Brain Mapping seminar abstracts 2012-13


Thomas Nichols, PhD
University of Warwick, UK

Sensitive and interpretable modelling of neuroimaging meta-analysis data
Neuroimaging Meta-analysis is growing in importance as the number of available studies grows. Unfortunately, the only data widely available for meta-analysis are the [x,y,z] coordinates of peak activation foci. Most existing methods convert these coordinate data into images and then apply traditional imaging modelling and inference proceedures. However, these methods are mass-univariate, make inference on individual voxels (or clusters) and require fixed tuning parameters. Such methods do not provide an interpretable fitted model, and cannot produce spatial confidence intervals on location of activation. Using a Bayesian hierarchical point process approach, modelling brain activation as a mixture of latent activation centers, and these activation centers are in turn modelled as off-spring from latent population centers. When our fully Bayesian model fit to multiple groups it is trival to make predictions of the group label for new data and, through an importance sampling trick, leave-one-out cross validation accuracy for the sample studied. Joint work Jian Kang, Emory Biostatistics, and Tim Johnson, University of Michigan Biostatistics.


Blaise Frederick, PhD
McLean Hospital

Extracting quantitative cerebral hemodynamic measures and removing physiological noise from BOLD fMRI data using time delay processing
BOLD fMRI data is affected by the oxygenation and volume of blood moving through the circulatory system. Because these properties are carried by the blood itself, fluctuations in these parameters arrive at different parts of the brain at different times. Time delay processing extracts hemodynamic information from BOLD fMRI data by characterizing the time delay between a regressor reflecting these parameters and the BOLD data throughout the brain. Global endogenous random variations of blood volume and oxygenation can be tracked as they pass through the highly perfused tissue of the brain through their effect on the BOLD signal by determining the strength and peak time delay of their cross correlation with regressors generated from near infrared spectroscopy (NIRS) data, or extracted from the BOLD data itself. Blood oxygenation can also be manipulated with a gas challenge to increase the SNR of the technique. Using this technique, BOLD data can be separated into global hemodynamic effects and local hemodynamic variations due to neuronal activity.


Jaakko Nieminen, PhD
Aalto University, Finland

Hybrid ultra-low-field MRI and MEG: brain imaging and more with a multichannel instrument
Magnetic resonance imaging (MRI) and magnetoencephalography (MEG) are well-established modalities for imaging brain anatomy and function, respectively. Traditionally, MRI is performed in high magnetic fields (> 1 T), which has the side effect that the required scanner is massive and imaging loud. On the other hand, MEG operates at the other extreme: in a magnetically shielded environment, the weak magnetic field arising from brain electrical activity is mapped around the head with a multichannel instrument. In this talk, I will describe our instrumentation that combines MRI and MEG into a single silent device and the motivation behind the development. I will also explain how the underlying technique, so-called ultra-low-field (ULF) MRI, where the imaging field is comparable to the Earth's magnetic field, differs from conventional high-field MRI. We have used our hybrid system for MRI of the human brain and for MEG studies. The results are compared with those obtained with a 3-T scanner and a commercial MEG device. In addition, we have performed several ULF-MRI experiments demonstrating, e.g., the suitability of ULF MRI for temperature mapping.


Nicolas Bolo, PhD
Beth Israel Deaconess Medical Center
Dr. Bolo is Director of Neuroimaging in Psychiatry at the Beth Israel Deaconess Medical Center in Boston and Assistant Professor of Psychiatry at Harvard Medical School. Dr. Bolo did his undergraduate studies at the University of Paris, France, Pierre et Marie Curie, where he obtained his BS and Master’s degrees in Physical Chemistry. He did his graduate studies at the University of California, Berkeley, where he obtained his PhD in Biophysics. After a short post-doctoral fellowship at the Lawrence Berkeley Laboratory, he returned to France to work at the Magnetic Resonance Unit of a Non-Profit Clinical Research Center associated with the psychiatric hospital in Rouffach (East of France). First as a research scientist and later as director of biological research and development, Dr. Bolo used a 3T scanner - the second 3T to be operational in France - to apply MRS and fMRI to investigations of neuropsychiatric disorders including, schizophrenia, Alzheimer’s disease, depression and epilepsy. Dr. Bolo joined the Brain Imaging Center at McLean Hospital in 2001 to work as an Associate Biophysicist using its new 4T scanner. There he started collaborations with the Joslin Diabetes Center investigating the effects of diabetes on brain function, structure and neurochemistry. He continued this line of investigation after taking the position of director of neuroimaging in psychiatry at BIDMC about three years ago. He will be talking about some of this recent work on diabetes and the brain.

