Journal of Motor Behavior, Vol. 41, No. 6, 2009 Copyright C 2009 Heldref Publications and in Parkinson’s Disease

Jurgen¨ Konczak1,6, Daniel M. Corcos2,FayHorak3, Howard Poizner4, Mark Shapiro5,PaulTuite6, Jens Volkmann7, Matthias Maschke8 1School of , University of Minnesota, Minneapolis. 2Department of Kinesiology and Nutrition, University of Illinois at Chicago. 3Department of Science and Engineering, Oregon Health and Science University, Portland. 4Institute for Neural Computation, University of California–San Diego. 5Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, Illinois. 6Department of , University of Minnesota, Minneapolis. 7Department of Neurology, Universitat¨ Kiel, Germany. 8Department of Neurology, Bruderkrankenhaus,¨ Trier, Germany.

ABSTRACT. Parkinson’s disease (PD) is a neurodegenerative dis- cles, , and capsules. These receptors provide order that leads to a progressive decline in motor function. Growing information about muscle length, contractile speed, muscle evidence indicates that PD patients also experience an array of tension, and joint position. Collectively, this latter informa- sensory problems that negatively impact motor function. This is es- pecially true for proprioceptive deficits, which profoundly degrade tion is also referred to as proprioception or muscle . motor performance. This review specifically address the relation According to the classical definition by Goldscheider (1898) between proprioception and motor impairments in PD. It is struc- the four properties of the muscle sense are (a) passive mo- tured around 4 themes: (a) It examines whether the sensitivity of tion sense, (b) active motion sense, (c) limb position sense, kinaesthetic , which is based on proprioceptive inputs, is and (d) the sense of heaviness. Alternatively, some use the actually altered in PD. (b) It discusses whether failed processes of proprioceptive-motor integration are central to the motor problems term proprioception to indicate the limb position sense and in PD. (c) It presents recent findings focusing on the link between kinaesthesia to refer to limb motion sense (Gardner, Mar- the proprioception and the problems in PD. And (d) it dis- tin, & Jessell, 2000), a definition we do not adopt. Within cusses the current state of knowledge of how levodopa medication the framework of this review, we use the term kinaesthesia and deep stimulation affect proprioceptive and motor func- to refer to the conscious perception of limb and body mo- tion in PD. The authors conclude that a failure to evaluate and to map proprioceptive information onto voluntary and reflexive motor tion. We use the term proprioception to refer to the uncon- commands is an integral part of the observed motor symptoms in scious processing of proprioceptive signals used for reflexive PD. and postural motor control while recognizing that proprio- ceptive information also forms the basis for kinaesthesia. Keywords: basal ganglia, kinaesthesia, movement disorder, senso- rimotor integration The importance of proprioception for motor function such as reaching and grasping, static balance, and locomotion has been well documented (Butler et al., 2004; Diener, Dichgans, Guschlbauer, & Mau, 1984; Dietz, 2002; Sainburg, Ghilardi, ovement abnormalities such as tremor, bradykinesia, Poizner, & Ghez, 1995). Patients with a loss of proprioception Mrigidity, and postural problems constitute the clinical are still able to execute motor tasks, yet their motor behav- hallmarks of Parkinson’s disease (PD). They are thought to ior is gravely compromised. Goal-directed movements lack arise primarily from the loss of producing precision and postural and spinal reflexes are altered leading and subsequent dysfunction of the basal ganglia-thalamo- to problems with balance and gait (Dietz; Ghez, Gordon, & cortical pathway. Yet, a growing body of research demon- Ghilardi, 1995; Rothwell et al., 1982). strates that PD also is associated with an array of perceptual It is the purpose of this review to summarize the current deficits, such as odor and and detec- knowledge of the extent of kinaesthetic deficits in PD. The tion (Herting, Schulze, Reichmann, Haehner, & Hummel, review is guided and structured around four main questions: 2008; Mesholam, Moberg, Mahr, & Doty, 1998; Pratorius,¨ First, is there evidence that kinaesthetic sensitivity is altered Kimmeskamp, & Milani, 2003; Sathian, Zangaladze, Green, in PD? Second, are the motor problems in PD the result of Vitek, & DeLong, 1997; Zia, Cody, & O’Boyle, 2003), failed processes of proprioceptive-motor integration? Third, weight and perception (Maschke, Tuite, Krawczewski, what is the link between the proprioception and the balance Pickett, & Konczak, 2006; Nolano et al., 2008), or the per- problems in PD? And fourth, how does levodopa medication ception of visual depth (Maschke, Gomez, Tuite, Pickett, & and deep brain stimulation (DBS) affect proprioceptive and Konczak, 2006). Recent evidence suggests that kinaesthesia motor function in PD? Before addressing these four ques- is especially affected by PD and that such loss of kinaesthetic tions, we briefly review neurophysiological evidence that sensitivity is closely linked to the motor deficits (Adamovich, links proprioceptive function to neural processes in the basal Berkinblit, Hening, Sage, & Poizner, 2001; Contreras-Vidal & Gold, 2004; Demirci, Grill, McShane, & Hallett, 1997; O’Suilleabhain, Bullard, & Dewey, 2001). Correspondence address: Jurgen¨ Konczak, Sensorimo- Kinaesthesia is commonly defined as the conscious aware- tor Control Laboratory, School of Kinesiology, University of Min- ness of body or limb position and motion in space. It is based nesota, 1900 University Ave. SE, Minneapolis, MN 55455, USA. on sensory information derived from receptors in the mus- e-mail: [email protected]

