Clinical Neurophysiology 124 (2013) 273282

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Clinical Neurophysiology
journal homepage: www.elsevier.com/locate/clinph

Cortical rhythm of No-go processing in humans: An MEG study

Hiroki Nakata a,b,c,, Kiwako Sakamoto a,b, Asuka Otsuka b, Masato Yumoto b, Ryusuke Kakigi a
a

Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan Department of Clinical Laboratory, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan c Faculty of Sport Sciences, Waseda University, Tokorozawa, Japan
b

a r t i c l e

i n f o

h i g h l i g h t s
 We investigated the characteristics of cortical rhythmic activity in No-go processing during a somatosensory Go/No-go paradigm, by magnetoencephalography (MEG).  A rebound in amplitude was recorded in the No-go trials for theta, alpha, and beta activity, peaking at 600900 ms.  The cortical rhythmic activity clearly has several dissociated components relating to different motor functions, including response inhibition, execution, and decision-making.

Article history: Accepted 27 June 2012 Available online 3 August 2012 Keywords: MEG Response inhibition Somatosensory Go/No-go

a b s t r a c t
Objective: We investigated the characteristics of cortical rhythmic activity in No-go processing during somatosensory Go/No-go paradigms, by using magnetoencephalography (MEG). Methods: Twelve normal subjects performed a warning stimulus (S1) imperative stimulus (S2) task with Go/No-go paradigms. The recordings were conducted in three conditions. In Condition 1, the Go stimulus was delivered to the second digit, and the No-go stimulus to the fth digit. The participants responded by pushing a button with their right thumb for the Go stimulus. In Condition 2, the Go and No-go stimuli were reversed. Condition 3 was the resting control. Results: A rebound in amplitude was recorded in the No-go trials for theta, alpha, and beta activity, peaking at 600900 ms. A suppression of amplitude was recorded in Go and No-go trials for alpha activity, peaking at 300600 ms, and in Go and No-go trials for beta activity, peaking at 200300 ms. Conclusion: The cortical rhythmic activity clearly has several dissociated components relating to different motor functions, including response inhibition, execution, and decision-making. Signicance: The present study revealed the characteristics of cortical rhythmic activity in No-go processing. 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction The cortical rhythmic activity relating to response inhibitory processing has been claried by using scalp electroencephalography (EEG). EEG has been frequently used to examine the dynamics of synchronized cortical activity, and offers a high temporal resolution in the order of milliseconds. Several studies of EEG spectral power have examined the characteristics of cortical oscillations in No-go trials during Go/No-go paradigms (Shibata et al., 1997, 1998, 1999; Leocani et al., 2001; Kamarajan et al., 2004; KirmiziAlsan et al., 2006; Barry, 2009; Harmony et al., 2009). A common nding is that the power of the theta, alpha, and beta frequency
Corresponding author at: Faculty of Sport Sciences, Waseda University, 2-57915 Mikajima, Tokorozawa, Saitama 359-1192, Japan. Tel.: +81 4 2947 4614; fax: +81 4 2947 6826. E-mail address: nakata@aoni.waseda.jp (H. Nakata).

bands decreases or increases at 300900 ms after the onset of a No-go stimulus. For example, Leocani et al. (2001) reported that the spectral power at 10 Hz and 1822 Hz decreased at 300600 ms after stimulus onset, and the power at 10 Hz and 1822 Hz increased at 9001200 ms and 600900 ms, respectively. Harmony et al. (2009) showed a complex spatiotemporal pattern of spectral power decreases and increases in Go- and No-go conditions. These power changes may be due to a decrease or increase in synchrony of the underlying neuronal populations. The former case is called event-related desynchronization (ERD) (i.e. suppression), and the latter, event-related synchronization (ERS) (i.e. rebound) (Pfurtscheller and Lopes da Silva, 1999). There has been interest in the role of cortical oscillatory activity in sensory, motor and cognitive processing as a key factor in binding mechanisms (Farmer, 1998; Alegre et al., 2002). The oscillations have been suggested to reect an idling cortex generated by a large area of highly

1388-2457/$36.00 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2012.06.019

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synchronous neuronal ring in the absence of inputs, or alternatively, changes in coherent activity resulting from synchronous inputs from other brain regions (Jurkiewicz et al., 2006). However, the neurophysiological mechanisms and functional signicance for No-go-related cortical oscillations are not well understood, although a number of studies have investigated movement-related cortical oscillations with ERD and ERS (Pfurtscheller and Lopes da Silva, 1999). We considered that other methodological approaches were needed to improve understanding of the mechanisms, rather than the use of EEG or standard Go/No-go paradigms. Based on these previous studies, the objective of the current study was to clarify the dynamics of the neuromagnetic cortical rhythm related to response inhibitory processing in the main frequency components (theta, alpha, and beta), by using magnetoencephalography (MEG). MEG has theoretical advantages over EEG, because the magnetic elds recorded on the scalp are less affected by volume currents and anatomical inhomogeneity. MEG also has a high temporal resolution, permitting neural activity to be differentiated on a time scale of milliseconds (see reviews, Kakigi et al., 2000; Kaneoke, 2006). Thus, MEG can detect neural activities in the cerebral cortex directly. To our knowledge, however, no study has used MEG to investigate the cortical rhythmic activity of response inhibitory processing. In the present study, we used Temporal Spectral Evolution (TSE) to extract the spatiotemporal characteristics of cortical oscillations, following previous MEG studies (Salmelin and Hari, 1994; Salmelin et al., 1995; Nagamine et al., 1996; Salenius et al., 1997; Simoes et al., 2004; Tamura et al., 2005). To obtain the waveforms of TSE, the signals were rstly ltered through a passband suggested by a spectral analysis and, subsequently, the absolute signal values were averaged with respect to the event (see a review, Hari et al., 1997). This demonstrates event-related changes of the average amplitude level of oscillatory activities in a given passband in the same unit as the original signals. The present study used somatosensory Go/No-go paradigms, in which the second or fth digit of the left hand was stimulated. Some event-related potential (ERP) studies found that the amplitude of the N2 component was much smaller following auditory than visual stimuli (Falkenstein et al., 1995, 1999; Kiefer et al. 1998). Falkenstein et al. (1999) suggested that the inhibitory processing as reected in N2 is modality specic. In a monkey study, Gemba and Sasaki (1990) also reported that No-go potentials after an auditory stimulus were observed in the rostral part of the dorsal bank of the principal sulcus, as opposed to the caudal part of the same bank after a visual stimulus. Therefore, the present study aimed to investigate the dynamics of the neuromagnetic cortical rhythm during somatosensory Go/No-go paradigms. We also designed a target and non-target stimulus with the same probability to avoid the effect of stimulus probability and to minimize differences in response conict between event types (Braver et al., 2001; Nakata et al., 2005). 2. Methods 2.1. Participants Twelve normal right-handed subjects (three females and nine males; mean age 31.3 years, range 2542 years) participated. The participants had no previous history of neurological or psychiatric disorders. Informed consent was obtained from all subjects. The study was approved by the Ethical Committee of the National Institute for Physiological Sciences. 2.2. Experimental paradigm The participants performed a warning stimulus (S1) imperative stimulus (S2) task with Go/No-go paradigms. S1 was an

