1 Center for Magnetic Resonance Research, University of Minnesota School, Minneapolis, MN, USA, 2 Department of Neuroradiology, CHU Salpêtrière, Paris, France, 3 Laboratoire de Neurophysiologie et Nouvelles Microscopies ESPCIINSERM EPI 00-02, Paris, France, 4 Max-Planck Institute of Cognitive Neuroscience, Leipzig, Germany, 5 INSERM U289, CHU Salpêtrière, Paris, France
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Abstract |
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Key Words: basal ganglia, diffusion tensor imaging, fiber tracking, human, supplementary motor area
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Introduction |
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Based on anatomical and physiological evidence in animals, the SMA has been subdivided in two distinct areas, the SMA-proper or (SMA) and the pre-SMA. Anatomically, the limit between the SMA-proper and the pre-SMA is usually defined by the VAC line, a vertical line that intersects the anterior commissure and that is perpendicular to the anterior commissureposterior commissure plane (Picard and Strick, 1996, 2001; Rizzolatti et al., 1996
). The SMA has many similarities with executive motor areas. It receives precentral and postcentral afferents from the primary motor cortex, caudal premotor areas and primary and secondary sensory areas, sends direct corticospinal efferences and projects to the primary motor cortex (Picard and Strick, 1996
). The SMA has a somatotopic organization (Picard and Strick, 1996
, 2001; Rizzolatti et al., 1996
). Comparatively, the pre-SMA is organized as an associative area. It receives its afferents from associative frontal and parietal areas, does not project to motor areas and the spinal cord and is not somatotopically organized.
Invasive tracing studies used in animals are not applicable to human studies. The anatomical cortico-basal ganglia connectivity is largely based on primate-human extrapolations and has not been demonstrated directly until now. Diffusion tensor imaging (DTI) is a new technique that allows demonstration of fiber tracts in vivo in humans (Conturo et al., 1999; Mori et al., 1999
; Basser et al., 2000
; Poupon et al., 2000
). Water diffusion in brain tissue is directionally dependent in the white matter, a property called anisotropy. Anisotropy in the white matter was attributed to the organization of axons and myelin sheaths. Diffusion is higher following the direction of axons and fiber bundles. A previous study has shown that DTI fiber tracking was able to differentiate the connections of the sensorimotor, associative and limbic compartments of the human striatum with the frontal lobes (Lehericy et al., 2004
). This study aimed to compare cortico-striatal projections from the pre-SMA, SMA and MC using diffusion tensor imaging (DTI) axonal tracking.
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Materials and Methods |
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Eight healthy right-handed volunteers were studied (three males, five females, age range 2433 years, mean 29 years). The National Ethics Committee approved the study. All subjects gave informed consent.
Imaging
DTI was performed using echo-planar imaging (EPI) at 1.5 T (GE) with standard head coil for signal reception. DTI axial slices were obtained using the following parameters: repetition time = 10 s, echo time = 88 ms, flip angle = 90°, matrix = 128 x 128, field of view = 380 x 380 mm2, slice thickness = 3 mm, no gap (3 mm isotropic voxels), acquisition time = 320 s. Four averages were used with signal averaging in the scanner buffer. Diffusion weighting was performed along six independent directions, with a b-value of 900 s/mm2. A reference image with no diffusion weighting was also obtained. High-resolution 3-D anatomical images were used for display and anatomical localization (110 axial contiguous inversion recovery three dimensional fast SPGR images, 1.5 mm thick, TI = 400 ms, FOV = 240 x 240 mm2, matrix size = 256 x 256).
