) Research Fellow and was initially focused on mathematical analysis of neurophysiological time series. Since moving to Cambridge as Professor of Psychiatry in 1999, his interest in human brain function and structure has increasingly focused on complex brain networks identified in MRI and other brain scanning data. Since 2005, he has worked half-time for GlaxoSmithKline first as Head of GSK’s Clinical Unit in Cambridge and since 2013 as Vice-President, Experimental Medicine in ImmunoPsychiatry. He is Clinical Director of the Wellcome Trust/MRC funded Behavioural & Clinical Neuroscience Institute, Scientific Director of the Wolfson Brain Imaging Centre, and Co-Chair of Cambridge Neuroscience, in the University of Cambridge; and an honorary Consultant Psychiatrist and Director of R&D in Cambridgeshire & Peterborough Foundation NHS Trust. Since October 2014 he has been Head of the Department of Psychiatry at the University of Cambridge. He has published about 400 scientific papers with an h-index (Scopus) of 101. He has been elected as a Fellow of the Royal College of Physicians, the Royal College of Psychiatrists, and the Academy of Medical Sciences. |
|
| 16:00 - 17:00 |
Overview and panel discussion
Professor David Attwell FRS, University College London, UK
Professor David Attwell FRS, University College London, UKDavid Attwell studied physics as an undergraduate in Oxford, and then did a PhD working on nerve and muscle with Julian Jack. After a post-doc in Berkeley working on the retina with Frank Werblin, he came to UCL as a Lecturer and is now Jodrell Professor of Physiology. His research has covered synaptic transmission and information processing in the CNS, the properties of glial cells, glutamate uptake and how it reverses and releases glutamate in ischaemia, the energy supply to the brain and its regulation at the capillary level by pericytes, and the cellular basis of BOLD imaging. He is a Fellow of the Royal Society and of the Academy of Medical Sciences. |