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			![]() J. Biomedical Science and Engineering, 2009, 2, 30-35  Published Online February 2009 in SciRes. http://www.scirp.org/journal/jbise                               JBiSE  Investigating connectional characteristics of  motor cortex network*  Dong-Mei Hao1, Ming-Ai Li2  1School of Life Science and Bioengineering. 2School of Electronic Information and Control Engineering, Beijing University of Technology, Beijing 100124,  China. Correspondence should be addressed to Dong-Mei Hao (haodongmei@bjut.edu.cn)  Received September 10th, 2008; revised November 12th, 2008; accepted December 11th, 2008  ABSTRACT  To understand the connectivity of cerebral cor- tex, especially the spatial and temporal pattern  of movement, functional magnetic resonance  imaging (fMRI) during subjects performing finger  key presses was used to extract functional  networks and then investigated their character- istics. Motor cortex networks were constructed  with activation areas obtained with statistical  analysis as vertexes and correlation coefficients  of fMRI time series as linking strength. The  equivalent non-motor cortex networks were  constructed with certain distance rules. The  graphic and dynamical measures of motor cor- tex networks and non-motor cortex networks  were calculated, which shows the motor cortex  networks are more compact, having higher sta- tistical independence and integration than the  non-motor cortex networks. It indicates the  motor cortex networks are more appropriate for  information diffusion.  Keywords: Motor Cortex Network, Connectivity,  Correlation Coefficient, Functional Magnetic  Resonance Imaging (fMRI), Activation Area  1. INTRODUCTION  Neuroanatomical studies have revealed a large number  of connections linking different brain structures. There is  a wealth of information about the patterning and func- tional impact of connection pathways linking segregated  areas of the cerebral cortex. The brain consists of net- works of highly interconnected regions, coordinating  major aspects of behaviour. The brain is inherently a  dynamic system, in which the traffic between regions,  during behavior or even at rest, creates and reshapes  continuously complex functional networks of correlated  dynamics [1]. The cerebral motor cortex which is closely  associated with movement is innervated by a number of  anatomical and functional connections.  Over recent years, neurophysiological and neuroi- maging experiments as well as detailed computer simu- lations of neuronal networks have contributed to our  understanding of the neural mechanisms generating  functional connectivity. Functional magnetic resonance  imaging (fMRI) is a non-invasive and widely available  technique for mapping brain functions. It is based upon  the blood oxygenation level-dependent (BOLD) effect.  As concerns the motor system, the available functional  imaging studies indicate a mass activation effect within  the hand representation area during finger-tapping or  finger-to-thumb opposition tasks in terms of either a  stepwise or a linear function between movement rate and  hemodynamic response [2].  Some computational approaches such as covariance  structural equation modelling (SEM) aim at inferring  causal relations between brain areas from their pattern of  covariance, by extracting networks of effective connec- tivity [3]. Dynamic causal modelling (DCM) character- izes the dynamics of interactions among states of brain  regions with bilinear approximations of intrinsic cou- pling among neuronal states and the influence of exter- nal inputs [4]. Granger causality mapping (GCM) ex- tends the vector autoregressive (VAR) technique to cap- ture interactions among brain regions, assuming a causal  and dynamic system of linear interactions, driven by  stochastic innovations [5]. A graphical approach linking  the notions of graphical models and Granger causality  has been applied to describe dynamic dependencies in  neural systems [6, 7]. Several principled approaches  such as non-metric multidimensional scaling [8], hierar- chical analysis [9] and cluster analysis [10] have been  used to derive numerical descriptions of the organization  of the network from neuroanatomical connection data.  Using basic and general concepts from information the- ory, entropy and mutual information, O. Sporns et al.  have developed a theoretical measure that captures the  interplay of functional segregation and integration within  a given system [11]. A close look at the anatomical and  functional organization of the cerebral cortex provides  important clues for formulating a potential general  mechanism for neural integration.  In this paper we present our current research investi- gating the connectivity of the motor system, the network  underlying the generation of movement. We propose a  *This work was supported by the National Natural Science Foundation  of China (30670543).  