Image Processing
Raw diffusion-weighted data were corrected for geometric distortion secondary to eddy currents using a registration technique based upon the geometric model of distortions (Haselgrove and Moore, 1996; Mangin et al., 2002
). Each diffusion-weighted slice was aligned with the corresponding T2-weighted image of the series. For convenience, the image was in the XY plane of the magnet axes with the phase-encoding direction along Y. The following distortion model was used: (i) residual gradient in the slice-encoding direction Z produced uniform translation along Y; (ii) residual gradient in the frequency-encoding direction X produced a shear parallel to Y (i.e. a translation linearly related to X); and (iii) residual gradient in the phase-encoding direction Y produced a uniform scaling in the Y direction. Hence, the geometric model was written for each column X as Y' = S.Y + T0 + T1.X, which amounted to a simple slice-dependent affine transformation (S is the scale factor, T0 a global translation and T1 a shear). An additional global multiplicative correction by 1/S was applied to the slice intensities, which was done after estimation of (S, T0, T1). This latest correction stemmed from an energy-conservation-based MR principle. To estimate the affine transformation, which brought a diffusion-weighted slice into spatial alignment with the standard T2-weighted slice, a similarity measure taking into account the complex dependence between intensities was chosen, the mutual information which came from information theory (Maes et al., 1997
). The optimal affine transformation (S, T0, T1) corresponded to the maximization of the mutual information between the transformed diffusion-weighted image and the reference T2-weighted image. Diffusion tensors, fractional anisotropy (FA) and fiber tracks were calculated using in-house software. The tracking algorithm employed is based on the method described in Basser et al. (2000
). At any position along the track trajectory, a diffusion tensor was interpolated and eigenvectors were computed. The eigenvector associated with the greatest eigenvalue indicated the principal direction of water diffusion. The track was propagated along this direction over a small distance (<0.5 mm) to the next point where a new diffusion tensor was interpolated. Tracking terminated when the angle between two consecutive eigenvectors was >60°, or when the FA value was <0.1, indicating a region of low diffusion anisotropy. A spherical shape marker indicated the fiber termination points. High-resolution anatomical images and DTI images were spatially co-registered to allow for the simultaneous display of tracks and anatomical images. DTI-anatomical images co-registration was performed by matching reproducible landmarks (such as the hand area in the motor cortex, the anterior commissure, the corpus callosum, the borders of the striatum) between the two images.
Anatomical Localization of Tracks
Regions-of-interests (ROIs) were determined using reproducible anatomical landmarks on high-resolution 3-D T1-weighted images (Fig. 1). ROIs were hand drawn by one experimenter (S.L.) on DTI images to avoid mis-registration effects between DTI and T1-weighted images. Three ROIs were defined in the cortex. The motor cortex (MC) included the precentral gyrus (mean ROI volume ± SD: 2422 ± 608 and 2403 ± 693 mm3 in the right and the left hemispheres, respectively). The central sulcus was located using the characteristic shape of the hand motor area or hand knob. This ROI probably included part of the adjacent posterior premotor cortex. The supplementary motor area (SMA) extended from the brain vertex to the cingulate sulcus in the supero-inferior direction and from the precentral sulcus caudally to the VAC line rostrally (mean ROI volume ± SD: 8563 ± 970 and 9084 ± 1116 mm3 in the right and the left hemispheres, respectively). The pre-SMA extended rostral to the VAC line to a virtual line passing through the genu of the corpus callosum parallel to the VAC line (Picard and Strick, 1996, 2001) (mean ROI volume ± SD: 9901 ± 1711 and 10310 ± 1237 mm3 in the right and the left hemispheres, respectively). The volumes of cortical ROIs were different (Friedman test, P < 0.001). The difference was not related to differences in volumes between the two hemispheres (Wilcoxon test). Then, right and left values were averaged. Paired comparisons (Wilcoxon test) showed that preSMA was larger than SMA (P < 0.05) and MC (P < 0.02) and SMA was larger than MC (P < 0.02). Four ROIs were defined in the striatum. These ROIs included the posterior, middle and anterior putamen and the head of the caudate nucleus (Fig. 1). In the supero-inferior direction, ROIs