Neuroplasticity

Definition:

The adaptive capacities of the brain; its ability to modify its own structure, e.g., organization and functioning.

The brain’s ability to act and react in ever-changing ways.

Introduction:

This special characteristic allows the brain’s estimated 100 billion nerve cells “gray matter” to constantly lay down new pathways for neural communication and to rearrange existing ones throughout life, thereby aiding the processes of learning, memory, and adaptation through experience. The neuroplasticity is the result of many different, complex processes that occur in our brains throughout our lifetime.

Without the ability to make such functional changes, our brains would not be able to memorize a new fact or master a new skill, form a new memory or adjust to a new environment; we, as individuals, would not be able to recover from brain injuries or overcome cognitive disabilities.

There is generally at least some recovery after the brain is damaged. Various mechanisms contribute to early and late reorganization of the brain. Much of the recovery, which is maximized by appropriate rehabilitation, occurs within months of the damage, but functional gains can be obtained even many years after the damage has occurred.

The degree of recovery depends on many factors, including age, the brain area and amount of tissue damaged, the rapidity of the damage, the brain's mechanisms of functional reorganization, and environmental and psychosocial factors.

If recov­ery is not expected or sought with the active participa­tion of the disabled person, little recovery is obtained.

Genetic and environmental factors:

While genetics certainly play a role in establishing the brain’s plasticity, the environment also exerts heavy influence in maintaining it.

For example, the newborn’s brain, which every day is flooded with new information. When the infant body receives input through its many different sensory organs, neurons are responsible for sending that input back to the part of the brain best equipped to handle it – and this requires each neuron to “know” something about the proper neural pathways through which to send its bits and pieces of information. To make this mental roadmap work, each neuron develops an axon to send information to other brain cells via electrical impulses, and also develops many dendrites that connect it to other neurons so that it can receive information from them. Each point of connection between two neurons is termed a “synapse.”

Our genes have, at birth, laid down the basic directions for neurons to follow along this roadmap, and have built its major “highways” between the basic functional areas of the brain. Environmental influence then plays the key role in forging a much denser, more complex network of interconnections. These smaller avenues and side roads, always under construction, can make the transfer of information between neurons more efficient and rich with situation-specific detail.

This is clearly evidenced by the rapid increase in synaptic density that can be seen in a normally developing human.

Genetics form a neural framework that, at birth, starts each neuron off with roughly 2,500 connections. By age two or three, however, sensory stimulation and environmental experience have taken full advantage of the brain’s plasticity; each neuron now boasts around 15,000 synapses. This number will have declined somewhat by the time we enter adulthood, as many of the more ineffective or rarely used connections – formed during the early years, when neuroplasticity is at its peak -- are done away with.

 

Neuroplasticity can work in two directions; it is responsible for deleting old connections as frequently as it enables the creation of new ones. Through this process, called “synaptic pruning,” connections that are inefficient or infrequently used are allowed to fade away, while neurons that are highly routed with information will be preserved, strengthened, made even more synaptically dense.

 

Four major patterns of plasticity that seem to work best in different situations:

  1. Functional map expansion: healthy cells surrounding an injured area of the brain change their function, even their shape, so as to perform the tasks and transfer the signals previously dealt with by the now-damaged neurons at the site of injury. results in changes to the amount of brain surface area dedicated to sending and receiving signals from some specific part of the body.
  2. Compensatory masquerade: Brain cells can reorganize existing synaptic pathways; this form of plasticity allows already-constructed pathways that neighbor a damaged area to respond to changes in the body’s demands caused by lost function in some other area.
  3. Homologous region adoption: allows one entire brain area to take over functions from another distant brain area (one not immediately neighboring the compensatory area, as in functional map expansion) that has been damaged.
  4. Cross model reassignment: allows one type of sensory input to entirely replace another damaged one. Cross-model reassignment allows the brain of a blind individual, in learning to read Braille, to rewire the sense of touch so that it replaces the responsibilities of vision in the brain areas linked with reading.

 

Current research suggests that neuroplasticity may be key to the development of many new and more effective treatments for brain damage, whether resulting from traumatic injury, stroke, age-related cognitive decline, or any number of degenerative diseases (Alzheimer’s, Parkinson’s, and cerebral palsy, among many others). Plasticity also offers hope to people suffering from cognitive disabilities such as ADHD, dyslexia, and Down Syndrome; it may possibly lead to breakthroughs With “directed neuroplasticity,” scientists and clinicians can deliver calculated sequences of input, and/or specific repetitive patterns of stimulation, to cause desirable and specific changes in the brain. Thus, increasing our understanding of neuroplasticity holds great promise – through its complex workings – skills lost can be relearned; the decline of abilities can be staved off, even reversed; and entirely new functions can even, perhaps, be gained.

 

The brain can reorganize on the basis of the structures that remain after brain damage, possibly mobilizing mechanisms such as unmasking of previously present but relatively "weak" neural paths, neuronal sprout­ing, and the up- and downregulation of receptors at synaptic and nonsynaptic sites.

Both human and animal studies have demonstrated mechanisms of brain plasticity and the reorganization of function following brain damage. The adult brain can reorganize itself in areas that were long thought to be completely 'hardwired'.

 

The neurosciences have been influenced primarily by concepts of:

  • Strict localization of function in the brain
  • The synapse as the only important means of cell-to-cell commu­nication
  • The irreversibility (beyond a certain period of time) of functional deficits produced by brain damage.
  • The functional results of ablating some area of cortex, or of eliminating some sensory input, have been interpreted as meaning that that particular part of the cortex is essential for a particular function, or that particular sensory input is required during a particular developmental stage for a particular function to develop.

 

Although brain plasticity is generally positive for recovery, some negative effects, such as:

  1. The develop­ment of spasticity and kindling causing epilepsy can occur.
  2. Furthermore, the presence of mechanisms for plasticity does not automatically lead to recovery of function; appropriate rehabilitation and the appro­priate physical and psychosocial environments can play decisive roles in the reorganization.

 

Rehabilitation and the developmental learning process have some aspects in common. Both include important elements of inhibition in regard to selective function and precisely coordinated movements. For example, a child learning to write initially demon­strates electromyographic activity in virtually all the muscles related to the hand. As ability increases, muscle activity decreases progressively until there is a minimum of activity, which is coordinated precisely to produce just the muscle action necessary for writing. It then becomes virtually fatigue-free.

 

Following brain damage, coordinated movements are often disturbed. Patients become fatigued when attempting controlled movements; rehabilitation is then oriented toward the restoration of precise, fatigue-free movements.

 

Postulated Mechanisms of Neuroplasticity (Reorganization of Function)

Many mechanisms intervene in the reorganization following damage to the brain.

In the first stages, it is likely that surviving cells that have been totally or partially denervated may have one or more of three responses:

  • The "strengthening" of synapses from secondary connections (unmasking).
  • The development of extrasynaptic receptors on the mem­brane of the surviving cells, which respond by means of nonsynaptic diffusion neurotransmission (NDN) me­
  • Receptor development related to the new synapses formed by the sprouting of processes from surviving cells.