SciRes Copyright © 2009  ![]() D. M. Hao et al. / J. Biomedical Science and Engineering 2 (2009) 30-35               31  SciRes Copyright © 2009                                                               JBiSE  method to extract motor networks and non-motor net- works, as revealed by fMRI when humans perform fin- ger tasks, and then analyze them in the context of the  current understanding of complex networks.  2. MATERIALS AND METHODS  Considering the multiple processes taking place at dif- ferent brain regions and interacting with one another in  executing a specific task, extracting brain connectivity  from fMRI data facilitates our understanding of brain  function. The states of activated brain regions are fully  observed as intensity variations of fMRI time-series.  2.1. Data Acquisition  The fMRI data center [12] afforded the fMRI data sub- mitted by Kathleen Y. Haaland [13]. Fourteen healthy  right-handed volunteers between the ages of 20 and 40  participated in this study. Subjects performed finger key  presses in response to numeric sequences presented  visually on the screen. The index (“1”), middle (“2”),  and ring (“3”) fingers of the right or left hand were  placed on response keys. Two sequence conditions were  used. The simple condition required repetition of one of  three sequences (i.e., 11111, 22222, or 33333) and the  complex condition consisted of heterogeneous sequences  (i.e., 12131, 23231, or 32321). Each 3-sec trial began  with the appearance of a five-digit number sequence  presented vertically on the screen for 2.5 sec, cueing  subjects to immediately perform the sequence as quickly  and accurately as possible. The task paradigm consisted  of ten 12-s epochs alternating between rest and activa- tion.  Functional MRI was obtained on a 1.5-T General  Electric Signa scanner. Echo-planar (EP) images were  collected using a single-shot, blipped, gradient echo EP  pulse sequence: echo time (TE)=40 msec, data acquisi- tion time =40 msec, field of view (FOV)=24 cm, resolu- tion=64×64. Twenty-two contiguous sagittal 6-mm thick  slices provided coverage of the entire brain (voxel size:  3.75×3.75×7mm). Prior to functional imaging, high-  resolution 3-D spoiled gradient-recalled at steady-state  anatomic images were collected: TE =5 msec, repetition  time (TR)=24 msec, 40° flip angle, number of excitations  =1, slice thickness=1.2 mm, FOV=24 cm, resolution=256×  128. Refer to [13] for detail.  2.2. Motor Cortex Network, MCN  fMRI data were analyzed using SPM5 (Welcome De- partment of Cognitive Neurology, London, UK) and  MATLAB 7 (The Mathworks Inc.) for all subjects. The  first six images of each time series were discarded to  eliminate signal intensity variations arising from pro- gressive saturation. Echo-planar images were realigned  to the first functional image of each time series to re- move residual head movement. The functional images of  each subject were coregistered with the mean functional  image from realignment, normalized to MNI (Montreal  Neurological Institute) standard space and spatially  smoothed using a Gaussian filter of 6 mm FWHM. First  level analysis of each individual was conducted;  one-tailed Student t-tests were used to identify brain  regions most responsive for finger key presses. The  maximum intensity projection of the statistical map and  coordinates in MNI space for each maximum were ob- tained.  We define the maximum intensity voxels (activation  areas) as vertexes of a motor cortex network (MCN).  The activity of voxel x at time t is denoted as V(x, t)  after fMRI pre-processing. We calculate the linear cor- relation coefficient between any pair of voxels, x1 and x2  as formula (1), where 222 ),(),())(( 〉〈−〉〈= txVtxVxV σ ,  〈 •〉   represents temporal averages. The correlation coefficient  is used as the connection strength or weight between  these two nodes. Therefore MCN is constructed with  motor association cortices as vertexes and their correla- tion coefficients as linking weights.  ))(())(( ),(),(),(),( ),( 21 2121 21 xVxV txVtxVtxVtxV xxr σσ 〉〈〉〈−〉〈 =  (1)  2.3. Non-motor Cortex Network, Non-MCN  The equivalent non-motor cortex network composes of k  vertexes which were generated randomly in the spatial  coordinates range of cerebral cortex and were far away  from (greater than threshold) any vertex in MCN. Sup- pose (xn, yn, zn) is a voxel coordinates in non-motor cor- tex and (xmi , ymi, zmi) is the i voxel coordinates in motor  cortex. For all i (i=1…k), it satisfies the following con- dition :  thredzzyyxx minminmin >−+−+− 222 )()()(     (2)  Therefore non-MCN was constructed with k voxels as  nodes and the correlation coefficients among them ac- cording to formula (1) as connection strength.  2.4. Measures of the Brain Functional Network  Structural aspects are captured using concepts and  measures provided by graph theory. All structural analy- ses are performed on the network’s connection matrix,  which provides a complete description of all connections  and pathways between the network’s individual units.  Functional connectivity which is the temporal correla- tion between remote neurophysiological events can be  reflected by information theory.  