Inhibitory control in children with attention-deficit/hyperactivity disorder: event-related potentials identify the processing component and timing of an impaired right-frontal response-inhibition mechanism.

BACKGROUND: A core deficit in inhibitory control may account for a wide range of dysfunctional behaviors in attention-deficit/hyperactivity disorder (ADHD). METHODS: Event-related potentials were measured in 10 children with ADHD and 10 healthy children during a task specifically involving response inhibition (Stop signal task). RESULTS: In response to all Stop signals, control participants produced a large negative wave at 200 msec (N200) over right inferior frontal cortex, which was markedly reduced in ADHD children. The N200 amplitude was significantly correlated across subjects with response-inhibition performance. In response to the Go stimuli, ADHD children showed a reduced slow positive wave (250-500 msec) in anticipation of failed inhibitions over right frontal scalp regions. CONCLUSIONS: ADHD children appear to have an abnormality in an early-latency, right inferior frontal processing component critical to the initiation of normal response-inhibition operations. They also appear to have a right frontal abnormality associated to the covert processing of Go stimuli preceding failed inhibitions. By providing timing and processing component specificity, these results extend the findings of recent functional MRI studies of inhibitory control reporting right frontal abnormalities in ADHD.     

Deficient inhibition as a marker for familial ADHD.

OBJECTIVE: The authors investigated whether deficient inhibitory control, as measured by the stop-signal paradigm, delineates a familial subgroup of attention deficit hyperactivity disorder (ADHD). METHOD: Subjects were 54 ADHD children defined as having poor or good inhibition (on the basis of stop-signal paradigm performance) and 26 healthy comparison children. Family history of ADHD and measures of neurobiological and psychosocial risk were compared among the three groups. RESULTS: ADHD was significantly more prevalent in the families of the children with ADHD who exhibited poor inhibition (48.1%) than in the families of those exhibiting good inhibition (18.5%) or in the families of healthy comparison children (7.7%). No differences in neurobiological or psychosocial risk were found for the three groups. CONCLUSIONS: Deficient inhibition delineates a familial subtype of ADHD. Psychosocial and neurobiological factors did not account for inclusion in the good inhibition group and did not act conjointly with inhibition to increase the risk for ADHD in the poor inhibition group. This study demonstrates that cognitive measures such as a laboratory measure of inhibition can serve as phenotype markers for genetic analyses.     

Motivational effects on inhibitory control in children with ADHD

OBJECTIVE: The problems children with attention-deficit/hyperactivity disorder (ADHD) encounter in tasks measuring inhibitory control are often theoretically related to deficits in cognitive processes. This study investigated the effects of different motivational incentives on the ability of children to inhibit intended or ongoing actions. METHOD: In a large German industrial town, 33 children with ADHD were compared with 33 members of a combined group of children with major depressive disorder, anxiety disorders, oppositional defiant disorder, or conduct disorder, and 33 children without any psychiatric disorder with respect to their performances in a stop-signal task. The children received continuous feedback under high- or low-incentive conditions. The children's performance was compared in terms of qualitative (inhibition rate) and quantitative (reaction time) measures. RESULTS: There were no indications of deficits in sustained attention in children with ADHD. Under conditions of low incentives, children with ADHD were less able to inhibit their reactions and had longer stop-signal reaction times. But when given high incentives, children with ADHD performed the task as well as both other groups. CONCLUSIONS: Supposed deficits in children with ADHD should be regarded from a perspective that differentiates performance from ability. Furthermore, the findings support a motivational explanation of the origins of lowered inhibitory control in children with ADHD.     

Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children.

OBJECTIVE: This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. METHODS: A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. RESULTS: ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. CONCLUSIONS: ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.     

