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Scand J Rehab Med 31: 165-173, 1998 Scand J Rehab Med 30 FUNCTIONAL MAGNETIC RESONANCE IMAGING OF THE HUMAN MOTOR CORTEX BEFORE AND AFMR WHOLE-HAND AFFERENT ELECTRICAL STIMULATION S. Golaszewski 1 , Ch. Kremser 1 M. Wagner 1 , S. Felber 1,2 F. Aichner l,2 and M. M. Dimitrijevic 3 From the Departments of 1 Magnetic Resonance and 2 Neurology, University of Innsbruck, Austria and the 3 Department Of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas, USA ABSTRACT. Electrical stimulation of the whole hand using a mesh-glove has been shown to improve volitional movement of the hand and arm, and decrease muscle hypertonia after hemispherical stroke in patients who have reached a recovery plateau. The goal of this study was to investigate the effect of stimulation of the nerve afferents of the hand on brain cortical activity elicited by whole-hand subthreshold stimulation for sensation in humans with intact nervous systems. Brain cortical activity in 6 healthy subjects (30-45 years) was studied using blood oxygenation level-dependent functional Mag- netic Resonance Imaging during a test motor task, finger-to-thumb tapping and after 20 minutes of mesh-glove stimulation of the resting hand prior to performance of an identical motor task, to test the changes in the conditioned motor task established after 20 minutes of mesh-glove stimulation. Fifteen contiguous echo-planar sequences parallel to the bicommissural plane were acquired for functional magnetic resonance. Post-processing of image data included correction of motion artefacts and calcula- tion of correlation coefficients between the signal intensity of pixels during rest and finger tapping and a rectangular reference wave function. The func- tional Magnetic Resonance Imaging examinations revealed a signal increase in the primary and secondary motor and somatosensory areas when comparing the number of activated pixels during test and conditioned motor tasks. Our preliminary study indicated that change occurred in a definite pattern in the region of the regional cerebral blood flow of the brain cortex after mesh-glove whole-hand stimulation at the subthreshold level for sensation. We assumed that this increase in regional cerebral blood flow also reflected augmented neuronal activity. Key words: mesh glove; functional MRI; sensory stimulation; motor paradigm. INTRODUCTION We have reported previously that impaired movement of the hand and arm and altered muscle tone of the affected side after hemispherical stroke lesions can be amelio- rated by using a wire mesh-glove to stimulate the afferents of the hand (7). The novelty of this method is that the whole hand is the target of stimulation rather than only the cutaneous, cutaneous-motor and motor nerves, as is the case in functional and neuromuscular electrical stimulation (14, 19, 22). Mesh-glove stimula- tion generates (tonic) synchronous input to the brain below the conscious sensory threshold, probably due to depolarization of the large afferents of the whole hand. The beneficial effects of mesh-glove stimulation are the suppression of muscle hypertonia, augmentation of residual volitional movement and increased awareness of the affected hand (7-10). On the basis of this finding, we developed the hypothesis that mesh-glove stimulation involved neuro- physiological mechanisms triggered by externally in- duced kinesthetic input to posterior column nuclei, thalamus and cortical brain structures. We have specu- lated that the effect is mediated through an extended spinal-brain mechanism rather than being restricted to the segmental spinal response. In order to investigate whether whole-hand mesh-glove stimulation at the subsensory threshold level for conscious sensation can elicit changes in cortical brain activity, we developed the present functional Magnetic Resonance Imaging (fMRI) study of human cortex activity before and after whole-hand afferent electrical stimulation in a group of 6 healthy adult subjects. The aim of this study was to investigate whether changes in regional cerebral blood flow (rCBF) could be demonstrated by fMRI after whole-hand afferent elec- trical stimulation. fMRI based upon the blood oxy- genation level dependent (BOLD) effect allows the identification of physiologically activated brain areas by means of local and transient magnetic resonance signal increases (21). The most accepted explanation is that a local decrease in deoxyhemoglobin concentration within

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Page 1: FUNCTIONAL MAGNETIC RESONANCE IMAGING OF …Scand J Rehab Med 31: 165-173, 1998 Scand J Rehab Med 30 the venous microcirculation will result in an increase of the magnetic resonance

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FUNCTIONAL MAGNETIC RESONANCE IMAGING OF THE HUMAN MOTORCORTEX BEFORE AND AFMR WHOLE-HAND AFFERENT ELECTRICAL

STIMULATION

S. Golaszewski1, Ch. Kremser1 M. Wagner1, S. Felber1,2 F. Aichnerl,2 and M. M. Dimitrijevic3

From the Departments of 1Magnetic Resonance and 2Neurology, University of Innsbruck, Austria and the 3Department OfPhysical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas, USA

