Grip force control during object manipulation in cerebral stroke

Clinical Neurophysiology 114 (2003) 915–929 www.elsevier.com/locate/clinph

Grip force control during object manipulation in cerebral stroke J. Hermsdo¨rfera,*, E. Hagla, D.A. Nowakb, C. Marquardta a

Clinical Neuropsychology Research Group (EKN), Department of Neuropsychology, Mu¨nchen-Bogenhausen Hospital, Dachauerstrasse 164, D-80992 Munich, Germany b Department of Neurology, Mu¨nchen-Bogenhausen Hospital, Englschalkinger Str. 77, 81925 Munich, Germany Accepted 23 January 2003

Abstract Objective: To analyze impairments of manipulative grip force control in patients with chronic cerebral stroke and relate deficits to more elementary aspects of force and grip control. Methods: Nineteen chronic stroke patients with fine motor deficits after unilateral cerebral lesions were examined when performing 3 manipulative tasks consisting of stationary holding, transport, and vertical cyclic movements of an instrumented object. Technical sensors measured the grip force used to stabilize the object in the hand and the object accelerations, from which the dynamic loads were calculated. Results: Many patients produced exaggerated grip forces with their affected hand in all types of manipulations. The amount of finger displacement in a grip perturbation task emerged as a highly sensitive measure for predicting the force increases. Measures of grip strength and maximum speed of force changes could not account for the impairments with comparable accuracy. In addition to force economy, the precision of the coupling between grip and load forces was impaired. However, no temporal delays were typically observed between the grip and load force profiles during cyclic movements. Conclusions: Impaired sensibility and sensorimotor processing, evident by delayed reactions in the perturbation task, lead to an excessive increase of the safety margin between the actual grip force and the minimum force necessary to prevent object slipping. In addition to grip force scaling, cortical sensorimotor areas are responsible for smoothly and precisely adjusting grip forces to loads according to predictions about movement-induced loads and sensory experiences. However, the basic feedforward mechanism of grip force control by internal models appears to be preserved, and thus may not be a cortical but rather a subcortical or cerebellar function, as has been suggested previously. q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Science Ireland Ltd. All rights reserved. Keywords: Grip force control; Object manipulation; Fine motor deficits; Stroke; Sensorimotor integration

1. Introduction The precise regulation of grip forces according to the physical requirements of a manipulated object is one of the most elaborate examples of highly skilled fine motor performance. The grip forces anticipate the physical properties of objects, such as weight, surface friction, and shape in a highly economical fashion (Johansson and Westling, 1984; Westling and Johansson, 1984; Johansson and Edin, 1993; Jenmalm and Johansson, 1997). A safety margin is established which ensures that the grip force is on the one hand, high enough to prevent slippage of the object, but on the other, not too high, so as to avoid fatigue and to optimize sensory information from the grasping digits. * Corresponding author. Tel.: þ 49-89-1577895; fax: þ 49-89-156781. E-mail address: [email protected] (J. Hermsdo¨rfer).

However, grip forces not only anticipate static object properties, but also dynamic loads, which arise when an object is lifted from a supporting surface or when it is accelerated in space (Flanagan and Tresilian, 1994; Wing, 1996; Flanagan and Lolley, 2001). In such instances, there is a precise temporal coupling between grip forces and timevarying loads. This coupling is synchronous without any time lags, thus indicating that the grip forces are regulated in a feedforward manner. It has been suggested that an internal model of the dynamics of the own body and the object predicts the physical consequences of the manipulation so that grip forces can anticipate loads at the time of their appearance (Flanagan and Tresilian, 1994; Blakemore et al., 1998; Wolpert et al., 2001). Skilled grip force control depends on the integrity of the sensorimotor system. Disturbances occur in a number of pathological conditions. For example, patients with a

1388-2457/03/$30.00 q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S1388-2457(03)00042-7

CLINPH 2002730

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dysfunction of the basal ganglia due to Parkinson’s disease or Huntington’s disease prolonged the duration of grip force production and frequently used increased forces during the lifting and holding of an object (Ingvarsson et al., 1997; Fellows et al., 1998; Gordon et al., 2000; Schwarz et al., 2001; Wenzelburger et al., 2002). It has been suggested that impairments of sensorimotor processing following striatal damage or strategies to compensate for motor deficits underlie the disturbances. When cerebellar patients executed a comparable task, the smoothness of force production and grip force magnitudes were typically disturbed, whereas indices of the speed of grip production were in the normal range (Mu¨ller and Dichgans, 1994; Fellows et al., 2001). Various explanations have been suggested to account for the deficits, such as disturbed processing of sensory input, timing or force scaling problems. There is also evidence that cerebellar damage may impair the temporal aspects of the coupling between grip forces and movement-induced loads. During up and down movements of a hand-held object, some patients with cerebellar atrophy produced uniform grip force patterns which did not anticipate the directiondependent load profile (Babin-Ratte´ et al., 1999; Nowak et al., 2002). It was concluded that the ability to predict the dynamic consequences of the action had been lost, and thus the patient used a stereotyped and conservative pattern of grip force production. This observation fits well with theoretical considerations, which suggested that the cerebellum may be physiologically best suited to develop, refine, and maintain the internal models enabling predictive grip force control (Wolpert et al., 1998a). In contrast to the pathologies of the basal ganglia and the cerebellum mentioned above, studies on grip force control after cerebral stroke with cortical involvement are rare. Apart from studies of grip strength (e.g. Colebatch et al., 1986; Boissy et al., 1999), a few elementary aspects of force control such as tracking a target force, producing fast force changes, and reacting to load perturbations have been examined (Jeannerod et al., 1984; Mai et al., 1989; Hermsdo¨rfer and Mai, 1996; Wolpert et al., 1998b; Grichting et al., 2000). However, studies of force control during voluntary daily-living-related object manipulation after cerebral stroke are largely lacking. We therefore measured grip forces during manipulative tasks in a sample of stroke patients. The patients were in the chronic stage of their disease. They had recovered from the acute functional deficits following a single cerebrovascular accident (CVA), but their fine motor control with hand and fingers was still impaired. We were particularly interested in the relationship between more elementary measures of the sensorimotor impairment and the patient’s ability to control grip forces during manipulative tasks. We therefore assessed the decrease of grip strength and the slowing of the speed of grip force changes, since these are typical symptoms of hemiparesis after cortical damage (see above). To assess the sensory function of the affected hand, we established a

