Motor Control Abnormalities in Parkinson’s Disease

Motor Control Abnormalitiesin Parkinson’s Disease

Pietro Mazzoni, Britne Shabbott, and Juan Camilo Cortes

Motor Performance Laboratory, The Neurological Institute, Columbia University, New York,New York 10032

Correspondence: [email protected]

The primary manifestations of Parkinson’s disease are abnormalities of movement, includingmovement slowness, difficulties with gait and balance, and tremor. We know a considerableamount about the abnormalities of neuronal and muscle activity that correlate with thesesymptoms. Motor symptoms can also be described in terms of motor control, a level ofdescription that explains how movement variables, such as a limb’s position and speed,are controlled and coordinated. Understanding motor symptoms as motor control abnor-malities means to identify how the disease disrupts normal control processes. In the case ofParkinson’s disease, movement slowness, for example, would be explained bya disruption ofthe control processes that determine normal movement speed. Two long-term benefits ofunderstanding the motor control basis of motor symptoms include the future design of neuralprostheses to replace the function of damaged basal ganglia circuits, and the rational designof rehabilitation strategies. This type of understanding, however, remains limited, partlybecause of limitations in our knowledge of normal motor control. In this article, wereview the concept of motor control and describe a few motor symptoms that illustrate thechallenges in understanding such symptoms as motor control abnormalities.

The effects of Parkinson’s disease (PD) can bedescribed atdifferent levels. Within thebrain,

the major pathological change is progressive de-generation of neurons in the pars compacta ofthe substantia nigra, one of the nuclei that con-stitute the basal ganglia (BG). These neuronsnormally transmit dopamine to another BG nu-cleus, the striatum, but their degeneration leadsto dysfunction of these neuronal circuits thatinclude the BG and motor cortical areas. At thelevel of an individual’s behavior, these changesresult in movement abnormalities, which are the

major manifestations of the disease. These dif-ficulties, in turn, cause major disruptions thatrange from an individual’s quality of life to soci-ety-wide economics. Our goal in this article is todescribe motor symptoms of PD at the level ofmotor control. We briefly review what is meantby “motor control” and describe the process ofunderstanding a symptom as a motor controlabnormality. We then focus on selected symp-toms that, among the many and varied motorsymptoms of PD, have been most studied froma motor control perspective.

Editor: Serge Przedborski

Additional Perspectives on Parkinson’s Disease available at www.perspectivesinmedicine.org.

Copyright # 2012 Cold Spring Harbor Laboratory Press; all rights reserved.

Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a009282

1

ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org

Press on December 10, 2021 - Published by Cold Spring Harbor Laboratoryhttp://perspectivesinmedicine.cshlp.org/Downloaded from

http://perspectivesinmedicine.cshlp.org/

MOTOR SYMPTOMS OF PARKINSON’SDISEASE

PD can cause a variety of motor symptomsand signs, several of which are listed in Table 1.Note that we will interchangeably use the terms“symptom” (a disease manifestation experi-enced by the patient) and “sign” (a disease man-ifestation detectable by a clinician) in this articlebecause the distinction between these terms

does not affect the present discussion. Severalsymptoms (Table 1, “Common”) are very com-mon and appear in most patients at some pointin the course of the illness. Bradykinesia, akine-sia, and hypokinesia are nearly universal symp-toms, in that they eventually appear in nearlyevery patient. They are typically present earlyin the course of the disease. Although the usageof these terms varies, “bradykinesia,” “akinesia,”and “hypokinesia” generally refer to a paucityand generalized slowing of movements in theabsence of weakness (Hallett 1990; Fahn 2003).Movements take more time, and there is reducedfrequency of spontaneous movements, such asblinking, smiling, and grimacing, which givesthe face a mask-like, expressionless appearance.In this article, we use “bradykinesia” in referenceto movement slowing; “hypokinesia” for reduc-tion of movement amplitude (and/or force);and “akinesia” for the two phenomena of pau-city of movements and delayed movement initi-ation. “Postural instability” refers to impairedreaction when balance is perturbed. For exam-ple, tripping on an uneven sidewalk may lead toa fall because the patient’s response is inadequatefor recovery of balance. “Rigidity” refers to in-creased muscular tone. There is more resistancethan normal when the limb is passively moved(e.g., by a clinician). Rigidity is usually experi-enced as a sense of feeling stiff and uncomfort-able. “Stooped posture” is an abnormal posturemarked by shoulder dropping and head bow-ing. “Rest tremor” is a repetitive back-and-forthmovement of any limb, or the jaw, head, or trunk,which occurs when that part of the body is notactively moving. Common types of tremor in-clude pronation–supination of the forearm andflexion–extension of the fingers. Some patientswith PD never develop tremor.

The remaining symptoms (Table 1, “Vari-ably present”) are of variable occurrence. Aninteresting aspect of these symptoms is thatmany appear related, at least superficially, tothe “Common” symptoms listed in Table 1.Hypomimia (masking of facial expression), forexample, has already been mentioned as a man-ifestation of akinesia-hypokinesia, and micro-graphia (decreased size of handwriting) is likelypart of the same symptom complex. Drooling is

Table 1. Selected motor symptoms and signs ofParkinson’s disease

Common Akinesia (paucity of movements; delayedmovement initiation)

Bradykinesia (movement slowness)Hypokinesia (paucity of movements;

reduced movement amplitude)Postural instability (impaired recovery

when balance is perturbed)Rigidity (increased resistance to passive

joint movement)Stooped postureTremor at rest

Variablypresent

Camptocormia (severe flexion of thetrunk)

Decreased arm swingDecreased dexterityDecrement of amplitude of repeated

movementsDifficulty arising from a chairDifficulty performing simultaneous

actionsDroolingDysarthria (slurred speech)Dysphagia (difficulty swallowing)Dystonia (abnormal posture of a body

part)FatigueFestination (gait acceleration with step

shortening)Freezing of gait (sudden brief

interruptions in the gait cycle)Hypomimia (reduced facial

expressiveness)Hypophonia (reduced voice volume)Micrographia (reduced size of

handwriting)Shuffling gait with short stepsTachyphemia (acceleration of speech

segments)

P. Mazzoni et al.

2 Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a009282

ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



likely not due to excessive saliva production, butrather to a combination of reduced swallowingfrequency and a tendency for the mouth to staypartly open, which are manifestations of akine-sia-hypokinesia-bradykinesia.

It is not entirely clear, however, to what ex-tent PD symptoms are related to one another.Consider the case of movement slowing of in-dividual movements (bradykinesia) and slow-ing of sequential and simultaneous movements.When asked to make a series of movements, PDpatients perform each movement abnormallyslowly, but also wait longer than normal be-tween each movement (Benecke et al. 1987).When asked to perform two movements simul-taneously, the amount of slowing is greater thanwould be expected if one simply added togetherthe slowing of each individual movement. It isdifficult to discern whether this effect truly rep-resents a separate difficulty from bradykinesia.A normal action, such as getting dressed, in-cludes multiple simultaneous and sequentialtasks. If these are executed less simultaneouslyand with longer intervals between each move-ment, the total movement time can easily be-come considerably long (Schwab et al. 1954).

A difficulty in interpreting the slowing ofsequential and simultaneous movements forPD patients is that comparison with normalperformance is not trivial. It is possible that con-trolling the sequential and simultaneous per-formance of movements that are individuallyslow takes extra time because they are controlleddifferently from normal movements. Thus theextra time needed to execute sequential or si-multaneous movements could be due not toPD, but a general difficulty in sequential or si-multaneous execution of slow movements. Todistinguish between these possibilities, onewould, ideally, slow the individual movementsof healthy subjects artificially to match theslower speed of patients’ individual movements,and then record how fast these subjects can ex-ecute those slow movements sequentially or si-multaneously. If they did not show additionalslowing, then one could conclude that PD pa-tients’ difficulty with sequential and simultane-ous movements is a separate motor abnormalityfrom bradykinesia.

