Document Type : Full Research Paper


1 Assisstant Professor, Electrical Engineering Department, Faculty of Engineering, University of Neyshabur

2 Associate Professor, Electrical and Computer Engineering Department, Tarbiat Modares University

3 Assisstant Professor of Statistics, Department of Mathematics, Faculty of Science, Ilam University



Functional changes in the brain motor network are responsible for the major clinical features of Parkinson’s disease (PD). Recent studies on investigation of the brain function show that there are spontaneous fluctuations between regions at rest as resting state network affected in various disorders. In this paper, we examine changes of functional dependency between brain regions of interest associated with known anatomical pathology in Parkinson Disease (PD) using copula theory on resting state fMRI. Five types of copulas were tested: Gaussian and t (Euclidean), Clayton, Gumbel and Frank (Archimedean). We used an efficient maximum likelihood procedure for estimating copula parameters. Goodness of fits was tested using root mean square error (RMSE) and kulback-leibler divergence between each copula function and joint empirical cumulative distribution. Control vs PD group comparison was also done on dependency parameter using parametric and nonparametric tests. The results show that functional dependency between cerebellum and basal ganglia is much stronger in PD than in control. In this paper, we proposed for the first time that joint distribution characteristics could potentially provide information on discriminative features for functional connectivity analysis between healthy and patients.


