Does the cerebellum play a role in podokinetic adaptation?

Transcription

1 Exp Brain Res (2002) 146: DOI /s y RESEARCH NOTE Gammon M. Earhart William A. Fletcher Fay B. Horak Edward W. Block Kimberly D. Weber Oksana Suchowersky Geoffrey Melvill Jones Does the cerebellum play a role in podokinetic adaptation? Received: 12 April 2002 / Accepted: 15 July 2002 / Published online: 7 September 2002 Springer-Verlag 2002 Abstract After sustained stepping in-place on a rotating disc, healthy subjects will inadvertently turn in circles when asked to step in-place on a stationary surface with eyes closed. We asked whether the cerebellum is important for this adaptive phenomenon, called podokinetic after-rotation (PKAR). Subjects with cerebellar degeneration and age-matched control subjects performed 15 min of stepping in-place with eyes open on a rotating disc, then 30 min of attempting to step in-place with eyes closed on a stationary surface. Rotational velocity of PKAR was measured during this 30-min period. All control subjects demonstrated PKAR; average initial rotational velocity for control subjects was /s. Five of the eight cerebellar subjects demonstrated impaired PK adaptation, defined as PKAR with an initial velocity more than two standard deviations below the control mean initial velocity. Average initial rotational velocity for cerebellar subjects was /s. Impaired PK adaptation was not associated with impaired time constants of decay and was not correlated with variability of PKAR velocity. Our results suggest that the cerebellum is important for regulation of the amplitude of PK adaptation and that reduced PKAR amplitude is not likely the result of dyscoordination or variability of movement in the subjects tested. Keywords Cerebellum Locomotion Sensorimotor adaptation Podokinetic G.M. Earhart ()) W.A. Fletcher E.W. Block K.D. Weber O. Suchowersky G. Melvill Jones Department of Clinical Neurosciences and Neuroscience Research Group, The University of Calgary, Calgary, Alberta T2N 2T9, Canada earhartg@ohsu.edu Tel.: Fax: G.M. Earhart F.B. Horak Balance Disorders Laboratory, Neurological Sciences Institute, Oregon Health and Science University, Beaverton, OR 97006, USA Introduction One of the major roles attributed to the cerebellum is involvement in motor learning. Lesions of the inferior olive or cerebellum impair or prevent adaptation of many different movements, including reaching and catching (Martin et al. 2000; Lang and Bastian 1999). Adaptation of throwing and pointing movements while looking through prisms is reduced or abolished following cerebellar lesions (Baizer et al. 1999; Martin et al. 1996). Cerebellar damage reduces acquisition of the lower-limb, conditioned-withdrawal response (Timmann et al. 2000). Adaptation of the gains of postural responses, saccades, and the vestibuloocular reflex (VOR) are impaired by cerebellar lesions (Mummel et al. 1998; Timmann and Horak 1997; Straube et al. 2001; Cohen et al. 1992). Locomotor adaptations in response to changes in treadmill belt speed are also lessened when cerebellar function is abnormal (Rand et al. 1998; Yanagihara and Kondo 1996). In the present experiment, we investigated the role of the cerebellum in podokinetic adaptation. Healthy subjects, following a period of stepping in-place on a rotating circular treadmill, will inadvertently turn when asked to step in-place without vision on a stationary surface (Weber et al. 1998). This phenomenon, termed podokinetic after-rotation (PKAR), represents a remodeling of the relationship between trunk rotation relative to the foot and the perception of trunk rotation in space (Gordon et al. 1995). We hypothesized that this adaptation, like the many others mentioned previously, involves the cerebellum. As such, we expected subjects with cerebellar damage to show impaired podokinetic adaptation. Materials and methods Subjects Eight subjects with a diagnosis of cerebellar degeneration and/or spinocerebellar ataxia [mean age ( SD): 47.8 ( 11.2) years] and

