Variability of behavioural responses to transcranial magnetic stimulation: Origins and predictors

Neuropsychologia

Volumn 74, Issue , 2015, Pages 137-144

  Nicolo, Pierre ^a,b   Ptak, Radek ^a,b   Guggisberg, Adrian G ^a,b  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^b UNIVERSITY OF GENEVA   (Switzerland)

Author keywords

Attention networks; Brain stimulation; Electroencephalography; Motor cortex; Spatial attention; Transcranial magnetic stimulation

Indexed keywords

ACTION POTENTIAL AMPLITUDE; ARTICLE; ATTENTION; BEHAVIOR; BRAIN DAMAGE; CONNECTOME; ELECTROENCEPHALOGRAPHY; EVOKED MUSCLE RESPONSE; FREQUENCY MODULATION; FUNCTIONAL MAGNETIC RESONANCE IMAGING; HUMAN; NERVE CELL NETWORK; NERVE CELL PLASTICITY; NERVE EXCITABILITY; NEUROMODULATION; PRIMARY MOTOR CORTEX; RESTING STATE NETWORK; TRANSCRANIAL MAGNETIC STIMULATION; BRAIN MAPPING; COGNITION; MEMORY; MOTOR CORTEX; MOTOR EVOKED POTENTIAL; NEUROIMAGING; PHYSIOLOGY;

BRAIN MAPPING; COGNITION; ELECTROENCEPHALOGRAPHY; EVOKED POTENTIALS, MOTOR; HUMANS; MEMORY; MOTOR CORTEX; NERVE NET; NEUROIMAGING; TRANSCRANIAL MAGNETIC STIMULATION;

EID: 84934335509     PISSN: 00283932     EISSN: 18733514     Source Type: Journal    
DOI: 10.1016/j.neuropsychologia.2015.01.033     Document Type: Article

References (96)

