Proprioceptive evoked potentials in man: cerebral responses to changing weight loads on the hand

Neuroscience Letters 288 (2000) 111±114

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Proprioceptive evoked potentials in man: cerebral responses to changing weight loads on the hand Sidse Arnfred a,*, Andrew C.N. Chen b, Derek Eder c, Birte Glenthùj a, Ralf Hemmingsen a a

Department of Psychiatry, University Hospital of Copenhagen, Bispebjerg, Bispebjerg Bakke 23, DK-2400 Kùbenhavn NV, Denmark Human Brain Mapping and Cortical Imaging Laboratory, The International Doctoral School in Biomedical Sciences and Engineering, SMI, Aalborg University, DK-9220, Aalborg, Denmark c GoÈteborg University, Institute of Clinical Neuroscience, Section of Psychiatry, SU/Sahlgrenska, SE-413 45 GoÈteborg, Sweden

b

Received 17 December 1999; received in revised form 10 May 2000; accepted 19 May 2000

Abstract We studied cerebral evoked potentials on the scalp to the stimulation of the right hand from a change in weight of 400± 480 g in ten subjects. Rise-time was 20g/10 ms, Inter Stimulus Interval 2s and stimulus duration was 100 ms. The cerebral activations were a double positive contralateral C3'/P70, P190, and a single negative frontal Fz/N70 component. We conclude that a brisk change of a hand held load elicits a signi®cant evoked potential (EP) unlike the electrical somatosensory EP (SEP). The stimulus is perceived as applied force. For this reason we call it a proprioceptive EP (PEP). Further studies of the PEP are needed to assess the in¯uence of load manipulations and of muscle contraction and to explore the effect of attentional manipulation. q 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Proprioception; Proprioceptive evoked potential; Somato-sensory evoked potential; `Long-latency' electromyographic response; Frontal negativity

Proprioception has been de®ned as encompassing four kinds of sensations; (1) Sensation of passive movements. (2) Sensation of active movements. (3) Appreciation of position in space and (4) appreciation of force applied [16]. If electrical stimulation is used for evoked potential (EP) generation, the natural pattern of receptor ®ring is abolished and the felt sensation is highly arti®cial and does not resemble any commonly encountered combination of receptor activity. The purpose of the study was to explore one quality of proprioception ± appreciation of force applied ± by scalp recordings of EPs. The stimulus was developed to resemble a sudden inadequacy of maintained muscle contraction and, to generate an EP, the stimulus was very brisk resulting in a sensation best described as `the feeling of carrying a basket of apples when another apple is suddenly thrown into it'. The sense of heaviness has been suggested to emerge from motor efferent activity in combination with afferent feedback of both deep and super®cial tactile receptors as * Corresponding author. Tel.: 145-35-31-26-61; fax: 145-35-3139-53. E-mail address: [email protected] (S. Arnfred).

well as tendon organ and muscle stretch receptors [3,8,12]. Probably, all of these afferents contribute to all of the types of proprioceptive sensations [5,6,14], even though an early study by Roland and Ladegaard-Pedersen in 1977 [16] concluded that the sensation of force applied could be attributed solely to receptors in tendons and muscles. The attribution of the different afferents to the EP is not explored in this study. Ten right-handed male healthy volunteers aged 24±35 years gave informed consent in accordance with the Helsinki declaration. Silver/silverchloride cup scalp electrodes were placed according to the International 10±20 System at FP1, FP2, Fz, Cz, Pz, C3 0 , and C4 0 ±- the lst two placed 2 cm posterior to C3 and C4 ± referenced to bilateral earlobes. Electroencephalograph (EEG) signals were ampli®ed 50 000 times with a frequency pass band of 1±280 Hz. Sampling rate was 1 kHz. All electrode impedances were below 5 kOhm. Electromyogram (EMG) was recorded from disposable 3M electrodes 3 cm apart on m.extensor carpi radialis longus in four subjects. EMG was recorded at a sample rate of 1 kHz, with a pass band of 1±200 Hz. The subjects had closed eyes. The experimental set-up is

0304-3940/00/$ - see front matter q 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 0 0) 01 23 3- 7