Diabetes and the Brain: What Magnetic Resonance Studies Tell Us
In 2011, about 26 million people in the US -- 8.3% of the population -- had diabetes. Peripheral complications such as heart disease, kidney disease and neuropathy are relatively well known, however we have only recently been able to examine the impact of diabetes on the central nervous system using advanced neuroimaging technology. Dr. Bolo will be talking about recent studies of brain metabolism, function and structure and their relationship to emotional and cognitive disorders in type 1 and type 2 diabetes using magnetic resonance spectroscopy and imaging.


Javeria Hashmi, PhD
MGH

Predictive Dynamics in Brain Networks of Chronic Pain Patients.
The advent of new imaging methods and data modeling techniques has revolutionized our capacity to understand and utilize brain signals. With these techniques, the dynamic interactions between the complex elements of the brain can be used to effectively decode the neurological substrates of pain perception and modulation. The task to discover how intricately connected brain networks process psychological cues and interpret them into analgesia is an important scientific challenge that can segue into novel clinical tools and improved pain therapeutics. This talk will present evidence that brain network properties can be used to predict treatment outcomes and the time course of pain experiences. We have reported that synchronizations in specific brain networks in particular BOLD frequency bands forecast outcomes of placebo treatment in chronic back pain patients that were tested in clinical trial conditions. More recently we have discovered that computationally characterized whole brain network alignments predict subsequently induced placebo analgesia in a clinical population of knee pain patients. These findings indicate a role of network configurations in facilitating adaptive pain modulation. On the other hand, brain properties also provide several clues into maladaptive pain processing associated with chronic pain. We will report in how brain activity related to the perception of back pain shifts in location from regions involved in acute pain to engage emotion circuitry as the condition persists, thereby providing a percept linked brain signature for the transition to chronic pain.


Kwanghun Chung, PhD
MIT

CLARITY and beyond: towards integrative understanding of the brain in health and disease.
Obtaining detailed structural and molecular information from complex biological systems while simultaneously maintaining the global perspective has long been a fundamental challenge in neuroscience and throughout biology. Current pioneering methods, while proven adequate to study small-scale fine structures, fall short of providing integrated system-wide information. To address this challenge, we have developed a novel technology (which we term CLARITY) that rapidly transforms intact tissue into a hydrogel hybrid that is optically-transparent and macromolecule-permeable while retaining structural and molecular information. This unique framework enables effective and complete access of intact tissue using both light microscopy and molecular phenotyping techniques (immunohistochemistry and in situ hybridization). Exogenous macromolecules can rapidly penetrate deep into transmuted tissue for labeling and can be completely removed after imaging, enabling multiple rounds of molecular interrogation in 3D volumes of tissue. The application of CLARITY to the adult mouse brain has enabled imaging of long-range circuits, local circuits, subcellular morphological details, and molecular architectures. Finally, we find that this technique allows fine structural analysis of postmortem human brain, opening the door to the possibility of mapping the human brain at single cellular resolution with integrated molecular information. Taken together, this technology promises to provide high-content system-wide structural and molecular information that may enable integrative understanding of large-scale intact biological systems.


Ruth Rosenholtz, PhD
MIT

Rethinking the roles of selective attention and economical encoding in vision.
Considerable research points to a bottleneck in visual processing. According to the traditional view, at any given moment selective attention allows only a small portion of the visual input to get through the bottleneck for further processing. Some processing can occur "preattentively" and guide this selection. Much of the early research on visual search aimed at determining what processing could occur preattentively, and what required selective attention. This work pointed to a need for selective attention in order to bind basic features and locations. While this view of visual processing has held sway for many years, it has also been problematic. How is it that we can have such trouble searching for a simple symbol in a display, and yet be so good at getting the gist of a scene and navigating through our environment? My lab proposes an alternative, in which the visual system's strategy for dealing with limited capacity focuses on compression of the visual input, rather than on selective attention. I will demonstrate that this model can predict not only classic results in visual search, but also phenomena that were problematic for the traditional selective attention story. This suggests that there may be a fundamental, relatively low-level limit to a diverse array of visual tasks, from visual search and object recognition, through perception of our spatial environment and understanding of complex displays.


