Bilateral representation of sequential finger movements in human cortical areas

Neuroscience Letters 269 (1999) 95±98

Bilateral representation of sequential ®nger movements in human cortical areas Patrizia Baraldi a,*, Carlo Adolfo Porro b, Marco Sera®ni c, Giuseppe Pagnoni a, Cristina Murari d, Ruggero Corazza a, Paolo Nichelli e a

Dipartimento di Scienze Biomediche, Universita' di Modena, Via Campi 287, 41100 Modena, Italy Dipartimento di Scienze e Tecnologie Biomediche, Universita' di Udine, P.le Kolbe, 33100 Udine, Italy c Azienda Policlinico, Via del Pozzo 71, 41100 Modena, Italy d CICAIA, Universita' di Modena, Via Campi 213/B, 41100 Modena, Italy e Dipartimento di Patologia Neuropsicosensoriale, Universita' di Modena, Via del Pozzo 71, 41100 Modena, Italy b

Received 22 December 1998; received in revised form 26 March 1999; accepted 10 May 1999

Abstract The spatial distribution of cortical neural clusters activated during movement of either hand (`bilateral' population), or only of one hand, was investigated in healthy right-handed volunteers performing a sequential ®nger opposition task, using echo-planar functional magnetic resonance imaging. `Bilateral' clusters were found in the mesial premotor, perirolandic and adjacent lateral premotor cortex of the two hemispheres, and in the left superior parietal lobule. In the precentral gyrus, their spatial extent was larger on the left hemisphere. Clusters activated exclusively during contralateral ®nger movements were equally distributed in the left and right perirolandic cortex. No cluster activated exclusively during ipsilateral ®nger movements was detected. These ®ndings support a role of the motor/lateral premotor cortex of the dominant hemisphere in bilateral motor control. q 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Functional magnetic resonance imaging; Motor cortex; Finger movement; Bilateral motor representation; Brain mapping; Human

Activation of the ipsilateral primary sensorimotor cortex during sequential ®nger movements has been described in healthy volunteers, using positron emission tomography (PET) [8,14] and functional magnetic resonance imaging (fMRI) [2,5,9,10,17]. The spatial extent of the ipsilateral activation appears to be larger in the dominant hemisphere [5,9,17] and increases with the complexity of the motor task [17]; in the primary motor cortex ipsilateral to the dominant hand, it is inversely related to the degree of handedness [5]. The functional signi®cance of these ®ndings is still not completely understood. Speci®cally, it is unknown whether the ipsilateral hemodynamic changes re¯ect the activity of neural populations involved uniquely in ipsilateral hand movements, which have been described in the motor cortex of non-human primates [16], or of cortical networks activated during movements of either hand. We have investigated this issue using echo-planar fMRI techniques, during a sequential ®nger opposition task performed alternatively * Corresponding author. Tel.: 139-059-428-221; fax: 139-059428-236. E-mail address: [email protected] (P. Baraldi)

with the right and left hand. The experimental design allowed us to test directly the occurrence and spatial distribution of contralateral, bilateral, and ipsilateral motor representations in the two hemispheres. Ten male right-handed volunteers aged 25±30 years were investigated after written informed consent. None had any record of neurological disease. The study was approved by the Ethics Committee of the University of Modena Medical School. The experiments were performed using a GE Horizon Hispeed 77 1.5 T MR system equipped with rapidly switching whole body gradients (22 mT/m) and quadrature RF head coils. Head motion was minimized by an adjustable padded head-holder and orthopedic collar. To locate the regions of interest, sixteen T1-weighted spin-echo axial images of the brain were acquired. Functional images were obtained from the same planes by a T2*-weighted EPI sequence (nihepi: courtesy of P. Jezzard, NIH, Bethesda, MD) (TR ˆ 4 s, TE ˆ 40 ms, 64 £ 64 matrix, 3:75 £ 3:75 £ 5 mm voxels), while subjects performed periods of sequential ®nger-to-thumb opposition movements of

0304-3940/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 9 9) 00 43 3- 4

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P. Baraldi et al. / Neuroscience Letters 269 (1999) 95±98

were assumed as signi®cance thresholds. These yielded an overall signi®cance level of 0.002, corrected for the number of comparisons, as estimated by a Monte Carlo simulation of the process of image generation, spatial correlation of voxels, voxel intensity thresholding and cluster identi®cation (routine by B.D. Ward, Biophysics Research Institute, Medical College of Wisconsin, WI). The resulting maps were resized into the standard anatomical space of the atlas of Talairach and Tournoux [15], using the AFNI package [4]. Three regions of interest were manually outlined on each side of the brain onto the individual structural images, according to anatomical landmarks [12,18]: the middle portion of the pre- and postcentral gyri, including the puta-

