In the course of brain development, very complex processes take place to establish an intricate and highly specific network of millions of cells interconnected by billions of dendritic arborizations and synapses. The complexity of this process and of the end-result is daunting. Therefore, it is reasonable to assume that once development is completed, the brain might be resilient to change. This notion of a rather static and unchanging brain has been the pervasive belief for many years. However, in recent years it has become increasingly clear that this notion is wrong. The brain does not only undergo reorganization, but it is in fact constantly reorganizing throughout life (Fuster, 1995; Kaas, 1997; 2000).

This capacity of the brain to change is referred to as 'plasticity'. It represents an intrinsic property of the human nervous system that persists throughout the human lifespan. The nervous system is constantly reorganizing in response to changes in the afferent input of any particular neural system or changes in the targets of its efferent connections. These changes might be demonstrable at the level of behavior, anatomy and physiology, and down to the cellular and molecular levels. However, changes at one level do not predict nor do they necessarily imply changes at all other levels.

An obvious benefit of the central nervous system's capacity of change is the acquisition of new skills. In the process of learning, the brain has to change to be able to code for, and appropriately implement the new knowledge. Neuroimaging studies have found decreases, increases, and shifts in activations as consequences of practice, priming, proficient learning and overlearning with automatization (Poldrack, 2000; van Mier, 2000).

Plastic changes are also induced by a large number of pathological conditions, including injury to central and peripheral nervous system (Chollet, 2000; Kaas, 2000). In this setting, plasticity may well represent the mechanisms by which recovery of function after the injury is possible, though this is far from established (Chollet and Weiller, 2000). However, reorganization does not necessarily mean recovery of function. In other words, plasticity at the neural level does not speak to the question of behavioral change and certainly does not imply necessarily functional recovery or even functional change. It is reasonable to assume that plasticity is a characteristic of the nervous system that evolved for coping with changes in the environment associated with learning and development and that is then 'co-opted' as a response to brain injury.

Therefore, plasticity does not necessarily have to be beneficial for the subjects. Indeed, plastic changes might result in a behavioral gain or loss for a given subject and may underlay the development of symptoms in a given disease. The concept of "maladaptive plasticity" was introduced to capture the idea of potentially functionally undesirable consequences of plasticity. However, we might be better served discarding the concept of an obligatory link between plasticity and adaptation and focusing on the separation between brain changes and behavioral desirability.

There are a number of mechanisms for plasticity in humans that can be studied at different levels, ranging from systems physiology all the way down to cellular and molecular levels. Thus far, our understanding of these mechanisms remains incomplete. Expansion of a specialized cortical area or recruitment of a remote area as a result of learning, brain disease or injury comprises the two most characteristic forms of brain plasticity at a systems level. The underlying general phenomenon is that neurons in one area assume properties of neurons in an adjacent or remote area. Such remodeling might take place within the cortex but could also implicate related subcortical levels. Similarly, remodeling can take place across brain areas within a given modality, for example within visual, tactile or motor systems (homotypic or intramodal plasticity), or may bridge across modalities (heterotypic or cross-modal plasticity), as in the case of tactile information processing in the occipital ('visual') cortex in the blind (Kujala et al 2000; Hamilton and Pascual-Leone, 1998). The time course of plasticity is extended, with some changes appearing within seconds of the initial event and continuing many years after an intervention or injury.

A series of principles of plasticity can be put together. First, changes in the balance between excitatory and inhibitory influences can take place in established connectivity. This process is commonly known as "unmasking". Second, existing synapses can be modulated, strengthening or weakening their influence on their target neurons. Processes such as long-term potentiation (LTP), or long-term depression (LTD), are examples of such mechanisms. Third, neuronal membrane excitability may be changed by a variety of different mechanisms, which have been shown with the use of cell and patch clamp techniques and implicate the function of calcium and sodium channels, calcium-dependent potassium channels and other potassium channels, as well as different neurotransmitters and genes affecting the function of cell membrane components. Fourth, there can be true anatomical change with axonal and dendritic sprouting and the establishment of new synaptic connections. Finally, there is the possibility that new neurons might be generated or mature that can then be incorporated into preexisting networks. This possibility has generated a great deal of excitement lately but the data are as yet inconclusive and there are both supporters and detractors of the idea that new neurons are generated in the cerebral cortex of the mature human brain, which can establish functionally relevant connectivity.

We have discussed that plasticity is an intrinsic property of the human nervous system with changes in neuronal circuits occurring for many different reasons throughout life and being part of the normal physiologic range of life. Such changes can be implemented by a variety of mechanisms, some fast, in the range of seconds while others occur over years of normal development or rehabilitation. A variety of techniques can be used to probe all of these forms of plasticity in humans. These methods include functional brain imaging, such as positron emission tomography or functional magnetic resonance imaging, evoked potentials, magnetoencephalography, or transcranial magnetic stimulation. Plasticity does not obligatorily lead to a functional gain for a given subject. Indeed, plastic changes account for adaptation to disease as well as for their pathogenesis and symptomatology. The challenge that we face is not one of "activating" plasticity, but rather one of modulating it, enhancing certain plastic processes and suppressing others to achieve the most beneficial outcome for each subject.

• Chollet F. Plasticity of the Adult Human Brain. In: Mazziotta JC, Toga AW and Frackowiak RS, editors. Brain Mapping: The Systems. San Diego: Academic Press, 2000: 621-638.
• Chollet F, Weiller C. Recovery of Neurological Function. In: Mazziotta JC, Toga AW and Frackowiak RS, editors. Brain Mapping: The Disorders. San Diego: Academic Press, 2000: 587-597.
• Fuster JM. Memory in the cerebral cortex. An empirical approach to neural networks in the human and nonhuman primate. Cambridge, Mass.: The MIT press, 1995.
• Hamilton R, Pascual-Leone A. Cortical plasticity associated with Braille learning. Trends Cognitive Sciences 1998; 2: 168-174.
• Kaas JH, editor. Functional Plasticity in Adult Cortex. Vol 9. Orlando, FL: Academic Press, 1997.
• Kaas JH. The reorganization of somatosensory and motor cortex after peripheral nerve or spinal cord injury in primates. Prog Brain Res 2000; 128: 173-9.
• Kujala T, Alho K, Naatanen R. Cross-modal reorganization of human cortical functions. Trends Neurosci 2000; 23: 115-20.
• Pascual-Leone A. The Brain that Plays Music and is Changed by It. In: Zatorre R and Peretz I, editors. Music and the Brain. New York: New York Academy of Sciences, 2001.
• Pascual-Leone A, Nguyet D, Cohen LG, Brasil-Neto JP, Cammarota A, Hallett M. Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills. J Neurophysiol 1995; 74: 1037-1045.
• Poldrack RA. Imaging brain plasticity: conceptual and methodological issues--a theoretical review. Neuroimage 2000; 12: 1-13.
• Pujol J, Roset-Llobet J, Rosines-Cubells D, Deus J, Naberhaus B, Valls-Solé J, et al. Brain cortical activation during guitar-induced hand dystonia studied by functional MRI. Neuroimage 2000; 12: 257-267.
• van Mier H. Human Learning. In: Mazziotta JC, Toga AW and Frackowiak RS, editors. Brain Mapping: The Systems. San Diego: Academic Press, 2000: 605-620.