The contributions of stem cells and neurogenesis have yet to be evaluated, but exciting recent findings open the possibility that they may contribute to functional recovery.

Some mechanisms of brain reorganization are briefly discussed. Some may be active in both early and late reorganization.

 

  1. Multiplexing and Unmasking:

Multiplexing in the brain consists of the multiple uses of neurons and fibers so that they participate in various functions. Many studies have demonstrated multiple sensory and motor representations of a single brain.

The role of unmasking may be of considerable importance in functional reorganization. A series of studies have demonstrated the unmasking of normally ineffective connections that may become active if the dominant inputs are put out of action.

In one study, peripheral nerves were cut, removing the normal sensory input to a population of spinal cord cells, without anatomical evidence of degeneration or va­cated synaptic sites. Large numbers of cells in a region of the cord that were normally dominated by afferents from the foot and toes began to respond to other areas of the leg days or weeks after section of the peripheral axons that previously supplied their excitatory drive.

The unmasking-related reorganization can be prac­tically instantaneous:

During temporary altered sen­sory input, the injection of local anesthetic into the receptive fields of neurons of the dorsal column neurons uncovered new receptor fields that emerged within minutes, probably due to the unmasking of previously ineffective inputs.

Another of the important studies of unmasking demonstrated cortical plasticity related to training:

Both blind and sighted persons reading Braille had expanded sensorimotor cortical representation of the reading finger, and cortical representation is affected by learning to play the piano. One of the most dramatic examples showed that after limited sensory deafferentation in adult primates, somatosensory cortical maps reorganize, over a period of years, over distances previously thought to be impossible (more than 1 cm).

Interesting direct evidence for the unmasking of pathways:

A study of monkeys that had spent the first year of life with the eyelids sutured. Microelectrode studies of cells in area 19 revealed that 20% of the cells responded to somesthetic stimuli, whereas in the normal monkey no somesthetic responses are recorded.

It had pre­viously been shown that almost half of the visual cortical cells that responded to visual stimuli also responded to auditory and/or pinprick stimuli, but these nonvisual responses had considerably longer latencies and were easily blocked.

In blind persons, the visual cortex is metabolically very active in response to auditory and tactile stimuli, such activity may repre­sent the unmasking of nonvisual inputs to the visual cortex.

Comparable changes may occur following brain damage:

A specific human case of recovered function has been interpreted in the context of unmasking: Following brain damage, the unmasking activated previously existent pathways that (previous to the injury) had not had the same relationship to the function. The extensive damage included the destruc­tion of a pyramidal tract that, at autopsy 7 years after the stroke, was composed of scar tissue except for approximately 3% of normal appearing fibers scat­tered through the scar tissue. The recovery was interpreted in terms of the possible unmasking of pathways to the dendrites of the cells with long pyramidal tract fibers and their axonal ramifications. It is possible that connections to large numbers of motor neurons that had previously been relatively inactive were rendered active, possibly in part due to postinjury receptor plasticity in those motor neurons.

 

  1. Nonsynaptic Diffusion Neurotransmission (NDN) and Receptor Plasticity:

A postulated example of this class of responses is the dopamine receptor upregulation that had been de­monstrated in human stroke patients following the destruction of dopamine pathways (and the synaptic and nonsynaptic dopamine release sites).

Upregula­tion of receptors may have occurred on the extra-synaptic membrane (comparable to the response noted on denervated muscle fibers) following the loss of those dopamine release sites. This may have led to super-sensitivity to the neurotransmitters in the extracellular fluid, with activation by nonsynaptic transmission.

Information in the brain appears to be transmitted both by synaptic connectivity and by NDN.

NDN includes the diffusion through the extracellular fluid of neurotransmitters released at points that may be remote from the target cells, with the resulting activation of extrasynaptic receptors.

The existence of many receptor subtypes offers the possibility of selective neurotransmission at a distance by NDN.

Individual movements or functions, such as playing the piano or watching a tennis game, require great selectivity, rapid initiation, and rapid ending; for such functions, synaptic action is essential. However, for mass sustained functions (e.g., sleep, mood, and hunger), sustained, widespread activity (rather than speed and selectivity) is required, which may be largely mediated by NDN.

Many functions may be produced by combinations of both types of neurotransmission. For example regarding piano playing, in addition to the relevant synaptic mechanisms, the finger move­ments can be more precise in the presence of adequate preparation including changes in brain tone (probably mediated by noradrenaline). Also, the visual percep­tion of the tennis game may require neuronal recep­tivity to be set at a high level, probably involving several neurotransmitters, including nitric oxide and dopamine in the retina, serotonin and histamine in the lateral geniculate nucleus, and noradrenaline in the visual cortex. These effects appear to be primarily nonsynaptically mediated.

Some of them have been called modulation; the modulation of synaptic activity by diffusion outside the synaptic gap is also a nonsynaptic, diffusion-mediated activity.

NDN can be modeled by students in a university classroom, who can be equated to neurotransmitter molecules in a vesicle. Upon release, they must go to specific other classrooms throughout the campus (receptor sites). They flow out into the halls and the grounds between buildings (extracellular fluid), where they mix with other students (neurotransmitter mole­cules) from other classrooms (vesicles) going to other target classrooms. They walk (diffuse) to their specific classrooms (receptors), which they enter (bind). In contrast, "synaptic transmission" students would be propelled along enclosed walkways connecting the point-of-origin classroom with each target classroom.

This conceptual model of information transmission in the brain, involving both synaptic transmission and NDN, may have considerable relevance to the func­tional reorganization following brain damage.

Recep­tor plasticity, both at synapses and on the cell membrane away from synapses (reached by nonsy­naptic diffusion neurotransmission), may play a major role in the reorganization of function following brain damage.

NDN may be the principal means of neurotransmis­sion in the noradrenergic system, which is involved in many activities related to recovery from brain damage.

Both acetylcholine and norepinephrine can provide a state of excitability consistent with cognition, which is consistent with inhibition of the locus ceruleus activity during lack of vigilance.

These findings may directly relate to the results of rehabilitation programs:

  • When vigilance is high and the patient is actively involved in the rehabilitation program, good results are more likely to be obtained.
  • There may also be a relationship to functional rehabilitation programs that are based on the interests of the individual patient and to the positive results obtained with some home programs.
  • In all these cases, the increased vigilance and participa­tion may lead to greater locus ceruleus production of noradrenaline.
  • This and other neurotransmitter changes may also be mechanisms by which psychosocial factors influence recovery.

In 1949, Hebb developed the concept of brain "cell assembly," (جمعبة) which continues to be a major model of brain function. He considered that any frequently repeated particular stimulation will lead to the slow development of a cell assembly, a diffuse structure capable of acting as a closed system.