Fig. 1. Coincidence statistical maps of the bilateral population in four axial sections, overlaid on the averaged (from all subjects) T1-weighted structural images, transformed in the Talairach space. The left side of the brain is on the right side of the ®gure. The color scale indicates the number of subjects showing the same activation coordinates.

the right hand (R) or of the left hand (L) at a frequency of about 2 Hz. The order of tapping was 2±3±4±5±2±3±4±5. Periods of movements were alternated with Rest, during which subjects were asked to relax, keeping their arms still with the ®ngers in a mid¯exion position. Two repetitions of Rest - R movement - Rest - L movement (32 s for each task) occurred in each acquisition session. Four sessions, each comprising 64 scans, were recorded for each subject. Whole-head high-resolution T1-weighted images were then acquired to be used as anatomical reference for trasformations into the Talairach space [15]. Functional volumes were aligned by a software procedure implemented by Cox [4]. One subject was excluded from the study due to large residual head movement artifacts. For each subject, the four sessions were combined averaging the signals on a voxel by voxel basis after the removal of linear trends. Voxels with signal intensity of ^2 SD from the mean of all brain voxels of the ®rst functional volume were excluded from analysis. To identify activated foci, the signal time course of each voxel was compared with task-related square waveforms (Figs. 2 and 3), thus creating statistical maps based on Pearson's correlation coef®cient r [1]. A value of j r j ˆ 0.55 (corresponding to z ˆ 4:82) and a cluster size of two voxels

Fig. 2. Bilateral population: time pro®le of mean normalized signal intensity during movements of either hands, in selected brain regions. L and R ˆ movements of the left and of the right hand, respectively. Values from the left and right SMA have been pooled together. Each point represents mean ^ SEM (n ˆ 8). The signal intensity changes during movements of the right (IR) or of the left (IL) hands were signi®cantly different in the right precentral gyrus (IR ˆ 1:3% vs. IL ˆ 2:15%, repeatedmeasured ANOVA, P , 0:003; IR vs. Rest, P , 0:002; IL vs. Rest, P , 0:0001) as well as in the left precentral gyrus (IR ˆ 2:7% vs. IL ˆ 1:3%, P , 0:001; IR vs. Rest, P , 0:0001; IL vs. Rest, P , 0:0001). No signi®cant difference was found during R or L movements in the SMA (IR ˆ 1:8%, IL ˆ 1:6%; IR vs. Rest, P , 0:0001; IL vs. Rest, P , 0:0001).

P. Baraldi et al. / Neuroscience Letters 269 (1999) 95±98

Fig. 3. Contralateral population: time pro®le of mean normalized signal intensity in the precentral gyri. L and R ˆ movements of the left and of the right hand, respectively. Each point represents mean ^ SEM of nine subjects. The mean signal intensity changes during movement of the contralateral hand were higher on the left side of the brain (2.8 vs. 1.8%, P , 0:01).

tive hand representation areas of the primary motor and sensory cortex [18] (axial planes approximately between 135 and 160 z levels), and the mesial premotor area, including the proper and pre-supplementary motor area (SMA) [12,13]. In all subjects, clusters were identi®ed whose signal time courses were signi®cantly correlated with a square waveform (Fig. 2) which modeled activation during movement of either hand (`bilateral' population). These clusters were present on both hemispheres in the SMA, in the post- and precentral gyri and in the adjacent lateral premotor cortex,

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whereas in most subjects on the left side only in the superior parietal lobule (Fig. 1). In the precentral gyrus, the spatial extent of the `bilateral' population was larger on the left hemisphere (Table 1) in seven subjects (average L/R ratio: 2:56 ^ 0:33); one subject showed an inverse ratio of 0.47. In the postcentral gyrus, the spatial extent of the bilateral population was lower and the L/R ratio was more variable (4:7 ^ 1:2 in ®ve subjects and 0:47 ^ 0:08 in three subjects). No side difference was found in the SMA (Table 1). Mean signal intensity changes, relative to rest, were signi®cantly higher during movements of the contralateral hand than during movements of the ipsilateral hand in both precentral gyri. No signi®cant difference was found in the postcentral gyrus and SMA (Fig. 2). Separate clusters exhibiting signal changes only during movements of the contralateral hand (`contralateral' population) were found in all subjects in the precentral and postcentral gyri, but not in the SMA. Their spatial extent was similar on both hemispheres (Table 1). Mean signal intensity changes during movement of the contralateral hand were larger in the left than in the right precentral gyri (Fig. 3). In both right and left precentral gyri, the center of mass of the `contralateral' population was located posteriorly with respect to the `bilateral' one (Table 1). No clusters exhibiting activation only during movements of the ipsilateral hand were found in any regions. This study indicates the existence of two separate neural populations both in the motor and premotor cortex of righthanders. The ®rst population is activated only during contralateral ®nger movements and the second one displays signal changes during movements of either hand. The latter has not, to the authors' knowledge, been described so far in the human cortex. The observed differences in the functional characteristics of bilateral neural populations in the investigated regions are in line with a predominant role of SMA in motor planning, and a more direct involvement of the motor/premotor prerolandic cortex in the control of contralateral hand movements. It is still a matter of debate whether the hemodynamic changes in motor areas ipsilateral to the moving hand may re¯ect activation of corticospinal neurons projecting ipsilat-

