Brain Mapping seminar abstracts 2011-12

Archana Venkataraman, PhD
Archana is a Ph.D. candidate in the department of Electrical Engineering and Computer Science (EECS) at MIT. She works in the Medical Vision Group under the supervision of Prof. Polina Golland. She earned a B.S. in Electrical Engineering from MIT in 2006. In 2007, she completed my M.Eng. in Electrical Engineering at MIT under the supervision of Prof. Alan V. Oppenheim. Her thesis focused on signal approximation using an anti-aliasing frequency warping.

Generative Models of Brain Connectivity for Population Studies
Connectivity analysis focuses on the interaction between brain regions. Such relationships inform us about patterns of neural communication and may heighten our understanding of neurological disorders. Here, we propose a generative framework that uses anatomical and functional connectivity information to find impairments within a clinical population. Anatomical connectivity is measured via Diffusion Weighted Imaging (DWI), and functional connectivity is assessed using resting-state functional Magnetic Resonance Imaging (fMRI). We first develop a probabilistic model to merge information from DWI tractography and resting-state fMRI correlations to infer latent templates of connectivity within the brain. We also present an intuitive extension to population studies and demonstrate that our model learns stable differences between a control and a schizophrenia population. Despite the promise of our joint model, connectivity results are difficult to interpret and validate given our region-centric knowledge of the brain. To alleviate these concerns, we present a novel approach to identify regions, which we call disease foci, associated with the disorder based on connectivity information. This allows us to aggregate pairwise connectivity changes into a region-based representation of the disease. Once again, we use a probabilistic formulation: latent variables specify a template organization of the brain, which we indirectly observe through resting-state fMRI correlations and DWI tractography. The inference algorithm simultaneously identifies both the afflicted regions and the network of aberrant connectivity. Our framework offers a principled method to explore brain connectivity. This allows us to tackle challenging and unexplored problems such as multi-modal analysis and region localization.

Kiho Im, PhD
Boston Children's Hospital
Dr. Im received his PhD in Biomedical Engineering at Hanyang University in Korea, where he investigated sulcal folding patterns, shape, and variability using a surface-based method in adult brains. At the FNNDSC, he has been focusing on the more challenging problem of characterizing sulcal pattern development in fetal brains. He hopes that his analysis tool development will ultimately provide innovative imaging markers for monitoring brain health and development unlike any that have previously been developed.

Individual Gyral Pattern-based Structural Connectivity and Network Analysis: Application to Polymicrogyria Brains
For the structural brain network analysis based on DTI tractography, most previous studies parcellated cortical regions to serve as nodes using volume- or surface-based registration to an atlas. However, an atlas-based node definition at the macroscopic scale appears to be too coarse to characterize short U-fibers connections between adjacent gyri. In addition, typical gyral patterns cannot be identified in some patients with cortical malformation because of abnormal cortical folding shape. We suggested novel node definition and structural connectivity analysis using individual gyral pattern and topology, which is biologically more meaningful and able to provide more explicit description of individual network organization. Using our approach, we investigated the white matter network in polymicrogyria (PMG), which is a cortical malformation with multiple small gyri and abnormal cortical lamination. The connectivity analysis for different fiber groups subdivided based on gyral topology revealed severely reduced connectivity between neighboring gyri (short U-fibers) in PMG, which was highly correlated with the regional involvement and extent of abnormal gyral folding. The patients also showed significantly reduced connectivity between distant gyri (long association fibers) and between the two cortical hemispheres. With relation to these results, gyral node based-graph theoretical analysis revealed significantly altered topological organization of the network (lower clustering and higher modularity) and disrupted network hub architecture in association cortical areas involved in cognitive and language functions in PMG patients. Consequently, our analysis provided more detailed findings and interpretation for the disrupted structural connectivity and network related to the abnormal cortical structure in PMG, overcoming the limitations of an atlas-based approach.

Lauren Atlas, PhD
New York University
Lauren received a PhD in Psychology from Columbia University in 2011, where she completed her doctoral research under the mentorship of Tor Wager. Her research combines human brain imaging, psychophysiological measures, pharmacological manipulations, and behavioral outcomes to understand how expectations shape affective experience. Lauren is currently a post-doctoral fellow at New York University working with Elizabeth Phelps.

Mediation analysis for fMRI: Identifying brain pathways that link experimental manipulations with behavior
Though a great deal is known about how informational cues affect visual perception, far less is known about how they shape affective processes such as pain and pleasure. In this talk I will present recent work examining the brain mechanisms that formally link expectations to dynamic affective experience. I will introduce whole-brain multi-level mediation analysis, a path modeling approach we developed that jointly considers the effects of psychological manipulations on brain responses and the relationship between brain responses and changes in reported experience. The first part of this talk will focus on expectancy effects on pain perception. We used mediation analysis to identify brain regions that 1) are modulated by predictive cues, 2) predict trial-to-trial variations in pain reports, and 3) formally mediate the relationship between cues and reported pain. We found that a subset of "pain matrix" regions mediated cue effects on pain, and that effects on these regions were in turn mediated by cue-evoked anticipatory activity in medial orbitofrontal cortex and ventral striatum, regions not previously directly implicated in nociception. In the second part of this talk, I will present new data identifying brain mediators of the relationship between expectations about healthfulness (i.e. claims of "light" versus "regular" foods) and experienced taste, and discuss the relationship between within- and between-subjects factors in the context of multi-level mediation. Finally, I will address the relationship between causal inference and path modeling approaches, and hypotheses about domain-general versus domain-specific processes.

