Paired transcranial magnetic stimulation (TMS) has been applied as a probe to test
functional connectivity within distinct cortical areas of the motor system. Depending
on the intensity of a conditioning stimulus applied to different areas of the cortical
motor network both facilitation and inhibition may be detected in the primary motor
cortex (M1), ipsilaterally or contralaterally to the site of conditioning stimulation.
Civardi (2001) and our group (Koch; unpublished data) reported that conditioning stimuli
applied to the dorsal premotor cortex (PMd) may induce distinct effects on ipsilateral
M1 depending on the intensity of stimulation. Low conditioning intensities provoked
inhibition with a maximum at 90% active motor threshold (AMT) which turned into facilitation
when higher intensities (120% AMT and 110% RMT, respectively) were applied.
Very recently, Lemon and co-workers have demonstrated robust facilitation of M1 motor
outputs to intrinsic hand muscles by conditioning the ipsilateral ventral premotor
cortex (PMv/area F5) in the Macaque monkey (Cerri et al., 2003; Shimazu et al., 2004).
Here we report data on an area anterolateral to the PMd in humans that elicits strong
facilitation on motor outputs of the ipsilateral M1 hand area as tested with single
pulse TMS.
We tested five different conditioning stimulus intensities (CSI) (70, 80 and 90% AMT
and 90 and 110% RMT, respectively). Interestingly, we found complementary results
to those reported on the PMd. Repeated measures ANOVA showed that different effects
were obtained depending on the CSI (ANOVA main factor F=13.2; p<0.001), with no specific
time course profile. Whereas low intensities evoked facilitation of ipsilateral M1
motor output with a maximum at an interstimulus interval (ISI) of 6 ms and a conditioning
stimulus intensity of 80% AMT (140% of the MEP evoked by the test pulse alone; p=0.008),
higher intensities provoked inhibition (maximum: ISI 4 ms; CSI 90% RMT; 80% of the
baseline MEP; p=0.04). The facilitating effect was even stronger when paired conditioning
stimuli were applied (at ISI of 2.6 ms; p=0.013).
In a stereotactically (Brainsight) guided control experiment the area of conditioning
stimulation turned out to be slightly anterior to the area of Broca (area 44), in
the range of what Rizzolatti and co-workers proposed to be the human ventral premotor
cortex and homologue of monkey F5 (Rizzolatti et al., 1998).