auditory pure tone (60 dB SPL, 50 ms duration), presented binaurally through earphones. For S2, we stimulated the second or fth digit of the left hand with ring electrodes. The electrical stimuli were a current constant square-wave pulse 0.2 ms in duration, and the stimulus intensity was 2.5 times the sensory threshold, which yielded no pain or unpleasant sensation. The anode was placed at the distal interphalangeal joint and the cathode at the proximal interphalangeal joint of the corresponding digit. The probability of the stimulus for the second and fth digits was even. A pair of S1 and S2 stimuli was delivered to the participants at an interval of 1500 ms. The S1S1 interval was 5 s. The recordings were conducted in three conditions. In Condition 1, the Go stimulus was delivered to the second digit of the left hand, and the No-go stimulus to the fth digit of the left hand. The participants had to respond to it by pushing a button with their right thumb (contralateral to the stimulated side) as quickly as possible only after the presentation of a Go stimulus. In Condition 2, the stimulation was reversed, that is, the Go stimulus was delivered to the fth digit and the No-go stimulus to the second digit. The response task was the same as in Condition 1. Condition 3 was the resting control, in which the subjects were asked to relax and rest quietly with no task. During the recordings, the participants were instructed to keep their eyes open and look at a small xation point positioned in front of them at a distance of approximately 1.5 m. One run comprised 160 epochs of stimulation, which included 80 epochs for the Go stimuli and 80 for the No-go stimuli. The order of conditions was randomized for each participant and counterbalanced across all participants. A practice session consisting of 20 stimuli preceded the recordings. 2.3. MEG recordings and analysis Brain activities in Go/No-go paradigms were recorded with a helmet-shaped 306-channel detector array (Vectorview; ELEKTA Neuromag Oy, Helsinki, Finland), which comprises 102 identical triple sensor elements, in a magnetically shielded room. Each sensor element consists of two orthogonal planar gradiometers and one magnetometer coupled to a multi-SQUID (Superconducting Quantum Interference Device) and thus provides three independent measurements of the magnetic elds. In the present study, we analyzed MEG signals from 204-channel planar-type gradiometers, because the data from magnetometers are usually susceptive to global magnetic noise including changes in geomagnetic elds (Hmlinen et al., 1993) (the noise can be successfully canceled out in recording with planar sensors). The signals were recorded with a bandpass lter (0.1100 Hz) and digitized at 900 Hz. Before the recordings, four head position indicator (HPI) coils were attached to specic sites on the subjects head, and then electric current was fed to the HPI coils to determine the exact location of the head with respect to the MEG sensors. The x-axis was xed with the preauricular points, pointing to the right, the positive y-axis traversing the nasion, and the positive z-axis pointing up. From the continuous MEG raw data, epochs from 1000 ms before the onset of S1 to 1500 ms after the onset of S2 were collected for the off-line analysis (i.e. 4000 ms in total). The data were ltered at around the theta band (48 Hz), alpha band (812 Hz), and beta band (1822 Hz). The ltered signals were then rectied and averaged across epochs. The baseline was set from 1000 ms before S1 onset to S1 onset. The magnetic responses from three regions of 22 channels in each hemisphere (LF = left frontal, LC = left central, LP = left parietal, RF = right frontal, RC = right central, RP = right parietal) were averaged, and used for the analyses of amplitude and latency (Fig. 1). The epochs containing eye motion artifacts or blinks, which were inspected visually, were excluded from the off-line analysis using the Graph in Elekta Neuromag software. In this software to view raw data, the artifacts were

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assumption was violated. If the test result was signicant and the assumption of sphericity was violated, the GreenhouseGeisser adjustment was used to correct the sphericity by altering the degrees of freedom using a correction coefcient epsilon. When signicant effects were identied, the Bonferroni post hoc multiple comparison was used to identify specic differences. Statistical tests were performed using computer software (SPSS for windows ver. 16.0, SPSS). Statistical signicance was set at p < 0.05. 3. Results 3.1. Behavioral performance Table 1 shows the mean RT, SD of RT, commission error rate, and omission error rate in Conditions 1 and 2. For the mean RT, a signicant main effect of Condition was found (F(1, 11) = 24.509, p < 0.001), indicating that the responses were faster for the second digit than for the fth digit. In addition, a signicant main effect of Condition was observed for the commission error rate (F(1, 11) = 11.312, p < 0.01), showing that the commission error rate was signicantly larger in Condition 2 than Condition 1. There were no signicant differences between conditions in the SD of RT or omission error rate.
Fig. 1. Location of sensors in the regions of interest. LF = left frontal, LC = left central, LP = left parietal, RF = right frontal, RC = right central, RP = right parietal.