Jyrki Ahveninen, PhD
MGH Martinos Center
PhD, Psychology, University of Helsinki, Finland

Multimodal Studies on Neuronal Representations of Distance in Human Auditory Cortex
Determining the distance of objects is of key value in many everyday situations. For objects that fall outside the field of vision, hearing is the only sense that provides such information. However, neuronal mechanisms of auditory distance perception are still poorly understood. One of the reasons is that contributions of intensity and distance processing have been difficult to differentiate. Typically, the received intensity increases when sound sources approach us. Nonetheless, we can also distinguish between soft-but-nearby and loud-but-distant sounds, indicating that distance processing can also be based on intensity-independent cues. We combined behavioral experiments, fMRI measurements, and computational analyses to identify neuron populations representing distance, independent of intensity. In a virtual reverberant environment, sound sources were simulated at varying distances (15-100 cm) along the right-side interaural axis. For such stimuli, two intensity-independent depth cues are available: direct-to-reverberant ratio (D/R) and interaural level difference (ILD). Our acoustic analysis suggested that, of these cues, D/R is more reliable and robust than ILD. However, based on our behavioral results, subjects' discrimination performance was more consistent with complex intensity-independent distance representations, combining both available cues, than with representations based on either D/R or ILD individually. fMRI activations to sounds varying in distance (containing all cues, including intensity), as compared to activations to sounds varying in intensity only, were significantly increased in the planum temporale and posterior superior temporal gyrus contralateral to the direction of stimulation. This suggests that neurons in posterior non-primary auditory cortices, in or near the areas processing other auditory spatial features, are sensitive to intensity-independent sound properties relevant for auditory distance perception.

Christos Papadelis, PhD
Boston Children's Hospital
Christos Papadelis is Instructor in Neurology at Harvard Medical School, Research Associate at Boston Children's Hospital, and Manager of the BabyMEG laboratory. He received the diploma in Electrical Engineering from the Aristotle University of Thessaloniki, Greece, in 1998, and his MSc and PhD in Medical Informatics, in 2001 and 2005 respectively, from the same institution.

Tracking Noninvasively the Information Flow along Fibers in the Human Brain: from Accurate Localization of Brain Sources to Functional Connectivity
In order to understand how the brain processes information, we must find out how this information is represented in a distributed fashion among different regions, and how it travels from region to region along neural fibers. Magnetoencephalography (MEG) is the ideal neuroimaging tool to assess the functional dynamics of the human brain activity since it offers both unparalleled temporal resolution and good localization accuracy especially for cortical neural sources. MEG is able to localize accurately even weak superficial sources that generate magnetic activity resembling the human brain high frequency oscillations (Papadelis et al., 2009). The accurate localization of these sources is possible even when just few trials are available, and is more pronounced when special instrumentation is used (Okada et al., 2006). Deeper thalamic sources can be localized with an accuracy of ~2 cm by averaging a high number of trials (Papadelis et al., 2012) in contrast to the traditional belief. The good localization accuracy of MEG let us link the macroscopic observed brain activity with the microscopic cytoarchitectonic identity of the activated regions (Papadelis et al., 2010) in healthy adults. The next step is to assess the functional connectivity among these regions and estimate how the information flows from one region to another. The functional connectivity among different brain regions was assessed in a visuomotor experiment by using well-established techniques from the fields of source localization, cytoarchitectonic anatomy, and multivariate autoregressive signal processing. A large-scale brain network oscillating in the alpha band was found that was active during visuomotor integration involving early visual areas, the dorsolateral prefrontal cortex and the hand motor area. These findings support a new model of how the frontal lobe makes use of visual information to produce conscious choices between competing behaviours, and emphasize the critical role of MEG in studying functional connectivity in the human brain. In more simple tasks, where a very high number of trials can be collected and averaged, the millisecond by millisecond afferent information flow along the thalamocortical fibers can be tracked by using MEG.

Iiro Jaaskelainen, PhD
Brain and Mind Laboratory, Department of Biomedical Engineering and Computational Science, Aalto University School of Science, Espoo, Finland

Movies as Naturalistic Affective-Social Stimuli in Functional Magnetic Resonance Imaging Studies
Functional magnetic resonance imaging (fMRI), which allows non-invasive measurement of brain hemodynamic activity over timescales of ~seconds, has significantly increased possibilities to study the neural basis of human perceptual and cognitive functions, including emotions and social cognition. Pioneering studies published in 2004 by Bartels et al. and Hasson et al. paved way for the use of highly naturalistic stimuli such as feature films in fMRI studies. While these early studies focused on sensory-cortical processing of visual perceptual features, we showed in 2008 that prefrontal cortical and subcortical (e.g., amygdala) areas involved in emotions and social cognition also exhibit across-subjects replicable responses when watching a contextually primed and emotionally engaging movie clip. In our recent studies, we have utilized movie clips as naturalistic stimuli to probe the cerebral mechanisms underlying emotions and social cognition in healthy volunteers. Results from these studies will be presented in this talk. We have also tested and developed new data analysis methods, including ones that allow estimation of instantaneous (i.e., single-TR) synchrony of hemodynamic activity between subjects and brain areas to study dynamic network activity of the human brain when subjects are watching movies. These freely available data analysis methods will also be briefly introduced in this talk.