2 539 Table 1 Information on cerebellar subjects (S sporadic ataxia, AD autosomal dominant ataxia (gene not localized), SCA 6 spinocerebellar ataxia type 6) Impaired PK adaptation Balance impairment Gait ataxia Lower limb ataxia Cerebellar atrophy severity per MRI Gender Diagnosis Length of illness (years) Cerebellar subject Age (years) 1 38 M S 9 Severe Moderate Moderate Severe Yes 2 45 M S 3 Mild Mild Moderate Moderate Yes 3 45 F AD 11 Moderate Mild Mild Moderate No 4 52 M AD 5 Mild Mild Moderate Moderate Yes 5 47 M S 7 Mild Moderate Mild Moderate No 6 61 F SCA 6 3 Severe Moderate Mild Moderate No 7 64 M SCA 6 8 Normal Mild Mild Moderate Yes 8 30 F S 15 Severe Mild Mild Mild Yes eight age-matched control subjects [44.6 ( 17.9) years] participated in this experiment. Cerebellar disease was confirmed by neurological and genetic testing and/or MRI. None of the subjects had loss of position sense or clinical features of other neurological dysfunction. See Table 1 for cerebellar subject information, including clinical ratings for gait and lower limb ataxia and balance (Trouillas et al. 1997). A subject s gait ataxia was rated mild if he had slightly wide-based or unsteady gait and was rated moderate if he had moderately wide-based or unsteady gait but was able to walk independently. A subject s limb ataxia was rated mild if he was able to perform the heel-shin test with little or no jerkiness of movement and slight lateral oscillation as the heel moved along the shin; it was rated moderate if he performed the test with jerky movements that went laterally off the shin. A subject s balance impairment was rated as mild if he had difficulty with tandem stance, rated as moderate if he could not perform tandem stance without support, and rated as severe if he could not stand with the feet together without support. Balance measures were performed with eyes open. All subjects provided informed consent prior to participation. Protocol and data collection Each subject underwent a neurological exam at the beginning of the experimental session. Subjects were then exposed to a podokinetic stimulus that consisted of 15 min of stepping in-place over the axis of a 76-cm disc rotating in the clockwise direction at 45 /s. Each subject wore a safety harness (NeuroCom, Clackamas, Ore.) and held onto a low-friction overhead wheel at all times while on the disc. The wheel provided postural stability, but did not provide subjects with information regarding turning direction or velocity (Weber et al. 1998). Stepping frequency was maintained at 2 Hz by matching cadence to a metronome affixed to the trunk. Following the 15-min period of adaptation, subjects performed 30 min of stepping in-place over the axis of the stationary disc while wearing a blindfold and earplugs. During this 30-min period, PKAR responses were recorded by means of the overhead wheel. The wheel, equipped with a rotational potentiometer, registered angular position of the body in space. All subjects kept their hands on the wheel throughout the period during which PKAR was measured. Data analysis Angular velocity of body rotation was calculated from body position data by taking the slopes between successive data points at 5-s intervals. Plots of angular velocity versus time were generated using Sigmaplot 5.0 (SPSS, Richmond, Calif.). The first 2 min of each plot were fitted with an exponential growth function to yield 2-min rise maxima and rise time constants. The remaining 28 min of each plot were fitted with a three-parameter exponential decay function to obtain values for initial velocity, decay time constant, and final asymptote. Group averages for the cerebellar and control groups were obtained, and comparisons between the two groups were performed using paired t-tests. Individual cerebellar subjects were said to have impaired PK adaptation if their initial PKAR velocity was more than two standard deviations below the control mean initial PKAR velocity. Initial PKAR velocity was compared with decay time constant and with the variance of PKAR velocity from minutes 25 to 30, using Pearson product moment correlations. Variability was examined from 25 to 30 min because the PKAR response has reached an asymptote at this point. Variability would be falsely increased if measured at a time when the response was still decaying. Results All subjects were able to step in-place on the rotating disc and maintain a steady heading for 15 min. Some

3 540 Fig. 1 Illustration of PKAR in two control subjects and two cerebellar subjects. Plots show rotational velocity plotted vs time for the 30-min period of PKAR. Note that the cerebellar subjects showed lower maximum and initial velocities, lower y-intercepts and shorter rise time constants but similar asymptotes and decay time constants cerebellar subjects required several steps to become familiar with the task and stay in-place. The 15-min time period began after this initial short period of familiarization. Figure 1 shows the time course of PKAR for two control subjects and two cerebellar subjects with impaired PK adaptation. Both cerebellar subjects had very low angular velocities (approximately 5 /s) at the start of PKAR compared with control velocities (approximately 15 /s). Note that cerebellar subject 2 also demonstrated increased variability of velocity throughout PKAR. Overall, the cerebellar group was significantly more variable than the control group in terms of PKAR velocity, as assessed by measuring variance of PKAR velocity during the last 5 min of the 30-min recording session. Mean PKAR velocity variance of the cerebellar group was 2.1 /s, significantly higher than the control group variance of 0.93 /s (t-test, P<0.05). The cerebellar group had significantly lower mean initial PKAR velocities, maximum PKAR velocities, and y-intercepts compared with the control group (Table 2). The cerebellar group also had a significantly shorter rise time constant. Despite these differences, the cerebellar group had a decay time constant and an asymptote very similar to those of the control group. There was no substantial correlation (r=0.12, P=0.82) between initial PKAR velocity and decay time constant in the cerebellar group. Figure 2 shows initial PKAR velocities for all subjects. Values below the horizontal dotted line represent im- Table 2 Group means (with standard deviations) for podokinetic adaptation PKAR characteristics Cerebellar a Control a Maximum (/s) 10.0 b (4.3) 18.0 (7.0) Rise time constant (min) 0.3 b (0.2) 0.8 (0.4) Initial velocity (/s) 7.8 b (3.2) 16.4 (3.5) Y-intercept (/s) 9.5 b (3.5) 17.6 (6.5) Asymptote (/s) 1.7 (2.9) 1.0 (2.4) Decay time constant (min) 12.4 (10.3) 9.6 (4.9) a Values are means, plus SDs in parentheses b A significant difference between the cerebellar and control groups (P<0.05)