One consideration for understanding howsymptoms might be related is whether symp-toms are correlated to each other in their occur-rence and severity. The idea is that if two symp-toms result from the disruption of a commonnormal mechanism, then they should co-occur.This approach is helpful for symptoms that af-fect the same body region. The lack of correla-tion between severity of bradykinesia and rigid-ity, for example, suggests that these symptomsconstitute separate motor abnormalities, andspecifically, that bradykinesia is not simply aconsequence of rigidity (Marsden 1989). Thisreasoning, however, is less useful when consid-ering symptoms that affect different body reg-ions. Indeed, based on correlation, microgra-phia and postural instability should be con-sidered unrelated, because PD often begins byaffecting an upper limb first, and only later af-fects gait and balance. However, PD symptomsoften have a particular topography that dependson the stage of the disease, that is, they affect agiven body region first and then spread to adja-cent regions. It is therefore possible for micro-graphia and postural instability not to coexist,simply because the arm has been affected butgait has not. And yet, it is quite plausible thatthe two symptoms might both reflect hypokine-sia. Reduced movement amplitude can causehandwriting to be smaller. Reduced movementamplitude can also cause a step to be smaller, sothat if a patient trips over an obstacle, she mightnot recover because she does not take a largeenough step to avoid falling.

A more reliable approach to understandinghow motor symptoms relate to one another isto determine, if possible, how they relate to nor-mal motor control. For example, decreased armswing could result from rigidity, because of in-creased resistance to passive movements. Howev-er, the arm swing is not only a passive movement,but also has an active component from coordi-nated muscle contractions (Elftman 1939). Aki-nesia/hypokinesia, therefore, could also contrib-ute to arm swing reduction. These potentialrelationships beg the questions: How is armswing amplitude normally controlled? What isthe role of normal tone in enabling normal-am-plitude movements?

Motor Control Abnormalities in Parkinson’s Disease

Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a009282 3

ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



Understanding relationships among PDsymptoms is only one reason to try to investi-gate the nature of these symptoms as motorcontrol abnormalities. More generally, motorsymptoms represent functional impairmentsand are mixed with compensatory strategies tocope with them. Treatment like medications,physical therapy, and neurosurgical interven-tions are designed to restore normal motor abil-ities. Understanding the nature of motor symp-toms as motor control abnormalities can helpto establish the functional effects of the diseaseon various motor functions and can help tooptimize therapeutic strategies. In addition, animportant direction for the treatment of braindisorders is the development of neural prosthe-ses, that is, artificial circuits that can replace thefunction of damaged brain regions (Brunneret al. 2011). Existing ones, such as artificial co-chleas (Liu and Delbruck 2010), were designedbased on the normal function of biological co-chleas. Designing artificial basal ganglia will re-quire understanding how these structures con-tribute to normal motor control and how theirdysfunction causes specific motor symptoms.

MOTOR CONTROL

To gain an understanding for how motor con-trol is affected in Parkinson’s disease, it is worthreviewing what is meant by “motor control.”Many of the following concepts were explicitlyintroduced by Nikolai Bernstein, in a landmarkbook that was translated into English in 1967(Bernstein 1967). Modern accounts of motorcontrol can be found, for example, in Winter(2009) and Shadmehr and Wise (2005). In gen-eral, movements have features that are tightlycontrolled and others that require less precisecontrol. For instance, when you are sitting at abanquet and reach for a glass of wine, your handtravels along a path through three-dimensionalspace. The wrist and elbow also travel throughspace, and yet their position is less important,because it is the hand that must reach the glass.Conversely, when we elbow our spouse at thetable to alert them that someone importantjust walked into the banquet hall, the handmoves in space, but its position matters less

than that of the elbow, because it is the elbowthat must hit our dinner companion’s ribs. It isthus useful to describe what feature is controlled:hand position when we reach, and elbow posi-tion when we nudge. The motor system faces thetask of controlling various aspects of movement,as dictated by specific task demands. Somemovement features may be tightly controlled,such as the final position of the effector (handor elbow), whereas others may be controlledmore loosely. In other tasks, multiple featuresmay need to be tightly controlled. When one iskicking a soccer ball, the foot’s speed, the pointof contact of the foot on the ball, and the angle ofthe hip are all crucial to the task’s goal. The mo-tor system also controls movement features out-side the body, such as the trajectory and speed ofthe head of a hammer when hitting a nail.

Controlling different aspects of movementis not trivial, given that the nervous system can-not directly influence the position of hand, el-bow, foot, or hammer head. It can only causemuscle contractions, which result in forces thatcause joint rotation. Achieving a desired move-ment requires devising the desired path of therelevant moving body part (such as hand tra-jectory when reaching for an object); translatingthis movement goal into the appropriate set ofmuscle activations; accounting for how otherbody parts (such as the elbow) will move along;and monitoring the movement as it unfolds incase corrections are needed. The nervous systemmust also account for external factors that in-fluence movement goals (such as the speed of anoncoming soccer ball). These are all compo-nents of motor control.

To understand motor control abnormalitiesin PD, one would, ideally, start from a detailedunderstanding of normal motorcontrol and theninfer what changes to control strategies are nec-essary to explain PD motor symptoms. In prac-tice, this approach is difficult because our un-derstanding of normal motor control is limited.In particular, we have limited understanding ofthe normal motor functions that are particularlyaffected by PD. For bradykinesia, for example,we would need to understand how movementspeed is normally selected; for rigidity, whatcontrol principles dictate normal muscle tone.

P. Mazzoni et al.


ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



MOTOR SYSTEM: LEVELS OF DESCRIPTION

Our concern is to address the relationship be-tween motor symptoms and motor control. Thisis a distinct endeavor from reviewing the neu-rophysiology of motor symptoms, although thetwo are closely related. The distinction is per-haps best described in the language of DavidMarr’s levels of description of an informationprocessing system (Marr 1982). The motor sys-tem can be considered such a system, in thesense that it receives information (e.g., locationof an object to be reached, current position of allbody parts, behavioral goals) and produces out-puts (muscle activations). Therefore, like all in-formation processing systems, the motor systemcan be described at three levels: computational,algorithmic, and physical.

The computational level is a description ofwhat the system does and why. In the case ofreaching movements, the motor system enablesone to accomplish a behavioral goal, such asprocuring a glass of water. The hand’s trajectoryhas certain features. It is mostly straight, reachespeak velocity near the middle of the movement,and has a particular duration. There are likelyimportant reasons for moving in this manner.A straight trajectory takes less time and effortthan a curved trajectory. Thus, trajectories maybe straight in order to minimize time or energy.Minimizing a quantity is an example of a com-putational principle, which provides insight asto why the computation is performed in a cer-tain way. Theories that attempt to explain thefeatures of real movements are computationaltheories, and developing and testing computa-tional theories is the concern of the discipline ofmotor control.

The other two levels of description are thealgorithmic and implementation levels. Where-as the computational level describes what themotor system does and why, algorithms de-scribe how the goals are accomplished. For areaching movement, the motor system mightfirst represent the desired trajectory in spaceand then activate muscles as needed in orderto keep the hand on course along the desiredpath. The implementation level describes theoperation of the physical structures (the hard-

ware) that actually perform the computation.The motor system’s hardware mainly consistsof neurons and muscles, which communicatevia electrical impulses and chemical substancesand are connected together as circuits.

Bradykinesia can illustrate the distinctionbetween the computational level and algorithm/implementation levels. Slowing of movementin PD is associated with abnormal balanceof activity among multiple parallel pathwayswithin the BG (Alexander et al. 1986; Albinet al. 1989; Obeso et al. 2008). This abnormalbalance is a consequence of a reduction in dop-amine signals sent from the substantia nigrato the striatum, and the net result is excessiveactivity in BG’s output activity, which reducesactivation of the motor cortex for a given move-ment. Such a description is at the hardwarelevel. It tells us how the circuitry behaves differ-ently from normal. A description at the algo-rithmic level is that the BG in PD fails to suffi-ciently energize the motor cortex to producea movement of normal speed (Hallett andKhoshbin 1980; Hallett 2003). What is neededat the computational level of description is atheory of how movement speed is normally de-termined. What principles (maximization ofmovement accuracy, minimization of energy)influence movement speed determination, andhow does dopamine loss in PD disrupt thesecomputations?

