vier.com/locate/ijpsycho

International Journal of Psychophy

Short communication

N2 event-related potential correlates of response inhibition in an

auditory Go/Nogo task

Stefan Kaiser a,*, Oliver Weiss a, Holger Hill a, Jaana Markela-Lerenc a,

Markus Kiefer b, Matthias Weisbrod a

a University of Heidelberg Department of Psychiatry, Section of Experimental Psychopathology, Voss-Strasse 4, 69115 Heidelberg, Germanyb University of Ulm Department of Psychiatry III, Germany

Received 22 March 2005; received in revised form 8 June 2005; accepted 29 September 2005

Available online 17 November 2005

Abstract

The aim of this study was to investigate the event-related potential correlates of response inhibition in the N2 time window, specifically in the

auditory modality. A paired tone Go/Nogo paradigm elicited an enhanced fronto-central negativity in the Nogo condition, which was accompanied

by a concurring inferior fronto-temporal positivity. In contrast to most previous studies our data provide evidence for a fronto-central Nogo-N2

component in the auditory modality.

D 2005 Elsevier B.V. All rights reserved.

Keywords: Response inhibition; N2; Nogo; ERP

Response inhibition can be studied in Go/Nogo paradigms,

which require the execution of a motor response on a Go

stimulus and its inhibition on a Nogo stimulus. The neural

correlates of this response inhibition process have been

investigated using event-related potentials (ERPs) in several

variations of the paradigm. Two ERP components have

emerged as neurophysiological markers of the response

inhibition process. First, the P300 component has consistently

be found to have a more anterior topography in the Nogo

condition compared to the Go condition (Fallgatter and Strik,

1999; Roberts et al., 1994). Second, in visual Go/Nogo tasks a

negative shift in the N2 time window has been observed over

fronto-central electrodes and has been termed Nogo-N2 (Jodo

and Kayama, 1992; Simson et al., 1977). However, in the

studies employing auditory Go/Nogo paradigms, the fronto-

central Nogo-N2 was either found to be absent (Falkenstein et

al., 1995; Karlin et al., 1970; Kiefer et al., 1998) or very small

(Falkenstein et al., 2002; Schroger, 1993). In our previous

studies we have observed an enhanced positivity in the N2 time

window over inferior fronto-temporal regions, which we

interpreted as a polarity inverted Nogo-N2 representing activity

0167-8760/$ - see front matter D 2005 Elsevier B.V. All rights reserved.

doi:10.1016/j.ijpsycho.2005.09.006

* Corresponding author. Tel.: +49 6221 565412; fax: +49 6221 565998.

E-mail address: stefan_kaiser@med.uni-heidelberg.de (S. Kaiser).

of the same generators (Kiefer et al., 1998). In order to explain

the diverging findings between auditory and visual Go/Nogo

paradigms, Falkenstein has suggested modality-specific inhib-

itory generators on the basis of human as well as animal studies

(Falkenstein et al., 1999; Gemba and Sasaki, 1990).

Since we employ auditory Go/Nogo paradigms to investi-

gate response inhibition in psychiatric disorders, it was of great

interest to clarify the significance of the different components

in the N2 time window (Kaiser et al., 2003; Weisbrod et al.,

2000). More specifically, we asked whether modifications of

the paradigm could elicit an auditory Nogo-N2 over fronto-

central electrodes. Furthermore, if a fronto-central Nogo-N2

and the previously observed inferior fronto-temporal positivity

can be elicited in parallel, this would relate both components to

a common process, namely response inhibition. For this

purpose, we developed an auditory paired stimulus task, which

required motor preparation after a warning tone and either

motor execution or inhibition after the second tone. We

hypothesized that the preparatory phase would increase the

inhibition requirements and would therefore lead to clearer

findings regarding the auditory Nogo-N2. Specifically, we

expected to find an increased fronto-central negativity as well

as a concurrent inferior fronto-temporal positivity in the Nogo

condition.

siology 61 (2006) 279 – 282

www.else

-2.0 µV 2.0 µV0 µV

64

5

17

1654

53

42

63

22

23

59

55

Fig. 1. Topographic map and Electrode positions on the 65 channel Geodesic

sensor net. Regions of interest were defined according to our previous studies

(Kiefer et al., 1998) as inferior fronto-temporal (electrode pairs 63/64, 22/59

23/55) and fronto-central (electrode pairs 16/53, 5/54, 17/42). A spherica

spline map was calculated for the Nogo-Go difference waveform at 268 ms

corresponding to the center of the selected N2 time window.