1. Ameli M., Grefkes C., Kemper F., Riegg F.P., Rehme A.K., Karbe H., Fink G.R., Nowak D.A. Differential effects of high-frequency repetitive transcranial magnetic stimulation over ipsilesional primary motor cortex in cortical and subcortical middle cerebral artery stroke. Ann. Neurol. 2009, 66:298-309.
2. Andoh J., Zatorre R.J. Interhemispheric connectivity influences the degree of modulation of TMS-induced effects during auditory processing. Front. Psychol. 2011, 2:161.
3. Arai N., Okabe S., Furubayashi T., Mochizuki H., Iwata N.K., Hanajima R., Terao Y., Ugawa Y. Differences in after-effect between monophasic and biphasic high-frequency rTMS of the human motor cortex. Clin. Neurophysiol. 2007, 118:2227-2233.
4. Arai N., Okabe S., Furubayashi T., Terao Y., Yuasa K., Ugawa Y. Comparison between short train, monophasic and biphasic repetitive transcranial magnetic stimulation (rTMS) of the human motor cortex. Clin. Neurophysiol. 2005, 116:605-613.
5. Barker A.T., Jalinous R., Freeston I.L. Non-invasive magnetic stimulation of human motor cortex. Lancet 1985, 1:1106-1107.
6. Bestmann S., Baudewig J., Siebner H.R., Rothwell J.C., Frahm J. Subthreshold high-frequency TMS of human primary motor cortex modulates interconnected frontal motor areas as detected by interleaved fMRI-TMS. Neuroimage 2003, 20:1685-1696.
7. Bestmann S., Baudewig J., Siebner H.R., Rothwell J.C., Frahm J. Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits. Eur. J. Neurosci. 2004, 19:1950-1962.
8. Bestmann S., Baudewig J., Siebner H.R., Rothwell J.C., Frahm J. BOLD MRI responses to repetitive TMS over human dorsal premotor cortex. Neuroimage 2005, 28:22-29.
9. Bienenstock E.L., Cooper L.N., Munro P.W. Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J. Neurosci. 1982, 2:32-48.
10. Bisley J.W., Goldberg M.E. Attention, intention, and priority in the parietal lobe. Annu. Rev. Neurosci. 2010, 33:1-21.
11. Brodie S.M., Borich M.R., Boyd L.A. Impact of 5-Hz rTMS over the primary sensory cortex is related to white matter volume in individuals with chronic stroke. Eur. J. Neurosci. 2014, 40:3405-3412.
12. Cardenas-Morales L., Nowak D.A., Kammer T., Wolf R.C., Schonfeldt-Lecuona C. Mechanisms and applications of theta-burst rTMS on the human motor cortex. Brain Topogr. 2010, 22:294-306.
13. Cardenas-Morales L., Volz L.J., Michely J., Rehme A.K., Pool E.M., Nettekoven C., Eickhoff S.B., Fink G.R., Grefkes C. Network connectivity and individual responses to brain stimulation in the human motor system. Cereb. Cortex 2014, 24:1697-1707.
14. Cazzoli D., Muri R.M., Schumacher R., von Arx S., Chaves S., Gutbrod K., Bohlhalter S., Bauer D., Vanbellingen T., Bertschi M., Kipfer S., Rosenthal C.R., Kennard C., Bassetti C.L., Nyffeler T. Theta burst stimulation reduces disability during the activities of daily living in spatial neglect. Brain 2012, 135:3426-3439.
15. Cheeran B., Talelli P., Mori F., Koch G., Suppa A., Edwards M., Houlden H., Bhatia K., Greenwood R., Rothwell J.C. A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS. J. Physiol. 2008, 586:5717-5725.
16. Chen R., Classen J., Gerloff C., Celnik P., Wassermann E.M., Hallett M., Cohen L.G. Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 1997, 48:1398-1403.
17. Conte A., Belvisi D., Iezzi E., Mari F., Inghilleri M., Berardelli A. Effects of attention on inhibitory and facilitatory phenomena elicited by paired-pulse transcranial magnetic stimulation in healthy subjects. Exp. Brain Res. 2008, 186:393-399.
18. Conte A., Gilio F., Iezzi E., Frasca V., Inghilleri M., Berardelli A. Attention influences the excitability of cortical motor areas in healthy humans. Exp. Brain Res. 2007, 182:109-117.
19. Corbetta M., Kincade M.J., Lewis C., Snyder A.Z., Sapir A. Neural basis and recovery of spatial attention deficits in spatial neglect. Nat. Neurosci. 2005, 8:1603-1610.