Hebbian cell assemblies consist of enormous numbers of individual cells, with every cell connected to every other cell. With such architecture, however, the length of the links among cells and the resulting volume of the assembly would easily exceed space constraints.

In contrast, a "wireless" mechanism, such as NDN, might be consistent with volume limitations.

However, the space and energy considerations in synaptic and nonsynaptic neurotransmission have been calculated, and it has been shown that synaptic connectivity in cell assemblies would be too costly in terms of the metabolic energy and the space required, thus suggest­ing NDN to be a less expensive means for intercellular communication.

 

  1. Extracellular Space Volume Fraction:

The extracellular space in the brain plays a role in many functions, including nonsynaptic diffusion neu­rotransmission.

In an assembly of cells in the brain, the distance between neurons can be reduced by 50% with neuron activity that causes them to swell. This has an effect on the excitability and metabolism of the cells by means of changes in the distance between the neurons, which produces changes in ionic concentrations and dynamics.

Changes in the size of the extracellular compartment [volume fraction (VF)] may play a role in membrane excitability in pathological brain states such as epi­lepsy, brain damage, and in the survival of partially denervated neurons during the postinjury period of receptor upregulation that can lead to reorganization of brain function by unmasking and other mechan­isms.

The extracellular VF is reduced in:

  1. Under pathological conditions such as anoxia.
  2. In hyperexcitability (reduced by up to 50%).
  3. By changes in the concentration of potassium (reduced by up to 50%).
  4. With epileptiform discharges (reduced by up to 50%).

However, it is also possible that hyper­excitability due to a VF decrease, either independently or in combination with excitotoxic activity, may increase secondary cell death following brain damage.

 

  1. Reactive Synaptogenesis:

Usually called "sprouting", however, a case can be made for calling this "reactive synaptogenesis" when considering re­covery of function.

Although reactive synaptogenesis may participate in the recovery of function in some cases, it may also compete with the process of restoration by introducing aberrant connections.

It has been proposed that the takeover of muscle fibers when motor neuron loss occurs, such as in polio, may occur through vestigial pathways (أثرى) since in the embryonic stage the muscle fibers are polyneuronally innervated.

Although all connections except those from one motor neuron disappear shortly after birth, vestigial remains of the polyneuronal pathways could conceivably serve as tracks for the growth of pathways from surviving motor neurons to the muscle fibers denervated by the motor neuron loss.

If such pathways could be demonstrated in the nerve-muscle fiber preparation (which has served very well as a model of central nervous system nerve-cell connectivity), it would be interesting to consider the implications for central nervous system repair mechanisms.

In parti­cular, reactive synaptogenesis would have to be considered in the context of the reestablishment of connections that had existed during an early stage of brain development.

Hemishperectomy is a model for recovery of function since remarkable recoveries have been recorded both in experimental animals and in young and adult humans. Thus, an extensive reorganiza­tion of the brain may account for the remarkable recovery of function.

 

  1. Diaschisis:

Diaschisis relates recovery of function to the recovery from the neural depression of sites remote from, but connected to, the site of injury. 

Changes in neurotransmitter function following injury have been suggested as a mechanism by which diachisis could operate.

Following a unilateral sensorimotor cortex injury in rats, a depression in norepinephrine function occurs in the cerebellum contralateral to the lesion at 1 day postinjury.

The norepinephrine depression, and the hemiplegia, can be resolved by infusions of norepinephrine into the contralateral, but not the ipsilateral, cerebellum. The recovery is maintained permanently.

The anatomical mechanism may be via the simultaneous projection of individual locus coeruleus cells to both the contralateral cerebellum and the ipsilateral sensorimotor cortex.

Damage to the sensor­imotor cortex also damages fibers to the locus coeruleus, which may shift the body's energy from neurotransmitter production to protein synthesis for repair of the damaged terminal. While the body attempts repair, the undamaged terminals elsewhere (e.g., in cerebellum) may not be functioning normally.

However, long-term mechanisms are also probably involved since crossed-cerebellar inhibition has also been demonstrated in humans several years after brain lesion by positron emission tomography studies.

 

  1. Trophic Factors:

Trophic factors such as nerve growth factor have also been shown to be related to cell survival and recovery after brain damage.

Transmembrane glycoproteins (e.g., integrins), gangliosides, and putrecine have been suggested to have roles in recovery of function.

 

  1. Synapsins:

Changes in synapsins may provide a mechanism for brain plasticity, based on regulation of neurotrans­mitter release.

Synapsins are neuronal phosphoproteins that coat synaptic vesicles and bind to the cytoskeleton. Membrane depolarization and neuro­transmitter release have been correlated with phosphorylation of the synapsins.

The synapsins, a novel class of actin-binding proteins, are located in the presynaptic nerve terminal and contribute a significant portion of the total synaptic vesicle protein. They may connect synaptic vesicles to each other, to the cytoskeletal, or both, and they may play a role in positioning synaptic vesicles in the nerve terminal, thus regulating transmitter release.

Studies on synapsins may form a framework for understanding how these molecules function in organizing presynaptic intracellular space, and they could provide a mechanism for reorganizing function.

 

  1. Parallel and Adjoining Cortical Representation Areas:

Parallel motor areas could substitute for lost function in brain-injured persons.

In a study of the anatomy of motor recovery assessing motor function in 23 patients following capsular or striatocapsular stroke, small capsular lesions, which can disrupt the output of functionally and anatomically distinct motor areas selectively, were considered to reveal the capability of the different motor pathways to substitute each other functionally in the process of recovery from hemiparesis.

Contribution of the undamaged hemisphere to the process of recovery was suggested by both electro-physiological and metabolic studies, mediated by either bilateral pathways or uncrossed or recrossing pyramidal tract fibers, which may also play an important role.

The reorganization of parallel-acting multiple motor areas ipsilateral to the lesion site was considered to be the central mechanism in motor recovery.

Motor and sensory cortical representation can expand into adjoining cortical areas either following a lesion (e.g., limb amputation) or following specific training, such as in monkeys highly trained in tactile tasks.

The cortical representational plasticity may play a role in functional recovery following brain damage.

  1. Emergent Mechanisms:

Recent findings that may increase our understanding of the mechanisms of brain reorganization include the isolation of stem cells, which are the primordial cells from which all others evolve.

They can potentially be made into neural cells that can migrate through the brain to where they are needed after a lesion or that can be implanted in the brain.

Neural cells grown in labs have been implanted in the brains of persons who have had a stroke, with resulting improved function.

It has been shown in adult humans, that neurogenesis can occur (at least in the hippocampus). Adult neural stem cells have been shown to have very broad developmental capacities that may potentially be used to generate a variety of cell types for transplantation. Regeneration has been shown to be possible in some brain regions

We are currently at a stage in which, although much new evidence is accumulating regarding these emerging research areas, conclusions as to their roles in recovery from brain damage cannot be drawn.

