The neuroimaging research program comprises a diverse group of laboratories and affiliated initiatives that seek to understand psychiatric illness using neuroimaging approaches.
Laboratories and Initiatives Associated with Psychiatric Neuroimaging
Laboratory for Interdisciplinary Affective Science
Director: Lisa Feldman Barrett, Ph.D.
The Laboratory for Interdisciplinary Affective Science studies the nature of emotions as psychological and natural phenomena, the role of emotion in vision, the role of language in emotion experience and perception, and sex differences in emotion. At the center of this work is the hypothesis that emotional states arise from combinations of more basic psychological processes. The work in our laboratory combines behavioral and functional MRI approaches to answer the question, “What is emotion?” at psychological and neuroscientific levels. These explorations have direct implications for the study of mood and anxiety disorders.
Laboratory for Mood and Movement Disorders
Director: Anne J. Blood, Ph.D.
The Laboratory for Mood and Movement Disorders takes a systems-level and translational approach to studying the neural basis of movement disorders and mood disorders. Behavioral approaches and neuroimaging are used to test the idea that both motor and mood control are strongly modulated by the baseline “tone” of function in the basal ganglia and related structures. The laboratory is also testing a specific model for dystonia that suggests, first, that all dystonias are disorders of amplified postural function, and secondly that the indirect pathway of the basal ganglia controls posture through a dual-mode (tonic and phasic) system, while the direct pathway controls specific motor programs. While evaluating these basic concepts of neural organization, our work uses imaging to biologically subtype dystonia and major depressive disorder and to test the effects of treatment on the sets of abnormalities detected.
Laboratory for Systems Neuroscience of Psychopathology
Director: Joshua W. Buckholtz, Ph.D.
The Systems Neuroscience of Psychopathology Laboratory (SNPlab) utilizes multimodal neuroimaging (molecular imaging with PET and functional/structural/connectivity imaging with MRI), personality and behavioral assessment, and genomic approaches to understand how genes and environments affect brain chemistry and function to influence variability in human self-control. Individuals vary widely in their capacity to deliberate on the potential adverse consequences of their choices before they act. Highly impulsive people frequently make rash, destructive decisions, and trait differences in self-control are strongly associated with susceptibility to a range of psychiatric disorders, such as substance use disorders, antisocial behavior, and attention deficit/hyperactivity disorder. We are particularly focused on elucidating the mechanisms through which genetic and environmental susceptibility factors act and interact to dysregulate neural circuitry involved in reward and motivation, leading to increased susceptibility to antisocial behavior and drug use. In addition, we are interested in using neuroimaging and genetic approaches to understand how genes impact the brain to influence social behaviors that are relevant to self-control, such as social cooperation, norm-following, and norm-enforcement.
The Brain Genomics Superstruct Project explores links between genes, brain function, and behavior. The barrier to brain genomics has been the cost associated with acquiring neuroimaging data from thousands of participants. As a result of recent breakthroughs in imaging technologies, it is now possible to acquire detailed structural and functional imaging in less than 15 minutes. Over 3,000 patients with psychiatric disorders and controls participate in research studies across the local neuroimaging community each year. The Superstruct project provides imaging techniques to all investigators who are willing to pool these common sequences and provide saliva samples for DNA extraction. The project provides investigators genetic information and image analysis tools, thereby enhancing their own research opportunities. The goals of the project are to construct a “brain bank” with genetic data to anchor more targeted investigator-initiated studies, and to facilitate access to emerging tools for genetic explorations of brain function and dysfunction.
Laboratory for Cingulate Cortex Research
Director: George Bush, M.D., M.M.Sc.
The Laboratory for Cingulate Cortex Research develops novel functional MRI paradigms and employs them to study cingulate cortex function in normal cognitive/emotional processing and psychiatric disorders. Our main areas of interest include attention-deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), and mood and anxiety disorders. Elucidating how the cingulate cortex functions is vital to understanding the neurobiology of psychiatric disorders as its subregions play roles in cognitive, emotional, reward, and motor processes. Cingulate subdivisions are also key components of the default network, which is a network of brain regions that contributes to vigilance functions and judgments about the self and social situations. Our lab utilizes functional MRI, intracranial recordings, cognitive neuroscience, and clinical research methods, as well as collaborative studies of cingulate cortex anatomy and physiology. Functional MRI is also employed to study the substrate of pharmacological effects on attention and ADHD, as well as to characterize the neural substrate of relaxation response and social attachment processes.