4 Fig. 2 Plot of individual initial PKAR velocities for cerebellar and control subjects. Points below the horizontal dotted line (2 SDs below the control mean initial PKAR velocity) represent impaired PK adaptation paired PK adaptation, defined as a velocity that was more than two standard deviations below the control mean initial velocity. According to this criterion, five of the eight cerebellar subjects showed impaired PK adaptation. This reduction in PKAR amplitude was not related to variability of PKAR velocity. There was no substantial correlation (r=0.26, P=0.53) between PKAR initial velocity and PKAR velocity variance (measured between minutes 25 and 30, see Materials and methods) in the cerebellar group. In fact, of the four cerebellar subjects with the most variability in PKAR velocity, two had unimpaired PK adaptation (i.e., normal initial PKAR velocities). Discussion It is not surprising that the cerebellum may play a role in PKAR, as cerebellar damage is known to impair many types of adaptation (Thach et al. 1992). Our results suggest that PKAR is not strictly a peripheral phenomenon since the cerebellum is important for PK adaptation. Over half of the cerebellar subjects, but none of the control subjects, exhibited impaired adaptation of locomotor trajectory. This impairment was in the form of low amplitude PKAR, while the decay time constant and asymptote of cerebellar subjects were similar to those of control subjects. These similarities suggest that the cerebellum is important for regulation of PKAR response gain, but that cerebellar disease does not impair retention of the adaptive response. The increased variability of the cerebellar group may be a result of the dyscoordination and balance deficits exhibited by some subjects in the group. We attempted to minimize the influence of variability of movement, dyscoordination, and imbalance by having subjects support themselves with an overhead wheel. Subjects were also supported via a parachute harness on a universal joint. Additionally, we included only subjects who were able to maintain a steady heading and match the metronome-specified cadence, which further helped to standardize the stimulation received while walking on the rotating disc. There was no correlation between variability of PKAR velocity and initial PKAR velocity amplitude. Thus, while dyscoordination was likely a contributing factor in the increased variability of PKAR velocity observed in some cerebellar subjects, it was not a likely source of overall reduction in PKAR velocity. In fact, reduced PKAR velocity did not correlate well with severity of cerebellar atrophy or with the assessed clinical impairments of balance, gait, or lower limb movements. The importance of the cerebellum in adaptation of response amplitude is not unique to the podokinetic system. Subjects with anterior lobe cerebellar damage have difficulty adjusting the gain of postural responses to predictable perturbations of the support surface (Timmann and Horak 1997). Monkeys with lesions to the flocculus and paraflocculus demonstrate disrupted adaptation of vestibuloocular reflex (VOR) gain. This VOR gain control is distinct from VOR time constant control, which is not affected by floccular/parafloccular lesions (Cohen et al. 1992). PKAR may have similar distinct components for regulation of gain and time constants. This is supported by the lack of correlation between initial PKAR velocity and decay time constants in the cerebellar group. The cerebellum is clearly important for regulation of PKAR amplitude, but may or may not be important for regulation of PKAR time constants. Future studies of subjects with specific lesions of the cerebellum are warranted to examine this issue and to determine which regions of the cerebellum are particularly important for PK adaptation. Acknowledgements This work was supported by NIH grants 1F32 NS and R01-DC040082, and by MRC grant MA We thank Dr. Lew Nashner of NeuroCom for donation of the support harness. References 541 Baizer JS, Kralj-Hans I, Glickstein M (1999) Cerebellar lesions and prism adaptation in macaque monkeys. J Neurophysiol 81: Cohen H, Cohen B, Raphan T, Waespe W (1992) Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum. Exp Brain Res 90: Gordon CR, Fletcher WA, Melvill Jones G, Block EW (1995) Adaptive plasticity in the control of locomotor trajectory. Exp Brain Res 102: Lang CE, Bastian AJ (1999) Cerebellar subjects show impaired adaptation of anticipatory EMG during catching. J Neurophysiol 82: Martin TA, Keating, JG, Goodkin HP, Bastian AJ, Thach WT (1996) Throwing while looking through prisms I. Focal olivocerebellar lesions impair adaptation. Brain 119: Martin JH, Cooper SE, Hacking A, Ghez C (2000) Differential effects of deep cerebellar nuclei inactivation on reaching and adaptive control. J Neurophysiol 83:

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