Spencer Bowen, PhD
MGH Martinos Center

Influence of Partial Volume Effect Correction on Kinetic Parameter Estimation for Dynamic Brain PET Imaging
The combination of MR and dynamic PET exams via combined MR-PET may offer significant advantages over standalone imaging for assessing brain function in both healthy volunteers and dementia patients. Loss of quantification in the measurement of tracer uptake for structures with dimensions on the level of the PET spatial resolution (deemed the partial volume effect), however, can significantly bias such studies if not corrected for. Although partial volume effect correction (PVEC) methods have been well characterized for static PET imaging, PVEC on dynamically acquired PET images reconstructed with unregularized iterative algorithms (e.g. OSEM) creates unique challenges that have not been addressed previously. As the reconstructed spatial resolution of PET images may change during the course of a dynamic scan, and accurate PVEC requires an accurate estimate of image resolution, bias may result in the estimated kinetic parameters if this phenomena is not considered. We present several MR based PVEC methods and optimize these techniques for dynamic FDG PET imaging via a combination of studies, including: experimental phantom data, a Monte Carlo simulation of a dynamic brain acquisition using a digital patient phantom, and dynamic MR-PET imaging of healthy volunteers. Results show that kinetic parameter bias and noise are significantly influenced by the choice of the PVEC method, with performance differences between implementations the greatest for structures with the smallest features and most hypometabolic uptake.

Michael Fox, MD, PhD
Dr. Fox completed his MD/PhD with Marcus Raichle at Washington University in St. Louis followed by Neurology Residency training at the Partners Neurology Program in Boston. He has extensive experience with resting state functional connectivity MRI with over 20 publications, 3,900 citations, and multiple invited lectures and international presentations. He is presently a post-doctoral fellow enrolled in a self-designed clinical and research fellowship focused around brain stimulation. His clinical training is in movement disorders and deep brain stimulation at Partners (Massachusetts General Hospital, Brigham and Women’s Hospital) while his research training focuses on noninvasive brain stimulation at Beth Israel Deaconess Medical Center with Dr Alvaro Pascual-Leone. His goal is to use neuroimaging to better understand and improve therapeutic brain stimulation.

Clinical Applications of Resting State Functional Connectivity MRI: A Guiding Light for Brain Stimulation
Resting state functional connectivity MRI (rs-fcMRI) has several theoretical and practical advantages for use in clinical applications and is witnessing an exponential increase in popularity. Although its primary use has been investigating differences that occur in various brain diseases, increasing evidence suggests that it might be used to directly guide therapeutic intervention including neurosurgical resection and brain stimulation. After providing an introduction and overview of these topics, this talk will focus primarily on how rs-fcMRI may be used to guide transcranial magnetic stimulation for diseases such as depression. Potential application in other diseases benefiting from brain stimulation will be discussed.

Ofer Pasternak, PhD
Brigham and Women's Hospital
Dr. Ofer Pasternak is an Instructor in Psychiatry at the Brigham and Women's Hospital, Harvard Medical School. He has a Ph.D. in Computer Science from Tel-Aviv University, Israel, where he developed variational calculus methods for the analysis of diffusion MRI. He was a Fulbright postdoctoral fellowship in the Psychiatry Neuroimaging Laboratory (director, Dr. Martha E. Shenton) and the Laboratory for Mathematics in Imaging (director, Dr. Carl-Fredrik Westin). He was recently awarded the NARSAD young investigator award. His main interest is in the development of imaging tools that help understand the relation between degeneration and neuroinflammation in psychiatric and neurodegenerative brain disorders.

Free-Water Imaging for the Estimation of Extracellular Volume in the Human Brain
Recent diffusion MRI studies have pointed out that eliminating the contribution of extracellular water increases the sensitivity of the diffusion measures to alterations in tissue architecture. Moreover, in brain imaging, estimation of the extracellular volume appears to indicate pathological processes such as atrophy, edema and neuroinflammation. In my talk I will present the free-water imaging method, which assumes a bi-tensor model that accounts for the freely diffusing water molecules that can only be found in the extracellular space. I will discuss various estimation alternatives for the model, and will demonstrate how the method can be used for the study of neurodegenerative brain disorders as well as schizophrenia and traumatic brain injuries.

Jonathan Brooks, PhD
University of Bristol, UK

Pain: cause, consequence and control
Our understanding of pain has been transformed over recent years. Historically, the pain system was thought to be a relatively simple network conveying nociceptive signals via peripheral and spinal nerves to the thalamus and somatosensory cortex. However, through the use of non-invasive techniques to record brain activity, it is now apparent that a widespread network of cortical areas are involved in creating the sensation we know as pain. The multiplicity of brain regions responding to pain reflects its multi-dimensional nature: there are sensory components that tell us which part of the body has been damaged, we are able to relate how much it hurts by reflecting on previous painful episodes (memory), and we feel how unpleasant the pain is (affect). Furthermore, how much pain we experience depends on factors such as depression, mood, attentiveness, gender, age, coping mechanisms, etc. During this talk I will attempt to describe some of the techniques that have been used to explore pain processing in the brain, brainstem and spinal cord, and introduce some recent developments that are demonstrating how pain, particularly when it becomes chronic, can re-shape the brain. Lastly, I will discuss the principles of endogenous pain control, and show some recent human imaging data highlighting the role of the brainstem and spinal cord in this process.

Sylvain Bouix, PhD
Brigham and Women's Hospital

Increased Diffusion Anisotropy in Gray Matter in Mild TBI with Persistent Post-Concussive Symptoms
A significant percentage of individuals diagnosed with mild traumatic brain injury experience persistent post-concussive symptoms that do not resolve. Little is known about the pathology of these symptoms and there is often no radiological evidence based on conventional clinical imaging. We aimed to find a physiogenic basis to PPCS following mTBI using DTI. A novel analysis method was developed to identify abnormalities when the location of brain injury is heterogeneous across subjects. The foundation of our method is a normative atlas of diffusion measures built from a population of normal controls across different brain regions of interest.

