| | Arousal-state modulation in children with AD/HDAccepted 29 September 2008. Abstract ObjectiveTo investigate the effect of arousal-state modulation, via manipulation of stimulus event-rate, on response inhibition in children with Attention-Deficit/Hyperactivity disorder (AD/HD) using behavioural and ERP measures. MethodsEighteen children with AD/HD, aged 7–14 years, and 18 age-and sex-matched controls performed a cued visual Go/Nogo task (70% Go) with stimuli presented at fast, medium and slow event-rates. Task performance and ERPs to Warning, Go and Nogo stimuli, as well as preparation between the S1–S2 interval, were examined for group differences. ResultsAD/HD subjects displayed poorer response inhibition during the fast condition, accompanied by a reduced Nogo P3. Group differences during the fast rate extended to Warning cues, with the AD/HD group showing ERP evidence of atypical orienting/preparation, as indexed by the early and late CNV, and early sensory/attentive processing prior to S2. ConclusionsAlthough deficient response inhibition has been proposed as the core deficit in AD/HD, the results of the present study highlight the key role of energetic factors. Furthermore, group differences found to cues suggest that this effect extends to the processing of task-irrelevant stimuli. SignificanceThis was the first ERP Go/Nogo task investigation using three event-rates, and the results support the theory that state factors may contribute to response inhibition deficits in AD/HD. 1. Introduction  Attention-Deficit/Hyperactivity Disorder (AD/HD) is a developmental disorder characterised by age-inappropriate levels of inattention, and/or hyperactivity and impulsivity that occurs prior to 7years of age (APA, 1994). It is estimated to effect 3–6% of school-age children (Pelham et al., 1992), making the disorder one of the most widespread psychiatric conditions of childhood (Barkley, 1997a). Leading neuro-psychological models of AD/HD have converged on the view that AD/HD is characterised by a core deficit in behavioural inhibition, arising from neuro-developmental anomalies in brain activity (Barkley, 1997b, Quay, 1997). These perspectives, however, have only received limited support (Sergeant et al., 2003), with an increasing number of investigations failing to find inhibition deficits in AD/HD samples (e.g. Borger and van der Meere, 2000, Banaschewski et al., 2004), raising questions as to whether these theories can fully account for the neuro-psychologic heterogeneity of AD/HD (Nigg, 2005, Sergeant, 2005, Sonuga-Barke and Sergeant, 2005), with other accounts focusing instead on the role of energetic factors, such as arousal, activation and effort (Sergeant et al., 1999, Sergeant, 2000). A theory that emphasises the key influence of energetic state on AD/HD is the cognitive–energetic model, applied to AD/HD by Sergeant et al., 1999. According to the model, event-rate, i.e. the speed with which stimuli are presented, alters a subject’s energetic state. Compared with the medium event-rate, a fast event-rate is said to induce over-arousal/activation, whereas, a slow event-rate may induce under-arousal/activation (Sergeant, 2000). In order to offset a decline in task performance, subjects have to correct their state during fast and slow conditions. van der Meere et al., 1995 underscored the idea that inhibitory control in children with AD/HD is associated with energetic state regulation. They compared children with AD/HD with and without a Tic Disorder (TD) and a normal control group, using a modified Go/Nogo task presented at three event-rates: fast (1s), medium (4s) and slow (8s). Findings indicated that behavioural inhibition was strongly related to event-rate, with AD/HD subjects making more errors of commission during both the fast and slow rates, but a similar number of errors in the medium condition; an effect found to be resistant to methlyphenidate and clonidine medication (van der Meere et al., 1999), and across different age groups (between 7 and 12 years) in children with AD/HD (van der Meere and Stemerdink, 1999). More recent research, however, has provided mixed results, with some reporting more commission errors only during fast (Potgeiter et al., 2000), slow (Wiersema et al., 2005, Wiersema et al., 2006a, Wiersema et al., 2006b), all (Raymaekers et al., 2007) or neither event-rate condition (Borger and van der Meere, 2000). The primary aim of this study was to examine the effect of energetic state modulation, via manipulation of stimulus event-rate, on performance of inhibitory processing during a cued Go/Nogo task in children with AD/HD and controls. A limitation of the research outlined above is that it relied upon the quantification of inhibition in terms of behavioural outcomes (e.g. reaction time and errors), which reveals little about the specific information processing stages underlying inhibition. In contrast, Event-related Potential (ERP) measures allow a direct investigation of these processes, with ERP amplitude sensitive to changes in the mobilisation of energetical mechanisms involved during task performance (e.g. Gopher and Donchin, 1986, Mulder, 1986). In the only previous state regulation ERP investigations in children with AD/HD and controls, Wiersema et al., 2005, Wiersema et al., 2006b examined the effect of fast and slow event-rates on the inhibition-related components of the N2 and P3 (e.g. Kok, 1986, Jodo and Kayama, 1992, Smith et al., 2006, Smith et al., 2007, Smith et al., 2008). Contrary to expectations, no differences were found between the groups in Nogo N2 amplitude or commission errors. Slower and more variable performance was accompanied by an attenuated Go P3 during the slow event-rate in AD/HD group; interpreted as reflecting the inability of these subjects to adjust their underaroused state during this condition. However, this research was limited by the use of only two event-rates (i.e. fast, 2s, and slow, 8s), and an analysis restricted to midline electrode sites. Given that the cognitive-energetic model emphasises consideration of group differences between children with AD/HD and controls during fast/slow rates in comparison to moderate Inter-stimulus Intervals (ISIs), the present study includes a medium event-rate, as well as an increased number of electrodes. Although the main focus of this article is the influence of event-rate on inhibitory processing, the addition of a fixed cue-to-target interval preceding Go/Nogo stimuli allows examination of the Contingent Negative Variation (CNV) – including the early CNV (CNV-E), linked to orienting/expectancy (Loveless, 1979), and the late CNV (CNV-L), an index of preparation for the target (Walter et al., 1964). Previous research has generally reported an attenuated CNV-E (van Leeuwen et al., 1998, Hennighausen et al., 2000), and an atypical CNV-L (e.g. Aydin et al., 1987, Hennighausen et al., 2000, Perchet et al., 2001) in children with AD/HD relative to controls. Given that the cognitive–energetic model predicts a pervasive influence of energetic factors on children with AD/HD, it is expected