Laboratory for Bipolar Neuroimaging
Director: Thilo Deckersbach, Ph.D.
The Laboratory for Bipolar Neuroimaging studies the functional neuroanatomy of Bipolar Disorder and how imaging techniques can be used as diagnostic tools and predictors of treatment response. Current projects using molecular PET techniques and functional MRI are exploring the interaction between cognition and emotion as well as the neural processes of resilience in Bipolar Disorder. This work has recently led to a characterization of the cognitive impairments in euthymic, recovered patients with Bipolar Disorder. The long-term goal of our research is to improve rehabilitation approaches for cognitive impairments in unipolar and bipolar disorder.
Division of Neurotherapeutics
Director: Darin D. Dougherty, M.D.
The Division of Neurotherapeutics pioneers device and surgical treatments for intractable psychiatric illness. These interventions include electroconvulsive therapy (ECT), ablative limbic system surgery (including anterior cingulotomy, subcaudate tractotomy, and limbic leucotomy), vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), cortical stimulation (CS), and deep brain stimulation (DBS). They also explore interoperative microelectrode recording and neuroimaging methods to assess these interventions. As a basis for this work, the Division also conducts non-invasive neuroimaging studies examining cognition and emotional processing in subjects with affective illness.
Program in Aesthetics and Well-Being
Director: Nancy Etcoff, Ph.D.
The Program in Aesthetics and Well-Being conducts research and promotes education and therapeutic advances in the science of beauty, body image, and well-being. Current research focuses on the underlying cognitive processes and neural substrates of the recognition of attractiveness, emotion, personality, and character from the face, and on specifying the contribution of the biological phenotype versus the extended phenotype (the effects of the genes beyond the body) to recognition and perception of people. Using longitudinal data, a collaborative study explores the effects of physical appearance on ill-being (depression and social anxiety) and well-being across the lifespan. Dr. Etcoff teaches two undergraduate seminars on the Science of Happiness at Harvard University.
Laboratory for Neuroimaging of Anxiety and Respiratory Psychophysiology
Director: Karleyton C. Evans, M.D., M.Sc.
Breathing is essential to human life, by providing oxygen and removing carbon dioxide. The homeostasis in gas exchange is often disordered in patients with diseases of the lungs, heart, and central nervous system. Treatment of these conditions is complicated by limited understanding of the neural circuits serving respiratory control and perception. The Laboratory for Neuroimaging of Anxiety and Respiratory Psychophysiology uses functional MRI to study respiratory neural circuitry in healthy and diseased populations. Our central focus is the modulation of breathing and the perception of dyspnea (breathlessness) in anxiety and affective states. Notably, an NIMH funded study is currently testing a novel neural circuit model in Panic Disorder (PD) that attributes the misinterpretation of respiratory sensations to dysfunctional limbic circuitry. This study aims to differentiate the primary circuitry that triggers panic attacks from other secondary circuits thought to mediate physiological responses. We expect the findings from this study to inform the development of more effective, targeted therapies for PD. As a complement to this work the Laboratory is also engaged in studies of opioid modulation of breathlessness as well as studies of cerebral vascular responses to elevated carbon dioxide (hypercapnia) in health and disease.
Laboratory for Clinical Neuroscience of Sex Differences in the Brain
Director: Jill M. Goldstein, Ph.D.
The Clinical Neuroscience Laboratory of Sex Differences in the Brain seeks to understand genetic, hormonal, and inflammatory factors that are disrupted during fetal development and that contribute to the vulnerability for sex differences in psychiatric disorders in adulthood such as depression and psychoses. The laboratory also examines these factors in relation to comorbidity with other medical disorders, such as cardiovascular risk and endocrine dysfunction. The work is contributing to our understanding of how hormones and genes affect the sex-specific development and functioning of the healthy brain, brain regulation of multiple systems in the body, and the implications of this knowledge for understanding sex differences in health and disease. The laboratory combines brain imaging with neuroendocrinology, immunology, genetics, psychiatry, and epidemiology, and the team works with basic scientists mapping out mechanisms for understanding sex differences in disorders. Current work focuses on the stress response circuitry, working memory, declarative memory, and food motivation circuitry (neural circuitry of obesity).
