Nakata Et Al, 2013

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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, Japanb Department of Clinical Laboratory, Graduate School of Medicine, The University of Tokyo, Tokyo, Japanc Faculty of Sport Sciences, Waseda University, Tokorozawa, Japan

a r t i c l e i n f o

Article history:Accepted 27 June 2012

Available online 3 August 2012

Keywords:

MEG

Response inhibition

Somatosensory

Go/No-go

h i g h l i g h t s

We investigated the characteristics of cortical rhythmic activity in No-go processing during a somato-sensory 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

600–900 ms.

The cortical rhythmic activity clearly has several dissociated components relating to different motor

functions, including response inhibition, execution, and decision-making.

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 fifth 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, peak-ing at 600–900 ms. A suppression of amplitude was recorded in Go and No-go trials for alpha activity,

peaking at 300–600 ms, and in Go and No-go trials for beta activity, peaking at 200–300 ms.

Conclusion: The cortical rhythmic activity clearly has several dissociated components relating to different

motor functions, including response inhibition, execution, and decision-making.

Significance: The present study revealed the characteristics of cortical rhythmic activity in No-go

processing.

Ó 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 clarified by using scalp electroencephalogra-phy (EEG). EEG has been frequently used to examine the dynamics

of synchronized cortical activity, and offers a high temporal resolu-

tion 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; Kirmizi-

Alsan et al., 2006; Barry, 2009; Harmony et al., 2009). A common

finding is that the power of the theta, alpha, and beta frequency

bands decreases or increases at 300–900 ms after the onset of a

No-go stimulus. For example, Leocani et al. (2001) reported

that the spectral power at 10 Hz and 18–22 Hz decreased at

300–600 ms after stimulus onset, and the power at 10 Hz and18–22 Hz increased at 900–1200 ms and 600–900 ms, respectively.

Harmony et al. (2009) showed a complex spatiotemporal pattern of

spectral power decreases and increases in Go- and No-go condi-

tions. 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. suppres-

sion), and the latter, event-related synchronization (ERS) (i.e. re-

bound) (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 sug-

gested to reflect an idling cortex generated by a large area of highly

1388-2457/$36.00 Ó 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

⇑ Corresponding author at: Faculty of Sport Sciences, Waseda University, 2-579-

15 Mikajima, Tokorozawa, Saitama 359-1192, Japan. Tel.: +81 4 2947 4614; fax: +81

4 2947 6826.

E-mail address: [email protected] (H. Nakata).

Clinical Neurophysiology 124 (2013) 273–282

Contents lists available at SciVerse ScienceDirect

Clinical Neurophysiology

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c l i n p h

http://dx.doi.org/10.1016/j.clinph.2012.06.019

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synchronous neuronal firing in the absence of inputs, or alterna-

tively, changes in coherent activity resulting from synchronous in-

puts from other brain regions ( Jurkiewicz et al., 2006). However,

the neurophysiological mechanisms and functional significance

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 fre-

quency components (theta, alpha, and beta), by using magnetoen-

cephalography (MEG). MEG has theoretical advantages over EEG,

because the magnetic fields recorded on the scalp are less affected

by volume currents and anatomical inhomogeneity. MEG also has

a high temporal resolution,permitting neural activityto be differen-

tiated 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 re-

sponse inhibitory processing. In the present study, we used Tempo-

ral Spectral Evolution (TSE) to extract the spatiotemporal

characteristics of cortical oscillations, following previous MEG stud-

ies (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 firstly filtered

through a passband suggested by a spectral analysis and, subse-

quently, 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 thesame unit as theoriginal signals.

The present study used ‘somatosensory Go/No-go paradigms’, in

whichthe second or fifth digit of the left handwas stimulated. Some

event-related potential (ERP) studies found that the amplitude of

theN2 componentwas much smallerfollowingauditory than visualstimuli (Falkenstein et al., 1995, 1999; Kiefer et al. 1998). Falken-

stein et al. (1999) suggested that the inhibitory processing as re-

flected in N2 is modality specific. 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 opposedto the caudal part of the same bank

after a visual stimulus. Therefore, the present study aimed to inves-

tigate 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 ef-

fect of stimulus probability and to minimize differences in response

conflictbetween eventtypes(Braveret 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 25–42 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 Insti-

tute for Physiological Sciences.

2.2. Experimental paradigm

The participants performed a warning stimulus (S1) – impera-tive stimulus (S2) task with Go/No-go paradigms. S1 was an

auditory pure tone (60 dB SPL, 50 ms duration), presented binau-

rally through earphones. For S2, we stimulated the second or fifth

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 fifth digits was even.

A pair of S1 and S2 stimuli was delivered to the participants at an

interval of 1500 ms. The S1–S1 interval was 5 s.