David Salat, PhD
MGH Martinos Center

Deterioration of Structural Connectivity in the Aging Brain
A range of work has demonstrated that the neural tissue representing the structural basis of inter-regional connectivity, cerebral white matter (WM), is highly vulnerable to an array of insults as a result of normal and pathologic aging. However, the biological conditions that contribute to such degenerative changes and the cognitive and behavioral consequences of such deterioration are less well understood. Neuroimaging technologies, such as diffusion tensor imaging (DTI) have progressed over the last decades to provide sensitive measures of tissue microstructure that allow for the detailed quantitative assessment of brain anatomy and pathology. Such procedures can provide novel insight into patterns of compromised connective integrity resulting from aging and from age-associated conditions including Alzheimer.s disease (AD) and can contribute to understanding mechanisms that contribute to these conditions. Studies using DTI have provided greater appreciation for spatial patterns of WM deterioration in older adults and individuals with age-associated disease and ongoing work is exploring potential mechanisms by which poor vascular health may interact with risk factors for AD to promote the progression from a mild cognitive syndrome to a debilitating dementia.

Stephen LaConte, PhD
Virginia Tech

Brain Computer Interfaces Increase Whole-Brain Signal-to-noise
Overt actions allow us to interact directly with our environment. By definition, though, covert mental activity is unobservable by a third party and does not translate to action in the outside world. Real-time functional magnetic resonance imaging (rtfMRI) is a nascent technology that can convert thought into action by transducing noninvasive brain measurements into a control signal to drive physical devices and computer displays, and enable neurofeedback. We have developed an rtfMRI system that is based on multivariate predictive models (e.g. support vector machines) that determine the relationship between the image data and the corresponding sensory/behavioral conditions (brain states). This talk will present recent studies in which we have found that subject-based control involved frontoparietal circuitry and increased the signal-to-noise ratio (SNR) of task-related brain activity. Importantly, the enhanced SNR was highly correlated to improved prediction accuracy of brain state classifiers, and because these classifiers serve as the control signal for neurofeedback, this work suggests the exciting possibility that brain-computer interfaces can be substantially enhanced by taking advantage of this effect.

Mehdi Moghari, PhD
Beth Israel Deaconess Medical Center
Mehdi Hedjazi Moghari received B.Sc. and M.Sc. degrees in Electrical Engineering from Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran in 1999 and 2002. He received Ph.D. degree in Electrical and Computer Engineering at Queen’s University, Kingston, Ontario, Canada, in 2008. During 2009 and 2012, he continued his research at the cardiac MRI Center of Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, MA, USA. He is now with the Department of Cardiology at Boston Children’s Hospital. His research interest is on cardiovascular MRI including: pulse sequence design, motion compensation, image registration, and reconstruction.

Cardiovascular Magnetic Resonance Imaging: An Emerging Field in Clinical Practice
Cardiovascular magnetic resonance imaging (MRI) is an emerging modality that provides unique measurements and observations to cardiologists. Although echocardiography, X-ray angiography, and multi-detector computed tomography are conventionally used in clinical practice, cardiac MRI is a noninvasive and complementary technique that offers gold standard measurements for the assessment of regional and global cardiac function, myocardial infarction, and coronary artery disease. To improve the prognostics and diagnostic value of cardiac MRI, images with a high spatial-resolution needs to be acquired. However, the acquisition of high spatial-resolution images is challenging in cardiac MRI due to the respiratory motion of the heart. Prospective compensation of the respiratory motion unpredictably prolongs scan-time that impedes the acquisition of images with a high spatial-resolution. In this talk, the conventional prospective respiratory motion compensation algorithm in cardiac MRI is briefly presented. A new adaptive algorithm is introduced that minimizes the respiratory-induced heart motion in a predictable scan-time. Next, a novel algorithm based on Compressed Sensing (CS) is presented to reduce scan-time while minimizing the respiratory motion of the heart. The reduction in scan-time is then used to improve the spatial-resolution.

Alexandra Golby, MD
Brigham and Women's Hospital

Multi-modal brain imaging for pre-operative neurosurgical planning and intra-operative guidance
Over the last few decades, intracranial surgery has been transformed from a dangerous, unpredictable intervention with significant morbidity and mortality to a routine elective procedure with most patients leaving the hospital in a few days usually in better or equivalent neurologic condition than they were preoperatively. The change is due to the tremendous advances in imaging, visualization, and operative techniques that allow the surgeon to have a much better understanding of the anatomy and pathology that are the targets of the intervention. Nevertheless, there remain many times when neurosurgeons find themselves uncertain of how to proceed due to a lack of information. An important example is in surgery for primary brain tumors that arise from the brain parenchyma and may variably infiltrate, compress, or destroy brain tissue and that can be very difficult to differentiate from normal brain tissue. All brain surgery needs to consider the functional organization of the brain tissue around the lesion to avoid causing a new neurologic deficit. However, differentiating critical functional areas from areas that can be resected is not possible either on conventional imaging or by inspection at the time of surgery. To decide whether surgery is feasible for a patient with a given lesion, the surgeon requires a complete and accurate map of the complex and critical functional and structural anatomy of that individual’s brain. A further challenge results from the progressive deformation of anatomy that takes place during the surgical intervention (brain shift), making preoperative images and associated neuronavigation increasingly inaccurate. To address these major issues in modern neurosurgery requires the development of new techniques to demonstrate critical brain anatomy and pathology. Numerous pre-operative and intra-operative techniques are now available which can provide the surgeon with helpful information to guide surgical resection. Advances in neuro-imaging acquisition, computing, and image processing include neuronavigation, intra-operative MRI, multi-modality integration, advanced modeling, and image-analysis. In preoperative planning, functional MRI (fMRI) may be used to locate eloquent cortex and Diffusion tensor imaging (DTI) may be used to demonstrate white matter tracts. Together these methods allow the evaluation of surgical risks, selection of the best method of intervention, and planning of the safest surgical approach. Intraoperative imaging may be used to design the surgical flap, alert the surgeon of surrounding anatomy, define brain shift, assist in more complete lesion resection, and monitor for certain intraoperative complications.