in the putamen extended from the superior border of the structure to the ACPC plane. The ROI corresponding to the anterior putamen included all putamen rostral to the VAC line (mean ROI volume ± SD: 783 ± 216 and 775 ± 180 mm3 in the right and the left hemispheres, respectively). The putamen caudal to the VAC line was further subdivided in two parts (middle and anterior) by a virtual line parallel to the VAC line, located at mid-distance between the VAC line and the posterior border of the putamen. The ROI corresponding to the middle putamen included the anterior half of the putamen caudal to the VAC line (mean ROI volume ± SD: 771 ± 157 and 737 ± 107 mm3 in the right and the left hemispheres, respectively). The ROI corresponding to the posterior putamen included the posterior half of the putamen caudal to the VAC line (mean ROI volume ± SD: 702 ± 175 and 675 ± 228 mm3 in the right and the left hemispheres, respectively). The ROI in the head of the caudate nucleus was located rostral to the thalamus and was limited ventrally by the ventral part of the internal capsule (mean ROI volume ± SD: 790 ± 88 and 775 ± 114 mm3 in the right and the left hemispheres, respectively). There was no significant difference between ROIs volumes in the striatum (Friedman test, P = 0.58). One ROI in the cortex (left SMA) and one ROI in the striatum (left anterior putamen) were randomly selected to assess intra-rater reliability. These ROIs were traced twice by the same experimenter (S.L.). There was no difference between the two measurements (anterior putamen: 775 ± 180 and 802 ± 165 mm3 for the first and the second measurements, respectively, P = 0.18; SMA: 9084 ± 1116 and 9219 ± 1249 mm3 for the first and the second measurements, respectively, P = 0.34). Mean FA in the subcortical ROIs ranged from 0.20 ± 0.04 in the left posterior putamen to 0.23 ± 0.03 in the left anterior putamen. There was no statistical difference in FA values between ROIs. All ROIs overlapped with adjacent white matter because of partial voluming due to the relatively low resolution of DTI images. Tracking was initiated from all seeding points in each cortical ROI. A connectivity matrix was computed, which tested for the number of tracks connecting each of the cortical ROIs to the subcortical ROIs (Conturo et al., 1999
).
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Analyses were conducted using statistical software (v. 11.0; SPSS Inc., Chicago, IL). The dependant variable was the number (n) of tracks between each of the three cortical ROIs and each of the four striatal ROIs in both hemispheres, yielding 48 different possible connections (24 possible connections between the three cortical ROIs and the four subcortical ROIs in each hemisphere and 24 possible contralateral connections). All values are expressed as mean ± SD. Statistical comparisons were performed using non-parametric procedures because of repeated violations of the assumption of distribution normality: k-related samples test (Friedman test) and when these results were significant follow-up pairwise comparisons (Wilcoxon test). Correlation analyses were performed using Spearmans r' correlation coefficient. The significance level was set at P < 0.05.
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Results |
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To determine whether the number of tracks among ipsi- or contralateral connections were equally distributed or not, Friedman tests were conducted, which were significant both for ipsilateral connections (P < 0.001) and contralateral connections (P < 0.001). Friedman tests on individual ROIs showed significant differences for connections of the MC (P < 0.001), SMA (P < 0.001), pre-SMA (P < 0.01), posterior putamen (P < 0.001), middle putamen (P < 0.001), anterior putamen (P < 0.01) and caudate nucleus (P < 0.01).
Motor Cortex
The MC was only connected to the ipsilateral striatum with unequal distribution of tracks to striatal ROIs (P < 0.001). More tracks were directed to the posterior putamen than to the middle and anterior putamen and the caudate nucleus (P < 0.02 for each comparison).
SMA
The distribution of tracks were unequal among both ipsilateral (P < 0.001) and contralateral connections (P < 0.05). The number of SMA tracks directed to the ipsilateral striatum was larger for the posterior than the middle and anterior putamen and the caudate nucleus (P < 0.02 for each comparison) and larger for the middle than the anterior putamen and the caudate nucleus (P < 0.02 for each comparison). The number of SMA tracks directed to the contralateral striatum was more important for the posterior than the middle and anterior putamen (P < 0.03 for each comparison).