perturbation task (Hermsdo¨rfer et al., 1992, 1994). Sensory deficits are a frequent consequence of a stroke and may even constitute the only residual deficit (e.g. Jeannerod et al., 1984). The effect of cerebral sensory losses on the control of grip forces is of particular interest, since it has been repeatedly demonstrated that deterioration of the (peripheral) afferent information in healthy subjects impairs force control. Thus, grip forces increase massively and the durations of the initial phases during grasping and lifting are prolonged if digital nerves are blocked by local anesthesia (Johansson and Westling, 1984; Jenmalm and Johansson, 1997). The functional loss of distal cutaneous mechanoreceptors is mainly responsible for impaired force control (Ha¨ger-Ross and Johansson, 1996; Macefield et al., 1996; Macefield and Johansson, 1996). Experiments in patients with sensory deficits due to peripheral nerve damage such as carpal tunnel syndrome or polyneuropathy revealed contradictory findings. Grip force increases, comparable to those found in anesthetized normal subjects, were noted in some (Thonnard et al., 1997; Lowe and Freivalds, 1999) but surprisingly not in all patients (Thonnard et al., 1999; Nowak et al., 2003). The latter finding suggests that moderate sensory deficits of peripheral origin can in some cases be completely compensated for by an effective processing of the residual afferent information. On the basis of the above findings, we hypothesized that residual sensory impairments resulting from cerebral stroke may impair grip force control, and may in particular lead to excessive grip forces during object manipulation. However, it also seems conceivable that performance may be normal when some sensory function is preserved. Since high grip strengths and particular fast force changes are not prerequisites to handle a small test object at moderate movement speeds, we did not expect high correlations between these more elementary measures of grip force performance and the measures characterizing force control during object manipulation. Correlations might nevertheless emerge, since strength and speed are sensitive measures of the more general motor deficit after cerebral ischemia. Another aim of the present study was to analyze the precision of the temporal coupling of grip force and load in cerebral stroke patients. On the one hand, clinical data and theoretical considerations suggest that the coupling may be provided by calculations according to internal models within the cerebellum (see above). In addition, anesthetized subjects and patients with peripheral nerve damage may exhibit perfect coupling of grip and load forces (LFs) (Nowak et al., 2001, 2003), indicating that this aspect of force control is not necessarily disturbed by peripheral sensory deficits. These observations suggest that stroke with cerebral damage does not necessarily lead to disturbances of the temporal aspect of the grip force– load coupling even if the grip force level may be increased. On the other hand, slight disturbances, which may be related to cortical damage, have been noted in a sample of hemiparetic patients during a drawer-opening task (Grichting et al.,

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2000) and in children with cerebral palsy during a grasping and lifting task (Eliasson et al., 1991; Forssberg et al., 1999). We therefore hypothesized that the main temporal feature of a normal grip force– load coupling, namely the feedforward regulation of the grip force, may be preserved in cerebral stroke patients, whereas the precision of the coupling may be reduced. Tasks during which an object is constantly held within the grip and the movement is directed parallel to the gravity vector are particularly well suited for investigating the grip force –load coupling in patients, since inertial load changes are quite substantial and artifacts due to environmental constraints are minimized (e.g. an initially fixed object position during grasping may cause irregular grip and LFs due to inaccuracies of reaching or involuntary trunk movements). We decided to investigate cyclic vertical movements and used a wireless autonomous manipulandum that measured grip force and object accelerations, from which the dynamic loads were calculated. We examined two additional tasks to evaluate the dependency of performance deficits in the patients on task characteristics. During a holding task, the object was held stationary in the air for several seconds. A third task was to grasp and transport the object over a short distance. We hypothesized that the more time available for signal processing in the stationary condition may cause relatively small safety margins. In contrast, shorter intervals of contact with the object and high dynamics of the action during object transport may induce high safety margins and particularly slow movement execution by the patients. The cyclic vertical movements may exhibit intermediate safety margins, since the sensory information about object properties are available before the movement, which is nevertheless highly dynamic.

2. Materials and methods 2.1. Subjects Nineteen patients participated in the study (6 females, 13 males; mean age 51.4 years). All patients had had a unilateral CVA. In 15 patients, the lesion was located in the left hemisphere and in 4 patients in the right hemisphere. Typically, the stroke had affected the middle cerebral artery or intracerebral bleeding had occurred within the territory of the middle cerebral artery. The individual etiologies as well as clinical and demographic data of the patients are summarized in Table 1. The affected brain structures were localized for the patients with current radiographic data available at the time of data analysis. Table 1 shows that cortical sensorimotor areas and the underlying white matter were usually affected. In some cases, the lesion also included parts of the basal ganglia or the thalamus. The time since onset of the CVA was at least 1 month and on the average more than half a year (6.7 months); therefore,

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patients were in the chronic stage of their disease when tested. The patients were selected on the basis of a clinical examination showing deficits of fine motor control with or without sensory deficits. Table 1 indicates the scores derived from clinical examination. Paresis was typically mild or mild-to-moderate. In two cases, the paresis was scored moderate-to-severe (P17 and P19); although these patients could still perform the object manipulation tasks, the strength of the precision grip and the speed of force changes could not be determined due to their inability to produce stable thumb– index opposition. In one patient (P15), the deficits were limited to severe sensory losses. None of the patients exhibited a pronounced spasticity of the affected upper extremity which might have hampered task performance. None of the patients had a history or clinical signs of other neurological diseases. Nineteen healthy subjects without any history of neurological diseases or any movement restriction of the hand or arm served as the control group. The control subjects had a similar age and gender distribution as the patients (8 females, 11 males; 23– 70 years, mean age 51.3 years). All control subjects were right-handed. Informed consent was obtained from all subjects. The study was conducted in accordance with the Declaration of Helsinki and was approved by a local ethical committee. 2.2. Measurement of grip strength, fast force changes, and grip perturbation To assess the strength of the precision grip and the speed of force changes, the subject held a small cylindrical manipulandum (diameter 20 mm, length 15 mm, weight 5 g) containing a force transducer between the thumb and the index finger (for details see Hermsdo¨rfer and Mai, 1996). The grip force signal was digitized and stored in a personal computer; it could be displayed on the monitor as a vertical bar, the length of which indicated the applied force. Grip strength was measured during 3 attempts to press the transducer as hard as possible for 1 or 2 s. Care was taken that only the thumb and index finger participated in the grip. Visual feedback was provided to encourage the subject to optimize performance. The mean of the maximum grip force (Fmax) achieved in the 3 trials was calculated to represent the grip strength. To assess the speed of force changes, the subjects were required to repeatedly press and release the same transducer used for the measurement of grip strength. Two horizontal target lines, representing 10 and 20% of the individual grip strength, were displayed on the monitor. The subject was instructed to produce fast force changes with maxima exceeding the 20% level and minima remaining below the 10% level. Thus, individual strength differences were taken into consideration. However, the instruction did not emphasize accuracy but rather speed, i.e. the number of force changes achieved within a certain time. Following

