WHAT CAN NEUROBIOLOGY TELL US ABOUT THE REHABILITATION
OF GOLFERS WITH CENTRAL NERVOUS SYSTEM DISEASE?
Steven L. Small, M.D., Ph.D.
The University of Chicago
Chicago, IL
Ana Solodkin, Ph.D.
The University of Chicago
Chicago, IL
Introduction
With diseases of the central nervous system (CNS), particularly cerebrovascular diseases, playing
a paramount role in mortality and morbidity, the clinical and basic scientific study of acute care of
CNS disease has blossomed. Concomitant advances in acute management have led both to increased
survival and to increasing numbers of people with disabilities. Neurobiological study of the chronic
form of these diseases has lagged behind investigation of the acute syndromes. Although the focus of
this article will be on stroke, since this is the most prevalent of these diseases, the main thrust of the
article equally applies to traumatic brain injury and infectious diseases, as well as to the chronic
degenerative diseases, such as Parkinson’s Disease and Alzheimer’s Disease. People with expert
motor skills, such as musicians and athletes, are equally affected by these diseases as are others, but
the neurobiological underpinnings of the expert skill may include some additional circuits that might
be an additional focus of rehabilitative efforts.
Rehabilitative measures for CNS diseases are generally based on empirical concepts of functional
outcome rather than on basic neurological principles. While there is significant knowledge about
neuropharmacological and neuroanatomical changes that take place immediately after stroke and
brain injury, and some knowledge of the neurobiology of the more chronic recovery phase, clinical
neurorehabilitation does not generally use this information. The practice of rehabilitation remains
rooted in empirical concepts leading to functional outcome, without any attempt to delve into the
underlying biology. Whereas such information could be helpful for general motor (or sensory or
cognitive) rehabilitation, it could be particularly useful in the recovery of specialized motor skills
such as musical performance or sports.
In the case of golfing, motor performance requires a complex interaction between brain systems
for both motor planning and execution. Of the component processes involved in taking a golf shot,
several involve general (non-motor) skills that have been specialized for golf, and others involve
primarily motor areas of the brain. Experts and novices probably differ in the exact stages of this task,
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with experts having highly practiced and overlearned behaviors and significant commonality among
individuals, but with novices having less practiced skills that require more spontaneous motor
planning and execution and are more likely to manifest large individual differences. These differences
in performance suggest differences in neurobiological substrate. Expert skill at golf may resemble the
overlearned simple activities of more mundane motor tasks, whereas novice performance may
resemble other motor tasks that are novel and unpracticed. One plausible inference from this analogy
is that the relearning of simple tasks may be akin to novel skill acquisition.
Some of the attempts to alter the course of neurobiological recovery in animal models (Feeney,
Gonzalez, & Law, 1982) and humans (Crisostomo, Duncan, Propst, Dawson, & Davis, 1988; McNeil,
Doyle, Spencer, Goda, Flores, & Small, 1997; Small, 1994) have shown promise, but have not yet
demonstrated the potential to have a major impact.
In this review, we discuss several lines of research that are leading toward a neurobiological basis
for rehabilitation of central nervous system injury. These efforts encompass both animal models and
human studies, and focus on the chemical and/or anatomical changes occurring in the brain after
stroke. This review pays special attention to those neurobiological data that might be exploited in
developing a clinical neurorehabilitation that is grounded in basic scientific principles and in data that
are particularly relevant to the recovery of highly skilled motor activities. Our survey begins with
some general features of cerebral cortical anatomy relevant to motor recovery, considers some issues
related to expert motor skill, and then discusses interventional strategies that have made use of this
information as well as functional neuroimaging approaches to monitoring recovery and therapy.
Aspects of Human Cortical Anatomy
Prior to the most recent studies of cortical organization using functional imaging methods, most
knowledge of the functional anatomy of the human cerebral cortex was derived from two sources,
lesion analysis (Damasio & Damasio, 1989) of patients with focal cerebral injury and cortical
electrical stimulation or recording in patients undergoing neurosurgical procedures (Ojemann,
Ojemann, Lettich, & Berger, 1989).
A lesion to the primary motor cortex (M1) in man (precentral gyrus; Brodmann area = BA 4)
causes motor weakness in the contralateral face and limbs (Brodal, 1981). Lesions in the inferior
aspects of the precentral gyrus cause weakness to the muscles of the mouth and face. More superiorly,
lesions lead to weakness in the hand and arm. Lesions in the paracentral lobule cause weakness to the
leg and foot.