Alan Anticevic
Yale University
BIO

Connectivity, Pharmacology and Computation: Towards a Mechanistic Understanding Cognitive and Connectivity Deficits in Schizophrenia
Neuropsychiatric diseases such as schizophrenia and bipolar illness alter the structure and function of distributed neural networks and presents a massive health and economic burden. Functional neuroimaging tools have evolved sufficiently to reliably detect systems-level disturbances in neural networks. This two-part presentation first focuses on emerging findings in schizophrenia and bipolar illness using resting-state neuroimaging, an advantageous approach for biomarker development given its ease of data collection and lack of task-based confounds. Findings in schizophrenia suggest that disruptions in sensory-thalamic-prefrontal networks may hold promise as a marker for treatment effects in future clinical studies and might constitute a final common pathway of neural system disturbances in schizophrenia. However, neuroimaging does not yet allow the evaluation of individual neurons within local circuits, where pharmacological treatments ultimately exert their effects. This limitation constitutes an important obstacle to the effort to translate findings from animal research to humans and from healthy humans to patient populations. Integrating new neuroscientific tools may help to bridge some of these gaps. Two complementary approaches are discussed in the context of understanding cognitive deficits in schizophrenia: First, causal pharmacological manipulations in healthy volunteers that transiently mimic some cardinal features of psychiatric conditions. Specific focus is placed on recent neuroimaging studies using the NMDA receptor antagonist, ketamine, to probe glutamate synaptic dysfunction associated with schizophrenia. Second, human pharmacologic imaging is discussed in combination with biophysically-informed computational models developed to guide the interpretation of functional imaging studies and to inform the development of pathophysiologic hypotheses. This approach is illustrated via recent findings showing how computational modeling has guided inferences drawn from studies in healthy subjects administered ketamine and evaluations of schizophrenia patients. In summary, the argument is presented that linking experimental studies in humans with computational models will advance to effort to bridge cellular, systems, and clinical neuroscience approaches to psychiatric disorders.


Kay Tye
MIT
BIO

Dissecting neural circuits underlying behaviors relevant to psychiatric disease in animal models
The ability to differentiate between positive and negative environmental stimuli is critical to an animal's survival. However, the neural circuits that endow the brain with the ability to differentiate positive and negative motivationally significant stimuli have been difficult to disentangle and represent one of the most important fundamental neuroscience questions today. The development and application of optogenetic approaches has allowed us to probe the causal relationships between activity in specific circuit elements and animal behavior relevant to psychiatric disease states such as anxiety, addiction and depression. In this seminar, Kay Tye will discuss her research on the corticolimbic circuits that mediate valence processing.


Marta Bianciardi
MGH Martinos Center
BIO

Echo-planar imaging of cerebral physiology and metabolism at 7 Tesla
This seminar will summarize our recent efforts in quantifying physiology and metabolism of the brain by means of echo-planar imaging (EPI) at high magnetic field strength (7 Tesla). Quantification of brain function by fMRI techniques based on EPI is hampered by the presence of physiological sources of instability due to motion, heartbeat, and respiration. In our previous research, we investigated novel methods to deal with this limitation, by optimizing physiologic noise removal. In our current research, we exploited this limitation as an opportunity to investigate cerebral physiology, by considering physiological noise as a “signal of interest”. In this seminar we will talk about the effects in EPI time-courses of: paramagnetic oxygen moving inside the chest during respiration; cardiac and respiratory pressure waves traveling in the brain; changes in the cardiac rate and in the respiratory volume rate. We will show the different contribution of these effects to magnitude and phase EPI time-courses, and how they can be used to investigate cerebrovascular compliance and the hemodynamic waveform in the brain.


Nikola Stikov
McGill University
Dr. Nikola Stikov is a postdoctoral fellow at the Montreal Neurological Institute, currently working with Dr. Bruce Pike on measuring white matter microstructure using quantitative magnetic resonance imaging. He completed his B.S., M.S., and Ph.D. degrees in Electrical Engineering at Stanford University under the supervision of Dr. John Pauly. In collaboration with the Stanford Radiology and Psychology departments, he identified novel magnetic resonance biomarkers for the study of cartilage in the knee and myelin in the brain.

In vivo magnetic resonance imaging of the myelin g-ratio
The myelin g-ratio, defined as the ratio between the inner and the outer diameter of the myelin sheath, has been proposed as an important biomarker for studying normal brain development, as well as brain pathology. Recent studies have suggested that the sexual dimorphism in white matter development is due to a higher g-ratio (thinner myelin) in adolescent boys. Variations in the g-ratio have also been detected in the frontal white matter of patients with schizophrenia, and have been associated with differences in brain connectivity in autism. Finally, in vivo imaging of the myelin thickness in multiple sclerosis can provide a real-time tool for tracking myelination in lesions, facilitating the development and evaluation of new therapeutic agents that promote remyelination. In this lecture, a unique combination of quantitative magnetic resonance imaging, histology, and numerical simulations will be presented, resulting in a novel method for in vivo measurement of the myelin g-ratio. The ramifications of this method will be discussed in the context of applications and validation in animal models.


