Mirror Therapy in Lower Limb Amputees – A Look Beyond Primary Motor Cortex Reorganization

Zusammenfassung

Ziel: Untersuchungen an Armamputierten konnten einen Zusammenhang zwischen Reorganisation im primären sensomotorischen Kortex und Phantomschmerz zeigen. Die Spiegeltherapie wird als nicht invasives Therapieverfahren zur Behandlung von Phantomschmerzen eingesetzt. Ziel dieser Studie war die Untersuchung kortikaler Reorganisationsphänomene vor und nach Spiegeltherapie bei Beinamputierten. Material und Methoden: Acht Beinamputierte absolvierten 12 Spiegeltherapiesitzungen, bei denen repetitive Extensions- und Flexionsbewegungen der gesunden unteren Extremität durchgeführt wurden. Vor der ersten und nach der letzten Therapiesitzung wurden fMRT-Messungen durchgeführt, bei denen die funktionelle Organisation repetitiver Bewegungen im gesunden und amputierten Sprunggelenk getestet wurde. Ergebnisse: Die mittlere Intensität des subjektiven Phantomschmerzes betrug vor der Spiegeltherapie 4,6 ± 3,1 auf einer visuellen Analogskala und verringerte sich auf 1,8 ± 1,7 (p = 0,04) nach der Therapie. Es konnten keine konsistenten Aktivierungen des primären sensomotorischen Kortex während der Bewegungen des Phantomsprunggelenks im Vergleich zur Ruhebedingung nachgewiesen werden. Nach der Spiegeltherapie zeigten die Patienten erhöhte Aktivität im rechten orbitofrontalen Kortex während Bewegungen des Phantomsprunggelenks. Der Vergleich zwischen Bewegungen des gesunden und des Phantomsprunggelenks zeigte eine signifikant höhere Aktivität im linken inferioren frontalen Kortex (Pars triangularis). Schlussfolgerung: Diese Ergebnisse stellen den bisher bekannten Zusammenhang zwischen kortikaler Reorganisation im primären sensomotorischen Kortex und Phantomschmerzen infrage und weisen auf die Veränderungen im sogenannten „Motor-Netzwerk“ hin. Die Phantomschmerzreduktion nach Spiegeltherapie wurde von einer erhöhten präfrontalen kortikalen Aktivität begleitet.

Abstract

Purpose: Phantom pain in upper limb amputees is associated with the extent of reorganization in the primary sensorimotor cortex. Mirror visual feedback therapy has been shown to improve phantom pain. We investigated the extent of cortical reorganization in lower limb amputees and changes in neural activity induced by mirror therapy. Materials and Methods: Eight lower limb amputees underwent 12 sessions of MVFT and functional magnetic resonance imaging (fMRI) of the brain before the first and after the last MVFT session. FMRI sessions consisted of two runs in which subjects were instructed to perform repetitive movement of the healthy and phantom ankle. Results: Before MVFT, the mean phantom pain intensity was 4.6 ± 3.1 on a visual analog scale and decreased to 1.8 ± 1.7 (p = 0.04). We did not observe a consistent pattern of cortical activation in primary sensorimotor areas during phantom limb movements. Following MVFT, increased activity was obtained in the right orbitofrontal cortex during phantom ankle movements. Comparison of cortical activity during movements of the phantom ankle and the intact ankle showed significantly higher activity in the left inferior frontal cortex (pars triangularis). Conclusion: These results question the known association between phantom pain and primary sensorimotor reorganization and propose reorganizational changes involving multiple cortical areas in lower limb amputees. Finally, reduction of phantom pain after mirror visual feedback therapy was associated with increased prefrontal cortical activity during phantom ankle movements.

