Harry S. Koelega

Stimulant drugs and vigilance performance: a review

The literature on the effects of some stimulant drugs (amphetamine, methylphenidate, caffeine, and nicotine) on vigilance performance is reviewed. Improvement of overall level of performance (both accuracy and speed) after the intake of amphetamine, caffeine, and nicotine has often been reported, and the decrement in performance with time has been shown to be prevented especially with amphetamine and nicotine. Effects on false alarms are negligible. In studies where a test battery was employed, vigilance tasks appeared to be the most sensitive performance tests in detecting the effects of stimulants; however, different vigilance tasks may measure different aspects of mental functions. There is no support for earlier conclusions that improvements are noticed only in fatigued subjects in protracted sessions. Evidence from several studies does not support the hypothesis that improvements are only a recovery of withdrawal-induced impairment. Because positive effects have been obtained with drugs possessing different mechanisms of action, there is as yet no clear support for a noradrenergic, dopaminergic, or cholinergic theory of sustained attention. Simple neurotransmitter theories of attention and information processing may be untenable.

Alcohol and vigilance performance: a review.

In the literature on the effects of alcohol on driving-related skills, it is sometimes claimed that vigilance tasks are insensitive instruments whereas divided-attention tasks are extremely sensitive to the effects of alcohol. The results of the present review, based on the analysis of 38 comparisons of alcohol and placebo in vigilance tasks, require that these claims be restated. Both types of attentional task (concentrated and divided) are indispensable in test batteries, although not all types of vigilance and divided-attention task are equally sensitive, e.g. some types of vigilance task, using spatial stimuli, were sensitive to BAC levels of 0.03% whereas other types were insensitive to levels of 0.10%. In contrast, the usefulness of tasks of questionable validity and/or low sensitivity (such as the DSST, CFF, digit span, simple RT and choice RT) is questioned. Apart from issues of validity and sensitivity of tests, the ways in which alcohol may affect performance are also discussed. The main effect of moderate doses of alcohol is on attention and information processing. The capacity to divide and sustain attention is already impaired at BAC levels of 0.02–0.03%. Further, alcohol effects appear to some extent to be time-dependent, and are greatest during periods of sleepiness (the early afternoon and after mid-night). Some current BAC levels concerning drinking and driving are far too generous. There is sufficient evidence from the literature on performance indicating that the BAC standard for driving should be lowered to 0.02% for driving after midnight and for special risk groups (young and less experienced drivers).

SOME EXPERIMENTS ON SEX DIFFERENCES IN ODOR PERCEPTION

Some eighty years ago, Toulouse and Vaschidel reported conflicting results of various research workers studying sex differences in olfactory sensitivity. These French authors found a distinct difference in sensitivity to the odor of camphor in favor of females, whereas some years previously Bailey and his coworkersz.3 had concluded that males were more sensitive. Since then many studies have been carried out to settle this issue, but even today the evidence is conflicting. Sex differences in sensitivity were not found, among others, by Mesolella,4 Kloek,B Matzker,a Amoore and Venstrom,T Venstrom and Amoore,* and Griffiths and Patterson.9 Kloek examined several hundred subjects of both sexes and used, besides “neutral” odors like coffee, cloves, nutmeg, and cinnamon, odors that probably have a biological (sexual) significance, steroid sex hormynes and their metabolites, and also pentadecanolide (Exaltolide). He did not, however, obtain quantitative data on sensitivity but merely asked his subjects to state whether they perceived the compounds, and if so, how strongly; he also asked them to verbalize their impressions. Amoore and Venstrom used a number of neutral odors and a substance related to Exaltolide, namely Thibetolide. Griffiths and Patterson used androstenone and found that 7.6y0 of the women were unable to detect the odor, in contrast to 44.3% of the men. From those who could smell the odor a number of subjects was selected and their thresholds were determined. There was a highly significant difference between sexes in hedonic scores, women finding the odor more unpleasant, but not in threshold values. Among the authors who found females to be more sensitive, in addition to Toulouse and Vaschide, were Le Magnen,lo Schneider and Wolf,ll and Koelega.12 Le Magnen used mainly the odor of pentadecanolide, Schneider and Wolf used a neutral odor, citral, and Koelega found differences for both biological odors, pentadecanolide and oxahexadecanolide (Musk R-I) and a neutral odor (amylacetate). According to Le Magnen,lo adult women are very sensitive to pentadecanolide and many women experience the odor as very intense, whereas young children and adult men can hardly smell it; about 50% of the adult males show an anosmia for this substance. Le Magnen formulated the hypothesis that the sensitivity to pentadecanolide and urinoid odors (including pyridine) is determined by sex hormones: estrogens would improve sensitivity, whereas androgens would lead to a low sensitivity to these biological odors and to a higher sensitivity for neutral odors (safrol, for example).+

