One of the most exciting and dramatic observations to come from human brain mapping with a wide range of structural and functional techniques has been the dynamic plasticity of function in both normal brains and the brains of patients with neurological and neuropsychiatric disorders. Brain maps must therefore be viewed as dynamic, changing with development, disease progression, and normal learning and in the recovery of function after acute injury. The dynamic plasticity of functional brain maps provides an exiting opportunity to study these processes. It also means that the use of brain maps must take into account such variability in the design of brain mapping studies for patients with cerebral disorders.

For example, just as structural and functional studies must be normalized for spatial variability in the population, disease-based maps must be normalized in time to account for dynamic changes that occur with progression. Thus, a comparison of patients with Alzheimer's disease or other neurodegenerative disease should be stratified by time of onset or other variables that take into account the pattern of changing functional maps. The same is true after an acute brain injury, such as trauma or cerebral infarction. The complex interaction and highly variable changes in blood flow, blood volume, water diffusion, oxygen, and glucose extraction and metabolism will all be more appropriately interpreted if they are stratified by time from onset of cerebral injury. So too will plastic changes associated with recovery and reorganization after irreversible damage. Compensatory properties of the human nervous system have been clearly demonstrated in studies of patients following stroke who recover motor function (Fig. 14). The study of drug-induced, behaviorally associated and surgically promoted plasticity will, we predict, be an important part of brain mapping in the study of patients with neurological, neurosurgical, and psychiatric disorders.

The value of imaging data depends on an appreciation of the changing landscape of functional patterns.

Figure 14 Compensatory reorganization of the brain after acute injury induced by cerebral infarction. (A) Normal response of a group of control subjects performing a motor task with the right upper extremity. Relative increases in cerebral blood flow derived from PET measurements demonstrating increased perfusion in the contralateral hand area of the motor cortex and the ipsilateral cerebellum. (B) The same motor task and methods were applied to a group of patients who had small subcortical cerebral infarctions associated with upper extremity paresis, all of whom recovered in the days to week following the acute ischemic injury. Note that when these subjects perform the same task, not only are there responses in the expected areas previously identified in the normal controls—that is, the contralateral hand area of the motor cortex and ipsilateral cerebellum—but also there are relative increases in cerebral blood flow in the ipsilateral hand area of the motor cortex and the contralateral cerebellum. Such studies provide useful insights into how the brain reorganizes following acute injury and can also be used to study compensation in more chronic states such as might be encountered in neurodegenerative disorders. These types of insights may be useful for designing more efficient, effective, and timely neurorehabilitation protocols employing behavioral, pharmacolo-gic, or, potentially, surgical interventions for the restoration of function or its maintenance following acute or, chronic injury to the brain [courtesy of Francois Chollet and colleagues, Toulouse, France. From Chollet et al. (1991). Ann. Neurol. 29, 63-71].

This is particularly true for techniques that make relative measurements. For example, relative cerebral blood flow measurements obtained with fMRI, SPECT, or PET may be misleading in patients with large cerebral infarctions. The evaluation of motor reorganization after cerebral infarction in a patient or group of patients must take into account a variable cerebral blood flow baseline in the setting of hemody-namically unstable tissue. Cerebral blood flow may be very low acutely, rise dramatically soon thereafter, and then reach some stable new level days, weeks, or months later. Currently, it is uncertain how increments or decrements in blood flow associated with neuronal firing changes that are task induced will behave under these different conditions of baseline blood flow. Is it valid to compare motor task activation in a cortical region when the "resting state'' blood flow is altered from the normal value by 50-200%? Are there ceiling or floor effects in these responses? These issues need to be addressed before a proper interpretation of scans from such patients will be possible.

We predict that the ability to image plastic reorganization, both in normal and in pathologic states, will provide new insights, previously unavailable, about the constant reorganization of the human brain. Such information will be valuable in the design of behavioral, surgical, and pharmacological interventions in patients that facilitate and maximize the efficiency of the natural recovery processes. The imaging techniques should also provide a means to evaluate specific rehabilitation interventions, to determine their appropriateness, effectiveness, and timing, and to select patients for them. These abilities are currently lacking because the necessary information about the variables discussed has not been previously available.

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