Abnormal brain activity related to performance monitoring and error detection in children with ADHD

Brain electrical activity associated with inhibitory control was recorded in ten ADHD and ten healthy children using high density event related potentials (ERPs) during the Stop Signal Task (SST). SST is a two-choice reaction time (RT) paradigm, in which subjects are required, on 25% of the trials, to withdraw their response upon presentation of a "Stop Signal". In the healthy children, the ERP evoked by the Stop Signal differed for successful inhibitions (SI) compared to failed inhibitions (FI), with greater amplitude of a positive wave peaking around 320 msec over anterior medial frontal scalp (P3a). Such success-related P3a activity was significantly reduced in amplitude in the ADHD group. In addition, the error related negativity (ERN), a sharp negative wave that is present selectively on error trials in choice RT experiments, peaking 100 ms after motor onset, and distributed over anterior medial frontal scalp, was also markedly reduced in the ADHD group. The scalp distribution of the group differences in P3a and the ERN is consistent with a reduction of activity of sources in dorsal anterior cingulate cortex (dACC), suggesting a global deficit in cognitive control operations subserved by dACC in ADHD.     

Neuroimaging of inhibitory control areas in children with attention deficit hyperactivity disorder who were treatment naive or in long-term treatment

OBJECTIVE: Difficulty with response inhibition is a cardinal symptom of attention deficit hyperactivity disorder (ADHD), combined type. Prefrontal and cingulate brain regions are known to be involved in inhibitory control. Event-related functional magnetic resonance imaging (fMRI) might establish if these regions differ in their activity in ADHD children relative to healthy comparison subjects. METHOD: Fifteen healthy comparison subjects and 17 children with ADHD, combined type, completed fMRI studies while performing the Stop Signal Task. Eight ADHD subjects were treatment naive; the remainder had a history of long-term treatment with stimulants, but they were medication free at the time of the fMRI. No subject had a learning disorder or a comorbid psychiatric condition (other than oppositional defiant disorder in the ADHD subjects). RESULTS: Both the ADHD and comparison subjects activated the right dorsolateral prefrontal cortex on "stop" trials relative to "go" trials; this increase was greater in ADHD subjects. When inhibition was unsuccessful (relative to successful inhibition), healthy comparison subjects strongly activated the anterior cingulate cortex and the left ventrolateral prefrontal cortex. In contrast, the ADHD subjects did not show these differences. Activations in treatment-naive and ADHD subjects treated in the long term did not differ significantly in any brain regions. CONCLUSIONS: In relation to comparison subjects, ADHD subjects failed to activate the anterior cingulate cortex and the left ventrolateral prefrontal cortex after unsuccessful inhibition. These findings appear in treatment-naive ADHD individuals and are unlikely to be an artifact of long-term treatment with stimulants or of abrupt termination of stimulants before imaging.     

Shifting-related brain magnetic activity in attention-deficit/hyperactivity disorder.

BACKGROUND: Current theories suggest a role for frontal-striatal circuits in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). METHODS: We used magnetoencephalography (MEG) to measure event-related brain activity during a simplified version of the Wisconsin Card Sorting Test in children with DSM-IV combined type ADHD (ADHD-C) or predominantly inattentive type ADHD (ADHD-PI) and in age- and intelligence-matched control children. RESULTS: In control children, set-shifting cues evoked a higher degree of activation in the medial temporal lobe (MTL) between 200 and 300 msec than non-shifting cues, with MTL activation predicting later activity in left anterior cingulate cortex (ACC) (at 400-500 msec). This MTL-ACC response pattern was diminished in children with ADHD. By contrast, children with ADHD showed early activity in regions barely activated in control children, such as left inferior parietal lobe and posterior superior temporal gyrus. CONCLUSIONS: These preliminary data support theories of frontal dysfunction in ADHD but also suggest that deficits in higher-level functions might be secondary to disruptions in earlier limbic processes.     

Attention shifts and anticipatory mechanisms in hyperactive children: an ERP study using the Posner paradigm.