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Table 1 Clinical and demographic data of the patients Age (years)

Sex

Hand dominance

Etiology

Localization

Time since onset (months)

Affected hand

Paresis

Tactile sensibility

P01 P02 P03 P04 P05 P06 P07 P08 P09 P10 P11 P12 P13 P14 P15 P16 P17 P18 P19

55 31 52 36 39 57 28 60 64 68 61 39 67 54 63 69 30 33 69

f m m m m f m m m m m f m m m m f f f

l r r r r l l r r r r r r r r r r l r

MCA l MCA (SAB) l MCA l ICB r ICB l Venous ischemia r ICB l ICB l MCA l MCA þ PCA l MCA l MCA l PCA r MCA l MCA l MCA l ICB l MCA (SAB) r MCA l

F, BG, C.r. C.i., Th T, BG, C.r. BG, C.e., C.r. BG, C.e., C.r. P F, BG, C.i., C.e. P, O P P, O, BG T, P T, P, O Th, T, O, P P, O – P BG, C.e. – Th, BG, C.i.

1 2.5 4 3 5 4.5 12 8 1.5 2 2 1.5 4 40 8 4 9 7 9

r r r l r l r r r r r r l r r r r l r

1 1– 2 1 1 1 2 2 1 1– 2 1 1 0– 1 0– 1 2 0 1 2– 3 1 2– 3

0 0 1 1 1 1 1 0 0 0 0 0 2–3 3 3 3 3 2 3

Proprioception 0 0 1 1 0 1 1 2–3 0 2 1 0 1 3 3 3 3 1–2 2

Hand: l, left; r, right; etiology: MCA, middle cerebral artery infarction; PCA, posterior cerebral artery infarction; ICB, intracerebral bleeding; MCA (SAB), MCA infarction after subarachnoidal bleeding; localization: F, frontal cortex; P, parietal cortex; T, temporal cortex; O, occipital cortex; BG, basal ganglia; Th, Thalamus; C.r., corona radiata; C.e. and C.i., capsula externa and interna; – , no CT- or MRI-scan available; paresis: 0, none; 1, slight; 2, moderate; 3, severe paresis; tactile sensibility: 0, none; 1, slight; 2, moderate; 3, severe loss (perception of light touch and two-point discrimination of thumb and index finger); proprioception: 0, none; 1, slight; 2, moderate; 3, severe loss (contralateral reproduction of passive finger and hand movements).

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practice trials, the grip force during 3 8 s trials was registered. Fifteen to 18 cycles were selected from the force trace, and the frequency was calculated from the corresponding duration. The mean frequency of the 3 trials (Freq) was taken as an indicator for the speed of repetitive force changes. To assess the capacity of processing sensory information in a precision grip, the reaction to a perturbation of a constant grip configuration was quantified. The subject held a manipulandum in a precision grip similar to the procedure used for measurements of grip strength and speed. However, the manipulandum was larger and could be compressed over a distance of 20 mm against an adjustable counteracting load. The load was generated pneumatically during computer control (for details see Hermsdo¨rfer et al., 1992). At the beginning of each trial, the subject compressed the manipulandum to an intermediate length using a visual feedback of the finger distance. Then feedback was switched off, and after a variable delay (1 – 2 s) the load increased (2.5 – 7.5 N, duration of the perturbation: 1 s). This load increase inevitably caused an increase of the finger distance until an active reaction occurred. It is important to note that this perturbation was relatively slow and did not evoke fast reflective responses (see Pauli et al., 1993). The subject was instructed to resist the perturbation as quickly as possible and to return to the initial grip configuration. The above-described perturbation was tested in 3 trials. These trials were intermingled with 4 unperturbed trials and 3 trials with a slower perturbation, which, however, were not analyzed. Hand and fingers were placed behind a screen and invisible for the subject during the whole measurement. The amount of finger opening (dS) until the displacement was stopped and reversed was determined from the signal of finger distance. The median of 3 trials was used to represent the precision and speed of the subject’s reaction to the grip perturbation. 2.3. Assessment of manipulative grip force control 2.3.1. Instrumented object Subjects performed 3 tasks testing different aspects of manipulative grip force control. In all tasks, a spherical instrumented object with a diameter of 9 cm, a width of 4 cm, and a mass of 372 g was manipulated (Fig. 1A). The object was completely autonomous with no connection to external devices during the measurements. It was grasped with the thumb and the 4 fingers in opposition at the circular grip surfaces, which were covered with a plastic material (polysterol). The object’s center of gravity was located in the volumetric center. The grip assured that loads from rotational torques were negligible. The object contained a force sensor that measured the grip force (0 –80 N, accuracy ^ 0.1 N) and 3 acceleration sensors that measured the acceleration in the 3 spatial dimensions (^ 50 m/s2, accuracy ^ 0.2 m/s2). By means of internal electronics, the data were A/D-converted (12 bit) with a sampling rate of

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100 Hz and stored inside the object. After the experiment, the object was connected to a PC for data transfer. Several additional measures were calculated from the directly measured variables. The vertical kinematic acceleration (AccZ) was determined by subtracting the constant of gravity (G) from the measured acceleration, which included the gravitational acceleration. The net LF during object movements was determined as the vectorial summation of the load due to the object’s weight (acting vertically: m £ GÞ and the acceleration-dependent inertial loads in the vertical and sagittal directions ðm £ AccZ; m £ AccYÞ; both of which acted tangentially to the grip surface and therefore had to be compensated for by the grip. Thus, the LF was calculated as: LF ¼ m £ ððAccZ þ GÞ2 þ AccY2 ÞÞ1=2 : 2.3.2. Hold In this task, the subject was requested to grasp the object in the described way, lift it 8 cm above the table surface (height indicated by a fixed marker), keep it stationary in this position for about 8 s, and then replace it on the table. Six trials were performed with each hand. To represent the subject’s performance, the average grip force during 3 s of stationary holding (GFhold) was calculated for each trial. The 3 s interval was adjusted so that it started 2 s after the acceleration changes of the lifting movement had returned to baseline, indicating the absence of movement (Fig. 1B). 2.3.3. Transport Two platforms (height 5 cm, diameter 16 cm) were placed on the table; their centers were 30 cm apart and lay in the sagittal plane through the subject’s shoulder. In the starting position, the subject’s hand rested on the near platform and the object was positioned in the center of the more distant platform. It stood upright on a small base mounted on the bottom of the object; the grip surfaces were vertical and slightly rotated (158) out of the sagittal plane so that the object could be grasped with the wrist in a neutral position. The distance and the orientation of the object permitted a comfortable movement execution by all subjects. With a verbal command, the subject was requested to reach out, grasp the object, transport it towards the platform close to the body, and replace it there. The movement was to be performed at the preferred speed. Eight trials were measured with each hand. The initial peak of the force signal (GFtr_peak), which occurs during the first movement phase of lifting and grasping the object, was determined in order to represent the grip force produced during this task (Fig. 1C). GFtr_peak coincided almost invariably with the maximum grip force produced during the movement. Grip force can be affected by movement speed because load varies with object acceleration. To control for possible differences in movement speed between patients and control subjects, the peak grip force was related to the momentary load by calculating

