Episode #51 of the Charged podcast
The neuroimaging research program at Massachusetts General Hospital 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
Neuroscience at the Center for Addiction Medicine
Director: Jodi Gilman, PhD
At the Center for Addiction Medicine (CAM), we incorporate multimodal neuroimaging, personality, neuropsychological and clinical measures to investigate how addiction and other neuropsychiatric disorders affect the brain. We are currently conducting neuroimaging studies of young adult cannabis users, along with those with depression and PTSD in order to understand how cannabis interacts with neuropsychiatric disorders. We are also conducting neuroimaging scans at part of a year-long study assessing brain changes in medical marijuana patients. 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.
Program in Aesthetics and Well-Being
Director: Nancy Etcoff, PhD
The Program in Aesthetics and Well-Being conducts research and promotes advances in the psychology and neuroscience of aesthetics, emotions, body image and well-being. Current research focuses on perception of visual art, faces, bodies and architecture, the psychology of feelings of expansiveness and boredom versus engagement. Dr. Etcoff teaches seminars in neuroaesthetics at Harvard University and serves on the Neuroscience Advisory Board of the Peabody Essex Museum.
Interdisciplinary Affective Science Laboratory
Director: Lisa Feldman Barrett, PhD, Karen Quigley, PhD
The Interdisciplinary Affective Science Laboratory (IASLab) studies the nature of emotions as psychological, physiological and neurobiological phenomena and a variety of related topics including the role of language and concepts in emotion experience and perception, sex differences in emotion, cultural variation in emotion, and the nature, dynamics and age-related changes in affect and how affect influences perception and supports memory and other forms of cognitive performance. Our lab explicitly takes a systems neuroscience approach centered on the hypothesis that emotional states, like all mental states, emerge from the interaction of more basic ingredients. We combine behavioral, physiological, experience-sampling and brain imaging approaches (including functional MRI and PET) to study the question, “What is emotion?" and then use our discoveries as a way of probing larger issues such as the nature of consciousness and the evolution and development of human nature. These explorations have direct implications for the study of mood and anxiety disorders, as well as mood-related symptoms in neurodegenerative disorders and metabolic illness.
Laboratory for Bipolar Neuroimaging
Director: Thilo Deckersbach, PhD
The Laboratory for Bipolar Neuroimaging studies the functional neuroanatomy of bipolar disorder, the use of imaging techniques 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.
Director: Joshua L. Roffman, MD, MMSc
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. We also seek a better understanding how early life experiences and exposures influence risk for serious mental illnesses (SMI) such as schizophrenia by themselves and in conjunction with genomic markers. As is true for many other medical illnesses, SMI risk may be ascribed to specific modifiable and non-modifiable factors. Our lab is focused on developing strategies to optimize the prenatal environment, especially for those at increased risk due to non-modifiable factors such as genetic loading. In one recent example, we linked increased prenatal folic acid exposure to altered development of the cerebral cortex through childhood and adolescence in ways that appear to protect against psychosis risk. We collaborate with the Schizophrenia Clinical and Research Program and other clinics at Mass General to link these innovations directly to patient care.
Center for Morphometric Analysis (CMA)
Directors: Dr. Nikos Makris and Dr. Marek Kubicki
The mission of the Center for Morphometric Analysis (CMA) is to generate methodologies for quantitative brain anatomy inspired from developmental, comparative and clinical perspectives. The end goal of these methods is apply them in basic human and non-human anatomy and to neuropsychiatric conditions to inform diagnosis, guide treatments and elucidate mechanisms of disease process. The CMA develops custom-made methods targeting specific clinical problems using imaging technology inspired by its collaborations and informed by neurobiological factual knowledge and theory. The CMA has contributed many brain atlases to the neuroimaging community, most notably the Harvard Oxford Atlas (HOA) or to the SPL/3D Slicer atlas and served as the gold standard for the validation of the fully automated Free Surfer subcortical segmentation and cortical parcellation system. Currently, the CMA is supporting 24 colleagues in clinical research programs across the Departments of Psychiatry, Neurology, Neurosurgery and Radiology at Mass General as well as within the broader Mass General Brigham community.