BACKGROUND: The aim of this study was to assess attentional, decisional, and motor processing stages during the performance of an attention shifting paradigm, both in normal children and children with attention-deficit/hyperactivity disorder (ADHD). METHODS: We recorded event-related potentials (ERPs) and performance measures during a variant of the Posner paradigm in 13 control subjects and 24 ADHD children. Subjects responded with a spatially concordant motor response to left or right visual targets, which could be either preceded by a spatial cue ("valid" = same side; "invalid" = opposite side) or presented uncued. RESULTS: Patients made significantly more errors than control subjects, with predominance of the anticipatory type. As compared to control subjects, ADHD children had faster reaction times, as well as a shortened interval between the N2 and P3 ERPs and the motor response. Patients also showed a decreased attentional priming effect on early sensory responses (P1). Finally, the slow negativity (contingent negative variation/readiness potential) that preceded the target in the "no cue" condition was absent in ADHD patients. CONCLUSIONS: The combined analysis of electrophysiological and behavioral data suggest a characteristic mode of response of ADHD in attention shifting tasks, characterized by "motor impulsivity" with release of motor responses before stimulus processing is adequately completed, as well as a lack of strategic planning/anticipatory mechanisms in the absence of warning stimulus. These deficits may be partly attributed to dysmaturation of executive frontal functions. In addition, a minor deficit in early attentional priming was also observed in ERPs, with no apparent behavioral counterparts.     

Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Response inhibition is an executive function that requires voluntary control over responses when there is a change of context. The right inferior frontal cortex is necessary for response inhibition, and a deficit in right frontostriatal circuitry might underlie attention-deficit/hyperactivity disorder (ADHD). Many studies of childhood ADHD have demonstrated impaired response inhibition and its amelioration by methylphenidate (MPH). The current study tested response inhibition and the effect of MPH in adult ADHD. METHODS: Response inhibition was assessed with the "tracking" stop-signal test in 13 adults with a diagnosis of ADHD, both while taking and while not taking medication, and 13 healthy, unmedicated, age- and intelligence quotient-matched control subjects. RESULTS: Stop-signal reaction time was significantly slower in unmedicated adults with ADHD relative to healthy control subjects, and this deficit was significantly ameliorated by medication. CONCLUSIONS: Adult ADHD patients had a response inhibition profile similar to that produced by lesions to the right inferior frontal cortex, which was remedied by stimulant medication.     

An FMRI auditory oddball study of combined-subtype attention deficit hyperactivity disorder

OBJECTIVE: Studies of attention deficit hyperactivity disorder (ADHD) have reliably found reduced amplitude event-related potentials (ERPs) measuring attention-related brain function, indicating impairment in the brain's ability to automatically orient attention to odd or novel environmental stimuli and to represent that information in working memory. However, the relationship between abnormal neurocognition and dysfunction in specific brain regions in ADHD remains unclear. METHOD: The authors used functional magnetic resonance imaging (fMRI) to identify brain regions with abnormal hemodynamic activity during processing of target and novelty oddball stimuli that engage attention. Forty-six boys 11-18 years of age participated in the study, including 23 diagnosed as having ADHD with hyperactivity and impulsivity (combined type) and 23 demographically matched control subjects. Event-related fMRI data were collected while participants performed a three-stimulus auditory oddball task. Hemodynamic activity was compared between ADHD participants and control subjects in brain regions previously linked to P3 ERPs. RESULTS: Participants with ADHD showed deficits in brain activity elicited by infrequent attentionally engaging stimuli in regions associated with attentional orienting and working-memory cognitive processes. These deficits co-occurred with highly variable and slow task performance. CONCLUSIONS: This study links ADHD attentional orienting and working-memory deficits to dysfunction in specific cortical brain regions. The results indicate that ADHD pathophysiology impairs brain systems that are important for allocating attention and using cognitive representations to guide cognition and behavior. Attention-related neural dysfunction is thus an important factor to consider in neurobiological theories of ADHD.