Functional Magnetic Resonance Imaging and Brain Morphometry in the Dartmouth Brain Imaging LaboratoryFunctional MRI (fMRI) is a noninvasive technology that uses local changes in blood oxygenation to map brain activity. Morphometry is the study of structural aspects of the brain such as volume, 3D shape features, density of grey matter, and thickness of the cortex. Our research program is a collaborative, multidisciplinary effort, with investigators from Psychiatry, Radiology, Neurology, Genetics, Neurosurgery and other departments at Dartmouth Medical School and Dartmouth College; as well as external collaborators.Our clinical and research program has five major goals:Clinical Neuroscience Research – Apply advanced functional and anatomic imaging technology to better understand brain disorders and their mechanisms, with the ultimate aim of enhancing diagnostic assessment, treatment planning and outcome measurement.
Study Normal Human Brain Function – Further the understanding of normal brain function from a developmental life-span perspective including sources of variability among individuals.
Neurogenetics – Investigate the relationship between relevant genetic polymorphisms and brain structure and function in health and illness.
Advanced Education and Training – Provide training and experience in functional and morphometric neuroimaging research and clinical neuropsychology for new, highly motivated neuroscientists.
Technical Development – Develop, assess and validate emerging technologies that optimize the use of fMRI, including stimulus delivery systems and image processing strategies.
Facilities for fMRI at DHMC include the Neuroimaging Research Center at the Advanced Imaging Center at Dartmouth, which houses a research dedicated 3T Philips MRI system; the Brain Imaging Laboratory located in the Department of Psychiatry at DHMC; and several 1.5T GE MRI units in Diagnostic Radiology.
An integrated program of sponsored neuroimaging and neuropsychological research investigates a range of psychiatric, neurological, and neuropsychiatric disorders. Our program emphasizes disorders affecting memory, attention, and executive functions. Sponsored research at the BIL includes studies of preclinical Alzheimer’s disease, traumatic brain injury, schizophrenia, multiple sclerosis, obsessive-compulsive disorder, bipolar affective disorder, substance use disorders, and Parkinson’s disease. Parallel work examines the normal brain circuitry that underlies cognitive function in healthy volunteers.
An important goal of the Dartmouth Brain Imaging Laboratory has been training young scientists in neuropsychological, neuroimaging and computational techniques. The two year postdoctoral fellowship program in Clinical Neuropsychology and Neuroimaging Research developed at Dartmouth was the first in the country to graduate clinical neuroscientists with combined formal training in both areas. Psychology interns, medical students, residents in Neurology and Psychiatry, and undergraduates from pre-medical and science programs have participated in research projects.
Highlights from Recent Published Research by the Brain Imaging Laboratory include:
Traumatic Brain Injury (TBI). The TBI team, led by Thomas McAllister, MD, published the first controlled study using fMRI to examine brain activation patterns during working memory after mild TBI. These results suggest that, in the absence of visible structural abnormalities, there are physiological activation differences during working memory. One of our goals is to study whether such differences occur in all people with traumatic brain injury, or in only some people depending on the severity of the injury and factors such as genetic risk. Two ongoing grants are using fMRI to evaluate neuropharmacological treatment of TBI-induced memory problems by stimulating dopamine and adrenergic pathways. Other studies are investigating whether an attention and memory training program can improve cognitive abnormalities as seen on fMRI in patients with TBI.
Psychiatric Disorders. The BIL Psychiatric Research team, led by Laura Flashman, PhD-ABPP/CN and Robert M. Roth, Ph.D., have been conducting studies on schizophrenia, bipolar disorder, as well as adult and pediatric OCD. Studies of schizophrenia include investigations into the neural substrates of unawareness of illness, apathy, and episodic memory and executive deficits, as well as studies, conducted in collaboration with Alan Green, MD (Chair of Psychiatry), have been looking at brain reward circuitry in patients with schizophrenia having a co-occurring substance use disorder. Other investigations have been using neuroimaging to elucidate the neural substrates of executive control in patients with OCD and those with bipolar disorder.
Multiple Sclerosis.The MS team, led by Heather Wishart, PhD, used fMRI and MRI-based lesion analysis to examine brain reorganization of motor and memory systems in response to “lesion load” in MS. (MS involves distributed plaques in the brain, and “lesion load” or “burden” refers to the total volume of brain tissue classified as plaques.) She found that the brain’s neural circuitry reprograms or adapts in response to the injury from the lesion. In collaboration with the Multiple Sclerosis Center at Dartmouth, we are also using MRI to quantify how some novel immunomodulating medications for MS affect lesion burden and brain activation patterns.
Mild Cognitive Impairment and Alzheimer’s Disease. The Dartmouth Aging Study produced the first fMRI findings on memory in AD and the relation of fMRI changes to atrophy. Other studies have used fMRI to measure medication effects suggesting that cholinergic enhancement boosts frontal lobe function during working memory in patients with MCI. Our team has also been studying healthy elderly with normal cognitive functioning on formal testing, but who subjectively report significant cognitive problems (Cognitive Complaint group or CCs as we call them). We have recently shown that CCs show loss of grey matter density in similar regions to patients with MCI, in a degree that is intermediate between MCI and healthy elderly without cognitive complaints. One aim of our research is to determine if such functional enhancements in Alzheimer’s patients (expanded regions of activation, and enhanced frontal lobe function) have temporary or longer lasting effects, and whether genetic risk factors can predict outcomes.
Neurogenetics. Recent research in the BIL has demonstrated that polymorphisms of the APOE gene are associated with changes in grey matter density and brain activation patterns during working memory task performance in healthy adults. Other work has shown that polymorphism of a dopamine gene impacts on sustained attention in adults with TBI. Ongoing studies are investigating polymorphisms in genes related to neurotransmitter systems and genes involved in brain repair, and their impact on neuropsychological functioning, brain morphology, and brain activation in healthy adults and patient populations of interest.