ABSTRACT. Electrical stimulation of the wholehand using a mesh-glove has been shown to improvevolitional movement of the hand and arm, anddecrease muscle hypertonia after hemisphericalstroke in patients who have reached a recoveryplateau. The goal of this study was to investigate theeffect of stimulation of the nerve afferents of thehand on brain cortical activity elicited by whole-handsubthreshold stimulation for sensation in humanswith intact nervous systems. Brain cortical activity in6 healthy subjects (30-45 years) was studied usingblood oxygenation level-dependent functional Mag-netic Resonance Imaging during a test motor task,finger-to-thumb tapping and after 20 minutes ofmesh-glove stimulation of the resting hand prior toperformance of an identical motor task, to test thechanges in the conditioned motor task establishedafter 20 minutes of mesh-glove stimulation. Fifteencontiguous echo-planar sequences parallel to thebicommissural plane were acquired for functionalmagnetic resonance. Post-processing of image dataincluded correction of motion artefacts and calcula-tion of correlation coefficients between the signalintensity of pixels during rest and finger tapping anda rectangular reference wave function. The func-tional Magnetic Resonance Imaging examinationsrevealed a signal increase in the primary andsecondary motor and somatosensory areas whencomparing the number of activated pixels during testand conditioned motor tasks. Our preliminary studyindicated that change occurred in a definite patternin the region of the regional cerebral blood flow ofthe brain cortex after mesh-glove whole-handstimulation at the subthreshold level for sensation.We assumed that this increase in regional cerebralblood flow also reflected augmented neuronalactivity.

Key words: mesh glove; functional MRI; sensorystimulation; motor paradigm.

INTRODUCTION

We have reported previously that impaired movement ofthe hand and arm and altered muscle tone of the affectedside after hemispherical stroke lesions can be amelio-rated by using a wire mesh-glove to stimulate theafferents of the hand (7). The novelty of this method isthat the whole hand is the target of stimulation ratherthan only the cutaneous, cutaneous-motor and motornerves, as is the case in functional and neuromuscularelectrical stimulation (14, 19, 22). Mesh-glove stimula-tion generates (tonic) synchronous input to the brainbelow the conscious sensory threshold, probably due todepolarization of the large afferents of the whole hand.The beneficial effects of mesh-glove stimulation are thesuppression of muscle hypertonia, augmentation ofresidual volitional movement and increased awareness ofthe affected hand (7-10).

On the basis of this finding, we developed thehypothesis that mesh-glove stimulation involved neuro-physiological mechanisms triggered by externally in-duced kinesthetic input to posterior column nuclei,thalamus and cortical brain structures. We have specu-lated that the effect is mediated through an extendedspinal-brain mechanism rather than being restricted tothe segmental spinal response. In order to investigatewhether whole-hand mesh-glove stimulation at thesubsensory threshold level for conscious sensation canelicit changes in cortical brain activity, we developed thepresent functional Magnetic Resonance Imaging (fMRI)study of human cortex activity before and afterwhole-hand afferent electrical stimulation in a group of 6healthy adult subjects.

The aim of this study was to investigate whetherchanges in regional cerebral blood flow (rCBF) could bedemonstrated by fMRI after whole-hand afferent elec-trical stimulation. fMRI based upon the blood oxy-genation level dependent (BOLD) effect allows theidentification of physiologically activated brain areas bymeans of local and transient magnetic resonance signalincreases (21). The most accepted explanation is that alocal decrease in deoxyhemoglobin concentration within

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the venous microcirculation will result in an increase ofthe magnetic resonance signal detected during brainactivation (24, 25). Therefore, we applied fMRI to studybrain cortical activity in healthy volunteers duringvolitional motor tasks before and after whole-handmesh-glove stimulation (28, 29).

In this report, we show that whole-hand afferentelectrical stimulation below the threshold for perceptionof sensation can significantly increase responsiveness inrCBF within several cortical regions of the contra- andipsilateral hemispheres.

MATERIALS AND METHODS

Our study was carried out in 6 healthy, right-handed mate volunteers(age 30-45 years), who signed the written consent form. The studyprotocol was approved by the local ethic committee. The subjectswere asked to perform a finger-to-thumb-tapping on/off motorparadigm with the hand, which consisted of consecutive forward andbackward tapping of the second to the fifth finger with the thumb,with a frequency of approximately 3 Hz. Each sequence of fingertapping began with an auditory signal. The subjects were instructedto position the tapping hand over the abdomen and keep their eyesclosed during the fMRI recording. Repeated measurements weremade for each subject on two different days. Furthermore a thirdidentical study was performed in the same subjects, but with shamstimulation, meaning that the subjects were not aware that electricalstimulation was being applied.

All experiments were performed on a 1.5 Tesla whole bodyscanner (Magnetom VISION, Siemens, Germany) with an echoplanarcapable gradient system (rise time 600 gsec, 25 mT/ms) and acircular polarized head coil (FoV = 250mm). For fMRI, we employedT2* weighted single shot echo-planar sequences (TRrrE/' =1.64ms/64ms/90', matrix = 64 x 128, voxel dimension = 2.94 x 1.95 x3 mm). As shown in Fig. 1, we acquired 15 slices parallel to thebicommissural plane (1, 20). Foam padding and a special helmetfixed to the head coil were used to restrict head motion. A series of60 sequential images was acquired, each consisting of 10 imagesduring rest alternating with 10 images during finger tapping.