Laboratory for Cerebellar Psychiatric Research
Director: Eve M. Valera, PhD
We are using MRI in conjunction with measures of cognitive functioning to assess the effects of physical abuse resulting in traumatic brain injury (TBI) in women sustaining intimate partner-violence (IPV). IPV-related TBI has rarely been studied, and we showed that approximately 75% of a sample of 99 women who had experienced IPV sustained at least one partner-related TBI and 50% sustained multiple partner-related TBIs. Additionally, brain injury severity was negatively related to memory, learning and cognitive flexibility. This work confirmed the critical need for additional research in this area. In our current work, we are using a range of methodologies including neuroimaging, neuropsychological assessment, blood biomarkers and interviews to characterize women's partner-related TBI history and its relationship to neural, cognitive and psychological functioning.
We also have a focus on understanding the role of the cerebellum and associated corticocerebellar circuits in psychiatric illness. Although the cerebellum has traditionally been studied in relation to motor function, a plethora of data now show that the cerebellum is involved in a range of cognitive, affective, and motor behaviors. Other data show that there are numerous corticocerebellar circuits, and the study of various psychiatric disorders has implicated disruption of these circuits in such disorders. Our lab is actively exploring cerebellar contributions to psychiatric illness including work on ADHD. Neuroimaging (fMRI, structural MRI and diffusion tensor imaging (DTI)), neuropsychological and motor assessment methodologies serve as the basis for these explorations.
Laboratory for Systems Neuroscience of Psychopathology
Director: Joshua W. Buckholtz, PhD
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 ADHD. 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.
Laboratory for Emotion and Social Neuroscience
Director: Daphne J. Holt, MD, PhD
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.
Cognition, and Psychopathology Laboratory (SCAN Lab)
Director: Dara S. Manoach, PhD
Cognitive deficits in neuropsychiatric disorders are profoundly disabling and effective treatments are lacking. The Sleep, Cognition and Psychopathology Laboratory is using multimodal neuroimaging to investigate the contribution of abnormal sleep to the cognitive deficits and symptoms of schizophrenia and autism spectrum disorders. We are guided by the principle that understanding the bases of cognitive deficits–from genes to physiology to circuit dysfunction to diagnosis–will lead to effective prevention and treatment. To achieve this goal, we collaborate with a multidisciplinary team of researchers. Our group has demonstrated deficient sleep-dependent memory consolidation in schizophrenia and has linked this deficit to a specific brain oscillation during sleep. In addition to further characterizing the genetic and neural bases of this deficit, we are developing and evaluating novel treatments targeting its mechanism. The ultimate goal is to improve function and outcome in individuals at risk of or suffering from neuropsychiatric disorders.
Genomics Superstruct Project
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 the Study of the Brain Basis of Individual Differences
Director: Hesheng Liu, PhD
The Laboratory for the Study of the Brain Basis of Individual Differences seeks to understand what makes an individual’s brain 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.
Laboratory for Anxiety Disorders and Affective Neuroscience
Director: Lisa M. Shin, PhD
The Laboratory for Anxiety Disorders and Affective Neuroscience seeks to understand the structural and functional brain abnormalities in PTSD. In collaboration with the PTSD Research Laboratory 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 Mood and Movement Disorders
Director: Anne J. Blood, PhD
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 that all dystonias are disorders of amplified postural function and 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 test the effects of treatment on the sets of abnormalities detected.
Laboratory for the Neuroscientific Investigation of Meditation and Mind-Body Medicine
Director: Sara W. Lazar, PhD
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 clinical populations and healthy individuals who are participating in meditation training 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.
Systems investigations (CNSi)
Directors: Nikos Makris, MD, PhD and Bradford C. Dickerson, MD
The Center for Neural Systems investigations (CNSi) 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. CNSi collaborates closely with the Center for Morphometric Analysis (CMA) and the Morphometric Analysis Center (MMAC).
NeuroCognition of Language Lab
Director: Gina R. Kuperberg, MD, PhD
The NeuroCognition of Language Lab investigates the neural mechanisms underlying language processing in healthy adults using multimodal neuroimaging techniques (including fMRI, MEG, ERP) and multiple different approaches (including neuropsychological testing and computational modeling). The lab also investigates how these mechanisms break down in individuals with neuropsychiatric disorders such as schizophrenia.