543 J. Konczak et al. ganglia and describe how the neural output of the basal gan- glia is altered by PD.

Proprioception and the Basal Ganglia Animal studies have long established that many basal gan- glia neurons have proprioceptive receptive fields, responding both to passive and active joint motions (Crutcher & DeLong, 1984a, 1984bb; DeLong, Crutcher, & Georgopoulos, 1985). In , single cell recordings in PD patients submitted to neurosurgery revealed that a third of the neurons in the nucleus subthalamicus responded to passive or active move- ments of limbs, the oromandibular region, or the abdominal wall (Rodriguez-Oroz et al., 2001). These neuronal responses are joint specific with several reports showing that the vast majority of neurons in the monkey globus pallidus internal FIGURE 1. The basal ganglia-thalamocortical circuitry. (GPi) respond to passive motion of a single joint (Boraud, Degeneration of the nigrostraital dopamine pathway (SNc → ) leads changes in the two striato-pallidal pro- Bezard, Bioulac, & Gross, 2000; Filion, Tremblay, & Bedard, jections (direct and indirect pathways). STN = nucleus sub- 1988). However, when these monkeys were made parkinso- thalamicus; SNr = , pars reticulata; SNc = nian through 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine substantia nigra, pars compacta; GPe = globus pallidus ex- (MPTP) treatment, the number of cells responding to passive ternus; GPi = globus pallidus internus; PPN = pedunculo- movement increased, with most neurons now responding to pontine nucleus. movements of several . Researchers also observed this loss in neuronal response specificity in the efferent projec- tions of the basal ganglia to the (Pessiglione et al., synchronization means a reduced responsiveness to signals 2005) and supplementary motor area (Escola et al., 2002). related to a particular context or action. In addition, the out- Therefore, this disturbance of neural function is propagated put may lose topographic specificity (Bergman et al., 1998). throughout the striato-pallido-thalamo-cortical system. For In information processing terms, this implies that the signal example, in intact monkeys, thalamic neurons receiving basal to noise ratio of basal ganglia neural processing is altered ganglia afferents mostly respond to movement around a sin- in parkinsonism (Bar-Gad & Bergman, 2001). Such an in- gle joint. Following MPTP-induced parkinsonism, the tuning crease in neural noise in the basal ganglia likely impairs the of the proprioceptive receptive fields of these thalamic neu- facilitation and modulation of premotor regions that must act rons was markedly broadened thus providing much noisier synergistically to generate accurate and well-timed move- and less differentiated proprioceptive information to cortical ment (Graybiel, 1998, 2005; Leiguarda et al., 2000). motor regions. In general, the neurodegenerative processes associated Altered Kinaesthetic Sensitivity in PD with PD may lead to abnormal neural hyper- or hypoac- tivity in the basal ganglia and could act as a constant facil- Although routine clinical examination often fails to itator or brake on its efferent target structures (Pessiglione demonstrate sensory changes, sensory alterations have been et al., 2005). The classical view regards an imbalance be- documented in PD (Snider, Fahn, Isgreen, & Cote, 1976). tween the direct and indirect pathways projecting from the Early reports showed that approximately 40% of PD patients striatum to the globus pallidus internus/substantia nigra pars experience spontaneous abnormal sensations despite having reticulata (GPi/SNr) as the major cause of the increased fir- a normal neurological examination (Koller, 1984). ing rate in GPi/SNr (DeLong, 1990). This increased firing Neurophysiological studies have demonstrated that pa- inhibits thalamic projections to cortical motor areas thus re- tients with Parkinson’s or Huntington’s disease show severely ducing excitation (see Figure 1). The reduced depressed frontal somatosensory-evoked or proprioception- activation of motor cortical neurons is then believed to be related potentials (Abbruzzese & Berardelli, 2003; Rossini, responsible for the observed bradykinesia, the patients’ in- Filippi, & Vernieri, 1998; Seiss, Praamstra, Hesse, & ability to activate a selected or their failure Rickards, 2003). Behavioral studies have suggested that basal to inhibit competing motor programs (Mink, 1996). A more ganglia dysfunction leads to an altered sensitivity of arm po- recent, alternative view is that basal ganglia neurons become sition sense (Klockgether, Borutta, Rapp, Spieker, & Dich- excessively synchronized at low frequencies in PD and the gans, 1995; Schneider, Diamond, & Markham, 1987; Zia, MPTP model of PD (Bevan, Magill, Terman, Bolam, & Wil- Cody, & O’Boyle, 2000, 2002). However, it has remained son, 2002; Gatev, Darbin, & Wichmann, 2006; Goldberg, unclear whether these findings were solely because of im- Rokni, Boraud, Vaadia, & Bergman, 2004; Raz et al., 2001; paired kinaesthesia or could be attributed to problems in vi- Raz, Vaadia, & Bergman, 2000). This excessive neuronal sual and cognitive processing; both of which are known to be

544 Journal of Motor Behavior Proprioception and Motor Control in Parkinson’s Disease impaired in PD (Antal, Bandini, Keri, & Bodis-Wollner, detecting changes in limb position sense is reduced at distal 1998; Diederich, Raman, Leurgans, & Goetz, 2002). In ad- and proximal arm joints in PD. dition, the possibility needs to be excluded that kinaesthetic The previously mentioned studies have established that PD deficits are simply the result of the known motor deficits of patients have difficulties detecting or determining limb posi- PD or are caused by some compensatory motor strategy. tions. Another important aspect of kinaesthesia is the ability Recently, researchers in several psychophysical studies at- to sense limb motion. Researchers still have an incomplete tempted to address the concerns that vision or active limb understanding to what extent the limb motion sense is al- motion contributed to or was responsible for the kinaesthetic tered by PD, but in a recent study, Konczak, Krawczewski, impairments. These studies investigated kinaesthetic sensi- Tuite, and Maschke (2007) investigated the sensitivity to tivity of PD patients under conditions of blocked vision and detect passive limb motion. They assessed blind-folded par- those in which the patients were not actively moving and mus- ticipants for their ability to detect motion of their arm placed cle activation was monitored. Using a passive motion appara- in a passive motion apparatus, which horizontally extended tus, Maschke, Gomez, Tuite, and Konczak (2003) examined or flexed the elbow joint at a range of velocities between the sensitivity of PD patients to detect small changes in limb 1.65◦/s and 0.075◦/s. PD patients needed significantly larger position by passively displacing the forearm at velocities less limb displacements before they could judge the presence of than 0.5◦/s. After each displacement (between 0.2–8.0◦), par- passive motion. With decreasing velocity, the detection time ticipants indicated whether their forearm had been moved. increased exponentially in both control and PD participants. They tested three groups: individuals with mild to moderate However, in comparison with healthy controls, the detec- PD, patients with spinocerebellar , and control partici- tion times of the PD group were increased 92–166% for the pants. The detection thresholds at the 75% correct response various velocity conditions. level were 1.03◦ for controls, 1.15◦ for cerebellar patients, A third aspect of kinaesthesia, the sense of heaviness, was and 2.10◦ for PD patients, indicating that the PD group had recently evaluated in mild to moderately affected PD patients elevated detection thresholds that were on average twice as (Maschke, Tuite, et al., 2006). The sense of heaviness is high as the control and the cerebellar patient group. Only related to the perception of weight. Maschke, Tuite, et al. at displacements greater than 5◦ did PD patients exhibit the determined psychophysical thresholds for detecting weight same sensitivity as controls and cerebellar patients (see Fig- sensations by applying a gradually increasing load to the ure 2). This kinaesthetic impairment significantly correlated index finger by means of two slings of different width (low vs. with the severity and duration of PD (r = –0.7, for both mea- high skin pressure). Although healthy age-matched control sures). In a similar study, Putzki et al. (2006) replicated these participants sensed a load at 31–33 g, the mean thresholds for findings for the index finger, indicating that the sensitivity for the PD group were significantly increased in both pressure conditions (48–52 g). The increase in detection thresholds correlated positively with the severity of PD as measured by the Unified Parkinson’s Disease Rating Scale, indicating that the sensitivity to detect a load decreases as the disease progresses. Further evidence for altered proprioceptive sensitivity in PD comes from a study investigating haptic acuity. Using a robotic manipulandum to create virtual contours, Konczak, Li, Tuite, and Poizner (2008) assessed the ability of PD and control participants to judge, without vision, the curvature of their arm passively or actively moved in a concave or convex trajectory. Of 11 PD patients, 9 (82%) showed ele- vated thresholds for detecting convex curvatures in at least one test condition. The respective median threshold for the PD group was increased by 343% when compared with the control group, indicating that the acuity of the haptic sense becomes reduced in PD. That the patients in the previously FIGURE 2. Forearm position sense acuity. The forearm was passively moved to 10 different positions (elbow joint mentioned studies were only mildly to moderately affected angular displacement 0.2–8◦). Graph shows the sensitivity underlines the notion that haptic as well as kinaesthetic im- functions of healthy control participants (N = 11), a group pairments may become manifest already in the early stages of cerebellar patients (N = 9), and a group of mild to moder- of the disease. That is, proprioceptive or kinaesthetic deficits = ately affected Parkinson’s disease (PD) patients (N 9). The can appear very early in the disease and may precede motor perceptual detection threshold was defined at 75% correct response level. Each data point represents the mean response deficits. However, current clinical examination protocols are rate of each group (reprinted with permission, M. Maschke, not sensitive enough to detect these perceptual abnormalities. C. M. Gomez, P. J. Tuite, & J. Konczak, 2003). Because all of the previously mentioned psychophys- ical studies involved no active motion, monitored for