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Fig. 1. (A) Instrumented object containing sensors to measure the grip force (GF) and object accelerations in 3 spatial dimensions (AccZ, AccY, AccX). G, vertical gravity vector; m, mass of the object. (B) Vertical acceleration (AccZ) and grip force (GF) in a control subject during one trial of lifting and stationary holding of the object (hold task). The mean grip force (GFhold) was evaluated in the 3 s interval. (C) Vertical and sagittal accelerations (AccZ and AccY), resulting load (LF) and grip force (GF) when moving the object between two locations (transport task). The peak of grip force (GFtr_peak) and the time points t0, t1, and t2 were evaluated (see text). (D) Vertical acceleration (AccZ), resulting load (LF), grip force (GF), and force ratio (GF/LF) during vertical cyclic movements of the object. The maximum grip forces (GFcy_max) and the minimum force ratios (GF/LFcy) during each cycle were determined and averaged.

the ratio between both forces (GF/LFtr). Two temporal measures were determined. The duration of the first phases of grasping and object lifting (Ttr_1) was represented by the interval between the beginning of grip force increase (t0) and the occurrence of the grip force peak (t1). The duration of the whole transport movement (Ttr_all) was defined as the interval between the beginning of grip force increase (t0) and brisk changes in the acceleration signals (t2), which indicated the first contact of the object with the platform close to the body. 2.3.4. Cyclic vertical movements The subject was requested to move away from the table and to sit upright in the chair. The object was held in front of the trunk with the grip surfaces vertical and approximately parallel to the trunk. At a verbal command, the object had to be repeatedly moved up and down along a vertical line without tilting it. Movement amplitude was approximately 30 cm and frequency was approximately 1.5 Hz. Correct movement execution was trained during practice trials by

holding a ruler beside the moving hand and inspection of a visual sinusoidal signal of 1.5 Hz. Three trials, each comprising 10 up-and-down cycles, were recorded. Two methods were used to quantify performance. (1) Computer algorithms searched for the positive peaks in the vertical acceleration signal. These time points corresponded to the lower turning points of the movement path when the load is maximal due to the summation of gravitational and inertial load (see Fig. 1D and, e.g. Flanagan and Wing, 1995). The algorithm then determined the maximum grip force (GFcy_max) and the minimum force ratio (GF/LFcy) in a window around each load peak (cf. Fig. 1D). GFcy_max and GF/LFcy were then averaged across the cycles of the trial. (2) The profiles of the grip force (GF) and the load (LF) were compared using Fourier analyses. Cross-correlations were computed to determine the temporal relationship between the two time series. The coefficient of maximum cross-correlation (RXcy) represented the similarity of the two profiles in the time domain. The time lag corresponding to the maximum cross-correlation (TLAGcy) indicated

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phase differences. A positive value indicated that grip force modulation occurred after load modulations. 2.3.5. Assessment of slip force To determine the minimum grip force necessary to hold the object, the standard procedure originally suggested by Johansson and Westling (1984) was used. The object was held stationary and the grip was slowly released until the object slipped from the fingers. The grip force at the moment the slip started (identified in the acceleration signal) was taken as the slip force. The average value of 3 attempts was calculated. No differences were detected between the slip forces of patients and control subjects (patients’ affected hand: mean 1.85 N, SD 0.80 N; control subjects: mean 1.75 N, SD 0.64 N; t test: P . 0:1Þ:

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relationships between different tasks and measures, in particular, to evaluate the effects of deficits in elementary aspects of grip control (strength, speed, reaction to perturbation) on functional aspects during manipulative tasks in the patients.

3. Results 3.1. Grip strength, fast force changes, and grip perturbation The reduction of grip strength in the patients was expressed as percentage of the maximum force produced with the affected contralesional hand relative to the force produced with the ipsilesional hand. Fig. 2A shows the

2.4. Procedure The different tests were performed in the order of their description above. There were two exceptions. Slip force was measured before the first object manipulation task (Hold). The hold task was divided into two parts (half of the trials before and half after the transport task); however, no statistically significant differences emerged (t test, P . 0:05Þ: All patients and control subjects were tested on both hands. In the patients, each task was first tested on the ipsilesional hand. This ensured that the patient was already confident in performing the task, when the affected contralesional hand was examined. Half of the control subjects started with the left hand and the other with the right hand. Statistical analysis ensured that there were no effects of sequence. Only the results of the patients’ affected hands and of the matched hands of the control subjects (see Section 2.5) are reported here. In order to demonstrate the contrast between both hands in the patients, the performance of the ipsilesional hand is shown in some of the figures; however, this hand was not analyzed further in the present article. The whole examination lasted about 90 min including breaks and was typically conducted in two parts on two successive days. Control subjects were not tested on the perturbation task. Normative data were available from a previous study (Hermsdo¨rfer et al., 1994). 2.5. Statistical analysis Each patient was age-matched with a control subject. To control for the effects of handedness, the affected hand of the patient was matched with the same hand of the control subject if they had the same hand dominance, and with the contralateral hand if hand dominance differed. Data of single trials belonging to one task were averaged for each subject. The performance of patients and control subjects was compared using t tests for independent samples, with the level of significance set at P ¼ 0:05. Correlation analyses were performed to assess the inter-

Fig. 2. Performance of the contralesional hand of stroke patients in elementary aspects of force and grip control. (A) Maximum force produced with the contralesional hand relative to the ipsilesional hand (Fmax%). (B) Frequency (Freq) of fast force changes. (C) Displacement (dS) until the grip perturbation was stopped. The inset shows traces of finger distance of a patient with sensory deficits (P15, cf. Table 1) during the unexpected load increases (between vertical lines). Three trials of the ipsilesional left and of the affected contralesional right hand are superimposed and synchronized at load onset. The shaded areas in the graphs indicate the normative range (10th–90th percentile, broken line: mean). For the perturbation task, the normative data were taken from a former study in which the same methods were used (Hermsdo¨rfer et al., 1994). The patients are ordered by increasing displacement in all graphs. Two patients (P19 and P17 only in the force tasks) were not able to stabilize the manipulandum in their hands and thus were not included in the tasks.