Although motor cortical lesions characteristically cause contralateral deficits, they can also
produce some ipsilateral impairments, particularly when the lesion occurs on the side of the dominant
hand (Kim, Ashe, Hendrich, Ellermann, Merkle, Ugurbil, & Georgopoulos, 1993). The presence of
ipsilateral impairment might not be surprising, given that about 10% of fibers do not cross at the
medullary decussation and are found in the lateral corticospinal tract on the same side (Brodal, 1981;
Nyberg-Hanson & Rinvik, 1963). Since these ipsilateral efferent fibers innvervate proximal muscles,
the ipsilateral motor deficits may reflect disruption in the complex interactions between M1 and the
association motor cortices (which in fact tend to be bilateral). Hemispheric asymmetry for motor
function has not received as much attention as other asymmetries, and certainly we are in the early
stages of research into the complex interactions among different motor cortices(Solodkin, Hlustik,
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Noll, & Small, 2001). Both the bilateral hemispheric innervation of the peripheral motor system and
its asymmetry have important implications for neuroanatomical recovery from stroke.
Direct cortical stimulation has provided the most specific details about the fine somatotopic
structure of the cerebral cortex. Following the demonstration in 1870 of this method (Fritsch &
Hitzig, 1870), Ferrier (1876) demonstrated a correlation between site of stimulation near the central
sulcus and motor response in a macaque monkey. This technique was applied to mapping in awake
patients, demonstrating somatotopy for the motor system (Penfield & Rasmussen, 1950).
Interestingly, even though Penfield showed some degree of overlapping representations in his
somatotopic maps, his reading audience over the years (including the authors of textbooks) has
overgeneralized the concept. Using functional imaging, we have recently re-examined the extent of
this somatotopy, and have described a graded overlapping topography in this region (Hlustik,
Solodkin, Gullapalli, Noll, & Small, 2001a).
Functional neuroimaging has confirmed the basic anatomy of the motor cortex, thus
demonstrating in a reliable functional system the significant role that imaging can play in anatomical
studies in human subjects. These methods have also begun to play a role in tracking recovery from (or
progression of) neurological disease.
Neuroimaging studies of the motor
system, particularly involving finger
Cognitive (Non-Motor) Assessment
movements, have revealed features of
Assess
the functional cortical anatomy. Both
distance
View
Choose club
PET and fMRI studies demonstrate
Terrain
activation sites in the contralateral
Assess wind
primary motor cortex with finger
movements (Colebatch, 1991; Grafton,
Woods, Mazziotta, & E., 1991;
Roland, Meyer, Shibasaki, Yamamoto,
"Pre-Shot Routine"
? PM, S MA, CM A, M1
& Thompson, 1982). Some fMRI
Novice: Plan
studies have also demonstrated
motor
sequence
Integrate enviipsilateral activation with these
ronmental
movements (Boecker, Kleinschmidt,
variables
Expert: Instantiate
Requardt, Hanicke, Merboldt, &
? Pre-frontal
motor pla n
Frahm, 1994; Kim, et al., 1993). Other
? PM, CMA, BG
studies
have
implicated
the
supplementary motor cortex (SMA) in
complex but not simple finger
Motor Execution
movements (Boecker, et al., 1994;
Rao, Binder, Bandettini, Hammeke,
Initiate
Execute
Follow
Yetkin,
Jesmanowicz,
Wong,
motor
motor
through
Estkowski, Goldstein, Haughton, &
sequence
sequence
?limbic
Hyde, 1993).
?PM, M1
?SMA
One study that we have conducted
demonstrates significant differences Figure 1: Tentative Framework for Taking a Golf Shot
between brain activation patterns in
left handers and right handers, and between simple and complex movements (Solodkin, et al., 2001).
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These results have significant bearing on the understanding of advanced motor skill, including
sporting and musical performance. In golf, for example, taking any form of shot, from driving the ball
from the tee to putting from a short distance away, involves a complicated set of motor plans and
executions. Since such performance is even more complex than the sequential movements described
by Solodkin et al (2001), it would be expected that making a golf shot might require not only
contralateral M1, but the other cortical motor areas as well, including ipsilateral M1 and bilateral
premotor areas, both medial (cingulate motor area (CMA) and supplementary motor area (SMA)) and
lateral premotor area (PM).
