Roles of the cerebellum and basal ganglia in temporal integration: Insights from a synchronized tapping task.

OBJECTIVE: The aim of this study was to clarify the roles of the cerebellum and basal ganglia for temporal integration. METHODS: We studied 39 patients with spinocerebellar degeneration (SCD), comprising spinocerebellar atrophy 6 (SCA6), SCA31, Machado-Joseph disease (MJD, also called SCA3), and multiple system atrophy (MSA). Thirteen normal subjects participated as controls. Participants were instructed to tap on a button in synchrony with isochronous tones. We analyzed the inter-tap interval (ITI), synchronizing tapping error (STE), negative asynchrony, and proportion of delayed tapping as indicators of tapping performance. RESULTS: The ITI coefficient of variation was increased only in MSA patients. The standard variation of STE was larger in SCD patients than in normal subjects, especially for MSA. Negative asynchrony, which is a tendency to tap the button before the tones, was prominent in SCA6 and MSA patients, with possible basal ganglia involvement. SCA31 patients exhibited normal to supranormal performance in terms of the variability of STE, which was surprising. CONCLUSIONS: Cerebellar patients generally showed greater STE variability, except for SCA31. The pace of tapping was affected in patients with possible basal ganglia pathology. SIGNIFICANCE: Our results suggest that interaction between the cerebellum and the basal ganglia is essential for temporal processing. The cerebellum and basal ganglia and their interaction regulate synchronized tapping, resulting in distinct tapping pattern abnormalities among different SCD subtypes.

Temporal synchronization for in-phase and antiphase movements during bilateral finger- and foot-tapping tasks.

Appropriate motor performance, which must be precisely processed and timed to temporal and spatial requirements, can be studied using a synchronized tapping task. For gait rehabilitation, estimation of bilateral foot-tapping accuracy is important, as walking involves bilateral movements, usually antiphase, of the lower extremities. Rhythmic control of lower limb movements, such as gait, involves voluntary control and may also be automatically regulated by the central pattern generator. This study investigated the temporal synchronization of in-phase and antiphase movements using synchronized bilateral finger and foot-tapping tasks. Thirty healthy young adult volunteers were enrolled and instructed to tap the finger or foot button synchronously with the tones presented at fixed inter-stimulus intervals (ISIs). One of 10 different ISIs (250-4800 ms) was selected for each block, in which 110 tones were presented. Taps were performed by either unilateral or bilateral fingers or feet, either in-phase (to move bilateral fingers or ankles simultaneously) or antiphase (to move bilateral fingers or ankles alternately). The synchronization error (SE) and coefficient of variation (CV) of the inter-tap interval (ITI) were evaluated. In all trials with short ISIs, SEs were narrowly distributed, either clustered around 0 ms or with a slightly negative value. Although SE variability gradually increased with increasing ISI, the CV of ITI was significantly lower for antiphase movement than for unilateral or in-phase movement in the foot-tapping task, but not in the finger-tapping task. The preserved temporal synchronization for antiphase movement of the foot, but not finger tapping, may be due to the neural mechanisms underlying locomotion.

Time Distortion in Parkinsonism.

Although animal studies and studies on Parkinson's disease (PD) suggest that dopamine deficiency slows the pace of the internal clock, which is corrected by dopaminergic medication, timing deficits in parkinsonism remain to be characterized with diverse findings. Here we studied patients with PD and progressive supranuclear palsy (PSP), 3-4 h after drug intake, and normal age-matched subjects. We contrasted perceptual (temporal bisection, duration comparison) and motor timing tasks (time production/reproduction) in supra- and sub-second time domains, and automatic versus cognitive/short-term memory-related tasks. Subjects were allowed to count during supra-second production and reproduction tasks. In the time production task, linearly correlating the produced time with the instructed time showed that the "subjective sense" of 1 s is slightly longer in PD and shorter in PSP than in normals. This was superposed on a prominent trend of underestimation of longer (supra-second) durations, common to all groups, suggesting that the pace of the internal clock changed from fast to slow as time went by. In the time reproduction task, PD and, more prominently, PSP patients over-reproduced shorter durations and under-reproduced longer durations at extremes of the time range studied, with intermediate durations reproduced veridically, with a shallower slope of linear correlation between the presented and produced time. In the duration comparison task, PD patients overestimated the second presented duration relative to the first with shorter but not longer standard durations. In the bisection task, PD and PSP patients estimated the bisection point (BP50) between the two supra-second but not sub-second standards to be longer than normal subjects. Thus, perceptual timing tasks showed changes in opposite directions to motor timing tasks: underestimating shorter durations and overestimating longer durations. In PD, correlation of the mini-mental state examination score with supra-second BP50 and the slope of linear correlation in the reproduction task suggested involvement of short-term memory in these tasks. Dopamine deficiency didn't correlate significantly with timing performances, suggesting that the slowed clock hypothesis cannot explain the entire results. Timing performance in PD may be determined by complex interactions among time scales on the motor and sensory sides, and by their distortion in memory.