that group differences will extend to the preparation for, and orienting to, the imperative Go/Nogo stimulus. In sum, this study sought to extend the previous AD/HD ERP state regulation literature by considering three event-rate conditions as outlined in the cognitive–energetic model, with a secondary focus on the investigation of the ERP correlates of preparing/orienting to stimuli. It was expected that children with AD/HD would perform more poorly than control children, as indicated by increased errors across conditions. Further, it was hypothesised that children with AD/HD would show more errors in the fast and slow event-rates, compared to the medium condition. It was also anticipated that children with AD/HD would show the typical indices of poor response inhibition (i.e. smaller Nogo N2 and P3), relative to controls. While no specific predictions were made for the CNV and early exogenous/sensory components to the Warning cue, given the potentially cascading nature of early processing issues on later endogenous aspects of processing, any differences that were found would be explored. 2. Methods 2.1. Participants Thirty-six subjects participated in this study. The AD/HD group consisted of 12 males and 6 females aged between 7years 9months and 14years and 7months, diagnosed as having AD/HD of the Combined type according to the DSM-IV criteria, with confirmation by an independent psychologist. The control group consisted of 18 children without AD/HD matched on age and sex to the clinical group. In the AD/HD group, 14 children were currently taking stimulant or other treatment medication, but all were free of medication for at least 24h (5 half-lives) before testing. Three subjects in each group were left-handed. General inclusion criteria required subjects to have (a) an estimated IQ of not less than 80, (b) no disorders of consciousness or head injuries and (c) no comorbid disorders. Parent(s) of all children in the study completed the Child Behaviour Checklist (CBCL: Archenbach and Edelbrock, 1991), Conners’ Parent Scale-Revised (CPRS-R: Conners, 1997), a DSM-IV screener (APA, 1994), and a questionnaire which considered physical and health concerns – these allowed confirmation of the diagnosis for clinical subjects, and screened control children for significant behavioural problems. Control children were recruited via an advertisement in the local area newspaper, while children with AD/HD were recruited either through a local community sporting organisation, parental support group, or from Northfields Clinic, the university’s public psychology facility. Regardless of their performance, all children received a certificate of appreciation and a small chocolate bar at completion of the session. Parents received A$20 to compensate for travel expenses and a report on their child’s reading and spelling ability. The joint University of Wollongong/Illawarra Area Health Service Human Research Ethics Committee approved the research protocol prior to the start of testing. 2.2. Stimuli Stimuli for the cued visual Go/Nogo task consisted of a fixation cross, a yellow “Warning” square, a green “go” sign, and a red “stop” sign. The trial sequence included: the fixation cross for 500ms, which was replaced by a yellow square for 1500ms (i.e. the S1, indicating that subjects should prepare to respond), followed by the Go or Stop stimulus (i.e. the S2) for 1500ms, and a variable blank S2–S1 period depending on the event-rate condition: fast (range 250–750ms, mean=500ms), medium (range 3250–3750ms, mean=3500ms), or slow (range 6250–6750ms, mean=6500ms). Therefore, total mean ISIs between imperative stimuli were 2500ms (range 2000–3000), 5500ms (range 5000–6000ms), and 8500ms (range 8000–9000ms), for the fast, medium and slow conditions, respectively (see Fig. 1). In all three conditions subjects responded via a button press with the thumb of the right hand, irrespective of handedness. Only presses to the Go stimulus were regarded as correct, while incorrect responses (i.e. pressing to Nogo or Warning stimuli) were recorded to calculate error rates. After an initial practice block of 10 trials (40% Nogo probability), three experimental blocks (i.e. one each of the fast, medium, slow conditions) of 120 trials each (30% Nogo probability) were completed. The order of the event-rate conditions was counterbalanced across subjects. Total task time was 42min. 2.3. Procedure The experiment was conducted over two sessions. In both sessions the child and parent(s) were familiarised with the testing equipment and procedure. Informed written consent was obtained from the parent(s) and verbal assent obtained from the child, after being given an outline of the procedure. It was stressed that consent could be withdrawn at any time. In session one, parent(s) completed the information sheet as well as the CPRS-R, CBCL, DSM-IV screener and demographic questionnaires. Concurrently, each child completed, in order, the Neale Analysis of Reading Ability (Neale, 1999), the South Australian Spelling Test (SAST: Westwood, 1979), and the Raven’s Standard Progressive Matrices (SPM: Raven, 1989). Electrophysiological testing was conducted in session two. After the recording electrodes were fitted the child was seated in a sound-attenuated electrically-shielded booth. The Go/Nogo task was explained to the child such that they would see four symbols. First, a fixation cross, and then a yellow square which was a Warning signal telling them to “get ready and press the button”, followed by either a green “go” sign or a red “stop” sign. The Go stimulus meant press the button, and the stop/Nogo stimulus required the participant to refrain from responding. Participants were instructed to focus on a central fixation cross, and press the response button as quickly and accurately as possible with the thumb of their right hand when they saw the Go stimulus. 2.4. Electrophysiological recording An electrode cap containing tin electrodes was fitted with continuous EEG, recorded at 19 sites (Fp1, Fp2, F7, F3, Fz, F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1 and O2) of the international 10–20 system (Jasper, 1958). The electro-oculogram was measured vertically (vEOG) with two tin electrodes, 1cm above and below the left eye. All electrodes were referenced to linked ears. Impedances for ears and eyes were below 3kΩ, with scalp electrodes below 5kΩ. The subject was grounded by a cap electrode located midway between FPz and Fz. The EEG and vEOG signals were amplified 19 times, with bandpass down 3dB at 0.01 and 100Hz, via a NuAmps 40-channels amplifier system from Neuroscan (Compumedics Limited, Melbourne, Australia). Prior to processing, the EEG data were digitally filtered using low-pass filter 3dB down at 30Hz. 2.5. Data extraction The ERP epoch was defined as 100ms pre-stimulus to 900ms post-stimulus. Epochs were excluded from averaging if they contained activity exceeding ±150μV at any non-frontal site. An ocular artefact reduction procedure (Semlitsch et al., 1986) was used to reduce the influence of eye movements based on the vEOG channel. To ensure compatibility within-subjects, the number of epochs available for averaging was determined for Nogo stimuli initially, with Go and Warning epochs restricted to the same number, being selected randomly from the total available. Grand average ERP waveforms for each stimulus were displayed for the purpose of defining each component’s latency range. Peak quantification was conducted using an automatic peak-picking program, and was measured relative to a 100-ms pre-stimulus baseline. For both Warning and Go/Nogo stimuli, the latency ranges, relative to stimulus onset, were as follows: N1: 80–180ms, P2: 180–280ms, N2: 230–370ms, P3: 280–500ms. Negative peaks were time-locked to the greatest minimum value at site Fz, while positive peaks were time-locked to the greatest maximum value at site Pz, in the specified latency range. 