Search

Background: The masked-priming paradigm is used to test unconscious inhibitory processes of the brain. A tendency towards responses that are incompatible with the prime, designated as negative compatibility effect (NCE), emerges when the perception of a priming visual stimulus is "masked" afterwards. This effect presumably stems from a subliminal inhibitory process against the masked-prime. Prior lesions as well as activation studies suggest a key role of SMA in this effect., Objective: This study was conducted to elucidate a causal role of SMA in the subliminal response inhibition represented by the NCE., Methods: Using a repeated-measures pre-post design with a group of healthy people, physiological measures (resting and active motor thresholds and motor evoked potential (MEP) amplitude) and behavioral ones (choice reaction time (CRT), positive compatibility effect (PCE) and NCE) were obtained before and after three quadripulse stimulation (QPS), namely sham, M1-QPS, and SMA-QPS, on different days. CRT and PCE served as indices for different aspects of motor execution., Results: Motor thresholds were not altered after any QPS, although the M1-QPS increased MEP amplitude. Neither CRT nor PCE was altered significantly after QPS protocols. NCE was abolished after the SMA-QPS., Conclusions: Abolished NCE after the SMA-QPS in the absence of MEP changes suggests that (1) SMA plays a cardinal role in the NCE, and (2) the network involved in NCE is different from that of MEP generation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Caffeine, an adenosine receptor antagonist, is known to affect sleep-awake cycles, the stress response, and learning and memory. It has been suggested that caffeine influences synaptic plasticity, but the effects of caffeine on synaptic plasticity in the human brain remain unexplored. The present study aimed to investigate the effects of caffeine on long-term potentiation (LTP)-like effects in the primary motor cortex of healthy humans. Twelve healthy participants (six women and six men; mean age: 44.8 ± 1.5 years) underwent quadripulse magnetic stimulation with an inter-stimulus interval of 5 ms (QPS5) to induce LTP-like effects, 2 h after administration of either a caffeine (200 mg) or placebo tablet in a double-blind crossover design. We recorded motor-evoked potentials (MEPs) before and after QPS5. The degree of MEP enhancement was compared between the placebo and caffeine conditions. Neither active nor resting motor thresholds were influenced by caffeine administration. Following caffeine administration, the degree of potentiation significantly decreased in "significant responders", whose average MEP ratios were greater than 1.24 in the placebo condition. The observed reduction in potentiation following caffeine administration is consistent with the A 2A receptor antagonistic effect of caffeine. This is the first report of an effect of caffeine on neural synaptic plasticity in the human brain, which is consistent with the caffeine-induced plasticity reduction observed in primate studies. Because we studied only a small number of subjects, we cannot firmly conclude that caffeine reduces LTP in humans. The present results will, however, be helpful when considering further or new clinical uses of caffeine.

The reduction of plasticity with age has been shown by many previous papers in animal experiments. This issue can be studied in humans because several non-invasive brain stimulation techniques induce synaptic plasticity in the human brain. We investigated the influence of individuals' age on the responder rate of the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS). The participants were 107 healthy volunteers: 53 older participants (Mean ± SD 65.0 ± 1.5 years) and 54 younger participants (37.2 ± 8.7). The quadripulse stimulation with 5-ms inter-pulse interval (QPS5) was applied over the primary motor cortex (M1). We measured motor evoked potentials (MEPs) before QPS, and at five time points after QPS for up to 25 min. In each participant, average MEP amplitude (size) ratios were quantified. We first classified participants as responders and non-responders simply by comparing the size ratio with 1.0 for consistency with previous studies, then as "significant responders", "non-responders", and "opposite responders" for more detailed analysis by comparing the size ratio with the mean and standard deviation of the MEP size ratios of the sham condition. The degree of LTP-like effects induced by QPS5 was significantly smaller in the older group compared to the younger group. Also, the rates of responders and significant responders were lower in the older group (58 and 47%, respectively) compared to the younger group (80 and 76%, respectively). The age of the participants significantly affected the LTP-like effect induced by QPS5, which suggests that brain plasticity decreases with age.