3.2. Theta band Fig. 2A displays the grand-averaged waveforms of theta bands in the three conditions across all participants for the second digit stimulation. Judging from the morphology, a rebound in amplitude was recorded in No-go trials after the onset of S2. No remarkable suppression or rebound was evident during Go and Control trials. A rebound similar to that in the No-go trials was found for the fth digit stimulation (Fig. 2B). The latency in the No-go trials peaked at around 800 ms (Table 2 and Supplementary Table S1). ANOVAs with Hemisphere and Region as factors did not show any signicant main effects or interactions. ANOVAs for the mean amplitude of theta bands revealed main effects of Condition (F(2, 22) = 9.699, p < 0.01) and Digit (F(1, 11) = 6.015, p < 0.05), DigitRegion interaction (F(2, 22) = 7.357, p < 0.01), and ConditionRegion interaction (Greenhouse Geisser correction: F(2.432, 26.751) = 4.303, e = 0.608, p < 0.05) (Table 3 and Supplementary Table S2). Furthermore, three-way ANOVAs with Digit, Condition, and Hemisphere showed a signicant main effect of Condition in the frontal region (F(2, 22) = 3.531, p < 0.05), signicant main effects of Digit (F(1, 11) = 8.182, p < 0.05) and Condition (F(2, 22) = 11.123, p < 0.001) in the temporal region, and signicant main effects of Digit (F(1, 11) = 6.091, p < 0.05) and Condition (F(2, 22) = 7.819, p < 0.001) in the parietal region. A post hoc analysis revealed that mean amplitude was signicantly more positive in No-go than Go and Control in the temporal region (p < 0.001, and p < 0.01, respectively), and in No-go than Go and Control in the parietal region (p < 0.01, and p < 0.05, respectively). 3.3. Alpha band

monitored in frontal regions, but detailed scales of the artifacts could not be represented as a limitation of the system. Thus, we checked them carefully to average. This method was followed by previous studies using the same Neuromag system (Nagamine et al., 1996; Tamura et al., 2005). When analyzing the data, we investigated the neuromagnetic cortical rhythm in Go (Condition 1), No-go (Condition 2), and Control (Condition 3) for the second digit stimulation, and Go (Condition 2), No-go (Condition 1), and Control (Condition 3) for the fth digit stimulation. If visible differences in the activity of Go and/or No-go were observed for each region, the peak latency was subjected to an analysis of variance (ANOVA) with repeated measures using within-subject factors. The peak latency of the suppression and rebound was dened for each individual as the time when the maximum deection of the oscillation was observed in the text data. In addition, the mean TSE amplitudes were calculated from 300 to 1200 ms after the onset of S2 in each band, which included peak amplitudes of both maximal suppression and rebound. The mean amplitudes in preparatory periods were analyzed from 500 ms to 1500 ms after the onset of S1. The data on mean amplitude was subjected to ANOVAs with Digit (Second vs. Fifth), Condition (Go, No-go, and Control), Region (Frontal, Central and Parietal), and Hemisphere (Left vs. Right) as within-subjects factors. The behavioral data on the mean reaction time (RT), the standard deviation (SD) of RT, commission error, and omission error were subjected to repeated measures ANOVAs with Condition (Condition 1 vs. Condition 2) as a factor. For all repeated measures factors with more than two levels, it was tested whether Mauchlys sphericity

Table 1 The mean reaction time and error rates in the two movement conditions. RT (ms) Con. 1 Con. 2 248.8 (17.8) 271.0 (18.3) SD of RT (ms) 56.1 (6.9) 64.3 (6.7) Com (%) 1.0 (0.3) 4.0 (0.9) Omi (%) 0.8 (0.6) 1.1 (0.6)

Con.: Condition; Com: commission error; Omi: omission error. Values in parentheses are the standard error (SE).

Fig. 3A represents the grand-averaged waveforms of alpha bands in each condition for the second digit. The rebound in No-go trials was recorded in all regions, peaking at around 700800 ms for the second digit stimulation. The rebound was conrmed in the central and parietal regions for the fth digit stimulation (Fig. 3B). ANOVAs for the peak latency in the second and fth digit stimulation did not show any signicant main effects or interactions. Suppression for the second digit was recorded only in Go

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Fig. 2. (A) (B) Grand-averaged waveforms of theta bands in the frontal, central, and parietal regions for the second and fth digit stimulation. Left and right hemispheric data were collapsed. Blue, red, and green lines indicate waveforms for Go, No-go, and Control, respectively. Thick and thin gray zones indicate periods analyzed for the mean amplitudes, involving the preparatory period and the rebound, respectively. Red arrows demonstrate the peak in the rebound for No-go.

Table 2 Peak latency of suppression and rebound in theta, alpha, and beta bands for the second digit stimulation. (ms) Theta No-go Alpha No-go Go Beta No-go No-go Go Rebound Rebound Suppression Rebound Suppression Suppression LF 789 (33) 733 (77) LC 825 (32) 727 (64) 556 (60) 743 (58) 230 (22) 330 (38) LP 758 (44) 712 (61) 498 (39) 715 (51) RF 797 (33) 766 (74) RC 774 (39) 754 (60) 595 (73) 713 (55) 195 (25) 255 (45) RP 758 (37) 805 (67) 424 (79) 666 (54)

654 (61)

623 (50)

LF = left frontal, LC = left central, LP = left parietal, RF = right frontal, RC = right central, RP = right parietal. Values in parentheses are the standard error (SE).