z Density [14]  Density is defined as the sum of the ties divided by  the number of possible ties (i.e. the ratio of all tie  strength that is actually present to the number of possible  ties). The density of a network may give us insights into  such phenomena as the speed at which information dif- fuses among the nodes, and the extent to which nodes  have high levels of communicating capital and /or com- municating constraint.  z Characteristic path length: lpath  lpath is the global mean of the lengths of the shortest  path linking any pairs of nodes, and can be used to de- scribe the connectivity of a network.  ![]() 32                  D. M. Hao et al. / J. Biomedical Science and Engineering 2 (2009) 30-35  SciRes Copyright © 2009                                                                   JBiSE  z System entropy [11]  The cerebral cortex networks are implemented as dy- namical system. The neural activities can be described as  a Gaussian multidimensional stationary stochastic proc- ess. The network units interact with each other and devi- ate from statistical independence through connections.  The entropy H(X) of a system measures its overall de- gree of independence. Assuming stationarity, the entropy  of a system X composed of n units is computed as for- mula (3) with⋅indicating the matrix determinant. COV  is the covariance matrix of the system and can be ob- tained analytically from the connection matrix  ))()2ln((5.0)( XCOVeXH n π =        (3)  z Integration I(X) [11]  The integration I(X) measures the overall degree to  which a system deviates from statistical independence.  This measure is derived as the difference between entro- pies of the individual components of X, considered in- dependently, and the entropy H(X) of the entire system:  )()()( 1 XHxHXI n i i−= ∑ =               (4)  3. RESULTS  We analyzed the fMRI data of 14 subjects with finger  key presses task. 4 subjects had only one activation area  in the simple condition, 3 subjects had none or only one  activation area in the complex condition. Therefore we  only studied the other 10 subjects in the simple condition  and 11 subjects in the complex condition, and con- structed a MCN and 50 non-MCNs for each of  them.Figure 1 is an example of SPM showing bilateral  activation of motor cortex of subject 5, in which (a) is  the left hand simple condition and (b) is the left hand  complex condition. It lists all clusters above the chosen  level of significance with details of significance thresh- olds. Figure 2 shows the motor cortex networks (MCNs)  of the same subject in left hand simple and complex  conditions. A vertex indicates an activation area, a line  indicates a bidirectional connection, and the thicker a  line is, the stronger a connection is. Figure 3 shows the  non-motor cortex networks (non-MCNs) of the left hand  simple and complex conditions for subject 5. A vertex  representing a non-activation area is at least 15mm apart  from the activation area according to experience [15],  and a thicker line also indicates a stronger connection. In  Figure 2 (a) vertex 1, 3, 9, 10 locate in BA10 (Brodmann  Area), vertex 2 in BA6, vertex 4 in BA10, vertex 5, 8 in  BA32, vertex 6, 7 in BA47, vertex 11 in BA7, vertex 12  in BA11, vertex 13 in BA22, vertex 14 in BA18; (b)  vertex 1, 2 locate in BA8, vertex 3, 8 in BA47, vertex 4  in BA11, vertex 6 in BA10, vertex 7 in BA9, vertex 10  in BA46, vertex14 in BA31 using Talairach Client 2.4  (Research Imaging Center, University of Texas Health  Science Center at San Antonio) [16]. We calculated the  average characteristic parameters of 50 non-MCNs and  compared them with the corresponding MCNs for each  subject in the simple and complex conditions, see Figure  4 and Figure 5, in which “*” indicates a MCN and “º”  indicates a non-MCN. We noticed the density (p=0.000), (a) left hand simple condition (b) left hand complex condition  Figure 1. SPM showing activation of motor cortex  SPMmip  [0,0,0]  SPMmip  [-26.25,33.75,60]  \ s05_epi_r01_LS  H eigh t thr es ho ldT=4.996301   {P<0.05(FWE)}  Ex ten t thr es ho ld k=0 v ox els  \ s05_epi_r01_LS Height threshold T=4.920125   {P<0.05(FWE)} Extent threshold k=0 v oxels  Table shows 3 local maxima more than 8.0mm apart  Height threshold: T = 5 . 