We designed this study to investigate the conditioning effect ofmesh-glove stimulation on brain cortical activity elicited by thesimple sequential movement of a self-paced tapping motor task (4,31, 34). We applied mesh-glove stimulation for 20 minutes to therelaxed hand, while the subject was removed from the magnet. Thus,the first experiment involved a test motor task (TMT) and the seconda conditioned motor task (CMT).

The mesh-glove was connected to a two-channel stimulator(Medtronic Model 3128 Respond 11) with a common anode foroutput to the mesh glove and a pair of separated surface electrodes ascathodes just above the wrist, over the tendons of the extensors andflexors of the forearm. A train of stimuli of 50 Hz with a pulse widthof 0.3 ins was used for subthreshold stimulation. The subthresholdlevel of stimulation was definedby decreasing the stimulus strength to a level at which the subjectreported that the tingling sensation had disappeared. The amplitudefor subthreshold stimulus was between 0.85 and 0.95 mA.

To correct involuntary head movements, the fMRI were realignedoff-line using the Woods et al. algorithm (36). To quantify changes inrCBF during cortical activation, we identified only those pixels withsignal changes that corresponded to the temporal pattern of the motortask. This was accomplished by correlating the normalized imaging

data from each voxel with a reference waveform (2, 3). In this study,we assumed that functional activity resembled a rectangularwaveform. All pixels with a correlation less than r = 0.45 and pixelclusters of less than 4 pixels were excluded from further analysis. Forquantitation of pixel intensity we used a two-tailed paired Student'st-test (3, 32). The functional images were coloured according topositive values of the cross-correlation coefficient (i.e. pixels inphase with the reference waveform), and were displayed on a scalefrom red (minimum) to yellow (maximum). The pixels not reachingthe cut-off point were made transparent. These coloured functionalimages were then superimposed onto the original echo-planarsequence images. Then, the anatomical location of the activated areaswas evaluated using coordinates by Talairach & Toumoux (35).

RESULTS

Table I summarizes the data obtained in all 6 volunteersstudied for rCBF changes determined by the number ofactivated pixels. There is a consistent profile of changesbetween the studied brain cortical areas of the primarymotor cortex, primary sensory cortex and cortical areasof higher order within the sensorimotor system (gyrusfrontalis superior, gyrus frontalis medius, lobulusparietalis superior, and lobulus parietalis inferior). Thesefindings were reproducible in the same subjects onanother recording day (day 2). The repeated recordingsrevealed a similar magnitude of change between the firsttest and the conditioned motor task. Ipsilateral hemi-spheric cortical activity after mesh-glove whole-handstimulation, as expected, was much less pronounced.

Slices adjacent to the acquired 15 slices (Fig. 1) thatpassed the motor hand area and showed the mainactivation centers were evaluated. The numbers ofactivated pixels within these areas are summarized inTable I. In subject 1 (day 1), fMRI measurements duringTMT showed 15 activated pixels within the contralateralgyrus precentralis, but 23 activated pixels within thissame area during CMT. Within the ipsilateral hemi-sphere, we found 5 activated pixels for TMT and 8 forCMT within the gyrus precentralis. During the secondexamination, TMT and CMT revealed similar results.

Subjects 2, 5 and 6 showed the same contralateral andipsilateral responses within the gyrus precentralis.Subjects 3 and 4 showed increased activity only withinthe contralateral gyrus precentralis during CMT. Withinthe primary somatosensory region in the gyruspostcentralis contralateral to the tapping fingers, wecould see that each subject activated pixels during TMT(pixel range: 6-37) and CMT (pixel range: 9-45).Subjects 1, 2, 5 and 6 also showed ipsilateral activationat first in CMT during both recordings carried out ondifferent days, whereas subjects 3 and 4 only showedcontralateral activation.

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Table 1. Activated pixel numbers during the finger-tapping motor task, test motor task and after conditioning of the resting left handbefore identical finger-tapping conditioned motor task with 20 minutes of subthreshold, electrical whole-hand mesh-glove stimulation.Number of activated pixels during the first day (day 1) and subsequent day (day 2) of the recording sessions from the cortical areas ofthe gyrus precentralis (GPrC) gyrus postcentralis (GPC) lobulus parietalis superior (LPs), lobulus parietalis inferior (LPi),gyrusfrontalis superior (GFs) and gyrusfrontalis medius (GFm)