Pre-SMA
Friedman test was significant (P < 0.01) only for ipsilateral connections. The number of pre-SMA tracks directed to the ipsilateral striatum was larger for the middle than the posterior and anterior putamen (P < 0.02 for each comparison) and the caudate nucleus (P < 0.03).
Posterior Putamen
Friedman tests showed differences among the numbers contralateral tracks (P < 0.01) and a trend for ipsilateral tracks (P = 0.05). Ipsilateral connections of the posterior putamen to SMA and MC were similar (P = 0.26). The posterior putamen was more connected with the SMA and MC than with the pre-SMA (P < 0.03 for each comparison). The number of contralateral connections was higher with the pre-SMA than the SMA (P < 0.03).
Middle Putamen
Distribution of tracks were unequal among both ipsilateral (P < 0.01) and contralateral connections (P < 0.01). The middle putamen was more connected to the pre-SMA than to the MC and SMA for both ipsilateral (P < 0.02 for each comparison) and contralateral hemispheres (P < 0.05 for each comparison).
Anterior Putamen
Difference in the distribution of tracks to both ipsilateral (P = 0.09) and contralateral hemispheres (P = 0.06) did not reach significance, thus no further statistical analysis was conducted.
Caudate Nucleus
Distribution of tracks were unequal among both ipsilateral (P < 0.05) and contralateral connections (P < 0.03). The caudate nucleus was more connected to the ipsilateral pre-SMA than SMA (P < 0.05) and MC (P < 0.06) and was more connected to the contralateral pre-SMA than MC (P < 0.05).
For all striatal regions, absence of contralateral connection to the MC yielded significant differences when compared to pre-SMA (P < 0.05 for each comparison). When compared to SMA, a significant difference was only detected for the posterior putamen.
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Discussion |
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Pre-SMA projections were mainly directed to anterior parts of the striatum extending caudal to the AC in the middle portion of the putamen and almost no track was found in the caudal tier of the putamen. In contrast, SMA projections predominated in the caudal tier of the putamen, fewer tracks were found in the middle portion of the putamen and almost no fiber was found in the anterior striatum. Similarly to SMA projections, the MC projected to the posterior putamen with only few tracks to the middle portion of the putamen. This pattern was highly concordant with monkey studies (Kunzle, 1978; Selemon and Goldman-Rakic, 1985
; Parthasarathy et al., 1992
; Inase et al., 1996
, 1999; Takada et al., 1998
). In the macaque monkey, cortico-striatal inputs from pre-SMA were distributed mainly in the striatal cell bridges connecting the rostral aspects of the caudate nucleus and the putamen and in the neighboring striatal areas (Inase et al., 1999
). In this study, although SMA and pre-SMA projections were found on the same coronal slices at the level of the AC and on the slices immediately caudal to the AC, they did not overlap (Inase et al., 1999
). In the present study, spatial resolution was not high enough to determine whether these tracks are separated in the middle portion of the putamen. In monkeys, MC projections were located in comparable portions of the posterior putamen, distributing from the level of the AC to the most posterior extent of the putamen (Inase et al., 1996
). The present study also confirms that SMA and MC tracks end in territories in the striatum that are largely overlapped, as already reported in monkeys (Inase et al., 1996
).
Results show that SMA projections to the striatum were bilateral but largely predominated in the ipsilateral hemisphere. Pre-SMA projections to the contralateral striatum were larger than SMA projections to the contralateral striatum. No fiber originating from the MC was directed to the contralateral striatum. Overall, these results are in line with monkey studies. In monkeys, both the SMA and pre-SMA send bilateral projections to the striatum (McGuire et al., 1991a,b; Wiesendanger et al., 1996
; Inase et al., 1999
), although these projections predominate in the ipsilateral hemisphere (McGuire et al., 1991a
,b; Inase et al., 1996
, 1999; Wiesendanger et al., 1996
). Similarly to the present findings, the pre-SMA had more transcallosal connections than the SMA (Liu et al., 2002
). In contrast to the present findings, a small fraction of motor cortical areas projected contralaterally via the corpus callosum although most connections projected to ipsilateral subcortical structures (Flaherty and Graybiel, 1993
; Wiesendanger et al., 1996
). This difference with animal studies may reflect an anatomical variability in cortico-striatal connections in humans as compared to monkeys or more likely it may result from a failure of DTI fiber tracking to detect crossed tracks coming from the motor cortex. Fiber direction estimated with DTI is the average of all fiber directions within each voxel. When fiber tracts cross, kiss, kink, merge or diverge within one voxel, then the eigenvector associated with the largest eigenvalue of the diffusion tensor corresponds to the average of these fiber directions in the voxel. The complexity of fiber directions in the frontal lobe may prevent the detection of crossed motor cortex tracks. Increased spatial resolution or improved fiber tracking method may help overcome this limitation.