trials at LC, LP, RC, and RP, peaking at 400600 ms (Table 2). Suppression for the fth digit was obtained in Go and No-go trials at LP and RP, peaking at 300400 ms (Supplementary Table S2). ANOVAs with Condition and Hemisphere demonstrated a signicant main effect of Condition (F(1, 11) = 7.217, p < 0.05), indicating that the peak latency of the suppression was earlier in No-go than Go. ANOVAs for the mean amplitude of alpha bands revealed a main effect of Condition (F(2, 22) = 14.996, p < 0.001), DigitHemisphere interaction (F(1, 11) = 9.297, p < 0.05), and ConditionRegion interaction (GreenhouseGeisser correction: F(2.012, 22.128) = 6.656, e = 0.503, p < 0.01) (Table 3 and Supplementary Table S2). In

addition, three-way ANOVAs with Digit, Condition, and Hemisphere demonstrated signicant main effects of Condition in the frontal region (F(2, 22) = 13.762, p < 0.05), in the temporal region (F(2, 22) = 17.724, p < 0.001), and in the parietal region (F(2, 22) = 10.442, p < 0.01). Post hoc testing showed that the mean amplitude was signicantly more positive in No-go than Go and Control in the frontal region (p < 0.001, and p < 0.01, respectively), more positive in No-go than Go and Control in the central region (p < 0.001, and p < 0.01, respectively), more positive in No-go than Go in the parietal region (p < 0.001).

H. Nakata et al. / Clinical Neurophysiology 124 (2013) 273282 Table 3 Mean amplitude of theta, alpha, and beta bands in three conditions for the second digit stimulation. (fT/cm) Theta Go No-go Control Alpha Go No-go Control Beta Go No-go Control LF 0.5 (1.7) 5.1 (2.3) 1.0 (1.5) 2.2 (2.1) 8.9 (3.2) 2.0 (1.6) 5.1 (1.8) 8.4 (2.4) 4.6 (1.5) LC 0.6 (2.3) 10.6 (3.4) 1.4 (1.8) 0.3 (3.9) 17.0 (7.1) 4.4 (3.4) 0.0 (1.6) 11.6 (3.3) 7.8 (2.3) LP 0.7 (2.1) 11.3 (4.7) 1.2 (1.7) 3.0 (4.4) 19.4 (9.6) 9.5 (6.3) 0.3 (1.1) 7.6 (3.4) 4.1 (1.6) RF 0.6 (1.8) 2.2 (1.5) 0.8 (1.7) 0.9 (2.4) 4.5 (2.5) 0.5 (1.3) 2.2 (0.9) 5.6 (1.4) 3.1 (1.3) RC 3.1 (2.3) 8.0 (2.9) 1.0 (2.1) 7.6 (5.1) 11.5 (6.1) 2.7 (3.9) 0.5 (2.0) 11.1 (2.1) 9.5 (2.9) RP

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0.1 (2.7) 10.3 (3.7) 1.9 (3.0) 2.9 (7.1) 11.7 (7.0) 6.6 (5.5) 0.2 (1.7) 8.6 (1.8) 7.5 (2.2)

Values in parentheses are the standard error (SE).

Fig. 3. (A) (B) Grand-averaged waveforms of alpha bands in the frontal, central, and parietal regions for the second and fth digit stimulation. Left and right hemispheric data were collapsed. Blue, red, and green lines indicate waveforms for Go, No-go, and Control, respectively. Thick and thin gray zones indicate periods analyzed for the mean amplitudes, involving the preparatory period and the rebound, respectively. Red arrows directed downward show the peak of the rebound. Red and blue arrows directed upward indicate the peak of the suppression.

3.4. Beta band Fig. 4A displays the grand-averaged waveforms of beta bands in each condition for the second digit stimulation. The rebound

in No-go was recorded in all regions, peaking at around 700 ms, and a similar rebound was recorded in the fth digit stimulation (Fig. 4B). The suppressions for the second and fth digits were recorded in Go and No-go trials at LC and RC,

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Fig. 4. (A) (B) Grand-averaged waveforms of beta bands in the frontal, central, and parietal regions for the second and fth digit stimulation. Left and right hemispheric data were collapsed. Blue, red, and green lines indicate waveforms for Go, No-go, and Control, respectively. Thick and thin gray zones indicate periods analyzed for the mean amplitudes, involving the preparatory period and the rebound, respectively. Red arrows directed downward demonstrate the peak of the rebound. Red and blue arrows directed upward show the peak of the suppression.

peaking at around 200 ms (Table 2 and Supplementary Table S1), and ANOVAs with Condition (Go vs. No-go), Digit, and Hemisphere as factors demonstrated no signicant main effect or interaction. ANOVAs for the mean amplitude of beta bands revealed main effects of Condition (F(2, 22) = 14.476, p < 0.001) and Digit (F(1, 11) = 6.826, p < 0.05), and ConditionDigit interaction (F(2, 22) = 4.160, p < 0.05), ConditionRegion interaction (GreenhouseGeisser correction: F(2.334, 25.669) = 8.389, e = 0.583, p < 0.001), HemisphereRegion interaction (F(2, 22) = 8.647, p < 0.01), and DigitHemisphereRegion interaction (F(2, 22) = 5.654, p < 0.05) (Table 3 and Supplementary Table S2). Furthermore, one-way ANOVAs showed signicant main effects of Condition in the frontal region (F(2, 22) = 8.002, p < 0.01), in the temporal region (F(2, 22) = 17.859, p < 0.001), and in the parietal region (F(2, 22) = 7.606, p < 0.01), and signicant main effects of Digit in No-go trials (F(1, 11) = 9.076, p < 0.05) and Control (F(1, 11) = 8.112, p < 0.05). Post hoc testing showed that the mean amplitude was signicantly more positive in No-go than Go and Control in the frontal region (p < 0.05, and p < 0.01, respectively), more positive in No-go than Go in the central region (p < 0.001), more positive in No-go than Go in the parietal region (p < 0.01).