Earl Miller
The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
Earl Miller is the Picower Professor of Neuroscience at the Massachusetts Institute of Technology. He has academic appointments in The Picower Institute for Learning and Memory and the Department of rain and Cognitive Sciences at MIT. Professor Miller uses experimental and theoretical approaches to study the neural basis ofhe high-level cognitive functions that underlie complex goal-directed behavior. The focus is on the frontal lobe, the region of the brain most elaborated in humans and linked to neuropsychiatric disorders. His laboratory has provided insights into how categories, concepts, and rules are learned, how attention is focused, and how the braincoordinates thought and action. They have innovated techniques for studying the activity of many neurons in multiple brain areas simultaneously, which has provided insight into how different brain structures interact and collaborate. This work has established a foundation upon which to construct more detailed, mechanistic accounts of how executive control is implemented in the brain and its dysfunction in diseases such as autism, schizophrenia and attention deficit disorder.

Cognition is Rhythmic
How are some thoughts favored over others? A wealth of data at the level of single neurons has yielded candidate brain areas and mechanisms for our best understood model: visual attention. Recent work has naturally evolved toward efforts at a more integrative, network, understanding. It suggests that focusing attention arises from interactions between widespread cortical and subcortical networks that may be regulated via their rhythmic synchronization. This could extend to all cognitive processes, suggesting our brain does not operate continuously, but rather discretely, with pulses of activity routing packets of information. Such discrete cycles would provide a backbone for coordinating computations (and their results) across disparate networks. However, it comes at a cost: it is naturally limited in bandwidth; only so many things can be computed or carried in a single oscillatory cycle. This can explain the most fundamental property of conscious thought, its limited capacity, which is the reason why we evolved attention in the first place.


Fahmeed Hyder
Yale University
Professor, Biomedical Engineering & Diagnostic Radiology Technical Director, MRRC (mrrc.yale.edu) Program Director, QNMR Core Center (qnmr.yale.edu)

Energetic Footprint of Cortical Function
Energy demand of neural activity in cerebral cortex is extraordinarily high, a necessity met by glucose oxidation yielding ATP abundantly. My narrative trails through folklore and dogma to discoveries from various independent observations about how brain’s insatiable appetite for glucose and oxygen dynamically tracks neural activity, from regions as small as cortical columns to large cortical swathes across hemispheres. Results show that imaging oxidative energy provides an integrated perspective on brain networks, where oxidative energy demand of cortical workspace is quite uniform. Diagnosis of brain disorders and diseases can be improved by mapping the oxidative energetic footprint of cortical function.


Emad Eskander
Mass General Hospital
Neurosurgeon at the Massachusetts General Hospital (MGH) Associate Professor of Surgery at Harvard Medical School.

Basal Ganglia: Learning & Motivation
The Basal Ganglia play a central role in theories of learning, motivation, depression and drug addiction. His group uses microelectrode and electrochemical recordings to evaluate the role of the basal ganglia in both primates and humans performing complex behavioral tasks. The group also uses electrical stimulation to directly modulate neuronal activity during complex behaviors. This is a unique approach in that ideas from the laboratory can quickly be tested in the clinical arena and vice-versa. In a recent study, they have shown that a part of the brain called the cingulate cortex plays an important role in linking reward information with action selection. Another recent study found that delivering micro-stimulation in one part of the basal ganglia, the caudate nucleus, significantly increases the rate of learning beyond baseline rates. These findings suggest that the caudate plays a critical role in learning, and that learning can be enhanced to promote recovery after brain injury.


Richard Born
Harvard University
Department of Neurobology, Harvard Medical School

Anatomical, Physiological and Computational Studies of Cortico-cortical Feedback.
Feedback connections are prevalent throughout the cerebral cortex, yet their function remains poorly understood. Previous studies in anesthetized monkeys found that inactivating feedback from extrastriate visual cortex produced effects in striate cortex that were relatively weak, generally suppressive, largest for visual stimuli confined to the receptive field center, and detectable only at low stimulus contrast. We studied the influence of corticocortical feedback in alert monkeys using cortical cooling to reversibly inactivate visual areas 2 (V2) and 3 (V3) while characterizing receptive field properties in primary visual cortex (V1).We show that inactivation of feedback results in both response suppression and facilitation for stimuli restricted to the receptive field center, in most cases leading to a small reduction in the degree of orientation selectivity but no change in orientation preference. For larger-diameter stimuli that engage regions beyond the center of the receptive field, eliminating feedback from V2/V3 results in strong and consistent response facilitation, effectively reducing the strength of surround suppression in V1 for stimuli of both low and high contrast. For extended contours, eliminating feedback had the effect of reducing end stopping. Inactivation effects were largest for neurons that exhibited strong surround suppression before inactivation, and their timing matched the dynamics of surround suppression under control conditions. Our results provide direct evidence that feedback contributes to surround suppression, which is an important source of contextual influences essential to vision.


