Madeleine J. Groom

Task-Related Default Mode Network Modulation and Inhibitory Control in ADHD: Effects of Motivation and Methylphenidate.

BACKGROUND Deficits characteristic of attention deficit/hyperactivity disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the default mode network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation. METHOD We obtained functional magnetic resonance images from 18 methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate. RESULTS When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off-methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition. CONCLUSIONS During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children.

Cognitive deficits in early-onset schizophrenia spectrum patients and their non-psychotic siblings: A comparison with ADHD

BACKGROUND Previous research has shown cognitive deficits in patients with schizophrenia spectrum disorders in the areas of executive function, verbal memory and attention. Subtle deficits have been shown in healthy first-degree relatives of patients, suggesting that they may be trait markers. The specificity of these markers for schizophrenia compared with another neurodevelopmental disorder, Attention Deficit Hyperactivity Disorder (ADHD) has not been reliably established. METHODS The Rey Auditory Verbal Learning Test (RAVLT), Hayling Sentence Completion Test (HSCT), FAS Test of orthographic verbal fluency (FAS) and Continuous Performance Test-Identical Pairs (CPT-IP) were administered to adolescent schizophrenia spectrum patients (SZ; n=30), adolescent siblings of schizophrenia spectrum patients (SZ-SIB; n=36), healthy control participants (HC; n=72); a neurodevelopmental comparison group of adolescents with ADHD (n=27). RESULTS The SZ group were impaired on all measures. The SZ-SIB group were impaired on IQ, immediate recall (RAVLT), target sensitivity (CPT-IP), response initiation (HSCT); error rates for the FAS and HSCT. There were no significant differences between the SZ-SIB and ADHD groups on individual measures of cognitive function. Principal Components Analysis revealed four factors on which further analyses were conducted. The SZ-SIB and ADHD groups showed different profiles of impairment on components related to response initiation and sustained attention/vigilance when each was compared with the HC group. CONCLUSIONS Deficits in intellectual function, verbal memory and response initiation/inhibition were found in the SZ-SIB group indicating that these are markers of risk for schizophrenia. Subtle differences in profiles of impairment in the SZ-SIB and ADHD groups on composite measures of attention and response initiation require further investigation.

Effects of Motivation and Medication on Electrophysiological Markers of Response Inhibition in Children with Attention-Deficit/Hyperactivity Disorder

Background Theories of attention-deficit/hyperactivity disorder (ADHD) posit either executive deficits and/or alterations in motivational style and reward processing as core to the disorder. Effects of motivational incentives on electrophysiological correlates of inhibitory control and relationships between motivation and stimulant medication have not been explicitly tested. Methods Children (9–15 years) with combined-type ADHD (n = 28) and matched typically developing children (CTRL) (n = 28) performed a go/no-go task. Electroencephalogram data were recorded. Amplitude of two event-related potentials, the N2 and P3 (markers of response conflict and attention), were measured. The ADHD children were all stimulant responders tested on and off their usual dose of methylphenidate; CTRLs were never medicated. All children performed the task under three motivational conditions: reward; response cost; and baseline, in which points awarded/deducted for inhibitory performance varied. Results There were effects of diagnosis (CTRL > ADHD unmedicated), medication (on > off), and motivation (reward and/or response cost > baseline) on N2 and P3 amplitude, although the N2 diagnosis effect did not reach statistical significance (p = .1). Interactions between motivation and diagnosis/medication were nonsignificant (p > .1). Conclusions Motivational incentives increased amplitudes of electrophysiological correlates of response conflict and attention in children with ADHD, towards the baseline (low motivation) amplitudes of control subjects. These results suggest that, on these measures, motivational incentives have similar effects in children with ADHD as typically developing CTRLs and have additive effects with stimulant medication, enhancing stimulus salience and allocation of attentional resources during response inhibition.

Autistic spectrum disorder traits in children with attention deficit hyperactivity disorder.

BACKGROUND Current classification systems do not allow for comorbid diagnoses of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). Children with ADHD are often screened for ASD during clinical assessment and when recruited to clinical trials. We predicted that children with ADHD would have more autistic traits than controls and that certain traits would be more prevalent. METHODS The clinically referred sample consisted of 30 children with ADHD and 30 matched controls aged 9-15 years. Children were screened for ASD traits using the Social Aptitudes Scale (SAS) and the Social Communication Questionnaire (SCQ). RESULTS We found that ASD traits were significantly higher in children with ADHD than controls. None of the children received a diagnosis of autism or ASD. However, a large proportion (28% using the SCQ and 62% using the SAS) of children with ADHD reached screening thresholds for a predictive diagnosis of ASD. Relative to controls, children with ADHD had significantly higher levels of communication and social deficits, but not repetitive behaviours. CONCLUSION Further work is needed to establish whether autistic-like communication and social difficulties in children with ADHD are part of the broader ASD phenotype or are specific to ADHD.