Inhibition in children with attention-deficit/hyperactivity disorder: a psychophysiological study of the stop task.

BACKGROUND The purpose of the study was to investigate and identify abnormal brain activity, as revealed by event-related potentials (ERPs) concurring with deficient inhibitory control in children with attention-deficit/hyperactivity disorder (ADHD). METHODS Performance and ERPs from 16 children with ADHD and 16 control subjects were compared in the stop-signal paradigm. RESULTS The ADHD children showed a lower inhibition percentage and their (estimated) response time to the stop signal was disproportionally longer compared to the slowing of reaction times to primary-task stimuli. In normal control subjects, fronto-central positivity (100-400 msec) after the onset of the stop-signal was larger in case of successful inhibition, relative to failed inhibition; this was less so in ADHD children. A late positive wave (500-700 msec), maximal at Oz on failed inhibition trials, and possibly related to error-detection, was smaller in ADHD children. CONCLUSIONS These results point to abnormalities in brain processes involved in motor inhibition and error-detection in ADHD children.

Event-related potentials and performance of attention-deficit hyperactivity disorder: Children and normal controls in auditory and visual selective attention tasks

Attention-deficit hyperactivity disorder (ADHD) children and normal controls (7-13 yrs old) performed an auditory and visual selective attention task. Subjects were instructed to respond to the infrequent (10%) stimuli in the relevant channel. Processing negativity (PN) and several other ERP peaks were scored at the midline electrodes. In the auditory task, controls had more correct detections (hits), less false alarms, larger P3b amplitudes to nontarget stimuli (but not to hits), a larger central PN and larger early frontal positivity (100-250 ms) to target stimuli than ADHD subjects. In the visual modality, controls had more correct detections, less false alarms, larger P3b amplitudes to nontarget stimuli (but not to hits), and larger frontal P3(1) amplitudes to infrequent than to frequent stimuli. It was hypothesized that in ADHD children in both the auditory and the visual task, there is a deficit in the activation of the P3b process. Incorrect triggering of the P3b process might be caused by disturbances in other aspects of the attention process, preceding the P3b.

Associations Between Event-Related Potentials and Measures of Attention and Inhibition in the Continuous Performance Task in Children With ADHD and Normal Controls

OBJECTIVES First, to differentiate between inattention and impulsivity based on type of errors made in the AX version of the Continuous Performance Task (CPT), and second, to investigate whether differences in performance between children with attention-deficit hyperactivity disorder (ADHD) and normal controls also occur in specific forms of brain activity, namely event-related potentials (ERPs), presumably related to inattention and impulsivity or inhibition. METHOD Sixteen ADHD and 16 normal control children performed the CPT-AX. ERPs were recorded at occipital (Oz), parietal (Pz), central (Cz), and frontal (Fz) leads. RESULTS The ADHD children had a higher CPT-Inattention score and showed smaller parietal positive waves at a latency of approximately 300 msec in reaction to target stimuli, target P3s, likewise indicating less attention. In contrast, they showed neither higher CPT-Impulsivity nor a smaller frontocentral negative wave at about 200 msec (N2); the N2 is generally seen as reflecting inhibition. A subgroup of children with ADHD and oppositional defiant disorder (n = 6) had smaller N2 waves than controls, however. CONCLUSIONS The ADHD group studied showed deficits in attention but not in impulsivity (or inhibition).