Subjects Day Hand GPrC GPoC LPs Lpi GFs GFm

1 1 R 15/23 6/9 18/30 4/7 0/4 0/7L 5/11 4/7 4/13 0/0 0/0 0/4

2 R 21/23 14/17 10/28 0/6 6/9 0/7L 4/7 0/4 0/9 0/0 0/0 0/0

2 1 R 17/41 17/35 11/17 0/5 6/10 0/7L 4/11 0/5 0/5 0/6 0/0 0/0

2 R 12/18 18/20 9/18 0/4 8/12 0/9L 7/13 0/6 0/7 0/4 13/14 0/0

3 1 R 21/35 13/28 9/17 13/27 5/11 0/9L 4/17 0/9 4/7 0/4 0/4 0/7

2 R 30/32 37/45 13/21 0/6 10/13 0/7L 0/0 0/0 0/6 0/9 0/5 0/0

4 1 R 16/23 6/9 0/5 0/9 0/0 13/27L 6/9 0/0 0/0 0/0 5/9 4/24

2 R 17/23 14/17 12/21 0/9 11/13 0/5L 0/0 0/0 0/5 0/0 0/0 0/0

5 1 R 18/41 17/35 9/17 0/7 7/7 0/7L 4/8 0/6 0/5 0/4 0/0 0/0

2 R 12/18 13/20 8/12 0/8 8/13 0/9L 6/11 0/7 0/6 0/5 80 0/0

6 1 R 15/18 21/27 7/15 0/9 7/12 0/7L 5/9 0/5 0/7 0/6 0/5 0/0

2 R 25/32 37/45 9/14 0/7 6/19 0/6L 4/6 0/4 0/6 0/9 0/6 0/0

Subjects 1-6 showed increased contralateral activationwithin the lobulus parietalis superior during CMT, andipsilateral activation increased from no activity to 5 and17 pixels. However, there was no activity in the lobulusparietalis inferior within the contra- and ipsilateralhemispheres in response to TMT, but CMTmeasurements showed rCBF activity in both hemi-spheres in nearly all cases.

Within the gyrus frontalis superior, we observedcontralateral TMT and CMT activation when subjects 1,2, 4, 5 and 6 were examined on two different days. Onthe second day of examination, subject 2 showed bothipsilateral TMT and CMT activation. In subject 3, thenwas a response only during CMT on the second daySubject 6 showed ipsilateral activation to CMT in bothrecordings carried out on different days. The gyrusfrontalis medius showed contra- and ipsilateral responseto TMT and CMT only in subject 4 (day 1), whilecontralateral activation to CMT was seen constantly inall subjects, and in all subjects there was an increase inthe maximum intensity of the activated pixels afterCMT.

In order to simplify the illustration of data presented inTable 1, we calculated the mean value of all recorded

activated pixels of the contralateral (right) hemispherewithin the cortical regions studied for the 12 measure-ments in all 6 subjects (Fig. 2). There was a significantchange (p < 0.01) in rCBF between TMT and CMT ingyrus precentralis activity (Fig. 2).

When the same experimental procedure was per-formed in the same subjects, but with sham mesh-glovestimulation, there was no increase in rCBF activity ofCMT. The results are summarized in Table II. Beforeand after sham stimulation, there was bilateral activationwithin the GPrC in subjects 1, 2, 5 and 6, and onlycontralateral. GPrC activation in subjects 3 and 4 duringthe two recordings carried out on different days. Thelobulus parietalis inferior pattern of activation duringsham stimulation was similar to the previously describedgyrus precentralis pattern of activation. Activationwithin the lobulus parietalis superior was seen onlycontralaterally during sham stimulation.

The same was true for the gyrus frontalis superior Thelobulus parietalis inferior and the gyrus frontalis mediusshowed no activation during sham measurements. Therewas no statistically significant increase in the number ofpixels activated after sham stimulation (Fig. 3).

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Fig. 1. Slice orientation parallel to bicommissural plane. The block of 15 slices covers the whole motor cortex. Slices 3 and 4 (from the top) passthrough the motor hand area, which is the main site of activity during the finger-tapping motor task with the contralateral (left) hand.

Figs. 4 and 5 illustrate functional image findingsduring TMT and applied mesh-glove stimulation beforeCMT (Fig. 4) and applied sham stimulation prior toCMT (Fig, 5) by means of the coloured functionalimages superimposed on the original echo-planarsequence images. Fig. 4 is composed of functionalimages from left to right of subject 1 (day 1), subject 3(day 1) and subject 4 (day 1) during TMT (upper row)and CMT (lower row). Fig. 5 consists of functionalimages during sham stimulation before CMT in subject 4(day 2), subject 5 (day 1) and subject 6 (day 1). Thesequence, as in Fig. 4, is from left to right; TMT isillustrated in the upper row and CMT in the lower row.

The pixels in phase with the reference brain waveformare displayed on a scale from red (minimum) to yellow(maximum), and the pixels not reaching the cut-off pointare transparent. By comparing these two figures offunctional image findings, we see an obvious differencein the rCBF changes after 20 minutes of subthresholdstimulation for sensory perception, and no changes inrCBF when sham mesh-glove stimulation was appliedfor 20 minutes prior to CMT.