Factors affect Neuroplasticity:

 

  1. Psychosocial and Environmental Factors in Recovery of Function
  • Family support, mood, the environment, resistance to change, the attitudes of the rehabilitation profession­als, and hope and expectations for recovery are some of the factors related to recovery.
  • These factors appear to be intimately related to neurotransmitters and to the effectiveness of rehabilitation programs.
  • The type of physical environment in which the brain-damaged person is placed may be closely related to the recovery.
  • In addition to the physical environ­ment for rehabilitation, and the content and timing of the rehabilitation programs, psychosocial factors and fitness level can affect outcome of rehabilitation programs.
  • Fitness also affects many functional mea­sures: Physically active men have been shown to have shorter event-related cortical potentials, stronger cen­tral inhibition, better neurocognitive performance, and better visual sensitivity.
  • The excellent functional recovery noted in some unusual cases of recovery from brain damage with home rehabilitation programs may be related not only to neuroplasticity factors but also to psychosocial and environmental considerations and to the functionality of the rehabilitation program.
  1. Temporal Factors
  • Lesions of the brain early in life have effects that differ from those that occur in adulthood.
  • Functional results can be either better or worse, depending on the age at injury and on the area injured.
  • Furthermore, the age at which the lesion occurs may influence motor as well as behavior lesion effects.
  • Damage in infancy yields more profound socioemotional effects than does damage in adulthood.
  • Compensatory mechanisms do not always operate to ensure recovery of functions after early brain damage.
  • Early lesions (such as in persons with congenital hemispherectomy), resulting in acquisition of lan­guage in the right hemisphere, may interfere with right hemisphere nonverbal functions due to the "crowding effect"; this may be a case of functional plasticity being of limited advantage to individuals with regard to total cognitive capacities.
  • Tactile stimulation with premature babies leads to faster growth. Similarly, tactile stimulation of brain-lesioned laboratory rats led to unexpectedly large attenuation of the behavioral deficits, correlated with reversal of atrophy of cortical neurons normally associated with these lesions.
  • Both premature infants and laboratory rats have in common that both are in impoverished environments. Thus, the positive re­sponses with tactile stimulation can be considered to be related to an improvement in the direction of a normal environment.
  • Reorganization and recovery of function does not cease at any arbitrary time, such as 6 months; the potential can exist for many years after injury. It is becoming an important area in the field of neurologic rehabilitation since it appears that, in humans, specific late (postacute) rehabilitation programs are necessary to exploit that potential.

 

Neuroplasticity in the Aging Brain

Neurotransmitter levels and mechanisms in the aged brain appear to vary from those in young and adult brains in many ways.

Implants of young tissue into aged hosts, and those of aged tissue into young hosts, have been studied in order to determine the relative importance of intrinsic versus extrinsic influences in such factors as age-related adrenergic deficits.

Recep­tor plasticity, the up- or downregulation of receptors for specific neuroactive substances, is an important mechanism of neuroplasticity. Many changes in brain function lead to receptor changes since they must result in changes in neurotransmitters and other neuroactive substances.

One study of receptor plasti­city of the aged human brain demonstrated upregulation of dopamine Dl receptors in the brains of three persons, 80, 81, and 87 years of age who had died respectively 9, 19, and 27 days following a unilateral infarct of the ventral midbrain, producing a relative dopamine depletion on the lesioned side. In the autopsy material, an increase of between 27 and 37% of dopamine receptors was demonstrated on the lesioned side.

The receptor plasticity demonstrated in stroke patients has been discussed in regard to the possible role of NDN in the functional results of that plasticity. The Dl receptor upregulation may occur on the nonsynaptic cell membrane following the loss of synapses due to the partial denervation. That and comparable up- and downregulation may result in adaptive or maladaptive responses to the brain damage:

Many neurotransmitter substances have been demonstrated by microdialysis in the extra cellular fluid, and some of these may produce responses in cells hypersensitive due to receptor plasticity following denervation. A possible maladaptive response is convulsive activity; it has been reported that 10-15% of stroke patients have convulsions.

Recovery of function following brain damage in the aged is also evidence for neuroplasticity; unusual cases of recovery stimulate investigators to explore the mechanisms of such recovery and the means of mobilizing those mechanisms to obtain the maximum possible recovery of function following brain damage.

Several unusual cases have been described in the literature that reveals plasticity in the aged brain. Among these is the recovery of function in a patient who, at 65 years of age, had major brain damage (demonstrated on autopsy 7 years later) but who made a good recovery with a home-based rehabilitation program during the 5 years following the stroke. Aged patients with facial paralysis showed significant im­provement with a rehabilitation program started years after the damage.

 

  1. NEUROLOGIC REHABILITATION

Clinical rehabilitation has developed in an ad hoc fashion. The first formal stroke rehabilitation method, published by Frenkel in the mid- 19th century, emerged from a program that a nonprofessional wife had developed to successfully rehabilitate her hus­band. Rehabilitation clinicians still rely on nontheory-related methodologies. Little has been written about the fact that rehabilitation as currently practiced has such meager carryover to real-life activities, and even little carryover from one session to another. This has had the effect of reinforcing the widespread view in the physical rehabilitation field that once a patient reaches a plateau, usually 6-12 months after a stroke, further administration of rehabilitation therapy does not have useful results. With standard rehabilitation, a study showed that there was a difference in what the stroke patients could do in the hospital stroke unit and what the patients did at home. Each activity of daily living was less well performed in the home situation in 25-45% of the cases, and in 52% of the cases the chief caretaker claimed that the patient did not do two or more activities at home that the patient was capable of performing in the day hospital.

Ideally, therapy should be based on experimental findings. Carryover to real-life activities requires programs specifically developed to do so. Issues such as the nature of the interaction between behavioral and neural plasticity and the nature of rehabilitation programs that produce functional carryover should be evaluated. Programs based on conditioned re­sponses have no carryover, whereas those based on shaping and on constraint-induced facilitation have been shown to have excellent carryover to real-life tasks.

A cat hemispherectomy model has provided some of the most reliable information on mechanisms under­lying recovery of function in adult cats as well as the functional compensation in the developing animal following neonatal lesion. Forced exercise of the impaired limb was effective in reversing paw prefer­ence bias in all cases; however, the adult lesioned cats required more trials and extensive food deprivation. All cats continued improved performance indefinitely in their home cages. Thus, an impressive potential for recovery of directed purposeful movements remains after hemispherectomy, and recovery of function can be enhanced by forced exercise. Although 1 month of recovery time was needed in the adult hemispherect­omy cases, recovery time for directed self-feeding movements could be reduced with passive mobiliza­tion and treadmill walking and running immediately after the experimental surgery. This provides animal experimental evidence that supports clinical rehabili­tation applications of passive movements (which prevent contractures that lead to limited limb range of motion) in the early stages following brain damage.