20. Corbetta M., Patel G., Shulman G.L. The reorienting system of the human brain: from environment to theory of mind. Neuron 2008, 58:306-324.
21. Dubovik S., Bouzerda-Wahlen A., Nahum L., Gold G., Schnider A., Guggisberg A.G. Adaptive reorganization of cortical networks in Alzheimer's disease. Clin. Neurophysiol. 2013, 124:35-43.
22. Dubovik S., Pignat J.M., Ptak R., Aboulafia T., Allet L., Gillabert N., Magnin C., Albert F., Momjian-Mayor I., Nahum L., Lascano A.M., Michel C.M., Schnider A., Guggisberg A.G. The behavioral significance of coherent resting-state oscillations after stroke. Neuroimage 2012, 61:249-257.
23. Duque J., Hummel F., Celnik P., Murase N., Mazzocchio R., Cohen L.G. Transcallosal inhibition in chronic subcortical stroke. Neuroimage 2005, 28:940-946.
24. Eldaief M.C., Halko M.A., Buckner R.L., Pascual-Leone A. Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner. Proc. Natl. Acad. Sci. USA 2011, 108:21229-21234.
25. Emara T., El Nahas N., Elkader H.A., Ashour S., El Etrebi A. MRI can predict the response to therapeutic repetitive transcranial magnetic stimulation (rTMS) in stroke patients. J. Vasc. Interv. Neurol. 2009, 2:163-168.
26. Fujiwara T., Rothwell J.C. The after effects of motor cortex rTMS depend on the state of contraction when rTMS is applied. Clin. Neurophysiol. 2004, 115:1514-1518.
27. Gamboa O.L., Antal A., Moliadze V., Paulus W. Simply longer is not better: reversal of theta burst after-effect with prolonged stimulation. Exp. Brain Res. 2010, 204:181-187.
28. Gangitano M., Valero-Cabre A., Tormos J.M., Mottaghy F.M., Romero J.R., Pascual-Leone A. Modulation of input-output curves by low and high frequency repetitive transcranial magnetic stimulation of the motor cortex. Clin. Neurophysiol. 2002, 113:1249-1257.
29. Gentner R., Wankerl K., Reinsberger C., Zeller D., Classen J. Depression of human corticospinal excitability induced by magnetic theta-burst stimulation: evidence of rapid polarity-reversing metaplasticity. Cereb. Cortex 2008, 18:2046-2053.
30. Gilio F., Rizzo V., Siebner H.R., Rothwell J.C. Effects on the right motor hand-area excitability produced by low-frequency rTMS over human contralateral homologous cortex. J. Physiol. 2003, 551:563-573.
31. Golay L., Schnider A., Ptak R. Cortical and subcortical anatomy of chronic spatial neglect following vascular damage. Behav. Brain Funct. 2008, 4:43.
32. Grefkes C., Nowak D.A., Wang L.E., Dafotakis M., Eickhoff S.B., Fink G.R. Modulating cortical connectivity in stroke patients by rTMS assessed with fMRI and dynamic causal modeling. NeuroImage 2010, 50:233-242.
33. Guggisberg A.G., Honma S.M., Findlay A.M., Dalal S.S., Kirsch H.E., Berger M.S., Nagarajan S.S. Mapping functional connectivity in patients with brain lesions. Ann. Neurol. 2008, 63:193-203.
34. Guggisberg A.G., Honma S.M., Findlay A.M., Dalal S.S., Kirsch H.E., Berger M.S., Nagarajan S.S. Mapping functional connectivity in patients with brain lesions. Ann. Neurol. 2008, 63:193-203.
35. Guggisberg A.G., Rizk S., Ptak R., Di Pietro M., Saj A., Lazeyras F., Lovblad K.O., Schnider A., Pignat J.M. Two intrinsic coupling types for resting-state integration in the human brain. Brain Topogr. 2014, 10.1007/s10548-014-0394-2.
36. Hallett M. Transcranial magnetic stimulation: a primer. Neuron 2007, 55:187-199.
37. Hamada M., Hanajima R., Terao Y., Okabe S., Nakatani-Enomoto S., Furubayashi T., Matsumoto H., Shirota Y., Ohminami S., Ugawa Y. Primary motor cortical metaplasticity induced by priming over the supplementary motor area. J. Physiol. 2009, 587:4845-4862.
38. Heide G., Witte O.W., Ziemann U. Physiology of modulation of motor cortex excitability by low-frequency suprathreshold repetitive transcranial magnetic stimulation. Exp. Brain Res. 2006, 171:26-34.