Table 1 Mean ^ SEM volume (mm 3) and mean ^ SEM Talairach coordinates (x, y, z, in mm) of the centers of mass of the `Bilateral' and `Contralateral' populations in selected ROIs a ROI

Left precentral gyrus Right precentral gyrus Left postcentral gyrus Right postcentral gyrus Left SMA Right SMA a

`Bilateral'

`Contralateral'

Volume

n

x

y

z

Volume

n

x

y

z

1195 ^ 129* 606 ^ 78 659 ^ 152 316 ^ 62 747 ^ 182 914 ^ 181

8 8 8 8 8 8

232 ^ 2 34 ^ 1 238 ^ 2 38 ^ 3 28 ^ 1 6^1

213 ^ 1 210 ^ 1 221 ^ 2 221 ^ 2 22 ^ 2 2^2

51 ^ 1 54 ^ 1 48 ^ 1 50 ^ 2 54 ^ 1 53 ^ 1

1336 ^ 211 1328 ^ 193 574 ^ 149 502 ^ 80 ± ±

9 9 6 7 ± ±

231 ^ 1 34 ^ 1 234 ^ 2 39 ^ 1

215 ^ 1** 215 ^ 1** 223 ^ 1 218 ^ 1 ± ±

51 ^ 1 53 ^ 1 52 ^ 2 49 ^ 2

*Signi®cantly higher than the right precentral gyrus at P , 0.05, Student's t-test; **signi®cantly different from the bilateral population (left hemisphere, P , 0:006; right hemisphere, P , 0:002).

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P. Baraldi et al. / Neuroscience Letters 269 (1999) 95±98

erally [3,10]. The present work shows a spatial segregation within the precentral gyrus between the bilateral population and the purely contralateral one: the former is centered on the anterior part of the gyrus, a region likely to correspond to Brodmann area 6. These results are in line with the hypothesis that the ipsilateral cortical activation may re¯ect bilateral networks connected through rapid callosal pathways [7], involved in motor planning rather than motor execution. The asymmetry of the activation in the two hemispheres deserves a ®nal comment. Taking into account the overall spatial extent of the two neural populations and the intensity of their signal changes, the left motor/lateral premotor cortex displayed higher activity than the corresponding area in the right hemisphere, both during the contralateral and the ipsilateral movements. This is in accordance with previous reports [5,9], and is likely to be related to the predominance of the left hemisphere in bilateral motor control in right-handers. In this regard, it is noteworthy the `bilateral' activation in the left superior parietal cortex, which con®rms and extends recent ®ndings on the involvement of this region during complex movements [6,17]. The presence of a `bilateral' population in the postcentral gyrus may be ascribed to the proposed role of the somatosensory cortex, particularly of the left (dominant) hemisphere, in sensorimotor integration [11]. This work was supported by grants from Ministero Universita' Ricerca Scienti®ca e Tecnologica, Consiglio Nazionale delle Ricerche and Azienda Policlinico di Modena (Italy). [1] Bandettini, P.A., Jesmanowicz, A., Wong, E.C. and Hyde, J.S., Processing strategies for time-course data sets in functional MRI of the human brain. Magn. Res. Med., 30 (1993) 161±173. [2] Bastings, E.P., Gage, H.D., Greenberg, J.P., Hammond, G., Hernandez, L., Santago, P., Hamilton, C.A., Moody, D.M., Singh, K.D., Ricci, P.E., Pons, T.P. and Good, D.C., Co-registration of cortical magnetic stimulation and functional magnetic resonance imaging. NeuroReport, 9 (1998) 1941±1946. [3] Chen, R., Gerloff, C., Hallett, M. and Cohen, L., Involvement of the ipsilateral motor cortex in ®nger movements of different complexities. Ann. Neurol., 41 (1997) 247±254. [4] Cox, R.W., AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput. Biomed. Res., 29 (1996) 162±173.

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