Event-related potentials in adolescents with schizophrenia and their siblings: a comparison with attention-deficit/hyperactivity disorder.

BACKGROUND Identifying trait markers specific to schizophrenia might uncover mechanisms underlying illness susceptibility. Previous research shows the N2 and P3 event-related potentials are abnormal in schizophrenia; specificity of these potential trait markers has not been well established. METHODS Electroencephalogram data were recorded from four adolescent groups: early-onset schizophrenia patients (SZ; n = 30); non-psychotic siblings of schizophrenia patients (SZ-SIB; n = 36); healthy control subjects (HC; n = 36); a neurodevelopmental attention-deficit/hyperactivity disorder (ADHD) comparison group (n = 27), during auditory oddball and visual go/no-go tasks. The P3 was measured to targets in the oddball task. The N2 and P3 were measured to go and no-go stimuli in the go/no-go task. RESULTS Compared with the HC group, the SZ and SZ-SIB groups showed significantly reduced auditory oddball P3 amplitude. Visual P3 amplitude was significantly reduced in the SZ group for no-go stimuli and the SZ-SIB group for go and no-go stimuli. The P3 amplitude in the ADHD group was not significantly reduced for either paradigm. The SZ and ADHD groups showed significantly reduced N2 amplitude in the go/no-go task; the SZ-SIB group was not significantly different from the HC group. CONCLUSIONS Results revealed reduced P3 amplitude in schizophrenia patients and adolescent non-psychotic siblings in an auditory oddball and a visual go/no-go task. The SZ-SIB and ADHD groups showed a different ERP profile when each was compared with the HC group: siblings showed reduced P3 amplitude in both tasks and normal N2 in the go/no-go task; the opposite pattern was observed in the ADHD group.

Error processing-associated event-related potentials in schizophrenia and unaffected siblings.

A reduction in the error-related negativity (ERN), a response-locked event-related potential (ERP) observed when participants commit errors during processing of stimuli, is a well-replicated cerebral abnormality in schizophrenia. However, the extent to which this abnormality reflects susceptibility to schizophrenia rather than overt change in behavioural state is unclear. As the unaffected siblings of individuals with schizophrenia are at an increased genetic risk, this study examines whether they display abnormality of the ERN similar to that observed in individuals with schizophrenia. ERPs were recorded from 29 individuals with schizophrenia, 36 unaffected siblings and 35 healthy control participants while they performed a simple Go/No-Go task. Group differences in the ERN and also in the error positivity (Pe), a response-locked positive component that follows the ERN, were investigated. Reductions of ERN amplitudes were found in both individuals with schizophrenia and siblings. No significant abnormalities were observed in Pe. The finding of reduced ERN amplitudes in siblings without prodromal symptoms supports the hypothesis that the abnormality is not a consequence of behavioural disturbance, and that it is a trait marker for susceptibility to schizophrenia, rather than being a result of illness or medication.

Looking before you leap: A theory of motivated control of action

The acquisition of volitional control depends, in part, on developing the ability to countermand a planned action. Many tasks have been used to tap the efficiency of this process, but few studies have investigated how it may be modulated by participants’ motivation. Multiple mechanisms may be involved in the deliberate exercise of caution when incentives are provided. For example, control may involve modulation of the efficiency of the countermanding process, and/or inhibitory modulation of the impulse to go. One of the most commonly used paradigms to assess control of action is the Stop Signal Task, in which a primary Go stimulus is occasionally followed by a countermanding Stop signal, allowing a Stop Signal Reaction Time (SSRT) to be inferred as the outcome of a “horse race” between the go and countermanding processes. Here, we present a computational model in which high task motivation modulates proactive pre-stimulus inhibition of the go response. This allows responses to be calibrated so as to fall within a time-window that maximizes the probability of success, regardless of trial type, but does not decrease the observed SSRT. We report empirical support for the model from a sample of typically developing children, and discuss the broader implications for operationalizing measures of volitional control.

Differential modulation of the N2 and P3 event-related potentials by response conflict and inhibition.