Van Wedeen, MD
MGH Martinos Center

Not so tangled - Understanding the geometric structure of the brain pathways
By investigating the spatial relationships of pathways of the brain with diffusion MRI, in particular the relation of effective path adjacency, we make a surprising observation. The fiber pathways of the forebrain observable with diffusion MRI are organized as a highly curved yet highly precise 3-dimensional Cartesian grid, in which all pathways travel in only one of its 3 cardinal axes. This picture contrasts sharply with the more familiar image of brain pathways as a network of independent links. Pathways can no longer be considered independent, but components in a path continuum. Among its implications, this continuous structure makes it easier to understand the required changing connectivity in plasticity or in evolution. The 3-axis structure would simplify developmental pathfinding, reducing it to a code in 3 axes. In imaging, the exceptional character of the structure would allow it to be used as validation test or accuracy metric for diffusion tractography, possibly the first such test applicable in vivo or in the human brain. Evidence of the extension of this pattern to the cerebral cortex and functional implications will also be discussed.

Stefan Carp
MGH Martinos Center

Non Invasive Tissue Perfusion Measurement using Diffuse Correlation Spectroscopy
Diffuse correlation spectroscopy (DCS) is a novel optical technique that offers non-invasive monitoring of tissue perfusion with high temporal resolution (1 Hz+). DCS uses near-infrared light to measure speckle fluctuations that are primarily driven by red blood cell motion. Significantly, DCS enables non-invasive continuous monitoring of the tissue metabolic rate of oxygen (MRO2) in conjunction with near-infrared oximetry measurements. DCS currently only offers a blood flow (BF) index (thus allowing relative BF measurements). However, this index has been extensively validated against established BF measurement techniques, and has been used successfully by a number of groups for neuroscience, neurology, cancer research as well as other areas where tissue blood flow is clinically relevant. In this talk I will review DCS theory and implementation, summarize validation efforts and progress towards absolute blood flow quantification and describe several application domains.

Suzanne Haber, PhD
University of Rochester Medical Center

Rules ventral prefrontal cortical axons use to reach their targets
Dr. Haber will discuss the how understanding the organizational rules that fibers use to reach their targets based on nonhuman primate tracing studies can be used to interpret diffusion imaging studies in humans. The talk will first briefly describe the techniques used in animal experiments. It will then will address organizational rules that govern the fiber trajectories from specific prefrontal cortical areas; the ventral prefrontal surface, (ventral medial and orbital cortices), and the dorsal anterior cingulate cortex. Emphasis will be placed on the internal capsule, uncinate fasciculus, corpus callosum, and cingulum bundle. Finally, these results will be related to human imaging studies. Time permitting; Dr. Haber will demonstrate how we can use these results to predict the pathways affected by deep brain stimulation for psychiatric disorders at various stimulation sites.

Larry Wald, PhD
MGH Martinos Center

Technology for studying the human connectome
Perhaps more than any other "-omics" endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain will depend on the capabilities of the imaging technology used. The current tools are remarkable; for example allowing the formation of an "image" of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the complex organization of connection pathways in vivo is acquisition limited. The problem is one of sensitivity, image resolution, and efficiency of encoding for fMRI, and also resolution in encoding the diffusion probability distribution for diffusion tractography. The goal of our Human Connectome Project is two-fold; optimize the acquisition sequence over the wide and non-orthogonal parameter space of the acquisition methods, and also to fundamentally increase the breadth of this space by optimizing the hardware of the MRI scanner specifically for the connectome problem. We have therefore examined the MR scanner architecture and developed a scanner optimized for diffusion structural connectivity measurements. By increasing the gradient strength 7 fold with a diffusion dedicated gradient, as well as improving the detection coils and acquisition sequences we expect to provide new levels of detail to the connectome measurement. These tools have provided rich engineering challenges and are found to be enabling technology for improved structural connectomics with MRI.

Mohammed R Milad, PhD
Associate Professor of Psychiatry, MGH, Harvard Medical School

Neuroscience of fear extinction: relevance to anxiety disorders
In my talk, I will discuss progress in the past 10 years in the domain of fear extinction in the human brain, and how such findings are translated to the psychopathology of posttraumatic stress disorder and Obsessive Compulsive Disorder. In addition, I will present some recently published and unpublished data illustrating our efforts on 1) developing biological markers to predict fear learning, and 2) recent findings that could help enhance our understanding of why men and women may differ in the prevalence of anxiety and mood disorders.