2.6. Data analysis Error rates (both omission and commission) were calculated as the number of responses divided by the total number of presentations. Group differences on age, psychometric and behavioural performance variables were assessed using a Mixed ANOVA, including (control vs. AD/HD)×IQ1 (High vs. Low)×Event-rate (Fast vs. Medium vs. Slow) with repeated measures on the within-subjects factors. To further investigate within group effects on Nogo errors, group data was analysed separately using a Mixed ANOVA. Primary analyses of the ERP data were restricted to the sites F3, Fz, F4, C3, Cz, C4, P3, Pz and P4. Go and Nogo data were subject to a Group (control vs. AD/HD)×IQ1 (High vs. Low)×Event-rate (Fast vs. Medium vs. Slow)×Lateral (Left vs. Midline vs. Right)×Sagittal (Frontal vs. Central vs. Parietal) mixed ANOVA, with repeated measures on the within-subjects factors. To investigate the effect of Stimulus, an additional mixed ANOVA including Stimulus Type (Go vs. Nogo) was also conducted. Planned contrasts within the Lateral factor compared activity in the left hemisphere (mean of F3, C3 and P3) with the right (mean of F4, C4 and P4), and the mean of these with activity in the midline region (mean of Fz, Cz and Pz). Contrasts within the Sagittal factor compared frontal activity (mean of F3, Fz and F4) with parietal (mean of P3, Pz and P4), and the mean of these with activity in the central region (mean of C3, Cz and C4). These contrasts allow insight into the topographic distribution of each component, and since these analyses were planned with no more of them than the degrees of freedom for each effect, no Bonferroni type adjustment to α were necessary (Tabachnick and Fidell, 1996). Single degrees of freedom contrasts are not affected by violations of symmetry assumptions common in repeated measures analyses, and thus do not require Greenhouse–Geisser-type corrections. As these analyses are carried out over a substantial number of variables, each of which may be considered to constitute a separate experiment. It should be noted that this increases the frequency of type 1 errors, however, as this is an increase in frequency, rather than probability, it cannot be ‘controlled’ by adjustment of α levels (Howell, 1997). Similarly to the Go/Nogo data, Warning ERP and CNV data were subject to Group×IQ×Lateral×Sagittal mixed ANOVA, with repeated measures on the last two factors. All ERP statistics have (1,34) degrees of freedom. Data were normalised using the method described by McCarthy and Wood (1985) and interactions with the Lateral or Sagittal factors which were not significant in the normalised data are not reported here. 3. Results 3.2. Task performance Across conditions, the AD/HD group showed an increased percentage of Warning (F(1,34)=4.73, p<.05), Go (F(1,34)=4.84, p<.05), total commission (Warning+Nogo; F(1,34)=4.67, p<.05), and overall errors, (F(1,34)=4.07, p=.05), relative to controls. Between event-rates, no significant group differences were found for errors or reaction time (RT) to Go stimuli, but the AD/HD group made more Warning errors during the Fast than Slow rate, in contrast to controls, who showed the opposite pattern (Fig. 2; F(1,34)=4.89, p<.05). As reflected in Fig. 2, controls made more Nogo errors in the Fast than Slow condition, which differed for AD/HD subjects, who showed a Medium>Fast/Slow effect – highlighting an increased percentage of Nogo errors during the Fast event-rate for the AD/HD subjects (F(1,34)=4.44, p<.05). This Medium>Fast/Slow interaction for the AD/HD group was supported by a within group analyses of Nogo errors (F(1,16)=10.81, p<.05). 3.3. ERPs to Warning stimuli Group mean ERPs to Warning stimuli can be seen in Fig. 3, while effect summaries for all components are shown in Table 2. Group mean latencies for each component and stimulus type are displayed in Table 3. Due to limited space, we do not describe or discuss the topographic results unrelated to Group. | | |  | Peak | Effect | Contrast | Details | F | |
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| N1 | S | f vs. p | −4.2 vs. −1.1 | 42.29**** | | | | | c vs. f/p | −4.8 vs. −2.9 | 19.88*** | | | | L×S | cz to c3/c4 vs. fz/pz to f3f4/p3p4 | −4.5 to −3.9 vs. −5.6 to −2.9 | 4.55** | | | | S×G | f vs. p | AD/HD, −4.1 vs. −1.8: control, −5.5 vs. −0.4 | 6.01** | | | | L×S×G | f3 to f4 vs. p3 to p4 | AD/HD, −3.7 to −4.0 vs. −2.3 to −1.4; control, −5.5 to −5.5 vs. 0.9 to 0.6 | 4.75** | | | | R×G | Med vs. Fast/Slow | AD/HD, −5.6 vs. −2.1; control, −3.4 vs. −3.5 | | | | | | | P2 | S | f vs. p | −0.3 vs. 3.6 | 40.28**** | | | | | c vs. f/p | 3.5 vs. 1.7 | 33.61**** | | | | L | m vs. l/r | 3.5 vs. 1.7 | 28.18**** | | | | L×S | f3 to f4 vs. p3 to p4 | −1.4 to −0.8 vs. 4.0 to 2.5 | 7.82*** | | | | | fz to f3/f4 vs. pz to p3/p4 | 1.4 to −1.1 vs. 4.4 to 3.2 | 6.47** | | | | L×R×G | Med, m to l/r vs. Fast/Slow m to l/r | AD/HD, 0.6 to 0.1 vs. 4.6 to 2.2; control, 4.1 to 2.0 vs. 3.2 to 1.9 | 8.91*** | | | | | | N2 | S | f vs. p | −1.1 vs. 0.6 | 4.06** | | | | R×G | Fast vs. Slow | AD/HD, 2.3 vs. −1.6; control, −0.6 vs. −0.5 | 5.35** | | | | | Med vs. Fast/Slow | AD/HD, −2.8 vs. 0.3; control, 0.6 vs. −0.6 | 5.94** | | | | L×R×G | Fast, m to l/r vs. Slow, m to l/r | AD/HD, 3.3 to. 1.8 vs. −3.6 to −0.6: control, −0.7 to −0.6 vs. −0.8 to −0.4 | 4.88** | | | | | | P3 | S | f vs. p | 2.9 vs. 4.8 | 10.11*** | | | | |
| | | | Component | Control | AD/HD | |
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| Fast | Medium | Slow | Fast | Medium | Slow | |
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| Warning | | | N1 | 131.3 (16.8) | 126.9 (14.8) | 131.5 (12.6) | 126.5 (29.6) | 130.4 (26.9) | 135.9 (31.0) | | | P2 | 212.8 (28.6) | 199.3 (37.6) | 223.0 (27.5) | 206.8 (34.1) | 201.3 (36.8) | 216.8 (31.1) | | | N2 | 278.9 (50.3) | 266.0 (64.8) | 288.4 (47.8) | 280.4 (53.4) | 259.3 (52.4) | 286.7 (45.5) | | | P3 | 382.7 (50.8) | 371.2 (66.1) | 370.1 (59.9) | 365.4 (63.4) | 347.9 (57.2) | 372.4 (64.8) | | | | | | Go | | | N1 | 134.3 (14.6) | 131.2 (12.6) | 132.3 (20.2) | 136.7 (16.3) | 138.4 (16.4) | 136.9 (19.3) | | | P2 | 220.6 (30.5) | 217.2 (19.5) | 223.8 (19.0) | 212.3 (31.9) | 219.6 (33.7) | 230.0 (21.1) | | | N2 | 298.6 (29.7) | 295.0 (48.2) | 294.8 (48.1) | 276.6 (33.4) | 294.3 (33.8) | 310.8 (32.9) | | | P3 | 408.1 (81.7) | 409.6 (68.1) | 401.3 (73.9) | 394.7 (73.7) | 386.0 (51.1) | 409.7 (72.9) | | | | | | Nogo | | | N1 | 130.6 (11.6) | 128.1 (21.3) | 127.8 (19.9) | 131.4 (20.2) | 137.5 (21.3) | 133.4 (25.2) | | | P2 | 215.5 (24.9) | 217.8 (24.3) | 221.0 (13.2) | 206.7 (24.9) | 222.0 (28.6) | 228.6 (11.8) | | | N2 | 293.2 (29.5) | 297.6 (31.5) | 300.9 (30.3) | 281.6 (43.4) | 296.2 (26.25) | 298.0 (31.5) | | | P3 | 412.2 (54.4) | 411.5 (77.7) | 418.7 (92.7) | 393.0 (68.1) | 401.0 (54.0) | 421.6 (67.7) | | | | |