Overall, there was no correlation between ROI volumes and the number of cortical tracks projecting to striatal ROIs, except that larger pre-SMA volume was associated with a larger number of tracks to the anterior putamen and that larger posterior putamen volume was associated with a larger number of tracks to the SMA. There was no significant difference in the number tracks that intersected the striatum between the three cortical ROIs in line with monkey studies (Inase et al., 1996), although sizes of these ROIs were different. Thus, ROI volume was not a factor explaining the general pattern of cortico-subcortical connectivity, e.g. the predominant connections of the MC and SMA to the posterior putamen and of the pre-SMA to more rostral parts of the putamen.
This anatomic organization of SMA and pre-SMA connections is paralleled by functional differences (Picard and Strick, 1996, 2001; Rizzolatti et al., 1996
; Tanji, 1996
). In monkeys, the pre-SMA is involved in higher-order aspects of motor control (Picard and Strick, 1996
; Tanji, 1996
). Motor-related activation occurred mainly in the SMA, whereas neurons with preparatory activity are located more rostrally in the pre-SMA (Alexander and Crutcher, 1990
; Romo and Schultz, 1992
). Similarly, motor-related activation occurred mainly in the putamen caudal to the anterior commissure, whereas neurons with working-memory and preparatory activity are located more rostrally in the anterior part of the striatum (Alexander and Crutcher, 1990
). In humans, functional imaging studies have shown that the pre-SMA has an important role in supramotor activities such as visuo-motor associations, learning, selection, preparation and sequencing of movements (Colebatch et al., 1991
; Deiber et al., 1991
, 1996; Rao et al., 1993
; Humberstone et al., 1997
; Hikosaka et al., 1999
; Sakai et al., 1999
), whereas the SMA along with the motor cortex is more closely related to movement execution (Deiber et al., 1996
; Jenkins et al., 2000
; Krainik et al., 2001
). For example, SMA activation observed during movement preparation was located more rostrally than during movement execution (Deiber et al., 1996
; Humberstone et al., 1997
; Toni et al., 1999
). Similarly, activation in the putamen during preparation was rostral to the one observed during movement execution (Jenkins et al., 2000
; Lehericy and Gerardin, 2002
). Our data provide anatomical support for the observation that preparatory and executive aspects of movements are conveyed in distinct cortico-striatal circuits.
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Notes |
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Address correspondence to Stéphane Lehéricy, CMRR, 2021 6th Street SE, Minneapolis, MN 55455, USA. Email: lehericy{at}cmrr.umn.edu.
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References |
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---|
Alexander GE, DeLong, MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357381.[CrossRef][ISI][Medline]
Basser PJ, Pajevic S, Pierpaoli C, Duda J, Aldroubi A (2000) In vivo fiber tractography using DT-MRI data. Magn Reson Med 44:625632.[CrossRef][ISI][Medline]
Colebatch JG, Deiber MP, Passingham RE, Friston KJ, Frackowiak RS (1991) Regional cerebral blood flow during voluntary arm and hand movements in human subjects. J Neurophysiol 65:13921401.