Eric Moulton, PhD
Assistant Professor of Anesthesia, P.A.I.N. Group, Boston Children's Hospital, Harvard Medical School
Dr. Moulton is an Assistant Professor in the Department of Anesthesiology at Boston Children's Hospital. He earned his PhD in Neuroscience from the University of Maryland, Baltimore in 2004, where he did his thesis work with Dr. Joel Greenspan. Following graduation, he did his post-doctoral training under the guidance of Dr. David Borsook in the Pain & Analgesia Imaging and Neuroscience Group at the Brain Imaging Center at McLean Hospital. His research interests are in central nervous system sensory processing relating to pain, and its translation into perception/behavior.

Temporal evaluation of fMRI responses to contact heat: disentangling heat sensation from pain processing
The discovery of cortical networks that participate in pain processing has led to the common generalization that blood oxygen level-dependent responses in these areas indicate the processing of pain. However, many somesthetic cortical areas receive both innocuous and noxious neural signals. For example, electrophysiological recordings from primate S1 and S2 cortices have revealed that while most neurons there respond exclusively to innocuous stimuli, a subset responded selectively or differentially to noxious stimuli. Functional neuroimaging studies extend these observations to humans, where both types of stimuli activate the cortical areas S1 and S2. Given this overlap, it may be difficult to distinguish between innocuous and nociceptive processing with functional neuroimaging data. Regardless of the stimulus modality used, differentiation of these responses is essential for the interpretation of cerebral processing related to pain. Further complicating this is the recent suggestion that pain activation may simply represent a multimodal saliency process. This presentation will summarize evidence that suggests that different temporal segments of the fMRI response to contact heat may reflect different dimensions of sensory processing.

Marc Normandin, PhD
Instructor, Department of Radiology, MGH

PET imaging of the cannabinoid CB1 receptor with [11C]OMAR
The central cannabinoid system has essentials roles in regulating the signaling of other neurotransmitters and has emerged as a target of interest in psychiatric research and drug development. Several radioligands have recently been developed for imaging the cannabinoid CB1 receptor using PET. In this presentation, we will describe the characterization of one such tracer, [11C]OMAR, beginning with preclinical validation in non-human primates and subsequent translation to evaluation in healthy humans. Results from [11C]OMAR imaging in clinical research studies will be shown. Image quantification methods will be compared and the importance of using an appropriately validated analysis technique will be demonstrated. Recommendations and directions for future work in PET imaging of the cannabinoid system will be discussed.

Lisa Nickerson, PhD
McLean Hospital
Dr. Nickerson is an Assistant Physicist at the Imaging Center at McLean Hospital. She obtained a Bachelor's degree in Physics from Purdue University and a PhD. in Medical Physics from the Univ of TX Health Science Center at San Antonio. Although her PhD thesis was related to positron emission tomography statistics and image reconstruction, she came to McLean Hospital in 2001 as a post-doc in Perry Renshaw's group to learn about FMRI. She has been there since and through a NIDA T32 and a K25, she focused her training on FMRI statistics in the context of substance abuse problems. The highlight of the K25 is some of the work she will discuss today on the group ICA with dual regression approach.

Assessing Group Differences in Functional Connectivity using ICA with Dual Regression: Methodological Investigations
Independent Component Analysis (ICA) is one of the most popular techniques for the analysis of resting state FMRI data because it has several advantageous properties when compared with other techniques. Most notably, in contrast to a conventional seed-based correlation analysis (SCA), it is model-free and multivariate. This switches the focus from evaluating the functional connectivity of single brain regions identified a priori to evaluating brain connectivity in terms of all brain resting state networks (RSNs) that simultaneously engage in oscillatory activity. Unlike SCA however, the framework for applying ICA at the group level to study resting state functional connectivity is not straightforward. In this talk, I present our recent work investigating methodological aspects of one approach for group level resting state functional connectivity studies, group ICA with dual regression implemented in FSL. I also will discuss work we have done using this analysis approach that sheds insight into the underlying properties of RSNs.

Douglas Rosene, PhD
Boston University

Neuroantomical and Cellular Correlates of Diffusion MR Tractography: What are we Really Seeing?
There is no doubt that brain function is dependent upon the wiring of the brain - the interconnections among neurons. In some simple organisms with only neurons in that number in the hundreds or less, the exact complement of neurons is known and their exact interconnections have been specified. This offers the opportunity to investigate how information is processed within this network of neurons and connections and hence how that nervous system functions. Understanding the function of more complex mammalian brains including human and non-human primate brains will also depend upon understanding the network of interconnections but this involves many billions of neurons with unknown patterns of interconnections and synaptic contacts. Modern neuroimaging methods have provided unique insights into the 3D structure of the intact brain that has only been inferred from methods that slice the brain into sections for microscopic examination. Yet the exquisite pictures of connectivity reconstructed using diffusion MRI data remains largely unvalidated leaving open multiple questions of how to identify "tracts" that are missed as well as to exclude tracts that are false positives. In a collaborative effort to address some of these problems we have been applying neuroanatomical methods to rhesus monkey brains that have been scanned and reconstructed from diffusion MR. This talk will present preliminary results from labeling of specific pathways using modern tract tracers as well as applications of state of the art immunohistochemistry to identify the total complement of axons for comparison to diffusion MRI tractography.

Christian Langkammer, PhD
Medical University of Graz, Austria
Christian focuses on quantitative MRI methods for structural imaging in multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer's disease. He is employed at the Department of Neurology at the Medical University of Graz in Austria ( where he investigates pathologic iron deposition in the brain and high resolution diffusion MRI methods. To validate these findings and for assessing underlying biophysical mechanisms, he utilizes in situ postmortem MR imaging.