Effects of methylphenidate, desipramine, and l-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder

The objective of this study was to investigate the effects of methylphenidate (MPH) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder (ADHD) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were. In addition to MPH, two other drugs were administered in order to affect both transmitter systems more selectively, L-dopa (dopamine (DA) agonist) and desipramine (DMI) (noradrenaline (NA) re-uptake inhibitor). Sixteen children with ADHD performed a stop-task, a laboratory task that measures the ability to inhibit an ongoing action, in a double-blind randomized within-subjects design. Each child received an acute clinical dose of MPH, DMI, L-dopa, and placebo; measures of performance and plasma were determined. The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa. The response-time to the stop-signal was marginally shortened after intake of DMI. MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone. No effects of L-dopa whatsoever were noted. Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo. It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms. The improved inhibition under DMI could be serotonergically mediated.

Perceptual and response interference in children with attention-deficit hyperactivity disorder, and the effects of methylphenidate

Fourteen children with attention-deficit hyperactivity disorder (ADHD) and 14 normal control children were compared with respect to stimulus- and response-related processes. Subjects with ADHD took part in two additional sessions under methylphenidate or placebo. In both experiments, performance and electrophysiological measures such as the P2, N2, and P3 components of event-related potential and electromyogram (EMG) activity were measured during an Eriksen flanker task. In both groups of children, reaction times (RTs) to arrow stimuli incongruent with the target were longer than those to neutral stimuli (response interference), which were again slower than RTs to target-alone stimuli (perceptual interference). Children with ADHD made more errors to incongruent stimuli and showed more response interference. For correct responses, no differences between the groups in response interference effects on reaction time, P2, N2, and P3 latency, or EMG onset were found. Methylphenidate had a general enhancing effect on accuracy but did not specifically reduce interference from the flanking stimuli. Methylphenidate had no effects on RT, N2 and P2 latency, P3 amplitude or latency, or EMG activity. The conclusion that methylphenidate did not influence response processes contrasts sharply with findings reported by authors using the Sternberg memory search task.

Attentional capacity, a probe ERP study : differences between children with attention-deficit hyperactivity disorder and normal control children and effects of methylphenidate

In the present study it was investigated whether the smaller P3s in attention-deficit hyperactivity disorder (ADHD) children are caused by a shortage of capacity underlying P3 processes or whether they are due to a capacity allocation problem. Also, effects of methylphenidate on these processes were investigated. Performance and event-related potentials (ERPs) of 14 ADHD and 14 control children were measured using an irrelevant-probe technique. Three types of task irrelevant visual probes (standards, deviants, and novels) were presented against the background of two visual tasks that varied in task difficulty. The parietal P3 wave was measured in response to task stimuli and probes. ADHD subjects made significantly fewer correct detections than normal controls in both the easy and the hard tasks. Controls showed an enhanced P3 to task-relevant stimuli in the hard task, whereas ADHD children did not. Probe (novel) P3 amplitudes decreased from the easy to the hard task to the same extent in both groups. Methylphenidate enhanced the percentage of correct responses and task P3 amplitudes in both the easy and the hard task but probe P3 amplitudes were not influenced by methylphenidate. It was concluded that ADHD children do not suffer from a shortage in attentional capacity; rather, the evidence is in favor of a problem with capacity allocation. Furthermore, methylphenidate had enhancing effects on performance and ERPs, but did not improve the capacity-allocation deficit.

Effects of methylphenidate on event-related potentials and performance of attention-deficit hyperactivity disorder children in auditory and visual selective attention tasks

Attention-deficit hyperactivity disorder (ADHD) children participated in a double-blind placebo-controlled study in which the effects of a dosage of 15 mg methylphenidate (MPH) on auditory and visual selective attention tasks was determined by presenting frequent (90%) and infrequent (10%) stimuli in both relevant and irrelevant input channels. The subjects task was to respond to the infrequent tones in the relevant input channel. Processing activity (negativity and positivity) was assessed for both tasks. N1, P2, N2, and P3b peaks were scored in the auditory task and N1, P1, N2, P2, P3(1), and P3b peaks were scored in the visual task. Effects of MPH were more prevalent in the visual than in the auditory condition. In the visual condition MPH enhanced the percentage of hits, caused higher central, parietal, and occipital P3b amplitudes to attended stimuli (both standards and deviants), and also enhanced the frontal processing negativity (PN). In the auditory task MPH did not influence performance, but it enhanced the frontal PN as well as the parietal and occipital P3b amplitudes to all stimulus types. In ADHD children, MPH ameliorates some, but not all, deficits and also improves processing where no differences with normal children are present.