Longitudinal changes of motor cortical excitability and transcallosal inhibition after subcortical stroke.

OBJECTIVE: A general lack of longitudinal studies on interhemispheric interactions following stroke led us to use transcranial magnetic stimulation (TMS) to examine changes in corticospinal/intracortical excitability and transcallosal inhibition over a 1-year period following subcortical stroke. METHODS: We measured TMS parameters such as motor threshold (MT), short-interval intracortical inhibition (SICI), and ipsilateral silent period (iSP) and evaluated clinical scores at three time-points (T1, T2, and T3) in 24 patients and 25 age-matched healthy subjects. RESULTS: At T1, we observed reduced MTs and SICIs with prolonged iSPs in the unaffected hemisphere (UH). In contrast, increased MTs and reduced SICIs were observed in the affected hemisphere (AH). These abnormalities gradually reduced and no MEP response to TMS at T1 predicted a worse prognosis. The prolonged iSP at T1 was associated with more severe impairments, but it did not necessarily predict a worse prognosis after 1year. CONCLUSIONS: UH excitability was increased at the post-acute time-period, which may have resulted in enhanced transcallosal inhibition to the AH. However, it is unclear whether there was a causal relationship between the enhanced transcallosal inhibition and the extent of clinical recovery. SIGNIFICANCE: This is the first study to demonstrate changes in transcallosal inhibition over a longitudinal period following stroke.

Handedness: dependent asymmetrical location of the human primary gustatory area, area G.

In magnetoencephalogram studies, the primary gustatory area, area G, is not always seen in the same coronal plane in both hemispheres. We investigated possible asymmetry in right-handed and left-handed individuals by functional MRI. Group analyses revealed a significant difference in the antero-posterior coordinates of the area G between the right and left hemispheres in the right-handed group, but not in the left-handed group, indicating significant morphometric asymmetry in the former group and ambiguous morphometric asymmetry in the latter. However, in left-handed individuals with motor speech areas detected in the right hemisphere, area G was more posteriorly located in the right than in the left hemisphere. These findings suggest that the motor speech area contributes to the asymmetric location of area G.

Parallel inhibition of cortico-muscular synchronization and cortico-spinal excitability by theta burst TMS in humans.

OBJECTIVE: To investigate the after-effects of theta burst TMS (TBS) on cortico-muscular synchronization, and on cortico-spinal excitability, in humans. METHODS: We studied 10 healthy subjects using a continuous paradigm of TBS (cTBS), i.e. 600 pulses in 40s. Before and after the cTBS, coherence function was computed as a measure of cortico-muscular synchronization by recording electroencephalogram (EEG) from 19 scalp sites and electromyogram (EMG) from right first dorsal interosseous (FDI) muscle during the isometric contraction. In a separate experiment, motor-evoked potentials (MEPs) in response to single TMS pulses were recorded from the FDI muscle before and after the cTBS, to measure cortico-spinal excitability. RESULTS: When the cTBS was applied over the left primary motor cortex (M1), the beta-band cortico-muscular coherence for the C3 scalp site, as well as the MEP amplitude significantly decreased in 30-60 min, and then recovered to the original levels in 90-120 min. Neither sham stimulation nor cTBS applied over 2 cm posterior to M1 produced significant effects. CONCLUSIONS: cTBS-over-M1 can inhibit the cortico-muscular synchronization in parallel with the decline of cortico-spinal excitability. SIGNIFICANCE: Our results provide the first evidence that TBS can efficiently alter the functional cortico-muscular coupling in humans.

Effect of theta burst stimulation over the human sensorimotor cortex on motor and somatosensory evoked potentials.

OBJECTIVE: To study the after-effect of theta burst stimulation (TBS) over the left sensorimotor cortex on the size of somatosensory as well as motor evoked potentials evoked from both hemispheres in healthy human subjects. METHODS: We used a continuous TBS paradigm for 40 s (600 pulses) in which a burst of 3 transcranial magnetic stimuli at 50 Hz is repeated at 5 Hz [Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron 2005;45:201-6]. Somatosensory evoked potentials (SEPs) following electrical stimulation of right or left median nerve and motor evoked potentials (MEPs) in the right or left first dorsal interosseous (FDI) muscles were recorded before and after TBS over the left motor cortex (M1) or a point 2 cm posterior to left M1. RESULTS: Amplitudes of P25/N33 (parietal components) following right median nerve stimulation were significantly increased for at least 53 min after TBS over the left M1, whereas this component was suppressed for 13 min after TBS over a point 2 cm posterior. MEPs in right as well as left FDI muscles were suppressed with a similar time course after TBS over the left M1. CONCLUSIONS: A single-session of TBS over the sensorimotor cortex can induce a short-lasting change in the size of ipsilateral cortical components of SEPs as well as MEPs evoked from both hemispheres. SIGNIFICANCE: TBS is an interventional tool that can induce rapid reorganization within cortical somatosensory as well as motor networks in humans.