Dara Manoach
Harvard University
Associate Professor of Psychology, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School.

Abnormal sleep in schizophrenia: A novel target for improving cognition?
Cognitive deficits are the strongest predictor of functional outcome in schizophrenia, and effective treatments are lacking. Accordingly, treating cognitive deficits is now a priority of the schizophrenia research community and the focus of large-scale studies. A limitation to these efforts is that cognition is measured in cross-section. While this provides a valid snapshot of function, it fails to capture critical aspects of learning and memory that happen offline, over time and with sleep. A burgeoning basic literature suggests that sleep spindles, a defining characteristic of stage 2 sleep, index human intelligence and mediate memory consolidation. Concurrently, our findings in schizophrenia demonstrate dramatically reduced sleep spindles that correlate with marked impairments of sleep-dependent memory consolidation. I will present evidence suggesting that the sleep spindle deficit in schizophrenia is a marker of genetic vulnerability to illness, contributes to impaired memory consolidation and symptoms and can be effectively treated. I will also describe new fMRI/MEG/EEG studies of the contribution of sleep spindles to memory. Given that sleep spindles correlate with a wide range of cognitive measures in health, our findings expand current models of cognitive deficits in schizophrenia and raise intriguing questions about whether pharmacological enhancement of sleep spindles can improve outcomes.


Anastasia Yendiki, PhD
MGH Martinos Center
Anastasia received a Ph.D. in Electrical Engineering: Systems from the University of Michigan at Ann Arbor, where she worked on statistical image reconstruction for nuclear imaging. Her thesis addressed the analytical optimization of reconstruction methods with respect to lesion detectability. Upon graduation she came to the Martinos Center to learn about functional MRI but quickly got distracted by the pretty, colorful strands of diffusion tractography. She has since developed TRACULA, a probabilistic method for the automated reconstruction of white-matter pathways that uses prior information on the anatomical neighborhood of each pathway along its trajectory. She is currently an Assistant Physicist at Massachusetts General Hospital and Assistant Professor in Radiology at Harvard Medical School.

Spurious findings due to head motion, and other exciting news for diffusion MRI group studies
I will present results from two lines of work related to our development of tools for the analysis of diffusion MRI (dMRI) data. First, we have recently investigated the effects of head motion on dMRI group studies, using data from children with autism spectrum disorders (ASD) and typically developing (TD) children. We show that, as the differences in head motion between groups increase, so do the differences in dMRI-derived anisotropy and diffusivity measures. The group that moves more tends to have lower fractional anisotropy, higher radial diffusivity, and lower axial diffusivity. We observe similar patterns when we compare groups of TD children only, as we do when we compare groups of ASD vs. TD children. Our results have implications for any dMRI study where one group is less likely to remain still in the scanner than the other. Second, we have developed a novel framework for reconstructing white-matter pathways from longitudinal dMRI data. The challenge that conventional streamline tractography faces in the presence of degeneration is that, e.g., it may miss part of the pathway in later time points, making side by side comparisons of anisotropy and diffusivity to earlier time points problematic. Our approach is to reconstruct the pathway jointly using a subject's dMRI and T1 data from all time points at once. This method is unbiased, making no assumptions on the direction of longitudinal change. By design, it allows longitudinal analysis of anisotropy and diffusivity measures to be performed as a function of position along the trajectory of a tract. We demonstrate that the proposed approach improves both specificity and sensitivity compared to the conventional approach of performing tractography in each time point independently. All analyses that I will describe in this talk can be performed with our publicly available tool for automated probabilistic tractography, TRActs Constrained by UnderLying Anatomy (TRACULA). http://surfer.nmr.mgh.harvard.edu/fswiki/Tracula


Swathi Kiran, PhD
Boston University and MGH
BIO

Changes in task based effective connectivity following rehabilitation in individuals with post-stroke aphasia
In this talk, I will first review the latest research into the examination of language recovery and its neural underpinnings. I will review the current neuroimaging evidence for language recovery and then talk about studies that have examined changes in connectivity as a function of recovery in post-stroke aphasia. In particular, I will discuss two studies from our lab that have examined changes in connectivity (using graph-metrics and DCM) following rehabilitation of word retrieval in individuals with post-stroke aphasia. In both these preliminary studies, results show that language rehabilitation is associated with positive behavioral and neural changes in the left language network, and right hemisphere homologues. Connectivity analyses reveal that across patients, LIFG and LMTG are important nodes in the network that are modulated as a function of rehabilitation.