We have recently begun an fMRI study of motor planning and execution in golfers imagining a
shot, and have some unpublished pilot data suggesting that such activity may indeed involve premotor
structures. Published electroencephalographic data suggest that an expert taking a golf shot requires
specialized motor planning and attentional mechanisms (Crews & Landers, 1993), and based on
studies of apraxia (Heilman, Maher, Greenwald, & Rothi, 1997) and imaging (Hlustik, Solodkin,
Gullapalli, Noll, & Small, 1998; Hlustik, Solodkin, Noll, & Small, 2001b), we would suggest that the
left lateral premotor cortex plays a special role in this pre-execution behavior. Studies of expert
performance (including golfing) using electrographic methods have suggested a hemispheric
difference, with left hemisphere activity diminishing just prior to execution of a complex motor skill,
whether one conducted with solely the right hand (such as shooting) or those conducted with both
hands (such as archery or putting).
Based on a large literature in motor performance, but only limited data on expert performance, we
suggest that the execution of a golf shot incorporates many subcomponents subserved by a complex
interactive circuit including numerous brain regions. At the risk of over-speculation, our conception
of planning and executing a golf shot appears in Figure 1. An expert golfer assesses the environment
carefully prior to doing any overt motor planning or execution, and this is indicated in the Figure
without comment. The motor activity related to taking a golf shot differs between experts and
novices, and this is also indicated in the Figure. Overall, the expert is likely to perform a different
type of planning, not only because he can maintain more selective attention than novices, but also
because he likely makes access to a number of over-trained circuits related to the execution of
particular golf shots. In contrast, the novice, needs more planning, since he cannot maintain the same
degree of selective attention as the expert, and does not yet have these over-trained circuits that
underly the experts’ representations. Under these two conditions (experts and novices), the interaction
among motor areas is likely to differ significantly, since the circuits involved will subserve different
actions.
Acute Brain Injuries and Cerebral Cortical Plasticity
Functional representations in the cerebral cortex are dynamic, with constant reshaping, remolding,
and rearrangement. The most persuasive examples are the recent studies showing remarkable changes
in cortical anatomy with repeated sensory (Wang, Merzenich, Sameshima, & Jenkins, 1995) or motor
stimulation (Hlustik, Solodkin, Noll, & Small, 2000; Karni, Meyer, Jezzard, Adams, Turner, &
Ungerleider, 1995). The ubiquity of representational changes as part of the normal functioning of the
cerebral cortex should facilitate the processes of functional recovery from stroke. The overall extent
and permanency of possible anatomical changes is controversial due in part to the relationship
between plasticity and age. In this section, we consider several types of plasticity thought to be
possible in adults, including growth of neurons themselves, axonal sprouting with new synapse
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formation, or modification of existing synapses.
Functional anatomical codes in the cerebral cortex are not static structures, but are constantly
changing and reshaping with environmental influences. Changes that occur relatively fast (i.e., hours
or days) include the sizes of cortical topographic regions devoted to the sensory or motor function of
the digits (Gilbert, 1992; Jacobs & Donoghue, 1991). Slower alterations (i.e., months or years) occur
in the process of learning new skills (e.g., complex sensorimotor skills) (Gilbert, 1992). In the case of
stroke recovery, anatomical reorganization probably occurs in several phases. Evidence suggests that
within the faster time frame are processes of "unmasking" existing circuits that follow pre-existing
anatomical connections. On the longer time frame, axonal sprouting and synaptogenesis may mediate
more substantial anatomical changes and concomitant improvements in recovery.
The unmasking of existing viable circuits has been postulated to explain fast (hours to days)
reorganization in motor, sensory, and visual systems after acute CNS injury (Das & Gilbert, 1995;
Jacobs & Donoghue, 1991; Kaas, Krubitzer, Chino, Langston, Polley, & Blair, 1990; Keller,
Weintraub, & Miyashita, 1996). In young and adult rat somatosensory cortex, for example, cortical
movement representations change over a short time scale with alterations in input (tactile experience
via whiskers) (Keller, et al., 1996). This was true for groups of both young and old animals. Shortterm changes in spatio-temporal reasoning have recently been demonstrated following complex
musical experience (Rauscher, Shaw, & Ky, 1995).