39. Hillebrand A., Barnes G.R., Bosboom J.L., Berendse H.W., Stam C.J. Frequency-dependent functional connectivity within resting-state networks: an atlas-based MEG beamformer solution. Neuroimage 2012, 59:3909-3921.
40. Hinder M.R., Goss E.L., Fujiyama H., Canty A.J., Garry M.I., Rodger J., Summers J.J. Inter- and intra-individual variability following intermittent theta burst stimulation: implications for rehabilitation and recovery. Brain Stimul. 2014, 7:365-371.
41. Hovington C.L., McGirr A., Lepage M., Berlim M.T. Repetitive transcranial magnetic stimulation (rTMS) for treating major depression and schizophrenia: a systematic review of recent meta-analyses. Ann. Med. 2013, 45:308-321.
42. Hsu W.Y., Cheng C.H., Liao K.K., Lee I.H., Lin Y.Y. Effects of repetitive transcranial magnetic stimulation on motor functions in patients with stroke: a meta-analysis. Stroke 2012, 43:1849-1857.
43. Huang Y.Y., Kandel E.R. Theta frequency stimulation induces a local form of late phase LTP in the CA1 region of the hippocampus. Learn. Mem. 2005, 12:587-593.
44. Huang Y.Z., Rothwell J.C., Edwards M.J., Chen R.S. Effect of physiological activity on an NMDA-dependent form of cortical plasticity in human. Cereb. Cortex 2008, 18:563-570.
45. Huang Y.Z., Rothwell J.C., Lu C.S., Wang J., Weng Y.H., Lai S.C., Chuang W.L., Hung J., Chen R.S. The effect of continuous theta burst stimulation over premotor cortex on circuits in primary motor cortex and spinal cord. Clin. Neurophysiol. 2009, 120:796-801.
46. Hubl D., Nyffeler T., Wurtz P., Chaves S., Pflugshaupt T., Luthi M., von Wartburg R., Wiest R., Dierks T., Strik W.K., Hess C.W., Muri R.M. Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field. Neuroscience 2008, 151:921-928.
47. Huerta P.T., Volpe B.T. Transcranial magnetic stimulation, synaptic plasticity and network oscillations. J. Neuroeng. Rehabil. 2009, 6:7.
48. Iezzi E., Conte A., Suppa A., Agostino R., Dinapoli L., Scontrini A., Berardelli A. Phasic voluntary movements reverse the aftereffects of subsequent theta-burst stimulation in humans. J. Neurophysiol. 2008, 100:2070-2076.
49. Jerde T.A., Curtis C.E. Maps of space in human frontoparietal cortex. J. Physiol. Paris 2013, 107:510-516.
50. Joseph C. Plasticity. Handb. Clin. Neurol. 2013, 116:525-534.
51. Jung S.H., Shin J.E., Jeong Y.S., Shin H.I. Changes in motor cortical excitability induced by high-frequency repetitive transcranial magnetic stimulation of different stimulation durations. Clin. Neurophysiol. 2008, 119:71-79.
52. Karnath H.O., Fruhmann Berger M., Küker W., Rorden C. The anatomy of spatial neglect based on voxelwise statistical analysis: a study of 140 patients. Cereb. Cortex 2004, 14:1164-1172.
53. Kim Y.H., Park J.W., Ko M.H., Jang S.H., Lee P.K. Facilitative effect of high frequency subthreshold repetitive transcranial magnetic stimulation on complex sequential motor learning in humans. Neurosci. Lett. 2004, 367:181-185.
54. Kinsbourne M. Mechanisms of unilateral neglect. Neurophysiological and Neuropsychological Aspects of Spatial Neglect 1987, 69-86. North-Holland, Amsterdam. M. Jeannerod (Ed.).
55. Kinsbourne M. Orientational bias model of unilateral neglect: evidence from attentional gradients within hemispace. Unilateral Neglect: Clinical and Experimental Studies 1993, 63-86. Lawrence Erlbaum Associates, Hove. I.H. Robertson, J.C. Marshall (Eds.).
56. Koch G., Bonni S., Giacobbe V., Bucchi G., Basile B., Lupo F., Versace V., Bozzali M., Caltagirone C. Theta-burst stimulation of the left hemisphere accelerates recovery of hemispatial neglect. Neurology 2012, 78:24-30.
57. Koch G., Oliveri M., Cheeran B., Ruge D., Lo Gerfo E., Salerno S., Torriero S., Marconi B., Mori F., Driver J., Rothwell J.C., Caltagirone C. Hyperexcitability of parietal-motor functional connections in the intact left-hemisphere of patients with neglect. Brain 2008, 131:3147-3155.