The different levels are, of course, related,and a clean distinction among them is not al-ways possible or appropriate. But brain circuitsand their activity must implement algorithmsthat in the end must subserve computations. Afull understanding of motor dysfunction in PDwill be obtained when we can describe the nor-mal computations and algorithms that are im-plemented by the motor system and how thephysical changes caused by PD disrupt these al-gorithms and, in turn, the computations thatnormally govern movement.

Our understanding of motor symptoms ofPD has made phenomenal advances in terms ofkinematics (how are movements different inPD?) and neurophysiology (Hallett 2003), whichare largely concerned with the second and thirdlevels of description, respectively: algorithm and



ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



physical realization. The major approach hasbeen to link the nature of dysfunction in neu-ronal circuits and activity (i.e., the disruptionof the hardware) to motor abnormalities orsymptoms. A comprehensive description ofPD motor symptoms at the computational lev-el, on the other hand, remains elusive. A tem-plate for this type of understanding exists for amotor symptom that is not part of PD, namely,cerebellar ataxia (Box 1). Here we describe howtwo major symptoms, rigidity and the complexof bradykinesia-hypokinesia-akinesia, may beunderstood as abnormalities of normal motorcontrol.

RIGIDITY AND MOTOR CONTROL

When a joint is moved passively (i.e., by the ex-aminer, without any effort by the patient to helpor resist the motion), there is a normal amount of“tone” (resistance to passive movement). “Rigid-ity” refers to increased tone, or increased resis-tance to passive movement. To understand rigid-ity as a motor control abnormality, we must askwhat is the role of muscle tone in motor control.The full answer to this question is not yet clear, butnormal tone is likely part of a general mechanismfor maintaining stability, that is, resistance to per-turbations. When a limb is at rest and relaxed, the

BOX 1. FROM MOTOR SYMPTOM TO MOTOR CONTROL

It has long been a tradition in neurology to infer normal nervous system function from analysis ofneurological symptoms. It may seem almost obvious that a neurological abnormality might directlyreflect the loss of a corresponding normal function. Weakness after a corticospinal tract lesion mightlead to the conclusion that the motor cortex controls muscle power. In reality, translating symptominto normal function is a complex process, full of logical traps. Although muscle power does requireproper activation patterns in motor cortex and motor cortex stimulation causes muscle contraction(Ferrier 1876), motor cortical activity might encode other aspects of movement, such as speed, thathappen to correlate with muscle power. Indeed, activity in motor cortex is correlated with so manyaspects of movement (Thach 1978; Scott 2003) that it remains unclear, more than 130 years afterFerrier’s stimulation experiments, what role the motor cortex plays in motor control (Scott 2008).

What does it mean to understand a symptom in terms of motor control? It may be helpful todescribe an example in which this type of understanding has arguably been achieved. Consider thesymptom of “cerebellar ataxia.” This term refers to the fact that patients with cerebellar disease make“irregular” movements. For example, movements of the finger from the patient’s nose to the exam-iner’s fingers weave along an irregular path to the target. Furthermore, when a movement is repeated,the path traced weaves along a slightly different trajectory, compared with the previous one. How arewe to interpret ataxia in terms of normal cerebellar function? By noticing that the finger path is notstraight, we are implying that finger paths in goal-directed movements are normally straight, leadingone to consider that the cerebellum’s normal function is to control the straightness of the trajectory. Toa large extent, however, this is simply a restatement of the neurological symptom in the negative. Amore mechanistic hypothesis is needed.

Briefly, key insights arose from the ideas that muscle contractions and relaxations in cerebellarpatients seem delayed (Holmes 2007) and that these patients have difficulty managing interactiontorques (the reactive forces between limb segments, such as between the forearm and upper arm)(Bastian et al. 1996). These explanations were insightful, but what was missing was a theory of howand why delays and interaction torques mattered in normal motor control.

A breakthrough came from the field of computational motor control, which is concerned withidentifying principles and mechanisms that operate in normal motor control. The novel hypothesiswas that the motor system handles delays, interaction torques, and other factors by computing a“forward model” (Kawato et al. 1987; Wolpert et al. 1995; Miall and Wolpert 1996). The joint forcesneeded early in the movement, for example, differ from those needed in the middle, where the arm ismoving faster. This higher speed causes mechanical forces between the upper arm and forearm, andthe motor command must be adjusted to account for these forces. But the adjusted motor command

P. Mazzoni et al.


ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



muscles are not active. If an external force, such asa physician’s hand, moves the limb, some musclesare stretched. Some resistance to such a movementis produced by the physical properties of the limb’stissues (muscles, tendons, skin, etc.). Additionalresistance is caused by stretch reflexes. Sensoryfibers detect lengthening of the muscles and causemotor neurons in the spinal cord to contract thesame muscles. If the limb is truly relaxed, theseresponses are limited to short-latency reflexes(i.e., they appear 25–50 msec after the onset ofthe stretch), only involving circuits within thespinal cord. If the stretch is applied (Fig. 1A)when the muscle is contracting, additional re-flexes contribute to resistance (Marsden et al.1972; Shemmell et al. 2010). These are long-la-tency reflexes. They appear 50–100 msec afteronset of the stretch and are seen as muscle acti-vation that occurs after activity caused by spinalreflexes, but before any voluntary reaction to thepassive movement (Fig. 1B).

A major contributor to rigidity in PD isan exaggeration of long-latency reflexes (Tatton

and Lee 1975; Berardelli et al. 1983; Rothwellet al. 1983). These are larger than normal(Fig. 1C), and they can occur even if the stretchis applied when muscles are not contracting.This abnormality suggests that the BG contrib-utes to the generation of long-latency reflexes.Does this physiologic basis of rigidity offer in-sights into rigidity as a possible motor controlabnormality? The answer requires understand-ing what long-latency reflexes contribute to nor-mal motor control. This question remains anarea of intense investigation. Long-latency re-flexes are generated in the cerebral hemispheresand thus can be influenced by a variety of infor-mation available to BG and other brain struc-tures. A current theory of motor control, knownas “optimal feedback control” (Todorov and Jor-dan 2002; Diedrichsen et al. 2010), suggests thatfor every movement, the motor system sets howeasily the movement can be changed. If we reachfor a wine glass that is sitting between two can-dles, forexample, the hand’s trajectory should bestable and precise. Should another person’s arm

will only arrive at the muscle after it has traveled through central and peripheral nerves (�100–130 msec). A “forward model” refers to an internal computation through which the motor systemaccounts for these changing conditions and delays. It monitors the state of the arm (its position andvelocity) and sends adjustments to the motor command that take into account transmission delays.Crucially, the computation involves a model of the arm that allows predicting, based on the mostrecently sensed arm position and velocity, where the arm will be by the time the motor commandreaches the muscles. By maintaining a model of the arm that takes into account neural transmissiondelays, the motor system can exert predictive control.

It soon became apparent that many motor abnormalities due to cerebellar dysfunction could beexplained as a disruption in predictive control. It was thus hypothesized that in normal motor control,the forward model is computed by the cerebellum (Miall et al. 1993; Bastian 2006). The idea is that anormal reaching movement requires motor commands that take into account the biomechanicalproperties of the arm, the arm’s changing state during the movement, and delays in signal transmis-sion. The cerebellum normally achieves predictive control by taking all these factors into account,making it possible for the hand to follow a straight path. Disrupting cerebellar function then leads toirregular hand paths because motor commands are no longer predictive and are not appropriate forthe current state of the arm. The path irregularity varies from one movement to the next becauseinappropriate adjustments to the motor command may vary in their nature and their effect dependingon exactly when they are released, and because their effects accumulate throughout the movement.

