Neural plasticity and neurorehabilitation:Teaching the new brain old tricks

Jeffrey A. Kleim *

School of Biological and Health Sciences Engineering, Arizona State University, Tempe, AZ, USA

1. Introduction

Medical advances have increased the average life expectancy in North America by over 30 years in the last century.Increased survival from traumatic brain injury, and an increase in the number of individuals suffering from age relatedneurological impairment, has significantly increased the number of individuals receiving neurorehabilitation. Unfortu-nately, this in turn has highlighted the relatively slow progress in neurorehabilitation as compared to other medicaldisciplines such as cardiology and immunology. Most major medical advances can be traced back to basic science researchthat first determined the fundamental properties of the dysfunctional biological system and then developed an appropriatetreatment. The biological system and causes of dysfunction that neurorehabilitation deals with are far more complicated anddiverse than those associated with heart disease or influenza. The brain is the most complex biological system on the planetand the sources of functional impairment are many ranging from the sudden loss of tissue due to a stroke or traumatic injuryto the decades long neurodegeneration associated with Parkinson’s or Alzheimer’s disease. A second issue is the historicallack of interaction between basic and clinical rehabilitation scientists. In academic settings, physical therapy, occupational

Journal of Communication Disorders 44 (2011) 521–528

A R T I C L E I N F O

Keywords:

Neural plasticity, Motor cortex, Stroke,

Synaptic plasticity

A B S T R A C T

Following brain injury or disease there are widespread biochemical, anatomical and

physiological changes that result in what might be considered a new, very different brain.

This adapted brain is forced to reacquire behaviors lost as a result of the injury or disease

and relies on neural plasticity within the residual neural circuits. The same fundamental

neural and behavioral signals driving plasticity during learning in the intact brain are

engaged during relearning in the damaged/diseased brain. The field of neurorehabilitation

is now beginning to capitalize on this body of work to develop neurobiologically informed

therapies focused on key behavioral and neural signals driving neural plasticity. Further,

how neural plasticity may act to drive different neural strategies underlying functional

improvement after brain injury is being revealed. The understanding of the relationship

between these different neural strategies, mechanisms of neural plasticity, and changes in

behavior may facilitate the development of novel, more effective rehabilitation

interventions for treating brain injury and disease.

Learning outcomes: Readers will be able to: (a) define neural plasticity, (b) understand

how learning in the intact and damaged brain can drive neural plasticity, (c) identify the

three basic neural strategies mediating functional improvement, and (d) understand how

adjuvant therapies have the potential to upregulate plasticity and enhance functional

recovery.

� 2011 Elsevier Inc. All rights reserved.

* Corresponding author. Tel.: +1 480 965 6832; fax: +1 480 727 7624.

E-mail address: jakleim@asu.edu.

Contents lists available at ScienceDirect

Journal of Communication Disorders

0021-9924/$ – see front matter � 2011 Elsevier Inc. All rights reserved.

doi:10.1016/j.jcomdis.2011.04.006

therapy, and physical medicine departments are isolated from basic science departments such as neuroscience,biochemistry or physiology. They publish in different scientific journals, attend different scientific conferences, and speakdifferent scientific languages. This has hindered our ability to develop effective, clinically relevant, interventions that areinformed by basic neurobiology. All of this has, however, begun to change over the last several years. This is not because basicscience has suddenly discovered some critical aspect of brain function that can be immediately translated into treatment.Rather, basic science disciplines such as neuroscience are simply beginning to more fully characterize a fundamentalproperty of the brain that was recognized over a hundred years ago: the capacity for neurons to structurally and functionallyadapt in order to reorganize neural circuits, i.e. the capacity for neural plasticity.

The purpose of the present review is to describe some of the key issues related to how understanding neural plasticitymight guide the development of more effective rehabilitation interventions. It is predicated on the hypothesis that functionalimprovement is in part related to the capacity for neural plasticity within residual neural circuits. Such plasticity affords theopportunity to train the new brain to perform old functions lost due to injury or disease.