December 2009, Vol. 41, No. 6 545 J. Konczak et al. unwanted muscle activity, and excluded vision, it is very Jackson, Harrison, Henderson, & Kennard, 1995; Muratori, unlikely that bradykinesia, tremor, or possible movement McIsaac, Gordon, & Santello, 2008; Schettino et al., 2006), compensation strategies can explain the reported decline in for the coordination of arm and trunk motion (Poizner et kinaesthetic sensitivity in PD. Moreover, these data argue al., 2000), sequential arm movements (Curra et al., 1997), that these kinaesthetic deficits are genuine manifestations walking (Lewis, Byblow, & Walt, 2000), or for compensat- of the disease that may occur very early in the disease ing for mechanical perturbations (Jacobs & Horak, 2006). In process and may even precede the known motor problems reaching movements, for example, PD patients are impaired in PD. when they cannot see their arm and thus must use proprio- ception to guide their reaches (Adamovich et al., 2001; see Figure 3). Sensorimotor Integration: The Link Between Likewise, when holding an object, afferent information Vision, Proprioception, and Motor Function in PD from the digits must be mapped onto motor commands spec- Multiple lines of evidence indicate that the basal ganglia ifying appropriate force levels. PD patients tend to develop are important for sensorimotor integration, the mechanisms elevated grip force levels when holding an object, despite by which sensory information is processed to guide motor the fact that they show both predictive and reactive modes of planning and execution. Single cell recordings in the striatum force control (Mueller & Abbs, 1990; Nowak & Hermsdor- of , cats, and monkeys have demonstrated that the activ- fer, 2006). Again, this suggests that their dysfunction consists ity of these cells depends on whether sensory information of defective central processing or gating of sensory input. is linked to movement (Alexander & Crutcher, 1990; Lid- PD patients also show deficits in visual saccades (Briand, sky & Manetto, 1987; Lidsky, Manetto, & Schneider, 1985; Hening, Poizner, & Sereno, 2001; Briand, Strallow, Hening, Schneider et al., 1987; West et al., 1987). Striatal cells can be Poizner, & Sereno, 1999; Chan, Armstrong, Pari, Riopelle, silent for a given sensory event but robustly active when that & Munoz, 2005; Hood et al., 2007; Shaunak et al., 1999). same sensory event functions as a cue for a movement (West Orienting to an environmental event with a saccade requires et al., 1987). In addition, the caudate nucleus and substantia integration of multimodal sensory information and a mech- nigra contain a large proportion of cells that are multisen- anism that controls the integration process to select a signal sory, cells that could be used to integrate sensory inputs (Hikosaka, Takikawa, & Kawagoe, 2000). Consistent with and form a multimodal representation of the environment a deficit in sensorimotor integration, PD patients’ voluntary in the basal ganglia (Nagy, Eordegh, Paroczy, Markus, & as opposed to reflex saccades are often markedly disrupted Benedek, 2006). Likewise, the primate putamen contains bi- (Briand et al., 2001, 1999). modal visual-tactile cells that provide a map of peripersonal Thus, PD may be considered, in part, as a disorder of visual space. This map of visual space is organized somato- gain control of sensorimotor integration (Kaji, 2001; Kaji, topically and “could function to guide movements in the an- Urushihara, Murase, Shimazu, & Goto, 2005). Within this imal’s immediate vicinity” (Graziano & Gross, 1993, p. 96). process, dopamine may help to set the threshold for this gain When basal ganglia processes become disrupted, such as in control by modulating the responsiveness of the organism to MPTP-treated parkinsonian monkeys, more pallidal neurons the environment (Schultz, 2007). Dopamine depletion in PD than normal respond to passive limb movement, suggesting then would disrupt the integration of environmental context an impaired gain mechanism because of dopamine deple- with action planning and execution. tion (Filion et al., 1988). Results from other animal studies Although the deficient sensory gating hypothesis points to corroborate this finding by showing that the ability to use a sensory origin of the motor symptoms, it fails to explain posture-relevant sensory information decreases with striatal why proprioceptive function seems to be especially affected dopamine loss (Henderson, Watson, Halliday, Heinemann, by PD. As outlined previously, numerous studies and clini- & Gerlach, 2003; Martens, Whishaw, Miklyaeva, & Pellis, cal observations confirm that PD patients may rely on visual 1996). Thus, there is a wealth of evidence that the basal gan- cues to initiate or maintain movements. This visual depen- glia receive suitable inputs from vision and proprioception dence is consistent with a loss of proprioceptive function and to play an important role in the sensorimotor integration and points to a largely intact visual function in PD. Such vision- that dopamine depletion negatively impacts this integration for-proprioception compensation strategy indirectly implies process. that a major basal ganglia function is proprioceptive-motor The pattern of deficits in PD is consistent with a disrup- integration, whereas visuomotor integration is accomplished tion of this integration mechanism. PD patients may become elsewhere in the brain. There is some neuroanatomical ev- increasingly dependent on external stimuli to initiate and idence to support this claim. The basal ganglia receive af- shape motor output and may be unable to effectively execute ferents from the whole cortical mantle including the visual movements when deprived of critical proprioceptive infor- cortex, yet the projections from the dorsal visual stream to the mation. This leads to a documented dependence on visual basal ganglia are minor compared with the visual afferents cues during reaching movements (Adamovich et al., 2001; to the (Glickstein, 2000). These cerebellar and Flash, Inzelberg, Schechtman, & Korczyn, 1992; Klock- posterior parietal circuits are known to be critical for on-line gether & Dichgans, 1994), grasping movements (Jackson, visuomotor control and may be largely spared by the disease,