What is successful about our current understanding of cerebellar ataxia is that a motor controlprinciple was identified (the need for predictive control through a forward model) that can accountfor important features of normal movements, and whose disruption can explain motor symptoms ofcerebellar dysfunction. Predictive control through a forward model is a crucial component of com-putational models of normal motor control. As a principle, it may have historically been suggested bythe symptoms of cerebellar dysfunction, but those symptoms can now be explained as disruptions ofthe principle of predictive motor control.



ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



accidentally bump into ours, we would want thearm to resist this perturbation. If, on the otherhand, we are trying to catch a fruit fly that isweaving in many directions, the hand’s trajecto-ry should be flexible, at the expense of being lessresistant to perturbations. Optimal feedbackcontrol theory posits that the brain sets “feed-back gains,” which determine how powerfullythe hand resists changes in trajectory (Liu andTodorov 2007). Long-latency reflexes may play arole in setting feedback gains. They can be craft-ed specifically for a given limb, task, and condi-tions, but are “automatic” enough that they canoccur earlier than voluntary responses.

Based on the hypothesis that muscle tone,mediated by long-latency reflexes, normallysets the amount of limb stability, it is possibleto interpret parkinsonian rigidity at the level ofmotor control. If the basal ganglia contribute tothe computation of normal tone required tomaintain appropriate stability, then rigiditycould be interpreted as a motor control dys-function in which the limbs are programmedto be excessively stable.

BRADYKINESIA, HYPOKINESIA,AND MOTOR CONTROL

Bradykinesia, or movement slowing, is a prom-inent symptom of PD. When a patient withbradykinesia reaches for a cup on a table, the

movement takes longer than for a person with-out PD. In addition, the initial movement isoften too short. The hand briefly pauses shortof the cup, and then additional small movementsbring it to the cup. This undershooting is a man-ifestation of hypokinesia. Combined bradykine-sia and hypokinesia can be elicited in the neuro-logical examination. When a patient with PD isasked to tap his fingers “big and fast,” the move-ments are both slower (fewer taps per second)and of smaller excursion than normal.

Bradykinesia and hypokinesia can be shownin the laboratory by recording an individual’sfingertip position while he follows the instruc-tion to tap the index finger and thumb “as bigand as fast as possible” (Fig. 2). Compared witha healthy individual’s finger taps (Fig. 2A),those of a PD patient have longer duration (bra-dykinesia) and reduced amplitude (hypokine-sia) (Fig. 2B).

This slowing and reduction of movementamplitude were initially interpreted as a mani-festation of weakness, which gave rise to the19th century name for PD, “paralysis agitans,”or shaking palsy (Parkinson 1817; Wilson 1925).The term “weakness,” however, later assumedthe more specific meaning of inability to pro-duce a normal level of maximum force. PD doesnot cause weakness thus defined. This was clear-ly shown by Schwab et al. (1959), who asked aPD patient to repeatedly squeeze a rubber bulb

A B C

0 10050 0 10050 0 10050Time (msec)

Wris

t ang

le (

degr

ee)

EM

G signal (μV

)

10°200

100

0

0°

Figure 1. Long-latency reflexes are larger than normal in Parkinson’s disease. The subject’s hand is linked to amechanical splint that suddenly displaces the hand so that the wrist is extended. This displacement, shown as atrace of wrist angle versus time (A), causes a sudden stretch of muscles that flexes the wrist. This stretch elicitsreflex muscle activity, shown in electromyographic recordings (EMG) from the flexor carpi radialis muscle for ahealthy individual (B) and a patient with PD (C). Although the amplitudes of short-latency (,50 msec)responses are similar for both subjects, the long-latency response (.50 msec) is exaggerated for the PD patient.(Adapted from Cody et al. 1986; reprinted, with permission, from Oxford University Press # 1986.)

P. Mazzoni et al.


ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



and recorded the pressure exerted. The pressuretracing showed a manifestation of hypokinesiaknown as “decrement,” that is, a gradual de-crease of the peak force with each repetition.However, if the examiner then reminded thepatient to squeeze more forcefully, the pressuretracing immediately became larger. If the pa-tient had been truly weak, then he shouldnot have been able to increase the squeezingpressure without resting first. These findingswere in contrast to those of a patient with my-asthenia, a disorder of the neuromuscular junc-tion that causes true weakness. The myasthenicpatient was not able to increase the squeezingpressure after a verbal reminder, but insteadneeded to rest for a few seconds first. Thesefindings showed that hypokinesia is not due toweakness.

Hypokinesia has been further studiedthrough movement analysis in the laboratory.The typical approach is to instruct the subjectto make specific goal-directed movements, suchas moving the finger to a visual target as fast aspossible, or moving a computer cursor with ajoystick. Movements are recorded with hightemporal resolution by a computer, so that akinematic analysis can later be performed. Thisallows the extraction of movement parameterssuch as time of onset, speed, and amplitude. Animportant observation regarding hypokinesia

and bradykinesia using this approach was madeby studying joystick movements to guide ascreen cursor to a visual target (Flowers 1975).The goal was to maintain the cursor on a visualtarget, which could randomly jump from oneposition to another. Healthy subjects movedthe cursor in a single movement from its initialposition to the target. Flowers noticed that themovements of PD patients were composed of aninitial movement that fell short of the target,followed by additional corrective movements.The initial undershooting was a manifestationof hypokinesia, and it suggested a close relation-ship between bradykinesia and hypokinesia. Ifthe initial movement is too short, then addition-al corrective movements are required, whichcauses the total movement duration to increase.

Flowers’s finding fit within Woodworth’stwo-component model for the control of goal-directed movements (Woodworth 1899), ac-cording to which movements reflect a set initialplan followed by corrections, based on visualand proprioceptive feedback, as the hand’strajectory unfolds. In this scheme, Parkinson’scauses the initial movement to be too short, thatis, inadequately scaled to the distance to thetarget, which requires more time to be spentcorrecting for the initial undershooting. Thisinsight, based on a motor control model of nor-mal movements, not only supported the idea

8

4

3210

8

4

Am

plitu

de (

cm)

3210

Time (sec)

A B

Figure 2. Bradykinesia and hypokinesia manifested in finger tapping. Individuals were asked to tap the indexfinger against the thumb “as big and as fast as possible.” The traces show distance between the tips of the thumband forefinger, recorded by a motion capture camera, for a healthy individual (A) and a patient with PD of similarage (B). Finger taps for the PD patient were of smaller amplitude (hypokinesia) and lower frequency (bradyki-nesia) compared with those for the healthy individual. (Data courtesy of Drs. R. McGovern and F. DiBiasio.)



ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



that bradykinesia and hypokinesia are related,but raised the question of what the primarydeficit is. If movements are inadequately plan-ned as too short and the extra time spent mov-ing is due to the need for additional corrections,then the main deficit caused by PD would beinadequate scaling of the motor command, anda longer movement duration would be a conse-quence of this problem.

The scaling hypothesis states that PD patientscan perform movements with a wide range ofspeeds and amplitudes, but inappropriately scalespeed amplitude (i.e., the motor command) tothe required goal distance (Berardelli et al. 1986).In a reaching task, a distant target might elicit amovement that is shorter and slower than nor-mal. Such a movement would be perfectly ade-quate if the target were closer. When the target isplaced closer, however, patients do not make theappropriate-size movement. Instead, they makea shorter, slower movement that is inadequatefor the shorter target.