The recordings were conducted in three conditions. In Condi-

tion 1, the Go stimulus was delivered to the second digit of the left

hand, and the No-go stimulus to the fifth 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 deliv-

ered to the fifth 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 partici-

pants were instructed to keep their eyes open and look at a small

fixation point positioned in front of them at a distance of approx-

imately 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 sen-

sor element consists of two orthogonal planar gradiometers andone magnetometer coupled to a multi-SQUID (Superconducting

Quantum Interference Device) and thus provides three indepen-

dent measurements of the magnetic fields. In the present study,

we analyzed MEG signals from 204-channel planar-type gradiom-

eters, because the data from magnetometers are usually susceptive

to global magnetic noise including changes in geomagnetic fields

(Hämäläinen et al., 1993) (the noise can be successfully canceled

out in recording with planar sensors). The signals were recorded

with a bandpass filter (0.1–100 Hz) and digitized at 900 Hz. Before

the recordings, four head position indicator (HPI) coils were at-

tached to specific sites on the subject’s head, and then electric cur-

rent was fed to the HPI coils to determine the exact location of the

head with respect to the MEG sensors. The x-axis was fixed with

the preauricular points, pointing to the right, the positive y-axistraversing the nasion, and the positive z -axis pointing up.

From the continuous MEG raw data, epochs from 1000 ms be-

fore 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 fil-

tered at around the theta band (4–8 Hz), alpha band (8–12 Hz),

and beta band (18–22 Hz). The filtered signals were then rectified

and averaged across epochs. The baseline was set from 1000 ms

before S1 onset to S1 onset. The magnetic responses from three re-

gions 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 soft-ware. In this software to view raw data, the artifacts were

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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 Con-

trol (Condition 3) for the second digit stimulation, and Go (Condi-

tion 2), No-go (Condition 1), and Control (Condition 3) for the fifthdigit stimulation. If visible differences in the activity of ‘Go’ and/or

‘No-go’ were observed for each region, the peak latency was sub-

jected to an analysis of variance (ANOVA) with repeated measures

using within-subject factors. The peak latency of the suppression

and rebound was defined for each individual as the time when

the maximum deflection 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 ampli-

tude was subjected to ANOVAs with Digit (Second vs. Fifth), Condi-

tion (Go, No-go, and Control), Region (Frontal, Central and Parietal),

and Hemisphere (Left vs. Right) as within-subjects factors. Thebehavioral data on the mean reaction time (RT), the standard devi-

ation (SD) of RT, commission error, and omission error were sub-

jected 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 Mauchly’s sphericity

assumption was violated. If the test result was significant and

the assumption of sphericity was violated, the Greenhouse–Geisser

adjustment was used to correct the sphericity by altering the de-

grees of freedom using a correction coefficient epsilon. When sig-

nificant effects were identified, the Bonferroni post hoc multiple

comparison was used to identify specific differences. Statistical

tests were performed using computer software (SPSS for windows

ver. 16.0, SPSS). Statistical significance was set atp

< 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

significant 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 fifth digit. In addition, a significant 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 significantly larger in Condition 2 than Condition 1. There

were no significant differences between conditions in the SD of RTor omission error rate.

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 fifth

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 signifi-

cant 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), Digit–Region interaction (F(2, 22) =

7.357, p < 0.01), and Condition–Region 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 signifi-

cant main effect of Condition in the frontal region (F(2, 22) =

3.531, p < 0.05), significant main effects of Digit (F(1,11) = 8.182,

p < 0.05) and Condition (F(2, 22) = 11.123, p < 0.001) in the tempo-

ral region, and significant 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 signifi-cantly 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

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 700–800 ms

for the second digit stimulation. The rebound was confirmed in

the central and parietal regions for the fifth digit stimulation

(Fig. 3B). ANOVAs for the peak latency in the second and fifth digit

stimulation did not show any significant main effects or interac-tions. Suppression for the second digit was recorded only in Go

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.

Table 1

The mean reaction time and error rates in the two movement conditions.

RT (ms) SD of RT (ms) Com (%) Omi (%)

Con. 1 248.8 (17.8) 56.1 (6.9) 1.0 (0.3) 0.8 (0.6)

Con. 2 271.0 (18.3) 64.3 (6.7) 4.0 (0.9) 1.1 (0.6)

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

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trials at LC, LP, RC, and RP, peaking at 400–600 ms (Table 2). Sup-

pression for the fifth digit was obtained in Go and No-go trials at

LP and RP, peaking at 300–400 ms (Supplementary Table S2). AN-

OVAs with Condition and Hemisphere demonstrated a significant

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), Digit–Hemisphere

interaction (F(1, 11) = 9.297, p < 0.05), and Condition–Region inter-

action (Greenhouse–Geisser 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 Hemi-

sphere demonstrated significant 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 signifi-

cantly more positive in No-go than Go and Control in the frontal re-

gion ( 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).