3.5. Preparatory periods The characteristics of the preparatory period differed among bands: that is, the amplitudes of the theta and alpha bands did not change in any regions, but the amplitude of the beta bands showed a gradual decrease over time before the onset of S2 (Fig. 4). ANOVAs for the amplitude of the theta bands revealed no significant main effect or interaction. ANOVAs for the amplitude of the alpha bands showed a significant main effect of Hemisphere (F(1, 11) = 5.733, p < 0.05), and DigitHemisphere interaction (F(1, 11) = 10.876, p < 0.01). ANOVAs for the amplitude of the beta bands revealed a signicant ConditionDigitRegion interaction (F(1.916, 21.076) = 4.094, e = 0.479, p < 0.05). Post-hoc testing collapsing the effect of Hemisphere demonstrated that the amplitudes for the second digit were significantly more negative in Go than Control in the central region (p < 0.05), but there were no signicant differences in the amplitudes for the fth digit. 3.6. The event-related magnetic eld Fig. 5 shows the event-related magnetic eld waveforms in a representative subject to compare the difference in waveforms

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Fig. 5. (Top) The event-related magnetic eld waveforms over 204 planar coils from the top of the head in a representative subject. (Bottom) An enlarged waveform recorded from four regions. Blue, red, and green lines indicate waveforms for Go, No-go, and Control, respectively. The arrows show the peak of the specic activity related to No-go processing after the onset of S2. All data were digitally ltered (0.140 Hz bandpass) for display purposes.

from band-related activity. The specic neural activity related to No-go processing was recorded after the onset of S2 in both hemispheres. A detailed analysis using an equivalent current dipole model was performed in our previous study (Nakata et al., 2005). 4. Discussion In the present study, we investigated the characteristics of cortical rhythmic activity in No-go processing, by using whole-head MEG. Our data demonstrated a rebound in amplitude in No-go

trials for theta, alpha, and beta bands, peaking at 600900 ms. Suppression was recorded in both Go and No-go trials for alpha bands, peaking at 300600 ms, and in both Go and No-go trials for beta bands, peaking at 200300 ms. TSE with MEG has been used to clarify the characteristics of cortical oscillations, especially for voluntary movement-related cortical activity (Salmelin and Hari, 1994; Salmelin et al., 1995; Nagamine et al., 1996; Salenius et al., 1997; Simoes et al., 2004; Tamura et al., 2005). To our knowledge, however, this is the rst MEG study to examine the response inhibitory processing in a Go/No-go paradigm, though the suppression (ERD) and rebound

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(ERS) phenomena have been found not only with EEG but also with MEG. 4.1. Behavioral performance The mean RT was signicantly faster in Condition 1 than Condition 2, and the commission error rate was signicantly larger in Condition 2 than Condition 1. These results indicate that the stimulus site in somatosensory Go/No-go paradigms is related to the difculty of each task. Indeed, it seems difcult to interpret these results, because our previous ndings did not reveal a signicant difference (Nakata et al., 2005), but other data showed that the responses were faster for the second digit than fth digit in the same Go/No-go paradigms (Nakata et al., 2006a). We hypothesized that the RT tended to be faster for the second digit than fth digit. The second and fth digits are anatomically dominated by the median nerve and ulnar nerve, respectively (Kimura, 2001), but conduction time from the digit to primary somatosensory cortex (SI) is almost the same (Huttunen et al., 2006). One possibility is that the information processing in the SI and activation of the primary motor cortex (MI) necessary to cause sequential reaction are more important following stimulation of the second digit than fth digit, since the somatosensory evoked magnetic elds ascending through the second digit would be greater (Hari et al., 1993). 4.2. The rebound in Go/No-go paradigms The strong rebound in amplitude of theta bands was recorded only in No-go trials for the second digit stimulation (Fig. 2A), and a similar weak rebound was also found in the waveforms for the fth digit stimulation (Fig. 2B). The latency peaked at around 800 ms. A rebound in amplitude of the alpha and beta bands was also observed in No-go trials, peaking at around 700800 ms (Figs. 3 and 4). The suppression/rebound (ERD/ERS) are generally thought to reect activation-based changes in functionally-related groups of cortical neurons (see a review, Pfurtscheller and Lopes da Silva, 1999), and considerable evidence for changes of amplitude in alpha and beta bands has been accumulated. The rebound observed after movement has been often interpreted as an indicator of idling in the cortex (Pfurtscheller et al., 1996), as well as the consequence of processes related to the end of the movement (Alegre et al., 2002). Within this framework, our current results indicate the specic neural activity related to No-go processing. A No-gospecic enhancement of power has been reported in previous EEG studies using auditory and visual Go/No-go paradigms (Shibata et al., 1997, 1998, 1999; Leocani et al., 2001; Kamarajan et al., 2004; Kirmizi-Alsan et al., 2006; Barry, 2009; Harmony et al., 2009). Consequently, the rebound in amplitude for No-go trials would be common to the visual, auditory, and somatosensory modalities. It was of particular interest that the rebound in No-go trials was found in the bilateral frontal, central, and parietal regions. Human neuroimaging has revealed that the neural networks for inhibitory processing include the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortices, supplementary motor area (SMA), anterior cingulate cortex (ACC), and temporal and parietal lobes (Kawashima et al., 1996; Konishi et al., 1999; Garavan et al., 1999; Chikazoe et al., 2007; Nakata et al., 2008a,b). The present study did not clarify which regions were responsible for the rebound in the No-go trials, suggesting that this rebound arises from widespread generators. As for the timing of occurrence in response inhibition, transcranial magnetic stimulation (TMS) also has been used to investigate both excitatory and inhibitory effects on the cerebral cortex during the performance of Go/No-go paradigms (Hoshiyama et al., 1996, 1997; Leocani et al., 2000; Waldvogel et al., 2000; Sohn et al.,