Fig. 2. Mean of activated pixels of the right hemisphere in all 6 subjectsstudied during test motor task JMT) of the left hand before mesh-glovestimulation, and during conditioned motor task (CMT) after mesh-glovestimulation. A statistically significant increase of activation (p < 0.01)after mesh-glove stimulation is found for the gyrus pre- and postcentralis(GPrC and GPoQ, superior and inferior parietal lobules (LPs and LPi)and superior and medial frontal gyrus (GFs and GFm).

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Table II. Recording conditions were identical to those in Table I; the only difference was that sham stimulation was applied instead of the previouswhole-hand mesh-glove subthreshold electrical stimulation for perception of sensation

Subjects Day Hand GPrC GPoC LPs Lpi GFs GFm

1 1 R 13/14 6/9 18/19 0/0 4/5 0/0

L 7/8 4/4 0/0 0/0 0/0 0/0

2 R 16/14 14/17 10/11 0/0 6/5 0/0

L 5/7 5/4 0/0 0/0 0/0 0/0

2 1 R 21/19 17/16 11/15 0/0 6/6 0/0

L 6/5 6/5 0/0 0/0 0/0 0/0

2 R 17/22 18/18 9/13 0/0 8/12 0/0

L 8/6 6/6 0/0 0/0 0/0 0/0

3 1 R 19/18 19/21 11/9 0/0 13/11 0/0

L 0/0 0/0 0/0 0/0 0/0 0/0

2 R 22/30 37/31 13/14 0/0 10/9 0/0

L 0/0 0/0 0/0 0/0 0/0 0/0

4 1 R 31/35 6/6 14/14 0/0 12/15 0/0

L 7/9 0/0 0/0 0/0 0/0 0/0

2 R 29/27 14/16 4/6 0/0 7/6 0/0

L 9/9 5/0 0/0 0/0 0/0 0/0

5 1 R 28/30 17/21 14/11 0/0 0/0 0/0

L 9/11 0/0 8/10 0/0 0/0 0/0

2 R 27/25 13/10 8/12 0/0 8/9 0/0

L 10/8 5/7 0/0 0/0 0/0 0/0

6 1 R 18/21 15/17 0/0 7/6 0/0 0/0

L 6/5 6/5 0/0 0/0 0/0 0/0

2 R 25/32 37/30 9/8 0/0 6/9 0/0

L 4/6 4/4 0/0 0/0 0/0 0/0

DISCUSSION

During self-paced simple finger movements, we foundan increase in the mean of activated pixels andmaximum number of pixels over the contralateralhemisphere within the gyrus precentralis, gyruspostcentralis, lobulus parietalis superior and gyrusfrontalis superior, as well as some increase in corticalbrain activity in the ipsilateral brain hemisphere withinthe gyrus postcentralis and lobulus parietalis superior.These findings were expected and had been reported byother investigators who studied the activity of humancortical motor areas during self-paced finger movements(6,23). When we applied 20 minutes of conditioningstimulation to the afferents of the whole hand, we foundan increase in cortical activity induced by CMT whencompared to that elicited by TMT without precedingmesh-glove stimulation. Thus, we concluded thatmesh-glove whole-hand stimulation augments corticalbrain activity elicited by a motor task in the specificcontralateral and ipsilateral motor and sensory areas ofthe frontal and parietal lobes. Findings that suchadditional excitatory effect was absent when the sham

paradigm was applied further confirmed the validity ofthe results presented.

In addition, we concluded that whole-hand mesh-glovestimulation below the threshold for sensation is an activesystem, which depolarizes a certain population ofkinesthetic afferents with cortical projections. There aredefinite experimental findings to confirm that muscleafferents of groups Ia, Ib, and II have short-latencyprojections to the contralateral somatosensory cortex,particularly areas 3a and 4 (motor cortex) (13). Thepresence of cortical projections of large afferents wasalso confirmed in a PET study in which the fingers ofhealthy adult humans were vibrated so that it waspossible to activate bilaterally the contralateral SI, theretroinsular cortex parietal operculum and SII (30).

By means of fMRI, we have demonstrated that afferentelectrical whole-hand stimulation with a mesh gloveleads to an increase in the responsiveness of thesomatosensory system and motor cortices during avolitional motor task. We still need to determine thenature of the relationship between increased rCBF and

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neuronal cortical activity. fMRI and PET scan studies ofthe rCBF have been carried out to identify the corticalareas activated during electrical stimulation of themedian nerve at the wrist (16). It was found thatmedian nerve stimulation from 4020 Hz evoked a singlefocus of activation in the primary somatosensory area.This study indirectly supports our finding, althoughstimulus strength was above the sensory threshold andapplied over the median nerve, in contrast to our whole-hand stimulation with stimulus below the sensorythreshold.