2. Functional improvement after brain injury is a relearning process

Restoring function after brain injury or disease is not trivial and although neuroscience has made major advances, we arefar from understanding brain circuitry at the level needed to place new neurons and synapses in just the right places torestore lost function after damage. One way to approach the problem is by recognizing that functional improvement afterinjury is a relearning process. During therapy, patients are guided through practice to try and re-acquire the ability toproduce behaviors lost after injury. As such, the brain will rely on the same fundamental neurobiological processes it used toacquire those behaviors initially. The basic rules governing how neural circuits adapt to encode new behaviors do not changeafter injury. Studying learning-dependent neural plasticity in the intact brain therefore provides some insight into how theinjured brain may adapt during rehabilitation.

3. Learning-dependent neural plasticity

Evidence for learning dependent neural plasticity can be found in every animal species across virtually every behavioralmodality. To review this literature is beyond the scope of the paper. However, much of what rehabilitation therapists dealwith involves motor training to re-establish lost motor abilities and, as such, this review will focus on plasticity within themotor system associated with motor training. Virtually all of our daily behaviors, from speaking to tying our shoes, involvethe expression of some acquired motor skill. As a result, large portions of the brain are devoted towards the production ofskilled movement and consequently motor brain areas are often affected by injury or disease. The capacity to produce skilledmovements persists in the absence of continued training, suggesting that they are encoded as enduring neurobiologicalchanges within brain. Indeed a wealth of empirical evidence now exists showing motor learning-dependent neural plasticitywithin various motor regions.

Much of the work investigating motor learning-dependent plasticity has been conducted in laboratory rats because oftheir highly evolved motor systems and extensive repertoire of motor abilities. When compared to animals that simply walkup and down a flat runway, rats trained to traverse an obstacle course consisting of various ladders, thin rods, and ropes havemore synapses within the motor cortex (Kleim, Lussnig, Schwarz, Comery, & Greenough, 1996) and cerebellum (Kleim,Pipitone, Czerlanis, & Greenough, 1998). Animals trained on a skilled reaching task show dendritic growth (Withers &Greenough, 1989), synaptogenesis (Kleim et al., 2002; Kleim et al., 2004), and enhanced synaptic responses (Hodgson et al.,2005; Monfils & Teskey, 2004) within forelimb motor cortex. In comparison to controls, reach-trained rats also exhibit anexpansion of wrist and digit movement representations in the motor cortex that is localized to regions of motor cortex thatalso undergo synaptogenesis (Kleim et al., 2002; Kleim et al., 1998). Similar changes have been observed in squirrel monkeystrained to pull a small food pellet out of a tiny well. After several weeks of training, these animals show an increase in the areaof finger representations in primary motor cortex (Nudo, Milliken, Jenkins, & Merzenich, 1996). In each of these differentmotor learning tasks there is a similar pattern of neural plasticity that reflects the increased dexterity. The neural circuitsthat control the trained movements reorganize by adding synapses resulting in an expansion in the amount of cortexinvolved in controlling these movements. All of these data show that skill learning, even in a laboratory rat, leads to aprofound rewiring of the motor cortex that is observable both anatomically and physiologically.

Such neural plasticity is not limited to laboratory animals but can be demonstrated in the human motor cortex usingcomparable but less invasive techniques. Transcranial magnetic stimulation (TMS) has been used to demonstrate similarlearning-dependent neural plasticity in human motor cortex with skill training. Subjects trained on a one-handed, five-fingerpiano playing task show an increase in the area of motor cortex controlling the muscles of the hand trained during the taskand motor evoked potential (MEP) amplitudes (Pascual-Leone et al., 1995). Training subjects on skilled ankle (Perez,Lungholt, Nyborg, & Nielsen, 2004) or tongue (Svensson, Romaniello, Arendt-Nielsen, & Sessle, 2003) tasks also increasesmovement representation area and MEP amplitude of the trained muscles in comparison to untrained controls. Crosssectional studies have revealed comparable changes amongst individuals with varying degrees of motor skill. For example,highly skilled racket players have larger representation of muscles of the trained hand and larger (MEP) amplitudes in thesemuscles in comparison to less proficient players and non-playing controls (Pearce, Thickbroom, Byrnes, & Mastaglia, 2000)(Table 1).