2002; Yamanaka et al., 2002; Nakata et al., 2006b). Common ndings of these studies were a decrease in the amplitude of motor evoked potentials (MEPs) at 100200 ms after No-go stimuli, and an increase after Go stimuli. In addition, Waldvogel et al. reported that inhibition of the amplitude of MEPs lasted for 500 ms after Nogo stimuli. There has been no study showing how long the No-go processing of the corticospinal tract lasted, but our TSE ndings may indicate the duration of neural activity in response inhibitory processing. 4.3. The suppression in Go/No-go paradigms The suppression in amplitude of alpha bands for the second digit stimulation was recorded in Go trials at LC, LP, RC, and RP, peaking at 400600 ms (Fig. 3A). Nagamine et al. (1996) using TSE with MEG provided evidence that alpha activity showed maximum suppression about 300 ms after the onset of electromyography (EMG) in both hemispheres. In the present study, the mean RT was about 250 ms in Condition 1 and 270 ms in Condition 2 (Table 1), suggesting that the onset of EMG occurred approximately 220 240 ms after the onset of S2. Subsequently, by adding 300 ms to the onset of EMG, the peak in suppression of alpha bands in our ndings becomes consistent with the results of Nagamine et al. Therefore, the suppression of alpha activity may be related directly to motor response execution (Go) processing. However, since the suppression for the fth digit stimulation was found in both Go and No-go trials at LP and RP (Fig. 3B), motor processing and other neural mechanisms would be related to the suppression of alpha activity. The suppression of beta activity was found in both Go and Nogo trials at LC and RC for the second and fth digit stimulation, peaking at around 200 ms (Fig. 4). These ndings suggested that the suppression was associated with stimulus discrimination and decision-making processing, rather than response execution and inhibition processing. In our past studies using functional magnetic resonance imaging (fMRI) during somatosensory Go/No-go paradigms, areas of the brain related to Go trials were located in the DLPFC, VLPFC, SMA and premotor area (PM), primary somato-motor area (SMI), inferior parietal lobule (IPL), insula, superior temporal gyrus (STG), temporoparietal junction (TPJ), posterior parietal cortex (PPC), and ACC (Nakata et al., 2008b). Brain activities related to the No-go trials were located in the DLPFC, VLPFC, pre-SMA/ middle frontal gyrus (MFG), primary somatosensory area (SI), IPL, insula, TPJ, and ACC (Nakata et al., 2008a). We did not perform a conjunction analysis for the regions activated during both Go and No-go trials, but judging from each specic activity, DLPFC, VLPFC, SMA, IPL, insula, TPJ, and ACC would be related to the overlapping regions in Go and No-go trials, indicating the neural networks for response selective and decision-making processing. 4.4. Cortical oscillations in the preparatory period Our neuromagnetic data for cortical oscillations in the preparatory period showed that the amplitudes of the theta and alpha bands changed little, but the amplitude of the beta bands gradually decreased. Alegre et al. (2004) utilizing auditory Go/No-go paradigms reported no changes in amplitude for alpha bands between S1 and S2 stimuli, which was in line with our nding. However, they did not show suppression in beta bands during the preparatory period. It seems difcult to interpret this nding, but in general, the beta pattern consists of a suppressive phase that begins at least 1.5 s before the movement starts (Stancak and Pfurtscheller, 1995, 1996), and the suppression has long been known to reect movement preparation. The amplitudes in preparatory periods were relatively similar between Go and No-go trials. In our S1S2 paradigms, S1 delivered

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the warning and set up the response and S2 indicated the Go/Nogo information (i.e. S2-centered-paradigm). By contrast, some studies have used a S1S2 paradigm in which S1 delivered Go/ No-go information and S2 merely showed the timing of the response after the Go-S1 stimulus (i.e. S1-centered-paradigm), showing the difference between Go and No-go activity during et al., 2001; Alegre et al., 2004). Takpreparatory periods (Filipovic ing our paradigms into consideration, our results are logical since participants should focus on both Go and No-go stimuli for S2. In the control condition, there were slow modulations of the oscillatory activity in the alpha band before the onset of S2, indicating that subjects might have paid some attention to the stimuli although they were instructed to relax. In a CNV paradigm without a motor task in response to an imperative stimulus (S2), well-pronounced negativity was recorded prior to S2 (Ruchkin et al., 1986; van Boxtel and Brunia, 1994). CNV has been associated with both motor preparation and cognitive processing including expectancy, motivation, attention, and arousal (Brunia, 1988; van Boxtel and Brunia, 1994; Ikeda et al., 1996). Therefore, we inferred that the slow modulation in alpha activity reected expectancy and attention to the S2. In conclusion, here we found that a rebound in amplitude was recorded in No-go trials for theta, alpha, and beta bands, peaking at 600900 ms. The suppression in amplitude was recorded in both Go and No-go trials for alpha and beta bands, peaking at 200 600 ms. These results in normal healthy subjects suggest that cortical rhythmic activity clearly has several dissociated components relating to different motor functions, including response inhibition, execution, and decision-making. Furthermore, our ndings might guide future studies of the neurophysiological changes in patients, and help to interpret the error proles seen in patients during Nogo trials. Indeed, several studies have shown differences in waveforms of ERPs and oscillation during No-go trials between normal subjects and patients (Weisbrod et al., 2000; Wiersema et al., 2006; Doege et al., 2010). The present study revealed the neuromagnetic activity of cortical rhythm in No-go processing. Acknowledgements We are very grateful to Mr. O. Nagata and Mr. Y. Takeshima for technical help during this study. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.clinph.2012. 06.019. References
Alegre M, Labarga A, Gurtubay IG, Iriarte J, Malanda A, Artieda J. Beta EEG changes during passive movements: sensory afferences contribute to the beta eventrelated desynchronization in humans. Neurosci Lett 2002;331:2932. Alegre M, Gurtubay IG, Labarga A, Iriarte J, Valencia M, Artieda J. Frontal and central oscillatory changes related to different aspects of the motor process: a study in Go/No-go paradigms. Exp Brain Res 2004;159:1422. Barry RJ. Evoked activity and EEG phase resetting in the genesis of auditory Go/ Nogo ERPs. Biol Psychol 2009;80:2929. Braver TS, Barch DM, Gray JR, Molfese DL, Snyder A. Anterior cingulate cortex and response conict: effects of frequency, inhibition and errors. Cereb Cortex 2001;11:82536. Brunia CHM. Movement and stimulus preceding negativity. Biol Psychol 1988;26:16578. Chikazoe J, Konishi S, Asari T, Jimura K, Miyashita Y. Activation of right inferior frontal gyrus during response inhibition across response modalities. J Cogn Neurosci 2007;19:6980. Doege K, Kumar M, Bates AT, Das D, Boks MP, Liddle PF. Time and frequency domain event-related electrical activity associated with response control in schizophrenia. Clin Neurophysiol 2010;121:176071.

