Massachusetts General Hospital

Overview

The Neuroimaging Lab within the Schizophrenia Program at Massachusetts General Hospital is housed in the Athinioula A. Martinos Center for Biomedical Imaging located in Charlestown, MA.

Imaging technologies are used to conduct research on the neurobiological basis of schizophrenia. The goals of this research are to:

• Understand the neural abnormalities that give rise to the symptoms and cognitive impairment associated with the illness
• Develop biomarkers for the purpose of early detection of psychosis
• Develop more effective treatments and means of assessing treatment response

Many of the most important MRI-based methods for studying human brain structure and function were first developed and continue to emerge from the Martinos Center, including:

• Functional MRI (fMRI)
• Event-related fMRI
• Automated measurement of the boundaries and sizes of brain structures (see example)

The schizophrenia neuroimaging investigators at Massachusetts General Hospital have been well-positioned to take advantage of these advanced methods, applying these techniques and their expertise in basic and cognitive neuroscience to answer critical questions about brain structure and function in schizophrenia.

Close collaboration with researchers at the Martinos Center, Harvard University, and Massachusetts Institute of Technology (MIT) creates a community of internationally-known experts in MRI-based technologies, cognitive neuroscience and psychiatry. This has allowed the Mass General Neuroimaging Lab to contribute important insights about the neural underpinnings of schizophrenia. Recent findings include:

• The first neuroimaging study to characterize the complex nature of functional changes within the prefrontal cortex during executive function in schizophrenia (Manoach et al, Biological Psychiatry, 2000)
• A precise analysis of the reductions in the thickness of the cortical mantle in schizophrenia (Kuperberg et al, Archives of General Psychiatry, 2003)
• The first report of a deficit in sleep-dependent procedural learning in schizophrenia (Manoach et al, Biological Psychiatry, 2004)
• One of the initial demonstrations of amygdala hyperactivity in schizophrenia (Holt et al, Schizophrenia Research, 2006)
• A technically sophisticated investigation of the neural basis of semantic associative abnormalities and their relationship to thought disorder in schizophrenia (Kuperberg et al, Archives of General Psychiatry, 2007)
• A novel study linking prefrontal white matter loss with performance deficits in schizophrenia (Manoach et al, Neuroimage, 2007)
• The first report of a specific gene interaction affecting brain activity in patients with schizophrenia (Roffman et al, PNAS, 2008)
• The first study of fear inhibition in schizophrenia (Holt et al, Biological Psychiatry 2009)
• The first study of how context is used to build up meaning through language in schizophrenia (Kuperberg et al, Biological Psychiatry, 2008)
• A state-of-the-art event-related potential (ERP) study of cognitive abnormalities during comprehension of real-world behaviors In schizophrenia (Sitnikova et al, J Abn Psychology, 2009)
• The first demonstration of abnormalities in midline cortical function during self-referential thinking in schizophrenia (Holt et al, Biological Psychiatry, 2011)

Imaging Technology

At the Martinos Center, we apply some of the most sophisticated imaging technology currently in use to questions about the changes in the brain in schizophrenia:

• Functional MRI (fMRI), which measures the activity of the brain during specific types of thought or behaviors with excellent anatomical resolution: on the order of millimeters
• Event-related fMRI can measure brain activity during these thought processes with a temporal resolution of 1-2 seconds
• Event-related potentials (ERP), which detects cortical activity with high temporal resolution: on the order of milliseconds
• Magnetoencephalography (MEG), which has both high anatomical and temporal resolution and can be combined with fMRI measurements in multimodal imaging studies
• Automatic measurements of the volume and location of brain structures using advanced anatomical MRI analysis methods
• An ultra-high-field 7-tesla MRI scanner capable of detecting subtle abnormalities that are not detectable by conventional MRI
• Combined MRI/PET technology that can locate changes in the distribution of molecules, such as neurotransmitter receptors, with good anatomical precision
• Diffusion tensor imaging (DTI), which measures the integrity of fiber tracts that connect distinct brain regions to one another Near-infrared spectroscopy (NIRS), which is a highly practical method to examine cortical function in a variety of clinical settings

Group Members

• Dara Manoach, PhD
• Gina Kuperberg, MD, PhD
• Daphne Holt, MD, PhD
• Joshua Roffman, MD
• Tatiana Sitnikova, PhD

Research Projects

• The neural basis of delusions in schizophrenia: studies of emotional perception (Holt)
• Abnormal safety signaling in schizophrenia (Holt)
• Effects of folate and l-methylfolate supplementation on brain function during working memory (Roffman)
• Effects of folate-related genes on error processing (Manoach, Roffman)
• Genetic determinants of prefrontal dopamine signaling using PET-MRI (Roffman)
• A multimodal imaging study of language processing in healthy adults and schizophrenia (Kuperberg)
• Genetic contributions to brain function supporting adaptive goal-directed behavior (Sitnikova)
• A study of behavioral automation in schizophrenia (Manoach)
• A combined fMRI and MEG study of the neural basis of response monitoring (Manoach)

Major Areas of Research

The investigators of this lab, who have each received independent funding from the National Institutes of Mental Health (NIMH) and the National Alliance for Research on Depression and Schizophrenia (NARSAD) as well as other funding sources, have focused on the study of the neural basis of many of the symptoms, cognitive deficits and functional impairments associated with schizophrenia, including:

• Impairment in executive functions including performance monitoring and working memory (Dr. Manoach)
• Thought and language dysfunction (Dr. Kuperberg)
• Abnormalities in emotion and social cognition (Dr. Holt)
• Real world functioning and comprehension (Dr. Sitnikova)
• The influence of genes on brain activity related to negative symptoms and cognitive impairment (Dr. Roffman)