Nan Liang

Increased corticospinal excitability during direct observation of self-movement and indirect observation with a mirror box

To explore the effect of mirror box therapy based on the mirror neuron (MN) system of the primary motor cortex (M1), we examined if direct (without a mirror) and indirect (with a mirror) observation of self-movement in healthy subjects induced changes in motor evoked potential (MEP) evoked by transcranial magnetic stimulation (TMS). MEPs were elicited from the first dorsal interosseous (FDI) and the flexor carpi radialis (FCR) muscles. Somatosensory evoked potentials (SEPs) during self-movement observation were also recorded. Both observations of self-movement with and without a mirror increased MEP amplitude. In addition, increase in MEP amplitude was specific to the prime mover muscle involved in the observed movement. The SEPs increased similar to the MEPs during both observations of self-movement with and without a mirror. We conclude that although the MN system can be activated by observing self-movement in a manner similar to that achieved by observing movement of another person, there were no detectable effect on corticospinal excitability that were specific to movements observed with a mirror.

Further evidence for excitability changes in human primary motor cortex during ipsilateral voluntary contractions.

The present study aimed to further investigate whether the intracortical neural circuits within the primary motor cortex (M1) are modulated during ipsilateral voluntary finger movements. Single- and paired-pulse (interstimulus intervals, ISIs; 3 ms and 12 ms) transcranial magnetic stimulations of the left M1 were applied to elicit motor evoked potential (MEP) in the right first dorsal interosseous (Rt-FDI) muscle during voluntary contractions (10% and 30% maximum voluntary contraction) of the left FDI (Lt-FDI) muscle. F-waves of Rt-FDI muscle were recorded under these left index-finger conditions for ensuring that the excitability changes occur at the supraspinal level. MEPs were also recorded during motor imagery of the left index-finger abduction instead of overt movement. The results showed that, in single-pulse transcranial magnetic stimulation (TMS) paradigm, MEPs in Rt-FDI muscle were markedly enhanced during voluntary contractions of Lt-FDI muscle compared with the complete resting state. In paired-pulse TMS paradigm, the short intracortical inhibition was significantly reduced in proportion to increments of the ipsilateral muscle contraction, whereas the intracortical facilitation had no change. F-wave of Rt-FDI muscle was unchanged under these conditions, while MEP in Rt-FDI muscle was also enhanced during motor imagery of the left index-finger abduction. Based on the present results, it is suggested that the intracortical inhibitory neural circuits may be modulated in the transition from rest to activity of the ipsilateral homonymous muscle. The excitability changes in M1 might be induced by overflows of voluntary drive given to the ipsilateral limb, probably via the transcallosal pathway.

Coactivation of renal sympathetic neurons and somatic motor neurons by chemical stimulation of the midbrain ventral tegmental area

We examined whether neurons in the midbrain ventral tegmental area (VTA) play a role in generating central command responsible for autonomic control of the cardiovascular system in anesthetized rats and unanesthetized, decerebrated rats with muscle paralysis. Small volumes (60 nl) of an N-methyl-D-aspartate receptor agonist (L-homocysteic acid) and a GABAergic receptor antagonist (bicuculline) were injected into the VTA and substantia nigra (SN). In anesthetized rats, L-homocysteic acid into the VTA induced short-lasting increases in renal sympathetic nerve activity (RSNA; 66 ± 21%), mean arterial pressure (MAP; 5 ± 2 mmHg), and heart rate (HR; 7 ± 2 beats/min), whereas bicuculline into the VTA produced long-lasting increases in RSNA (130 ± 45%), MAP (26 ± 2 mmHg), and HR (66 ± 6 beats/min). Bicuculline into the VTA increased blood flow and vascular conductance of the hindlimb triceps surae muscle, suggesting skeletal muscle vasodilatation. However, neither drug injected into the SN affected all variables. Renal sympathetic nerve and cardiovascular responses to chemical stimulation of the VTA were not essentially affected by decerebration at the premammillary-precollicular level, indicating that the ascending projection to the forebrain from the VTA was not responsible for evoking the sympathetic and cardiovascular responses. Furthermore, bicuculline into the VTA in decerebrate rats produced long-lasting rhythmic bursts of RSNA and tibial motor nerve discharge, which occurred in good synchrony. It is likely that the activation of neurons in the VTA is capable of eliciting synchronized stimulation of the renal sympathetic and tibial motor nerves without any muscular feedback signal.