Stepanie Jones, PhD
Brown University
Department of Neuroscience

Human Neocortical Rhythms: From Mechanism to Meaning via Computational Neural Modeling
Low frequency neocortical rhythms are among the most prominent activity measured in human brain imaging signals such as electro- and magneto- encephalography (EEG/MEG). Elucidating the role that these dynamics play in perception, cognition and action is a key challenge of modern neuroscience. We have recently combined MEG, computational neural modeling, and electrophysiological recordings in rodents and monkeys to explore the functional relevance and mechanistic underpinnings of rhythms in primary somatosensory cortex (SI), containing Alpha (7-14Hz) and Beta (15-29Hz) components. In this talk, I will review our findings showing this rhythm impacts tactile detection, changes with healthy aging and practice, and is modulated locally and in coordination with frontal cortex during attention. Constrained by the human imaging data, our biophysically principled computational modeling work has led to a novel prediction on the origin of this rhythm predicting that it emerges from the combination of two stochastic ~10 Hz thalamic burst drives to the granular/infragranular and supragranular cortical layers. Relative Alpha/Beta expression depends on the strength and delay between the thalamic drives. This model is able to accurately reproduce numerous key features of the human rhythm and proposes a specific mechanistic link to changes with attention and perception. Further, initial electrophysiological recordings in rodents and monkeys support out hypotheses and suggest a role for pallidal thalamus in coordinating the rhythmicity, with relevance to understanding disrupt Beta rhythmicity in Parkinson's Disease.


Michael Garwood, PhD
Center for Magnetic Resonance Research and Department of Radiology University of Minnesota, Minneapolis, Minnesota
BIO

Far Out Experiments in MRI using FM pulses
Magnetic resonance imaging (MRI) uses radiofrequency (RF) irradiation to excite and manipulate nuclear spins. In multiple disciplines of MRI, significant gains in experimental precision and new experimental capabilities are made possible by RF pulses that are frequency modulated (FM). This presentation will show clinically relevant examples of how FM pulses can be exploited for MRI. FM pulses can be used not only to improve data quality, but also to reveal spin dynamics, such as dipole-dipole interactions and exchange between spins on different molecules. The ability to modulate the pulse frequency, as well as the pulse amplitude, creates almost limitless possibilities to sensitize the MRI signal to molecular motions happening on slow time scales. This presentation will show how this novel approach can create contrast for better delineating normal anatomy and disease states. By exploiting unique features of FM pulses, we have also developed a radically different approach to produce MR images. The technique is called SWIFT (sweep imaging with Fourier transformation). The FM pulse used in SWIFT makes possible simultaneous or time-shared excitation and acquisition. The smooth change of gradient orientation used in SWIFT produces negligible acoustic noise, making image acquisition close to silent. Finally, spatiotemporal-encoding methods using FM pulses have been attracting much interest recently. In particular, the spatiotemporal domain allows direct treatment of spatial problems like B0 and B1 inhomogeneity. I will describe a new spatiotemporal MRI technique called STEREO (steering resonance over the object). This unique technique excites MR signals locally and steers the localized region over the object in a spatiotemporal manner. STEREO provides a means to accomplish multi-dimensional spatiotemporal-encoded MRI in a manner that permits compensation for extreme magnetic field inhomogeneity. With STEREO, MR images are reconstructed using exclusively an inverse problem solution (i.e., no Fourier transformation).


Clifford Woolf, MD/PhD
Boston Children's Hospital

Exploiting stem cell technology to model human neurological disease
Dr. Woolfs research focuses on understanding the mechanism of pain and in promoting the regeneration of the nervous system and in translating these basic science results into new therapeutics and diagnostics. He was the discoverer of central sensitization and the first to show the role of NGF in inflammatory pain. His current work includes human, mouse and Drosophila genetics, stem cell biology, and exploiting a novel strategy for silencing pain fibers. Most of his work is concentrated on primary sensory and motor neurons, and to the interaction of neurons and immune cells, using a multidisciplinary approach spanning stem cell, molecular and cell biology, electrophysiology, neuroanatomy, behavior and genetics. His group has established functional and comparative genomic strategies using expression profiling, bioinformatics and gain- and loss-of-function approaches, to screen for novel genes that contribute to neuronal plasticity and disease phenotypes.


Nathan McDannold, PhD
Brigham and Women's Hospital
I am the Research Director of the Focused Ultrasound Laboratory at The Brigham and Women's Hospital and an Associate Professor in Radiology at Harvard Medical School. I received my B.S. in Physics from the University of Virginia, Charlottesville and a Ph.D. in Physics from Tufts University in Boston, MA in 2001. My work has been primarily concerned with the development and implementation of MRI-based thermometry methods, animal experiments testing MRI and ultrasound related work, and clinical focused ultrasound treatments of breast tumors, uterine fibroids, and brain tumors. In recent years, a main focus of my work has been studying the use of ultrasound for temporary disruption of the blood-brain barrier, which may allow for targeted drug delivery in the brain.

