Transcranial Magnetic Stimulation Magnetic Stimulation Transcranial in Neurorehabilitation Neurorehabilitation in Giovanni Abbruzzese Abbruzzese Giovanni Department of Neurosciences, Ophthalmology& Genetics Department of Neurosciences, Ophthalmology& Genetics nd European School of 2 nd European School of Neuroengineering Neuroengineering 2 Genova, June 9 , June 9- -12 2004 12 2004 Genova
1. Basic principles of TMS 2. TMS studies on mechanisms of ‘plasticity’ 3. Future therapeutic perspectives of TMS in neurorehabilitation
Stimulating the the Brain Brain !! !! Stimulating Brain Brain Nerve Nerve TMS TMS Barker et al., 1985 al., 1985 Barker et
Principles of TMS Principles of TMS
Transcranial Magnetic Stimulation Magnetic Stimulation Transcranial • Currents induced by rapidly • Currents induced by rapidly transient magnetic fields with transient magnetic fields with variable flow direction and variable flow direction and intensity (1.5– –2.5 Tesla) 2.5 Tesla) intensity (1.5 • The amount of stimulated • The amount of stimulated brain tissue depends on: brain tissue depends on: - the stimulus intensity the stimulus intensity - - the coil shape the coil shape -
Magnetic fields with different shaped coils Magnetic fields with different shaped coils Stimulation is maximal, but not focal with a large large Stimulation is maximal, but not focal with a circular coil, , while a lower but more focal effect is while a lower but more focal effect is circular coil obtained with a figure figure- -of of- -eight coil eight coil. . obtained with a
Transcranial Magnetic Stimulation Magnetic Stimulation Transcranial • Magnetic stimulation (with a round coil parallel to the surface of the brain and threshold intensity) activates the pyramidal tract neurons trans-synaptically (to produce I-waves in the pyramidal tract), whereas electrical stimulation activates the axons directly to produce D- waves
Transcranial Magnetic Stimulation Magnetic Stimulation Transcranial Motor evoked potentials Motor evoked potentials (MEPs MEPs) ) ( - contralateral - contralateral distribution distribution - short latency with short latency with proximo proximo- - - distal progression distal progression - variable amplitude variable amplitude - (larger in distal muscles) (larger in distal muscles) - sensitivity to voluntary - sensitivity to voluntary contraction contraction
Coil orientation and activated neurons I 4 I 4 I 3 I 3 I 3 I 1 I 2 I 2 I 2 I 1 CSN All indirect I- -waves depend on synaptic input to waves depend on synaptic input to All indirect I cortico- -spinal neurons spinal neurons cortico
Cortico- -Motoneuronal Motoneuronal ‘ ‘conductivity conductivity’ ’ Cortico • Presence/Absence of Presence/Absence of • MEPs MEPs • MEP Latency (ms) MEP Latency (ms) • • Central Motor Central Motor • Conduction Time (ms) Conduction Time (ms) • loss of axons loss of axons • slowing of conduction slowing of conduction • • temporal dispersion of impulses temporal dispersion of impulses •
Cortico- -Motoneuronal Motoneuronal ‘ ‘excitability excitability’ ’ Cortico MEP Threshold and Amplitude MEP Threshold and Amplitude Cortical Maps Cortical Maps Measure of the portion of the spinal Measure of the portion of the spinal motoneurones discharged by TMS discharged by TMS motoneurones Measure of the number and Measure of the number and topographical representation topographical representation of excitable sites of excitable sites
Inhibitory effects of TMS Inhibitory effects of TMS Contralateral Ipsilateral Contralateral Ipsilateral Silent Period Silent Period
Paired- -pulse pulse TMS TMS Paired Kujirai Kujirai et et al. 1993 al. 1993
The physiological role of SICI The physiological role of SICI Focusing motor cortical excitation Focusing motor cortical excitation onto the pertinent groups of neurons onto the pertinent groups of neurons Ridding et Ridding et al. 1995 al. 1995 Abbruzzese et al. 1999 al. 1999 Abbruzzese et
GABA-A GABA-B SICI SP Hanajima et et al. 1998 al. 1998 Werhahn et et al. 1999 al. 1999 Hanajima Werhahn
TMS Applications Applications TMS TMS can be used to: TMS can be used to: • Test or measure conduction conduction of descending motor impulses of descending motor impulses • Test or measure • Map functional functional corticomotor corticomotor representations representations in the brain in the brain • Map • Assess excitability excitability of brain regions of brain regions • Assess • Induce a brief functional deactivation functional deactivation of brain regions of brain regions • Induce a brief • Improve transiently a distinct brain function • Improve transiently a distinct brain function