Main Subjects

[1]     J. P. Sieb, W. KÖhler, “Benefits from Sustained-release Pyridostigmine Bromide in Myasthenia Gravis: Results of a Prospective Multicenter Open-label Trial” Clin Neurol Neurosurg 112, 781–784, 2010.
[2]     R. A. Maselli, J. D. Henderson, J. Ng, D. Follette, G. Graves G, B. W. Wilson, “Protection of Human Muscle Acetylcholinesterase from Soman by Pyridostigmine Bromide” Muscle Nerve 43, 591–595, 2011.
[3]     Q. Y. Tan, M. L. Xu, J. Y. Wu, H. F. Yin, J. Q. Zhang, “Preparation and Characterization of Poly (lactic acid) Nanoparticles for Sustained Release of Pyridostigmine Bromide” Pharmazie 67 (4), 311-8, 2012.
[4]     N. Hegazy, M. Demirel, Y. Yazan, “Preparation and in vitro evaluation of pyridostigmine bromide microparticles” Int J Pharm 242, 171–174, 2002.
[5]     Y. Huang, T. Tsai, C. Cheng, T. Cham, “Formulation Design of a Highly Hygroscopic Drug (Pyridostigmine Bromide) for its Hygroscopic Character Improvement and Investigation of In vitro/In vivo Dissolution Properties” Drug Dev Ind Pharm, 33, 403–416, 2007.
[6]     N. Bolourchian, M. Rangchian, M. Foroutan, “Prolonged Release Matrix Tablet of Pyridostigmine Bromide: Formulation and Optimization Using Statistical Methods” Pak J Pharm Sci 25, 607-616, 2012.
[7]     Q. Tan, R. Jiang, M. Xu, G. Liu, S. Li, J. Zhang, “Nanosized sustained-release pyridostigmine bromide microcapsules: process optimization and evaluation, of characteristics” Int J Nanomed 8, 737-745, 2013.
[8]     S. Bagheri-Khoulenjani, H. Mirzadeh, M. Etrati-Khosroshahi, “Chitosan and Nanohydroxyapatite Roles in Physical and Chemical Characteristics of Gelatin/Chitosan/Nanohydroxyapatite Microspheres” Iran J Polym Sci Technol 23(6), 487-498, 2011.
[9]     S. Bagheri-Khoulenjani, S. M. Taghizadeh, H. Mirzadeh, “An Investigation on the Short-Term biodegradability of Chitosan with Various Moleculare Weight and Degree of Deacetylation” Carbohyd Polym 78, 773-778, 2009.
[10] L. Y. Jiang, Y. B. Li, X. J. Wang, L. Zhang, J. Q. Wen, M. Gong, “Preparation and Properties of Nano-hydroxy apatite/Chitosan/Carboxymethyl Cellulose Composite Scafoold” Carbohyd Polym 74, 680-684, 2008.
[11] F. Naimian, F. Khoylo, R. Beteshobabrud, “The Role of Solvent on Radiation Degradation and Antibacterial Activity of Chitosan Against Pectobacterium Carotovorum” Iran J Polym Sci Technol 23 (4), 305-310, 2010.
[12] H. Mirzadeh, F. Hormozi, M. A. Mohagheghi, N. Yaghobi, S. Amanpour, H. Ahmadi, “Preparation of Chitosan Derived from Shrimps Shell of Persian Gulf as a Blood Hemostasis Agent” Iran Polym J 11, 63-68, 2002.
[13] S. M. Taghizadeh, G. Davari, “Study on Mucoadhesion Properties of Xhitosan” Iran J Polym Sci Technol 20, 515-519, 2007.
[14]  Y. Mohamadi, H. Mirzadeh, F. Moztarzadeh, M. Soleimani, E. Jabbari, “Osteogenic Differentiation of Mesenchymal Stem Cells on Novel Three-Dimentional Poly (L-Lactic Acid) /Chitosan /Gelatin /Beta-Tricalcium Phosphate Hybrid Scaffolds” Iran Polym J 16 57-69, 2007.
[15] F. Afshar-Taromi, F. Nayeb-Habib, S. Salahshoor-Kordestani, Z. Shariatinia, “A Novel Topical Biocompatible Tissue Adhesive Based on Chitosan-modified Urethane Pre-polymer” Iran Polym J 20 (8), 671-680, 2011.
[16] H. Yang, S. Hua, W. Wang, A. Wang, “Composite Hydrogel Beads Based on Chitosan and Laponite: Preparation, Swelling, and Drug Release Behaviour” Iran Polym J 20 (6), 479-490, 2011.
[17] F. Ganji, M. J. Abdekhodaie, A. Ramazany, “Gelation Time and Degradation Rate of Chitosan as a Thermosensitive Injectable Hydrogel” J Sol-Gel Sci Technol 42, 47-53, 2007.
[18] J. Wu, W. Wei, L. Wang, Z. Su, G. Ma, “A Thermosensitive Hydrogel Based on Quaternized Chitosan and Poly (ethylene glycol) for Nasal Drug Delivery System” Biomaterials 28, 2220–2232, 2007.
[19] E. Khodaverdi, M. Tafaghodi, F. Ganji, K. Abnoos, H. Naghizadeh, “In Vitro Insulin Release from Thermosensitive Chitosan Hydrogel” AAPS Pharm Sci Tech 13 (2), 460-466, 2012.
[20] H. Y. Zhou, Y. P. Zhang, W. F. Zhang, X. G. Chen, “Biocompatibility and Characteristics of Injectable Chitosan-based Thermosensitive Hydrogel for Drug Delivery” Carbohyd Polym 83 (4), 1643-1651, 2011.
[21] A. Chenite, C. Chaput, D. Wang, C. Combes, M. Buschmann, C. Hoemann, J. Leroux, B. Atkinson, F. Binette, A. Selmani, “Novel Injectable Neutral Solutions of Chitosan form Biodegradable Gels In Situ” Biomaterials 21, 2155–2161, 2000.
[22] A. Chenite, C. Chaput, C. H. Combes, A. Selmani, F. Jalal, “Temperature-controlled pH-Dependent Formation of Ionic Polysaccharide Gels” US Patent 6, 344, 488, 2002.
[23] M. Berradaa, A. Serreqia, F. Dabbarha, A. Owusub, A. Guptaa, S. Lehnert, “A Novel Non-toxic Camptothecin Formulation for Cancer Chemotherapy” Biomaterials 26, 2115–2120, 2005.
[24] S. Kempe, H. Metz, M. Bastrop, A. Hvilsom, R. Contri, R. Mäder, “Characterization of Thermosensitive Chitosan-based Hydrogels by Rheology and Electron Paramagnetic Resonance Spectroscopy” Eur J Pharm Biopharm 68, 26–33, 2008 .
[25] J. Wu, Z. G. Su, G. H. Ma, “A Thermo- and pH-sensitive Hydrogel Composed of Quaternized Chitosan/glycerophosphate” Int J Pharm 315, 1-11, 2006.
[26] K. E. Crompton, R. J. Prankerd, D. M. Paganin, T. F. Scott, M. K. Horne, D. I. Finkelstein, K. A. Gross, J. S. Forsythe, “Morphology and gelation of thermosensitive chitosan hydrogels” Biophysic Chemist 117, 47–53, 2005.
[27] E. Ruel-Garie´py, A. Chenite, C. Chaput, S. Guirguis, J. C. Leroux, “Characterization of thermosensitive chitosan gels for the sustained delivery of drugs” Int J Pharm 203, 89–98, 2000.
[28] J. Yan, L. Yang, G. Wang, Y. Xiao, B. Zhang, N. Qi, “Biocompatibility Evaluation of Chitosan-based Injectable Hydrogels for the Culturing Mice Mesenchymal Stem Cells In Vitro” J Biomater Appl 24, 625-637, 2010.
[29] A. Chenite, M. Buschmann, D. Wang, C. Chaput, N. Kandani, “Rheological characterization of thermogelling chitosan/glycerol-phosphate solutions” Carbohyd Polym 46, 39-47, 2001.
[30] G. Arora, K. Malik, I. Singh, S. Arora, V. Rana, “Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum” J Adv Pharm Technol Res 2 (3), 163–169, 2011.