S. Kaiser et al. / International Journal of Psychophysiology 61 (2006) 279–282280

12 healthy medical students (10 male/2 female) with an

average age of 25 years (range 20–29 years) participated in the

study. According to the Edinburgh Handedness Inventory five

were classified as right handed, seven as left handed (Oldfield,

1971). The study was conducted in accordance with the

Declaration of Helsinki and all participants gave written

informed consent.

In the Go/Nogo task 200 pairs of pure tones of 40 ms

duration were presented with an intra-pair interval of 1.2 s and

an inter-pair interval of 1.8 s. These were either low pitched

tones with a frequency of 1000 Hz or high pitched tones with a

frequency adapted to the participant’s individual discrimination

ability. For high pitched tones the mean frequency was 1036

Hz (range 1015–1130 Hz). Counterbalanced across subjects

either of the two tones was designated as target stimulus. A

motor response with the index finger of the right hand was

required only in trials with two target stimuli (Go trial).

Therefore, a motor response had to be prepared, when the first

tone of a pair was a target stimulus. In trials where target was

followed by non-target tone, inhibition of the prepared motor

response was required (Nogo trial). All trials beginning with

non-target stimuli did not require motor preparation and

therefore results are not presented here.

Descriptive statistics of the behavioral data in the Go

condition showed a mean hit rate of 71% (range 65–94%) and

a mean reaction time of 416 ms (range 343–573 ms). In the

Nogo condition the mean false alarm rate was 2.7% (range 0–

10%).

Scalp voltages were collected using a 64 channel Geodesic

Sensor Net (Fig. 1). Electrical signals were recorded with

Synamps amplifiers (bandwith DC 70 Hz, 50 Hz notch filter)

and digitized (sampling rate 250 Hz). The EEG data were

processed using the BrainVision Analyzer Software. The

continuous EEG was segmented into epochs starting 100 ms

before the second tone and lasting until 900 ms after stimulus

onset. The EEG was digitally low-pass filtered (16 Hz) and

baseline corrected over the 100 ms prestimulus epoch. Artifact-

free trials were averaged separately for Go and Nogo trials. The

average reference transform was applied to obtain a reference-

independent estimation of scalp voltages. Based on our

previous studies we defined two regions of interest represented

by three electrodes on each hemisphere: fronto-central (anterior

16/53, intermediate 5/54, posterior 17/42) and inferior fronto-

temporal (anterior 64/63, intermediate 22/59, posterior 23/55).

Electrode positions on the Geodesic Net do not correspond

directly to the 10/10 system. Best approximations are FC3/

FC4, FC1/FC2, CP1/CP2 for fronto-central electrodes and Fp1/

Fp2, F9/F10, FT9/FT10 for inferior fronto-temporal electrodes.

Inspection of the ERP data in the N2 time window revealed

the hypothesized increase of fronto-central negativity in the

Nogo condition (waveforms in Fig. 2, topographic map in Fig.

1). This was accompanied by a concurrent inferior fronto-

temporal positivity (Figs. 1 and 2). Statistical analysis of the

data was conducted according to our previous studies (Kaiser et

al., 2003; Kiefer et al., 1998). A time window of 60 ms was

centered on the average peak latency in the Nogo condition,

which resulted in a window reaching from 238 ms to 298 ms.

,

l

Mean voltage in this time window was entered as dependent

variable in a repeated measures ANOVA with factors CONDI-

TION (Go/Nogo), HEMISPHERE (Left/Right) and ELEC-

TRODE (Anterior, Intermediate, Posterior). Separate ANOVAs

were conducted for fronto-central and inferior fronto-temporal

electrode sites. Geisser-Greenhouse corrections were applied

where appropriate. Since our hypotheses concerned differences

between conditions, we only report main effects and interac-

tions involving CONDITION.

For fronto-central electrodes the ANOVA resulted in a main

effect of CONDITION (F(1,11)=9.71, p <0.01). Mean ampli-

tude for Nogo trials (0.9T2.12 AV) was less positive than for Gotrials (1.68T2.29 AV). In the fronto-central region of interest noother effect involving CONDITION reached significance. Over

inferior fronto-temporal electrodes a main effect of CONDI-

TION was found (F(1,11)=4.84, p =0.05), showing that mean

voltage was more positive for Nogo (�0.38T2.4 AV) than for

Go trials (�1.63T2.4 AV). There was a trend towards a

CONDITION�HEMISPHERE interaction (F(2,22)=3.65,

p =0.08). Numerically the positive shift in Nogo trials was more

pronounced over the right hemisphere. Additionally, a trend

towards a CONDITION�HEMISPHERE�ELECTRODE in-

teraction was found (F(2,22)=3.24, p=0.06), suggesting that

the difference between hemispheres was most pronounced over

temporal electrodes (electrode pair 23/55).