An important hypothesis, which emergedfrom subsequent studies of bradykinesia, isthat the basal ganglia are responsible for “ener-gizing” a movement, that is, for setting the cor-rect size of motor commands so that muscles areadequately activated (Hallett and Khoshbin1980). In support of this idea, it has been shownthat PD patients produce normal muscle acti-vation patterns, but the muscle activity is notadequately scaled to the required force (Berar-delli et al. 1986; Turner and Desmurget 2010).These normal initial patterns are thus oftenfollowed by additional “corrective” muscle dis-charges in PD patients (Hallett and Khoshbin1980). Flowers’s data suggest that movements inPD have a normal initial organization (e.g., theyhave normal paths and velocity profiles) and aresimply scaled down in speed and amplitude.The overall movement looks abnormal partlybecause it is composed of additional correctivemovements that follow the initial underscaledmovement.

Further support for this idea emerged fromstudies of arm reaching movements executed atdifferent speeds (Mazzoni et al. 2007). Individ-uals made reaching movements to a visual targeton a computer display, without seeing their

hand during the movement. After each move-ment, the computer showed a marker indicat-ing the hand’s position at the end of the initialmovement. In these conditions, patients withPD were able to make movements of the appro-priate length, that is, without hypokinesia, andthe movement’s kinematic features (temporalprofiles of velocity and acceleration) were nor-mal. These findings favor the idea that the motorsystem in PD patients can produce normalmovements when specifically instructed to doso, but the disease causes a tendency for move-ments to be scaled down in speed and amplitude.

Why don’t PD patients make movements ofthe required size if they are capable of doing so?This question was addressed in a study (Maz-zoni et al. 2007) that asked the related questionabout normal motor control. Why don’t healthysubjects move faster than they normally do? Inother words, what determines normal move-ment speed? We hypothesized, in accordancewith the computational theory of optimal feed-back control, that the selection of movementspeed (or the scaling of the motor command)is normally influenced by how much effort amovement requires. We showed that it is normalfor speed to be selected based on required effort,a process that is driven by a form of motiva-tion, which we called “motor motivation.” Thechoice of this term was analogous to motivationfor explicit choices such as pressing a lever forfood (if you are a rat) or for accomplishing along-term task (if you are a graduate student).We found that PD patients were less likely thanhealthy subjects to self-select fast movements,even though both groups performed with equalaccuracy (Fig. 3). In other words, PD patientswere not limited in the maximum speed theycould achieve, but they selected lower speedsthan normal. This selection was consistent witha higher sensitivity to the effort required byfaster movements and thus suggested that PDcauses a reduced level of motor motivation.

This result suggests a possible motor controlframework for bradykinesia-hypokinesia, inwhich movement speed and amplitude are nor-mally influenced by motor motivation, that is,by the implicit willingness to expend a certainamount of effort. In this framework, tonic

P. Mazzoni et al.


ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



dopamine in the striatum sets the level of motormotivation, and dopamine reduction in PDleads to bradykinesia and hypokinesia as man-ifestations of reduced scaling, or energizing, ofmovements.

It is important to note that we are not tryingto indicate that PD reduces overall motivation orcauses a form of laziness. Instead, patients per-ceive a normal task as requiring more effort thanit should. Indeed, motor motivation may beseparate from other types of motivation. Move-ment parameters, such as speed and amplitude,are selected automatically, without consciouslythinking about them. Homework, a hobby, andrunning a marathon, on the other hand, arechoices that we make with considerable explicitthought and are influenced by a more generalbehavioral motivation. Patients with PD oftendescribe an increased sense of effort, without aloss of willingness to accomplish behavioralgoals. We thus consider it advisable to treat mo-tor motivation separately from other forms ofbehavioral motivation until their relationshipis clarified.

Understanding bradykinesia-hypokinesia asa result of increased sensitivity to a movement’senergy requirement makes it possible to under-stand certain aspects of PD that were previouslydifficult to explain. One of these is “kinesiaparadoxica,” the seemingly paradoxical abilityof PD patients to move considerably fasterthan the maximum speed at which they could

75

65

55

45

35

Pea

k ve

loci

ty (

cm/s

ec)

4236302418126

4236302418126

Movement number

A

75

65

55

45

35

Pea

k ve

loci

ty (

cm/s

ec)

B

Requiredpeak velocityrange

Nc

Nc

Nc

Nonvalid trialValid trial

50

45

40

35

30

25

20

35030025020015010050

Aavg (cm/sec2)

CTL

PD

C

Figure 3. Parkinson’s disease increases sensitivityto movement effort. Subjects made horizontal reach-ing movements to targets in a computer setup thatprovided feedback about movement speed. Move-ments that satisfied a given speed requirement were“valid” (gray circles), whereas all other movements

Figure 3. (Continued) were “nonvalid” (black circles).Subjects made movements until 20 valid trials accu-mulated. The total number of trials needed to achievethis criterion, trials to criterion (NC), was used as ameasure of how much a subject was struggling inmaking movements at the required speed. For thesame required speed, age-matched control subjects(A) tended to make fewer nonvalid movements thanPD patients (B), and thus required fewer total trials toreach criterion. As the speed requirement increased,subjects from both groups needed more trials to reachcriterion. Therefore, trials to criterion (NC) dependedon movement effort (quantified as average accelera-tion, Aavg) (C). As indicated by the difference inslopes, PD patients showed higher sensitivity tomovement effort than control subjects did.



ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



otherwise move (Souques 1921; Broussolle et al.2010). The example typically given is that a pa-tient with advanced PD, who is normally con-fined to a wheelchair, might be able to get upand run out of a theater if there is a fire. Thesituations described are characterized by a pow-erful urgent stimulus.

It has since been shown that this phenome-non is not peculiar to PD (Ballanger et al. 2006).Instead, it is normal for a powerful urgentstimulus to elicit a faster movement than a sim-ple “go” signal does. Thus, the speed of a move-ment is influenced by two opposing forces: theurgency of a stimulus to move, and the motorsystem’s sensitivity to the movement’s requiredeffort. Increasing the urgency leads both healthysubjects and PD patients to move faster thanusual. Healthy subjects, who have a normal sen-sitivity to movement effort, move faster thannormal; PD patients, who have greater sensitiv-ity to effort, move at speeds that are closer tonormal, that is, faster than their usual bradyki-netic speeds.

BRADYKINESIA AS ABNORMALSPEED SELECTION

In the past, a considerable amount of what weknow about the motor system has been based onperformance limits. Subjects in most studies areasked to move as fast as possible, or as accuratelyas possible, or in general to achieve best perfor-mance. Such studies allow us to understand cer-tain disorders, such as stroke, in terms of howmuch ability these disorders remove from nor-mal motor function. However, PD does not im-pair strength (Fahn 2003), and patients can usu-ally move faster, or apply more force, whenreminded to do so (Schwab et al. 1959). Instead,it is as if patients “select” abnormally slow move-ment speeds (Mazzoni et al. 2007). These con-siderations suggest that the core abnormality inbradykinesia should be described as a speedselection problem, and not as the loss of theability to move at normal speeds. PD may causepatients to lower the speed that they considernormal.

To investigate this hypothesis in the contextof normal motor control, we must identify the

corresponding normal speed selection process.In other words, is there a “natural speed” fornormal movements? Consider the act of reach-ing for a cup of water. We usually don’t thinkabout how fast we make this movement. Thespeed is selected automatically. However, wecould deliberately reach more slowly than usual,and, if in a rush, we can deliberately reach faster.And yet, we easily notice whether someone ismoving faster or slower than usual, which sug-gests that there is a typical speed for most move-ments, and that we are well attuned to it.

We recently looked for evidence for a speedpreference by asking healthy subjects to reachfor a visual target in one of two conditions, ei-ther at a “comfortable” speed, or at a speed in-structed by a computer (B Shabbott and P Maz-zoni, unpubl.). The remarkable finding was thatsubjects did show a preference for a particularspeed. They returned to this speed even afterthey were shown that they could move faster orslower without a change in accuracy, and theymoved at the same speed when they performedthe task again the next day (Fig. 4). These findingssupport the existence of a natural speed in normalmotor control, which is selected automaticallyand is resistant to the experience of other speeds.Bradykinesia could then be described as a re-duction in the selected natural speed, due to in-creased sensitivity to movement effort.