546 Journal of Motor Behavior Proprioception and Motor Control in Parkinson’s Disease

showed that, unlike healthy controls, PD patients do not modify postural response synergies immediately following a change in initial support conditions (Chong, Horak, & Wool- lacott, 2000; Chong, Jones, & Horak, 1999). For example, when healthy participants change postural support from free stance to sitting or to holding onto a stable support, their postural response synergies change immediately from leg to trunk or arm muscle activation (Horak, Nutt, & Nashner, 1992). In contrast, participants with PD do not reduce leg postural responses in the first trial after a change in initial support condition of sitting or holding, although they grad- ually adapt postural synergies with practice (Chong et al., 1999; Horak et al.). Similarly, healthy participants, but not PD participants, scale up the size of their anticipatory postural adjustments prior to step initiation in the first trial following an increase in stance width (Rocchi et al., 2006). The immediate increase in lateral reactive force to unload the initial stance leg with a wide stance, compared with a narrow stance, requires pro- prioceptive mapping of initial body posture and modification of postural adjustments prior to any feedback from body mo- tion. In addition, the inability to quickly increase anticipatory postural adjustments when stance width increases also may be related to bradykinetic force output. However, regardless of the mechanism, such failure to make anticipatory postural adjustments to unload the stepping leg may be responsible for the compensatory narrow stance width, start hesitation, FIGURE 3. Participants reached in the dark to five remem- or freezing in advanced PD. bered or actual targets presented in three-dimensional space with a robot arm. The target was an illuminated LED. There Two recent studies showed that PD patients have abnormal were three conditions of visual feedback in which partici- postural coordination only when vision was obscured, which pants were provided either no vision during the movement, is consistent with impaired proprioceptive mapping compen- only vision of the moving fingertip, or only vision of the sated by use of vision of the body. In one study, healthy, target but not the arm. Arm trajectories and endpoints across age-matched participants could accurately direct their auto- trials and conditions are presented for a control participants (top panel) and a Parkinson’s disease (PD) participant (bot- matically triggered, compensatory steps onto a small target tom panel). Green spheres represent movement endpoints on the ground in response to external postural perturbations, when participants reached to remembered targets without even when they could not view their stepping leg. In con- vision of their arms. Gray spheres represent movement end- trast, PD patients consistently undershot the targets when points when participants reached to remembered targets with they could not see their legs (Jacobs & Horak, 2006). Sim- vision of their moving fingertips, and blue spheres represent movement endpoints when participants reached to a visually ilarly, when PD patients closed their eyes, they showed a present target without vision of their arms. PD patients were breakdown in the temporal coordination between postural impaired in the two conditions in which they could not see adjustments and arm reaching during whole body reaching their arms. Thus, in reaching to remembered or to actual to a target (Tagliabue, Ferrigno, & Horak, 2009). targets, PD patients have difficulty in extracting and using Postural kinaesthesia also is disrupted in patients with PD. critical information from proprioception to map arm posi- tions onto spatial target locations to guide reaching move- Horak and coworkers tested the ability of PD patients to per- ments (adapted from S. V. Adamovich, M. B. Berkinblit, W. ceive surface inclination by asking blindfolded, standing par- Hening, J. Sage, & H. Poizner, 2001). ticipants to compare the relative dorsiflexion or plantarflexion of the support surface under a test foot with a 4-degree tilt of the surface under the reference foot (Wright et al., 2006). Par- which could explain the increased reliance on vision by PD ticipants with PD showed fewer percent correct trials when patients. indicating whether the surface under the reference foot was more or less plantar-flexed or dorsiflexed than the surface un- der the test foot (see Figure 4). Impaired kinaesthesia of the Proprioceptive Deficits and Postural Control in PD support surface was significantly correlated with the severity Several deficits of postural coordination observed in PD of PD. It is noteworthy that levodopa medication did not im- patients are consistent with the hypothesis that they have prove this kinaesthestic deficit, although it generally led to an impaired proprioceptive body map. A series of studies better motor performance.

December 2009, Vol. 41, No. 6 547 J. Konczak et al.

like the postural deficits associated with peripheral, propri- oceptive deficits that cause prolonged postural response la- tencies that are not observed in PD (Cameron, Horak, & Herndon, 2009; Inglis, Horak, Shupert, & Jones-Rycewicz, 1994).

Effects of Levodopa and DBS on Motor and Proprioceptive Function Dopamine replacement therapy is highly effective in ame- liorating many symptoms in PD. It is especially effective in early PD and results in an improvement of quality in life and survival (Miyasaki, Martin, Suchowersky, Weiner, & Lang, 2002). However, the effects of levodopa on pro- FIGURE 4. Kinaesthesia impairment during stance in par- prioception are not fully understood. Jobst, Melnick, Byl, ticipants with Parkinson’s disease in the on- and off- levodopa state compared with age-matched controls for per- Dowling, and Aminoff (1997) concluded that levodopa does ception of surface inclination (A) and torso rotation (B). (A) not improve kinaesthetic deficits in PD. During their on- Percent correct in judging one more degree of surface dor- medication state and with vision occluded, PD patients did siflexion in test compared with reference foot. (B)Percent not improve their sensitivity to perceive differences in move- correct in judging left or right direction of torso rotation. ment amplitudes made to a target away from the body, a task requiring the reliance on proprioceptive feedback (Jobst et al.). There is some indication that levodopa actually may The same group tested the kinaesthesia of axial trunk ro- have an added detrimental effect on kinaesthesia in PD. tation by asking participants to indicate the direction and For example, when comparing PD patients between their initial detection of yaw oscillations (1◦/s) of the support sur- off- and on-medication states, arm proprioception was im- face under their feet during stance (Wright et al., 2006). Axial paired by 31% 1 hour after administration of levodopa or rotation occurred either at the trunk, by stabilizing the shoul- dopamine agonists (O’Suilleabhain et al., 2001). In contrast, ders to earth and the pelvis to the rotating surface, or hips, psychophysical studies found no significant correlations be- by stabilizing the pelvis to earth (Gurfinkel et al., 2006). The tween levodopa dosage and elevated detection thresholds for ability of PD patients to accurately detect the direction and arm position sense, arm motion sense, or weight perception onset of axial rotation was impaired for both trunk and hip in a group of medicated and de novo (i.e., nonmedicated) PD twisting (see Figure 4), indicating that trunk position sense patients (Maschke et al., 2003; Maschke, Tuite, et al., 2006). was compromised. This finding corroborates and extends the In summary, there is some evidence that levodopa fur- results of previous studies showing that upper limb position ther degrades proprioceptive acuity with some authors ar- sense is altered by PD (Maschke et al., 2003; Maschke, Tuite, guing that levodopa enhanced proprioceptive deficits might et al., 2005). be one key in the development of levodopa induced dysk- When vision is absent, the control of sway on a firm sur- inesia (O’Suilleabhain et al., 2001). A role of levodopa in face depends primarily on proprioceptive feedback, whereas phasic pharmacological reduction of proprioception would control of sway on an unstable surface depends on vestibular be further supported if nondopaminergic medication such as feedback. The fact that PD patients may show larger postural amantadine was shown to improve proprioception. However, sway compared with controls when standing on a firm surface the only study investigating the influence of nondopaminer- than when standing on an unstable surface with eyes closed gic medication on proprioception revealed no influence of also is consistent with poor use of proprioceptive feedback the NMDA-antagonist flupirtine on automatic postural re- but excellent use of vestibular information, to control postu- sponses in PD (Putzki, Maschke, Drepper, Diener, & Tim- ral sway. In fact, sway characteristics of patients with PD are mann, 2002). consistent with increased proprioceptive feedback loop noise Although levodopa is a very effective treatment for PD, with abnormal feedback gain (Maurer, Mergner, & Peterka, motor complications develop over time with its use. The 2004). complications include the development of fluctuations in re- Thus, proprioceptive deficits may affect postural stability sponse to medication (i.e., motor fluctuations) and the ap- in PD by impairing (a) adaptation to changing support con- pearance of medication-induced abnormal involuntary move- ditions, (b) accuracy of compensatory stepping, (c) coupling ments (i.e., dyskinesia). In addition, antiparkinsonian medi- between postural adjustments and voluntary movement, (d) cation is not always that effective in treating tremor. Thus, as the perception of trunk and surface orientation, and (e) pos- the disease progresses, a subset of patients with PD become tural sway in stance. These postural deficits suggest a deficit candidates for DBS neurosurgical treatment, which can be in central integration of proprioception because they are un- very effective in alleviating motor certain symptoms in PD