Plasticity Plasticity • Synapse level Synapse level • changes of EPSP amplitudes changes of EPSP amplitudes • Cellular level Cellular level • changes in single neurons responses changes in single neurons responses • Regional level Regional level • changes in neuronal population responses changes in neuronal population responses
Remodeling of Neuronal Network Remodeling of Neuronal Network
Plastic changes of cortical Plastic changes of cortical representation in monkeys representation in monkeys Merzenick et al. 1990 al. 1990 Merzenick et
Peripheral Deafferentation Cohen et al. 1991 al. 1991 Cohen et In patients with amputation of the arm (at the elbow level) motor r In patients with amputation of the arm (at the elbow level) moto representation of muscles proximal to the stump were larger. representation of muscles proximal to the stump were larger. CHANGE IN EXCITABILITY OR MOTOR CHANGE IN EXCITABILITY OR MOTOR REPRESENTATION REPRESENTATION
• Regional anaesthesia or ischaemic ischaemic nerve block leads to nerve block leads to • Regional anaesthesia or an enlargement of MEPs MEPs proximal to the block proximal to the block an enlargement of (Brasil Brasil- -Neto Neto et al. 1992) et al. 1992) ( • Sensory deprivation (Rossini et al. 1996) (Rossini et al. 1996) or limb or limb • Sensory deprivation immobilization ( et al. 1997) can reduce the motor can reduce the motor immobilization (Liepert Liepert et al. 1997) maps of specific muscles maps of specific muscles Motor cortex is capable of fast modulating the Motor cortex is capable of fast modulating the outputs to specific muscle groups outputs to specific muscle groups
Plasticity and stroke Plasticity and stroke MEPs may be absent in acute stroke and reappear during motor recover may be absent in acute stroke and reappear during motor recovery y MEPs Traversa Traversa et et. al. 1997 . al. 1997
Plasticity and stroke Plasticity and stroke The cortical representation of paretic muscles is modified after stroke: r stroke: The cortical representation of paretic muscles is modified afte - ↓↑ ↓↑ size changes - size changes - topographical shifts topographical shifts - Traversa Traversa et et. al. 1997 . al. 1997
Plasticity and stroke Plasticity and stroke Ipsilateral pathway may assist recovery in stroke patients, pathway may assist recovery in stroke patients, Ipsilateral although ipsilateral MEPs ipsilateral MEPs have been documented usually in have been documented usually in although patients with poor motor recovery patients with poor motor recovery Caramia et al. 1996 al. 1996 – – Turton et Turton et al. 1996 al. 1996 Caramia et � Some patients with a Some patients with a � good motor recovery good motor recovery show in the paretic show in the paretic muscles larger MEPs MEPs muscles larger upon stimulation of the upon stimulation of the ipsilateral hemisphere hemisphere ipsilateral Trompetto et al. 2000 al. 2000 Trompetto et
Plasticity and recovery of Plasticity and recovery of bilaterally organized functions bilaterally organized functions Hamdy et al. 1996 al. 1996 Hamdy et Decreased cortical representation of pharynx muscles in the affected hemisphere cted hemisphere Decreased cortical representation of pharynx muscles in the affe During recovery of swallowing, the cortical representation of pharynx muscles in the arynx muscles in the During recovery of swallowing, the cortical representation of ph affected hemisphere remained small, whereas it increased in the unaffected hemisphere unaffected hemisphere affected hemisphere remained small, whereas it increased in the
TMS and Motor Learning Learning TMS and Motor • In proficient Braille readers the • In proficient Braille readers the representation of the FDI muscle of representation of the FDI muscle of the reading hand was significantly the reading hand was significantly larger than in the non- -reading hand reading hand larger than in the non or in blind controls or in blind controls Pascual Pascual- -Leone et al. 1993 Leone et al. 1993 Plastic cortical changes may Plastic cortical changes may occur in relation to occur in relation to behavior behavior
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