The Laboratory for Neuroimaging Applications to Pain, Acupuncture, and Placebo Research has two major areas of focus. One line of work explores the neural representation of acute and chronic pain and its modulation by acupuncture and placebo/expectation. Elucidating the neural substrates of placebo and related forms of expectation effect has important implications for the development of efficient clinical trials. A second line of work focuses on translating biomedical imaging technologies to applications in clinical neuroscience. Our recent work has included development, calibration and validation of MRI acquisition and analysis methods that can be used to pool data across sites, such as is required for clinical trials.
Laboratory for Emotion and Social Neuroscience
Director: Daphne J. Holt, M.D., Ph.D.
The Laboratory for Emotion and Social Neuroscience focuses on understanding the neural basis of emotional function and social behavior, and abnormalities in these domains in neuropsychiatric conditions such as schizophrenia and depression. We apply the methods of affective neuroscience and neuroimaging to study a variety of basic processes that support emotional and social function, such as emotional learning and memory, visual attention, and face perception. Recent studies have shown that aspects of emotional learning and memory are disrupted in people with schizophrenia and contribute to the symptoms of the disorder. Other work has focused on understanding changes in the neural systems mediating awareness of the self and others found in schizophrenia, depression, and at-risk populations.
Laboratory for NeuroCognition
Director: Gina R. Kuperberg, M.D., Ph.D.
The Laboratory for NeuroCognition seeks to understand how the brain processes the meaning of events that unfold over time and how these processes are abnormal in schizophrenia. For example, the many steps involved in cooking a meal are understood rapidly because we have a schema about what is involved and what comes next. Language, discourse, and perception are all guided by such schema. Studies within the laboratory focus primarily on the sequential processing of language and visual events using a cognitive neuroscience approach. In order to investigate the “when” and “where” of brain activity, multimodal imaging techniques are used. Event-related functional MRI detects brain activity with precise spatial (millimeter) resolution while event-related potentials (ERPs) and magnetoencephalography (MEG) detects brain activity with precise temporal (millisecond) resolution. Our recent investigations are integrating these techniques to give new insights into the spatiotemporal dynamics of normal and abnormal brain function.
Laboratory for the Neuroscientific Investigation of Meditation and Mind-Body Medicine
Director: Sara W. Lazar, Ph.D.
The Laboratory for the Neuroscientific Investigation of Meditation and Mind-Body Medicine studies the neural correlates of meditation and yoga, with the goal of understanding how these practices contribute to health and well-being. Research involves both individuals who have practiced meditation or yoga for several years in specific traditions, as well as individuals with no previous experience who are participating in meditation-based stress reduction programs. Structural and functional MRI are used to explore the effects of these practices on the brain, including stable changes in neural organization that are associated with changes in affect or cognitive abilities.
Laboratory for the Study of the Brain Basis of Individual Differences
Director: Hesheng Liu, Ph.D.
The Laboratory for the Study of the Brain Basis of Individual Differences seeks to understand what makes individual brain's distinct. Although human brains share common structural and functional properties, considerable differences exist between people. A major goal of our work is to improve surgical planning for epilepsy and brain tumor patients, which requires precise mapping of the brain systems in individual patients. Another goal is to find individual differences that mark psychiatric disorders such as schizophrenia. Using modern imaging and computational technologies, we aim to develop reliable signatures of psychiatric illness that can provide increased statistical power for investigating genetic associations and determining risk of illness. To facilitate these investigations, our laboratory has built a platform to merge information within an individual from multiple imaging modalities including anatomical and functional MRI, MEG/EEG, and intracranial ECoG.