Central command does not decrease cardiac parasympathetic efferent nerve activity during spontaneous fictive motor activity in decerebrate cats

To examine whether withdrawal of cardiac vagal efferent nerve activity (CVNA) predominantly controls the tachycardia at the start of exercise, the responses of CVNA and cardiac sympathetic efferent nerve activity (CSNA) were directly assessed during fictive motor activity that occurred spontaneously in unanesthetized, decerebrate cats. CSNA abruptly increased by 71 ± 12% at the onset of the motor activity, preceding the tachycardia response. The increase in CSNA lasted for 4-5 s and returned to the baseline, even though the motor activity was not ended. The increase of 6 ± 1 beats/min in heart rate appeared with the same time course of the increase in CSNA. In contrast, CVNA never decreased but increased throughout the motor activity, in parallel with a rise in mean arterial blood pressure (MAP). The peak increase in CVNA was 37 ± 9% at 5 s after the motor onset. The rise in MAP gradually developed to 21 ± 2 mmHg and was sustained throughout the spontaneous motor activity. Partial sinoaortic denervation (SAD) blunted the baroreflex sensitivity of the MAP-CSNA and MAP-CVNA relationship to 22-33% of the control. Although partial SAD blunted the initial increase in CSNA to 53% of the control, the increase in CSNA was sustained throughout the motor activity. In contrast, partial SAD almost abolished the increase in CVNA during the motor activity, despite the augmented elevation of 31 ± 1 mmHg in MAP. Because afferent inputs from both muscle receptors and arterial baroreceptors were absent or greatly attenuated in the partial SAD condition, only central command was operating during spontaneous fictive motor activity in decerebrate cats. Therefore, it is likely that central command causes activation of cardiac sympathetic outflow but does not produce withdrawal of cardiac parasympathetic outflow during spontaneous motor activity.

Central command contributes to increased blood flow in the noncontracting muscle at the start of one-legged dynamic exercise in humans

Whether neurogenic vasodilatation contributes to exercise hyperemia is still controversial. Blood flow to noncontracting muscle, however, is chiefly regulated by a neural mechanism. Although vasodilatation in the nonexercising limb was shown at the onset of exercise, it was unclear whether central command or muscle mechanoreflex is responsible for the vasodilatation. To clarify this, using voluntary one-legged cycling with the right leg in humans, we measured the relative changes in concentrations of oxygenated-hemoglobin (Oxy-Hb) of the noncontracting vastus lateralis (VL) muscle with near-infrared spectroscopy as an index of tissue blood flow and femoral blood flow to the nonexercising leg. Oxy-Hb in the noncontracting VL and femoral blood flow increased (P < 0.05) at the start period of voluntary one-legged cycling without accompanying a rise in arterial blood pressure. In contrast, no increases in Oxy-Hb and femoral blood flow were detected at the start period of passive one-legged cycling, suggesting that muscle mechanoreflex cannot explain the initial vasodilatation of the noncontracting muscle during voluntary one-legged cycling. Motor imagery of the voluntary one-legged cycling increased Oxy-Hb of not only the right but also the left VL. Furthermore, an increase in Oxy-Hb of the contracting VL, which was observed at the start period of voluntary one-legged cycling, had the same time course and magnitude as the increase in Oxy-Hb of the noncontracting muscle. Thus it is concluded that the centrally induced vasodilator signal is equally transmitted to the bilateral VL muscles, not only during imagery of exercise but also at the start period of voluntary exercise in humans.