Conturo TE, Lori NF, Cull TS, Akbudak E, Snyder AZ, Shimony JS, McKinstry RC, Burton H, Raichle ME (1999) Tracking neuronal fiber pathways in the living human brain. Proc Natl Acad Sci USA 96:1042210427.
Deiber MP, Passingham RE, Colebatch JG, Friston KJ, Nixon PD, Frackowiak RS (1991) Cortical areas and the selection of movement: a study with positron emission tomography. Exp Brain Res 84:393402.[ISI][Medline]
Deiber MP, Ibanez V, Sadato N, Hallett M (1996) Cerebral structures participating in motor preparation in humans: a positron emission tomography study. J Neurophysiol 75:233247.
Flaherty AW, Graybiel AM (1991) Corticostriatal transformations in the primate somatosensory system. Projections from physiologically mapped body-part representations. J Neurophysiol 66:12491263.
Flaherty AW, Graybiel AM (1993) Two input systems for body representations in the primate striatal matrix: experimental evidence in the squirrel monkey. J Neurosci 13:11201137.[Abstract]
Haselgrove JC, Moore JR (1996) Correction for distortion of echo-planar images used to calculate the apparent diffusion coefficient. Magn Reson Med 36:960964.[ISI][Medline]
Hikosaka O, Nakahara H, Rand MK, Sakai K, Lu X, Nakamura K, Miyachi S, Doya K (1999) Parallel neural networks for learning sequential procedures. Trends Neurosci 22:464471.[CrossRef][ISI][Medline]
Humberstone M, Sawle GV, Clare S, Hykin J, Coxon R, Bowtell R, Macdonald IA, Morris PG (1997) Functional magnetic resonance imaging of single motor events reveals human presupplementary motor area. Ann Neurol 42:632637.[ISI][Medline]
Inase M, Sakai ST, Tanji J (1996) Overlapping corticostriatal projections from the supplementary motor area and the primary motor cortex in the macaque monkey: an anterograde double labeling study. J Comp Neurol 373:283296.[CrossRef][ISI][Medline]
Inase M, Tokuno H, Nambu A, Akazawa T, Takada M (1999) Corticostriatal and corticosubthalamic input zones from the presupplementary motor area in the macaque monkey: comparison with the input zones from the supplementary motor area. Brain Res 833:191201.[CrossRef][ISI][Medline]
Jenkins IH, Jahanshahi M, Jueptner M, Passingham RE, Brooks DJ (2000) Self-initiated versus externally triggered movements. II. The effect of movement predictability on regional cerebral blood flow. Brain 123:12161228.
Krainik A, Lehericy S, Duffau H, Vlaicu M, Poupon F, Capelle L, Cornu P, Clemenceau S, Sahel M, Valery CA, et al. (2001) Role of the supplementary motor area in motor deficit following medial frontal lobe surgery. Neurology 57:871878.
Kunzle H (1975) Bilateral projections from precentral motor cortex to the putamen and other parts of the basal ganglia. An autoradiographic study in Macaca fascicularis. Brain Res 88:195209.[CrossRef][ISI][Medline]
Kunzle H (1978) An autoradiographic analysis of the efferent connections from premotor and adjacent prefrontal regions (areas 6 and 9) in Macaca fascicularis. Brain Behav Evol 15:185234.[ISI][Medline]
Lehericy S, Gerardin E (2002) Normal functional imaging of the basal ganglia. Epileptic Disord 4:S2330.[ISI][Medline]
Lehericy S, Ducros M, van de Moortele PF, Francois C, Thivard L, Poupon C, Swindale N, Ugurbil K, Kim DS (2004) Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans. Ann Neurol 55:522529.[CrossRef][ISI][Medline]
Liu J, Morel A, Wannier T, Rouiller EM (2002) Origins of callosal projections to the supplementary motor area (SMA): a direct comparison between pre-SMA and SMA-proper in macaque monkeys. J Comp Neurol 443:7185.[CrossRef][ISI][Medline]