The Center for Neural Systems investigations focuses on characterization of structural and functional regularities in normal humans and the breakdown in disease processes. In clinical neuroscience, the investigation of neural systems has many applications. Anatomical-clinical and functional-clinical correlations aim to elucidate abnormalities of perceptual, motor, cognitive, emotional/affective and autonomic systems in a variety of clinical conditions using structural and functional neuroimaging. This approach has already begun to lead to the discovery of novel endophenotypes for neuropsychiatric disorders. Many of these basic systems neuroscience findings in neuropsychiatric disorders could be considered for translational efforts toward biomarkers for clinical diagnosis or therapeutic intervention trials.
Laboratory for Multimodal Neuroimaging of Executive Function in Psychopathology
Director: Dara S. Manoach, Ph.D.
The Laboratory for Multimodal Neuroimaging of Executive Function in Psychopathology is guided by the principle that identifying the neural circuitry that underlies cognitive deficits in neuropsychiatric disorders can steer investigations of neuropathology and the development of targeted interventions. Our laboratory’s research program aims to elucidate the neural bases of executive functions in healthy adults as a foundation for understanding dysfunction in neuropsychiatric disorders. While schizophrenia is the primary focus, we also conduct studies of cognition in autism spectrum disorder (ASD) and OCD. A separate line of inquiry aims to understand the role of sleep in consolidating new learning. Patients with schizophrenia show a failure of sleep-dependent procedural learning and memory. New studies are investigating the basis of this failure using functional MRI, overnight polysomnography, and cognitive paradigms.
Laboratory for Behavioral Neuroscience
Director: Mohammed R. Milad, Ph.D.
The Laboratory for Behavioral Neuroscience is focused on understanding the neural mechanisms of fear extinction using classical fear conditioning. Our ongoing projects involve studies in human patients as well a rodent model of fear extinction. Functional MRI and psychophysiological tools are employed in humans to examine the role of limbic circuits in conditioned fear in various patient populations including PTSD, OCD, and schizophrenia, as well as the influence of sex and gonadal hormones on these circuits. Animal models are then used to examine the influence of the estrus cycle and gonadal hormones on fear extinction. These basic research efforts are actively being translated to test novel therapeutic agents to block reconsolidation of conditioned fear.
Laboratory for Brain Genomics
Director: Joshua L. Roffman, M.D., M.M.Sc.
The Brain Genomics Laboratory merges functional neuroimaging with "upstream" biological markers (genetic, epigenetic, molecular, and electrophysiologic) to make new inroads into the neurobiology of mental illness. One line of work combines functional MRI with dopamine-related positron emission tomography (PET) and genetic assays to parse the neural substrate of executive dysfunction in schizophrenia, and to leverage this information to help develop cognition-enhancing agents. Another project uses PET measures of brain metabolism in combination with quantitative EEG to characterize neural correlates of psychodynamic psychotherapy process and outcome in depression. The work within the laboratory is unified around the central theme of developing individualized, biomarker-driven treatment regimes for psychiatric illness. We collaborate with the MGH Schizophrenia and Depression Clinical and Research Programs to link these innovations directly to patient care.
Laboratory for Developmental Neuroimaging and Psychopathology
Director: Carl Schwartz, M.D.
The Laboratory for Developmental Neuroimaging and Psychopathology seeks to understand the relationship between early psychological predispositions and physiological states in infants (i.e. temperament) and the development of psychiatric disorders (particularly anxiety and mood disorders) and behavior problems in adolescents and young adults, through studies of cohorts of infants and children who have been followed longitudinally through development. Our laboratory utilizes multiple neuroimaging approaches including structural imaging, functional magnetic resonance brain imaging, and diffusion tensor imaging in conjunction with clinical assessments of psychopathology, direct observation of behavior and social interaction in the laboratory, neuropsychological studies of information processing, and assessment of autonomic reactivity to cognitive and social stress. In collaboration with the Psychiatric Genetics Program, the genetics of these temperamentally based behavioral and biologic intermediate phenotypes (or “endophenotypes”) indexing anxiety-proneness and depression are investigated. This approach offers an important alternative to examining phenotypes based on current existing diagnostic approaches. Thus, we are an interdisciplinary group both in terms of training (psychiatrists, developmental psychologists, neurologists, and neuroscientists are all welcome) and methods (behavioral observation, psychophysiology, structural and functional MRI).