Fig. 2. (A) (B) Grand-averaged waveforms of theta bands in the frontal, central, and parietal regions for the second and fifth 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) LF LC LP RF RC RP

Theta

No-go Rebound 789 (33) 825 (32) 758 (44) 797 (33) 774 (39) 758 (37)

Alpha

No-go Rebound 733 (77) 727 (64) 712 (61) 766 (74) 754 (60) 805 (67)

Go Suppression 556 (60) 498 (39) 595 (73) 424 (79)

Beta

No-go Rebound 654 (61) 743 (58) 715 (51) 623 (50) 713 (55) 666 (54)

No-go Suppression 230 (22) 195 (25)

Go Suppression 330 (38) 255 (45)

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).


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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 fifth digit

stimulation (Fig. 4B). The suppressions for the second and fifth

digits were recorded in Go and No-go trials at LC and RC,

Table 3

Mean amplitude of theta, alpha, and beta bands in three conditions for the second digit stimulation.

(fT/cm) LF LC LP RF RC RP

Theta

Go À0.5 (1.7) 0.6 (2.3) 0.7 (2.1) À0.6 (1.8) À3.1 (2.3) À0.1 (2.7)

No-go 5.1 (2.3) 10.6 (3.4) 11.3 (4.7) 2.2 (1.5) 8.0 (2.9) 10.3 (3.7)

Control À1.0 (1.5) 1.4 (1.8) 1.2 (1.7) À0.8 (1.7) 1.0 (2.1) 1.9 (3.0)

Alpha

Go 2.2 (2.1) 0.3 (3.9) À3.0 (4.4) À0.9 (2.4) À7.6 (5.1) À2.9 (7.1)

No-go 8.9 (3.2) 17.0 (7.1) 19.4 (9.6) 4.5 (2.5) 11.5 (6.1) 11.7 (7.0)

Control 2.0 (1.6) 4.4 (3.4) 9.5 (6.3) 0.5 (1.3) 2.7 (3.9) 6.6 (5.5)

Beta

Go 5.1 (1.8) 0.0 (1.6) À0.3 (1.1) 2.2 (0.9) À0.5 (2.0) 0.2 (1.7)

No-go 8.4 (2.4) 11.6 (3.3) 7.6 (3.4) 5.6 (1.4) 11.1 (2.1) 8.6 (1.8)

Control 4.6 (1.5) 7.8 (2.3) 4.1 (1.6) 3.1 (1.3) 9.5 (2.9) 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, andparietal regions for the second andfifth digit stimulation. Left and right hemispheric data


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.


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peaking at around 200 ms (Table 2 and Supplementary Table S1),

and ANOVAs with Condition (Go vs. No-go), Digit, and Hemi-

sphere as factors demonstrated no significant 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 Condition–Digit interaction

(F(2,22) = 4.160, p < 0.05), Condition–Region interaction (Green-house–Geisser correction: F(2.334, 25.669) = 8.389, e = 0.583,

p < 0.001), Hemisphere–Region interaction (F(2,22) = 8.647,

p < 0.01), and Digit–Hemisphere–Region interaction (F(2,22) =

5.654, p < 0.05) (Table 3 and Supplementary Table S2). Further-

more, one-way ANOVAs showed significant main effects of Condi-

tion 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 significant 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 signifi-

cantly more positive in No-go than Go and Control in the frontal re-

gion ( 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-gothan 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 signif-

icant main effect or interaction.ANOVAs for the amplitude of the alpha bands showed a signif-

icant main effect of Hemisphere (F(1,11) = 5.733, p < 0.05), and Di-

git–Hemisphere interaction (F(1, 11) = 10.876, p < 0.01). ANOVAs

for the amplitude of the beta bands revealed a significant Condi-

tion–Digit–Region 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 signif-

icantly more negative in Go than Control in the central region

( p < 0.05), but there were no significant differences in the ampli-

tudes for the fifth digit.

3.6. The event-related magnetic field

Fig. 5 shows the event-related magnetic field waveforms in arepresentative subject to compare the difference in waveforms

Fig. 4. (A) (B) Grand-averaged waveforms of beta bands in the frontal, central, and parietal regions for the second and fifth digit stimulation. Left and right hemispheric data


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.


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from band-related activity. The specific 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 cor-

tical rhythmic activity in No-go processing, by using whole-headMEG. Our data demonstrated a rebound in amplitude in No-go

trials for theta, alpha, and beta bands, peaking at 600–900 ms. Sup-

pression was recorded in both Go and No-go trials for alpha bands,

peaking at 300–600 ms, and in both Go and No-go trials for beta

bands, peaking at 200–300 ms.