J.A. Kleim / Journal of Communication Disorders 44 (2011) 521–528522

4. Recovery versus compensation

Although this paper presents neurorehabilitation as a relearning process there is one clear difference between learning inthe intact brain and relearning in the damaged brain. Specifically, unlike in normal learning conditions, rehabilitation cantake advantage of previously learned behaviors that may still exist within the residual neural circuits of the damaged brain.These behaviors may have been masked due to some neurobiological phenomenon such as inflammation, edema, orincreased neural inhibition (Cramer, 2008). This is not the case during normal learning conditions where behaviors areacquired de novo. Thus, there are two mechanisms by which functional improvement can occur in the damaged brain:recovery and compensation. Historically there have been several conflicting, misinterpreted, or poorly defined termsdescribing recovery and compensation used by scientists across several disciplines and clinicians (Levin, Kleim, & Wolf,2009). The different terminologies used to describe these concepts, particularly in the context of neural plasticity, are apotential confound in inter-disciplinary communication. Most neuroscientists would argue that there is never true recoverybecause once neural tissue is gone, it does not return and therefore any functional improvement has to be accomplishedthrough compensation. Many therapists argue functional improvements represent recovery because the patient can nowperform tasks that they could not perform immediately after injury, such as drinking from a cup or brushing their teeth. Weneed definitions that allow neuroscientists and therapists to use a common language and that encompass underlying aspectsof mechanism in order to be meaningful for neurorehabilitation. Levin et al. (2009) have recently proposed unambiguousdefinitions of recovery and compensation for motor function using the framework of the World Health OrganizationInternational Classification of Function (ICF) framework (Table 2). The ICF distinguishes between the underlyingpathophysiology of the health condition, impairments at the body function level, and disability at the activity level. Thedefinitions therefore recognize that recovery and compensation can be observed at both behavioral and neural levels.Further, they differentiate between behavioral measures of movement ability (Body Function) from task performance(Activity). Distinguishing recovery from compensation at both a neural and behavioral level is key towards understandingthe relationship between neural plasticity and rehabilitation-dependent changes in function. It provides insight into thespecific neural strategies an individual patient may employ or be guided towards through rehabilitation.

5. Neural strategies for motor improvement after brain injury

Neurorehabilitation therapists face several variables that can contribute to the capacity for functional improvementwhen treating neurological injury or disease. These include patient health status, age, lifestyle, and time after injury inaddition to the nature and locus/extent of the brain injury. All of these factors compound to create a brain that is verydifferent from the ‘‘normal’’ brain and an incredibly diverse range of impairments even within the same injury domain. Thisleads to further heterogeneity in the way that the residual brain areas adapt to the injury and potentially respond to therapythrough neural recovery and compensation. However, different neural strategies can be identified that involve neuralrecovery and/or compensation and take advantage of the inherent functional redundancy within the brain. They includerestoration, recruitment, and retraining (Table 2). These strategies are not mutually exclusive and occur in concert with oneanother during rehabilitation, so it can be difficult to clearly dissociate them especially in clinical studies. Although examplesof these strategies can be found in all behavioral domains including sensory and cognitive processing, they are most clearlyshown in cases of motor rehabilitation after stroke. Motor recovery refers to the capacity to perform a previously lost orimpaired motor task in exactly the same manner as before the injury. Motor compensation refers to the use of new

Table 2

The relationship between the different neural strategies used by the brain to support functional improvement after brain injury and the neural mechanisms

of recovery versus compensation.

Resuscitation Recruitment Retraining

Strategy Re-engaging residual brain

areas initially dysfunctional after

injury or disease.

Engaging new

residual brain areas.

Training residual brain areas to

perform new functions.

Neural Mechanism Recovery Compensation Compensation

Table 1

Distinguishing the behavioral and neural definitions of recovery versus compensation.

Recovery Compensation

Neural Restoring function in neural tissue that was

initially lost due to injury or disease.

Residual neural tissue takes over a function lost

due to injury or disease.