548 Journal of Motor Behavior Proprioception and Motor Control in Parkinson’s Disease

(Samii, Nutt, & Ransom, 2004). Since the first documented the related tactile and haptic progressively diminishes report on the effects of DBS of the subthalamic nucleus (STN in PD (Konczak et al., 2007, 2008; Maschke et al., 2003; DBS) for PD (Limousin et al., 1995), there have been many Maschke, Tuite, et al., 2006; Maschke et al., 2005; Pratorius¨ reports on the efficacy of STN DBS for improving limb move- et al., 2003; Putzki et al., 2006). If, as suggested, a main ment in patients with PD. For example, STN DBS has been pathomechanism of PD lies in altering the gain of gating shown to be efficacious for simple force generation across and integrating proprioceptive and other sensory informa- a variety of effectors (Alberts, Elder, Okun, & Vitek, 2004; tion (Abbruzzese & Berardelli, 2003; Kaji et al., 2005), it Brown et al., 1999; Pinto, Gentil, Fraix, Benabid, & Pollak, becomes plausible that a failure to evaluate and map pro- 2003; Wenzelburger et al., 2003). It also has been shown prioceptive information onto voluntary and reflexive motor to be effective for single joint ballistic movements involv- commands underlies many of the observed motor symptoms ing either the elbow or joint (Vaillancourt et al., 2006; in PD. Levodopa medication may further decrease propri- Vaillancourt, Prodoehl, VerhagenMetman, Bakay, & Corcos, oceptive sensitivity, which would then explain the decrease 2004). These studies of single joint movement have shown in postural stability commonly observed in levodopa med- that STN DBS causes dramatic changes in both the agonist icated PD patients (Beuter, Hernandez, Rigal, Modolo, & and antagonist muscle activation that underlie the changes Blanchet, 2008; Horak, Frank, & Nutt, 1996; O’Suilleabhain in motor performance. STN DBS also has been shown to be et al., 2001). In contrast, STN DBS improves propriocep- efficacious for much more complicated movements such as tive acuity, which may explain the reported positive effect on movements performed in a sequence to a series of targets some aspects of postural function (Guehl et al., 2006; Rocchi, (Agostino et al., 2008). Chiari, Cappello, Gross, & Horak, 2004). However, the im- Although numerous studies have shown that DBS may proved kinaesthetic function because of STN DBS does not improve motor symptoms in PD, especially tremor, little is translate necessarily into improved postural function. Thus, known about the direct effect of DBS on proprioception. A the effects of other interventions such as STN DBS on pro- recent psychophysical experiment determining limb position prioceptive sensitivity and posture require further evaluation. detection thresholds in more severely affected, medicated PD patients reported a 20% improvement in kinaesthetic ACKNOWLEDGMENTS acuity during DBS on-state when compared with DBS-off (Maschke, Tuite, Pickett, Wachter, & Konczak, 2005). How- The idea for this review originated from an international ever, during DBS, forearm position sense acuity was not fully workshop on Motor Control and Proprioception in Parkin- restored and the mean threshold of the PD patient group was son’s Disease, which was held in Minneapolis on September still twice as high as the threshold of healthy control group. 18–19, 2008. All authors attended this workshop that was Given that levodopa potentially decreases kinaesthetic acuity supported in part by the Minnesota Medical Foundation, the in some PD patients (O’Suilleabhain et al., 2001), the pos- University of Minnesota Center for Clinical Movement Sci- itive effects of DBS on kinaesthetic acuity may have been ence, the University of Minnesota Academic Health Center, further enhanced, if the patients also were tested in their off- and by the University of Minnesota School of Kinesiology. medication state. However, the lack of clinical improvements Aspects of the research were supported in part by NIH grants in kinesthesia after DBS surgery is consistent with the lack of NS036449 (HP) and NS40902 (DMC). improvement in postural control and speech and the increase in falls with DBS. In summary, there are numerous reports indicating that REFERENCES DBS ameliorates certain motor symptoms in PD, such as Abbruzzese, G., & Berardelli, A. (2003). Sensorimotor integration tremor and bradykinesia (Anderson & Lenz, 2006; Perlmut- in movement disorders. Movement Disorders, 18, 231–240. Adamovich, S. V., Berkinblit, M. B., Hening, W., Sage, J., & ter & Mink, 2006). Its benefit for posture and balance func- Poizner, H. (2001). The interaction of visual and proprioceptive tion remains less clear. DBS also has been shown to improve inputs in pointing to actual and remembered targets in Parkinson’s kinaesthetic acuity in PD patients (Maschke et al., 2005), disease. , 104, 1027–1041. although the impact of improved kinaesthetic acuity on pos- Agostino, R., Dinapoli, L., Modugno, N., Iezzi, E., Gregori, B., tural control and upper limb function in PD patients is still Esposito, V., et al. (2008). Ipsilateral sequential arm movements after unilateral subthalamic deep-brain stimulation in patients poorly understood. Part of the problem of clearly discerning with Parkinson’s disease. Movement Disorders, 23, 1718–1724. the effects of both treatments, levodopa and DBS, on propri- Alberts, J. L., Elder, C. M., Okun, M. S., & Vitek, J. L. (2004). oception and motor control in PD stems from the fact that Comparison of pallidal and subthalamic stimulation on force researchers (a) still lack a full understanding of the physio- control in patients with Parkinson’s disease. Motor Control, 8, logical mechanisms of DBS and (b) do not fully know how 484–499. Alexander, G. E., & Crutcher, M. D. (1990). Neural representations DBS and levodopa medication interact in PD. of the target (goal) of visually guided arm movements in three motor areas of the monkey. Journal of Neurophysiology, 64, Summary 164–178. Anderson, W. S., & Lenz, F. A. (2006). Surgery insight: Deep brain On the basis of the findings of an array of psychophysical stimulation for movement disorders. Nature Clinical Practice in studies, it is clear that the acuity of the proprioceptive and Neurology, 2, 310–320.

December 2009, Vol. 41, No. 6 549 J. Konczak et al.