N1 was fronto-centrally maximal with a mean latency of 130ms (with no latency group differences). An Fz>Pz effect was larger in controls than AD/HD, due mainly to reduced N1 amplitude at frontal regions for clinical subjects. A Rate×Group interaction indicated that while the children with AD/HD showed a Medium>Fast/Slow effect, controls were relatively equipotential, revealing a reduction in N1 amplitude during the Fast condition, and an enhancement of this component at the Medium rate in the AD/HD group (Fig. 4a). P2 peaked at 209ms (no group differences in latency), was centro-parietally maximal in the Sagittal dimension and midline maximal in the lateral dimension. A Lateral×Rate×Group interaction revealed that while children with AD/HD showed a large midline>hemispheres effect in the Fast/Slow compared to the Medium event rate, controls displayed the opposite pattern, highlighting an increased midline P2 in the Fast condition, and a reduced amplitude during the Medium condition for the AD/HD group (Fig. 4c). N2 peaked at 273ms and was frontally maximal in the Sagittal dimension (no latency group differences). Event-rate×Group interactions showed, that while controls displayed only minor amplitude variation between conditions, the AD/HD group showed a reduced N2 at the Fast rate, but an augmented component during the Medium condition (Fig. 4b). P3 peaked at 356ms and was parietally maximal, with no group differences in either amplitude or latency. Effect summaries for CNV components are shown in Table 4. CNV-E (350–750ms) showed a hemisphere>midline effect that was larger parietally than frontally (due mainly to increased left hemisphere amplitude). Between event-rates, Lateral (Fig. 4d) and Sagittal interactions revealed a reduced centro-parietal CNV-E for the AD/HD group during the Fast condition. | | | | Peak | Effect | Contrast | Details | F | |
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| CNV_E | S | f vs. p | 1.2 vs. −1.4 | 41.22**** | | | L | m vs. l/r | 0.2 vs. −0.1 | 4.10** | | | L×S | fz to f3/f4 vs. pz to p3/p4 | 1.2 to 1.2 vs. −2.1 to −1.3 | 6.11** | | | L×R×G | Med, m to l/r vs. Fast/Slow m to l/r | AD/HD, −1.1 to −0.7 vs. 0.8 to 0.6: control, 0.4 to −0.3 vs. 0.2 to 0.1 | 8.89*** | | | S×R×G | Med, cz to fz/pz vs. Fast/Slow cz to fz/pz | AD/HD, −1.0 to −0.7 vs. 0.7 to 0.3; control, 0.6 to 0.0 | 6.90** | | | | | | CNV_L | S | f vs. p | −2.2 vs. −5.4 | 55.22**** | | | L×S | f3 to f4 vs. p3 to p4 | −1.9 to −2.5 vs. −5.6 to −4.8 | 7.09*** | | | S×G | c vs. f/p | AD/HD, −3.1 vs. −3.5: control, −4.6 vs. −4.1 | 4.58** | | | R×G | Med vs. Fast/Slow | AD/HD, −6.3 vs. −1.8; control, −5.3 vs. −3.8 | 3.29* | | | L×R×G | Med, m to l/r vs. Fast/Slow m to Fast/Slow l/r | AD/HD, −7.1 to −6.0 vs. −1.6 to −2.0: control, −5.5 to −5.1 to −4.0 to −3.7 | 5.68** | | | | |
CNV-L (1150–1500ms) was parietally maximal and was greater in the right hemisphere frontally, while parietally there was a left hemisphere maximum. A significant Lateral×Group×Event-rate interaction (Fig. 4e), and also a tendency (Quadratic p=.07) towards an increased Medium>Fast/Slow effect in the AD/HD than control group, highlighted a reduced CNV-L during the Fast condition for AD/HD subjects. 3.4. ERPs to Go/Nogo stimuli Group mean ERPs to Go and Nogo stimuli can be seen in Fig. 5a and b, with effect summaries shown in Table 5. Peaking at 133ms, N1 showed a frontocentral and midline maximum with no group differences in latency, amplitude or stimulus. | | | | Peak | Effect | Contrast | Details | F | |
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| N1 | S | f vs. p | −5.2 vs. 1.8 | 250.83**** | | | | c vs. f/p | −3.6 vs. −1.7 | 111.69**** | | | L | m vs. l/r | −3.3 vs. −1.9 | 93.66**** | | | L×S | fz to f3/f4 vs. pz to p3/p4 | −5.5 to −5.0 vs. −0.1 to 2.7 | 63.87**** | | | | | | P2 | S | f vs. p | 5.1 vs. 6.6 | 11.95*** | | | L | m vs. l/r | 6.4 vs. 4.9 | 76.16**** | | | G | Control vs. AD/HD | 6.4 vs. 4.5 | 5.75** | | | S×G | c vs. f/p | AD/HD, 4.5 vs. 4.5: control, 4.6 vs. 7.2 | 8.18*** | | | | | | N2 | S | f vs. p | −3.7 vs. 5.4 | 160.18**** | | | L | l vs. r | 1.4 vs. 0.6 | 5.48** | | | L×S | f3 to f4 vs. p3 to p4 | −2.8 to −4.0 vs. 5.6 to 5.8 | 6.42** | | | stim | Go vs. Nogo | 2.4 vs. −0.7 | 28.84**** | | | | | | P3 | S | f vs. p | 5.0 vs. 15.3 | 185.05**** | | | L | m vs. l/r | 10.9 vs. 9.9 | 14.97**** | | | Stim | Go vs. Nogo | 10.9 vs. 9.7 | 7.84** | | | S×Stim | f vs. p | Go, 4.7 vs. 16.2: Nogo, 5.1 vs. 14.2 | 7.87*** | | | G | Control vs. AD/HD | 11.2 vs. 9.0 | 4.39** | | | Nogo P3×R×G | Fast vs. Slow | AD/HD, 9.2 vs. 9.8; control, 13.6 vs. 8.9 | 4.32** | | | | |
P2 (mean latency 220ms) showed a parietal maximum, with a midline>hemispheres effect also reaching significance (no differences in latency for Group or Stimulus). A main effect of Group revealed a global reduction in P2 amplitude for the AD/HD group relative to controls. Controls showed a frontal/parietal>central effect, in contrast to AD/HD subjects, who displayed similar amplitude along the Sagittal dimension, highlighting a reduced P2 at frontal and parietal sites for the clinical group. N2 (peaking at 295ms with no significant group differences in latency) was frontally maximal, with a right>left effect. Across the scalp, N2 was larger to Nogo than Go stimuli, with an increased frontal>parietal effect for Nogo relative to Go stimuli in the Sagittal dimension. P3 latency averaged 410ms and was longer for Nogo than Go stimuli (420 vs. 401ms; F=4.62, p<.05). P3 was maximal parietally, with a midline>hemispheres effect also reaching significance. A parietal>frontal effect was reduced in Nogo compared to Go stimuli (Pz−Fz difference=9.0 vs. 11.5μV), reflecting the anteriorisation of P3 to Nogo relative to Go stimuli. P3 was larger to Go than Nogo stimuli, with a main effect of Group revealing a global reduction of this component in children with AD/HD relative to controls. Controls showed a large Fast>Slow Nogo P3 effect, in contrast to the AD/HD subjects, who displayed an opposite pattern of much smaller magnitude, revealing a reduced Nogo P3 during the Fast event-rate for the clinical group. 