Behavioral: Body Function

(Impairment)

Restoring the ability to perform movement

in the same manner as it was performed

prior to injury or disease.

Performing movement in a manner different

from how

it was performed prior to injury or disease.

Behavioral: Activity (Function) Restoring the ability to perform a task in

exactly the same manner as it was performed

prior to injury or disease.

Performing a task in a manner different from

how it was performed prior to injury or disease.

J.A. Kleim / Journal of Communication Disorders 44 (2011) 521–528 523

movements or movement sequences to perform a task in a manner different from that used prior to injury. Studies of motorcortex plasticity after stroke have revealed that both recovery and compensation can be observed at a neurophysiologicallevel. Recovery refers to the restoration of motor function within an area of motor cortex that was initially lost after injury.Compensation occurs when areas of motor cortex adapt to take on motor functions lost after the injury.

5.1. Restoration

Residual brain areas undergo profound neurobiological changes following brain injury or disease resulting in dysfunctionwithin structurally intact brain areas both proximal and distal to the infarction. This phenomenon was first described by VonMonakow and termed diaschisis. The loss of function is due to a number of pathological changes in metabolism, blood flow,inflammation, edema, and neuronal excitability and is particularly evident during the acute phase (Duncan, Goldstein,Matchar, Divine, & Feussner, 1992). Functional improvement during this phase can occur in response to the progressiveresolution of these secondary factors that allows the motor cortex to return to a more normal functional state and begincontributing to motor improvement. However, restoration is also not limited to the acute phase after stroke, and one of theconsequences of damage within the motor system is learned nonuse. Many patients will avoid performing movements thatengage compromised but intact regions of motor cortex because it is simply too difficult or counterproductive. Patients mayadopt compensatory behaviors that avoid the use of the compromised regions of motor cortex that continue on well after theacute phase. This has distinct consequences for motor map topography as the motor representations corresponding to theignored movements may degrade despite maintaining some residual function. Rehabilitation training that forces orencourages the use of the avoided movements can re-engage the neglected neural circuits within motor cortex and reinstatethese movement representations. This has been demonstrated in both animal models and human patients.

Randy Nudo’s lab published a series of seminal papers demonstrating both restoration, recruitment, and retraining insquirrel monkey motor cortex after focal cortical infarctions. The experiments involve first using intracorticalmicrostimulation to create very detailed maps of hand movement representations. A small cortical infarction stroke isthen produced by devascularizing an area of cortex containing wrist and digit representations. The monkeys exhibitdifficulty in producing skilled wrist and digit movements when tested on a Kluver board where they are required to retrievefood pellets from a small well. The initial motor impairments are accompanied by a loss of hand representations that extendsinto undamaged areas of the map (Nudo, Wise, SiFuentes, & Milliken, 1996). However, with several weeks of training on thistask, the monkeys progressively improve and the wrist and digit representations can be partially restored within theundamaged cortex. The restoration of function is likely due to re-establishing neural connectivity within these areas. Studiesin rat motor cortex show that within 24 h of creating a small focal ischemic infarct, within approximately 30% of forelimbmovement representations there is an additional loss of movement representations within undamaged cortex. The loss ofmovement representations is accompanied by a loss of synapses presumably from the neurons within the infarct. Thus, theneurons within these circuits have not been lost but have become dysfunctional because of a lack of synaptic input. Withseveral days of motor rehabilitation, both the movement representations and the synapses can be restored (Fig. 1).

In clinical studies, similar restoration of motor maps can be shown using TMS. Motor maps are smaller in patients withmore severe impairments (Escudero, Sancho, Bautista, Escudero, & Lopez-Trigo, 1998) and increases in motor map size andcorticospinal output is correlated with motor improvement (Koski, Mernar, & Dobkin, 2004). Some of these changes are alsoreminiscent of those evidenced in the healthy subjects during motor skill learning (Karni et al., 1995). In other words, those

Fig. 1. Motor map of forelimb movement representations within rat motor cortex prior to and after stroke. Two weeks of motor rehabilitation restores

movement representations within residual cortical areas but not in animals without motor rehabilitation. The increase in motor map area is accompanied

by increases in the number of synapses per neuron within residual cortical areas.

