Involvement of the basal ganglia and cerebellar motor pathways in the preparation of self-initiated and externally triggered movements in humans.

The subthalamic nucleus (STN) is part of the cortico-basal ganglia (BG)-thalamocortical circuit, whereas the ventral lateral nucleus of the thalamus (VL) is a relay nucleus in the cerebello-dentato-thalamocortical (CTC) pathway. Both pathways have been implicated in movement preparation. We compared the involvement of the STN and VL in movement preparation in humans by recording local field potentials (LFPs) from seven patients with Parkinson's disease with deep-brain stimulation (DBS) electrodes in the STN and five patients with tremor and electrodes in VL. LFPs were recorded from DBS electrodes and scalp electrodes simultaneously while the patients performed self-paced and externally cued (ready, go/no-go) movements. For the self-paced movement, a premovement-related potential was observed in all patients from scalp, STN (phase reversal, five of six patients), and VL (phase reversal, five of five patients) electrodes. The onset times of the potentials were similar in the cortex, STN, and VL, ranging from 1.5 to 2 s before electromyogram onset. For the externally cued movement, an expectancy potential was observed in all patients in cortical and STN electrodes (phase reversal, six of six patients). The expectancy potential was recorded from the thalamic electrodes in four of five patients. However, phase reversal occurred only in one case, and magnetic resonance imaging showed that this contact was outside the VL. The cortico-BG-thalamocortical circuit is involved in the preparation of both self-paced and externally cued movements. The CTC pathway is involved in the preparation of self-paced but not externally cued movements, although the pathway may still be involved in the execution of these movements.

Representation of facial muscles in human motor cortex.

Whether there is a projection from the primary motor cortex (M1) to upper facial muscles and how the facial M1 area is modulated by intracortical inhibitory and facilitatory circuits remains controversial. To assess these issues, we applied transcranial magnetic stimulation (TMS) to the M1 and recorded from resting and active contralateral (C-OOc) and ipsilateral orbicularis oculi (I-OOc), and contralateral (C-Tr) and ipsilateral triangularis (I-Tr) muscles in 12 volunteers. In five subjects, the effects of stimulating at different scalp positions were assessed. Paired TMS at interstimulus intervals (ISIs) of 2 ms were used to elicit short interval intracortical inhibition (SICI) and ISI of 10 ms for intracortical facilitation (ICF). Long interval intracortical inhibition (LICI) was evaluated at ISIs between 50 and 200 ms, both at rest and during muscle activation. The silent period (SP) was also determined. C-OOc and I-OOc responses were recorded in all subjects. The optimal position for eliciting C-OOc responses was lateral to the hand representation in all subjects and MEP amplitude markedly diminished when the coil was placed 2 cm away from the optimal position. For the I-OOc, responses were present in more scalp sites and the latency decreased with more anterior placement of the coil. C-Tr response was recorded in 10 out of 12 subjects and the I-Tr muscle showed either no response or low amplitude response, probably due to volume conduction. SICI and ICF were present in the C-OOc and C-Tr, but not in the I-OOc muscle. Muscle activation attenuated SICI and ICF. LICI at rest showed facilitation at 50 ms ISI in all muscles, but there was no significant inhibition at other ISIs. There was no significant inhibition or facilitation with the LICI protocol during muscle contraction. The SP was present in the C-OOc, C-Tr and I-OOc muscles and the mean durations ranged from 92 to 104 ms. These findings suggest that the I-OOc muscle response is probably related to the first component (R1) of the blink reflex. There is M1 projection to the contralateral upper and lower facial muscles in humans and the facial M1 area is susceptible to cortical inhibition and facilitation, similar to limb muscles.

Exploring the connectivity between the cerebellum and motor cortex in humans.

Animal studies have shown that cerebellar projections influence both excitatory and inhibitory neurones in the motor cortex but this connectivity has yet to be demonstrated in human subjects. In human subjects, magnetic or electrical stimulation of the cerebellum 5-7 ms before transcranial magnetic stimulation (TMS) of the motor cortex decreases the TMS-induced motor-evoked potential (MEP), indicating a cerebellar inhibition of the motor cortex (CBI). TMS also reveals inhibitory and excitatory circuits of the motor cortex, including a short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). This study used magnetic cerebellar stimulation to investigate connections between the cerebellum and these cortical circuits. Three experiments were performed on 11 subjects. The first experiment showed that with increasing test stimulus intensities, LICI, CBI and ICF decreased, while SICI increased. The second experiment showed that the presence of CBI reduced SICI and increased ICF. The third experiment showed that the interaction between CBI and LICI reduced CBI. Collectively, these findings suggest that cerebellar stimulation results in changes to both inhibitory and excitatory neurones in the human motor cortex.

Two phases of short-interval intracortical inhibition.

Short-interval intracortical inhibition (SICI) is a widely used method to study cortical inhibition, and abnormalities have been found in several neurological and psychiatric disorders. Previous studies suggested that SICI involves two phases and the first phase may be explained by axonal refractoriness. Our objectives are to further investigate the mechanisms of the two phases of SICI. SICI was studied in 11 normal volunteers by a paired transcranial magnetic stimulation (TMS) paradigm applied to the left motor cortex with a subthreshold conditioning stimulus (80% resting motor threshold for rest condition and 95% active motor threshold for active condition) followed by a suprathreshold test stimulus at interstimulus intervals (ISIs) of 1-4.5 ms in steps of 0.5 ms. Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle. Three different test stimulus intensities adjusted to produce 0.2, 1 and 4 mV MEPs at rest were studied with the target muscle relaxed and during 20% maximum contraction. Maximum inhibition was observed at ISIs of 1 ms and 2.5 ms for the rest condition and the difference among ISIs was reduced with voluntary contraction. SICI increased with larger test MEP amplitude and decreased with voluntary contraction. At test MEP of 0.2 mV, some subjects showed facilitation and this is likely related to short-interval intracortical facilitation. For rest SICI, the correlation between adjacent ISIs was much higher from 3 to 4.5 ms than from 1 to 2.5 ms or between 1 and 2.5 ms. There was no correlation between SICI at different test MEP amplitudes. We conclude that maximum SICI at ISIs of 1 and 2.5 ms are mediated by different mechanisms. SICI at 1 ms cannot be fully explained by axonal refractoriness and synaptic inhibition may be involved. SICI is a complex phenomenon and inhibition at different ISIs may be mediated by different inhibitory circuits.