58. Lang N., Harms J., Weyh T., Lemon R.N., Paulus W., Rothwell J.C., Siebner H.R. Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability. Clin. Neurophysiol. 2006, 117:2292-2301.
59. Lang N., Siebner H.R., Ernst D., Nitsche M.A., Paulus W., Lemon R.N., Rothwell J.C. Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects. Biol. Psychiatry 2004, 56:634-639.
60. Lopez-Alonso V., Cheeran B., Rio-Rodriguez D., Fernandez-Del-Olmo M. Inter-individual variability in response to non-invasive brain stimulation paradigms. Brain Stimul. 2014, 7:372-380.
61. Maeda F., Keenan J.P., Tormos J.M., Topka H., Pascual-Leone A. Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation. Clin. Neurophysiol. 2000, 111:800-805.
62. Mort D.J., Malhotra P., Mannan S.K., Rorden C., Pambakian A., Kennard C., Husain M. The anatomy of visual neglect. Brain 2003, 126:1986-1997.
63. Murakami T., Muller-Dahlhaus F., Lu M.K., Ziemann U. Homeostatic metaplasticity of corticospinal excitatory and intracortical inhibitory neural circuits in human motor cortex. J. Physiol. 2012, 590:5765-5781.
64. Murase N., Duque J., Mazzocchio R., Cohen L.G. Influence of interhemispheric interactions on motor function in chronic stroke. Ann. Neurol. 2004, 55:400-409.
65. Noh N.A., Fuggetta G., Manganotti P., Fiaschi A. Long lasting modulation of cortical oscillations after continuous theta burst transcranial magnetic stimulation. PLoS One 2012, 7:e35080.
66. Nowak D.A., Grefkes C., Dafotakis M., Eickhoff S., Kust J., Karbe H., Fink G.R. Effects of low-frequency repetitive transcranial magnetic stimulation of the contralesional primary motor cortex on movement kinematics and neural activity in subcortical stroke. Arch. Neurol. 2008, 65:741-747.
67. Nyffeler T., Cazzoli D., Wurtz P., Luthi M., von Wartburg R., Chaves S., Deruaz A., Hess C.W., Muri R.M. Neglect-like visual exploration behaviour after theta burst transcranial magnetic stimulation of the right posterior parietal cortex. Eur. J. Neurosci. 2008, 27:1809-1813.
68. Nyffeler T., Wurtz P., Luscher H.R., Hess C.W., Senn W., Pflugshaupt T., von Wartburg R., Luthi M., Muri R.M. Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation. Neurosci. Lett. 2006, 409:57-60.
69. Nyffeler T., Wurtz P., Pflugshaupt T., von Wartburg R., Luthi M., Hess C.W., Muri R.M. One-Hertz transcranial magnetic stimulation over the frontal eye field induces lasting inhibition of saccade triggering. NeuroReport 2006, 17:273-275.
70. Pascual-Leone A., Valls-Sole J., Brasil-Neto J.P., Cammarota A., Grafman J., Hallett M. Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation. Neurology 1994, 44:892-898.
71. Pascual-Leone A., Valls-Sole J., Wassermann E.M., Hallett M. Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 1994, 117(Part 4):847-858.
72. Peinemann A., Reimer B., Loer C., Quartarone A., Munchau A., Conrad B., Siebner H.R. Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5Hz repetitive TMS to the primary motor cortex. Clin. Neurophysiol. 2004, 115:1519-1526.
73. Pell G.S., Roth Y., Zangen A. Modulation of cortical excitability induced by repetitive transcranial magnetic stimulation: influence of timing and geometrical parameters and underlying mechanisms. Prog. Neurobiol. 2011, 93:59-98.
74. Plow E.B., Cattaneo Z., Carlson T.A., Alvarez G.A., Pascual-Leone A., Battelli L. The compensatory dynamic of inter-hemispheric interactions in visuospatial attention revealed using rTMS and fMRI. Front. Hum. Neurosci. 2014, 8:226.
75. Ptak R., Fellrath J. Spatial neglect and the neural coding of attentional priority. Neurosci. Biobehav. Rev. 2013, 37:705-722.