Does the Clock Tick Slower or Faster in Parkinson's Disease? - Insights Gained From the Synchronized Tapping Task.

The rhythm of the internal clock is considered to be determined by the basal ganglia, with some studies suggesting slower internal clock in Parkinson's disease (PD). However, patients may also show motor hastening when they walk (festination) or are engaged in repetitive tapping, indicating faster ticking of the internal clock. Is the internal clock slower or faster in PD? The purpose of this study was to answer this question, i.e., how fast and slow a rhythm they can synchronize with, especially with reference to the limit of sensorimotor synchronization or temporal integration, representing the threshold of slower pace they can entrain into their motor actions, which is known to lie between 2 and 3 s in normal subjects but not yet studied in PD. We employed a synchronized tapping task that required subjects to tap the key in synchrony with repetitive tones at fixed interstimulus intervals (ISI) between 200 and 4800 ms. Twenty normal subjects and sixteen PD patients were enrolled, who were classified into early and advanced PD groups by UPDRS-III (early: 15 or less, advanced: more than 15). The ISI at which the response changes from synchronizing with the tones to lagging behind them was considered to be the limit of temporal integration. Early PD patients responded ahead of the tones (negative asynchrony), which became more apparent with repeated tapping. This suggested "faster" ticking clock even in the presence of the pacing tones. In normal subjects, the limit of temporal integration was around 2-3 s: below this, subjects could synchronize with the tones, while above it they had difficulty in synchronization. In early PD patients, the limit of temporal integration was significantly longer than in normal subjects, pointing to their enhanced ability to synchronize also with slower paces of tones, but advanced PD patients had significantly shortened limits, suggesting that advanced patients lost this ability. In conclusion, the limit of temporal integration is initially longer but gets shorter as the disease progresses. It can be explained by the hastening of the internal clock at the earlier stages of PD, followed by the loss of temporal integration.

Somatosensory-evoked potential modulation by quadripulse transcranial magnetic stimulation in patients with benign myoclonus epilepsy.

OBJECTIVE: In patients with benign myoclonus epilepsy (ME), giant sensory-evoked potential (SEP) reflects the hyperexcitability of the sensory cortex. The aim of this study was to compare the effect of quadripulse transcranial magnetic stimulation (QPS) on the median nerve SEP between ME patients and healthy subjects. METHODS: Ten healthy volunteers and six ME patients with giant SEP participated in this study. QPSs at interpulse intervals (IPIs) of 5, 30, 50, 100, 500 and 1250 ms were applied over the left primary motor cortex (M1) for 30 min. The peak-to-peak amplitudes of N20 to P25 (N20-P25) and P25 to N33 (P25-N33) components were measured at the left somatosensory cortex. RESULTS: In healthy participants, the P25-N33 was bidirectionally modulated by QPS over M1, following the Bienenstock-Cooper-Munro (BCM) theory. The N20-P25 was not affected by any QPSs. In ME patients, the giant P25-N33 was potentiated after any QPSs. Furthermore, the N20-P25 was also potentiated after QPS at IPIs of 5, 30, 50 100 or 500 ms. CONCLUSIONS: In ME patients, the cascade for long-term depression-like effects may be impaired. SIGNIFICANCE: The giant SEP was furthermore enhanced by QPS.

The 3-second rule in hereditary pure cerebellar ataxia: a synchronized tapping study.