Analysis of the results (Figs. 2 and 3) of fMRImeasurements of mean activated pixels, and themaximum number of pixels, of the right and lefthemispheres during TMT and CMT after stimulating theleft hand showed that both parietal inferior lobules wereprofoundly activated during CMT. This ipsilateralincrease of activity of the inferior parietal lobule was theresult of additional kinesthetic input, since during TMTwe did not record any inferior parietal lobule activityeither ipsior contralaterally.

The hand can be a rich source of kinesthetic input. Thelarge afferents from the hand's intrinsic muscles havehigh-density muscle spindles (18), a large number ofjoint receptors with corresponding large afferents; andGolgi tendon organs, with a portion of the tendonswithin the hand, but belonging to the forearm muscles(5). Further neurophysiological research is necessary todetermine the kind and size of the population of handafferents depolarized under the experimental conditionsand parameters of mesh-glove stimulation (11). How-ever, regardless of which hand afferents such stimulationdepolarizes, we can be certain that there are afferentswhich are involved in proprioception, "which refers tothe sensing of the body's own movement" (27).

In this fMRI study, we described a definite pattern ofchanges in rCBF of the brain cortex after mesh-glovestimulation. We expected that an increase in rCBFresulting from such a definite and consistent pattern ofwhole-hand stimulation reflected an increase in theactual level of neuronal brain activity.

This externally induced input to the brain came fromthe resting hand, which was stimulated for a 20-minuteperiod, and the effect of this input was shown in thepost-stimulation period during simple motor tasks.Besides the increase in cerebral brain activity in the pre-and post-central gyrus, it is also important to notice theappearance of cortical activity of the inferior parietallobule within both hemispheres. The inferior parietallobule is the site of convergence of kinesthetic inputcontaining premotor and visual information. Duringreaching and grasping with the hand, the parietalassociation cortex is involved in a series of sensorimotortransformations to convert the signal to the target

location on the retina into a pattern of peripheral motoroutput signals to muscles, in order to move the hand tothe target (15, 33). The results reported in this studyencouraged us to expand our understanding about themodification of motor control of wrist extension elicitedby mesh-glove electrical afferent stimulation in strokepatients (10, 19, 22).

In future studies, it will be necessary to prove ourfindings in a larger population of subjects. Our currentimage processing method, which perhaps is not the mostoptimal, is based on magnetic resonance signal changeswhich are detected and correlated with a rectangularwaveform. Our finding that particular cortical areas arenot activated during the motor task does not exclude thepossibility that functional activity occurs within suchregions below threshold analysis. We applied the samethreshold for all subjects in each recording session, butthe question remained whether we should choose adifferent threshold for each subject and each experi-mental condition. Moreover, we did not attempt tocontrol the level of alertness and attention, or carry outany specific preparatory procedure before starting therecordings.

Fig. 3. Mean of activated pixels of the right hemisphere in all 6 subjectsduring test motor task (TMT) of the left hand before mesh-glove stimulation,and during conditioned motor task (CMT) after sham mesh-glove stimulation.There is no statistically significant increase (p > 0.02) of activation for thegyrus pre- and post-centralis (GPrC and GPoQ, superior parietal lobule (LPs)and superior frontal gyrus (GFs).

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Fig. 4. Functional images from left to right for 3 of the 6 subjects studied. The upper row (a) shows fMRI images during TMT and the lower row (b) fMRI images afterCMT.

Fig. 5. Functional images from left to right for 3 of the 6 subjects studied. The upper row (a) shows fMRI images during TMT and the lower row (b) fMRI imagesconditioned by sham stimulation.

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The regional areas of activation during TMT wereconstant: the contralateral primary motor and somato-sensory cortices in all subjects were activated in each ofthe fMRI experiments. The resultant activation maps areconsistent with those obtained from electrophysiological(26) and PET (12) studies. Activation within thepremotor, motor cortex and somatosensory associationareas occurred, but was less constant at a threshold levelof analysis with a positive correlation coefficient ofr = 0.45. We also examined the functional imaging datawith lower threshold levels of activity (r = 0.38 and0.35), but it was very difficult to differentiate elicitedactivity from background signal noise, since the changeswere less than 2% and below the analysis threshold ofour study.

The anatomical location of the activated regions hadan accuracy of approximately I mm, and was based onthe brain atlas of Talairach & Tournoux (35). Intra- andinter-individual reproducibility was very good. With theecho-planar imaging multi-slice technique, we were ableto cover the whole motor cortex to sample spatialactivation data. We found a large activation patternwithin two adjacent parallel slices with a distance of3mm passing through the motor hand area, asdetermined by the electrophysiological mapping of themotor cortex of Penfield & Boldrey (26), fMRI (17) andpositron emission tomography studies (12, 23).