Another productive, widely used model is the differential effect of serial lesions versus the one-stage lesion of the same amount of tissue, from the same brain area, as the total of all the serial lesions. Many studies have shown that the functional recovery is far greater in the animals that have had serial lesions than in those that have had one-step lesions. Reorganiza­tion of function, including reorganization in brain tissue different from the eventually removed tissue, must occur between lesions. This provides firm evi­dence for brain plasticity and recovery of function, even in the adult animal.

In addition to motor recovery with appropriate rehabilitation, animal models have also demonstrated sensory recovery, such as cat visual recovery from ambliopia with training and the ability to regain all fine sensory functions with rehabilitation following pri­mary somatosensory projection cortex ablations in monkeys trained in tactile discriminations prelesion. An incidental finding is that postlesion it is necessary to inhibit negative cues, and that lesion of the ipsilateral cortex can produce bilateral deficits

There are many excellent recent studies on the scientific basis of recovery of function with rehabilita­tion. The following are some conclusions drawn by the experimenters of these studies. Rehabilitation must be varied and must not be repetitive. Changes in the motor cortex are driven by the acquisition of new motor skills and not simply by motor use, which may indicate that the repetitive, boring activities of stan­dard rehabilitation are virtually useless. Functional plasticity is accompanied by structural plasticity. Unmasking, multiplexing, synaptic plasticity, sprout­ing, and inhibition are mechanisms of functional reorganization following brain damage. Functional plasticity in intact cortex is initiated immediately after injury. Activity (rehabilitation) results in an increase in the neuropil, in dendritic arborization, in the number of synapses, and in the separation between neurons, resulting in the reduction of the number of neurons per cubic millimeter. Spontaneous motor recovery cannot be explained by substitution of function in the spared motor cortex immediately adjacent to the lesion. The retention of functional representation in tissue adja­cent to the lesion requires motor training (rehabilita­tion), which appears to have a modulatory effect on plasticity in the surrounding tissue. Blocking the NMDA receptors may be neuroprotective in the early postinjury stage, but blocking them later may reinstate deficits. Immobilizing the good limb too soon after brain damage in a rat model can have extremely deleterious effects, both in behavioral responses and in causing a dramatic expansion of the original lesion, which suggests that either too much or too little activity can have profound negative consequences. In rats, forced disuse for 1 week has many measurable negative effects; thus, studies of the negative effect of forced bed rest in brain-damaged humans are neces­sary. Mild rehabilitation may improve functional outcome, whereas early moderate rehabilitation can have negative effects, including the exaggeration of infarct size. Human stroke patients had worse out­come with forced speech therapy for several weeks than with brief (15-min) conversations.

Many of these conclusions challenge several dogmas of rehabilitation; however, especially since they are based on experimental findings, they should lead to further studies and, undoubtedly, to changes in the practice of clinical rehabilitation. Clinical studies have rarely used prospective randomized methods. One such study, carried out at the Karolinska Institutet in Huddinge (Stockholm), revealed that for patients for whom early stroke rehabilitation was possible, home rehabilitation was effective. However, well-documen­ted individual case studies demonstrating unusual recovery are valuable, especially since they indicate what is possible and they may suggest effective rehabilitation approaches. In one such study, an elderly stroke patient with extensive brain damage (that was documented on autopsy 7 years later) followed a home rehabilitation program and recovered an extrodinary degree of function and returned to full-time work.

Little emphasis has been placed on late rehabilita­tion programs, possibly because late recovery has not generally been expected. However, reports of late recovery are not new; it was discussed in an article in the Journal of the American Medical Association in 1915, and many such reports have emerged from the treatment of war injuries. A case report of late recovery in a quadriplegic patient noted that since most quadriplegic patients are discharged 4 or 5 months postinjury, many patients have not achieved full motor recovery at discharge. It is possible that in many other cases of central nervous system damage the late recovery of function goes unnoticed since the patients have been discharged.

In addition to neural factors, learned nonuse has been demonstrated in human stroke patients. Al­though both lower extremities are almost always used as soon as possible in the recovery phase following the stroke since both are necessary for gait, the affected upper extremity is often not used, possibly because many tasks can be performed with one hand, leading to the development of learned nonuse. Behavioral train­ing provided even years after the lesion that could involve as few as 3 days of restraint of the normal limb, thus forcing the use of the affected limb, can reverse the learned nonuse, converting a useless limb into a limb capable of extensive movement. It had previously been shown that forced use of the paretic upper extremity of monkeys with experimentally produced hemiplegia (unilateral cortical area 4 ablation) produced signifi­cant recovery of function.

A sensory substitution model of late brain rehabi­litation has been developed based on the consideration that a major sensory loss, such as blindness, removes a large part of the input to the brain and, similar to an actual lesion, induces a major reorganization of the brain. Tactile vision substitution systems (TVSS's) have been developed to deliver visual information from a TV camera to arrays of stimulators in contact with the skin of one of several parts of the body, including the abdomen, back, thigh, forehead, finger­tip, and tongue. Mediated by the tactile receptors, images transduced from the camera are encoded as neural pulse trains. In this manner, the brain is able to recreate "visual" images that originate in a TV camera. Indeed, after sufficient training with the TVSS, subjects who were blind since early infancy reported experiencing the images in space instead of on the skin. They learned to make perceptual judgments using visual means of analysis, such as perspective, parallax, looming, and zooming, and to make depth judgments. They have been able to perform complex perception and "eye"-hand coordination tasks, including facial recognition, accurate judgment of speed and direction of a rolling ball with more than 95% accuracy in batting the ball as it rolls over a table edge, and complex inspection-assembly tasks. The results have been interpreted as demonstrating the capacity of the brain to reorganize even when the training (rehabilita­tion) of congenitally blind persons is initiated in adulthood.

Another post-acute program was developed for persons with long-standing facial paralysis due to facial nerve damage during the removal of an acoustic neuroma who had undergone a VII-XII cranial nerve anastomosis (connecting part of the tongue nerve to innervate the facial muscles). In this model, it is clear that the facial muscles are innervated by nerve fibers from structures genetically programmed to move tongue muscles. However, with appropriate rehabili­tation, persons recover spontaneous and voluntary bilateral facial symmetrical movements, and they learn to inhibit dyskinetic movements, even many years after the causitive event. The study was designed to evaluate brain plasticity in a human model in which the extent of the lesion is definitely known and in which, due to the complete loss of connectivity from the brain regions genetically programmed to control facial movements, another system (in this case, the brain regions that had previously controlled tongue move­ments) could be demonstrated to have reorganized to obtain the functional recovery.

Motivating therapy is effective. An example is the ingenious approach taken by a research group in France to obtain eye movement control in children with cerebral palsy who had eye coordination deficits. They noted, as had others before them, that watching a pendulum aided in the training, but they found that the children refused to watch because they found it too boring. They developed a fascinating functional pen­dulum by projecting children's movies (Snow White and Lassie) at a galvanometer-controlled mirror, which reflected the image to the back side of a projection screen. The children sat in front of the screen with their heads fixed so that to follow the pendular movements of the image they had to use eye movements. They underwent 6 hr a week of intense therapy (three movies) and within 1 month improved to the point that they could learn to read.