Key words

MR functional imaging - neural networks - brain

References

• 1 Moller F, Ulmer S, Wolff S et al. Cortical reorganization in children with connatal spastic hemiparesis – a functional magnetic resonance imaging (FMRI) study.  Fortschr Röntgenstr. 2005;  177 1552-1561
• 2 Flor H, Birbaumer N. Phantom limb pain: cortical plasticity and novel therapeutic approaches.  Curr Opin Anaesthesiol. 2000;  13 561-564
• 3 Yang T T, Gallen C, Schwartz B et al. Sensory maps in the human brain.  Nature. 1994;  368 592-593
• 4 Elbert T, Flor H, Birbaumer N et al. Extensive reorganization of the somatosensory cortex in adult humans after nervous system injury.  Neuroreport. 1994;  5 2593-2597
• 5 Flor H, Elbert T, Knecht S et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.  Nature. 1995;  375 482-484
• 6 Karl A, Birbaumer N, Lutzenberger W et al. Reorganization of motor and somatosensory cortex in upper extremity amputees with phantom limb pain.  J Neurosci. 2001;  21 3609-3618
• 7 Lotze M, Flor H, Grodd W et al. Phantom movements and pain. An fMRI study in upper limb amputees.  Brain. 2001;  124 2268-2277
• 8 Chen R, Corwell B, Yaseen Z et al. Mechanisms of cortical reorganization in lower-limb amputees.  J Neurosci. 1998;  18 3443-3450
• 9 Schwenkreis P, Pleger B, Cornelius B et al. Reorganization in the ipsilateral motor cortex of patients with lower limb amputation.  Neurosci Lett. 2003;  349 187-190
• 10 McCabe C S, Haigh R C, Blake D R. Mirror visual feedback for the treatment of complex regional pain syndrome (type 1).  Curr Pain Headache Rep. 2008;  12 103-107
• 11 Cacchio A, De Blasis E, De Blasis V et al. Mirror therapy in complex regional pain syndrome type 1 of the upper limb in stroke patients.  Neurorehabil Neural Repair. 2009;  23 792-799
• 12 Chan B L, Witt R, Charrow A P et al. Mirror therapy for phantom limb pain.  N Engl J Med. 2007;  357 2206-2207
• 13 Michielsen M E, Selles R W, Geest J N et al. Motor recovery and cortical reorganization after mirror therapy in chronic stroke patients: a phase II randomized controlled trial.  Neurorehabil Neural Repair. 2011;  25 223-233
• 14 Altschuler E L, Wisdom S B, Stone van der L et al. Rehabilitation of hemiparesis after stroke with a mirror.  Lancet. 1999;  353 2035-2036
• 15 Michielsen M E, Smits M, Ribbers G M et al. The neuronal correlates of mirror therapy: an fMRI study on mirror induced visual illusions in patients with stroke.  J Neurol Neurosurg Psychiatry. 2011;  82 393-398
• 16 MacIver K, Lloyd D M, Kelly S et al. Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery.  Brain. 2008;  131 2181-2191
• 17 Giraux P, Sirigu A. Illusory movements of the paralyzed limb restore motor cortex activity.  Neuroimage. 2003;  20 S107-S111
• 18 Rizzolatti G, Craighero L. The mirror-neuron system.  Annu Rev Neurosci. 2004;  27 169-192
• 19 Buccino G, Binkofski F, Fink G R et al. Action observation activates premotor and parietal areas in a somatotopic manner: an fMRI study.  Eur J Neurosci. 2001;  13 400-404
• 20 Perani D, Fazio F, Borghese N A et al. Different brain correlates for watching real and virtual hand actions.  Neuroimage. 2001;  14 749-758
• 21 Peyron R, Laurent B, Garcia-Larrea L. Functional imaging of brain responses to pain. A review and meta-analysis (2000).  Neurophysiol Clin. 2000;  30 263-288
• 22 Rodgers W M, Hall C R, Blanchard C M et al. Prediction of obligatory exercise by exercise-related imagery.  Psychol Addict Behav. 2001;  15 152-154
• 23 Flor H, Elbert T, Muhlnickel W et al. Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees.  Exp Brain Res. 1998;  119 205-212