In conclusion, our findings encouraged us to expandthis unique study of human brain activity under theinfluence of selective kinesthetic input by means ofnoninvasive methods such as fMRI. The results of thisstudy support our working hypothesis that whole-handcontinuous electrical stimulation at the subthresholdlevel for conscious sensation involves neuro-physiological mechanisms, which are activated byexternally controlled kinesthetic input.

ACKNOWLEDGEMENTS

This work was supported by the Biomed2 Project PL 950870of the European Community, and by a grant from the KentWaldrep National Paralysis Foundation, Dallas, Texas, USA.The authors express their gratitude to Professor Milan R.Dimitrijevic for his continuous support and encouragementduring the development of this study.

REFERENCES

1. Bandettini, P.A., Wong, E.C., Hinks, R.S., Tikofsky, R.S. 18 & Hyde,J.S.: Time course EPI of human brain function during task activation.Magn Reson Med 25: 390-397, 1992

2. Bandettini, P.A., Jesmanowicz, A., Wong, E.C. & Hyde, J.S.: Processingstrategies for time course data sets in functional MRI of the humanbrain. Magn Reson Med 30 161-173,1993.

3. Baudendistel, K., Schad, L.R., Friedlinger, M., Wenz, F. Schroder, J. &Lorenz, W.J.: Post-processing of functional MRI data of motor cortexstimulation measured with a standard 1.5 T imager. Magn ResonImaging 13: 701-707 1995.

4. Boecher, H., Kleinschmidt, A., Requardt, M., Hanicke, W. Merboldt,K.D. & Frahm, J.: Functional cooperativity of human cortical motorareas during self-paced simple finger movements. A high-resolutionMRI study. Brain 117: 12311239,1994.

5. Burne, J.A. & Lippold, J.C.O.: Reflex inhibition following electricalstimulation over muscle tendons in man. Brain 119: 1107-1114, 1996.

6. Deiber, M.P., Passingham, R.E., Colebatch, I.G., Friston K.J., Nixon,P.D. & Frackowiak, R.S.J.: Cortical areas and the selection ofmovement: a study with positron emission tomography. Exp Brain Res84: 393-402, 1991.

7. Dimitrijevic, M.M.: Mesh-glove. 1. A method for whole-hand electricalstimulation in upper motor neuron dysfunction. Scand J Rehabil Med 26:183-186, 1994.

8. Dimitrijevic, M.M. & Soroker, N.: Mesh-glove. 2. Modulation ofresidual upper limb motor control after stroke with whole-hand electricstimulation. Scand J Rehabil Med 26 187-190,1994.

9. Dimitrijevic, M.M., Soroker, N. & Pollo, F.E.: Mesh-glove electricalstimulation. Sci Med 3: 54-63, 1996.

10. Dimitrijevic, M.M., Stokic, D.S., Wawro, A.W. & Wun, C.C.:Modification of motor control of wrist extension by mesh-gloveelectrical afferent stimulation in stroke patients Arch Phys Med Rehabil77: 252-258, 1996.

11. Dimitrijevic, M.M., Pollo, F.E., Soroker, N., Stokic, D.S & Dimitrijevic,M.R.: Electrophysiological characteristic of the effective stimulus forthe modification of muscle tone and volitional activity in humans withspastic hand after stroke. Abstracts. Society for Neuroscience 21: 268,1995.

12. Fox, P. T., Bruton, H. & Raichle, M. E.: Mapping human somatosensorycortex with positron emission tomography. J Neurosurg 67: 34-43, 1987.

13. Gandevia, S.C.: Kinesthesia: roles for afferent signals and motorcommands. In Handbook of Physiology. Section 12 Exercise:Regulation and Integration of Multiple System (ed. L. Rowell & J.T.Shepherd) pp. 128-172. American Physiological Society, New York,1996.

14. Goldman, H.: Improvement of double simultaneous stimulationperception in hemiplegic patients. Arch Phys M Rehabil 47: 681-687,1996.

15. Grissolatti, M., Fogassi, L. & Gallese, V.: Parietal cortex from sight toaction. Curr Opin Neurobiol 7: 562-567, 1997

16. Ibanez, V., Deiber, M.P., Sadato, N., Toro, C., Grissom, J. Woods, R.P.,Mazziotta, J.C. & Hallet, M.: Effects o stimulus rate on regional cerebralblood flow after median nerve stimulation. Brain 118: 1339-1351, 1995.

17. Jack, C., Thompson, R.M., Butts, R.K., Sharbrough, F.W. Kelly, P.J.,Hanson, D.P., Rieder, S.J., Ehman, R.L. Hangiandreou, N.J. & Cascino,G.D.: Sensory motor cortex: correlation of presurgical mapping withfunctional MR imaging and invasive cortical mapping. Radiology 19085-92,1994.

18. Jami, L.: Golgi tendon organs in mammalian skeletal muscles:functional properties and central actions. Physio Rev 72: 623-666, 1992.