4. Discussion The primary aim of the current study was to examine the effect of arousal-state modulation, via manipulation of stimulus event-rate, on behavioural and ERP indices of inhibition in children with AD/HD and healthy controls. As a secondary focus, we also aimed to investigate whether differing event-rate conditions could also modulate pre-S2 ERPs, such as the early and late CNV components. Analysis of the CPRS-R and CBCL data revealed that the two groups were uniquely defined, generally confirming the diagnoses of AD/HD for the clinical subjects at the group level. The groups did not differ in terms of chronological, reading or spelling age. There was, however, a difference in IQ, with the clinical group showing a significantly lower mean IQ than controls. As noted in,1 to investigate the possible effect of IQ, both the control and AD/HD group were split into high- and low-IQ groups. However, since no significant interactions were found for any of the task performance, ERP amplitude or latency measures, IQ was not considered to have impacted on the results discussed below. 4.1. ERPs to Warning stimuli Across event-rate conditions, AD/HD subjects displayed a higher percentage of Warning errors than controls, accompanied by evidence of atypical early attentive processing of the cue stimulus (Näätänen and Picton, 1987), with a reduced N1 at frontal sites – consistent with previous AD/HD Go/Nogo research (e.g. Smith et al., 2004, Johnstone and Clarke, in press). N1 amplitude, however, was not stable between event-rate conditions for AD/HD subjects, who showed a reduced N1 during the fast condition, and an enhancement of this component during the medium rate relative to controls (see Fig. 4a). Interestingly, the clinical group displayed a similar pattern of atypical ERP modulation in the N2 (Fig. 4b), but the opposite for the P2 (i.e. overactivation in fast event-rate, and underactivation in the medium condition across the midline; Fig. 4c). The N1 can be modulated by arousal (Näätänen and Picton, 1987), while Oades (1998) has suggested that larger P2s in AD/HD are associated with the dysregulation of appropriate contextual information. During active attend conditions, the N2 has been linked with effective stimulus categorisation (Näätänen and Picton, 1986), and previous investigations have reported no differences in the cue-N2 between controls and hyperkinetic children (e.g. Banaschewski et al., 2003, Banaschewski et al., 2004). Thus, taken together, the present data potentially suggest a pervasive influence of arousal/state modulation on early sensory information extraction for these essentially task-irrelevant stimuli for the AD/HD group. During the fast rate, it appears that following earlier information extraction problems at N1, the children with AD/HD showed atypical processing at P2, with subsequent stimulus categorisation impairments at N2. While during the medium condition, the clinical group generally displayed an increased magnitude of responses (i.e. N1 and N2), possibly suggesting an optimal arousal level given the similar levels of task performance between the groups. Combined with a corresponding increase in Warning errors during the fast rate, this study provides the first evidence of group differences in the processing of cue stimuli, which although task irrelevant, can be differentially modulated by event-rate in children with AD/HD relative to controls. Evidence of altered information processing between event-rates in children with AD/HD was also seen in the later processing after the Warning cue. During the fast event-rate, the clinical group displayed reduced amplitudes for both the CNV-E (across the midline; Fig. 4d) and CNV-L (see Fig. 4e) components, respectively suggestive of a diminished ability to orientate (Rohrbaugh and Gaillard, 1983) and prepare (Walter et al., 1964) for the impending Go/Nogo stimulus. Tecce, 1972 has suggested that the CNV is an index of cortical arousal related to anticipatory attention, with reduced CNV-L amplitudes previously linked with elevated arousal levels (Higuchi et al., 1997a, Higuchi et al., 1997b). Accordingly, these findings may reflect a state of over-arousal in the AD/HD group, leading to impairments in adjusting to, and preparing for, upcoming stimuli. Findings, not only in line with previous research reporting atypical CNV amplitudes in AD/HD samples (e.g. Aydin et al., 1987, Dumais-Huber and Rothenberger, 1992, Banaschewski et al., 2003), but that provide novel evidence of the effect of arousal-state modulation on these processes. 4.2. ERPS to Go/Nogo stimuli This study provides further task performance and ERP evidence of atypical response activation/inhibition in children with AD/HD relative to controls. In regard to overall group differences, consistent with previous reports children with AD/HD showed higher total commission (Warning+Nogo) and overall errors (commission+omission), in addition to a greater percentage of Go errors, collectively indicative of deficient response execution (Holcomb et al., 1986, Yong-Liang et al., 2000) and inhibitory processing (Broyd et al., 2005; Johnstone and Clarke, in press). The current study also reports a globally reduced P3 in the AD/HD group, in line with previous reports of concurrent poorer performance and attenuated P3 amplitudes in AD/HD samples over a variety of paradigms (e.g. Loiselle et al., 1980, Overtoom et al., 1998, Barry et al., 2003). Finally, the AD/HD group showed further evidence of atypical processing of Go/Nogo stimuli with a reduced P2 across task conditions, which, while in partial agreement with one cued Go/Nogo task investigation (Smith et al., 2004), is in contrast to a number of studies using two- and three-tone oddball tasks that have reported either, larger P2s in children with AD/HD (for a review see Barry et al., 2003), or no differences to controls (e.g. Prichep et al., 1976, Karayanidis et al., 2000). Studies by Oades (1998) and Hegerl et al. (1993) have shown that the P2 is related to the suppression of distracting sensory information from further processing. Thus, the smaller P2 for the AD/HD group could reflect a reduced ability of this group to suppress irrelevant sensory activity during task performance. Further investigations, however, are required to clarify this effect, and to define the exact role of the P2 generally, and in AD/HD. Between event-rate conditions, the AD/HD group committed more Nogo errors in the fast event-rate, compatible with previous response inhibition (van der Meere et al., 1995, van der Meere et al., 1999) and task performance research (Chee et al., 1989, Leung et al., 2000). Interestingly, and in contrast to previous reports, the poorer inhibitory performance of AD/HD group was not accompanied by a reduction in N2 amplitude (e.g. Yong-Liang et al., 2000). Wiersema et al. (2006b) reported similar N2 amplitudes during fast event rate conditions between AD/HD and controls when the clinical sample excluded comorbid subjects. But after children with AD/HD with comorbid Oppositional Defiant (ODD) and Conduct disorder (CD) were included in the analysis, this group exhibited a smaller N2 and increased Nogo errors than controls. However, in the present study, the AD/HD group means for the CBCL and CRPS-R exceeded the clinical cut-off level predominantly on scales indexing attention and hyperactivity. In addition, the primary independent diagnosis of children in the clinical group was AD/HD, and none had a secondary diagnosis, making