Enabling targeted drug delivery in the brain via ultrasound-induced blood-brain barrier disruption
The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This presentation will review the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB.


Richard Carson, PhD
Yale University
BIO

High Resolution Brain PET Imaging: Challenges and Opportunities
The HRRT is the highest resolution human brain PET scanner in the world. Due to its high resolution and other unique aspects of its design (phoswich, panel gaps), the optimal use of this unique instrument depends on great care in the reconstruction. This presentation will discuss the cluster-based list mode reconstruction engine we have developed, called MOLAR. Unique components of this system include LOR-dependent point spread functions and event-by-event motion correction. Some unique applications that arise from this platform include quantification of carotid input functions and 4D reconstruction of kinetic parameters (direct from list mode data). Further, in using this system with various radiopharmaceuticals, optimizing the balance between resolution and noise poses ongoing challenges. The presentation will survey some of the challenges and opportunities that this platform and PET system have produced.


Andre Bastos, PhD

Ernst Strungmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society


Visual areas exert feedforward and feedback influences through distinct frequency channels
Visual cortical areas are thought to form a hierarchy and to subserve cognitive functions by interacting in both feedforward and feedback directions. While feedforward influences convey sensory signals, feedback influences modulate brain responses to a given sensory stimulus according to the current behavioural context. Many studies have demonstrated effects of feedback influences on feedforward driven responses and on behaviour. Also, anatomical projections in both directions have been identified. However, although these studies have revealed the anatomical paths and the neurophysiological consequences of influences in both directions, the neurophysiological mechanisms through which these influences are exerted remain largely elusive. Here we show that in the primate visual system, feedforward influences are carried by theta-band (~4 Hz) and gamma-band (~60-80 Hz) synchronization, and feedback influences by beta-band (~14-18 Hz) synchronization. These frequency-specific asymmetries in directed influences were revealed by simultaneous local field potential recordings from eight visual areas and an analysis of Granger-causal influences across all 28 pairs of areas. The asymmetries in directed influences correlated directly with asymmetries in anatomy and enabled us to build a visual cortical hierarchy from the influence asymmetries alone. Across different task periods, most areas stayed at their hierarchical position, whereas particularly frontal areas moved dynamically. Our results demonstrate that feedforward and feedback signalling use different frequency channels, which might subserve their differential communication requirements and lead to differential local consequences. The possibility to infer hierarchical relationships through functional data alone might make it possible to derive a cortical hierarchy in the living human brain.


Leah Sommerville, PhD
Assistant Professor of Psychology Director, Affective Neuroscience & Development Lab Harvard University

Emotion, cognition, and the adolescent brain
Some accounts of adolescents liken them to "mini-adults", whose psychological capabilities consistently fall between that of younger and older individuals. However, some psychological changes during adolescence are unique relative to older and younger individuals, such as increases in the frequency of risk-taking and mood and anxiety dsyregulation. Using healthy human participants ranging in age from childhood to early adulthood, my lab's research aims to reveal how neurodevelopmentally-mediated shifts in circuit-level brain function contribute to changes in motivational, emotional, and social behavior during adolescence. My talk will explore how normative trajectories of neural maturation and function relate to unique sensitivities to emotional and motivational cues during adolescence in social and nonsocial contexts. Ultimately, the aims of this work are threefold: to bolster fundamental understanding of human neurodevelopment in the second decade of life, to inform relationships between circuit-level brain function and human behavioral outcomes more generally, and to gain insight into the mechanisms underlying health risks that emerge during adolescence.


Xin Yu, PhD
Research Group Leader Translational Neuroimaging and Neural Control Group, Department of High Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany
Dr. Yu studied microbiology and immunology during his bachelor training in Wuhan University, China, 1996-2000. He developed strong interests on neuroimaging during his master training in Seton Hall University, NJ, where he studied the hypothalamo-pituitary-adrenal (HPA) axis of the drug addicted rats, 2000-2002. Then, he started to work with Dr. Daniel Turnbull in New York University Medical Center. From 2002 to 2007, he mainly studied the auditory midbrain developmental plasticity with Manganese-enhanced MRI. In his postdoctoral training, he joined Dr. Alan Koretsky’s group at NIH. He made significant effort to combine fMRI, MEMRI, and electrophysiology to study the systems-to-synaptic brain plasticity. He became a Junior Fellow in the International Society of Magnetic Resonance in Medicine in 2011. In Jan. 2014, he moved to Germany and started to build up his own research group in Max Planck Institute for Biological Cybernetics. Here, his main focus is to decipher the single unit of neurovascular coupling to switch the coma states of rats.

