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A quarter-century of progress

Yale Medicine Magazine, 2003 - Summer



Robert Shulman joins faculty

Robert G. Shulman, Ph.D., who had pioneered usage of nuclear magnetic resonance spectroscopy (MRS) in combination with carbon isotopes to follow cellular metabolic pathways, joins Yale’s Department of Molecular Biology and Biophysics from Bell Labs.


MRS brain studies

The first proton and carbon MRS studies of the brain are performed at Yale, demonstrating the technology’s potential to explore brain metabolism.


MRC opens

With its first magnet for human subjects, the School of Medicine opens the Magnetic Resonance Center (MRC) in Fitkin Memorial Pavilion basement. Shulman directs the research portion and Richard H. Greenspan, M.D., chair of diagnostic radiology, directs the clinical portion. The MRC’s two original magnets are still in use.


MRI group formed

Diagnostic radiology faculty launch research program aimed at the development of new approaches to magnetic resonance imaging (MRI) and improving the understanding of contrast mechanisms in MRI.


Crossing to humans

The first MRS spectra of glutamate in the human brain demonstrate that information similar to that gleaned from previous animal studies could be obtained from the human brain.


Glycogen synthesis in diabetes

MRS studies show that metabolic impairment of muscle glycogen synthesis leads to elevated post-meal blood glucose in non-insulin-dependent type 2 diabetes. This is first use of MRS (and of noninvasive imaging in general) to establish a fundamental mechanism in the etiology of a disease, and it paves the way to many pioneering studies of mechanisms of diabetes.


MR for brain function

Lactate, a substance sensitive to increased activity in the human brain, is shown to increase during visual stimulation. This first use of MR (imaging or spectroscopy) to study brain function leads to a major application of MRS and MRI in use today.


Cognitive fMRI

For the first time, functional MRI (fMRI) is proven able to measure single, brief, mental events without averaging across many seconds. The paradigm is now considered standard in many fMRI applications.


Measurement of GABA

Spectral editing in humans is developed and then used to demonstrate that MRS can measure the neurotransmitter gamma amino butyric acid (GABA). This opens the way to study alterations in GABA metabolism in neurological and psychiatric disease, starting with the observation that the mechanism of action of several anti-epileptic drugs is through elevation of cellular GABA.


Sex differences in brain

fMRI reveals that women and men use different brain regions to process language. Results demonstrate more bilateral activation in women during word processing compared to generally left-brain activity in men. Research provides direct evidence that helps to explain why women are less likely to lose language capabilities after strokes.

Functional localization verified

Studies validate the emerging method of fMRI by demonstrating that areas found to activate in fMRI are representative of true functional areas. Results also demonstrate many additional systems involved in complex cognitive processing.


Etiology of epilepsy

MRS is used to show that cellular GABA levels are low in epileptic patients with poor seizure control. This and subsequent studies have established low cellular GABA levels as a significant mechanism leading to cortical hyperexcitability in epilepsy.


Reading and brain activity

Phonological effects are linked to printed-word identification and reading performance. Many studies in fMRI now equate brain activity with subject performance.


Glutamate/glutamine cycle

First measurements of the glutamate/ glutamine cycle, a direct measure of excitatory neurotransmission, are made in awake human subjects and show high rates. Results overturn the existing paradigm that the awake brain has minimal neuronal activity while resting. Findings suggest that, rather than waiting to be ‘turned on,’ the brain is constantly functioning in anticipation of stimuli.

GABA and psychiatric disorders

MRS data show that GABA metabolism is altered in depression. Subsequent studies show alterations in panic disorder, premenstrual dysphoric syndrome and alcoholism. Findings lead to a new appreciation of the importance of inhibitory neurotransmission and amino acid metabolism in psychiatric disease.


Higher-order processing

Higher-order executive-processing regions in the brain are revealed for the first time, using fMRI, when subjects are asked to perform a dual task which requires focusing on some stimuli while ignoring others.


Functional reorganization in brain

Studies demonstrate cases of true functional plasticity in the adult brain and characterize the reorganization observed as a function of a specific type of brain lesion (epilepsy, tumor, arterial venous malformation).

Bioengineering research partnership

A large NIH-funded project combines state-of-the-art imaging resources, research development and computer vision to improve treatment planning and understanding of epilepsy.


Neurophysiological basis of fMRI

Quantitative fMRI methods are developed to map regional brain energetics directly. Further study shows that regional brain energy metabolism increases proportionately with neuronal firing during sensory stimulation in animal models, providing the first direct link between the imaging signal and electrical activity and opening up the possibility of using MRI to image brain function directly.

Differential processing of faces

Research demonstrates that autistic patients’ brains show similar activation patterns when processing pictures of objects and pictures of faces. Nonautistic control subjects activate a face-specific cortical region distinct from the object region when shown the same pictures.

Low birth weight and language

First study demonstrating not only structural but also functional differences between very-low-birth-weight infants and full-term infants.

A new home

The MRRC moves to a two-story, state-of-the-art facility in the new Anlyan Center for Medical Research and Education, uniting the MRS and MRI groups into one comprehensive center for magnetic resonance research.

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