Unilateral positive-negative myoclonus in Creutzfeldt-Jakob disease.

We report a patient with Creutzfeldt-Jakob disease who presented asymmetric myoclonus. Positive-negative myoclonus was seen only in the right extremities in association with periodic synchronous discharges (PSDs) on the electroencephalogram, although pure positive myoclonus was rarely seen in the left extremities, independently in PSDs. The duration of the silent period recorded in the right-hand muscle produced by transcranial magnetic stimulation was much longer than that in the left-hand muscle or that in normal subjects. Brain MRI diffusion-weighted images showed signal hyperintensities in the putamen and cerebral cortex, including the motor cortex, predominantly on the left side.

Isolation and molecular structure of the organo-persulfuranes [12-S-6(C6)].

Reactions of bis(2,2'-biphenylylene)sulfuranyl bis(tetrafluoroborate) [(8-S-4(C4)]2+ with organo-lithium reagents (PhLi and MeLi) gave bis(2,2'-biphenylylene)di-C-substituted persulfuranes as a first persulfurane [12-S-6(C6)] having only carbon ligands. These compounds have been characterized by 1H and 13C NMR and mass spectroscopies. The structure of the dimethyl derivative was determined by X-ray crystallographic analysis, revealing that it has a distorted octahedral geometry with the two methyl ligands cis to each other, and subsequently, it was analyzed by an ab initio calculation.

Muscle fatigue decreases short-interval intracortical inhibition after exhaustive intermittent tasks.

OBJECTIVE: Central fatigue is the inability of central commands to recruit maximum evocable muscle force during voluntary contraction. Here, we investigate how fatigue affects the inhibitory circuits of the motor cortex. METHODS: MEPs, short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated using a paired pulse transcranial magnetic stimulation (TMS) paradigm before, during and after a series of 5 isometric contractions of the FDI muscle to 50% maximal voluntary contraction (MVC). Each contraction lasted 2 min and was separated from the next by a pause of 2 min 40 s. Twelve male healthy subjects (range from 22 to 51 years) participated in experiment 1, in which the intensity of test stimulus was constant throughout the experiment. Eight of the same subjects (range from 26 to 51 years) participated in experiment 2, in which the intensity of test stimulus was adjusted so that the amplitude of the test MEP was kept constant throughout the measurement. RESULTS: As expected, test MEPs gradually decreased with progressive fatigue and recovered to control values with 5-10 min of rest. Because of the change in MEP amplitude, changes in percent SICI (reduced inhibition) and percent ICF (increased facilitation) in experiment 1 are difficult to interpret. When the test MEP was maintained at a constant size in experiment 2 there was no change in percent ICF, but the reduction in SICI was still present although it recovered to control values within the first 5-10 min of rest. CONCLUSIONS: SICI in FDI decreases transiently after a series of fatiguing isometric contractions. This decrease may compensate to some extent for reduced cortical excitability after muscle fatigue.

Increased corticospinal excitability after 5 Hz rTMS over the human supplementary motor area.

Transcranial magnetic stimulation (TMS) can produce effects not only at the site of stimulation but also at distant sites to which it projects. Here we examined the connection between supplementary motor area (SMA) and the hand area of the primary motor cortex (M1(Hand)) by testing whether prolonged repetitive TMS (rTMS) over the SMA can produce changes in excitability of the M1(Hand) after the end of the stimulus train. We evaluated motor-evoked potentials (MEPs) and the cortical silent period (CSP) evoked by a single-pulse TMS, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) produced by a paired-pulse TMS, and forearm flexor H reflexes before and after 750 pulses of 5 Hz rTMS over SMA at an intensity of 110% active motor threshold (AMT) for the first dorsal interosseous (FDI) muscle. The amplitude of MEPs recorded from the right FDI muscle at rest as well as during voluntary contraction increased for at least 10 min after the end of rTMS, although the duration of the CSP, SICI and ICF did not change. There was no effect on H reflexes in the flexor carpi radialis muscle, even though the amplitude of the MEP obtained from the same muscle increased after rTMS. The effects on MEPs depended on the intensity of rTMS and were spatially specific to the SMA proper. We suggest that 5 Hz rTMS over SMA can induce a short-lasting facilitation in excitability of the M1(Hand) compatible with the anatomical connections between SMA and the M1(Hand).

Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans.

OBJECTIVE: To study the after-effect of transcranial direct current stimulation (tDCS) over the sensorimotor cortex on the size of somatosensory evoked potentials (SEPs) in humans. METHODS: SEPs were elicited by electrical stimulation of right or left median nerve at the wrist before and after anodal or cathodal tDCS in 8 healthy subjects. tDCS was applied for 10 min to the left motor cortex at a current strength of 1 mA. RESULTS: Amplitudes of P25/N33, N33/P40 (parietal components) and P22/N30 (frontal component) following right median nerve stimulation were significantly increased for at least 60 min after the end of anodal tDCS, whereas P14/N20, N20/P25 (parietal components) and N18/P22 (frontal component) were unaffected. There was no effect on SEPs evoked by left median nerve stimulation. Cathodal tDCS had no effect on SEPs evoked from stimulation of either arm. CONCLUSIONS: Anodal tDCS over the sensorimotor cortex can induce a long-lasting increase in the size of ipsilateral cortical components of SEPs. SIGNIFICANCE: tDCS can modulate cortical somatosensory processing in humans and might be a useful tool to induce plasticity in cortical sensory processing.

The long-term high-frequency repetitive transcranial magnetic stimulation does not induce mRNA expression of inflammatory mediators in the rat central nervous system.

Repetitive transcranial magnetic stimulation (rTMS) has been applied for treatment of several diseases such as depression. However, the safety and biological effects of rTMS have not been fully elucidated. In this study, the effects of rTMS on the levels of inflammatory mediators in the central nervous system (CNS), which may be involved in neurodegenerative disorders, were investigated in comparison with the electric convulsive model. Long-term rTMS (1500 pulses at 30 Hz/day for series of 7 days) stimulation, which did not elicit convulsion, was given to rats (rTMS rats). Single high-frequency electrical stimulation (100 Hz, 0.5-ms pulse width, 1 s duration, 50 mA), which induced convulsion, was given to rats (ES rats). mRNA levels of interleukin (IL)-1beta, IL-6, cyclooxygenase (COX)-2 and inducible nitric oxide synthetase (iNOS) in the brain were evaluated by reverse transcription-polymerase chain reaction before and after these stimulations. mRNA of IL-1beta, IL-6 and COX-2 was induced in the brains of ES rats but not in the brains of long-term rTMS rats. mRNA of iNOS was not induced in the brain of long-term rTMS rats. These results suggest that long-term rTMS may safe and modulate neural function without up-regulation of inflammatory mediators, which may be involved in neurodegenerative disorders.

Early and late inhibition in the human motor cortex studied by paired stimulation through subdural electrodes.

OBJECTIVES: To evaluate the focal nature of the early and late inhibition of corticospinal neurons demonstrated by a paired-pulse stimulation paradigm. METHODS: We performed paired-electric pulse stimulation studies using subdural electrodes implanted in 4 patients with intractable partial epilepsy. RESULTS: Inhibition of motor evoked potentials in the first dorsal interosseous muscle was obtained by paired-pulse stimulation of the hand motor cortex (M1) with a subthreshold conditioning stimulus at conditioning-test intervals between 1 and 6ms. This early inhibition was abolished when the conditioning stimulus was moved to the sensory cortex (S1) or the arm M1. The inhibition was also produced by paired-pulse stimulation of the hand M1 with a suprathreshold conditioning stimulus between 50 and 300ms in all 3 patients. This late inhibition was still recognized when moving the conditioning stimulus to the hand S1 only in one of 3 patients. CONCLUSIONS: The early inhibition arises from very small areas in the M1 and is little mediated by neuronal circuits in the S1. On the other hand, the focal nature of the late inhibition is complicated and it arises mainly from the M1 but the S1 may be related to the generation of the late inhibition in some cases.