McGuire PK, Bates JF, Goldman-Rakic PS (1991a) Interhemispheric integration: I. Symmetry and convergence of the corticocortical connections of the left and the right principal sulcus (PS) and the left and the right supplementary motor area (SMA) in the rhesus monkey. Cereb Cortex 1:390407.[Abstract]
McGuire PK, Bates JF, Goldman-Rakic PS (1991b) Interhemispheric integration: II. Symmetry and convergence of the corticostriatal projections of the left and the right principal sulcus (PS) and the left and the right supplementary motor area (SMA) of the rhesus monkey. Cereb Cortex 1:408417.[Abstract]
Maes F, Collignon A, Vandermeulen D, Marchal G, Suetens P (1997) Multimodality image registration by maximization of mutual information. IEEE Trans Med Imaging 16:187198.[CrossRef][ISI][Medline]
Mangin JF, Poupon C, Clark C, Le Bihan D, Bloch I (2002) Distortion correction and robust tensor estimation for MR diffusion imaging. Med Image Anal 6:191198.[CrossRef][ISI][Medline]
Mori S, Crain BJ, Chacko VP, van Zijl PC (1999) Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 45:265269.[CrossRef][ISI][Medline]
Parent A, Hazrati LN (1995a) Functional anatomy of the basal ganglia. I. The cortico-basal gangliathalamo-cortical loop. Brain Res Brain Res Rev 20:91127.[ISI][Medline]
Parent A, Hazrati LN (1995b) Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev 20:128154.[ISI][Medline]
Parthasarathy HB, Schall JD, Graybiel AM (1992) Distributed but convergent ordering of corticostriatal projections: analysis of the frontal eye field and the supplementary eye field in the macaque monkey. J Neurosci 12:44684488.[Abstract]
Picard N, Strick PL (1996) Motor areas of the medial wall: a review of their location and functional activation. Cereb Cortex 6:342353.[Abstract]
Picard N, Strick PL (2001) Imaging the premotor areas. Curr Opin Neurobiol 11:663672.[CrossRef][ISI][Medline]
Poupon C, Clark CA, Frouin V, Regis J, Bloch I, Le Bihan D, Mangin J (2000) Regularization of diffusion-based direction maps for the tracking of brain white matter fascicles. Neuroimage 12:184195.[CrossRef][ISI][Medline]
Rao SM, Binder JR, Bandettini PA, Hammeke TA, Yetkin FZ, Jesmanowicz A, Lisk LM, Morris GL, Mueller WM, Estkowski LD, et al. (1993) Functional magnetic resonance imaging of complex human movements. Neurology 43:23112318.[Abstract]
Rizzolatti G, Luppino G, Matelli M (1996) The classic supplementary motor area is formed by two independent areas. Adv Neurol 70:4556.[ISI][Medline]
Romo R, Schultz W (1992) Role of primate basal ganglia and frontal cortex in the internal generation of movements. III. Neuronal activity in the supplementary motor area. Exp Brain Res 91:396407.[ISI][Medline]
Sakai K, Hikosaka O, Miyauchi S, Sasaki Y, Fujimaki N, Putz B (1999) Presupplementary motor area activation during sequence learning reflects visuo-motor association. J Neurosci 19:RC1.
Selemon LD, Goldman-Rakic PS (1985) Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. J Neurosci 5:776794.[Abstract]
Takada M, Tokuno H, Nambu A, Inase M (1998) Corticostriatal input zones from the supplementary motor area overlap those from the contra- rather than ipsilateral primary motor cortex. Brain Res 791:335340.[CrossRef][ISI][Medline]
Tanji J (1996) New concepts of the supplementary motor area. Curr Opin Neurobiol 6:782787.[CrossRef][ISI][Medline]
Toni I, Schluter ND, Josephs O, Friston K, Passingham RE (1999) Signal-, set- and movement-related activity in the human brain: an event-related fMRI study. Cereb Cortex 9:3549.
Wiesendanger M, Rouiller EM, Kazennikov O, Perrig S (1996) Is the supplementary motor area a bilaterally organized system? Adv Neurol 70:8593.[ISI][Medline]