Laboratory for Clinical Neuroscience and Developmental Neuropsychology
Director: Larry J. Seidman, Ph.D.
The Laboratory of Clinical Neuroscience and Developmental Neuropsychology studies memory and executive function in normal individuals, as well as disruption in developmental neuropsychiatric disorders, especially in schizophrenia, ADHD and Bipolar Disorder. Our laboratory has a longstanding focus on endophenotypes in schizophrenia (beginning in 1986) and in mapping the neural substrates of risk for psychosis in teens and young adults. A major accomplishment of the laboratory has been to show that the neurocognitive functions and neural circuitry underlying dysfunction in schizophrenia are present well before psychotic illness begins. Tools used include cognitive and neuropsychological assessment, functional MRI, and genetic analysis.
Laboratory for Anxiety Disorders and Affective Neuroscience
Director: Lisa M. Shin, Ph.D.
The Laboratory for Anxiety Disorders and Affective Neuroscience seeks to understand the structural and functional brain abnormalities in posttraumatic stress disorder (PTSD). In collaboration with the PTSD Research Group directed by Roger K. Pitman, MD, we are using a monozygotic twin design to determine whether brain abnormalities observed in PTSD are acquired signs of the disorder or familial vulnerability factors that increase the risk of PTSD after trauma exposure. Our laboratory is also currently investigating whether neuroimaging measures can help predict response to treatment in patients with PTSD.
Laboratory for Cognitive Neuropsychiatry
Director: Tatiana Sitnikova, Ph.D.
The goal of the Cognitive Neuropsychiatry Laboratory is to better understand debilitating deficits in goal-directed behavior in schizophrenia, with intent to inform therapeutic practices. Behavioral flexibility depends on knowledge representations of goal-relevant dimensions. Recent findings suggest that developmental abnormality of the prefrontal cortex in schizophrenia may disrupt the formation of such representations. Our laboratory examines the mechanisms of dysfunction by combining multimodal neuroimaging and molecular genetic methods. We developed a sensitive experimental paradigm to identify spatiotemporal neural abnormalities as patients attempt to recruit knowledge representations. To elucidate the underlying molecular pathways, we examine whether the observed abnormalities can be linked to genetic variation associated with neurotransmitter activity levels in prefrontal cortex. Against this background, we recently launched a proof-of-concept treatment study to supplement pharmacotherapy with an educational program that teaches patients with schizophrenia strategies to improve their adaptive behavior and cope with real-world pressures.
Laboratory for Addiction Neuroscience
Director: Luke Stoeckel, Ph.D.
The Laboratory for Addiction Neuroscience incorporates multimodal neuroimaging, personality, neuropsychological, and clinical measures to investigate brain-behavior relationships in neuropsychiatric disorders. We are currently developing real time fMRI neurofeedback as a tool to investigate the pathophysiology of disorders like addiction and obesity, with the aim of identifying rational, novel therapeutics based on this knowledge. The lab is comprised of an interdisciplinary team of scientists unified by a common goal of improving understanding of the pathophysiology of neuropsychiatric disorders in order to develop new, more effective individualized therapies to enhance neuropsychological functions. Our current projects involve collaborations with investigators at MGH, MIT, and McLean Hospital.
Laboratory for Cerebellar Psychiatric Research
Director: Eve M. Valera, Ph.D.
The Laboratory for Cerebellar Psychiatric Research focuses on understanding the role of the cerebellum and associated cortico-cerebellar circuits in psychiatric illness. The cerebellum has traditionally been studied in relation to motor function; anatomical work has shown various cerebral-cerebellar circuits, and study of various psychiatric disorders has suggested disruption of these circuits. Motivated by these novel observations, our laboratory is actively exploring cerebellar contributions to psychiatric illness, including work on ADHD. Neuropsychological and neurological testing as well as multiple imaging modalities, including diffusion tensor imaging (DTI) and structural and functional MRI, serve as the basis for these explorations. An additional project in the laboratory uses sensitive imaging approaches to document and study brain injuries that result from physical partner abuse.