No abstract

The supplementary motor area (SMA-proper) plays a key role in the preparation and execution of voluntary movements. Anatomically, SMA-proper is densely reciprocally connected to primary motor cortex (M1), but neuronal coordination within the SMA-M1 network and its modification by external perturbation are not well understood. Here we modulated the SMA-M1 network using MR-navigated multicoil associative transcranial magnetic stimulation in healthy subjects. Changes in corticospinal excitability were assessed by recording motor evoked potential (MEP) amplitude bilaterally in a hand muscle. We found timing-dependent bidirectional Hebbian-like MEP changes during and for at least 30 min after paired associative SMA-M1 stimulation. MEP amplitude increased if SMA stimulation preceded M1 stimulation by 6 ms, but decreased if SMA stimulation lagged M1 stimulation by 15 ms. This associative plasticity in the SMA-M1 network was highly topographically specific because paired associative stimulation of pre-SMA and M1 did not result in any significant MEP change. Furthermore, associative plasticity in the SMA-M1 network was strongly state-dependent because it required priming by near-simultaneous M1 stimulation to occur. We conclude that timing-dependent bidirectional associative plasticity is demonstrated for the first time at the systems level of a human corticocortical neuronal network. The properties of this form of plasticity are fully compatible with spike-timing-dependent plasticity as defined at the cellular level. The necessity of priming may reflect the strong interhemispheric connectivity of the SMA-M1 network. Findings are relevant for better understanding reorganization and potentially therapeutic modification of neuronal coordination in the SMA-M1 network after cerebral lesions such as stroke.

The supplementary motor area (SMA) is important for preparation and execution of voluntary movements and densely anatomically connected with the hand area of primary motor cortex (M1). However, little is known about the effective connectivity between SMA and ipsilateral M1 (SMA → M1). Here, we used paired-coil transcranial magnetic stimulation (pcTMS) to study the SMA → M1 effective connectivity in healthy human subjects. In Experiment 1, we tested the effects of different induced current directions in the SMA and M1, and different intensities of conditioning SMA stimulation. Coil placement over the SMA-proper was verified by MRI-navigation. We found a SMA → M1 facilitatory effect on motor evoked potential (MEP) amplitude that occurred very specifically only with an induced conditioning current directed from the midline towards the targeted SMA, an induced test current in M1 directed antero-medially and sufficient intensity of conditioning SMA stimulation. In Experiment 2, we selected these effective parameters to explore the effects of SMA → M1 on the active MEP amplitude, cortical silent period (CSP) duration, and using a triple-pulse protocol, on short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). None of these measures was affected by conditioning SMA stimulation. Our findings demonstrate that pcTMS identifies predominantly facilitatory connections from SMA-proper to the hand area of the ipsilateral M1. The successful activation of this connection depends on effective SMA-proper stimulation, is state dependent and likely mediated via excitatory interneurons in M1.

The aim of this study is to investigate the efficacy of 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) on acute pain induced by intradermal capsaicin injection and to elucidate its mechanisms by single-photon emission computed tomography (SPECT). We compared time courses of a subjective scale of pain induced by intradermal capsaicin injection in seven normal subjects under three different conditions: rTMS over M1, sham stimulation, and control condition (natural course of acute pain without any stimulation). In ten normal subjects, using SPECT, we also studied differences in regional cerebral blood flow (rCBF) after capsaicin injection between two conditions: rTMS over M1 and the control condition. rTMS over M1 induced earlier recovery from acute pain compared with the sham or control conditions. Under rTMS over the right M1 condition compared with the control condition, the SPECT study demonstrated a significant relative rCBF decrease in the right medial prefrontal cortex (MPFC) corresponding to Brodmann area (BA) 9, and a significant increase in the caudal part of the right anterior cingulate cortex (ACC) corresponding to BA24 and the left premotor area (BA6). A region-of-interest analysis showed significant correlation between pain reduction and rCBF changes in both BA9 and BA24. We conclude that rTMS over M1 should have beneficial effects on acute pain, and its effects must be caused by functional changes of MPFC and caudal ACC.

No abstract

Fractional anisotropy reflects functional abnormality of intracranial corticospinal tracts and can be used for objective evaluation of upper motor neuron impairment in amyotrophic lateral sclerosis.

The aim of the present paper is to study effects of short and long duration transcranial direct current stimulation (tDCS) on the human motor cortex. In eight normal volunteers, motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) were recorded from the right first dorsal interosseous muscle, and tDCS was given with electrodes over the left primary motor cortex (M1) and the contralateral orbit. We performed two experiments: one for short duration tDCS (100 ms, 1, 3 or 5 mA) and the other for long duration tDCS (10 min, 1 mA). The stimulus onset asynchrony (SOA) between the onset of tDCS and TMS were 1-7 and 10-120 ms for the former experiment. In the latter experiment, TMS was given 0-20 min after the end of 10 min tDCS. We evaluated the effect of tDCS on the motor cortex by comparing MEPs conditioned by tDCS with control MEPs. Cathodal short duration tDCS significantly reduced the size of responses to motor cortical stimulation at SOAs of 1-7 ms when the intensity was equal to or greater than 3 mA. Anodal short duration tDCS significantly increased MEPs when the intensity was 3 mA, but the enhancement did not occur when using 5 mA conditioning stimulus. Moreover, both anodal and cathodal short duration tDCS decreased responses to TMS significantly at SOAs of 20-50 ms and enhanced them at an SOA of 90 ms. Long duration cathodal tDCS decreased MEPs at 0 and 5 min after the offset of tDCS and anodal long duration tDCS increased them at 1 and 15 min. We conclude that the effect at SOAs less than 10 ms is mainly caused by acute changes in resting membrane potential induced by tDCS. The effect at SOAs of 20-100 ms is considered to be a nonspecific effect of a startle-like response produced by activation of skin sensation at the scalp. The effect provoked by long duration tDCS may be short-term potentiation or depression like effects.

No abstract