Excitability changes in human hand motor area induced by voluntary teeth clenching are dependent on muscle properties

To investigate whether the early effects of voluntary teeth clenching (VTC) among the first dorsal interosseous (FDI), abductor digiti minimi (ADM), and abductor pollicis brevis (APB) muscles are differently modulated depending on their muscle properties, we examined the responses of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation with selected current directions and by brainstem magnetic stimulation (BMS). Although MEP responses with anterior-medially current direction (preferentially elicited I1-waves) were facilitated in all three muscles, those responses with posterior-laterally current direction (preferentially elicited I3-waves) were different among FDI, ADM, and APB muscles. That is, MEP responses in FDI and APB muscles were significantly reduced, whereas those responses in ADM muscle were not significantly reduced. Further, inhibitory effects of VTC in FDI muscle were more potent than those in ADM or APB muscles. On the other hand, the responses to BMS were unchanged by VTC in all three muscles, suggesting that the modulations of MEP were attributed to the cortical origin. On the basis of our previous findings that the inhibitory connections in FDI muscle are more potent than those in ADM muscle (Takahashi et al. in Clin Neurophysiol 116:2757–2764, 2005), the cortical effects of VTC among three hand muscles are differently modulated, depending on muscle properties, presumably the extents of inhibitory connections to corticospinal tract neurons. Considering that the functional capacity in FDI muscle is higher than that in ADM or APB muscles, the cortical inhibitory effect of VTC might contribute to the sophisticated regulation of the motor outputs even during VTC.

Effects of motor imagery are dependent on motor strategies.

To investigate whether the facilitatory effects of motor imagery (MI) are dependent on motor strategies that vary with posture, we used transcranial magnetic stimulation to examine the effects of two forearm positions on motor-evoked potentials during an MI of index-finger abduction. MI-enhanced motor-evoked potentials of the first dorsal interosseous (prime mover) muscle in the forearm prone position were larger than those in the forearm neutral position. The opposite effects were seen in the extensor carpi radialis (synergist) muscle. These effects correspond to the different electromyography activities in the muscles when performing the actual movements in these two forearm positions. It is suggested that MI reflects different motor strategies in the contribution of agonist and synergist muscles towards a motor task.

Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.

Functional demanded excitability changes of human hand motor area

The present study was performed to examine if there are functional differences between the first dorsal interosseous (FDI) and the abductor digit minimi (ADM) muscles during different muscle contractions, namely dynamic and static contractions of the index and little finger abductions. It was also examined whether these functional differences occur at the cortical level. The motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and force curves, during the muscle contractions, were simultaneously recorded. Rest motor thresholds (RMTs) and active motor thresholds (AMTs), during dynamic and static contractions, were determined in the two muscles. In all trials, the background EMGs (B.EMGs) were kept at the same level in each muscle. Results showed that the target matching errors of dynamic contractions were statistically smaller in the FDI muscle than those in the ADM. In the FDI muscle, the AMT during dynamic contractions was significantly lower than during static ones and the MEPs elicited by TMS were larger during dynamic contractions than those during static ones. However, such results were not found in the ADM muscle. In order to investigate whether the differences were caused by the excitability changes that occurred in the cortical level, the responses elicited by subcortical stimulations were recorded using the same procedures as the experiment of TMS. Responses to subcortical stimulations during dynamic contractions were similar to those during static ones in either muscle. It is concluded that there are differences in the task-dependent MEP facilitations between the FDI and ADM muscles. And the differences are due to the functional demanded excitability changes accompanied by the cortical activation.

Effects of intermanual transfer induced by repetitive precision grip on input-output properties of untrained contralateral limb muscles

Although there were many reports relating to intermanual transfer of behavioral motor tasks in humans, it is still not well-known whether the transfer phenomenon between the trained and untrained hand is accompanied by corresponding changes in motor system. In the present study we applied transcranial magnetic stimulation to investigate the practice effects of unilateral fingertip precision grip on corticospinal excitability, regarding both the trained and untrained hand muscles. The results showed that after practice fingertip grip force became steady and safety margin dramatically decreased not only in the trained hand, but also in the untrained hand. Regarding MEP and background EMG (B.EMG) activities, the regression slope of MEP/B.EMG ratio in the first dorsal interosseous (FDI) muscle became significantly steeper after practice in both hands, but in the thenar (TH) muscle there were no clear modulations. These results indicated that through practice qualitative or functional changes of corticospinal systems related to the reorganization for a fingertip precision grip prominently reflect only on FDI muscle which plays a dominant role in the task. More importantly, such effects were simultaneously seen in the untrained hand correspondent to the trained hand, i.e., changes of input–output property in M1 occur not only in the trained hand, but also in the untrained hand. Based on the present results, we suggest that training-induced neural adaptations of the central nervous system may include improvement of its predicting fingertip grip force for self-lifting of the object in the untrained hand.