J.A. Kleim / Journal of Communication Disorders 44 (2011) 521–528524

neural circuits that normally contribute to the performance of arm movement were not being engaged after stroke. This mayreflect diaschisis or learned nonuse in these areas resulting from the injury. Motor rehabilitation may serve to re-engagethese circuits and works to return them to a more normal state that is manifested as a restoration of movementrepresentations and an overall expansion of motor map area.

Evidence for restoration is also not limited to motor function but also can be shown with improvements in language andattention. Meinzer et al. (2008) show that treatment-induced changes of fMRI brain activation are highly correlated withimproved naming of the trained pictures but occur selectively within the pre-training dysfunctional perilesional brain areas.In a study of two patients receiving a syntax treatment, Wierenga et al. (2006) showed that in a patient whose performancedemonstrated generalization from treated to untreated tasks, a significant re-engagement of Broca’s area occurred. Thisindicates a functional reintegration of language areas that had been lost after the initial stroke. Similarly, Sturm et al. (2004)examined training-induced changes in functional activation in patients with right-hemisphere stroke and attentionalimpairments. The patients were trained on a computerized alertness training program for four weeks and functionalactivations during performance of another (unpracticed) alertness task were assessed using PET both before and aftertraining. In patients showing a training-induced improvement in alertness after training, there was reactivation of the right-hemisphere functional network known to subserve alertness in healthy participants.

5.2. Recruitment

Recruitment refers to enlisting motor areas that have the capacity to contribute to the lost motor function but may notnormally have been making significant contributions to that behavior prior to the injury. These areas are asked to play alarger role in the performance of the impaired motor behavior compromised because of stroke but are not necessarilyacquiring new function (retraining). Within the motor cortex this can be demonstrated through the expansion of movementrepresentations within areas outside of the original motor map. For example, recovery of dexterity after unilateral motorcortex lesions in macaques appears to be mediated by the premotor cortex in the damaged hemisphere, as inactivation ofthis region abolishes recovered movement but does not affect performance in non-damaged animals (Liu & Rouiller, 1999).Large infarctions within the primary motor cortex of squirrel monkeys cause a profound expansion of movementrepresentations within premotor cortex (Frost, Barbay, Friel, Plautz, & Nudo, 2003).

In comparison to healthy controls, stroke patients can show significant increases in contralesional motor cortex activityduring movement of the affected foot (Enzinger et al., 2008) or arm (Zemke, Heagerty, Lee, & Cramer, 2003). Some of theincreased activity also occurs in the ipsilesional dorsal premotor cortex (Gerloff et al., 2006) and TMS-induced disruption ofthe function within this area impairs recovered movement of the stroke-affected hand (Fridman et al., 2004), suggesting thatsuch activity is functionally relevant.

Studies in aphasics also show evidence for neural recruitment. In most individuals, language production is lateralized tothe left inferior frontal cortex (Broca’s area). After a stroke, performance on language production tasks can involverecruitment of the same areas in the right hemisphere that can be related to changes in performance after rehabilitation(Crosson et al., 2005). Meinzer et al. (2006) presented a stroke patient that demonstrated improved naming performanceafter two weeks of constraint-induced language therapy. When correct responses from both the pre- and post-treatmentsessions were compared to incorrect responses from both sessions, significantly greater activity was seen in the right inferiorfrontal gyrus for correct versus incorrect responses. Crosson and colleagues used complex left-hand movement during apicture-naming treatment in an attempt to activate the right-hemisphere and promote a shift of language productiontowards the right hemisphere in two chronic stroke patients (Crosson et al., 2005). The first patient showed significantimprovement on the task and substantial increases in the extent of right lateral frontal cortex activation after training. Thesecond patient also showed improvement but already had lateralization of production mechanisms to the right hemispherethat continued after treatment.