Laboratory for Neuroimaging and Neuromodulation of Cognition
Director: Hamdi Eryilmaz, PhD
The Laboratory for Neuroimaging and Neuromodulation of Cognition focuses on neural underpinnings of cognitive processes such as attention and working memory and seeks to understand the mechanisms by which these processes are disrupted in psychopathology. For example, patients with schizophrenia show impairments in working memory. Identifying specific brain networks that underlie these deficits can open new avenues of targeted interventions. Our laboratory uses functional MRI to elucidate the mechanisms of working memory impairment and aims to take advantage of network-guided Transcranial Magnetic Stimulation (TMS) to modulate network dysfunction and improve cognitive outcomes.
Division of Neurotherapeutics
Director: Darin D. Dougherty, MD
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), 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.
Laboratory for Neuroimaging Applications to Pain, Alternative Medicine and Placebo Research
Directors: Jian Kong, MD, MS, MPH, and Randy L. Gollub, MD PhD
The objective of our lab is to apply cutting-edge neuroimaging technologies such as MRI/fMRI, PET, MEG/EEG to investigate the neural substrates of acute and chronic pain, placebo and nocebo phenomena, as well as neural modulation of pain by complementary and integrative medicine (acupuncture, mind-body interventions) and novel neuromodulation techniques (transcutaneous vagus nerve stimulation (tVNS), and transcranial direct current stimulation (tDCS). Our mission is to translate our findings to facilitate the development of new treatments for chronic pain disorders (low back pain, knee osteoarthritis and migraine) and other prevalent disorders, such as depression, age-related cognitive decline and autism.
Laboratory for Developmental Neuroimaging and Psychopathology
Director: Carl Schwartz, MD
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. 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 of Sex Differences in the Brain
Director: Jill M. Goldstein, PhD
The Clinical Neuroscience Laboratory of Sex Differences in the Brain integrates scientists from clinical and basic neuroscience perspectives to investigate why men and women are at different risks for psychiatric disorders and their comorbidity with general medical disorders, such as cardiovascular disease (CVD). The lab takes a lifespan approach to investigations targeting naturalistic windows of opportunity for the study of sex differences when the brain and body are differentially flooded or depleted of gonadal hormones, such as fetal development and puberty, and, for female-specific periods, pregnancy and the menopausal transition compared to age-matched men. The interdisciplinary team of investigators integrates structural, diffusion and functional magnetic resonance imaging (sMRI, dMRI, fMRI), genetics/genomics and physiology (steroid hormones, immune response, autonomic nervous system/heart rate variability and blood pressure). Brain circuitries of interest include the stress response circuitry, mood/anxiety and memory, with a recent focus on sex effects in major depression, comorbidity with CVD and risk for Alzheimer's disease later in life. The Women, Heart and Brain Global Initiative was launched as a collaboration between Mass General and the Harvard T.H. Chan School of Public Health, partnering with WomenAgainstAlzheimer's. We believe that an understanding of hormonal, genetic, immune and metabolic pathways will provide knowledge for the development of sex-dependent or sex-specific therapeutics and have begun to develop novel neuromodulation therapeutics to begin to address this. The work is contributing to understanding the nature of psychiatric disorders, the impact of one’s sex and normal properties of the male and female brain in the face of disease.
Sleep and Anxiety Disorders Laboratory
Director: Edward F. Pace-Schott, PhD
The Sleep and Anxiety Disorders Laboratory uses polysomnography, fMRI, psychophysiology, self-report and related techniques to investigate how sleep helps humans regulate their emotions. Specifically, the lab studies the influence of sleep disturbance on the development of anxiety and traumatic-stress related disorders. Preexisting sleep disturbance increases the odds of incident anxiety disorders and of PTSD following a traumatic stressor. Sleep plays an important role in the consolidation of emotional memory. Our lab is particularly interested in how sleep influences evolutionarily ancient learning and memory processes that contribute to human emotion regulation and are deficient in anxiety disorders and PTSD. Such processes include fear extinction (learning that a once feared object or event is no longer dangerous) and habituation, whereby we become less reactive to frequently encountered stimuli. Our research strives to identify the effects of sleep on these elemental forms of emotional memory at the levels of behavior, physiology and neural circuits. Extinction and habituation are key components of a first-line treatment for anxiety disorders and PTSD, exposure therapy, a process whereby therapeutically introduced extinction and habituation memories aid in overcoming debilitating fears. We examine sleep and brain activity using experimental models of extinction and habituation. Additionally, we examine sleep effects in clinical applications of extinction learning such those that occur during exposure therapy for anxiety disorders.
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