Y P O C T Paired-Pulse TMS to one Brain O Region N O D - PowerPoint PPT Presentation

Y P O C T Paired-Pulse TMS to one Brain O Region N O D Joyce Gomes-Osman E Research Fellow S Berenson-Allen Center for Non-Invasive A Stimulation E L P

Y P Paired-Pulse Paradigms O C T • Sequential pulses applied O to the same cortical N region – Variable intensities O – Various inter-stimulus D intervals (ISIs) E S • Terminology A – Conditional Pulse E – Test Pulse L P

Y P Reviewing... O D-waves and I-waves C T O N O D E S A E L P

Y P O Paired-Pulse TMS... Why? C T O N “Black box” 1 Paired-Pulse • O TMS D E S A E L “Black box” 2 P H-Reflexes •

Y P Main intracortical circuits O C T O • SICI (short-interval intracortical inhibition) N • ICF (intracortical facilitation) O • LICI (long-interval intracortical inhibition) D E S A E L P

Y P SICI (short-interval intracortical inhibition) O C T O N O D E S A E Subthreshold CS L Suprathreshold TS P ISI 1-6 miliseconds

Y P SICI attributed to the activation of O intracortical processes C T • Electrophysiologic evidence O N • The conditioning stimulus is sub-threshold O – No MEP is elicited D – The activation of this CS did not modulate H- E Reflexes (that assess excitability at the level of the S spinal motor neuron) A • Thus, effect caused by interneuron activation E within motor cortex L P (Di Lazzaro et al 1998a, 1998b, 1999; Kujirai et al 1993)

Y P SICI attributed to the activation of O GABA-a mediated circuits C T • Duration of inhibition (20ms) consistent O GABA-a-mediated inhibitory postsynaptic N potentials in animal preparations. O D • SICI (short-interval intracortical inhibition) E – Benzodiazepine (GABA-a agonist) increases SICI S A E L P (Krnjevic et al, 1964; 1965; Ziemann et al, 1996)

Y P Methods (things to look out for...) O C T • Voluntary contraction reduces SICI O – Test under resting conditions N – Monitor the EMG activity O – Clinical populations D • Intensity of the CS E – Subthreshold for activation of corticospinal S projections A E – Optimal at 70-80% RMT L P (Ridding et al, 1995; Di Lazzaro et al, 1998; Kujirai et al, 1993)

Y P SICI in Neurological Populations O C T • Parkinson’s Disease O • SICI Reduced N • Reduction in SICI correlated with reduced O blood-flow in the basal ganglia D • Normalized after dopaminergic treatment E S • Dystonia A E • SICI reduced L P (Hanajaima et al, 1996; Ridding et al, 1995)

Y P Main intracortical circuits O C T O • SICI (short-interval intracortical inhibition) N • ICF (intracortical facilitation) O • LICI (long-interval intracortical inhibition) D E S A E L P

Y P ICF (intracortical facilitation) O C T O N O D E S Subthreshold CS A Suprathreshold TS E ISI 8-30 miliseconds L P

Y P SICI attributed to the activation of O intracortical processes C T • Electrophysiologic evidence O N • The conditioning stimulus is sub-threshold O – No MEP is elicited D – The activation of this CS did not modulate H- E Reflexes (that assess excitability at the level of the S spinal motor neuron) A • Thus, effect caused by interneuron activation E within motor cortex L P (Ziemann et al ,1996)

Y P ICF attributed to net-facilitation in O NMDA mediated intracortical circuits C T • Net-facilitation: combination of prevailing O facilitation and weaker inhibition N O D • Mediated by glutamatergic NMDA receptors E – Decreased ICF with NMDA receptor antagonists S A • Less consistent between-individuals E L • Clinical usefulness?? P (Ziemann et al, 1998)

Y P Main intracortical circuits O C T O • SICI (short-interval intracortical inhibition) N • ICF (intracortical facilitation) O • LICI (long-interval intracortical inhibition) D E S A E L P

Y P LICI (long-interval intracortical inhibition) O C T O N O D E S A CS suprathreshold E TS suprathreshold L P ISIs 50-200 milliseconds (Valls-Sole et al, 1992)

Y P LICI attributed to the activation of O GABA-b mediated intracortical circuits C T • Electrophysiologic evidence indicating that O spinal networks were not affected by LICI N O • Pharmacological evidence D – Baclofen (GABA-b receptor agonist) enhances LICI E S A E L P (Nakamura et al, 1995; 1997; Mc Donnel et al, 2006)

Y P O LICI in clinical neurologic conditions C T • Parkinson’s disease O – LICI enhanced N – Correlation between enhanced LICI and severity of O bradykinesia D E • Cerebellar ataxia S – LICI enhanced A E L P (Berardelli et al, 1996; Tamburin et al, 2004)

Y P Practical step-by-step guide O C T 1. Determination of the “hot-spot” for target O muscle N 2. Determination of motor threshold for target O muscle D 3. Baseline MEPs at threshold (typically 50 E responses) S A 4. Paired-pulse measures (typically 50 E responses also) L P

Y P Thank you! O C T O N • J.gomes@miami.edu O • jgomes2@bidmc.harvard.edu D E S A E L P