Falkenstein M, Koshlykova NA, Kiroi VN, Hoormann J, Hohnsbein J. Late ERP components in visual and auditory Go/Nogo tasks. Electroencephalogr Clin Neurophysiol 1995;96:3643. Falkenstein M, Hoormann J, Hohnsbein J. ERP components in Go/Nogo tasks and their relation to inhibition. Acta Psychol 1999;101:26791. Farmer SF. Phythmicity, synchronization and binding in human and primate motor systems. J Physiol 1998;509:314. SR, Jahanshahi M, Rothwell JC. Uncoupling of contingent negative variation Filipovic and alpha band event-related desynchronization in a Go/No-go task. Clin Neurophysiol 2001;112:130715. Garavan H, Ross TJ, Stein EA. Right hemispheric dominance of inhibitory control: an event-related functional MRI study. Proc Natl Acad Sci USA 1999;96:83016. Gemba H, Sasaki K. Potential related to No-go reaction in Go/No-go hand movement with discrimination between tone stimuli of different frequencies in the monkey. Brain Res 1990;537:3404. Hmlinen M, Hari R, Ilmoniemi RJ, Knuutila J, Lounasmaa OV. Magnetoencephalography-theory, instrumentation, and applications to noninvasive studies of the working human brain. Rev Mod Phys 1993;65:41397. Hari R, Salmelin R, Mkel JP, Salenius S, Helle M. Magnetoencephalographic cortical rhythms. Int J Psychophysiol 1997;26:5162. Hari R, Karhu J, Hmlinen M, Knuutila J, Salonen O, Sama M, et al. Functional organization of the human rst and second somatosensory cortices: a neuromagnetic study. Eur J Neurosci 1993;5:72434. Harmony T, Alba A, Marroqun JL, Gonzlez-Frankenberger B. Timefrequencytopographic analysis of induced power and synchrony of EEG signals during a Go/No-go task. Int J Psychophysiol 2009;71:916. Hoshiyama M, Koyama S, Kitamura Y, Shimojo M, Watanabe S, Kakigi R. Effects of judgement process on motor evoked potentials in Go/No-go hand movement task. Neurosci Res 1996;24:42730. Hoshiyama M, Kakigi R, Koyama S, Takeshima Y, Watanabe S, Shimojo M. Temporal changes of pyramidal tract activities after decision of movement: a study using transcranial magnetic stimulation of the motor cortex in humans. Electroencephalogr Clin Neurophysiol 1997;105:25561. Huttunen J, Komssi S, Lauronen L. Spatial dynamics of population activities at S1 after median and ulnar nerve stimulation revisited: an MEG study. NeuroImage 2006;32:102431. Ikeda A, Lders HO, Collura TF, Burgess RC, Morris HH, Hamano T, et al. Subdural potentials at orbitofrontal and mesial prefrontal areas accompanying anticipation and decision making in humans: a comparison with Bereitschafts potential. Electroencephalogr Clin Neurophysiol 1996;98:20612. Jurkiewicz MT, Gaetz WC, Bostan AC, Cheyne D. Post-movement beta rebound is generated in motor cortex: evidence from neuromagnetic recordings. NeuroImage 2006;32:12819. Kakigi R, Hoshiyama M, Shimojo M, Naka D, Yamasaki H, Watanabe S, et al. The somatosensory evoked magnetic elds. Progr Neurobiol 2000;61:495 523. Kamarajan C, Porjesz B, Jones KA, Choi K, Chorlian DB, Padmanabhapillai A, et al. The role of brain oscillations as functional correlates of cognitive systems: a study of frontal inhibitory control in alcoholism. Int J Psychophysiol 2004;51:15580. Kaneoke Y. Magnetoencephalography: in search of neural processes for visual motion information. Progr Neurobiol 2006;80:21940. Kawashima R, Satoh K, Itoh H, Ono S, Furumoto S, Gotoh R, et al. Functional anatomy of Go/No-go discrimination and response selectiona PET study in man. Brain Res 1996;728:7989. Kiefer M, Marzinzik F, Wetsbrod M, Scherg M, Spitzer M. The time course of brain activations during response inhibition: evidence from event-related potentials in a go/no go task. NeuroReport 1998;9:76570. Kimura H. Assessment of individual nerves. In: kimura J, editor. Electrodiagnosis in diseases of nerve and muscle: principles and practice. 3rd ed. Philadelphia: Davis Company; 2001. p. 13077. Kirmizi-Alsan E, Bayraktaroglu Z, Gurvit H, Keskin YH, Emre M, Demiralp T. Comparative analysis of event-related potentials during Go/Nogo and CPT: decomposition of electrophysiological markers of response inhibition and sustained attention. Brain Res 2006;1104:11428. Konishi S, Nakajima K, Uchida I, Kikyo H, Kameyama M, Miyashita Y. Common inhibitory mechanism in human inferior prefrontal cortex revealed by eventrelated functional MRI. Brain 1999;122:98191. Leocani L, Cohen LG, Wassermann EM, Ikoma K, Hallett M. Human corticospinal excitability evaluated with transcranial magnetic stimulation during different reaction time paradigms. Brain 2000;123:116173. Leocani L, Toro C, Zhuang P, Gerloff C, Hallett M. Eventrelated desynchronization in reaction time paradigms: a comparison with event-related potentials and corticospinal excitability. Clin Neurophysiol 2001;112:92330. Nakata H, Inui K, Wasaka T, Akatsuka K, Kakigi R. Somato-motor inhibitory processing in humans: a study with MEG and ERP. Eur J Neurosci 2005;22:178492. Nakata H, Inui K, Wasaka T, Tamura Y, Kida T, Kakigi R. The characteristics of the nogo-N140 component in somatosensory Go/Nogo tasks. Neurosci Lett 2006a;397:31822. Nakata H, Inui K, Wasaka T, Tamura Y, Akatsuka K, Kida T, et al. Higher anticipated force required a stronger inhibitory process in Go/Nogo tasks. Clin Neurophysiol 2006b;117:166976. Nakata H, Sakamoto K, Ferretti A, Perrucci GM, Del Gratta C, Kakigi R, et al. Somatomotor inhibitory processing in humans: an event-related functional MRI study. NeuroImage 2008a;39:185866.

