Secondary brain changes following lesions: a new paradigm for lesion experimentation.

The surgically-induced lesion has traditionally been used to study the localization of functions in the brain. The basic tenets for its use are that (1) functions are represented in discrete brain structures such as nuclei and fiber tracts and that (2) lesions disrupt function by removal of functional tissue in circumscribed sites in the brain. Contrary to this traditional view, there is growing evidence that the secondary changes in the brain which are induced by a lesion, both directly (necrosis, anterograde and retrograde degeneration) and indirectly (transneuronal degeneration, regeneration and sprouting, denervation supersensitivity, alteration of neurochemical pools, vascular disruption, diaschisis), may comprise the more significant neurological changes which can account for alteration of behavior in a lesion experiment. This evidence is reviewed and a new strategy of research utilizing lesions is proposed, suggesting that greater emphasis be placed on the a posteriori assessment of secondary changes in the brain as they are correlated with changes in behavior. The implications of such considerations for establishing brain-behavior relationships are discussed.