this explanation unlikely. The lack of a reduction in N2 amplitude may indicate an equivalent level of response conflict between the groups (e.g. Nieuwenhuis et al., 2003, Donkers and van Boxtel, 2004; however, the data from the current study is unable to confirm this interpretation. Alternatively, visual inspection of the waveforms in Fig. 5 reveals that the N2 is superimposed on the ascending flank of the Go/Nogo P3. Consequently, it is possible that the general enhancement of the Go/Nogo P3 for controls relative to the clinical group could have masked differences in N2 amplitude between the groups. In contrast to the Nogo N2, evidence linking the Nogo P3 to response inhibition is accumulating (e.g. Smith et al., 2006, Smith et al., 2007, Smith et al., 2008). Correspondingly, the current study found a reduced Nogo P3, concomitant with increased Nogo commission errors for the AD/HD group during the fast event-rate. In terms of the cognitive–energetic model, this may indicate the AD/HD group were over-activated during this condition, causing cascading atypical early preparatory processing deficits (e.g. reduced CNV-E and CNV-L), leading to reduced processing of the Nogo P3 and subsequent impairments in inhibitory performance. Contrary to the predictions, no behavioural or ERP differences were found between the groups during the slow event-rate. Combined with poorer performance during the fast condition, this finding differs from previous AD/HD state regulation research reporting slower and more variable task performance of AD/HD subjects during slow, but not fast event-rate conditions (Wiersema et al., 2005, Wiersema et al., 2006a, Wiersema et al., 2006b). This inconsistency may be clarified by a variety of factors. First, further analysis of the within group data for the clinical group revealed a significant fast/slow>medium effect for Nogo errors, consistent with the predictions of the cognitive–energetic model, where variation in performance between event-rates for AD/HD subjects should be described by a quadratic trend, i.e. optimal performance in medium conditions, but relatively poorer performance during fast/slow rates (van der Meere et al., 1999). Accordingly, the present data suggest that the medium rate induced an optimal arousal level for the clinical group, with corresponding indications of aberrant information processing during the fast condition. However, these findings do not fully explain why this pattern did not differ significantly between the groups. Thus, perhaps a more complete explanation of these results may be in regard to the objective measurement of arousal/activation in the current study. It has been suggested that the effect of event-rate on arousal/activation level may be highly idiosyncratic, and that depending on the particular experimental setting and task requirements, it is difficult to accurately gauge the effect of a given ISI on an individual’s arousal/activation levels (Sikström and Söderlund, 2007). Consistent with this notion, is data indicating that event-rate differentially affects response inhibition in children with AD/HD more than controls, although the pattern of findings has been mixed (van der Meere, 2005). Indeed, as mentioned above, previous research has reported increased commission errors only during fast (Potgeiter et al., 2000), slow (Wiersema et al., 2006b), all (Raymaekers et al., 2007), or neither event-rate condition (Borger and van der Meere, 2000). It would therefore be advantageous to employ additional objective psychophysiological indices of arousal and activation in future research (e.g. skin conductance level, skin conductance response); allowing converging autonomic evidence of the effect of event-rate manipulations, rather than simply assuming changes in arousal/activation. While the findings of the present study are not in complete accordance with the predictions of the cognitive–energetic model, they are nonetheless of relevance to the Barkley, 1997b, Quay, 1997 models of AD/HD. That is, for an inhibition deficit explanation of AD/HD to be confirmed it needs to show that disinhibition occurs independently of event-rate, and our result of event-rate influencing Nogo errors in the current study implies that the inhibition deficit in AD/HD is not constant. Deficits in AD/HD may therefore potentially be understood in terms of a problem in state regulation and not response inhibition in the narrow sense. Finally, future studies could consider the influence of the CNV on later potentials, such as the Warning and Go/Nogo N2. Although previous investigations have sought to correct the influence of the CNV using Principal Component Analysis procedures (e.g. Oddy et al., 2005), due to the clinical focus of the data, additional decomposition methods were considered beyond the scope of this study. 5. Conclusions In summary, this study reports evidence of deficits in response inhibition in terms of Nogo commission errors in children with AD/HD during fast event-rates. This finding is in contrast to the notion that AD/HD is primarily a disorder of behavioural inhibition, and implicates the key role of energetic factors. Contrary to expectations, only the Nogo P3 (and not the Nogo N2) showed an association to atypical response inhibition in the AD/HD group. The results also show that ERP group differences are present in the processing of Warning stimuli, which while not required for successful task performance, are differentially modulated by event-rate in children with AD/HD relative to controls. Acknowledgements We thank the children who participated and their parents, Val Markovska, for assistance with data collection, and the anonymous reviewers for their helpful comments on this manuscript. This study was funded by an Australian Research Council Discovery Project Grant (DP0559048). References APA, 1994. 1.American Psychological Association. Diagnostic and statistical manual of mental disorders. Washington, DC: American Psychological Association; 1994. Archenbach and Edelbrock, 1991. 2.Archenbach TM, Edelbrock C. Manual for the child behaviour checklist and revised child behaviour profile. Burlington, VT: University of Vermont Department of Psychiatry; 1991;. Aydin et al., 1987. 3.Aydin C, Idiman F, Idiman E. Contingent negative variation in normal children and in children with attention deficit disorder. Adv Biol Psychiatry. 1987;16:187–190. Banaschewski et al., 2003. 4.Banaschewski T, Brandeis D, Heinrich H, Albrecht B, Brunner E, Rothenberger A. Association of ADHD & conduct disorder & brain electrical evidence for the existence of a distinct subtype. J Child Psychol Psychiatry. 2003;43:1–21.
CrossRef
Banaschewski et al., 2004. 5.Banaschewski T, Brandeis D, Heinrich H, Albrecht B, Brunner E, Rothenberger A. Questioning inhibitory control as the specific deficit of ADHD – evidence from brain electrical activity. J Neural Transm. 2004;111:841–864. MEDLINE Barkley, 1997a. 6.Barkley RA. Attention-deficit disorder, self-regulation, and time: toward a more comprehensive theory. J Dev Behav Pediatr. 1997;121:65–94. Barkley, 1997b. 7.Barkley RA. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull. 1997;121:65–94. MEDLINE |