Evidence from both the visual (Das & Gilbert, 1995; Gilbert, 1992) and motor systems (Huntley,
1997) suggests that unmasking in the cerebral cortex may be mediated by the intra-cortical connection
patterns present prior to a stroke. In particular, the pattern of horizontal connections between
damaged and undamaged brain areas may determine the precise nature of the short-term anatomical
changes that occur. The functional maps seem to shift to those areas linked to the damaged regions by
these horizontal connections, and where these are absent, the maps may be incapable of shifting
(Huntley, 1997; Jacobs & Donoghue, 1991).
Although certain animals generate new neurons in adaptation to environmental changes (Barnea
& Nottebohm, 1994), this is unlikely to be a relevant mechanism in adult stroke recovery. On the
other hand, there is growing evidence that changes in behavior can lead existing neurons to change
their patterns of synaptic connectivity. This has led to new receptive fields for cortical sensory
neurons. Such changes have been observed in the somatosensory system with both peripheral nerve
stimulation (Jenkins, Merzenich, Ochs, Allard, & Guic-Robles, 1990) and behavioral alterations
(Recanzone, Allard, Jenkins, & Merzenich, 1990). In the visual system, axonal sprouting has been
reported in the reorganizing adult cat striate cortex for several months following a retinal lesion
(Darian-Smith & Gilbert, 1994). Dendritic proliferation may be possible in adults of all ages,
including old age (Coleman & Flood, 1986).
In experimental lesions of the somatosensory cortex, animals were subsequently trained on
behavioral tasks to attempt to influence reorganization of cortical anatomy. Soon after the lesions, the
animals used the affected hands in a limited manner, avoiding tasks requiring the type of precise
somatosensory information as required for fine motor control. In this first few weeks,
electrophysiological study revealed little change in the somatosensory cortical maps for the hand.
However, after several months, electrophysiological recording revealed that skin areas previously
encoded by the damaged region of cortex became encoded by adjacent spared cortical regions
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(Jenkins & Merzenich, 1987). In the motor cortex, the same technique alters the cortical
representations of movement (Nudo, Jenkins, & Merzenich, 1990). In cat, long-term stimulation of
the ventroposterolateral nucleus of the thalamus has led to significantly increased synaptic density
and synaptic active zones in M1 (Keller, Arissian, & Asanuma, 1992). These studies provide
important data for neurobiological approaches to rehabilitation.
It has been recognized that the behavior of a patient with a focal brain lesion, e.g., from a vascular
insult, reflects less on the function the damaged region than on the function of the entire brain when it
is missing that region. Many therapists believe that performance actually reflects the adaptive
behavior of the entire organism (and especially the brain) in the presence of damage. The behavioral
implications change from restoration of lost function to improving the functional adaptation to
damage.
Although this article is concerned mostly with acute CNS injuries, it is nonetheless useful to note
that a strictly temporal property of vascular occlusions and traumatic injuries, i.e., their sudden onset,
contributes to morbidity. By way of contrast, slow growing tumors can become quite large before
affecting function at all. We recently studied patients with vascular malformations, none of whom had
noticeable functional deficits, including one with a lesion affecting the inferior frontal gyrus who had
a very mild dysnomia. In these patients, functional activation occurred near the region that would be
expected to be involved in the target task (Witt, Konziolka, Baumann, Noll, Small, & Lunsford,
1996). This suggests that in slowly developing brain lesions, where the damage occurs in small
increments over a long time period, local circuits can reorganize incrementally and successfully. In
the case of larger and/or more rapidly developing lesions, such adaptation does not occur as readily.
Brain regions encode functional information in a dynamic manner. In animal models, it has been
possible to perform electrophysiological mapping of areas of the primary sensory and motor cortex
before, during, and after altered behavior aimed at augmenting or reducing the functional
responsibility of parts of these cortical regions. With practiced motor activity of certain fingers, the
volume of motor cortical tissue dedicated to those fingers increased (Nudo, et al., 1990). Repetitive
peripheral nerve stimulation led to reorganization of the primary sensory cortex (SI) dedicated to the
stimulated area (Jenkins, et al., 1990). When two fingers were tied together and used as a single digit,
the functional organization of SI changed to encode the new structure as a single digit, losing the
previous cortical encoding of the inner surfaces of the two fingers (Allard, Clark, Jenkins, &
Merzenich, 1991). Amputation of a finger led to reorganization of SI, with loss of the cortical
encoding of the missing finger, and increase in size of the areas responsible for the adjacent fingers
(Merzenich, Nelson, Stryker, Cynader, Schoppmann, & Zook, 1984).