Besides a speed preference for a particularreaching movement, we also found a relation-ship between a movement’s amplitude and itsnatural speed. A specific natural speed seems tobe matched to a given movement amplitude.Reaching for a target at a given distance thuselicits the selection of a particular natural speed,perhaps learned through practice or optimiza-tion of kinematic parameters. This yoking ofspeed and amplitude could explain the link be-tween bradykinesia and hypokinesia observedin PD.

AKINESIA AND MOTOR CONTROL

The idea of scaling a motor command based onmotor motivation combines speed and ampli-tude as linked aspects of movement. It thus offersan explanation for bradykinesia and hypokinesia

P. Mazzoni et al.


ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



as two aspects of a single control problem. Howdoes akinesia fit into this scheme? Although theterm “akinesia” is often also used to describereduced movement amplitude (which we havehere referred to exclusively as “hypokinesia”),the other components of akinesia (paucity ofspontaneous movements and delayed move-ment initiation) may or may not be relatedto hypokinesia or bradykinesia (Hallett 2003).In this discussion, we use “akinesia” specificallyto refer to an abnormality in when a movementoccurs. For repetitive automatic movementssuch as blinking and swallowing, this abnormal-ity is manifest as a reduced frequency of thesemovements’ occurrence. For voluntary move-ments, it is a delay inwhen the movement begins.

The motor motivation hypothesis (Maz-zoni et al. 2007) is based on a modern theoryof normal motor control, that is, optimal feed-back control (Todorov and Jordan 2002), whichpredicts trajectory features of goal-directedmovements. Similarly, it would be desirable toexplain akinesia by resorting to theories that

account for how movements are normally initi-ated and how the frequency of spontaneousmovements, such as blinking and swallowing,is normally determined.

Unfortunately, motor control theories formovement initiation and spontaneous move-ment frequency are far less developed than thosefor the trajectories of voluntary movements.A motor control interpretation of akinesia,therefore, remains speculative. With respect tothe frequency of cyclical automatic movementssuch as blinking and swallowing, very little isknown at the control level. The benefits of thesemovements are clear, namely, clearing the eyes oflacrimal fluid and emptying the mouth of saliva,but these movements are not purely driven bythe accumulation of these fluids. They have acentral drive that is affected by basal gangliadopamine levels, and their frequency can be af-fected by external factors (Ponder and Kennedy1927; Lear et al. 1965; Karson 1983; Dodds 1989;Bentivoglio et al. 1997). However, a control-levelaccount of these movements is lacking.

Day 1 Day 2

Speed conditionRetestNaïve

Ave

rage

spe

ed (

cm/s

ec)

10

15

20

25

a

b

C I C I C I C I C I C I C C

Figure 4. Healthy individuals prefer certain movement speeds. Subjects performed horizontal reaching move-ments to a target in a virtual reality environment equipped to record arm motion. Subjects completed alternatingblocks of trials in which they reached with either their preferred “comfortable” speed (C, white circles) or withspeeds imposed by a computer (I, black squares). Each subject’s naıve speed preference (C naıve) was assessedbefore experiencing imposed speeds, and speed preference was also retested (C retest) following a day of rest. Thegraph shows the mean average speed for a single subject. During comfortable speed blocks, the subject wasreluctant to move at speeds that were either slower (see example, arrow a) or faster (see example, arrow b) than thenaıve preference. The tendency to return to a certain preferred speed is shown by the arrows and occurs despite thefact that movements performed with all speeds resulted in similar accuracies. On the second day of testing, speedpreference was similar to the naıve preference (the gray dotted line indicates the average of C naıve and C retest).



ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



Regarding delayed movement initiation, itspossible relationship to normal motor control issuggested by a variety of findings. It is possiblethat this symptom is not related to bradykinesia,because the severity of initiation delay does notcorrelate with the severity of movement slowing(Evarts et al. 1981). Thus, delayed movementonset may be due to a separable physiologicalmechanism.

The most common method to establishspeed of movement initiation is the reactiontime (RT) paradigm. A “go” signal, such as anauditory tone or the appearance of a visual tar-get, is given, and the subject is asked to make amovement as soon as possible; the time betweenthe signal and movement onset is the RT. Typicalvalues of RT for healthy older individuals are�300–500 msec for simple tasks, such as press-ing a button as soon as possible after a light isturned on. RT is increased in PD, by an amountthat ranges from 10% to 30% (Evarts et al. 1981).Measurements of RT in special conditions, suchas requiring subjects to use the “go” signal todecide which button to press (choice RT para-digm), have shown that the RT increase caused byPD is specific to starting movement executionand does not seem to reflect a delay in othermovement preparation processes (Jahanshahiet al. 1992).

The increase in RT is accompanied by slowerbuildup of neuronal activation over the motorcortex (Bereitschaftspotential, or “readiness” po-tential). The delay thus seems to reflect abnor-mally slow development of a motor commandsignal in the motor cortex. Once the motor com-mand leaves the motor cortex, its transmission isnormal (Dick et al. 1984). Therefore, PD affectsthe step between the preparation of a motorcommand and its manifestation in cortical mo-tor areas. The basal ganglia receive informationfrom multiple cortical areas and normally exerta net inhibitory action on the motor cortex (Al-exander et al. 1986; Albin et al. 1989; Obeso et al.2008). Just before a movement starts, this inhib-itory action of the BG on motor cortex is tran-siently reduced. Transient disinhibition is blunt-ed in PD, and this is part of the physiologicalbasis of several PD symptoms. However, thisphysiological activity has not yet been integrated

into a theory of how these signals determinenormal movement onset. Until a better appre-ciation is gained of these normal processes, ourunderstanding of akinesia will remain limited.

Akinesia could be related to bradykinesiaif we hypothesize that movement initiation re-quires overcoming a certain “activation thresh-old” (Hallett 2003). If the motor cortex needs tobe sufficiently “energized” for a movement to beof normal speed, then it may be necessary forthis activation to cross a threshold value for amovement to start in the first place. This acti-vation likely takes time to build up, as suggestedby the time course of the readiness potential, anelectrical signal recordable at the scalp that in-dicates activation of motor cortical areas beforea movement starts (Deecke et al. 1976). In PD,the readiness potential builds up more slowlythan normal (Shibasaki et al. 1978; Dick et al.1989). The slower buildup of activation in PDpatients could cause the activation threshold tobe crossed later than normal, delaying move-ment initiation.

The reduction in frequency of spontaneousmovement could also fit a threshold-crossingmechanism. Movements such as blinking andswallowing are performed automatically. Whena movement becomes automatic, activity in mo-tor cortical areas becomes reduced, which mayreflect increased efficiency of neural coding formotor programs (Wu et al. 2004). Such activitywould be expected to be further reduced in PDand thus may not cross the threshold required togenerate a blink or swallowing. With increasedtime between these events, the stimulus to per-form them might increase: buildup of lacrimalfluid over the eyes and accumulation of saliva inthe mouth. These increased stimuli could gen-erate sufficient motor drive to cross the activa-tion threshold required for the movement to oc-cur. Blinking and swallowing would thus stilloccur, but less frequently than normal.

MOTOR SYMPTOMS OF PD ANDNORMAL FUNCTION OF THE BG

Behavior can be described at the level of actionsor movements. A movement-level descriptionemphasizes graded variables such as movement

P. Mazzoni et al.


ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



speed, amplitude, force, onset time, and duration.An action-level description emphasizes discretechunks of behavior, such as what action wasperformed. The details of “how” a movementis performed (how fast, how long, etc.) are usu-ally separable from descriptions of “what” themovement is (reaching for a cup or a fork atdinner, turning left or right in a maze). Remark-ably successful descriptions of the role of BG inaction selection have been developed (Redgraveet al. 1999). The research efforts that have ledto these descriptions have encompassed multi-ple fields, including neuroanatomy, physiolo-gy, psychophysics, and computational theories.The result is a detailed tentative description ofthe BG as a “selection machine.” Given a contextand a behavioral goal, the BG may function tocombine prior experience and probability of re-ward to guide the selection of the next action(Redgrave et al. 1999).