CrossRef
Barry et al., 2003. 8.Barry RJ, Johnstone SJ, Clarke AR. A review of electrophysiology in attention-deficit/hyperactivity disorder. II: Event-related potentials. Clin Neurophysiol. 2003;114:184–198. Abstract | Full Text |
Full-Text PDF (383 KB)
|
CrossRef
Borger and van der Meere, 2000. 9.Borger N, van der Meere J. Motor control and state regulation in children with ADHD: a cardiac response study. Biol Psychol. 2000;247–267. Broyd et al., 2005. 10.Broyd SJ, Johnstone SJ, Barry RJ, Clarke AR, McCarthy R, Selikowitz M, et al. The effect of methylphenidate on response inhibition and the event-related potential of children with attention deficit/hyperactivity disorder. Int J Psychophysiol. 2005;58:47–58. MEDLINE |
CrossRef
Chee et al., 1989. 11.Chee P, Logan G, Schachar R, Lindsay P, Wachsmuth R. Effects of event rate and display time on sustained attention in hyperactive, normal, and control children. J Abnorm Child Psychol. 1989;17:371–391. MEDLINE |
CrossRef
Conners, 1997. 12.Conners CK. Conners parent rating scale revised. Chicago, IL: Springer; 1997;. Donkers and van Boxtel, 2004. 13.Donkers FCL, van Boxtel GJM. The N2 in go/no-go tasks reflects conflict monitoring not response inhibition. Brain Cogn. 2004;56:165–176. MEDLINE Dumais-Huber and Rothenberger, 1992. 14.Dumais-Huber C, Rothenberger A. Psychophysiological correlates of orienting, anticipation and contingency changes in children with psychiatric disorders. J Psychophysiol. 1992;6:225–239. Gopher and Donchin, 1986. 15.Gopher D, Donchin E. Workload: an examination of the concept. In: Boff KR, Kaufman L, Thomas JP, Boff KR, Kaufman L, Thomass JP editor. Handbook of perception and human performance: cognitive processes and performance. Oxford, England: John Wiley and Sons; 1986;p. 1–49. Hegerl et al., 1993. 16.Hegerl U, Juckel G. Intensity dependence of auditory evoked potentials as an indicator of central serotonergic neurotransmission: a new hypothesis. Biol Psychiatry. 1993;33:173–187. Abstract |
Full-Text PDF (1719 KB)
|
CrossRef
Hennighausen et al., 2000. 17.Hennighausen L, Schulte-Koerne G, Warnke A, et al. Contingent negative variation (CNV) in children with attention deficit hyperactivity disorder: an experimental study using the continuous performance test (CPT). Z Kinder Jugendpsychiatr Psychother. 2000;28:239–246. MEDLINE |
CrossRef
Higuchi et al., 1997a. 18.Higuchi S, Watanuki S, Yasukouchi A. Effects of reduction in arousal level caused by long-lasting task on CNV. Appl Hum Sci. 1997;16:29–34. Higuchi et al., 1997b. 19.Higuchi S, Watanuki S, Yasukouchi A, Sato M. Effects of changes in arousal level by continuous light stimulus on contingent negative variation (CNV). Appl Hum Sci. 1997;16:55–60. Holcomb et al., 1986. 20.Holcomb PJ, Ackerman PJ, Dykman RA. Auditory event-related potentials in attention and reading-disabled boys. Int J Psychophysiol. 1986;3:263–273. MEDLINE |
CrossRef
Howell, 1997. 21.Howell DC. Statistical methods for psychology. Belmont, CA: Wadsworth; 1997;. Jasper, 1958. 22.Jasper HH. The ten-twenty electrode system of the international federation in electroencephalography and clinical neurophysiology. EEG J. 1958;10:371–375. Jodo and Kayama, 1992. 23.Jodo E, Kayama Y. Relation of a negative ERP component to response inhibition in a Go/No-go task. Electroenceph Clin Neurophysiol. 1992;82:477–482. MEDLINE |
CrossRef
Johnstone and Clarke, in press. 24.Johnstone SJ, Clarke AR. Dysfunctional response preparation and inhibition during a visual go/nogo task in children with two subtypes of attention-deficit hyperactivity disorder. Psychiatry Res, in press. Karayanidis et al., 2000. 25.Karayanidis F, Robaey P, Bourassa P, de Koning D, Geoffroy G, Pelletier G. ERP differences in visual attention processing between attention-deficit/hyperactivity disorder and control boys in the absence of performance differences. Psychophysiology. 2000;37:319–333. MEDLINE |
CrossRef
Kok, 1986. 26.Kok A. Effects of degradation of visual stimuli on components of the event-related potential (ERP) in go/nogo reaction tasks. Biol Psychol. 1986;23:21–38. MEDLINE |
CrossRef
Leung et al., 2000. 27.Leung JP, Leung PWL, Tang CSK. A vigilance study of ADHD and control children: event rate and extra-task stimulation. J Dev Disabil. 2000;12:187–201. Loiselle et al., 1980. 28.Loiselle DL, Stamm JS, Maitinsky S, Whipple SC. Evoked potential and behavioral signs of attentive dysfunctions in hyperactive boys. Psychophysiology. 1980;17:193–201. MEDLINE |
CrossRef
Loveless, 1979. 29.Loveless NE. Event-related slow potentials of the brain as expressions of orienting function. In: Kimmel HD, Olst EHV, Orlebeke JF, Kimmel HD, Olst EHv, Orlebekes JF editor. The orienting reflex in humans. New Jersey: Lawrence Erlbaum Associates; 1979;p. 77–100. McCarthy and Wood, 1985. 30.McCarthy G, Wood CC. Scalp distributions of event-related potentials: an ambiguity associated with analysis of variance models. Electroenceph Clin Neurophysiol. 1985;62:203–208. MEDLINE Mulder, 1986. 31.Mulder G. The concept of mental effort. In: Gailard AK, Coles MG, Gailard AK, Coless MG editor. Energetics and human information processing. Matinus: Nijhoff; 1986;p. 175–198. Näätänen and Picton, 1986. 32.Näätänen R, Picton TW. N2 and automatic versus controlled processes. Electroencephal Clin Neurophysiol Suppl. 1986;38:169–186. Näätänen and Picton, 1987. 33.Näätänen R, Picton T. The N1 wave of the human electric and magnetic response to sound: a review and an analysis of the component structure. Psychophysiology. 1987;24:375–425. MEDLINE |
CrossRef
Neale, 1999. 34.Neale MD. Neale analysis of reading ability. Melbourne: Australian Council for Educational Research Limited; 1999;. Nieuwenhuis et al., 2003. 35.Nieuwenhuis S, Yeung N, Van Den Wildenberg W, Ridderinkhof KR. Electrophysiological correlates of anterior cingulate function in a go/no-go task: effects of response conflict and trial type frequency. Cogn Affect Behav Neurosci. 2003;3:17–26. MEDLINE |
CrossRef
Nigg, 2005. 36.Nigg JT. Neuropsychologic theory and findings in attention-deficit/hyperactivity disorder: the state of the field and salient challenges for the coming decade. Biol Psychiatry. 2005;57:1424–1435. Abstract | Full Text |
Full-Text PDF (301 KB)
|
CrossRef
Oades, 1998. 37.Oades RD. Frontal, temporal and lateralized brain function in children with attention-deficit hyperactivity disorder: a psychophysiological and neuropsychological viewpoint on development. Behav Brain Res. 1998;94:83–95. MEDLINE |
CrossRef
Oddy et al., 2005. 38.Oddy BW, Barry RJ, Johnstone SJ, Clarke AR. Removal of CNV effects from the N2 and P3 ERP components in a visual Go/NoGo task. J Psychophysiol. 2005;19:24–34. Overtoom et al., 1998. 39.Overtoom C, Verbaten MN, Kemner C, Kenemans JL, van Engeland H, Buitelaar J, et al. Associations between event-related potentials and measures of attention and inhibition in the continuous performance task in children with ADHD and normal controls. J Am Acad Child Adolesc Psychiatry. 1998;37:977–985. Abstract |