Important evidence is emerging that this cortical reshaping depends on the nature of practice,
rather than simply on its presence. In an experiment with adult squirrel monkeys, goal directed motor
training led to better outcomes in both performance and neuroanatomical reorganization than no
training or simple motor repetition (Nudo, Wise, SiFuentes, & Milliken, 1996). Some human patients
seem to exhibit "learned non-use" of a hemiparetic extremity, a maladaptive behavior pattern that can
be altered by specific types of physical practice of the impaired limb while the normal limb is
restrained (Taub, Miller, Novack, Cook, Fleming, Nepomuceno, Connell, & Crago, 1993).
This might be important for motor rehabilitation of the skilled athlete or musician. There are a
several pieces of relevant information. First is that skilled motor activities involve some of the same
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and some different cortical structures than unskilled activities. Second is the general premise that
recovery of motor function relates to reorganization of neural structures and/or employment of
accessory neural structures. Third is that compensatory skill acquisition can impede remediation.
Taken together, it might be the case that rehabilitation of expert golf skill requires some different
(additional) approaches than rehabilitation of more mundane motor activities. This would likely
depend on the precise nature of the brain lesion and the concomitant circuit disruption caused by the
injury. Further, this would depend on just how much of the "expert" network was necessary to relearn
the (previously) mundane motor skills, since existing evidence suggests that motor rehabilitation of
even simple motor activity involves re-integrating motor plans and skills into more automatic
networks, just the sort of thing requires to achieve expert proficiency at higher order motor skills. On
the other hand, the expert also requires tremendous planning and attentional activity prior to task
execution, something that may or may not be involved in more mundane tasks.
Recovery from Brain Injuries
Brain imaging has been of major importance in helping to understand brain metabolic changes
that occur following acute brain injuries such as stroke. In such studies, PET scans are performed
18
during rest after the administration of [ F] fluoro-deoxyglucose (FDG), an isotope that is transported
into cells with glucose, is phosphorylated as glucose, but then simply accumulates in the cell. Such
scans provide data about regional brain metabolism.
In patients with aphasia, it has been noted using structural imaging methods that the location of a
lesion does not correlate well with symptomatology (Alexander, Naeser, & Palumbo, 1990) or with
degree of recovery (Mezger & Busch, 1988). Studies of metabolism using FDG-PET have improved
upon this situation to a degree, demonstrating that infarcted brain areas are not the only ones affected
metabolically (Meyer, Obara, & Muramatsu, 1993). In particular, when FDG-PET hypometabolism is
taken into account in defining a lesion causing aphasia, the correlation with symptomatology is better
(Metter, Wasterlain, Kuhl, Hanson, & Phelps, 1981).
In motor system stroke, resting metabolic PET studies have shown that recovery correlates with
increased cortical metabolism in motor areas of the affected hemisphere (Di Piero, Chollet,
MacCarthy, Lenzi, & Frakowiak, 1992). In contrast, patients with striatocapsular stroke (Weiller,
Chollet, Friston, Wise, & Frackowiak, 1992) showed lower regional cerebral blood flow (rCBF) in
the basal ganglia, thalamus, sensorimotor, insular, and dorsolateral prefrontal cortices, and in the
brainstem contralateral to the side of the recovered hand and in the ipsilateral cerebellum. Increased
rCBF was found in the contralateral posterior cingulate and premotor cortices, and in the caudate
nucleus ipsilateral to the recovered hand.
In a set of pioneering neuroimaging studies of neurological recovery using PET, the functional
anatomy of the motor system was examined in groups of patients following motor system stroke
(Chollet, DiPiero, Wise, Brooks, Dolan, & Frackowiak, 1991; Weiller, et al., 1992; Weiller, Ramsey,
Wise, Friston, & Frackowiak, 1993). In a group of patients with different types of strokes (Chollet, et
al., 1991), movement of the normal fingers led to increased rCBF in contralateral primary
sensorimotor cortex and in the ipsilateral cerebellar hemisphere, whereas movement of the recovered
hand showed increased rCBF in sensorimotor cortex and cerebellum bilaterally. Insula, inferior
parietal, and premotor cortex were also bilaterally activated with movement of the recovered hand.
Movements of the recovered hand in patients with striatocapsular infarction (Weiller, et al., 1992)
activated the contralateral cortical motor areas and ipsilateral cerebellum to the same extent as did
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normal subjects, but showed increased activation in both insulae, inferior parietal (area 40),
prefrontal, and anterior cingulate cortices, ipsilateral premotor cortex and basal ganglia, and
contralateral cerebellum.