Despite the success of such theories in de-scribing normal action selection, it has beendifficult to reconcile these theories with the mo-tor symptoms of PD. These symptoms mainlyaffect how a patient moves, not what action heor she performs. In general, movement-leveldescriptions of behavior have not included arole for selection processes. Kinematic parame-ters such as speed and amplitude are positedto be precisely computed based on spatial andmechanical aspects of movement, and not to besubject to a selection step. Consequently, com-putational theories of motor control have large-ly focused on obligatory relationships amongkinematic variables, without entertaining a rolefor selection processes. However, selection ofmovement parameters is likely to play an im-portant role in motor control.

The concept of natural speed is helpful indeveloping the concept of kinematic parameterselection. Daily experience with normal move-ments points to a selection process for speed.We are usually free to move faster or slower,which means that we must be choosing a par-ticular speed. The nature of bradykinesia rein-forces this idea. As described above, PD patientscan move faster when reminded to (Schwabet al. 1959), and when they make faster move-ments, these are kinematically normal (Maz-

zoni et al. 2007). Thus, bradykinesia may simplyreflect a change in selection parameters, so thatthe speed that is selected as appropriate is lowerthan normal. This could occur, as suggested byour study, because of a change in sensitivity tothe factors that normally influence speed selec-tion (Mazzoni et al. 2007).

Conceptually, a view of normal speed andbradykinesia as results of selection processesopens the possibility of describing the functionof BG as a selection machine for movementparameters, in analogy to its role in action se-lection. Such a conceptual framework wouldassign the common role of performing selec-tions that guide behavior, both for “what”behavior is performed (action selection) andfor “how” it is performed (motor control). Adistinction between “what” and “how” has beenproposed for the separate visual processingstreams in temporal and parietal cortical areas(Goodale and Milner 1992). The basal gangliamay play an important role in integrating suchperceptual information, and through its parallelanatomical circuits, may perform computation-ally analogous processes (selection based oncontext, motivation, reward, risk) to both as-pects of behavioral control.

CONCLUDING REMARKS

The two PD symptoms discussed in this chap-ter—rigidity and the bradykinesia-hypokine-sia-akinesia complex—illustrate the evolutionof our understanding of these symptoms as mo-tor control abnormalities. For these symptoms,the exciting possibility of linking movement ab-normalities to theories of normal motor controlis on the horizon. For other symptoms, such astremor, we have an extensive understandingof the underlying physiological abnormalities(Hallett 2003), but it remains unclear how(or whether) they may be understood as motorcontrol problems. It is important to recognize,and hopefully sufficiently clear from this article,however, that the process of understanding mo-tor symptoms is not slave to understanding nor-mal motor control first. On the contrary, in thecase of bradykinesia, it was the remarkable as-pects of the symptom that forced researchers to



ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



realize that it is possible to move slowly in theabsence of weakness, and thus that speed mightnormally be governed by a selection process.Thus, even in the age of sophisticated compu-tational theories of motor control, neurologicalsymptoms continue to guide our understand-ing of normal brain function.

REFERENCES

Albin RL, Young AB, Penney JB. 1989. The functional anat-omy of basal ganglia disorders. Trends Neurosci 12: 366–375.

Alexander GE, DeLong MR, Strick PL. 1986. Parallel orga-nization of functionally segregated circuits linking basalganglia and cortex. Annu Rev Neurosci 9: 357–381.

Ballanger B, Thobois S, Baraduc P, Turner RS, Broussolle E,Desmurget M. 2006. “Paradoxical kinesis” is not a hall-mark of Parkinson’s disease but a general property of themotor system. Mov Disord 21: 1490–1495.

Bastian AJ. 2006. Learning to predict the future: The cere-bellum adapts feedforward movement control. Curr OpinNeurobiol 16: 645–649.

Bastian AJ, Martin TA, Keating JG, Thach WT. 1996. Cere-bellar ataxia: Abnormal control of interaction torquesacross multiple joints. J Neurophysiol 76: 492–509.

Benecke R, Rothwell JC, Dick JP, Day BL, Marsden CD. 1987.Disturbance of sequential movements in patients withParkinson’s disease. Brain 110: 361–379.

Bentivoglio A, Bressman S, Cassetta E, Carretta D, Tonali P,Albanese A. 1997. Analysis of blink rate patterns in nor-mal subjects. Mov Disord 12: 1028–1034.

Berardelli A, Sabra AF, Hallett M. 1983. Physiological mech-anisms of rigidity in Parkinson’s disease. J Neurol Neuro-surg Psychiatry 46: 45–53.

Berardelli A, Dick JP, Rothwell JC, Day BL, Marsden CD. 1986.Scaling of the size of the first agonist EMG burst duringrapid wrist movements in patients with Parkinson’s dis-ease. J Neurol Neurosurg Psychiatry 49: 1273–1279.

Bernstein NA. 1967. The coordination and regulation of move-ments. Pergamon, New York.

Broussolle E, Loiraud C, Thobois S. 2010. Achille AlexandreSouques (1860–1944). J Neurol 257: 1047–1048.

Brunner P, Bianchi L, Guger C, Cincotti F, Schalk G. 2011.Current trends in hardware and software for brain-computer interfaces (BCIs). J Neural Eng 8: 025001.

Cody FW, MacDermott N, Matthews PB, Richardson HC.1986. Observations on the genesis of the stretch reflex inParkinson’s disease. Brain 109: 229–249.

Deecke Ld, Grozinger B, Kornhuber HH. 1976. Voluntaryfinger movement in man: Cerebral potentials and theory.Biol Cybern 23: 99–119.

Dick JP, Cowan JM, Day BL, Berardelli A, Kachi T, RothwellJC, Marsden CD. 1984. The corticomotoneurone con-nection is normal in Parkinson’s disease. Nature 310:407–409.

Dick JPR, Rothwell JC, Day BL, Cantello R, Buruma O,Gioux M, Benecke R, Berardelli A, Thompson PD, Mars-

den CD. 1989. The Bereitschaftspotential is abnormal inParkinson’s disease. Brain 112: 233–244.

Diedrichsen J, Shadmehr R, Ivry RB. 2010. The coordina-tion of movement: Optimal feedback control and be-yond. Trends Cogn Sci 14: 31–39.

Dodds W. 1989. The physiology of swallowing. Dysphagia3: 171–178.

Elftman H. 1939. The function of the arms in walking. JohnsHopkins Press, Baltimore.

Evarts EV, Teravainen H, Calne DB. 1981. Reaction time inParkinson’s disease. Brain 104: 167–186.

Fahn S. 2003. Description of Parkinson’s disease as a clinicalsyndrome. Ann NY Acad Sci 991: 1–14.

Ferrier D. 1876. The functions of the brain. G.P. Putnam’sSons, New York.

Flowers K. 1975. Ballistic and corrective movements on anaiming task. Intention tremor and parkinsonian move-ment disorders compared. Neurol 25: 413–421.

Goodale MA, Milner AD. 1992. Separate visual pathways forperception and action. Trends Neurosci 15: 20–25.

Hallett M. 1990. Clinical neurophysiology of akinesia. RevNeurol (Paris) 146: 585–590.

Hallet M. 2003. Parkinson revisited: Pathophysiology of mo-tor signs. Adv Neurol 91: 19–28.

Hallett M, Khoshbin S. 1980. A physiological mechanism ofbradykinesia. Brain 103: 301–314.

Holmes G. 2007. The Croonian Lectures on the clinicalsymptoms of cerebellar disease and their interpretation.Lecture II. 1922. Cerebellum 6: 148–153.

Jahanshahi M, Brown RG, Marsden CD. 1992. Simple andchoice reaction time and the use of advance informationfor motor preparation in Parkinson’s disease. Brain 115:539–564.