76. Ptak R., Schnider A. The attention network of the human brain: relating structural damage associated with spatial neglect to functional imaging correlates of spatial attention. Neuropsychologia 2011, 49:3063-3070.
77. Quartarone A., Bagnato S., Rizzo V., Morgante F., Sant'angelo A., Battaglia F., Messina C., Siebner H.R., Girlanda P. Distinct changes in cortical and spinal excitability following high-frequency repetitive TMS to the human motor cortex. Exp. Brain Res. 2005, 161:114-124.
78. Ragert P., Camus M., Vandermeeren Y., Dimyan M.A., Cohen L.G. Modulation of effects of intermittent theta burst stimulation applied over primary motor cortex (M1) by conditioning stimulation of the opposite M1. J. Neurophysiol. 2009, 102:766-773.
79. Rengachary J., He B.J., Shulman G.L., Corbetta M. A behavioral analysis of spatial neglect and its recovery after stroke. Front. Hum. Neurosci. 2011, 5:29.
80. Rizk S., Ptak R., Nyffeler T., Schnider A., Guggisberg A.G. Network mechanisms of responsiveness to continuous theta-burst stimulation. Eur. J. Neurosci. 2013, 38:3230-3238.
81. Sack A.T., Kohler A., Bestmann S., Linden D.E., Dechent P., Goebel R., Baudewig J. Imaging the brain activity changes underlying impaired visuospatial judgments: simultaneous FMRI, TMS, and behavioral studies. Cereb. Cortex 2007, 17:2841-2852.
82. Siebner H.R., Lang N., Rizzo V., Nitsche M.A., Paulus W., Lemon R.N., Rothwell J.C. Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J. Neurosci. 2004, 24:3379-3385.
83. Silvanto J., Cattaneo Z., Battelli L., Pascual-Leone A. Baseline cortical excitability determines whether TMS disrupts or facilitates behavior. J. Neurophysiol. 2008, 99:2725-2730.
84. Sommer M., Lang N., Tergau F., Paulus W. Neuronal tissue polarization induced by repetitive transcranial magnetic stimulation?. Neuroreport 2002, 13:809-811.
85. Talelli P., Cheeran B.J., Teo J.T., Rothwell J.C. Pattern-specific role of the current orientation used to deliver theta burst stimulation. Clin. Neurophysiol. 2007, 118:1815-1823.
86. Taylor J.L., Loo C.K. Stimulus waveform influences the efficacy of repetitive transcranial magnetic stimulation. J. Affect. Disord. 2007, 97:271-276.
87. Terao Y., Ugawa Y. Basic mechanisms of TMS. J. Clin. Neurophysiol. 2002, 19:322-343.
88. Thickbroom G.W. Transcranial magnetic stimulation and synaptic plasticity: experimental framework and human models. Exp. Brain Res. 2007, 180:583-593.
89. Thut G., Pascual-Leone A. A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topogr. 2010, 22:219-232.
90. Tings T., Lang N., Tergau F., Paulus W., Sommer M. Orientation-specific fast rTMS maximizes corticospinal inhibition and facilitation. Exp. Brain Res. 2005, 164:323-333.
91. Torres J., Drebing D., Hamilton R. TMS and tDCS in post-stroke aphasia: Integrating novel treatment approaches with mechanisms of plasticity. Restor. Neurol. Neurosci. 2013, 31:501-515.
92. Touge T., Gerschlager W., Brown P., Rothwell J.C. Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses?. Clin. Neurophysiol. 2001, 112:2138-2145.
93. Vandenberghe R., Molenbergs P., Gillebert C.R. Spatial attention deficits in humans: the critical role of superior compared to inferior parietal lesions. Neuropsychologia 2012, 50:1092-1103.
94. Vossel S., Geng J.J., Fink G.R. Dorsal and ventral attention systems: distinct neural circuits but collaborative roles. Neuroscientist 2014, 20:150-159.
95. Zafar N., Paulus W., Sommer M. Comparative assessment of best conventional with best theta burst repetitive transcranial magnetic stimulation protocols on human motor cortex excitability. Clin. Neurophysiol. 2008, 119:1393-1399.
96. Zhang X., Mei Y., Liu C., Yu S. Effect of transcranial magnetic stimulation on the expression of c-Fos and brain-derived neurotrophic factor of the cerebral cortex in rats with cerebral infarct. J. Huazhong Univ. Sci. Technol. Med. Sci. 2007, 27:415-418.