00, p = 0.000 (0.050) {p<0.05 (FWE)}  Extent threshold: k = 0 voxels, p = 1.000 (0.050)  Expected voxels per cluster, <k> = 0.381  Expected number of clusters, <c> = 0.13  Expected false discovery rate, <= 0.00  Degrees of freedom = [1.0, 55.0]  FWHM = 10.8 10.0 10.7 mm mm mm; 2.9 2.7 1.8 {voxels};  Volume: 1344516; 15935 voxels; 982.5 resels  Voxel size: 3.8 3.8 6.0 mm mm mm; (resel = 13.65 voxels)  Page 1  Table shows 3 local maxima more than 8.0mm apart  Height threshold: T = 4.92, p = 0.000 (0.050) {p<0.05 (FWE)} Extent threshold: k = 0 voxels, p = 1.000 (0.050) Expected voxels per cluster, <k> = 0.409  Expected number of clusters, <c> = 0.12  Expected false discovery rate, <= 0.00 Degrees of freedom = [1.0, 55.0]  FWHM = 10.6 10.2 10.9 mm mm mm; 2.8 2.7 1.8 {voxels};    Volume: 1025747; 12157 voxels; 717.6 resels  Voxel size: 3.8 3.8 6.0 mm mm mm; (resel = 14.00 voxels)  ![]() D. M. Hao et al. / J. Biomedical Science and Engineering 2 (2009) 30-35               33  SciRes Copyright © 2009                                                               JBiSE  (a) left hand simple condition (b) left hand complex condition  Figure 2. Cerebral motor cortex networks  (a) left hand simple condition (b) left hand complex condition  Figure 3. Cerebral non-motor cortex networks  characteristic path length (p=0.000), system entropy  (p=0.000) and integration (p< MCNs are all significant  different from those of non-MCNs regardless of the sim- ple or complex condition. In Figure 6, we compared  some features of MCNs in the simple and complex condi- tion. “*” indicates a MCN in the simple condition and “º”  indicates a MCN in the complex condition. The density  (p=0.668), characteristic path length (p=0.728), system  entropy (p=0.411) and integration (p=0.243) in the simple  condition have no significant difference from those in the  complex condition.  3. DISCUSSION  As shown in Figure 2 and Figure 3, MCNs have denser  and stronger connections than non-MCNs. In Figure 4 and  Figure 5, the density of MCNs are much larger than that of  non-MCNs and the characteristic path length of MCNs are  much shorter than that of non-MCNs. It indicates the infor- mation such as motor strategy, spatial-temporal arrangement  and sensorimotor message can diffuse among motor regions  with high speed and high level. The entropy and integration  of MCNs are larger than those of non-MCNs, which indi- cate MCNs have higher overall degree of statistical inde- pendence than non-MCNs and at the same time there are  more statistical dependencies among the motor regions. We  can deduce that in our experiment, the simple task and the  complex task are at the same cognitive level and therefore  have similar functional connectivity patterns for healthy  subjects. It is different from other studies [17] in which  complex movement increases activity in regions and in- volvement of areas. Therefore how to define complexity in  an experiment context is to be considered.  Movement is an essential part of our daily life activi- ties and the movement handicapped cannot lead produc- tive independent lives due to inability to control their  activities of daily living. We attempt to understand the  ![]() 34                  D. M. Hao et al. / J. Biomedical Science and Engineering 2 (2009) 30-35  SciRes Copyright © 2009                                                                   JBiSE  01 234 567 8910 0 0. 1 0. 2 0. 3 0. 4 0. 5 0. 6 0. 7 0. 8 0. 9 1 Densi ty Subject No. Network in left hand simple condition 01 23 456 78 910 0 0. 1 0. 2 0. 3 0. 4 0. 5 0. 6 0. 7 0. 8 0. 9 1 Lpath Subject No. <*>motor, <o>non-motor 01 234 567 8910 0 10 20 30 40 50 Entropy Subject No. 01 23 456 78 910 0 5 10 15 Integration Subject No. Figure 4. Characteristics comparison of MCNs and non-MCNs in hand simple condition  0 123 45 67891011 0 0. 1 0. 2 0. 3 0. 4 0. 5 0. 6 0. 7 0. 8 Dens it y Subject No. Network in left hand complex condition 0 1234 56 7891011 0. 2 0. 3 0. 4 0. 5 0. 6 0. 7 0. 8 0. 9 1 Lpath Subject No. <*>motor, <o>non-motor 0 123 45 67891011 0 20 40 60 E ntropy Subject No. 0 1234 56 7891011 0 5 10 15 20 Integration Subject No. Figure 5. Characteristics comparison of MCNs and non-MCNs in left hand complex condition  ![]() D. M. Hao et al. / J. Biomedical Science and Engineering 2 (2009) 30-35               35  SciRes Copyright © 2009                                                               JBiSE  012345678910 0. 4 0. 5 0. 6 0. 7 0. 8 0. 9 1 Density Subject No. Network in left hand simple and complex condition 0123 45678910 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Lpath Subject No. <*>simple, <o>complex 012345678910 0 20 40 60 Entropy Subject No. 0123 45678910 0 5 10 15 20 Integration Subject No. Figure 6. Characteristics comparison of MCNs in left hand simple and complex conditions  features of motor cortex networks with some statistical  measures, which may be associated with movement  generation and information transfer and help to study the  motor skills disruption and rehabilitation.  ACKNOWLEDGEMENTS  The authors’ work was supported by grants from the National Natural  Science Foundation of China (30670543). The data sets were sup- ported by fMRIDC (The fMRI Data Center, Dartmouth College, http://  www. fmridc.org, accession number: 2-2003-114E5).  REFERENCES  [1] V. M. Eguíluz, D. R. Chialvo, G. A. Cecchi et al. (2005)  Scale-Free Brain Functional Networks. Physical Review Letters,  14 January: 018102-1~018102-4.  [2] A. Riecker, D. Wildgruber, K. Mathiak et al. (2003) Parametric  analysis of rate-dependent hemodynamic response functions of  cortical and subcortical brain structures during auditorily cued  finger tapping: a fMRI study. NeuroImage, 18: 731-739.  [3] J. C. 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