Push limits and extend boundaries of small animal fMRI
In this talk, I will first describe our effort to push the spatiotemporal limit of fMRI in the rodent brain. We developed a line-scanning fMRI method to demonstrate the laminar position of fMRI onset coincides with distinct neural inputs to the cortex (Yu et al. Nature Methods, 2014). Here, we acquired the fMRI signal across cortical depth in 50µm spatial resolution with 50ms sampling rate. Furthermore, we improved the method to image the BOLD and CBV fMRI signal from individual penetrating venules and arterioles across the cortex with 100x100µm spatial resolution and 100ms sampling rate. This work allows us to decipher the vascular contribution to the neurovascular coupling in the deep layer cortex. However, to provide specific neural control underlying the coupled vascular response, we need to elicit activity through different components across the vascular neural network. In the second part of my talk, I will show our recent effort to implement the fiber-optic insertion to drive activity through different neural circuit. The goal of the future work is to decipher the molecular, cellular, and neural-vascular circuit of the neurovascular coupling underlying fMRI.


David Yeomans, PhD
Professor, Stanford University

Brain stem mechanisms behind analgesic effects of nasal oxytocin
Chronic and high frequency migraine patients suffer with 15 or more or 8-14 moderate to severe headache days/month respectively, and are highly debilitated by these conditions. Treatment choices for these conditions are currently inadequate. For this presentation, we will show that trigeminal neurons, which are critical components in mechanisms underlying these conditions, possess oxytocin receptors the expression of which is highly dependent on inflammatory state. Inflammation also enhances release of the pain neurotransmitter/neuromodulator calcitonin gene related peptide (CGRP) in vitro, from dural afferent nerve endings, which can be attenuated by exposure to oxytocin. In addition, nasally-applied application of radiolabelled oxytocin in rats concentrates in the trigeminal system, suggesting direct access to trigeminal receptors. Though this access, nasal application of oxytocin attenuates responses of brainstem neurons to painful stimulation and produces profound analgesia in craniofacial behavioral assays in rats. These findings have led to Phase II clinical trials of a formulation of nasal oxytocin in chronic and high frequency episodic migraine. The results of these studies demonstrate both a pain-reducing effect as well as a robust and sustained decrease in the frequency of migraine attacks and secondary migraines symptoms including nausea and vomiting, photophobia, and phonophobia.


Daniel Baldauf, PhD.
Research Scientist, McGovern Institute for Brain Research, MIT

The neural mechanisms of object-based attention
How we attend to objects and their features that cannot be separated by location is not understood.We presented two temporally and spatially overlapping streams of objects, faces versus houses, and used magnetoencephalography and functional magnetic resonance imaging to separate neuronal responses to attended and unattended objects. Attention to faces versus houses enhanced the sensory responses in the fusiform face area (FFA) and parahippocampal place area (PPA), respectively. The increases in sensory responses were accompanied by induced gamma synchrony between the inferior frontal junction, IFJ, and either FFA or PPA, depending on which object was attended. The IFJ appeared to be the driver of the synchrony, as gamma phases were advanced by 20 ms in IFJ compared to FFA or PPA. Thus, the IFJ may direct the flow of visual processing during object-based attention, at least in part through coupled oscillations with specialized areas such as FFA and PPA.


Allyson Mackey, Ph.D.
Postdoctoral Fellow, McGovern Institute for Brain Research, MIT

Neuroanatomical Correlates of the Income Achievement Gap
In the United States, the difference in academic achievement between higher- and lower-income students (i.e., the income achievement gap) is substantial and growing. I will present data on neuroanatomical correlates of this gap in adolescents. I will compare cortical thickness between students from lower- and higher-income backgrounds, and relate cortical thickness to performance on the Massachusetts measure of academic achievement. I will discuss possible mechanisms that lead to income-related differences in brain structure, and the potential utility of brain measures in the design and evaluation of interventions to close the income achievement gap.


Linda Douw, PhD
Research Fellow, Harvard Medical school, Massachusetts General Hospital

From molecule to behavior: brain tumors and the connectome
Primary brain tumors are amongst the most lethal forms of cancer, with every patient eventually dying from this disease, despite extensive,multi-modal treatment. They are traditionally seen as a localized disease,but symptoms have a surprisingly global character. Gliomas, which arise from the brain's supporting glial tissue and are the most commonly occurring form of primary brain tumors, are often accompanied by idespread cognitive deficits and generalized epileptic seizures. Over the past decade, viewing the brain as a network has yielded important insights in normal functioning, and has also led to important advances in neuro-oncology. I will discuss the work that has been done in this field, starting with the altered network topology we see in glioma patients, which is associated with cognitive functioning and particularly epileptic seizures. Moreover, connectomics may provide an intermediate between molecular alterations characterizing the tumor, and behavioral symptomatology.