Karson CN. 1983. Spontaneous eye-blink rates and dopa-minergic systems. Brain 106: 643–653.

Kawato M, Furukawa K, Suzuki R. 1987. A hierarchical neu-ral-network model for control and learning of voluntarymovement. Biol Cybern 57: 169–185.

Lear CS, Flanagan JB, Moorrees CF. 1965. The frequency ofdeglutition in man. Arch Oral Biol 10: 83–100.

Liu SC, Delbruck T. 2010. Neuromorphic sensory systems.Curr Opin Neurobiol 20: 288–295.

Liu D, Todorov E. 2007. Evidence for the flexible sensori-motor strategies predicted by optimal feedback control. JNeurosci 27: 9354–9368.

Marr D. 1982. Vision. Freeman, New York.

Marsden CD. 1989. Slowness of movement in Parkinson’sdisease. Mov Disord 4: S26–S37.

Marsden CD, Merton PA, Morton HB. 1972. Servo action inhuman voluntary movement. Nature 238: 140–143.

Mazzoni P, Hristova A, Krakauer JW. 2007. Why don’t wemove faster? Parkinson’s disease, movement vigor, andimplicit motivation. J Neurosci 27: 7105–7116.

Miall RC, Wolpert DM. 1996. Forward models for physio-logic motor control. Neural Networks 9: 1265–1279.

Miall RC, Weir DJ, Wolpert DM, Stein JF. 1993. Is the cer-ebellum a Smith Predictor? J Mot Behav 25: 203–216.

Obeso JA, Marin C, Rodriguez-Oroz C, Blesa J, Benitez-Temino B, Mena-Segovia J, Rodriguez M, Olanow CW.

P. Mazzoni et al.


ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



2008. The basal ganglia in Parkinson’s disease: Currentconcepts and unexplained observations. Ann Neurol 64:S30–S46.

Parkinson J. 1817. An essay on the shaking palsy. Wittingham& Rowland, London.

Ponder E, Kennedy WP. 1927. On the act of blinking. ExpPhysiol 18: 89–110.

Redgrave P, Prescott TJ, Gurney K. 1999. The basal ganglia: Avertebrate solution to the selection problem? Neurosci-ence 89: 1009–1023.

Rothwell JC, Obeso JA, Traub MM, Marsden CD. 1983. Thebehaviour of the long-latency stretch reflex in patientswith Parkinson’s disease. J Neurol Neurosurg Psychiatry46: 35–44.

Schwab RS, Chafetz ME, Walker E. 1954. Control of twosimultaneous motor acts in normals and in Parkinson-ism. AMA Arch Neurol Psychiatry 72: 591–598.

Schwab RS, England AC, Peterson E. 1959. Akinesia in Par-kinson’s disease. Neurol 9: 65–72.

Scott S. 2003. The role of primary motor cortex in goal-directed movements: Insights from neurophysiologicalstudies on non-human primates. Curr Opin Neurobiol13: 671–677.

Scott SH. 2008. Inconvenient truths about neural processingin primary motor cortex. J Physiol 586: 1217–1224.

Shadmehr R, Wise SP. 2005. Computational neurobiology ofreaching and pointing: A foundation for motor learning.MIT Press, Cambridge, MA.

Shemmell J, Krutky M, Perreault E. 2010. Stretch sensitivereflexes as an adaptive mechanism for maintaining limbstability. Clin Neurophysiol 121: 1680–1689.

Shibasaki H, Shima F, Kuroiwa Y. 1978. Clinical studies ofthe movement-related cortical potential (MP) and therelationship between the dentatorubrothalamic pathwayand readiness potential (RP). J Neurol 219: 15–25.

Souques A-A. 1921. Rapport sur les syndromes parkinso-niens. Rev Neurol 37: 181.

Tatton WG, Lee RG. 1975. Evidence for abnormal long-loopreflexes in rigid Parkinsonian patients. Brain Res 100:671–676.

Thach WT. 1978. Correlation of neural discharge with pat-tern and force of muscular activity, joint position, anddirection of intended next movement in motor cortexand cerebellum. J Neurophysiol 41: 654–676.

Todorov E, Jordan MI. 2002. Optimal feedback control asa theory of motor coordination. Nat Neurosci 5: 1226–1235.

Turner R, Desmurget M. 2010. Basal ganglia contributionsto motor control: A vigorous tutor. Curr Opin Neurobiol20: 704–716.

Wilson SAK. 1925. The Croonian Lectures on some disor-ders of motility and of muscle tone with special referenceto the corpus striatum. Lancet 2: 1–10, 53–62.

Winter DA. 2009. Biomechanics and motor control of humanmovement. Wiley, New York.

Wolpert DM, Ghahramani Z, Jordan MI. 1995. An internalmodel for sensorimotor integration. Science 269: 1880–1882.

Woodworth RS. 1899. The accuracy of voluntary movement.Psychol Rev 3: 1–119.

Wu T, Kansaku K, Hallett M. 2004. How self-initiated mem-orized movements become automatic: A functional MRIstudy. J Neurophysiol 91: 1690–1698.



ww

w.p

ersp

ecti

vesi

nm

edic

ine.

org



published online March 27, 2012Cold Spring Harb Perspect Med Pietro Mazzoni, Britne Shabbott and Juan Camilo Cortés Motor Control Abnormalities in Parkinson's Disease

Subject Collection Parkinson's Disease

Functional Neuroanatomy of the Basal Ganglia

ObesoJosé L. Lanciego, Natasha Luquin and José A. Dysfunction in Parkinson's Disease

as a Model to Study MitochondrialDrosophila

Ming Guo

GeneticsAnimal Models of Parkinson's Disease: Vertebrate

DawsonYunjong Lee, Valina L. Dawson and Ted M. Pathways

and DJ-1 and Oxidative Stress and Mitochondrial Parkinsonism Due to Mutations in PINK1, Parkin,

Mark R. CooksonInnate Inflammation in Parkinson's Disease

V. Hugh PerryProgrammed Cell Death in Parkinson's Disease

Katerina Venderova and David S. Park

NeuropathologyParkinson's Disease and Parkinsonism:

Dennis W. DicksonDiseaseGenomics and Bioinformatics of Parkinson's

al.Sonja W. Scholz, Tim Mhyre, Habtom Ressom, et

Parkinson's DiseasePhysiological Phenotype and Vulnerability in

Sanchez, et al.D. James Surmeier, Jaime N. Guzman, Javier

DiseaseMotor Control Abnormalities in Parkinson's

CortésPietro Mazzoni, Britne Shabbott and Juan Camilo

ManagementFeatures, Diagnosis, and Principles of Clinical Approach to Parkinson's Disease:

João Massano and Kailash P. Bhatia

Parkinson's Disease: Gene Therapies

Patrick AebischerPhilippe G. Coune, Bernard L. Schneider and

The Role of Autophagy in Parkinson's DiseaseMelinda A. Lynch-Day, Kai Mao, Ke Wang, et al.

Functional Neuroimaging in Parkinson's Disease

EidelbergMartin Niethammer, Andrew Feigin and David

Parkinson's DiseaseDisruption of Protein Quality Control in

PetrucelliCasey Cook, Caroline Stetler and Leonard

Key QuestionsLeucine-Rich Repeat Kinase 2 for Beginners: Six

Lauren R. Kett and William T. Dauer

http://perspectivesinmedicine.cshlp.org/cgi/collection/ For additional articles in this collection, see

Copyright © 2012 Cold Spring Harbor Laboratory Press; all rights reserved


http://perspectivesinmedicine.cshlp.org/cgi/collection/

http://perspectivesinmedicine.cshlp.org/cgi/collection/


Date post:	10-Dec-2021
Category:	Documents
Upload:	others
View:	2 times
Download:	0 times

Motor Control Abnormalities in Parkinson’s Disease

Documents