The '3-second rule' has been proposed based on miscellaneous observations that a time period of around 3 seconds constitutes the fundamental unit of time related to the neuro-cognitive machinery in normal humans. The aim of paper was to investigate the temporal processing in patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration, using a synchronized tapping task. Seventeen SCA patients (11 SCA6, 6 SCA31) and 17 normal age-matched volunteers participated. The task required subjects to tap a keyboard in synchrony with sequences of auditory stimuli presented at fixed interstimulus intervals (ISIs) between 200 and 4800 ms. In this task, the subjects required non-motor components to estimate the time of forthcoming tone in addition to motor components to tap. Normal subjects synchronized their taps to the presented tones at shorter ISIs, whereas as the ISI became longer, the normal subjects displayed greater latency between the tone and the tapping (transition zone). After the transition zone, normal subjects pressed the button delayed relative to the tone. On the other hand, SCA patients could not synchronize their tapping with the tone even at shorter ISIs, although they pressed the button delayed relative to the tone earlier than normal subjects did. The earliest time of delayed tapping appearance after the transition zone was 4800 ms in normal subjects but 1800 ms in SCA patients. The span of temporal integration in SCA patients is shortened compared to that in normal subjects. This could represent non-motor cerebellar dysfunction in SCA patients.

Visual scanning area is abnormally enlarged in hereditary pure cerebellar ataxia.

The aim of paper was to investigate abnormalities in visual scanning using an eye-tracking device with patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration. Nineteen SCA patients (12 patients with SCA6 and 7 patients with SCA31) and 19 normal subjects in total participated in the study. While the subjects viewed images of varying complexity for later recall, we compared the visual scanning parameters between SCA patients and normal subjects. SCA patients had lower image recall scores. The scanned area in SCA patients was consistently larger than that in normal subjects. The amplitude of saccades was slightly larger in SCA patients than that in normal subjects, although it did not statistically differ between the two groups and correlated significantly with the scanned area in most images in SCA patients. The instability ratio of fixation, reflecting gaze-evoked nystagmus and downbeat nystagmus, was higher in SCA patients than that in normal subjects. Since SCA patients showed low scores despite wide visual scanning, the scanned area is considered to be abnormally enlarged. The larger scanned area in SCA patients was supposed mainly to result from the slightly larger saccade amplitude. Additionally, SCA patients showed prominent fixation disturbances probably due to gaze-evoked nystagmus and downbeat nystagmus. Consequently, SCA patients suffer from recognizing various objects in daily life, probably due to the impaired saccade control and impaired fixation.

Top-down but not bottom-up visual scanning is affected in hereditary pure cerebellar ataxia.

The aim of this study was to clarify the nature of visual processing deficits caused by cerebellar disorders. We studied the performance of two types of visual search (top-down visual scanning and bottom-up visual scanning) in 18 patients with pure cerebellar types of spinocerebellar degeneration (SCA6: 11; SCA31: 7). The gaze fixation position was recorded with an eye-tracking device while the subjects performed two visual search tasks in which they looked for a target Landolt figure among distractors. In the serial search task, the target was similar to the distractors and the subject had to search for the target by processing each item with top-down visual scanning. In the pop-out search task, the target and distractor were clearly discernible and the visual salience of the target allowed the subjects to detect it by bottom-up visual scanning. The saliency maps clearly showed that the serial search task required top-down visual attention and the pop-out search task required bottom-up visual attention. In the serial search task, the search time to detect the target was significantly longer in SCA patients than in normal subjects, whereas the search time in the pop-out search task was comparable between the two groups. These findings suggested that SCA patients cannot efficiently scan a target using a top-down attentional process, whereas scanning with a bottom-up attentional process is not affected. In the serial search task, the amplitude of saccades was significantly smaller in SCA patients than in normal subjects. The variability of saccade amplitude (saccadic dysmetria), number of re-fixations, and unstable fixation (nystagmus) were larger in SCA patients than in normal subjects, accounting for a substantial proportion of scattered fixations around the items. Saccadic dysmetria, re-fixation, and nystagmus may play important roles in the impaired top-down visual scanning in SCA, hampering precise visual processing of individual items.

Effects of electromagnetic fields emitted from W-CDMA-like mobile phones on sleep in humans.

In this study, we investigated subjective and objective effects of mobile phones using a Wideband Code Division Multiple Access (W-CDMA)-like system on human sleep. Subjects were 19 volunteers. Real or sham electromagnetic field (EMF) exposures for 3 h were performed before their usual sleep time on 3 consecutive days. They were exposed to real EMF on the second or third experimental day in a double-blind design. Sleepiness and sleep insufficiency were evaluated the next morning. Polysomnograms were recorded for analyses of the sleep variables and power spectra of electroencephalograms (EEG). No significant differences were observed between the two conditions in subjective feelings. Sleep parameters including sleep stage percentages and EEG power spectra did not differ significantly between real and sham exposures. We conclude that continuous wave EMF exposure for 3 h from a W-CDMA-like system has no detectable effects on human sleep.