Full-Text PDF (6414 KB)
Pelham et al., 1992. 40.Pelham W, Gnagy E, Greenslade K, Milich R. Teacher ratings of DSM-III-R symptoms for the disruptive behaviour disorders. J Acad Child Adolesc Psychiatry. 1992;31:210–218. Perchet et al., 2001. 41.Perchet C, Revol O, Fourneret P, Mauguiere F, Garcia-Larrea L. Attention shifts and anticipatory mechanisms in hyperactive children: an ERP study using the Posner paradigm. Biol Psychiatry. 2001;50:44–57. Abstract | Full Text |
Full-Text PDF (492 KB)
|
CrossRef
Potgeiter et al., 2000. 42.Potgeiter S, Borger N, van der Meere JJ, de Cock P. Motor inhibition in very low birth weight children associated with ADHD. Dev Med Child Neurol. 2000;42:17–18. Prichep et al., 1976. 43.Prichep LS, Sutton S, Hakerem G. Evoked potentials in hyperkinetic and normal children under certainty and uncertainty: a placebo and methylphenidate study. Psychophysiology. 1976;13:419–428. MEDLINE |
CrossRef
Quay, 1997. 44.Quay HC. Inhibition and attention deficit hyperactivity disorder. J Abnorm Child Psychol. 1997;25:7–13. MEDLINE |
CrossRef
Raven, 1989. 45.Raven JC. Standard progressive matrices. Victoria: Australian Council for Education Research; 1989;. Raymaekers et al., 2007. 46.Raymaekers A, van der Meere JJ, Wiersema JR, Roeyers H. HFA and ADHD: a direct comparison on state regulation and response inhibition. J Clin Exp Neuropsychol. 2007;29:418–427. MEDLINE |
CrossRef
Rohrbaugh and Gaillard, 1983. 47.Rohrbaugh JW, Gaillard AWK. Sensory and motor aspects of the contingent negative variation. In: Gaillard AWK, Ritters W, Gaillard AWK, Ritterss W editor. Tutorials in ERP research endogenous components. Amsterdam, Netherlands: North Holland; 1983;p. 269–310. Semlitsch et al., 1986. 48.Semlitsch HV, Anderer P, Schuster P, Presslich OA. A solution for reliable and valid reduction of ocular artifacts, applied to the P300 ERP. Psychophysiology. 1986;23:695–703. MEDLINE |
CrossRef
Sergeant, 2000. 49.Sergeant JA. The cognitive-energetic model: an empirical approach to attention-deficit hyperactivity disorder. Neurosci Biobehav Rev. 2000;24:7–12. MEDLINE |
CrossRef
Sergeant, 2005. 50.Sergeant JA. Modeling attention-deficit/hyperactivity disorder: a critical appraisal of the cognitive–energetic model. Biol Psychiatry. 2005;57:1248–1255. Abstract | Full Text |
Full-Text PDF (205 KB)
|
CrossRef
Sergeant et al., 1999. 51.Sergeant JA, Oosterlaan J, van Der Meere J. Information processing and energetic factors in attention-deficit/ hyperactivity disorder. Handb Disrupt Behav Disord. 1999;75–104. Sergeant et al., 2003. 52.Sergeant JA, Geurts H, Huijbregts S, Scheres A, Oosterlaan J. The top and the bottom of ADHD: a neuropsychological perspective. Neurosci Biobehav Rev. 2003;27:583–592. MEDLINE |
CrossRef
Sikström and Söderlund, 2007. 53.Sikström S, Söderlund G. Stimulus dependent dopamine release in attention-deficit/hyperactivity disorder. Psychol Rev. 2007;114:1047–1075.
CrossRef
Smith et al., 2004. 54.Smith JL, Johnstone SJ, Barry RJ. Inhibitory processing during the Go/NoGo task: an ERP analysis of children with attention-deficit/hyperactivity disorder. Clin Neurophysiol. 2004;115:1320–1331. Abstract | Full Text |
Full-Text PDF (214 KB)
|
CrossRef
Smith et al., 2006. 55.Smith JL, Johnstone SJ, Barry RJ. Effects of pre-stimulus processing on subsequent events in a warned Go/NoGo paradigm: response preparation, execution and inhibition. Int J Psychophysiol. 2006;61:121–133. MEDLINE |
CrossRef
Smith et al., 2007. 56.Smith JL, Johnstone SJ, Barry RJ. Response priming in the Go/NoGo tasl: the N2 reflects neither inhibition nor conflict. Clin Neurophysiol. 2007;118:343–355. Abstract | Full Text |
Full-Text PDF (422 KB)
|
CrossRef
Smith et al., 2008. 57.Smith JL, Johnstone SJ, Barry RJ. Movement-related potentials in the Go/NoGo task: the P3 reflects both cognitive and motor inhibition. Clin Neurophysiol. 2008;119:704–714. Abstract | Full Text |
Full-Text PDF (368 KB)
|
CrossRef
Sonuga-Barke and Sergeant, 2005. 58.Sonuga-Barke EJS, Sergeant J. The neuroscience of ADHD: multidisciplinary perspectives on a complex developmental disorder. Dev Sci. 2005;8:103–104.
CrossRef
Tabachnick and Fidell, 1996. 59.Tabachnick BG, Fidell LS. Using multivariate statistics. New York: Harper-Collins; 1996;. Tecce, 1972. 60.Tecce J. Contingent negative variation (CNV) and psychological processes in man. Psychol Bull. 1972;77:73–108. MEDLINE |
CrossRef
van der Meere, 2005. 61.van der Meere J. State regulation and attention-deficit hyperactivity disorder. In: Gozal D, Molfese DL, Gozal D, Molfeses DL editor. Attention-deficit/hyperactivity disorder: from genes to patients. Totowa, NJ: Humana Press; 2005;p. 413–433. van der Meere and Stemerdink, 1999. 62.van der Meere J, Stemerdink N. The development of state regulation in normal children: an indirect comparison with children with ADHD. Dev Neuropsychol. 1999;16:213–225.
CrossRef
van der Meere et al., 1995. 63.van der Meere J, Stemerdink N, Gunning B. Effects of presentation rate of stimuli on response inhibition in ADHD children with and without tics. Percept Motor Skills. 1995;81:259–262. MEDLINE van der Meere et al., 1999. 64.van der Meere J, Gunning B, Stemerdink N. The effect of methylphenidate and clonidine on response inhibition and state regulation in children with ADHD. J Child Psychol Psychiatry. 1999;40:291–298. MEDLINE |
CrossRef
van Leeuwen et al., 1998. 65.van Leeuwen T, Steinhausen H, Overtoom C, Pascual-Marqui R, van’t Klooster B, Rothenberger A, et al. The continuous performance test revisited with neuroelectric mapping: impaired orienting in children with attention deficits. Behav Brain Res. 1998;94:97–110. MEDLINE |
CrossRef
Walter et al., 1964. 66.Walter WG, Cooper R, Aldridge VJ, McCallum WC, Winter AL. Contingent negative variation: an electric sign of sensorimotor association and expectancy in the human brain. Nature. 1964;203:380–384. MEDLINE |
CrossRef
Westwood, 1979. 67.Westwood PS. South australian spelling test. Adelaide: Education Department of South Australia; 1979;. Wiersema et al., 2005. 68.Wiersema JR, van der Meere J, Roeyers H. State regulation and response inhibition in children with ADHD and children with continuously treated phenylketonuria: an event-related potential comparison. J Inherit Metab Dis. 2005;28:831–843. MEDLINE |
CrossRef
Wiersema et al., 2006a. 69.Wiersema JR, van der Meere J, Antrop I, Roeyers H. State regulation in adult ADHD: an event-related potential study. J Clin Exp Neuropsychol. 2006;28:1113–1126. MEDLINE |
CrossRef
Wiersema et al., 2006b. 70.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;47:560–567. MEDLINE |
CrossRef
Yong-Liang et al., 2000. 71.Yong-Liang G, Robaey P, Karayanidis F, Bourassa M, Pelletier G, Geoffroy G. ERPS and behavioral inhibition in a Go/No-go task in children with attention-deficit hyperactivity disorder. Brain Cogn. 2000;43:215–220. MEDLINE School of Psychology, Brain & Behaviour Research Institute, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia  Corresponding author. Tel.: +61 2 4221 4496; fax: +61 2 4221 4163.
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