In summary, the present ERP data in the N2 time window

show an enhanced negativity over fronto-central electrodes and

an accompanying positivity over inferior fronto-temporal sites.

The increased fronto-central negativity in the N2 time window

shows clearly that a Nogo-N2 can be found in auditory tasks,

LEFT RIGHT

FRONTO

CENTRAL

INFERIOR

FRONTO-

TEMPORAL

-4

-2

0

2

4

-4

-2

0

2

4

-4

-2

0

2

4

[µV]

[µV] [µV]

[µV]

0 200 400 600 800

0 200 400 600 800

[ms] 200 400 600 800 [ms]-4

-2

0

2

4

0

200 400 600 800 [ms]0

Fig. 2. ERP waveforms for Go (thin line) and Nogo (bold line) conditions over fronto-central and inferior fronto-temporal electrode sites of the left and right

hemispheres. Waveforms are represented for pooled electrodes from the respective regions of interest. The peaks of N2 and the concurring inferior fronto-temporal

positivity are marked by arrows. In addition the Nogo-Go difference waveform is shown (dotted line).

S. Kaiser et al. / International Journal of Psychophysiology 61 (2006) 279–282 281

which is in contrast to most but not all previous studies

(Falkenstein et al., 2002). This suggests that the diverging

results between auditory and visual Go/Nogo paradigms

involve other factors than stimulus modality. Our results

suggest that the differences between single and paired stimulus

paradigms can explain some of these disparities. The studies by

Falkenstein et al. and our own group, which failed to detect a

fronto-central Nogo-N2, have used single stimulus paradigms

(Falkenstein et al., 1999; Falkenstein et al., 1995; Kiefer et al.,

1998). In a recent study, Falkenstein et al. have observed an

auditory Nogo-N2, which was however very small compared to

visual stimulation (Falkenstein et al., 2002). In contrast,

Schroger has employed a visual cue for directing spatial

attention before an auditory target or non-target stimulus was

delivered (Schroger, 1993). A Nogo-N2 was described only

after cued Nogo stimuli, which was interpreted in terms of an

increased activity of inhibitory generators through attentional

processes.

Several factors could contribute to the differences between

single and paired stimulus paradigms. First, one could argue

along the lines of Schroger that the warning stimulus leads to

focused attention to the following stimulus (Schroger, 1993).

However, spatial attention is not involved in the present task.

Furthermore it is doubtful, whether this aspect differentiates the

present paradigm from single stimulus paradigms, since in the

latter all stimuli have to be attended to. A second explanation

holds that upon the presentation of the warning stimulus

subjects are prepared to respond, which places an stronger load

on the response inhibition process compared to single stimulus

paradigms. This would result in an enhanced activity of the

neural generators subserving response inhibition (Roberts et

al., 1994). It has to be mentioned that other methods have been

shown to increase response preparation, such as responding

under time pressure or increasing likelihood of the Go-

Stimulus (Bruin and Wijers, 2002; Falkenstein et al., 2002).

However the last approach did not lead to a fronto-central

Nogo-N2 in our previous studies (Kaiser et al., 2003; Kiefer et

al., 1998). A third factor might be the differential effect of

motor potentials between single and paired stimulus designs. In

our previous single stimulus studies the fronto-central N2 was

clearly overlapped by a lateralized motor potential in the Go

condition. Since these potentials induce a negative shift in the

Go condition as early as 200 ms after stimulus onset, the Nogo

negativity can well be obscured by motor potentials (Kaiser et

al., 2003; Karlin et al., 1970). In the present study this negative

shift was not seen and did not confound the Nogo-N2 effect.

As in our previous studies we found an enhanced inferior

fronto-temporal positivity in Nogo trials (Kiefer et al., 1998).

