1. TMS in Clinical Practice Non-Standard Methods
SILENT PERIOD: during voluntary contraction of the target muscle TMS evokes a MEP followed by a period of inhibition of the ongoing EMG activity
The SP:
- is expressed in msec and measured from the onset of MEP to the restart of a constant EMG activity (approximately >25% of pre-stimulus level)
- gives information on GABA-mediated mechanisms controlling motor cortex excitability

2. Cortical Silent Period

3. Cortical Silent Period
The SP evoked in the muscles of the upper limb originates largely from activation of cortical inhibitory interneurons, although spinal mechanisms are involved in the early part
The SP recorded from the facial muscles originates solely in the cortex
SP is longest in hand muscles and is shorter in proximal arm, leg muscles facial muscles diaphragm and anal sphincter
In upper limb muscles, the SP can be evoked at lower stimulus intensities than the MEP
SP duration is related to the intensity of stimulation but is not strongly related to the size of the preceding MEP nor to the levels of background EMG activity

4. Cortical Silent Period
SP duration can be modulated by physiological phenomena that change cortical excitability,
hyperventilation
sleep deprivation
muscle fatigue
high-frequency rTMS.
Pharmacological studies using benzodiazepines, selective agonists of the benzodiazepine receptor subtype BZ1, baclofen, tiagabine provided evidence that the SP reflects a long-lasting cortical inhibition mediated by GABAB receptors.
Dopaminergic drugs lengthen the SP in normal subjects

5. Contralateral and Ipsilateral SPs
A similar period of silence can be observed also in the ongoing EMG activity of the ipsilateral muscles.
Such ipsilateral silent period probably originates from transcallosal inhibition

6. Il periodo silente “ipsilaterale” origina dall’attivazione di vie inibitorie transcallosali, per cui può essere utilizzato per misurare la conduzione attraverso il corpo calloso

7. TMS in Clinical Practice Non-Standard Methods
80-90% RMT
95% AMT
1 mV
conditioning
test
PAIRED TMS: two magnetic stimuli can be delivered with:
different intensity of stimuli
variable interval between them (inter-stimulus intervals)

8. TMS in Clinical Practice Non-Standard Methods
The test stimulus (suprathreshold) can be inhibited by a conditioning (subthreshold-80-90% RMT) stimulus given 1-5 msec before (INTRACORTICAL INHIBITION - SICI) or can be facilitated when the interval is longer than 7 msec
(INTRACORTICAL FACILITATION - SICF)
The conditioned test MEP is measured from peak-to-peak and expressed as a percentage of the unconditioned test MEP.
Kujirai et al. 1993

9. Intracortical inhibition and facilitation
These phenomena originate in the cortex from different neuronal populations:
GABAA receptors mediate the enhancement of intracortical inhibition
glutamatergic receptors mediate intracortical facilitation

10. Abbruzzese et al. 2002

11. Intracortical Inhibition and Facilitation
GABAA-agonists: > ICI
< ICF
NMDA-antagonists: > ICI
DA-agonists: > ICI
DA-antagonists: < ICI
> ICF
GLU rec.
SICF
GABAA rec.
SICI

12. GABA-A
GABA-B
SICI SP
Hanajima et al. 1998
Werhahn et al. 1999

13. 13

14. 14

15. GABAA receptor subtype specific enhancement of inhibition
in human motor cortex:
SICI is not mediated by the α1-subunit-bearing subtype of the GABAAR
but by those bearing either the α2- or α3-subunit * * 15

16. Paired pulse transcranial magnetic stimulation at 10-25 ms ISIs
ICF
Paired pulse transcranial magnetic stimulation at ms ISIs 16

17. Excitatory circuits activated by TMS17

18. ISI= N20 + 2-8 ms Transcranial magnetic stimulation EMG recordings
(FDI)
Median nerve
stimulation
ISI= N ms 18

19. Short latency afferent inhibition19

20. Short latency afferent inhibition
Baseline After Scopolamine
Test
ISI=N20 latency + 3 ms 20

22. Gulledge AT, Stuart GJ. Cholinergic inhibition of neocortical pyramidal neurons. J Neurosci. 2005;25:

23. GABAA receptor subtype specific suppression of afferent inhibition in human motor cortex:
α5-subunit ? * * * *

24. Inhibitory circuits activated by TMS24

26. TMS-effetto intensità: curva dose-risposta del MEP
SMAP 26

27. Input-Output Curves Cortical Maps
Measure of the number and topographical representation of excitable sites