TSE with MEG has been used to clarify the characteristics of cor-

tical oscillations, especially for voluntary movement-related corti-

cal 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 first

MEG study to examine the response inhibitory processing in a

Go/No-go paradigm, though the suppression (ERD) and rebound

Fig. 5. (Top)The event-related magnetic field waveforms over 204 planarcoils from the topof the head in a representative subject. (Bottom) An enlarged waveformrecorded

from four regions. Blue, red, and green lines indicate waveforms for Go, No-go, and Control, respectively. The arrows show the peak of the specific activity related to No-go

processing after the onset of S2. All data were digitally filtered (0.1–40 Hz bandpass) for display purposes.


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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 significantly faster in Condition 1 than Condi-

tion 2, and the commission error rate was significantly larger in

Condition 2 than Condition 1. These results indicate that the stim-

ulus site in somatosensory Go/No-go paradigms is related to the

difficulty of each task. Indeed, it seems difficult to interpret these

results, because our previous findings did not reveal a significant

difference (Nakata et al., 2005), but other data showed that the re-

sponses were faster for the second digit than fifth 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 fifth digit.

The second and fifth 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 pri-

mary motor cortex (MI) necessary to cause sequential reaction are

more important following stimulation of the second digit than fifth

digit, since the somatosensory evoked magnetic fields 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

fifth 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 700–800 ms (Figs.

3 and 4). The suppression/rebound (ERD/ERS) are generally

thought to reflect 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 inalpha and beta bands has been accumulated. The rebound ob-

served after movement has been often interpreted as an indicator

of idling in the cortex (Pfurtscheller et al., 1996), aswell as the con-

sequence of processes related to the end of the movement (Alegre

et al., 2002). Within this framework, our current results indicate

the specific neural activity related to No-go processing. A No-go-

specific enhancement of power has been reported in previous

EEG studies using auditory and visual Go/No-go paradigms (Shiba-

ta 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 wasfound 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 re-

bound in the No-go trials, suggesting that this rebound arises from

widespread generators.

As for the timing of occurrence in response inhibition, transcra-

nial 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 find-

ings of these studies were a decrease in the amplitude of motor

evoked potentials (MEPs) at 100–200 ms after No-go stimuli, and

an increase after Go stimuli. In addition, Waldvogel et al. reported

that inhibitionof the amplitude of MEPs lasted for 500 ms after No-

go stimuli. There has been no study showing how long the No-go

processing of the corticospinal tract lasted, but our TSE findings

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 di-

git stimulation was recorded in Gotrials at LC, LP, RC, and RP, peak-

ing at 400–600 ms (Fig. 3A). Nagamine et al. (1996) using TSE with

MEG provided evidence that alpha activity showed maximum sup-

pression 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), sug-

gesting 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

findings 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 fifth 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 No-

go trials at LC and RC for the second and fifth digit stimulation,

peaking at around 200 ms (Fig. 4). These findings 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 para-

digms, areas of the brain related to Go trials were located in theDLPFC, VLPFC, SMA and premotor area (PM), primary somato-mo-

tor area (SMI), inferior parietal lobule (IPL), insula, superior tempo-

ral 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 specific 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 prepara-

tory 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 para-

digms reported no changes in amplitude for alpha bands between

S1 and S2 stimuli, which was in line with our finding. However,

they did not show suppression in beta bands during the prepara-

tory period. It seems difficult to interpret this finding, but in gen-

eral, the beta pattern consists of a suppressive phase that begins

at least 1.5 s before the movement starts (Stancak and Pfurtschel-

ler, 1995, 1996), and the suppression has long been known to re-

flect movement preparation.

The amplitudes in preparatory periods were relatively similarbetween Go and No-go trials. In our S1–S2 paradigms, S1 delivered


7/28/2019 Nakata Et Al, 2013


the warning and set up the response and S2 indicated the Go/No-

go information (i.e. S2-centered-paradigm). By contrast, some

studies have used a S1–S2 paradigm in which S1 delivered Go/

No-go information and S2 merely showed the timing of the re-

sponse after the Go-S1 stimulus (i.e. S1-centered-paradigm), show-

ing the difference between Go and No-go activity during

preparatory periods (Filipovic et al., 2001; Alegre et al., 2004). Tak-

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, indi-

cating 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-pro-

nounced 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 reflected expectancy and atten-

tion 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 600–900 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 cor-

tical rhythmic activity clearly has several dissociated components

relating to different motor functions, including response inhibition,

execution, and decision-making. Furthermore, our findings might

guide future studies of the neurophysiological changes in patients,

and help to interpret the error profiles seen in patients during No-

go trials. Indeed, several studies have shown differences in wave-

forms 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 corti-

cal 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.

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