Insights into tissue composition and microstructure by postmortem MRI
While postmortem MRI is mainly used to address forensic questions, there is increasing interest of its application for improving our understanding of the complex signal formation in MRI. By incorporating results from analyzing techniques such as mass spectrometry, analytical chemistry, histology, and SQUID it seems possible to identify specific tissue components and to study their interaction with the water proton signal. In many instances, such analyzes are the only way to improve our understanding of tissue composition and microstructure. In brain tissue, typical research questions are related to iron and myelin content, the orientation of myelinated fibers, and how this affects magnetic susceptibility and diffusion properties. However, the advantages of postmortem MRI come along with some pitfalls. Conditions that differ from in vivo MRI such as temperature, fixation, deoxygenated blood and varying postmortem intervals are substantially altering the relaxation properties and therefore cannot be neglected when postmortem imaging findings are translated to in-vivo conditions. Thus, this talk addresses approaches to overcome those restrictions so that postmortem MRI becomes a useful tool for investigating tissue microstructure and for exploring biophysical mechanisms underlying MRI contrasts.

Chongzhao Ran, PhD
MGH Martinos Center

Optical Imaging of Amyloidosis of Alzheimer’s Disease and Brown Adipose Tissue
The Amyloid β (Aβ) species of Alzheimer’s disease (AD) has been considered an important biomarker family. Soluble Amyloid beta species are considered to be biomarkers of the presymptomatic stage and early products of molecular abnormality. Our goal is to seek probes that have potential for early diagnosis, particularly at presymptomatic stage. To this end, we designed and synthesized a library of small molecules that are novel “smart” Near-Infrared Imaging probes for both soluble and insoluble Amyloid beta species. In vivo whole body NIR imaging data indicated that our probes could differentiate AD transgenic mice and wild type mice at very early stage of the amyloidosis pathology, and the developed probe could be used for monitoring therapeutic efficacy of drug treatment. Brown adipose tissue (BAT) or brown fat, widely known as ‘good fat’, has been considered as a furnace in the body for burning excess calories, and plays important roles in metabolism and energy expenditure. BAT has recently emerged as an important target for diabetes and obesity research after multiple studies have demonstrated that BAT mass levels inversely correlate with body-mass index (BMI), and that physical exercises could increase BAT mass. In the second part of my talk, I will present recently acquired results related to imaging brown adipose tissue with 18F-FDG via Cerenkov Luminescence Imaging.

Martha Shenton, PhD
Brigham and Women's Hospital

The Role of Neuroimaging in mTBI, Schizophrenia, and CTE: DTI, MRS, and Emerging PET Tau Imaging in CTE
Neuroimaging tools over the last two decades have provided new windows of opportunity to investigate brain alterations in such disorders as schizophrenia, and more recently mild traumatic brain injury. Previously schizophrenia had long been suspected of being a brain disorder that affected both the temporal and frontal regions of the brain but it was not until the decade of the 90's that sophisticated imaging tools made it possible to detect the kind of subtle brain alterations that are present in schizophrenia. Similarly, for the most part neuroimaging was not useful for diagnosing mild traumatic brain injury since conventional magnetic resonance imaging and CT scans are often normal and show no radiological evidence of brain alterations. Now, with more sophisticated imaging such as diffusion imaging, we are able to appreciate brain alterations that heretofore went unrecognized in mild traumatic brain injury. In today's talk, the role of neuroimaging in mild traumatic brain injury and schizophrenia will be reviewed, along with a form of progressive neurodegenerative changes called chronic traumatic encephalopathy (CTE), most likely resulting from repetitive brain trauma. With respect to the latter, the role of emerging PET tau imaging will be presented as the next important step to understanding CTE.

Evelina Fedorenko, PhD
MIT, Brain & Cognitive Sciences
Ev Fedorenko is a research scientist in the Department of Brain & Cognitive Sciences at MIT. She seeks to understand i) the representations and computations that underlie human communicative abilities, and ii) the relationship between the language system and other cognitive/neural systems. To do so, she is adopting individual-subject MRI analysis methods that have been successful in other domains (e.g., vision), supplementing those with behavioral investigations of healthy and brain-damaged individuals and more temporally-sensitive methods like ECoG.

A novel framework for a neural architecture of language
What are the cognitive and neural mechanisms underlying the uniquely and universally human capacity for language? Since Broca's and Wernicke's seminal discoveries in the 19th century, a broad array of brain regions have been implicated in linguistic comprehension, production and learning, spanning frontal, temporal and parietal lobes, both hemispheres, and subcortical and cerebellar structures. However, characterizing the precise contributions of these different structures to language has proven challenging. Furthermore, although evidence from the investigations of patients with brain damage has long suggested some degree of independence between language and other high-level cognitive functions, many neuroimaging studies have argued that brain regions implicated in language are also engaged in many non-linguistic processes. In this talk I will argue that language is supported by the joint engagement of two functionally and computationally distinct brain systems. The first is comprised of the classic “language regions” on the lateral surfaces of left frontal and temporal lobes. Using individual-subject analysis methods which surpass traditional neuroimaging methods in sensitivity and functional resolution (Fedorenko et al., 2010; Nieto-Castañon & Fedorenko, 2012; Saxe et al., 2006), I have shown that these brain regions are specifically engaged in language processing (Fedorenko et al., 2011; see also Monti et al., 2012). The second is the fronto-parietal "multiple demand" network, a set of regions that are engaged across a wide range of demanding cognitive demands (e.g., Duncan, 2001, 2010). Most past neuroimaging work on language processing has not explicitly distinguished between these two systems, especially in the frontal lobes, where subsets of each system reside side by side within the region referred to as “Broca’s area” (Fedorenko et al., 2012). Using a variety of research methods I am now beginning to characterize the important roles of both domain-specific and domain-general mechanisms in language.