Our interpretation as a polarity-inverted Nogo-N2 reflecting

activity of the same generator as the fronto-central Nogo-N2

has been a matter of debate. In the present study both

components are registered specifically in the Nogo condition

and with a similar time course, which provides evidence for a

common underlying generator. This is in line with our findings

that link the performance deficits of depressive patients to a

reduced amplitude of this component (Kaiser et al., 2003). In

S. Kaiser et al. / International Journal of Psychophysiology 61 (2006) 279–282282

contrast to findings from our previous studies, inspection of the

present data suggested a right lateralization of the fronto-

central Nogo-N2 and more pronounced of its concurring

inferior fronto-temporal positivity. However, statistical analysis

yielded a trend over inferior fronto-temporal sites only. A right

hemispheric dominance for response inhibition has been

reported in some previous imaging and electrophysiological

studies, but it has not been elucidated which characteristics of

the paradigms leads to this effect (Falkenstein et al., 2002;

Garavan et al., 1999; Jackson et al., 1999).

In summary, our present findings regarding the auditory

Nogo-N2 show that the diverging findings between visual and

auditory Go/Nogo paradigms involve other factors than

stimulus modality. The comparison of the present paired

stimulus paradigm with our previous single stimulus study

suggests that the specifications of the employed paradigm seem

to be at least equally important to the Nogo-N2 effect. A

warning stimulus facilitates the elicitation of a fronto-central

Nogo-N2, possibly due to an increased load on the response

inhibition process.

References

Bruin, K.J., Wijers, A.A., 2002. Inhibition, response mode, and stimulus

probability: a comparative event-related potential study. Clin. Neurophy-

siol. 113, 1172–1182.

Falkenstein, M., Koshlykova, N.A., Kiroj, V.N., Hoormann, J., Hohnsbein, J.,

1995. Late ERP components in visual and auditory Go/Nogo tasks.

Electroencephalogr. Clin. Neurophysiol. 96, 36–43.

Falkenstein, M., Hoormann, J., Hohnsbein, J., 1999. ERP components in

Go/Nogo tasks and their relation to inhibition. Acta Psychol. (Amst) 101,

267–291.

Falkenstein, M., Hoormann, J., Hohnsbein, J., 2002. Inhibition-related ERP

components: variation with age and time-on-task. J. Psychophysiol. 16,

167–175.

Fallgatter, A.J., Strik, W.K., 1999. The NoGo-anteriorization as a neurophys-

iological standard-index for cognitive response control. Int. J. Psychophy-

siol. 32, 233–238.

Garavan, H., Ross, T.J., Stein, E.A., 1999. Right hemispheric dominance of

inhibitory control: an event-related functional MRI study. Proc. Natl. Acad.

Sci. U. S. A. 96, 8301–8306.

Gemba, H., Sasaki, K., 1990. 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. 537, 340–344.

Jackson, S.R., Jackson, G.M., Roberts, M., 1999. The selection and suppression

of action: ERP correlates of executive control in humans. Neuroreport 10,

861–865.

Jodo, E., Kayama, Y., 1992. Relation of a negative ERP component to response

inhibition in a Go/No-go task. Electroencephalogr. Clin. Neurophysiol. 82,

477–482.

Kaiser, S., Unger, J., Kiefer, M., Markela, J., Mundt, C., Weisbrod, M., 2003.

Executive control deficit in depression: event-related potentials in a

Go/Nogo task. Psychiatry Res. 122, 169–184.

Karlin, L., Martz, M.J., Mordkoff, A.M., 1970. Motor performance and

sensory-evoked potentials. Electroencephalogr. Clin. Neurophysiol. 28,

307–313.

Kiefer, M., Marzinzik, F., Weisbrod, M., Scherg, M., Spitzer, M., 1998. The

time course of brain activations during response inhibition: evidence from

event-related potentials in a go/no go task. Neuroreport 9, 765–770.

Oldfield, R.C., 1971. The assessment and analysis of handedness: the

Edinburgh inventory. Neuropsychologia 9, 97–113.

Roberts, L.E., Rau, H., Lutzenberger, W., Birbaumer, N., 1994. Mapping P300

waves onto inhibition: Go/No-Go discrimination. Electroencephalogr. Clin.

Neurophysiol. 92, 44–55.

Schroger, E., 1993. Event-related potentials to auditory stimuli following

transient shifts of spatial attention in a Go/Nogo task. Biol. Psychol. 36,

183–207.

Simson, R., Vaughan Jr., H.G., Ritter, W., 1977. The scalp topography of

potentials in auditory and visual Go/NoGo tasks. Electroencephalogr. Clin.

Neurophysiol. 43, 864–875.

Weisbrod, M., Kiefer, M., Marzinzik, F., Spitzer, M., 2000. Executive control is

disturbed in schizophrenia: evidence from event- related potentials in a

Go/NoGo task. Biol. Psychiatry 47, 51–60.