A comparable approach was taken in the early 1970s with the early electronic pong games, which could be connected to home TV sets. One of the joystick controls was replaced with a device used in the clinic for hemiparetic persons to train arm movements. Instead of meaningless exercise, the arm could control a paddle (paddle size and ball speed were varied according to the capabilities of individual patients) allowing participation in a highly motivating game.

III. IMPLANTED AND ATTACHED INSTRUMENTATION

Miniaturized electronics and device technology (e.g., nanotechnology) offer the promise of overcoming some of the deficits produced by brain damage. Sensors and stimulators have been implanted in the brains of blind and paralyzed persons to interface with computers. An array of electrotactile stimulators built into a false palate (similar to an orthodontic retainer) may allow the tongue to act as a human-machine interface for information from many proposed artifi­cial receptors, such as a TV camera for blind persons, a pitch-and-roll sensor for persons who have lost vestibular function, or a robotic hand with position and touch sensors for paralyzed brain and spinal cord-injured persons. These are examples of the application of emerging technologies to compensate for functional loses.

  1. CONCLUSION

The brain is capable of reorganization during the organism's entire lifetime. Functional improvement after brain damage depends on many biological and psychosocial factors.

Neuroplasticity

(variously referred to as brain plasticity or cortical plasticity or cortical re-mapping) refers to the changes that occur in the organization of the brain as a result of experience. A surprising consequence of neuroplasticity is that the brain activity associated with a given function can move to a different location as a consequence of normal experience or brain damage/recovery.

The concept of neuroplasticity pushes the boundaries of the brain areas that are still re-wiring in response to changes in environment. Several decades ago, the consensus was that lower brain and neocortical areas were immutable after development, whereas areas related to memory formation, such as the hippocampus and dentate gyrus, where new neurons continue to be produced into adulthood, were highly plastic. Hubel and Wiesel had demonstrated that ocular dominance columns in the lowest neocortical visual area, V1, were largely immutable after the critical period in development. Critical periods also were studied for language and suggested it was likely that the sensory pathways were fixed after their respective critical periods. Environmental changes could cause changes in behavior and cognition by modifying the connections of the new neurons in the hippocampus.

Decades of research have now shown that substantial changes occur in the lowest neocortical processing areas, and that these changes can profoundly alter the pattern of neuronal activation in response to experience. According to the theory of neuroplasticity, thinking, learning, and acting actually change both the brain's functional anatomy from top to bottom, and its physical anatomy. A proper reconciliation of critical period studies, which demonstrate some functional and anatomical aspects of the neocortex are largely immutable after development, with the new findings on neuroplasticity, which demonstrate some functional aspects are highly mutable, are an active area of current research.

Canadian psychiatrist Norman Doidge has called neuroplasticity "one of the most extraordinary discoveries of the twentieth century

Brain plasticity and cortical maps

Cortical organization, especially for the sensory systems, is often described in terms of maps. For example, sensory information from the foot projects to one cortical site and the projections from the hand target in another site. As the result of this somatotopic organization of sensory inputs to the cortex, cortical representation of the body resembles a map (or homunculus).

In the late 1970s and early 1980s, several groups began exploring the impacts of removing portions of the sensory inputs. Michael Merzenich and Jon Kaas used the cortical map as their dependent variable. They found—and this has been since corroborated by a wide range of labs—that if the cortical map is deprived of its input it will become activated at a later time in response to other, usually adjacent inputs. At least in the somatic sensory system, in which this phenomenon has been most thoroughly investigated, JT Wall and J Xu have traced the mechanisms underlying this plasticity. Re-organization occurs at every level in the processing hierarchy to result in the map changes observed in the cerebral cortex. It is not cortically emergent.

Merzenich and William Jenkins (1990) initiated studies relating sensory experience, without pathological perturbation, to cortically observed plasticity in the primate somatosensory system, with the finding that sensory sites activated in an attended operant behavior increase in their cortical representation. Shortly thereafter, Ford Ebner and colleagues (1994) made similar efforts in the rodent whisker barrel (also somatic sensory system). These two groups largely diverged over the years. The rodent whisker barrel efforts became a focus for Ebner, Matthew Diamond, Michael Armstrong-James, Robert Sachdev, Kevin Fox, and Dan Feldman, and great inroads were made in identifying the locus of change as being at cortical synapses expressing NMDA receptors, and in implicating cholinergic inputs as necessary for normal expression. However, the rodent studies were poorly focused on the behavioral end, and Ron Frostig and Daniel Polley (1999, 2004) identified behavioral manipulations as causing a substantial impact on the cortical plasticity in that system.

Merzenich and DT Blake (2002, 2005, 2006) went on to use cortical implants to study the evolution of plasticity in both the somatosensory and auditory systems. Both systems show similar changes with respect to behavior. When a stimulus is cognitively associated with reinforcement, its cortical representation is strengthened and enlarged. In some cases, cortical representations can increase two to three fold in 1-2 days at the time at which a new sensory motor behavior is first acquired, and changes are largely finished within at most a few weeks. Control studies show that these changes are not caused by sensory experience alone: they require learning about the sensory experience, and are strongest for the stimuli that are associated with reward, and occur with equal ease in operant and classical conditioning behaviors.

An interesting phenomenon involving cortical maps is the incidence of phantom limbs. This is most commonly described in people that have undergone amputations in hands, arms, and legs, but it is not limited to extremities. The phantom limb feeling, which is thought[specify] to result from disorganization in the homunculus and the inability to receive input from the targeted area, may be annoying or painful. Incidentally, it is more common after unexpected losses than planned amputations. There is a high correlation with the extent of physical remapping and the extent of phantom pain. As it fades, it is a fascinating functional example of new neural connections in the human adult brain.

The concept of plasticity can be applied to molecular as well as to environmental events.[citation needed] The phenomenon itself is complex and can involve many levels of organization. To some extent the term itself has lost its explanatory value because almost any changes in brain activity can be attributed to some sort of "plasticity".

For example, the term is used prevalently in studies of axon guidance during development, short-term visual adaptation to motion or contours, maturation of cortical maps, recovery after amputation or stroke, and changes that occur in normal learning in the adult. Some authors[attribution needed] separate forms into adaptations that have positive or negative consequences for the animal. For example, if an organism, after a stroke, can recover to normal levels of performance, that adaptiveness could be considered an example of "positive plasticity". An excessive level of neuronal growth leading to spasticity or tonic paralysis, or an excessive release of neurotransmitters in response to injury which could kill nerve cells, would have to be considered perhaps as a "negative or maladaptive" plasticity.