5.3. Retraining

In some cases, areas of motor cortex may be asked to adapt existing function or take on additional functions to supportfunctional improvement. Although this strategy is integrally related to restoration and recruitment in that neural circuits donot simply use their existing functions to contribute to behavior but begin to perform novel or additional functions. Asdescribed above, focal lesions within motor cortex cause a loss of movement representations within residual cortical areasthat can be restored with motor rehabilitation. These same studies also provide clear examples of retraining. For example,when an area of motor cortex containing digit representations is removed, digit representations can be observed to re-emerge in areas of the remaining cortex that used to contain elbow or shoulder (Barbay et al., 2006).

6. Clinical implications

The goal of this research area is of course to gain sufficient knowledge of the key behavioral and neural signals that driveneural plasticity in order to develop patient specific therapies that increase the opportunity for functional improvement.Neuroscience has identified several such signals and treatments such as deep brain stimulation for Parkinson’s andConstraint-induced movement therapy in stroke have become prevalent in clinics. Preclinical studies in animals have also

J.A. Kleim / Journal of Communication Disorders 44 (2011) 521–528 525

identified several pharmacological- and device-assisted therapies that hold promise for translation into clinical trials. Again,much of this work has come from studies of motor impairment after stroke. These studies are based on the hypothesis thatsynaptic plasticity mediates rehabilitation-dependent functional reorganization within the brain and thereforeinterventions enhancing plasticity should improve functional outcome. Furthermore, the field of neurorehabilitation isbeginning to recognize the importance of individualizing therapy for individual patients. Characterizing the specificbehavioral and neural impairment profiles for each patient may guide the development of specific therapies that maximizethe opportunity for neural plasticity within specific domains and ultimately enhance functional outcome.

7. Why should therapists care about neural plasticity?

Most training programs for physical therapy, occupational therapy, or speech language pathology focus primarily onbehavioral interventions that may have the greatest impact on enhancing functional outcome. So why should therapistsneed to know at all about neural plasticity? There are several answers to this question. First, measures of neural plasticityprovide a surrogate marker for functional improvement that is independent from behavior alone. It allows us to determinewhat neural systems are engaged and adapted during rehabilitation. Such information can help guide the behavioralstrategies used and provide information with respect to the importance of timing and intensity required to instantiateenduring neurobiological changes. Secondly, we can use our knowledge of the neural and behavioral signals that drive neuralplasticity to develop ‘‘performance enhancing’’ therapies. One might liken the road to functional recovery after stroke to thatof a young healthy individual training for the Olympics: It takes years of practice and intense training to reach the desiredlevel of performance. However, unlike Olympics trainers, rehabilitation therapists are not prohibited from usingperformance enhancing, adjuvant treatments. Indeed, there have been several preclinical and clinical studies ofinterventions known to augment endogenous plasticity mechanisms in order to enhance functional outcome. In otherwords, we can harness and exploit neural plasticity.

7.1. Pharmacological treatments

One approach to enhancing neurorehabilitation is to employ pharmacological manipulations that upregulateendogenous intracellular signaling pathways that drive synaptic plasticity. Although numerous signaling pathways havebeen identified, the most well characterized is the cAMP/CREB pathway. A variety of experimental models and systems haveestablished the cAMP/CREB signaling pathway to be a key regulatory pathway in experience-dependent synaptic plasticity.Pharmacological agents that inhibit this signaling pathway impair memory formation (Wenk, Thallmair, Kartje, & Schwab,1999). Conversely, administration of the type IV-specific phosphodiesterase inhibitors (PDE 4) that enhance cAMP/CREBsignaling facilitate memory in normal and aged rodents (Monti, Berteotti, & Contestabile, 2006). PDE4 inhibitor treatment incombination with motor rehabilitation following a focal stroke significantly enhanced motor recovery (MacDonald et al.,2007). Further, the drug increased motor map area in residual cortex (restoration), increased the proportion of the mapsoccupied by distal forelimb representations (retraining), and expanded movement representations into new cortical areas(recruitment).