A follow-up to these studies (Weiller, et al., 1993) examined individual variability in this
reorganizing anatomy. In comparing individual patients with the averaged results from normal
subjects, it was found that most recovering stroke patients had increased activation of the ipsilateral
premotor cortex and about half in the contralateral primary motor cortex. Increased activation levels
occurred in other patients in combinations of ipsilateral and bilateral regions of the insula, parietal
cortex, prefrontal cortex, cerebellum, and anterior cingulate.
Biological Approaches to Treatment of Chronic Neurological Injury
During the initial phases of acute CNS injury, a wide variety of homeostatic mechanisms
supervene. The nature of these changes and their significance to the overall degree of brain injury and
development of morbidity is of great current interest (Coull, 1996). Additional biological changes
occur during the subsequent subacute and chronic stages of recovery, some of which might be
influenced to improve recovery. A small effort in the pharmacology of neurorehabilitation has led to
some interesting results.
Studies of catecholamine systems in animal models of stroke have attracted the most interest, with
the acute decreases in catecholamine concentration in the cortex and brainstem of the rat persisting
chronically, including a decrease in the concentration of norepinephrine (NE) in the ipsilateral cortex
and brainstem, and a decrease in the concentration of dopamine (DA) in the ipsilateral brainstem but
not cortex (Robinson, Shoemaker, Schlumpf, Valk, & Bloom, 1975). Bilateral reduction of glucose
utilization in the cortex and locus coeruleus (LC) and in the ipsilateral red nucleus are also present
(Feeney, Sutton, Boyeson, Hovda, & Dail, 1985).
Intravenous interventions with dextro-amphetamine, haloperidol, and phenoxybenzamine have
suggested that both dopamine and norepinephrine (via 1 receptors) might play a role in mediating
recovery. In general, the beneficial effects of catecholamines are only seen when drug intervention is
accompanied by experience (Small, 1994).
Dextro-amphetamine has been used in several human studies of motor and language recovery, all
suggesting some degree of benefit (Small, 2001). As in the case of experimental animals, the
beneficial effects of dextro-amphetamine seem to supervene only in the context of concomitant
behavioral or physical therapy. Whether or not such pharmacological adjuncts could play a role in
recovery of expert skill remains open.
Summary and Conclusions
Neurobiology can and must contribute to the study of central nervous system rehabilitation:
although recovery of human performance following brain injuries undoubtedly depends on both acute
and chronic recovery processes in the brain, clinical neurology only plays a role in the acute setting.
With a neurobiological approach to rehabilitation, this situation will change. Furthermore, as
discussed here, it will be possible to use specialized neurobiological insights regarding the specific
skill set of an individual to tailor therapy toward the critical neural circuits and/or reorganizational
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mechanisms. In the case of expert motor skill, the relevant networks include bilateral premotor areas,
both medial and lateral, as well as frontal and parietal areas that focus on memory and attention. It is
only by further study of these mechanisms in skilled performers will the full array of possibilities
become clear. At no point do we expect to uncover a phrenological "golf" area of the brain. Nor do
we expect to uncover circuits that are specific to golf at the exclusion of other skills. On the other
hand, we do expect that expert golfers make use of highly overtrained neural networks, and that by
adapting rehabilitative training to these networks, whether by golfing or through other types of
activities (e.g., selective attentional tasks, related motor planning tasks), individualized therapeutic
gains might be possible.
Four main points should be summarized. First, the anatomical organizations of functional brain
systems are less topographically precise as commonly believed and are highly variable across
individuals. Second, that cortical plasticity exists in adults and takes a number of forms, including
unmasking of existing circuits, growth of new synapses via axonal sprouting or dendritic
proliferation, and development of compensatory processes. Third, that is it possible to manipulate this
plasticity with behavioral and pharmacological interventions, and that such manipulation can have a
beneficial effect on recovery. Fourth, that by understanding the neural circuits underlying unusual
skills, these interventions might be tailored to rehabilitative gains in specialized areas.
Finally, it is our belief that functional neuroimaging, particularly the non-invasive method of
fMRI, can be used to study in vivo cerebral plasticity in normal skill acquisition as well as in recovery
from CNS injury. In addition, this method can play a role in assessing the mechanisms and efficacy of
interventions aiming to influence recovery by affecting this plasticity.
Acknowledgments
The support of the National Institutes of Health under grant NS-1-R01-37195 is gratefully
acknowledged.
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