Treatment of brain damage

Neuroplasticity is a fundamental issue that supports the scientific basis for treatment of acquired brain injury with goal-directed experiential therapeutic programs in the context of rehabilitation approaches to the functional consequences of the injury.

The adult brain is not "hard-wired" with fixed and immutable neuronal circuits. There are many instances of cortical and subcortical rewiring of neuronal circuits in response to training as well as in response to injury. There is solid evidence that neurogenesis, the formation of new nerve cells, occurs in the adult, mammalian brain--and such changes can persist well into old age.[6] The evidence for neurogenesis is restricted to the hippocampus and olfactory bulb. In the rest of the brain, neurons can die, but they cannot be created. However, there is now ample evidence for the active, experience-dependent re-organization of the synaptic networks of the brain involving multiple inter-related structures including the cerebral cortex. The specific details of how this process occurs at the molecular and ultrastructural levels are topics of active neuroscience research. The manner in which experience can influence the synaptic organization of the brain is also the basis for a number of theories of brain function including the general theory of mind and epistemology referred to as Neural Darwinism and developed by immunologist Nobel laureate Gerald Edelman. The concept of neuroplasticity is also central to theories of memory and learning that are associated with experience-driven alteration of synaptic structure and function in studies of classical conditioning in invertebrate animal models such as Aplysia. This latter program of neuroscience research has emanated from the ground-breaking work of another Nobel laureate, Eric Kandel, and his colleagues at Columbia University College of Physicians and Surgeons.

Brain plasticity during operation of brain-machine interfaces

Brain-machine interface (BMI) is a rapidly developing field of neuroscience. According to the results obtained by Mikhail Lebedev, Miguel Nicolelis and their colleagues (Lebedev et al. 2005), operation of BMIs results in incorporation of artificial actuators into brain representations. The scientists showed that modifications in neuronal representation of the monkey's hand and the actuator that was controlled by the monkey brain occurred in multiple cortical areas while the monkey operated a BMI. In these single day experiments, monkeys initially moved the actuator by pushing a joystick. After mapping out the motor neuron ensembles, control of the actuator was switched to the model of the ensembles so that the brain activity, and not the hand, directly controlled the actuator. The activity of individual neurons and neuronal populations became less representative of the animal's hand movements while representing the movements of the actuator. Presumably as a result of this adaptation, the animals could eventually stop moving their hands yet continue to operate the actuator. Thus, during BMI control, cortical ensembles plastically adapt, within tens of minutes, to represent behaviorally significant motor parameters, even if these are not associated with movements of the animal's own limb.

Active laboratory groups include those of John Donoghue at Brown, Richard Andersen at Caltech, Krishna Shenoy at Stanford, Nicholas Hatsopoulos of University of Chicago, Andy Schwartz at Pitt, Sandro Mussa-Ivaldi at Northwestern and Miguel Nicolelis at Duke. Donoghue and Nicolelis' groups have independently shown that animals can control external interfaces in tasks requiring feedback, with models based on activity of cortical neurons, and that animals can adaptively change their minds to make the models work better. Donoghue's group took the implants from Richard Normann's lab at Utah (the "Utah" array), and improved it by changing the insulation from polyimide to parylene-c, and commercialized it through the company Cyberkinetics. These efforts are the leading candidate for the first human trials on a broad scale for motor cortical implants to help quadriplegic or trapped patients communicate with the outside world.

Thought and neuroplasticity

The Dalai Lama invited Richard Davidson, a Harvard-trained neuroscientist at the University of Wisconsin-Madison's W.M. Keck Laboratory for Functional Brain Imaging and Behavior to his home in Dharamsala, India, in 1992 after learning about Davidson's innovative research into the neuroscience of emotions. Could the simple act of thinking change the brain? Most scientists believed this idea to be false, but they agreed to test the theory. One such experiment involved a group of eight Buddhist monk adepts and ten volunteers who had been trained in meditation for one week in Davidson's lab. All the people tested were told to meditate on compassion and love. Two of the controls, and all of the monks, experienced an increase in the number of gamma waves in their brain during meditation. As soon as they stopped meditating, the volunteers' gamma wave production returned to normal, while the monks, who had meditated on compassion for more than 10,000 hours in order to attain the rank of adept, did not experience a decrease to normal in the gamma wave production after they stopped meditating. The synchronized gamma wave area of the monks' brains during meditation on love and compassion was found to be larger than that corresponding activation of the volunteers' brains. Davidson's results were published in the Proceedings of the National Academy of Sciences in November, 2004 and TIME recognized Davidson as one of the ten most influential people in 2006 on the basis of his research

Neuroplasticity

The Brain's Natural Reparatory Ability

Scientists once thought that the brain stopped developing after the first few years of life. They thought that connections formed between the brain’s nerve cells during an early “critical period” and then were fixed in place as we age. If connections between neurons developed only during the first few years of life, then only young brains would be “plastic” and thus able to form new connections. (To learn more about neurons, click here.) Because of this belief, scientists also thought that if a particular area of the adult brain was damaged, the nerve cells could not form new connections or regenerate, and the functions controlled by that area of the brain would be permanently lost. However, new research on animals and humans has overturned this mistaken old view: today we recognize that the brain continues to reorganize itself by forming new neural connections throughout life. This phenomenon, called neuroplasticity, allows the neurons in the brain to compensate for injury and adjust their activity in response to new situations or changes in their environment.

How does neuroplasticity work? A large amount of research focuses on this question. Scientists are certain that the brain continually adjusts and reorganizes. In fact, while studying monkeys, they found that the neuronal connections in many brain regions appear to be organized differently each time they are examined! While it remains uncertain at this writing (April 2003) whether reorganization in the adult brain involves the formation of new neural connections, existing neural pathways that are inactive or used for other purposes do show the ability to take over and carry out functions lost to degeneration. Understanding the brain's ability to dynamically reorganize itself helps scientists understand how patients sometimes recover brain functions damaged by injury or disease.

Brain Reorganization

Genes are certainly not the only factor determining how our brain develops and forms its inner connections. Conditions in our environment, such as social interactions, challenging experiences and even fresh air can play a crucial role in brain cell survival and the formation of connections. Just as the brain changes in response to environmental conditions, it can also change and rearrange in response to injury or disease. Commonly, these rearrangements involve changes in the connection between linked nerve cells, or neurons, in the brain. Brain reorganization takes place by mechanisms such as "axonal sprouting", where undamaged axons grow new nerve endings to reconnect the neurons, whose links were severed through damage. Undamaged axons can also sprout nerve endings and connect with other undamaged nerve cells, thus making new links and new neural pathways to accomplish what was a damaged function. For example, although each brain hemisphere has its own tasks, if one brain hemisphere is damaged, the intact hemisphere can sometimes take over some of the functions of the damaged one. Flexible and capable of such adaptation, the brain compensates for damage in effect by reorganizing and forming new connections between intact neurons.