In addition to drugs that enhance plasticity, several neurochemicals have been identified that may block plasticity-inhibiting processes such as axonal sprouting. For example, myelin-associated inhibitory factors (such as Nogo-A) arepresent in neural tissue that block neurite outgrowth after damage. When antibodies for Nogo-A (IN-1) are applied to themotor cortex following ischemic lesion, there is an increase in apical and basilar dendritic arborization and spine density oncortical pyramidal neurons (Papadopoulos et al., 2006). In addition, new projections to the de-afferented striatum (Kartje,Schulz, Lopez-Yunez, Schnell, & Schwab, 1999) and red nucleus (Wenk et al., 1999) have been observed. ICMS (intracorticalmicrostimulation) mapping of the intact hemisphere following treatment with monoclonal antibody IN-1 results in asubstantial increase in ipsilateral movements (Emerick, Neafsey, Schwab, & Kartje, 2003). Such manipulations couldfacilitate compensation through recruitment of distal brain areas.

7.2. Neural stimulation

Some of the very first demonstrations of neural plasticity involved the use of electrical stimulation to enhance synapticstrength. There is a growing body of evidence that electrically stimulating the motor cortex facilitates recovery of motorfunction after brain injury, particularly stroke. Following cortical stroke, there is an imbalance between the cerebralhemispheres whereby the affected side becomes inactive and the unaffected side becomes overactive. Repetitivetranscranial magnetic stimulation (rTMS) has been used to excite the affected hemisphere and inhibit the unaffectedhemisphere in order to restore balance and promote functional reorganization in the affected hemisphere. This approach hasbeen used successfully in some stroke patients to enhance motor performance with rehabilitation (Khedr & Abo-Elfetoh,2010). Transcranial direct cortical stimulation (tDCS) provides a longer, more sustained, method for driving plasticity withinthe cortex and has been shown to improve motor function in patients with chronic motor impairments when anodal currentis delivered over lesioned motor cortex or cathodal current is delivered over the contralesional motor cortex (Fregni et al.,2006).

J.A. Kleim / Journal of Communication Disorders 44 (2011) 521–528526

The efficacy of cortical stimulation at enhancing motor recovery after stroke has also been demonstrated in rats (Kleim etal., 2003) and in monkeys (Plautz et al., 2003). The enhanced motor recovery is associated with increased cortical dendritichypertrophy (Adkins-Muir & Jones, 2003) and synaptogenesis (Adkins, Hsu, & Jones, 2008) in comparison to animals instandard rehabilitation. The increased post-synaptic space is also accompanied by an enlargement of the polysynapticcomponent of motor cortical evoked potentials (Teskey, Flynn, Goertzen, Monfils, & Young, 2003). Finally, corticalstimulation also induces a greater expansion of movement representations in rats (Kleim et al., 2003) and monkeys (Plautzet al., 2003). This suggests that cortical stimulation has the potential to upregulate plasticity within the lesioned cortex topromote functional reorganization.

8. Summary

This brief review highlights the importance of understanding neural plasticity in neurorehabilitation. Characterizing theneural and behavioral signals that drive plasticity in concert with identifying the neural strategies employed duringrehabilitative training can guide the development of novel, more effective, therapeutic strategies.

Appendix A. Continuing education

1. Neural plasticity can be defined as:a. The capacity for neurons to structurally and functionally adapt.b. The genesis of new neurons during development.c. The ability to recovery from brain injury.d. Changes in behavior observed during learning.

2. Functional improvement after brain injury:a. Is always dependent on rehabilitation.b. Only occurs in young healthy individuals.c. Is a relearning process involving neural plasticity.d. Requires drugs in order to boost endogenous neural plasticity.

3. The three basic neural strategies mediating functional improvement after brain injury are:a. Revisitation, Regeneration and Restoration.b. Restoration, Recruitment and Retraining.c. Recapitulation, Recruitment and Restoration.d. Regeneration, Restoration and Recapitulation.

4. Adjuvant therapies can aid in neurorehabilitation by:a. Allowing neural plasticity to occur in the absence of rehabilitation.b. Promoting self motivation.c. Inhibiting neurogenesis.d. Enhancing endogenous neural plasticity during rehabilitation.

5. Understanding the neural mechanisms mediating improvements in speech, hearing and language:a. Can only be obtained by studying these behaviors in brain injured patients.b. Can be inferred by studying plasticity in other systems.c. Is only observable in animal models.d. None of the above.

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