Cortical hemoglobin concentration changes underneath the coil after single-pulse transcranial magnetic stimulation: a near-infrared spectroscopy study.

Using near-infrared spectroscopy (NIRS) and multichannel probes, we studied hemoglobin (Hb) concentration changes when single-pulse transcranial magnetic stimulation (TMS) was applied over the left hemisphere primary motor cortex (M1). Seventeen measurement probes were centered over left M1. Subjects were studied in both active and relaxed conditions, with TMS intensity set at 100%, 120%, and 140% of the active motor threshold. The magnetic coils were placed so as to induce anteromedially directed currents in the brain. Hb concentration changes were more prominent at channels over M1 and posterior to it. Importantly, Hb concentration changes at M1 after TMS differed depending on whether the target muscle was in an active or relaxed condition. In the relaxed condition, Hb concentration increased up to 3-6 s after TMS, peaking at ∼6 s, and returned to the baseline. In the active condition, a smaller increase in Hb concentrations continued up to 3-6 s after TMS (early activation), followed by a decrease in Hb concentration from 9 to 12 s after TMS (delayed deactivation). Hb concentration changes in the active condition at higher stimulus intensities were more pronounced at locations posterior to M1 than at M1. We conclude that early activation occurs when M1 is activated transsynaptically. The relatively late deactivation may result from the prolonged inhibition of the cerebral cortex after activation. The posterior-dominant activation at higher intensities in the active condition may result from an additional activation of the sensory cortex due to afferent inputs from muscle contraction evoked by the TMS.

Quadri-pulse stimulation induces stimulation frequency dependent cortical hemoglobin concentration changes within the ipsilateral motor cortical network.

BACKGROUND: Imaging studies investigating repetitive transcranial magnetic stimulation (rTMS) mediated hemodynamic consequences revealed inconsistent results, mainly due to differences in rTMS parameters and technical difficulties with simultaneous recordings during rTMS. OBJECTIVE/HYPOTHESIS: Quadri-pulse rTMS (QPS) induces bidirectional long-term plasticity of the human primary motor cortex (M1). To evaluate its on-line effects, near infrared spectroscopy (NIRS) recordings were performed during QPS. We hypothesized that on-line effects during QPS are different from long-term aftereffects. METHODS: Using a novel TMS - on-line multi-channel NIRS setup we recorded hemoglobin concentration [Hb] changes at the stimulated M1 and adjacent sensory-motor areas during QPS protocols inducing oppositely directed aftereffects (QPS-5: interstimulus interval (ISI) 5 ms, potentiation; QPS-50: ISI 50 ms, depression). In two experiments we studied NIRS changes during either single or repeated QPS bursts. RESULTS: The repetitive QPS-5 bursts significantly decreased oxyhemoglobin concentration ([oxy-Hb]) in the ipsilateral M1. A single QPS-5 burst decreased [oxy-Hb] in the M1 and premotor cortex. QPS-50 induced no significant NIRS changes at any sites. CONCLUSIONS: QPS can significantly alter cortical hemodynamics depending on the stimulation frequency. While bidirectional long-term aftereffects of QPS reflect synaptic efficacy changes, unidirectional on-line effects during QPS may represent pure electrophysiological property changes within the cell membrane or synapse. Since neuronal postexcitatory inhibitory postsynaptic potentials typically peak within the first 10-20 ms, only pulses delivered at higher frequencies may lead to summation of the inhibitory effects, resulting in [oxy-Hb] decrease only after QPS-5. Our new TMS-NIRS setup may be valuable to investigate TMS induced neurovascular coupling mechanisms in humans.

Bidirectional modulation of sensory cortical excitability by quadripulse transcranial magnetic stimulation (QPS) in humans.