• 24 Roux F E, Lotterie J A, Cassol E et al. Cortical areas involved in virtual movement of phantom limbs: comparison with normal subjects.  Neurosurgery. 2003;  53 1342-1352
• 25 Kapreli E, Athanasopoulos S, Papathanasiou M et al. Lower limb sensorimotor network: issues of somatotopy and overlap.  Cortex. 2007;  43 219-232
• 26 Taylor K S, Anastakis D J, Davis K D. Cutting your nerve changes your brain.  Brain. 2009;  132 3122-3133
• 27 Rath J, Klinger N, Geissler A et al. An fMRI Marker for Peripheral Nerve Regeneration.  Neurorehabil Neural Repair. 2011;  25 577-579
• 28 Nedelko V, Hassa T, Hamzei F et al. Age-independent activation in areas of the mirror neuron system during action observation and action imagery. A fMRI study.  Restor Neurol Neurosci. 2010;  28 737-747
• 29 Weeks S R, Tsao J W. Incorporation of another person’s limb into body image relieves phantom limb pain: a case study.  Neurocase. 2010;  16 461-465
• 30 Jahn K, Deutschlander A, Stephan T et al. Brain activation patterns during imagined stance and locomotion in functional magnetic resonance imaging.  Neuroimage. 2004;  22 1722-1731
• 31 Lotze M, Montoya P, Erb M et al. Activation of cortical and cerebellar motor areas during executed and imagined hand movements: an fMRI study.  J Cogn Neurosci. 1999;  11 491-501
• 32 Szameitat A J, Shen S, Sterr A. Motor imagery of complex everyday movements. An fMRI study.  Neuroimage. 2007;  34 702-713
• 33 Olivetti B M, Palmiero M, Sestieri C et al. An fMRI investigation on image generation in different sensory modalities: the influence of vividness.  Acta Psychol. 2009;  132 190-200
• 34 Malouin F, Richards C L, Durand A et al. Effects of practice, visual loss, limb amputation, and disuse on motor imagery vividness.  Neurorehabil Neural Repair. 2009;  23 449-463
• 35 Molenberghs P, Brander C, Mattingley J B et al. The role of the superior temporal sulcus and the mirror neuron system in imitation.  Hum Brain Mapp. 2010;  31 1316-1326
• 36 Moulton E A, Pendse G, Morris S et al. Capsaicin-induced thermal hyperalgesia and sensitization in the human trigeminal nociceptive pathway: an fMRI study.  Neuroimage. 2007;  35 1586-1600
• 37 Halsband U, Lange R K. Motor learning in man: a review of functional and clinical studies.  J Physiol Paris. 2006;  99 414-424
• 38 Fink G R, Marshall J C, Halligan P W et al. The neural consequences of conflict between intention and the senses.  Brain. 1999;  122 497-512
• 39 Bantick S J, Wise R G, Ploghaus A et al. Imaging how attention modulates pain in humans using functional MRI.  Brain. 2002;  125 310-319
• 40 Johnson-Frey S H, Maloof F R, Newman-Norlund R et al. Actions or hand-object interactions? Human inferior frontal cortex and action observation.  Neuron. 2003;  39 1053-1058
• 41 Bookheimer S. Functional MRI of language: new approaches to understanding the cortical organization of semantic processing.  Annu Rev Neurosci. 2002;  25 151-188
• 42 Greenfield S A. A noncholinergic action of acetylcholinesterase (AChE) in the brain: from neuronal secretion to the generation of movement.  Cell Mol Neurobiol. 1991;  11 55-77
• 43 Diers M, Christmann C, Koeppe C et al. Mirrored, imagined and executed movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain.  Pain. 2010;  149 296-304
• 44 Dechent P, Frahm J. Functional somatotopy of finger representations in human primary motor cortex.  Hum Brain Mapp. 2003;  18 272-83
• 45 Schlamann M, Yoon M S, Maderwald S et al. Effects of MRI on the electrophysiology of the motor cortex: a TMS study.  Fortschr Röntgenstr. 2009;  181 215-219