New connections can form at an amazing speed, but in order to reconnect, the neurons need to be stimulated through activity. In one study, researchers damaged a small brain area in several monkeys, which resulted in the loss of particular hand movements. Due to the lack of hand activity, even the neurons surrounding the damaged brain area withered, resulting in further impairment of hand movements. These observations confirm the notion that it is important to provide stimulation to neurons in order for them to remain active and form new connections, promoting rehabilitation.

Unfortunately, this same brain reorganization may sometimes contribute to the symptoms of disease or impairment. For example, people who are deaf sometimes suffer from a continual ringing in their ears, which may be the result of the rewiring of brain cells starved for sound. It is important to stimulate the neurons in just the right way for them to form beneficial new connections. By better understanding how the brain reorganizes itself, we can better learn how this task can be accomplished.

Strategies for Promoting Brain Reorganization

A first key principle of neuroplasticity is this: brain activity promotes brain reorganization. In other words, "brain workouts" help the brain reorganize connections more quickly and stimulate reorganization when the brain is not capable of reorganizing on its own. Even simple brain exercises such as presenting oneself with challenging intellectual environments, interacting in social situations, or getting involved in physical activities will boost the general growth of connections. However, generalized stimulation may not be very helpful for rebuilding a specific damaged area of the brain.

Another way to promote neuronal connections in the brain has been learned from efforts to help stroke patients. Studies show that drugs that increase the availability of the hormone norepinephrine help in the rehabilitation of movement loss. These drugs stimulate or provoke the synapses of the nerve cells, making them more capable of forming new connections. Because they can be costly and have unintended side effects, drugs alone may not be the optimal approach to rehabilitation. However, drugs may well be beneficial when used in conjunction with a third approach: physical or rehabilitation therapy.

Building on the principle that neuronal activity promotes new connections, rehabilitation therapy attempts to stimulate particular neurons that have not been active for some time. Here the goal is to promote selective self-repair and reorganization through specific motor activity. Because brain reorganization generally becomes more difficult as we age (for reasons not yet fully understood), a damaged adult brain needs a specific "neuroplasticity jump-start" to rebuild. For example, practicing a particular movement over and over-referred to in the literature as "constraint-induced movement-based therapy"-helps your brain form and strengthen the connections necessary for that movement. Thus in Germany, seven patients who had lost the ability to walk were placed on a treadmill with a parachute and harness. They were given as much physical support as possible, but the treadmill forced the movement of their legs. By the end of therapy, this forced movement enabled some of the intact neurons in the damaged area of the brain to form new connections, which in turn enabled three of the patients to walk independently and another three to walk with supervision.

An important aspect of rehabilitation therapy is timing. If a person who has suffered from brain damage does not practice a lost movement, the damaged neurons-as well as surrounding neurons-are starved of stimulation and will be unable to reconnect. However, research on non-human animals indicates that if an injured limb is used immediately after the brain area has been damaged, damage to the brain actually increases. To be successful, rehabilitation must wait a week or two. By the second week, use of the injured limb stimulates damaged connections that would otherwise atrophy without input. Yet, a particular movement can be practiced too much. If practiced millions of times per month over years, for example, the pattern of connections can grow so much that it inhibits or "squeezes out" other patterns of connection, resulting in the inability to perform other movements. In short, rehabilitation therapy can indeed take advantage of the brain's natural flexibility for forming new neural connections; however, this is a delicate process that must be done carefully and under professional guidance.

The Limits of Innate Brain Plasticity

Neuroplasticity enables the brain to compensate for damage, but sometimes an area of the brain is so extensively damaged that its natural ability to reorganize is insufficient to regain the lost function. In the case of Huntington's Disease and other diseases that cause neuronal death, the death of many cells may render the brain unable to reorganize corrective connections. In order to have a chance of repair, a certain (as yet unknown) number of neurons must remain intact. Thus, if a highly specialized brain "circuit" is completely destroyed, the associated mental function may be lost. Currently there is no way of determining with certainty whether a lost function can be recovered. However, there is another source of hope. Recent research (discussed in the next section) has shown that the brain can sometimes generate new neurons, not simply new connections, and that these new neurons can sometimes "migrate" within the brain. This raises the possibility that, under certain conditions, new neurons could migrate to damaged areas, form new connections, and restore some or all lost functions. It is too early to tell for sure: we still have much to learn about neuroplasticity!

Neurons and Neurogenesis

Billions of tree-shaped nerve cells make up the human brain. Neurons are produced through a process called neurogenesis, which begins during the third week of development in humans. Nerve cells develop at an average rate of 250,000 per minute during the prenatal period, but by birth, the process of neurogenesis has largely ceased. (To read more about neurons, click here.)

A widely held belief is that neurons, unlike other cells, cannot reproduce after the first few years of life. This would mean that neurons that are destroyed couldn’t be replaced. However, recent research suggests that this belief is not supported by evidence. In 1999, production of new neurons was discovered in the neocortex of adult primates. Also in 1999, researchers at the Salk Institute in San Diego, California discovered neurogenesis occurring in the brains of adult humans, including in a 72-year-old adult. In this study, researchers used a chemical marker to identify new neurons and observed neurogenesis in the hippocampal region, a brain region that controls certain types of memory.

This research indicates that neurogenesis may well continue to occur throughout the human life span, although it occurs less rapidly in adults. Many of the new neurons that form in adults die almost immediately, but evidence suggests that some cells that are able to integrate themselves into the existing web of neural connections. Other researchers have also found definitive evidence that the brain does not stop producing new neurons after the "critical period" of development; the brain has been shown to generate new neurons from stem cells in select regions of the brain.

Research in the area of neurogenesis has resulted in an exciting recent discovery bearing on Huntington's Disease. By studying post-mortem brains of people with HD, researchers at the University of Auckland in New Zealand found evidence suggesting that HD-affected brains produce new neurons throughout the course of the disease. Moreover, there is a correlation between the rate of neurogenesis and the severity of the illness. The brains of individuals at the most severe stages of HD showed the most neurogenesis. It appears that the brain is attempting to compensate for the neural damage resulting from the disease. Unfortunately, however, brains damaged by HD seem to be unable to generate new neurons quickly enough to replace the dying ones. Another problem may be that the new neurons are unable to migrate to the areas where they are needed.

The model is based on Dr. Schwartz’s successful drug-free treatment of OCD patients using a mindfulness-based cognitive behavioral therapy. By learning to experience OCD symptoms as faulty brain messages and focusing their attention away from the negative urges and thoughts onto more adaptive actions, Schwartz’s patients were able to effect positive and lasting changes in both their behavior and their neurochemical processes. Informed by this groundbreaking finding, the authors demonstrate that the mind exists as separate from but dependent on the brain. Their findings illustrate that, contrary to mainstream science, the adult brain is capable of neuroplasticity—that is, rewiring itself—and that the mind can shape the function and structure of the physical brain. In a daring exploration of recent findings from neuroscience and quantum physics, the authors present integrated evidence that supports their model.