Antal, A., Bandini, F., Keri, S., & Bodis-Wollner, I. (1998). Visuo- DeLong, M. R., Crutcher, M. D., & Georgopoulos, A. P. (1985). cognitive dysfunctions in Parkinson’s disease. Clinical Neuro- Primate globus pallidus and subthalamic nucleus: Functional or- science, 5, 147–152. ganization. Journal of Neurophysiology, 53, 530–543. Bar-Gad, I., & Bergman, H. (2001). Stepping out of the box: In- Demirci, M., Grill, S., McShane, L., & Hallett, M. (1997). A mis- formation processing in the neural networks of the basal ganglia. match between kinesthetic and in Parkinson’s Current Opininion of Neurobiology, 11, 689–695. disease. Annals of Neurology, 41, 781–788. Bergman, H., Feingold, A., Nini, A., Raz, A., Slovin, H., Abeles, Diederich, N. J., Raman, R., Leurgans, S., & Goetz, C. G. M., et al. (1998). Physiological aspects of information processing (2002). Progressive worsening of spatial and chromatic pro- in the basal ganglia of normal and parkinsonian primates. Trends cessing deficits in Parkinson disease. Archives of Neurology, 59, in the , 21, 32–38. 1249–1252. Beuter, A., Hernandez, R., Rigal, R., Modolo, J., & Blanchet, P. Diener, H. C., Dichgans, J., Guschlbauer, B., & Mau, H. (1984). J. (2008). Postural sway and effect of levodopa in early Parkin- The significance of proprioception on postural stabilization as son’s disease. Canadian Journal of the Neurological Sciences, assessed by ischemia. Brain Research, 296, 103–109. 35, 65–68. Dietz, V. (2002). Proprioception and locomotor disorders. Nature Bevan, M. D., Magill, P. J., Terman, D., Bolam, J. P., & Wilson, C. Review Neuroscience, 3, 781–790. J. (2002). Move to the rhythm: Oscillations in the subthalamic Escola, L., Michelet, T., Douillard, G., Guehl, D., Bioulac, B., & nucleus-external globus pallidus network. Trends in the Neuro- Burbaud, P. (2002). Disruption of the proprioceptive mapping in sciences, 25, 525–531. the medial wall of parkinsonian monkeys. Annals of Neurology, Boraud, T., Bezard, E., Bioulac, B., & Gross, C. E. (2000). Ratio 52, 581–587. of inhibited-to-activated pallidal neurons decreases dramatically Filion, M., Tremblay, L., & Bedard, P. J. (1988). Abnormal in- during passive limb movement in the MPTP-treated monkey. fluences of passive limb movement on the activity of globus Journal of Neurophysiology, 83, 1760–1763. pallidus neurons in parkinsonian monkeys. Brain Research, 444, Briand, K. A., Hening, W., Poizner, H., & Sereno, A. B. (2001). Au- 165–176. tomatic orienting of visuospatial attention in Parkinson’s disease. Flash, T., Inzelberg, R., Schechtman, E., & Korczyn, A. D. (1992). Neuropsychologia, 39, 1240–1249. Kinematic analysis of upper limb trajectories in Parkinson’s dis- Briand, K. A., Strallow, D., Hening, W., Poizner, H., & Sereno, ease. Experimental Neurology, 118, 215–226. A. B. (1999). Control of voluntary and reflexive saccades in Gardner, E. P., Martin, J. H., & Jessell, T. M. (2000). The bodily Parkinson’s disease. Experimental Brain Research, 129, 38–48. senses. In E. R. Kandel, J. H. Schwartz, & T. M. Jessell (Eds.), Brown, R. G., Dowsey, P. L., Brown, P., Jahanshahi, M., Pollak, P., Principles of neural science (4th ed., pp. 430–450). New York: Benabid, A. L., et al. (1999). Impact of deep brain stimulation on McGraw-Hill. upper limb akinesia in Parkinson’s disease. Annals of Neurology, Gatev, P., Darbin, O., & Wichmann, T. (2006). Oscillations in the 45, 473–488. basal ganglia under normal conditions and in movement disor- Butler, A. J., Fink, G. R., Dohle, C., Wunderlich, G., Tellmann, L., ders. Movement Disorders, 21, 1566–1577. Seitz, R. J., et al. (2004). Neural mechanisms underlying reaching Ghez, C., Gordon, J., & Ghilardi, M. F. (1995). Impairments of for remembered targets cued kinesthetically or visually in left or reaching movements in patients without proprioception: II. Ef- right hemispace. Mapping, 21, 165–177. fects of visual information on accuracy. Journal of Neurophysi- Cameron, M., Horak, F. B., & Herndon, R. R. (2009). Imbal- ology, 73, 361–372. ance in multiple sclerosis: A result of slowed spinal somatosen- Glickstein, M. (2000). How are visual areas of the brain connected sory conduction. Somatosensory and Motor Research, 25, 113– to motor areas for the sensory guidance of movement? Trends in 122. the Neurosciences, 23, 613–617. Chan, F., Armstrong, I. T., Pari, G., Riopelle, R. J., & Munoz, D. P. Goldberg, J. A., Rokni, U., Boraud, T., Vaadia, E., & Bergman, (2005). Deficits in saccadic eye-movement control in Parkinson’s H. (2004). Spike synchronization in the cortex/basal-ganglia net- disease. Neuropsychologia, 43, 784–796. works of Parkinsonian primates reflects global dynamics of the Chong, R. K., Horak, F. B., & Woollacott, M. H. (2000). Parkin- local field potentials. Journal of Neuroscience, 24, 6003–6010. son’s disease impairs the ability to change set quickly. Journal Goldscheider, A. (1898). Physiologie des Muskelsinnes. Leipzig: of Neurological Science, 175, 57–70. Johann Ambrosius Barth. Chong, R. K., Jones, C. L., & Horak, F. B. (1999). Postural set Graybiel, A. M. (1998). The basal ganglia and chunking of action for balance control is normal in Alzheimer’s but not in Parkin- repertoires. Neurobiology of Learning and Memory, 70, 119–136. son’s disease. Journal of Gerontology A: Biological Science and Graybiel, A. M. (2005). The basal ganglia: Learning new tricks Medical Science, 54, M129–135. and loving it. Current Opinion in Neurobiology, 15, 638– Contreras-Vidal, J. L., & Gold, D. R. (2004). Dynamic estimation of 644. hand position is abnormal in Parkinson’s disease. Parkinsonism Graziano, M. S., & Gross, C. G. (1993). A bimodal map of space: and Related Disorders, 10, 501–506. Somatosensory receptive fields in the macaque putamen with cor- Crutcher, M. D., & DeLong, M. R. (1984a). Single cell studies of responding visual receptive fields. Experimental Brain Research, the primate putamen: I. Functional organization. Experimental 97, 96–109. Brain Research, 53, 233–243. Guehl,D.,Dehail,P.,deSeze,M.P.,Cuny,E.,Faux,P.,Tison, Crutcher, M. D., & DeLong, M. R. (1984b). Single cell studies of F., et al. (2006). Evolution of postural stability after subthalamic the primate putamen: II. Relations to direction of movement and nucleus stimulation in Parkinson’s disease: A combined clini- pattern of muscular activity. Experimental Brain Research, 53, cal and posturometric study. Experimental Brain Research, 170, 244–258. 206–215. Curra, A., Berardelli, A., Agostino, R., Modugno, N., Puorger, Gurfinkel, V., Cacciatore, T. W., Cordo, P., Horak, F., Nutt, J., C. C., Accornero, N., et al. (1997). Performance of sequential & Skoss, R. (2006). Postural muscle tone in the body axis arm movements with and without advance knowledge of motor of healthy humans. Journal of Neurophysiology, 96, 2678– pathways in Parkinson’s disease. Movement Disorders, 12, 646– 2687. 654. Henderson, J. M., Watson, S., Halliday, G. M., Heinemann, T., & DeLong, M. R. (1990). Primate models of movement disorders of Gerlach, M. (2003). Relationships between various behavioural basal ganglia origin. Trends in Neuroscience, 13, 281–285. abnormalities and nigrostriatal dopamine depletion in the