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resulting relative strength for each individual patient. Many patients had values near or even above 100%, indicating that paresis was absent or only slight. The greatest individual force reductions amounted to about 60% of the value of the ipsilesional hand; however, the remaining force was still clearly sufficient to perform the other tasks without significant fatigue. Control subjects produced a mean ratio of 116.3%. Most likely this ratio was higher than 100%, because the hand matched to the affected hand of the patients was more frequently the dominant hand (Table 1), which is typically stronger than the non-dominant hand (e.g. Mathiowetz et al., 1985). The difference between patients and control subjects was highly significant ðP ¼ 0:003Þ: Fig. 2B illustrates that fast force changes were highly effective for distinguishing patients from control subjects. On the average, patients changed their grip force with a frequency of 3.7 Hz, while control subjects produced 4.9 Hz ðP ¼ 0:002Þ: Two patients slowed to a frequency below 2 Hz. The inset in Fig. 2C shows the performance of an individual patient during the perturbation task. With his unaffected left hand, he successfully stopped and reversed the perturbation after only about 2 mm of displacement producing a slightly overshooting response. In contrast, with the right hand the displacement was much larger until a reaction occurred. Eleven patients exhibited displacements larger than the 90th percentile observed in the control group in a previous study (Hermsdo¨rfer et al., 1994). The fingers of two patients were extended until the manipulandum mechanically stopped without any reaction being obvious. Correlations with the clinical measures of sensory status (Table 1) revealed a relatively high agreement that was higher for the score of tactile sensibility than for the score of proprioception (Spearman rank correlation, proprioception: R ¼ 0:60; P ¼ 0:008; tactile: R ¼ 0:68; P ¼ 0:002Þ: 3.2. Object hold All patients were able to grasp the instrumented object, lift it to the required height, and stabilize it in the air. Fig. 3A shows the performance of one selected patient with the ipsilesional and the affected contralesional hand. The acceleration traces are very similar for both hands. Nearzero acceleration values after lifting confirm that the object was held stationary without movement. The spikes at the end of the traces were caused by the table contact during replacement. While the grip force of the left hand was nearly constant and amounted to less than 10 N, that of the affected right hand was massively increased and varied within and across trials. Seven patients exhibited increased grip forces of the hand contralateral to the lesion (Fig. 3B). The difference from control subjects was statistically highly significant ðP ¼ 0:012Þ: Since the patients are ordered by progressively worse performance in the grip perturbation task (cf. Fig. 2C), it is obvious that high grip forces are

Fig. 3. (A) Vertical acceleration (AccZ) and grip force (GF) of one patient (P15) with the ipsilesional left and contralesional right hand during the hold task. The traces show the grasping, lifting, stationary holding, and replacement of the object during 3 successive trials. (B) Grip force of 19 patients during stationary holding of the object with the contralesional hand. The shaded area indicates the range of performance of the control subjects with their matched hands (10th–90th percentile, broken line: mean).

associated with deficits in this task. This point will be treated in more detail later in Section 3. 3.3. Object transport During the transport task, all patients successfully reached for the instrumented object, grasped it, transported it over the distance of 30 cm, and finally replaced it at the location close to the body. Fig. 4A exemplifies the performance of one patient. With the ipsilesional left hand, the lifting and replacement of the object were visible from a signal change in the vertical acceleration (AccZ); the acceleration and deceleration of the transport movement corresponded to a positive and a negative peak in the sagittal acceleration (AccY). With the contralesional hand, both signals were attenuated and prolonged in time, indicating slowed execution of the whole movement. Ipsilesional grip force profiles were highly reproducible and exhibited a major peak associated with object acceleration and a second minor peak during deceleration. The patient produced much higher grip forces with the contralesional right hand and only one initial grip force peak occurred. Fig. 4B summarizes the performance of the affected contralesional hands of all patients for 3 selected measures. Peak grip force was increased in about half of the patients compared with that of control subjects ðP ¼ 0:011Þ: In some patients, peak grip forces were even much higher than in patient P17, in whom the force increase was only borderline, and most obvious when compared with the ipsilesional hand

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however, its main contribution arises from the actual transport movement between the two platforms. The transport time was also increased in the patients ðP ¼ 0:004Þ; but increases in transport time were not significantly associated with increases of peak grip force ðP . 0:1Þ: 3.4. Cyclic vertical movements Fig. 5 illustrates the performance of a patient during continuous vertical movements of the hand-held object. Changes in acceleration were very similar for both hands, suggesting that the patient was able to produce normal arm movements at the required amplitude and frequency with his contralesional right hand. Load variations resulted as a direct consequence of the acceleration; a maximum occurred at the lower turning point and a minimum at the upper turning point (cf. Section 2). The grip force anticipated the load changes. It oscillated with the same frequency, and maxima and minima closely corresponded in time with maxima and minima of the load. While, however, the grip force was modulated at a low force level with the ipsilesional left hand, the level was much higher on the affected contralesional hand. Preserved grip force modulation appears particularly striking, because in all phases of the movement the grip force produced by the affected right hand was much higher than on the left hand and there was never a danger of object slip. The bottom graph in Fig. 5 shows another representation of the increased grip force of the right hand by means of the force ratio, which relates the grip force to the momentary load. Minima of the force ratio occur at the load maxima, and represent the instances during

Fig. 4. (A) Vertical acceleration (AccZ), sagittal acceleration (AccY), and grip force (GF) of one patient (P17) for the ipsilesional left and contralesional right hand during the transport task. Three trials are superimposed and synchronized at maximum vertical acceleration. (B) Initial peak grip force (GFtr_peak), time to reach peak grip force (Ttr_1), and transport time (Ttr_all) of 19 patients during transport of the object between two horizontal locations with the contralesional hand. The shaded areas indicate the range of performance of the control subjects with their matched hand (10th– 90th percentiles, broken lines: mean).

(Fig. 4A). The time to reach peak grip force was prolonged in many patients ðP ¼ 0:004Þ: This slowing could not be accounted for by the increase of the peak grip forces in the patients, since the correlation between the time to reach peak force and the peak force failed (just) to reach statistical significance ðR ¼ 0:45; P ¼ 0:054Þ: In addition, there was some notable dissociation between both measures in individual patients (P9, P10, P14, P18 in Fig. 4B). The transport time contains the initial grip force development;

Fig. 5. Vertical acceleration (AccZ), load (LF), grip force (GF), and force ratio (GF/LF) of one patient (P15) for the ipsilesional left and contralesional right hand during vertical cyclic movements of the hand-held object. Several cycles from one trial are shown.