BACKGROUND Developing reliable and specific neural markers of cognitive processes is essential to improve understanding of healthy and atypical brain function. Despite extensive research there remains uncertainty as to whether two electrophysiological markers of cognitive control, the N2 and P3, are better conceptualised as markers of response inhibition or response conflict. The present study aimed to directly compare the effects of response inhibition and response conflict on the N2 and P3 event-related potentials, within-subjects. METHOD A novel hybrid go/no-go flanker task was performed by 19 healthy adults aged 18-25 years while EEG data were collected. The response congruence of a central target stimulus and 4 flanking stimuli was manipulated between trials to vary the degree of response conflict. Response inhibition was required on a proportion of trials. N2 amplitude was measured at two frontal electrode sites; P3 amplitude was measured at 4 midline electrode sites. RESULTS N2 amplitude was greater on incongruent than congruent trials but was not enhanced by response inhibition when the stimulus array was congruent. P3 amplitude was greater on trials requiring response inhibition; this effect was more pronounced at frontal electrodes. P3 amplitude was also enhanced on incongruent compared with congruent trials. DISCUSSION The findings support a role for N2 amplitude as a marker of response conflict and for the frontal shift of the P3 as a marker of response inhibition. This paradigm could be applied to clinical groups to help clarify the precise nature of impaired action control in disorders such as attention deficit/hyperactivity disorders (ADHD).

Impulsivity and drinking motives predict problem behaviours relating to alcohol use in University students

AIMS This study used a four-factor model of impulsivity to investigate inter-relationships between alcohol consumption, impulsivity, motives for drinking and the tendency to engage in alcohol-related problem behaviours. METHODS 400 University students aged 18-25 completed an online survey consisting of the following measures: Urgency, Premeditation, Perseverance and Sensation Seeking Scale (UPPS) to measure impulsivity; Student Alcohol Questionnaire to assess drinking quantity, frequency and rates of problem behaviours; Drinking Motives Questionnaire to assess motives for drinking. RESULTS The majority of the sample (94.5%) drank alcohol at least monthly. Path analysis revealed direct effects of urgency, sensation seeking and premeditation, as well as the quantity of alcohol consumed, on the tendency to engage in risky behaviours with negative consequences. The effect of urgency was mediated by drinking for coping motives and by a combined effect of drinking for social motives and consumption of wine or spirits. Conversely the effect of sensation seeking was mediated by the quantity of alcohol consumed, irrespective of drink type, and the effect of premeditation was mediated by the consumption of wine and spirits, in combination with enhancement motives. CONCLUSIONS Sensation seeking, urgency and lack of premeditation are related to different motives for drinking and also demonstrate dissociable relationships with the consumption of specific types of alcohol (beer, wine and spirits) and the tendency to engage in risky behaviours associated with alcohol consumption. Screening for high levels of urgency and for severe drinking consequences may be useful predictors of alcohol-related problems in UK University students aged 18 to 25 years.

Motivational incentives and methylphenidate enhance electrophysiological correlates of error monitoring in children with attention deficit/hyperactivity disorder

Background Children with attention deficit hyperactivity disorder (ADHD) are characterised by developmentally inappropriate levels of hyperactivity, impulsivity and/or inattention and are particularly impaired when performing tasks that require a high level of cognitive control. Methylphenidate (MPH) and motivational incentives may help improve cognitive control by enhancing the ability to monitor response accuracy and regulate performance accordingly. Methods Twenty-eight children with DSM-IV ADHD (combined type) aged 9–15 years and pairwise-matched typically developing children (CTRL) performed a go/no-go task in which the incentives attached to performance on no-go trials were manipulated. The ADHD group performed the task off and on their usual dose of MPH. CTRL children performed the task twice but were never medicated. EEG data were recorded simultaneously and two electrophysiological indices of error monitoring, the error-related negativity (ERN) and error positivity (Pe) were measured. Amplitudes of each ERP were compared between diagnostic groups (CTRL, ADHD), medication days (Off MPH, On MPH) and motivational conditions (baseline – low incentive, reward, response cost). Results Error rates were lower in the reward and response cost conditions compared with baseline across diagnostic groups and medication days. ERN and Pe amplitudes were significantly reduced in ADHD compared with CTRL, and were significantly enhanced by MPH. Incentives significantly increased ERN and Pe amplitudes in the ADHD group but had no effect in CTRL. The effects of incentives did not interact with the effects of MPH on either ERP. Effect sizes were computed and revealed larger effects of MPH than incentives on ERN and Pe amplitudes. Conclusions The findings reveal independent effects of motivational incentives and MPH on two electrophysiological markers of error monitoring in children with ADHD, suggesting that each may be important tools for enhancing or restoring cognitive control in these children.