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S. Arnfred et al. / Neuroscience Letters 288 (2000) 111±114

shown in Fig. 1. Subjects were instructed to hold the wrist in a steady straight position and a relaxed grip. Apart from the standardisation of the procedure, this would direct some attention towards the examined limb. Directing attention toward the stimulated limb enhances the intermediate-late latency components of the median nerve somato-sensory EP (SEP) [9,15] and if this effect occurred in our recordings, it could facilitate the recording of a small EP. The inter stimulus was ®xed at two seconds and each of the four runs consisted of 120 identical stimuli. EMG was recti®ed and EEG was baseline adjusted to the mean of the last ®ve pre-stimulus sample points. Averaged epochs of 1 s (2400±600 ms) were time-locked to stimulus onset trigger. Mean number of included blocks after removal of artefact contaminated blocks were 405 trials (range 254±467). Only the ®rst run was averaged for the EMG. Student's paired t-tests, one-tailed, were used to compare EP components to peak baseline (0 to 2200 ms) points of same polarity. The grand average demonstrated an intermediate latency and signi®cant but low amplitude EP (Fig. 2). Seven subjects had evident activity both at the contralateral and at the frontal sites. Two subjects did not show the contralateral activation and one subject did not demonstrate the frontal activation. Cortical activation manifested as a double positive waveform (denominated by approximate latency) with a mean onset of 37.7 ms at C3 0 and a negative compo-

nent at Fz. At C3 0 : P70 (t ˆ 3:16, P , 0:01), N130 (not signi®cant), and P190 (t ˆ 1:28, P , 0:03). At Fz: N70 (t ˆ 4:67, P , 0:01). We found signi®cant contralateral activation effect and signi®cantly larger frontal than parietal activation (Table 1). In the individual EPs we saw a small bifurcation negativity in the middle of C3 0 P70 in six subjects. The EMG showed activation with a mean onset latency of 42 ms and a mean peak latency of 70 ms. Our major observations are (a) a contralateral parietal C3 0 /P70/P190 activation and (b) a frontal Fz N70 activation. This pattern of nearly concomitant frontal and parietal activation of reverse polarity was described in two reports of passive movements, produced as the control situation in experiments on active movements, one at similar latencies (frontal N70, contralateral parietal P65) [18] and one at longer latencies (N93 and P97, respectively) [4]. Another study [19] could only demonstrate a frontal negativity. For a discussion of the post-movement potential and its passive counter-part, please see BoÈtzel et al. [4]. Two earlier EP studies of proprioception [2,13] both address passive movements. Alary et al. [2] describes a stimulus of a brisk maximal extension of the fore®nger induced by an assistant. As they did not report a time course for the stimulations, it is dif®cult to speculate why they found an early parietal positivity (35±56 ms) and a very much later large frontal negativity (96±115 ms). Mima Table 1 Statistical results of comparing contralateral (C3 0 ) to ipsilateral (C4 0 ) activation and frontal (Fz) to parietal (Pz) activation in a Proprioceptive EP a Latency (ms)

Mean

SD

0

Mean

SD

t

P

0

Onset P70 N130 P190

C3 37.7 74 128 188

8 9.6 21 13.9

C4 43.8 72 140.9 206.3

12.1 12.1 10.2 15.4

2.33 0.413 1.59 3.275

, 0.05 n.s n.s , 0.01

Onset N70 N150

Fz 39.6 71.1 151.8

8 7.4 25.7

Pz 53 90.8 177.3

7.7 9.4 17.6

na 6.115 3.414

na , 0.001 , 0.01

P70 N130 P190

C3 0 2.3 -0.94 2.4

1.13 1.19 1.49

C4 0 0.13 0.5 0.76

1.15 1.37 1.21

4.342 3.653 3.099

, 0.002 , 0.005 , 0.013

N70 N150

Fz -1.91 -0.35

1.24 1.53

Pz 1.89 1.25

1.02 1.34

8.893 5.45

, 0.001 , 0.001

Ampl. (mV)

Fig. 1. Stimulus set-up for a proprioceptive EP (PEP). The permanent load of 400 g is in a stable position by an isometric contraction of forearm and grip muscles. The right forearm and hand is supported to the level of the thumb metacarpea-phalangeal (MCPH) joint. Subjects were instructed to keep back of hand and forearm in 1808 position, but otherwise be as relaxed as possible. Stimulus was a linear weight increment of 20 g in 10 ms to a max of 480 g maintained for 100 ms. The stimulator was controlled by a PC, which delivered a trigger stimulus for the EEG event channel.

a n ˆ 10. Student's t-test (paired, two-tailed) are performed on both latencies and amplitudes. The non-signi®cant latency differences are due to the use of C3 0 and Fz latency criteria for peak detection in the non-signi®cant waveforms of C4 0 and Pz, respectively. na, t-Test not performed as no onset could be identi®ed in six out of ten subjects at Pz.