Rosalind W. Picard, Sc.D., FIEEE
MIT, Brain & Cognitive Sciences

What does skin conductance tell us about brain activity?
Our lab developed 24/7 wearable skin conductance sensors for measurement of the arousal component of emotion. Once we started getting clinical quality "arousal" data in natural life we learned many surprising things. The skin gives a sensitive measure of sympathetic nervous system activity with ipsilateral mappings that are strong and direct from several subcortical brain regions including amygdala, hippocampus and anterior cingulate. This information now enables us to detect patterns related to asymmetric brain functioning, as well as to detect seizures, quantify autonomic disruption, and predict duration of post-seizure generalized EEG suppression. These patterns can now be picked up with a non-invasive wristband. In partnership with Czeisler and Stickgold and their teams we are also identifying patterns that occur in sleep skin conductance, primarily in non-REM. This talk will share several scientific findings as well as personal stories from these investigations.

David Somers, PhD
Boston University
David did his PhD work in Computational Neuroscience at Boston University with Steve Grossberg and Nancy Kopell. He did his post-doctoral training with Mriganka Sur where he investigated cortical circuits and also with Ted Adelson on visual psychophysics, both at MIT. Then finally he "saw the light" and trained in fMRI methods at the Martinos Center in Roger Tootell's lab. He has been on faculty in the Psychology Dept at BU since 2000 and has recently been promoted to full professor (effective 9/2013).

Multiple Attention Networks in Human Fronto-Parietal Cortex Revealed by fMRI
It is well established that when attention is directed to sensory stimuli, a network of brain regions are recruited within the frontal and parietal cortices; however, this “fronto-parietal network” is only coarsely described in the human brain. I will present evidence from within-subject fMRI studies for the existence of four distinct attention networks. Two networks have previously been well described, while two other networks emerge from recent work in our laboratory. Endogeneous visual attention activates the “dorsal visual attention network,” which includes the frontal eye fields or superior precentral sulcus, inferior precentral sulcus, and the medial banks of the intraparietal sulcus. Exogenous visual attention activates the “ventral visual attention network,” which includes the temporo-parietal junction and the inferior frontal junction. We have investigated the role of explicit long-term memory in the guidance of visual attention and have observed a new sub-network, that we term the “memory-guided attention network,” that includes dorsal inferior parietal lobule, posterior dorsal precuneus and the pericallosal sulcus. In a separate set of studies we have contrasted auditory and visual attention and have observed that auditory attention recruits distinct lateral frontal cortical areas that are interleaved with frontal areas of the dorsal visual attention network. These auditory attention areas form a network at resting state. However, we argue that these cortical areas are not beholden to any sensory modality and that the information domain, spatial or temporal, is key to the functional organization of these areas, with the spatial domain strongly recruited for vision and the temporal domain strongly recruited for auditory. To support our argument, we demonstrate that a purely visual task with high temporal demands recruits the temporal/auditory network, while a purely auditory task with high spatial demands recruits the spatial/visual network.

Natalia Egorova, Ph.D.
Cambridge University, UK

Social communicative actions in the brain: neural correlates and temporal dynamics of processing the speech acts of Naming and Requesting
Although language is a tool for communication, little is known about neural processing of speech acts, that is, utterances with a communicative function. In a series of EEG, MEG, and fMRI experiments, in which participants observed communicative interaction, the temporal dynamics and neural basis of processing the speech acts of Naming and Requesting, expressed with single word utterances, were investigated. The results reveal that within the first 200 ms of the stimulus onset, Naming activates brain areas involved in lexico-semantic retrieval. In contrast, Requests engage mirror-neuron action-comprehension system in order to process action knowledge and the associated intentions, followed by activation in the theory of mind circuit between 200 and 300 ms to support mentalising the assumptions and high-order intentions of the communication partners. This cascade of interactive processing stages, subserved by a dynamic communicative action network, may be the basis of speech act comprehension.

Philip Corlett, Ph.D.
Yale University

Delusions and the Brain: Learning about odd beliefs through Cognitive Neuroscience
I'll discuss the psychology and neurobiology of belief formation, how it can inform our understanding of one of the cardinal symptoms of mental illness; delusions; the bizarre and tenacious beliefs that attend serious mental illnesses like schizophrenia. By drawing on recent advances in the biological, computational and psychological processes of reinforcement learning, memory, and perception, I will argue that it may be feasible to account for delusions in terms of cognition and brain function. My explanation focuses on a particular parameter, prediction error--the mismatch between expectation and experience--that provides a computational mechanism common to many disparate brain systems. I'll suggest that delusions result from aberrations in how brain circuits specify hierarchical predictions, and how they compute and respond to prediction errors. Defects in these fundamental brain mechanisms can vitiate perception, memory, bodily agency and social learning such that individuals with delusions experience an internal and external world that healthy individuals would find difficult to comprehend. Finally, I'll describe recent work on the fixity of delusions; which may also be explained in terms of aberrant prediction error processing. Surprising events demand a change in our expectancies. This involves making what we have learned labile, updating and binding the memory anew: a process of memory reconsolidation. I will argue that, under the influence of excessive prediction error, delusional beliefs are repeatedly reconsolidated, strengthening them so that they persist, apparently impervious to contradiction.