550 Journal of Motor Behavior Proprioception and Motor Control in Parkinson’s Disease

unilateral 6-OHDA-lesioned . Behavioural Brain Research, Lidsky, T. I., Manetto, C., & Schneider, J. S. (1985). A considera- 139, 105–113. tion of sensory factors involved in motor functions of the basal Herting, B., Schulze, S., Reichmann, H., Haehner, A., & Hummel, ganglia. Brain Research Bulletin, 356, 133–146. T. (2008). A longitudinal study of olfactory function in patients Limousin, P., Pollak, P., Benazzouz, A., Hoffmann, D., Le Bas, J. with idiopathic Parkinson’s disease. Journal of Neurology, 255, F., Broussolle, E., et al. (1995). Effect of parkinsonian signs and 367–370. symptoms of bilateral subthalamic nucleus stimulation. Lancet, Hikosaka, O., Takikawa, Y., & Kawagoe, R. (2000). Role of the 345, 91–95. basal ganglia in the control of purposive saccadic eye movements. Martens, D. J., Whishaw, I. Q., Miklyaeva, E. I., & Pellis, S. M. Physiological Review, 80, 953–978. (1996). Spatio-temporal impairments in limb and body move- Hood, A. J., Amador, S. C., Cain, A. E., Briand, K. A., Al-Refai, A. ments during righting in an hemiparkinsonian rat analogue: Rel- H., Schiess, M. C., et al. (2007). Levodopa slows prosaccades and evance to axial apraxia in humans. Brain Research, 733, 253– improves antisaccades: An eye movement study in Parkinson’s 262. disease. Journal of Neurology, Neurosurgery, and Psychiatry, 78, Maschke, M., Gomez, C. M., Tuite, P. J., & Konczak, J. (2003). 565–570. Dysfunction of the basal ganglia, but not the cerebellum, impairs Horak, F. B., Frank, J., & Nutt, J. (1996). Effects of dopamine on kinaesthesia. Brain, 126, 2312–2322. postural control in parkinsonian subjects: Scaling, set, and tone. Maschke, M., Gomez, C. M., Tuite, P. J., Pickett, K., & Konczak, J. Journal of Neurophysiology, 75, 2380–2396. (2006). in cerebellar and basal ganglia disease. Horak, F. B., Nutt, J. G., & Nashner, L. M. (1992). Postural inflexi- Experimental Brain Research, 175, 165–176. bility in parkinsonian subjects. Journal of Neurological Science, Maschke, M., Tuite, P. J., Krawczewski, K., Pickett, K., & Konczak, 111, 46–58. J. (2006). The perception of heaviness in Parkinson’s disease. Inglis, J. T., Horak, F. B., Shupert, C. L., & Jones-Rycewicz, C. Movement Disorders, 21, 1013–1018. (1994). The importance of somatosensory information in trigger- Maschke, M., Tuite, P. J., Pickett, K., Wachter, T., & Konczak, ing and scaling automatic postural responses in humans. Experi- J. (2005). The effect of subthalamic nucleus stimulation on ki- mental Brain Research, 101, 159–164. naesthesia in Parkinson’s disease. Journal of Neurology, Neuro- Jackson, S. R., Jackson, G. M., Harrison, J., Henderson, L., & Ken- surgery, and Psychiatry, 76, 569–571. nard, C. (1995). The internal control of action and Parkinson’s Maurer, C., Mergner, T., & Peterka, T. J. (2004). Abnormal reso- disease: A kinematic analysis of visually-guided and memory- nance behavior of the postural control loop in Parkinson’s disease. guided prehension movements. Experimental Brain Research, Experimental Brain Research, 157, 369–376. 105, 147–162. Mesholam, R. I., Moberg, P. J., Mahr, R. N., & Doty, R. L. (1998). Jacobs, J. V., & Horak, F. B. (2006). Abnormal proprioceptive- Olfaction in neurodegenerative disease: A meta-analysis of ol- motor integration contributes to hypometric postural responses factory functioning in Alzheimer’s and Parkinson’s diseases. of subjects with Parkinson’s disease. Neuroscience, 141, 999– Archives of Neurology, 55, 84–90. 1009. Mink, J. W. (1996). The basal ganglia: Focused selection and inhi- Jobst, E. E., Melnick, M. E., Byl, N. N., Dowling, G. A., & Aminoff, bition of competing motor programs. Progress in Neurobiology, M. J. (1997). Sensory perception in Parkinson disease. Archives 50, 381–425. of Neurology, 54, 450–454. Miyasaki, J. M., Martin, W., Suchowersky, O., Weiner, W. J., & Kaji, R. (2001). Basal ganglia as a sensory gating devise for Lang, A. E. (2002). Practice parameter: Initiation of treatment motor control. Journal of Medical Investigation, 48, 142– for Parkinson’s disease: An evidence-based review: Report of 146. the Quality Standards Subcommittee of the American Academy Kaji, R., Urushihara, R., Murase, N., Shimazu, H., & Goto, S. of Neurology. Neurology, 58, 11–17. (2005). Abnormal sensory gating in basal ganglia disorders. Jour- Mueller, F., & Abbs, J. H. (1990). Precision grip in parkinsonian nal of Neurology, 252, iv13–iv16. patients. Advances in Neurology, 53, 191–195. Klockgether, T., Borutta, M., Rapp, H., Spieker, S., & Dichgans, J. Muratori, L. M., McIsaac, T. L., Gordon, A. M., & Santello, M. (1995). A defect of kinesthesia in Parkinson’s disease. Movement (2008). Impaired anticipatory control of force sharing patterns Disorders, 10, 460–465. during whole-hand grasping in Parkinson’s disease. Experimental Klockgether, T., & Dichgans, J. (1994). Visual control of arm move- Brain Research, 185, 41–52. ment in Parkinson’s disease. Movement Disorders, 9, 48–56. Nagy, A., Eordegh, G., Paroczy, Z., Markus, Z., & Benedek, G. Koller, W. C. (1984). Sensory symptoms in Parkinson’s disease. (2006). in the basal ganglia. European Neurology, 34, 957–959. Journal of Neuroscience, 24, 917–924. Konczak, J., Krawczewski, K., Tuite, P., & Maschke, M. (2007). Nolano, M., Provitera, V., Estraneo, A., Selim, M. M.,Caporaso, The perception of passive motion in Parkinson’s disease. Journal G., Stancanelli, A., et al. (2008). Sensory deficit in Parkin- of Neurology, 254, 655–663. son’s disease: Evidence of a cutaneous denervation. Brain, 131, Konczak, J., Li, K. Y., Tuite, P. J., & Poizner, H. (2008). Haptic 1903–1911. perception of object curvature in Parkinson’s disease. PLoS ONE, Nowak, D. A., & Hermsdorfer, J. (2006). Predictive and reactive 3(7), e2625. control of grasping forces: On the role of the basal ganglia and Leiguarda, R., Merello, M., Balej, J., Starkstein, S., Nogues, M., & sensory feedback. Experimental Brain Research, 173, 650–660. Marsden, C. D. (2000). Disruption of spatial organization and in- O’Suilleabhain, P., Bullard, J., & Dewey, R. B. (2001). Propriocep- terjoint coordination in Parkinson’s disease, progressive supranu- tion in Parkinson’s disease is acutely depressed by dopaminergic clear palsy, and multiple system atrophy. Movement Disorders, medications. Journal of Neurology, Neurosurgery, and Psychia- 15, 627–640. try, 71, 607–610. Lewis, G. N., Byblow, W. D., & Walt, S. E. (2000). Stride length Perlmutter, J. S., & Mink, J. W. (2006). Deep brain stimulation. regulation in Parkinson’s disease: The use of extrinsic, visual Annual Review of Neuroscience, 29, 229–257. cues. Brain, 123, 2077–2090. Pessiglione, M., Guehl, D., Rolland, A. S., Francois, C., Hirsch, Lidsky, T. I., & Manetto, C. (1987). Context-dependent activity E. C., Feger, J., et al. (2005). Thalamic neuronal activity in in the striatum. In J. S. Schneider & T. I. Lidsky (Eds.), Basal dopamine-depleted primates: Evidence for a loss of functional ganglia and behavior: Sensory aspects of motor functioning (pp. segregation within basal ganglia circuits. Journal of Neuro- 123–133). Toronto, Canado: Hans Huber. science, 25, 1523–1531.

