Conference Coverage of 54th Annual Meeting of the American Academy of Neurology
Rohit Bakshi, MD
Neuroimager and Associate Professor of Neurology, University at Buffalo, State University of New York, Buffalo, New York
The growing importance of neuroimaging was highlighted at many of the scientific sessions at the 54th Annual Meeting of the American Academy of Neurology. These included key presentations on the use of emerging imaging technologies such as functional magnetic resonance imaging (MRI), voxel-based morphometry, and MRI tissue segmentation. Investigators emphasized the role of these techniques in studying healthy and disease states.
Multiple sclerosis (MS) has been recognized as not simply a disease of inflammation and demyelination in the brain and spinal cord. Recent data from MRI and pathologic studies have shown that axonal loss and atrophy are common, occur early in the disease process, and are closely related to irreversible functional neurologic and neurobehavioral impairments.[1,2] Several methods have recently been applied to the quantitative assessment of whole brain atrophy from MRI scans. However, few data are available on the quantification of regional brain atrophy, which is likely to be more important than global atrophy in determining the functional effect of axonal loss and neurodegeneration in MS.
Locatelli and colleagues used brain MRI to study 45 patients with relapsing-remitting MS. The regional brain parenchymal volumes (RBPV) of the frontal lobes and pons were obtained by a semiautomated and automated segmentation process on a computer workstation using customized software. To correct for intersubject differences in head size, the normalized regional brain parenchymal fraction (RBPF) was calculated as the ratio of RBPV to the total parenchymal and cerebrospinal fluid (CSF) (the outer contour of the total brain surface). To assess relative atrophy in particular regions as compared with the brain as a whole, the total fractional regional brain volume (TFRBV) was obtained. The technique showed excellent reproducibility. RBPF and TFRBV showed stronger correlations with quantitative MRI lesion measures compared with the RBPV, with the strongest correlations seen between TFRBV and lesion loads.
This study introduces a new method of assessing regional brain atrophy in MS patients and shows the importance of normalization of volumetric data. Further studies are needed to test the longitudinal sensitivity, specificity, and predictive value of this regional atrophy technique. It will be of interest in particular to determine whether regional lobar atrophy is associated with cognitive impairment, which is common in MS.
Functional MRI (fMRI)
Overview of fMRI
MRI can localize brain activity during activation associated with cognitive, motor, and sensory tasks. The most widely used method detects regional tissue changes in venous oxygenation. This technique is known as blood oxygen level dependent (BOLD) imaging or fMRI. This requires a significant increase in blood flow and blood oxygenation during cortical activation. Functional MRI has opened a new window on the circuitry and activation sites in a variety of normal and disease states and is key to mapping the human brain.
Motivation and Reward
The prefrontal cortex plays a key role in higher cognitive function and distinguishes humans from other mammals. The dorsolateral prefrontal cortex controls working memory while the ventral medial prefrontal cortex is associated with motivation and awareness of rewards that result from behaviors. There is a poor understanding of how cognitive and motivational systems are linked such that actions are planned and executed in a logical way.
Levy and colleagues used fMRI in 6 healthy subjects who performed working memory tasks (the "n-back" tasks) leading to monetary reward. Working memory tasks activated the posterior parietal (Brodmann area [BA] 7), lateral premotor (BA 6), and dorsolateral prefrontal (BA 9/46) cortical areas. Reward led to activation in the same areas associated with working memory and, in a supplementary region, the medial frontal pole (BA 10). With an increase in cognitive demand and increase in reward (more challenging task but higher monetary reward), there was deactivation of the ventral frontal (BA 11/47) and subgenual prefrontal (BA 25) cortices.
These are interesting and novel results providing insight into prefrontal circuitry as it relates to human behavior. Reward seems to reinforce activation in the working memory network. The medial frontal pole may play an important role in monitoring the likelihood and level of reward associated with cognitive tasks. Emotional gating through deactivation of the paralimbic and limbic systems may inhibit adverse emotional signals to optimize cognitive performance. Thus, higher cognitive processing seems to involve a balance between activation in higher cortical areas and deactivation in primitive structures. This line of research is key in mapping the complexity of the human brain to develop a better understanding of the abnormal neuropsychological states such as impulsivity, personality disorders, and criminality, that wield a powerful effect on humanity.
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