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each movement cycle when the danger of object loss was highest. The level of grip force was quantified by averaging across the grip force maxima for each cycle. Fig. 6 shows that maximum grip force was increased above the magnitudes produced by the control subjects in many patients ðP # 0:001Þ; particularly in those patients who exhibited large displacements in the grip perturbation task (and had high patient numbers, respectively). The coefficient of cross-correlation describes the similarity of the load and grip force time series irrespective of the force levels and an eventual phase lag. The coefficient is a highly sensitive indicator of the precision of the temporal coupling between the load and the grip force. On the average, control subjects produced coefficients close to unity (Fig. 6). In some cases, lower coefficients around 0.67 (10th percentile) were reached, which, however, still indicated a highly significant correlation between both signals. Most patients performed within or near the range of the control subjects (mean 0.77). Only two patients (P18 and P19, see Fig. 6) exhibited clearly

Fig. 6. Maximum grip force (GFcy_max), coefficient of cross-correlation (RXcy), and time lag (TLAGcy) of 19 patients during vertical cyclic object movements with the contralesional hand. The shaded areas indicate the range of performance of the control subjects with their matched hand (10th–90th percentiles, broken lines: mean). GFcy_max was obtained by evaluating the grip force profiles, RXcy and TLAGcy were derived from cross-correlation analyses (cf. Section 2).

decreased coefficients of cross-correlation. The difference between patients and control subjects was statistically significant ðP ¼ 0:035Þ; however, if patient P18 was considered an outlier and was excluded, the difference failed to reach statistical significance ðP . 0:2Þ: The time lag derived from cross-correlation analyses indicates the temporal shift between the time series of load and grip force. From Fig. 6, it is clear that such temporal shifts were typically negligible ðP . 0:1Þ: In most patients and control subjects, the time lag was within a window of ^ 10 ms and thus smaller than the sampling interval of the measurement system. Therefore, the grip force was produced simultaneously with the LF without a relevant temporal delay. There were, however, two exceptions. One patient (P19) had a time lag of 2 180 ms. However, since the coefficient of cross-correlation was low and the grip and LF varied largely independently, any calculated time lag may be just incidental (the same was true for patient P18, although his time lag was occasionally near zero, see Fig. 6). In a second patient (P17), a time lag of 2 470 ms was detected, although the cross-correlation was relatively high (see below, Fig. 7). Fig. 7 illustrates traces of the load and grip forces in two of the 3 patients who showed clear deviations from the controls’ performance in the cross-correlation analysis. Although patient P18 was able to produce continuous load changes by cyclic arm movements, her grip force profile was highly irregular, showed large fluctuations, and had no features in common with the load profile. The performance of patient P17 differed profoundly. She varied her grip force cyclically with the same frequency as the load, but shifted by a half cycle compared to normal performance. Consequently, her grip force was maximal at loads near zero and minimal at the moments of maximum load. Despite this highly uneconomical way of regulating grip force, she was never in danger of losing the object because her overall grip force level was increased (cf. Fig. 5). This pattern was stable across two examinations. In a third test 4 months after the first examination, she exhibited a more irregular grip force profile. The third patient (P19), who also deviated in crosscorrelation analysis, exhibited an inconsistent performance,

Fig. 7. Load and grip force profiles of two patients who greatly deviated from control subjects according to cross-correlations. Patient P18 exhibited a low precision of the coupling between grip force and load, as expressed by a low coefficient of cross-correlation (RXcy). Patient P17 had a particularly long time lag (TLAGcy) between both profiles (cf. Fig. 6).

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being similar to patient P18 in the first trial and showing a constant shift like patient P17 in the other two trials. The shift amounted to a quarter of a cycle, and grip force peaks were synchronized with irregularities in the arm movement and load halfway between the two turning points of the movement. 3.5. Correlation between deficits of elementary aspects of grip control and manipulative grip force control The grip strength deficit of the patients, expressed as the ratio of the maximum force produced with the contralesional hand relative to the force produced with the ipsilesional hand, yielded positive correlations with the grip force during holding of the object ðR ¼ 0:55; P ¼ 0:022Þ and with the peak grip force during object transport (R ¼ 0:78, P , 0:001Þ: This suggests a decrease of manipulative grip forces with a greater strength deficit. However, for the absolute magnitude of maximum force, a moderate correlation was found only for the maximum grip force during cyclic movements ðR ¼ 0:51; P ¼ 0:038Þ; suggesting that the amount of available grip force generally did not determine the grip force used. No other measure of manipulative force control correlated significantly with the measures of grip strength. The frequency of force changes produced by the patients with their contralesional hand did not correlate with any of the measures selected to represent the grip performance in the tasks involving object manipulation (Figs. 3, 5 and 6). In contrast, the amount of finger displacement during the grip perturbation task correlated strongly with many measures of manipulative force control. This was most evident in measures of the grip force level (cf. Figs. 3, 4 and 6). To calculate correlations, the force ratios were used to indicate the magnitude of the grip forces in the two tasks involving object movements (transport and cyclic movements). Force ratios relate absolute grip force values to actual loads, and are possibly a more precise alternative to absolute grip forces. In all 3 tasks, a high correlation was obvious between the indicators of force level and the amount of displacement (Spearman rank correlations, hold: R ¼ 0:80; transport: R ¼ 0:70; cyclic movements: R ¼ 0:77; P # 0:001Þ: The displacement also correlated with the time to reach peak grip force during transport movements ðR ¼ 0:71; P ¼ 0:001Þ: The total time needed to transport the object between the two platforms was independent of the displacement ðP . 0:1Þ: The coefficient of cross-correlation between grip and LF profiles during cyclic movements varied with the amount of displacement ðR ¼ 20:62; P ¼ 0:006Þ: the larger the displacement, the smaller the precision of the coupling between both profiles. It should be mentioned that although the time to peak grip force during transport and the coefficient of cross-correlation during cyclic movement correlated with the displacement, their intercorrelation was not significant ðP . 0:1Þ: The displace-

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ment also did not correlate with the time lag between both profiles. 3.6. Comparison between the 3 object manipulation tasks The grip force produced in the 3 manipulative tasks could be compared directly by means of the force ratios. For the stationary hold task, the ratio was calculated simply by dividing the grip force by the object’s weight. Fig. 8 shows the resulting means for the contralesional hands of the patients and the matched hands of the control subjects. On the average, the force ratio was higher in the transport task than in the other two tasks (P # 0:002; for separate pairwise comparisons in patients and control subjects), and slightly but significantly higher during the hold than during the cyclic task ðP # 0:047Þ: Interestingly, the average relationship between patients and control subjects was similar in the 3 tasks. The ratios in patients were increased by 70– 76% if compared to the ratios in the control subjects (hold: 71.7%, transport: 69.8%, cyclic: 76.4%). Thus, despite individual variations in the different tasks (see, for example, particular increase of force in patient P18 during transport movements in Fig. 4, or P11 during cyclic movements in Fig. 6), the patients generally adapted the magnitude of their grip forces in a similar way to the different tasks, although on a much increased force level in many of the patients.