S. Arnfred et al. / Neuroscience Letters 288 (2000) 111±114

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Fig. 2. Grand average of proprioceptive EP (PEP) in ten subjects. Arrow marks onset of the proprioceptive stimulus of a weight load change of 80 g in 40 ms. Subjects were instructed to keep hand in position. Epochs has been cut down: 2100 to 1450 ms. Onset of evoked responses is approximately at 40 ms in the contralateral and the frontal leads. EMG is an average of four subjects after rectifying and baseline adjusting the signals. Latency of EMG peak (M) is 70 ms.

and coworkers [13] observed a major positive peak at CP3 (latency 48.0 ms) using passive ¯exion of the PIP joint of the right middle ®nger [13]; they did not observe a later positive component, but the post stimulus recording time was only 100 ms. In comparison to the ®nding by Mima et al. [13], we identi®ed a 16 ms later onset frontal negativity; it might be because the end position of their passive ¯exion was reached in 25 ms, while the maximum load exerted in our experiment was reached in 40 ms. In accordance with our ®ndings they demonstrated near concomitance of peaks of reverse polarity at the contralateral and the frontal electrodes (Fz 45.5 ms; CP3 48.0 ms). Muscle afferents have a direct pathway to motor cortex, as established in studies of monkeys [7] and this feedback probably is the afferent part of the `long-latency' EMG response [1,10,11]. The negative frontal component of the PEP and of the above mentioned studies could be the central manifestation of this cortical sensorimotor loop. We stimulated a sustained contracted muscle; this in contrast to a study by Goodin et al. [10] who recorded a perturbation introduced in a ballistic movement. They found a N2 (approximately 110 ms in the ®gure) co-varying with the `long-latency' EMG response. As the `long-latency' EMG response has been considered speci®cally related to posture [11] and limb stiffness [10], we expected it to be induced by our experiment. The EMG activity, we recorded, peaking at 70 ms, is probably a `long-latency' EMG response, even though it was not preceded by an evident early spinal stretch re¯ex. This could be due to the stable muscle contraction as this has been shown to selectively enhance the `longlatency' EMG response [17]. We conclude that a brisk change of a hand held load elicits a signi®cant intermediate-latency EP unlike the

SEP elicited by electrical stimulation. The stimulus is perceived neither as tactile nor as passive movement but as applied force. For this reason, we call it a PEP. Further studies of the PEP are needed to assess the in¯uence of load manipulations and of degree of muscle contraction. Another research direction could be to relate the PEP to perceived heaviness and explore the effect of attentional manipulation. We very much appreciate the technical design and building of the stimulus equipment by S. Christoffersen, MSc, Department of Medical Physiology, University of Copenhagen. The study was supported by The Lundbeck Foundation and by the Danish Hospital Foundation for Medical Research, Region of Copenhagen, The Faroe Islands and Greenland. [1] Abbruzzese, G., Berardelli, A., Rothwell, J.C., Day, B.L. and Marsden, C.D., Cerebral potentials and electromyographic responses evoked by stretch of wrist muscles in man, Exp. Brain Res., 58 (1985) 544±551. [2] Alary, F., Doyon, B., Loubinoux, I., Carel, C., Boulanouar, K., Ranjeva, J.P., Celsis, P. and Chollet, F., Event-related potentials elicited by passive movements in humans: characterization, source analysis, and comparison to fMRI, Neuroimage, 8 (1998) 377±390. [3] Aniss, A.M., Gandevia, S.C. and Milne, R.J., Changes in perceived heaviness and motor commands produced by cutaneous re¯exes in man, J. Physiol. (Lond.), 397 (1988) 113±126. [4] Botzel, K., Ecker, C. and Schulze, S., Topography and dipole analysis of reafferent electrical brain activity following the Bereitschaftspotential, Exp. Brain Res., 114 (1997) 352±361. [5] Clark, F.J., Burgess, R.C. and Chapin, J.W., Proprioception with the proximal interphalangeal joint of the index ®nger. Evidence for a movement sense without a static-position sense, Brain, 109 (1986) 1195±1208.

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