OBJECTIVE: Quadripulse transcranial magnetic stimulation (QPS) is a newly designed patterned repetitive transcranial magnetic stimulation (TMS). Previous studies of QPS showed bidirectional effects on the primary motor cortex (M1), which depended on its inter-stimulus interval (ISI): motor evoked potentials (MEPs) were potentiated at short ISIs and depressed at long ISIs (homotopic effects). These physiological characters were compatible with synaptic plasticity. In this research, we studied effects of QPS on the primary sensory cortex (S1). METHODS: One burst consisted of four monophasic TMS pulses at an intensity of 90% active motor threshold. The ISI of four pulses was set at 5 ms (QPS-5) or at 50 ms (QPS-50). Same bursts were given every 5s for 30 min. QPS-5 and QPS-50 were performed over three areas (M1, S1 and dorsal premotor cortex (dPMC)). One sham stimulation session was also performed. Excitability changes of S1 were evaluated by timeline of somatosensory evoked potentials (SEPs). RESULTS: QPS-5 over M1 or dPMC enhanced the P25-N33 component of SEP, and QPS-50 over M1 depressed it. By contrast, QPSs over S1 had no effects on SEPs. CONCLUSIONS: QPSs over motor cortices modulated the S1 cortical excitability (heterotopic effects). Mutual connections between dPMC or M1 and S1 might be responsible for these modulations. SIGNIFICANCE: QPSs induced heterotopic LTP or LTD-like cortical excitability changes.

Where do neurologists look when viewing brain CT images? An eye-tracking study involving stroke cases.

The aim of this study was to investigate where neurologists look when they view brain computed tomography (CT) images and to evaluate how they deploy their visual attention by comparing their gaze distribution with saliency maps. Brain CT images showing cerebrovascular accidents were presented to 12 neurologists and 12 control subjects. The subjects' ocular fixation positions were recorded using an eye-tracking device (Eyelink 1000). Heat maps were created based on the eye-fixation patterns of each group and compared between the two groups. The heat maps revealed that the areas on which control subjects frequently fixated often coincided with areas identified as outstanding in saliency maps, while the areas on which neurologists frequently fixated often did not. Dwell time in regions of interest (ROI) was likewise compared between the two groups, revealing that, although dwell time on large lesions was not different between the two groups, dwell time in clinically important areas with low salience was longer in neurologists than in controls. Therefore it appears that neurologists intentionally scan clinically important areas when reading brain CT images showing cerebrovascular accidents. Both neurologists and control subjects used the "bottom-up salience" form of visual attention, although the neurologists more effectively used the "top-down instruction" form.

Inter-individual variation in the efficient stimulation site for magnetic brainstem stimulation.

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.

Small saccades restrict visual scanning area in Parkinson's disease.

The purpose of this study was to investigate abnormalities in visual scanning when Parkinson's disease patients view images of varying complexity. Eighteen nondemented Parkinson's disease patients and 18 normal subjects participated in the study. The ocular fixation position during viewing visual images was recorded using an eye-tracking device. The number of saccades, duration of fixation, amplitude of saccades, and scanned area in Parkinson's disease patients were compared with those in normal subjects. We also investigated whether the number of saccades, duration of fixation, or amplitude of saccades influenced the scanned area. While scanning images of varying complexity, Parkinson's disease patients made fewer saccades with smaller amplitude and longer fixation compared with normal subjects. As image complexity increased, the number of saccades and duration of fixation gradually approached those of normal subjects. Nevertheless, the scanned area in Parkinson's disease patients was consistently smaller than that in normal subjects. The scanned area significantly correlated with saccade amplitude in most images. Importantly, although Parkinson's disease patients cannot make frequent saccades when viewing simple figures, they can increase the saccade number and reduce their fixation duration when viewing more complex figures, making use of the abundant visual cues in such figures, suggesting the existence of ocular kinesie paradoxale. Nevertheless, both the saccade amplitude and the scanned area were consistently smaller than those of normal subjects for all levels of visual complexity. This indicates that small saccade amplitude is the main cause of impaired visual scanning in Parkinson's disease patients.

Cortico-conus motor conduction time (CCCT) for leg muscles.

OBJECTIVE: To measure the conduction time from the motor cortex to the conus medullaris (cortico-conus motor conduction time, CCCT) for leg muscles using magnetic stimulation. METHODS: Motor evoked potentials (MEPs) were recorded from tibialis anterior muscles in 51 healthy volunteers. To activate spinal nerves at the most proximal cauda equina level or at the conus medullaris level, magnetic stimulation was performed using a MATS coil. Transcranial magnetic stimulation of the motor cortex was also conducted to measure the cortical latency for the target muscle. To obtain the CCCT, the latency of MEPs to conus stimulation (conus latency) was subtracted from the cortical latency. RESULTS: MATS coil stimulation evoked reproducible MEPs in all subjects, yielding CCCT data for all studied tibialis anterior muscles. CONCLUSIONS: MATS coil stimulation provides CCCT data for healthy subjects. SIGNIFICANCE: This novel method is useful for evaluation of corticospinal tract function for leg muscles because no peripheral component affects the CCCT.