4. Discussion In this study, we tested fine motor skills in a population of patients who had had a unilateral CVA that caused contralateral motor and/or sensory deficits. An initial paresis had resolved, so that all patients were able to perform basic manual tasks such as reaching for, grasping, and moving an object. Elementary aspects of grip force control determined by measuring a precision grip between the thumb and index

Fig. 8. Mean force ratios for 3 tasks of manipulative grip force control by 19 patients with cerebral lesions using the contralesional hand and by control subjects. In the hold task, the force ratio was calculated by relating the grip force GFhold to the object’s weight.

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finger were nevertheless impaired when compared with that of control subjects. Strength, expressed as the relationship between the maximum grip force in the contralesional and ipsilesional hand, was mildly reduced, and the frequency of fastest grip force changes was markedly slowed. Grip force was the central measure used to analyze fine motor performance of the affected hand by 3 tasks involving the manipulation of an instrumented test object. The force level applied by the patients could be dissociated from more temporal aspects of force control, which were deduced from the coupling of the grip force with variations of the load. 4.1. Excessive grip forces The results demonstrated that patients produced in part massively increased grip forces in all manipulative tasks examined. These force increases represent an increase of the safety margin between the applied force and the minimum force necessary to prevent an object from slipping. The slip force did not differ between patients and control subjects. Increases of the grip force during object manipulation have been reported in various neurological diseases such as Parkinson’s disease, Huntington disease, or cerebellar diseases (see Section 1). We were able to attribute the grip force increases to deficits in the processing of sensory input, which was assessed by means of a perturbation setup. The perturbation induced reliable, automatic motor responses without any need for conscious verbal reports as are usually necessary in clinical examinations of sensibility (Hermsdo¨rfer et al., 1992, 1994). In addition, the perturbation does not elicit any electromyographic (EMG) responses faster than 90 ms, suggesting the reaction may be mediated cortically (Jenner and Stephens, 1982; Pauli et al., 1993). The amount of displacement correlated with the patients’ clinical scores of sensibility. The high correlation with the tactile score, which assessed only cutaneous qualities, suggests that cutaneous afferents may have been important in signaling and processing the grip perturbation. Experiments involving micro recordings of sensory nerves (Johansson and Westling, 1987; Macefield et al., 1996) or cutaneous anesthesia (Johansson and Westling, 1984; Johansson et al., 1992; Nowak et al., 2001) showed that cutaneous afferents are particularly involved in the regulation grip forces during manipulative tasks. Thus, the grip perturbation task is sensitive and accurate for predicting the scaling of the grip force level during object manipulation. The reason may be that it tests the processing precision of both sensory and motor aspects of elementary grip control; however, sensory tactile information may be especially important. Grip force increases in subjects with sensory deficits have been demonstrated in healthy subjects after local anesthesia of the grasping fingers (e.g. Johansson and Westling, 1984; Johansson et al., 1992; Nowak et al., 2001) and in patients with peripheral nerve diseases such as carpal

tunnel syndrome or polyneuropathy (Thonnard et al., 1997; Lowe and Freivalds, 1999). For the latter group, there were, however, also reports of normal grip forces despite clear sensory deficits (Thonnard et al., 1999; Nowak et al., 2003). This observation led to the suggestion that patients may have been able to compensate for their moderate sensory deficits. Successful compensation in our patient group would have predicted that patients with displacement values just above cut-off perform normally, while patient with large displacement or without any response are severely impaired. However, grip force increases were highly correlated with increasing displacements in the perturbation task. We may, therefore, conclude that patients with sensory deficits of central origin do not automatically compensate for the deleterious effects on grip force control, even if the deficits are moderate. It is interesting to note that manipulation with the ipsilesional hand (which was always tested first) just before using the affected contralesional hand also did not help substantially to integrate the physical object properties into contralesional force control. A comparably close relationship between grip force scaling and measures of tactile sensibility was reported in children with cerebral palsy (Gordon and Duff, 1999). In particular, the two-point discrimination threshold correlated with the children’s ability to scale the grip force level to a more or less slippery surface. The paretic children also exhibited an increasing force scaling deficit with more severe spasticity. This symptom, however, was negligible in the present patient sample. As in the present study, grip strength did not exhibit a reliable and consistent relationship to the force scaling abilities of the children. The increase of the safety margin between applied grip force and slip force can be viewed as a strategic response of the patients to prevent accidental slips of the object, which may occur due to the deficits in processing a sensory event and initiating a motor response (evidenced by impairments in the perturbation task). We used 3 different manipulative tasks to assess whether this safety margin might vary with task demands. A task-dependency indeed seemed to exist in patients and in control subjects, because the ratio between the grip force and the load was lowest during vertical cyclic movements, higher during stationary holding of the object, and highest during the transport task (Fig. 8). Since the ratio was constant in the hold task but varied in the other two tasks, comparisons of the force ratios between the tasks must perhaps be interpreted with caution. It is important, however, that the patients exhibited the same order of the ratios across the tasks as the control subjects, and, most interestingly, the average amount of grip force increase above that of the control subjects was nearly constant across the different tasks (70 – 76%). Thus, apart from some individual exceptions, the patients applied the same strategies as the healthy control subjects to adapt the safety margin to the different task demands, but solely increased the force level. Grip force increases of 70 and 76% represent the group