Several recent studies using functional magnetic resonance imaging (fMRI) have shown that repetitive transcranial magnetic stimulation (rTMS) affects not only brain activity in stimulated regions but also resting-state functional connectivity (RSFC) between the stimulated region and other remote regions. However, these studies have only demonstrated an effect of either excitatory or inhibitory rTMS on RSFC, and have not clearly shown the bidirectional effects of both types of rTMS. Here, we addressed this issue by performing excitatory and inhibitory quadripulse TMS (QPS), which is considered to exert relatively large and long-lasting effects on cortical excitability. We found that excitatory rTMS (QPS with interstimulus intervals of 5 ms) decreased interhemispheric RSFC between bilateral primary motor cortices, whereas inhibitory rTMS (QPS with interstimulus intervals of 50 ms) increased interhemispheric RSFC. The magnitude of these effects on RSFC was significantly correlated with that of rTMS-induced effects on motor evoked potential from the corresponding muscle. The bidirectional effects of QPS were also observed in the stimulation over prefrontal and parietal association areas. These findings provide evidence for the robust bidirectional effects of excitatory and inhibitory rTMSs on RSFC, and raise a possibility that QPS can be a powerful tool to modulate RSFC., (Copyright © 2013 Wiley Periodicals, Inc.)

The relationship between sensory and transcallosal inputs into the motor cortex may be important in motor performance, but it has not been well studied, especially in humans. The aim of this study was to reveal this relationship by investigating the interaction between short-latency interhemispheric inhibition (SIHI) and short-latency afferent inhibition (SAI) in humans with transcranial magnetic stimulation. SIHI is the inhibition of the primary motor cortex (M1) elicited by contralateral M1 stimulation given ∼10 ms before, and it reflects transcallosal inhibition. SAI is the inhibition of M1 elicited by contralateral median nerve stimulation preceding M1 stimulation by ∼20 ms. In this investigation, we studied the intensity dependence of SIHI and SAI and the interaction between SIHI and SAI in various conditioning intensities. Subjects were 11 normal volunteers. The degree of effects was evaluated by comparing motor evoked potential sizes recorded from the first dorsal interosseous muscle between a certain condition and control condition. Both SIHI and SAI were potentiated by increment of the conditioning stimulus intensity and saturated at 1.4 times resting motor threshold for SIHI and 3 times sensory threshold for SAI. No significant interaction was observed when either of their intensities was subthreshold for the inhibition on its own. Only when both intensities were strong enough for their inhibition did the presence of one inhibition lessen the other one. On the basis of these findings, we conclude that interneurons mediating SIHI and SAI have mutual, direct, and inhibitory interaction in a conditioning intensity-dependent manner.

The supplementary motor area (SMA) is a secondary motor area that is involved in various complex hand movements. In animal studies, short latency and probably direct excitatory inputs from SMA to the primary motor cortex (M1) have been established. Although human imaging studies revealed functional connectivity between SMA and M1, its electrophysiological nature has been less studied. This study explored the connection between SMA and M1 in humans using a single-pulse transcranial magnetic stimulation (TMS) over SMA. First, TMS over SMA did not alter the corticospinal tract excitability measured by the size of motor evoked potential elicited by single-pulse TMS over M1. Next, we measured short-interval intracortical facilitation (SICF), which reflects the function of a facilitatory circuit within M1, with or without a single-pulse TMS over SMA. When the intensity of the second pulse in the SICF paradigm (S2) was as weak as 1.0 active motor threshold for a hand muscle, SMA stimulation significantly enhanced the SICF. Furthermore, this enhancement by SMA stimulation was spatially confined and had a limited time window. On the other hand, SMA stimulation did not alter short-interval intracortical inhibition or contralateral silent period duration, which reflects the function of an inhibitory circuit mediated by gamma-aminobutyric acid A (GABA(A)) or GABA(B) receptors, respectively. We conclude that a single-pulse TMS over SMA modulates a facilitatory circuit within M1.

Objective: To investigate inter-individual variation in the efficiency of magnetic brainstem stimulation (BST) with regard to the stimulation site., Methods: We studied 31 healthy subjects, using a right hand muscle as a recording site. Three stimulation sites were compared: BST over the inion (inion BST), and BST over the midpoint between the inion and the right (ipsilateral BST) or left (contralateral BST) mastoid process. Five suprathreshold BSTs were performed for each stimulation site using the same stimulation intensity. The mean peak-to-peak amplitudes of motor evoked potential (MEP) were compared. The active motor threshold (AMT) and onset latency for inion BST and ipsilateral BST were also measured and compared., Results: Contralateral BST did not evoke discernible MEPs in most subjects. In 21 subjects (67.7%), ipsilateral BST elicited larger MEPs than inion BST did, and AMT for ipsilateral BST was lower than or equal to the AMT for inion BST in all subjects. Ipsilateral BST elicited shorter latency in such subjects., Conclusions: The suitable stimulation site for BST differed among subjects. About two-thirds showed larger MEP to ipsilateral BST., Significance: These findings might help us to find an efficient stimulation site for BST in each subject., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)