19. Kraft, G.H., Fitts, S.S. & Hammond, M.C.: Techniques to improvefunction of the arm and hand in chronic hemiplegia. Arch Phys Med Rehabil73: 220-227, 1992.

20. Kwong, K.K.: Functional magnetic resonance imaging with echo planarimaging. Magn Reson Q 1/: 1-20, 1995.

21. Kwong, K.K. Belliveau, J.W., Chesler, D.A., Goldberg, I.A., Weisskoff,R.M., Poncelet, B.P., Kennedy, D.N Hoppel, B.E., Cohen, M.S., Turner, R.,Cheng, H.M., Brady, T.J. & Rosen, B.R.: Dynamic magnetic resonanceimaging of human brain activity during primary sensory stimulation. ProcNatl Acad Sci USA 89: 5675-5679, 1992.

22. Levin, M. F. & Hui-Chan, C. W. Y.: Relief of hemiparetic spasticity byTENS is associated with improvement in reflex and voluntary motorfunctions. Eicctroencephalogr Clin Ncurophysiol 85: 131-142, 1992.

Page 9: FUNCTIONAL MAGNETIC RESONANCE IMAGING OF …Scand J Rehab Med 31: 165-173, 1998 Scand J Rehab Med 30 the venous microcirculation will result in an increase of the magnetic resonance

Scand J Rehab Med 31: 165-173, 1998

Scand J Rehab Med 30

23. Mazziotta, J.C. & Phelps, M.E.: Positron computed tomography studies ofcerebral metabolic responses to complex motor (asks. Neurology 34, Suppi 1:116, 1984.

24. Ogawa, S., Lee, T.M., Kay, A.R. & Tank, D.W.: Brain magnetic resonanceimaging with contrast dependent on blood oxygenation. Proc Nail Acad SciUSA 87. 98689872,1990.

25. Ogawa, S., Tank, D.W., Menon. R. Ellerniann, J.M., Kim, S.G., Merkle, H.& Ugurbil, K.: Intrinsic signal changes accompanying sensory stimulation:functional brain mapping with magnetic resonance imaging. Proc Nail AcadSci USA 89: 5951-5955, 1992.

26. Perifie1d, W. & Boldrey, E.: Somatic motor and sensory representation in thecerebral cortex of man as studied by electrical stimulation. Brain 15:389-443, 1938.

27. Prochazka, A.: Proprioceptive feedback and movement regulation. InHandbook of Physiology. Section 12. Exercise: Regulation and Integration ofMultiple Systems (cd. L. Rowell & J.T. Shepherd), pp. 89-127. AmericanPhysiological Society. New York, 1996.

28. Rao, S. M., Binder, J. R., Bandettini, P. A., Hammeke, T. A., Yetkin, F. Z.,Jesmanowicz, A., Lisk, L. M., Morris, G. L., Mueller, W. M. & Estkowski, L.D.: Functional magnetic resonance imaging of complex human movements.Neurology 43: 2311-2318, 1993.

29. Rao, S. M., Binder, J. R., Hammcke, T. A., Bandettini. P.A., Bobholz, J.A.,Frost, J.A., Myklebust, B.M., Jacobson, R.D. & Hyde, J.S.: Somatotopicmapping of the human primary motor cortex with functional magneticresonance imaging. Neurology 45: 919-924, 1995.

30. Roland, P.E., Larsen, B., Lassen, N.A. & Skinhoj, E.: Supplementary motorarea and other cortical areas in the organization of voluntary movements inman. J Neurophysiol 43: 118-136, 1980.

31. Roland, P. E. & Seitz, R.J.: Positron emission tomography studies of thesomatosensory system in man. In Exploring brain functional anatomy withpositron tomography. Ciba Foundation Symposium 163: 113-120, 1991.

32. Sachs, L. Angewandic Statistik. Hrsg. Lothar Sachs. Springer-Verlag, Berlin,1992.

33. Sakata, H., Taira, M., Kusunoki, M., Murata, A. & Tanaka. Y.: The parietalassociation cortex in depth perception and visual control of hand action.Trends Neurosci 20: 350356,.

34. Seitz, R. J., Roland, P. E., Bohm, C., Greitz, T. & Stone-Elander, S.:Somatosensory discrimination of shape: tactile exploration and cerebralactivation. Eur J Neurosci 3: 48 1 -492, 1991.

35. Talairach, J. & Tournoux, P.: Co-planar stereotaxic atlas of the human brain.Hrsg. Thieme Medical Publishers. Georg Thieme Verlag, Stuttgart, 1998.

36. Woods, R. P., Cherry. S. R. & Maziotta, J. C.: Rapid automated algorithm foraligning and reslicing PET images. J Comput Assist Tonnogr 16: 620-633,1992.

Accepted August 27, 1998

Address for offprints:

Dipl. Ing. Dr. Stefan GolaszewskiDepartment of Magnetic ResonanceUniversity of InnsbruckAnichstraβe 35A-6020 InnsbruckAustria