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mean. In individual patients, increases up to approximately 300% have been observed. Such overscaling is much greater than the values reported in other diseases of the central neural system (see Section 1). Load perturbations would hardly induce slips or object losses with such high grip forces, even if more irregular arm movements and load profiles of the patients than those of the healthy subjects or misalignments of the fingers on the grip surfaces producing perturbing torques are taken into account. Therefore, the applied grip forces are in many cases highly uneconomical and may seriously hamper the rehabilitation of impaired fine motor skills in stroke patients. 4.2. Impaired and preserved temporal aspects A major question of the present study was whether the feedforward nature of the grip force coupling with the load was preserved in the patients. To explore this issue, we analyzed the temporal relationship between the oscillating time series of the load and grip force during vertical cyclic movements using cross-correlations. Our results clearly indicated that there was no or only a negligible time lag between the time series in either group. This indicates that the motor commands to adjust the grip force were issued synchronously with the arm movement command. Researchers have interpreted such findings as evidence for the existence of internal models, which are able to predict the consequence of an action, so that they can be anticipated without waiting for a feedback signal (Flanagan and Tresilian, 1994; Flanagan and Wing, 1995; Wolpert and Flanagan, 2001). Thus, the principal functions of forward models were preserved in the patients. This was particularly impressive in patients who applied massively increased grip forces, but perfectly maintained the synchronous temporal covariation between grip force and load (e.g. Fig. 5). Recently, we reported qualitatively identical findings in healthy subjects after anesthesia of the grasping digits and in patients with peripheral nerve damage (Nowak et al., 2001, 2003). Our results therefore confirm that the magnitude aspect of the feedforward grip force regulation and the temporal aspect are separable processes that can be dissociated. A breakdown of the forward control was found in single patients. There were two patients in whom the grip force signal hardly resembled the LF, making an estimation of a time delay impossible. Apart from peculiarities of the lesions (see below), a seriously degraded motor output might account for the findings. Although grip strength and speed of force changes were only moderately impaired and the patients could still perform cyclic arm movements, the clinical ratings including the sensory status and/or the grip perturbation task indicated severe impairments. Therefore, the transformation of an adequate motor command into a corresponding motor output may have been severely disturbed in these patients. Another patient showed a very remarkable pattern. Her time series were highly correlated,

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but with a half-cycle phase shift so that LF peaks were responded to by grip force minima. This highly uneconomical behavior was verified in a second test and vanished in a subsequent examination. At the moment, no satisfying explanation can be given for this unusual finding. It may be of relevance that another patient sporadically synchronized his maximum grip force with an irregularity in the load profile, which, however, did not occur at the load maxima. Therefore, the patients may have altered or overwritten an original motor command, e.g. to anticipate a different event than suggested by grip force economy. Apart from the extreme patients mentioned above, some other patients showed a minor reduction of the precision of the grip force – load coupling. This was evident by coefficients of cross-correlation just below the normal range. Like grip force magnitude, these deficits were correlated with the displacement in the grip perturbation task. This finding indicates that although the basic feedforward mechanism may be preserved, the precision of the coupling may nevertheless be compromised. Temporal parameters were also impaired during the transport movement. As observed in many studies of the grasping and lifting movement in pathological populations (e.g. Fellows et al., 1998, 2001; Forssberg et al., 1999; Quinn et al., 2001), the time for grip formation and lift initiation (time to peak grip force) was prolonged in the patients. Reports of specific slowing of this phase after cutaneous anesthesia of the grasping fingers in healthy subjects (Johansson and Westling, 1984; Jenmalm and Johansson, 1997) fit well with the observed association between longer times to peak grip force and larger displacements in the perturbation task. It has been argued that the transition from one subphase during the initial lifting movement to the next affords sensory information about the termination of the last subphase (Johansson and Westling, 1984; Johansson and Edin, 1993). Thus, degraded sensory information may have slowed this process in our patients. In addition, the accuracy of the prehensile movement may have been reduced in the patients, so that additional time was necessary to establish the grip. However, prolongation of temporal measures during the initial phases of grasping and lifting do not necessarily indicate an impaired grip force –load coupling. In the present study, many patients with prolonged times to peak force exhibited perfect feedforward control as shown by time lags around zero during cyclic movements, and the time to peak force did not correlate with the coefficient of cross-correlation. The total movement time of the transport movement, which for the most part reflects the actual transport of the object from one platform to the other, was not affected by deficits during the grip perturbation task. Thus, a decreased capacity to react to external grip perturbations do not disturb all aspects of object manipulation but specifically affect precise grip force control.

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4.3. Cortical representation of grip force control The patients participating in the present study were a heterogeneous group who exhibited the common characteristics of fine motor deficits following a CVA within the territory of the middle cerebral artery. The lesions could include the cortical gray and underlying white matter, the thalamus, the basal ganglia, and the external or internal capsular. Deeper structures such as the brainstem and the cerebellum were not involved. Our findings of impaired grip force control after cerebral lesions within the sensorimotor areas agree with single cell studies in monkeys, which showed fine motor task related neuronal activity in various cortical regions (Wannier et al., 1991; Hepp-Reymond et al., 1994; Cadoret and Smith, 1997; Salimi et al., 1999; Kazennikov et al., 1999), and with neuroimaging studies in healthy subjects, which found that a widely distributed network subserves grip force control (Ehrsson et al., 2000, 2001; Kuhtz-Buschbeck et al., 2001). It has been suggested that the cerebellum is an anatomical substrate of internal models, which are able to predict the consequences of our actions; consequently, the loads arising from object movements can be anticipated synchronously with their appearance (see Instruction). Our finding of zero or near zero time delays between the load and the grip force during cyclic movements in nearly all of the patients indicates that the structures subserving load prediction are indeed located below the cortical level. In such a model, the cortical structures may be involved in various other aspects of further processing, which is suggested by the disturbances observed in our patients. Thus, cortical processing involves the adjustment of grip force according to selected safety margins, the grip force profile is smoothed and precisely adjusted to the predicted load or to sensory experiences from just preceding loads, and incoming sensory information is monitored to trigger or correct grip force output.

5. Conclusion Impaired control of grip forces during object manipulation is an essential aspect of fine motor control deficits following cerebral stroke. Grip forces may be massively increased and the safety margins may be excessive. Such alterations may substantially hamper skilled object manipulation, without being readily inferred by an observer. The major source of such force control deficits are sensory losses and impairments of sensorimotor integration. Reduced grip strength and slowed speed of force changes do not seem to be of comparable relevance. However, strength deficits combined with increased grip forces means that much higher grip forces relative to the (remaining) maximum force are used causing early fatigue. The precision of the coupling between grip and LFs and the duration of

manipulative acts may also be disturbed, whereas feedforward control mechanisms are typically preserved.

Acknowledgements We thank Dr Jens Phillip for designing and supporting the instrumented object and Andreas Zierdt for his contribution to the data analysis. We also thank the occupational therapists of the Neuropsychological Department in the Hospital Mu¨nchen-Bogenhausen for providing the clinical data of the patients. The present study is part of the second author’s (Elke Hagl) dissertation at the Faculty of Medicine of the Technical University of Munich, Germany.

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