282

H. Nakata et al. / Clinical Neurophysiology 124 (2013) 273282 Shibata T, Shimoyama I, Ito T, Abla D, Iwasa H, Koseki K, et al. The synchronization between brain areas under motor inhibition process in humans estimated by event-related EEG coherence. Neurosci Res 1998;31:26571. Shibata T, Shimoyama I, Ito T, Abla D, Iwasa H, Koseki K, et al. Event-related dynamics of the gamma-band oscillation in the human brain: information processing during a Go:Nogo hand movement task. Neurosci Res 1999;33:21522. Simoes C, Salenius S, Curio G. Short-term (approximately 600 ms) prediction of perturbation dynamics for 10- and 20-Hz MEG rhythms in human primary sensorimotor hand cortices. NeuroImage 2004;22:38793. Sohn YH, Wiltz K, Hallett M. Effect of volitional inhibition on cortical inhibitory mechanisms. J Neurophysiol 2002;88:3338. Tamura Y, Hoshiyama M, Nakata H, Hiroe N, Inui K, Kaneoke Y, et al. Functional relationship between human rolandic oscillations and motor cortical excitability: an MEG study. Eur J Neurosci 2005;21:255562. van Boxtel GJ, Brunia CH. Motor and non-motor aspects of slow brain potentials. Biol Psychol 1994;38:3751. Waldvogel D, van Gelderen P, Muellbacher W, Ziemann U, Immisch I, Hallett M. The relative metabolic demand of inhibition and excitation. Nature 2000;406:9958. Weisbrod M, Kiefer M, Marzinzik F, Spitzer M. Executive control is disturbed in schizophrenia: evidence from event-related potentials in a Go/Nogo task. Biol Psychiatry 2000;47:5160. Wiersema R, van der Meere J, Roeyers H, Van Coster R, Baeyens D. Event rate and event-related potentials in ADHD. J Child Psychol Psychiatry 2006;47:5607. Yamanaka K, Kimura T, Miyazaki M, Kawashima N, Nozaki D, Nakazawa K, et al. Human cortical activities during Go/Nogo tasks with opposite motor control paradigms. Exp Brain Res 2002;142:3017.

Nakata H, Sakamoto K, Ferretti A, Perrucci GM, Del Gratta C, Kakigi R, et al. Executive functions with different motor outputs in somatosensory Go/Nogo tasks: an event-related functional MRI study. Brain Res Bull 2008b;77:197205. Nagamine T, Kajola M, Salmelin R, Shibasaki H, Hari R. Movement-related slow cortical magnetic elds and changes of spontaneous MEG- and EEG-brain rhythms. Electroencephalogr Clin Neurophysiol 1996;99:27486. Pfurtscheller G, Stancak A, Neuper C. Post-movement beta synchronization. A correlate of an idling motor area? Electroencephalogr Clin Neurophysiol 1996;98:28193. Pfurtscheller G, Lopes da Silva FH. Event-related EEG/MEG synchronization and desynchronization: basic principles. Clin Neurophysiol 1999;110:184257. Ruchkin DS, Sutton S, Mahaffev D, Glaser J. Terminal CNV in the absence of motor response. Electroencephalogr Clin Neurophysiol 1986;63:44563. Salenius S, Schnitzler A, Salmelin R, Jousmki V, Hari R. Modulation of human cortical rolandic rhythms during natural sensorimotor tasks. NeuroImage 1997;5:2218. Salmelin R, Hari R. Spatiotemporal characteristics of sensorimotor neuromagnetic rhythms related to thumb movement. Neuroscience 1994;60:53750. Salmelin R, Hamalainen M, Kajola M, Hari R. Functional segregation of movement-related rhythmic activity in the human brain. NeuroImage 1995;2:23743. Stancak A, Pfurtscheller G. Desynchronization and recovery of beta rhythms during brisk and slow self-paced nger movements in man. Neurosci Lett 1995;196:214. Stancak A, Pfurtscheller G. Event-related desynchronisation of central beta-rhythms during brisk and slow selfpaced nger movements of dominant and nondominant hand. Brain Res Cogn Brain Res 1996;4:17183. Shibata T, Shimoyama I, Ito T, Abla D, Iwasa H, Koseki K, et al. The time course of interhemispheric EEG coherence during a Go:Nogo task in humans. Neurosci Lett 1997;233:11720.