December 2009, Vol. 41, No. 6 551 J. Konczak et al.

Pinto, S., Gentil, M., Fraix, V., Benabid, A. L., & Pollak, P. (2003). Effects of visual feedback and medication state. Experimental Bilateral subthalamic stimulation effects on oral force control in Brain Research, 168, 186–202. Parkinson’s disease. Journal of Neurology, 250, 179–187. Schneider, J. S., Diamond, S. G., & Markham, C. H. (1987). Parkin- Poizner, H., Feldman, A. G., Levin, M. F., Berkinblit, M. B., Hening, son’s disease: Sensory and motor problems in arms and hands. W. A., Patel, A., et al. (2000). The timing of arm-trunk coordi- Neurology, 37, 951–956. nation is deficient and vision-dependent in Parkinson’s patients Schultz, W. (2007). Multiple dopamine functions at different time during reaching movements. Experimental Brain Research, 133, courses. Annual Review of Neuroscience, 30, 259–288. 279–292. Seiss, E., Praamstra, P., Hesse, C. W., & Rickards, H. (2003). Pro- Pratorius,¨ B., Kimmeskamp, S., & Milani, T. L. (2003). The sensi- prioceptive sensory function in Parkinson’s disease and Hunting- tivity of the sole of the foot in patients with Morbus Parkinson. ton’s disease: Evidence from proprioception-related EEG poten- Neuroscience Letters, 346, 173–176. tials. Experimental Brain Research, 148, 308–319. Putzki, N., Maschke, M., Drepper, J., Diener, H. C., & Timmann, Shaunak, S., O’Sullivan, E., Blunt, S., Lawden, M., Crawford, T., D. (2002). Effect of functional NMDA-antagonist flupirtine on Henderson, L., et al. (1999). Remembered saccades with variable automatic postural responses in Parkinson’s disease. Journal of delay in Parkinson’s disease. Movement Disorders, 14, 80–86. Neurology, 249, 824–828. Snider, S. R., Fahn, S., Isgreen, W. P., & Cote, L. J. (1976). Primary Putzki, N., Stude, P., Konczak, J., Graf, K., Diener, H. C., & sensory symptoms in parkinsonism. Neurology, 26, 423–429. Maschke, M. (2006). Kinesthesia is impaired in focal dystonia. Tagliabue, M., Ferrigno, G., & Horak, F. B. (2009). Effects of Movement Disorders, 21, 754–760. Parkinson’s disease on proprioceptive control of posture and Raz, A., Frechter-Mazar, V., Feingold, A., Abeles, M., Vaadia, E., reaching while standing. Neuroscience, 158, 1206–1214. & Bergman, H. (2001). Activity of pallidal and striatal tonically Vaillancourt, D. E., Prodoehl, J., Sturman, M. M., Bakay, R. A., active neurons is correlated in mptp-treated monkeys but not in Metman, L. V., & Corcos, D. M. (2006). Effects of deep brain normal monkeys. Journal of Neuroscience, 21, RC128. stimulation and medication on strength, bradykinesia, and elec- Raz, A., Vaadia, E., & Bergman, H. (2000). Firing patterns tromyographic patterns of the ankle joint in Parkinson’s disease. and correlations of spontaneous discharge of pallidal neurons Movement Disorders, 21, 50–58. in the normal and the tremulous 1-methyl-4-phenyl-1,2,3,6- Vaillancourt, D. E., Prodoehl, J., Verhagen Metman, L., Bakay, R. tetrahydropyridine vervet model of parkinsonism. Journal of A., & Corcos, D. M. (2004). Effects of deep brain stimulation and Neuroscience, 20, 8559–8571. medication on bradykinesia and muscle activation in Parkinson’s Rocchi, L., Chiari, L., Cappello, A., Gross, A., & Horak, F. B. disease. Brain, 127, 491–504. (2004). Comparison between subthalamic nucleus and globus Wenzelburger, R., Kopper, F., Zhang, B. R., Witt, K., Hamel, W., pallidus internus stimulation for postural performance in Parkin- Weinert, D., et al. (2003). Subthalamic nucleus stimulation for son’s disease. Gait and Posture, 19, 172–183. Parkinson’s disease preferentially improves akinesia of proxi- Rocchi, L., Chiari, L., Mancini, M., Carlson-Kuhta, P., Gross, A., mal arm movements compared to finger movements. Movement & Horak, F. B. (2006). Step initiation in Parkinson’s disease: Disorders, 18, 1162–1169. influence of initial stance conditions. Neuroscience Letters, 406, West, M., Knowles, A., Chapin, J., Woodward, D., Schneider, J. 128–132. S., & Lidsky, T. I. (1987). Striatal unit activity and the linkage Rodriguez-Oroz, M. C., Rodriguez, M., Guridi, J., Mewes, K., between sensory and motor events. In Anonymous (Ed.), Basal Chockkman, V., Vitek, J., et al. (2001). The subthalamic nucleus ganglia and behavior: Sensory aspects of motor functioning (pp. in Parkinson’s disease: Somatotopic organization and physiolog- 28–35). Toronto: Hans Huber. ical characteristics. Brain, 124, 1777–1790. Wright, G., Horak, F. B., Fujiwara, K., Carlson-Kuhta, P., Gurfinkel, Rossini, P. M., Filippi, M. M., & Vernieri, F. (1998). Neurophysiol- V.S., & Jacobs, J. (2006, May). Parkinson’s disease affects kines- ogy of sensorimotor integration in Parkinson’s disease. Clinical thetic perception during postural tasks. Paper presented at the Neuroscience, 5, 121–130. Neural Control of Movement, Key Biscayne, FL. Rothwell, J. C., Traub, M. M., Day, B. L., Obeso, J. A., Thomas, Zia, S., Cody, F., & O’Boyle, D. (2000). Joint position sense is P. K., & Marsden, C. D. (1982). Manual motor performance in a impaired by Parkinson’s disease. Annals of Neurology, 47(2), deafferented man. Brain, 105, 515–542. 218–228. Sainburg, R. L., Ghilardi, M. F., Poizner, H., & Ghez, C. (1995). Zia, S., Cody, F. W., & O’Boyle, D. J. (2002). Identification of Control of limb dynamics in normal subjects and patients without unilateral elbow-joint position is impaired by Parkinson’s disease. proprioception. Journal of Neurophysiology, 73, 820–835. Clinical Anatomy, 15, 23–31. Samii, A., Nutt, J. G., & Ransom, B. R. (2004). Parkinson’s disease. Zia, S., Cody, F. W., & O’Boyle, D. J. (2003). Discrimination Lancet, 363, 1783–1793. of bilateral differences in the loci of tactile stimulation is im- Sathian, K., Zangaladze, A., Green, J., Vitek, J. L., & DeLong, M. paired in subjects with Parkinson’s disease. Clinical Anatomy, R. (1997). Tactile spatial acuity and roughness discrimination: 16, 241–247. Impairments due to aging and Parkinson’s disease. Neurology, 49, 168–177. Submitted April 9, 2009 Schettino, L. F., Adamovich, S. V., Hening, W., Tunik, E., Sage, J., Revised May 25, 2009 & Poizner, H. (2006). Hand preshaping in Parkinson’s disease: Accepted May 26, 2009

552 Journal of Motor Behavior