Influence of short-interval intracortical inhibition on short-interval intracortical facilitation in human primary motor cortex.

Using the paired-pulse paradigm, transcranial magnetic stimulation (TMS) has revealed much about the human primary motor cortex (M1). A preceding subthreshold conditioning stimulus (CS) inhibits the excitability of the motor cortex, which is named short-interval intracortical inhibition (SICI). In contrast, facilitation is observed when the first pulse (S1) is followed by a second one at threshold (S2), named short-interval intracortical facilitation (SICF). SICI and SICF have been considered to be mediated by different neural circuits within M1, but more recent studies reported relations between them. In this study, we performed triple-pulse stimulation consisting of CS-S1-S2 to further explore putative interactions between these two effects. Three intensities of CS (80-120% of active motor threshold: AMT) and two intensities of S2 (120 and 140% AMT) were combined. The SICF in the paired-pulse paradigm exhibited clear facilitatory peaks at ISIs of 1.5 and 3 ms. The second peak at 3 ms was significantly suppressed by triple-pulse stimulation using 120% AMT CS, although the first peak was almost unaffected. Our present results obtained using triple-pulse stimulation suggest that each peak of SICF is differently modulated by different intensities of CS. The suppression of the second peak might be ascribed to the findings in the paired-pulse paradigm that CS mediates SICI by inhibiting later I waves such as I3 waves and that the second peak of SICF is most probably related to I3 waves. We propose that CS might inhibit the second peak of SICF at the interneurons responsible for I3 waves.

The effect of electromagnetic field emitted by a mobile phone on the inhibitory control of saccades.

OBJECTIVE: To investigate whether exposure to a pulsed high-frequency electromagnetic field (pulsed EMF) emitted by a mobile phone has short-term effects on the inhibitory control of saccades. METHODS: A double-blind, counterbalanced crossover study design was employed. We assessed the performance of 10 normal subjects on antisaccade (AS) and cued saccade (CUED) tasks as well as two types of overlap saccade (OL1, OL2) task before and after 30 min of exposure to EMF emitted by a mobile phone or sham exposure. RESULTS: After EMF or sham exposure, we observed a slight but significant shortening of latency in the CUED and OL2 tasks. AS amplitude decreased as well as the saccade velocities in the AS, CUED, and OL1 tasks after exposure. These changes occurred regardless of whether exposure was real or sham. The frequencies of pro-saccades in the AS task, saccades to cue in the CUED task, and prematurely initiated saccades in the overlap (OL2) task did not change significantly after real or sham EMF exposure. CONCLUSIONS: Thirty minutes of mobile phone exposure has no significant short-term effect on the inhibitory control of saccades. SIGNIFICANCE: The cortical processing responsible for saccade inhibition is not affected by exposure to EMF emitted by a mobile phone.

Primary motor cortical metaplasticity induced by priming over the supplementary motor area.

Motor cortical plasticity induced by repetitive transcranial magnetic stimulation (rTMS) sometimes depends on the prior history of neuronal activity. These effects of preceding stimulation on subsequent rTMS-induced plasticity have been suggested to share a similar mechanism to that of metaplasticity, a homeostatic regulation of synaptic plasticity. To explore metaplasticity in humans, many investigations have used designs in which both priming and conditioning are applied over the primary motor cortex (M1), but the effects of priming stimulation over other motor-related cortical areas have not been well documented. Since the supplementary motor area (SMA) has anatomical and functional cortico-cortical connections with M1, here we studied the homeostatic effects of priming stimulation over the SMA on subsequent rTMS-induced plasticity of M1. For priming and subsequent conditioning, we employed a new rTMS protocol, quadripulse stimulation (QPS), which produces a broad range of motor cortical plasticity depending on the interval of the pulses within a burst. The plastic changes induced by QPS at various intervals were altered by priming stimulation over the SMA, which did not change motor-evoked potential sizes on its own but specifically modulated the excitatory I-wave circuits. The data support the view that the homeostatic changes are mediated via mechanisms of metaplasticity and highlight an important interplay between M1 and SMA regarding homeostatic plasticity in humans.