Introduction

Until the advent of technology for direct imaging of localized anatomically specific brain function became available in the 1970s, the clinico-pathologic correlation method of Charcot and his contemporaries, whereby CNS lesions on autopsy were correlated with behavioral deficits in life, formed the gold standard of clinical neurology. To this day, if a neurologist claims that a patient's behavioral deficit arises from a focal lesion, and if there is dispute over that claim, only an autopsy can settle the issue with satisfactory certainty. Structural imaging by computed tomography (CT) and especially by magnetic resonance imaging (MRI), of course, has become a widely acceptable substitute for the autopsy. It is nonetheless also widely accepted (and vigorously asserted whenever a lesion that is proposed to explain a patient's deficit is not visualized on MRI) that some “true” lesions can be invisible by MRI and hence will only “show up” on autopsy. Against this, technological advances mean that demonstration of a structural lesion by imaging or at autopsy may no longer be essential, as it is possible to show dysfunction of a brain region(s). A lesion might certainly still be implied, but the range of possible lesions could be much broader, to include subtler derangements of functional anatomy on levels of scale as small as the synapse itself, where the abnormality would only express itself when large aggregates of these synapses, or their associated neurons, functioned deviantly (thus making themselves visible to functional imaging).