Deciphering interference control in adults with ADHD by using distribution analyses and electromyographic activity.

A deficit in "interference control" is commonly found in adults with Attention Deficit Hyperactivity Disorder (ADHD). This has mainly been interpreted as difficulties in inhibiting inappropriate responses. However, interference control involves processes other than simply the ability to inhibit. Consequently, we used sophisticated analysis to decipher the additional processes of interference control in these patients. We compared interference control between 16 adults with ADHD and 15 control adults performing a Simon task. In most studies, performance is generally reported in terms of mean error rates and reaction times (RTs). However, here we used distribution analyses of behavioral data, complemented by analyses of electromyographic (EMG) activity. This allowed us to better quantify the control of interference, specifically the part that remains hidden when pure correct trials are not distinguished from partial errors. Partial errors correspond to sub-threshold EMG bursts induced by incorrect responses that immediately precede a correct response. Moreover, besides "online" control, we also investigated cognitive control effects manifesting across consecutive trials. The main findings were that adults with ADHD were slower and showed a larger interference effect in comparison to controls. However, the data revealed that the larger interference effect was due neither to higher impulse expression, nor to a deficit in inhibition but that these patients presented a larger interference effect than the controls after congruent trials. We propose and discuss the hypothesis that the interference control deficit found in adults with ADHD is secondary to impairments in sustained attention.

Detecting and correcting partial errors: Evidence for efficient control without conscious access.

Appropriate reactions to erroneous actions are essential to keeping behavior adaptive. Erring, however, is not an all-or-none process: electromyographic (EMG) recordings of the responding muscles have revealed that covert incorrect response activations (termed "partial errors") occur on a proportion of overtly correct trials. The occurrence of such "partial errors" shows that incorrect response activations could be corrected online, before turning into overt errors. In the present study, we showed that, unlike overt errors, such "partial errors" are poorly consciously detected by participants, who could report only one third of their partial errors. Two parameters of the partial errors were found to predict detection: the surface of the incorrect EMG burst (larger for detected) and the correction time (between the incorrect and correct EMG onsets; longer for detected). These two parameters provided independent information. The correct(ive) responses associated with detected partial errors were larger than the "pure-correct" ones, and this increase was likely a consequence, rather than a cause, of the detection. The respective impacts of the two parameters predicting detection (incorrect surface and correction time), along with the underlying physiological processes subtending partial-error detection, are discussed.

Simon effect in the rat: a new model for studying the neural bases of the dual-route architecture.

In humans, the Simon effect refers to the fact that choice reaction time (RT) is shorter when the stimulus corresponds spatially to the response than when it does not, albeit the location of the stimulus is irrelevant to the task. This effect has motivated innumerable empirical and theoretical studies and is considered to reflect elementary cognitive processes. We report an experiment demonstrating that rats also display a Simon effect, the dynamics of which--as assessed by factorial manipulations and RT distribution analyses--partly corresponds to those of the effect studied in human participants. The present results are consistent with the ideas that in rats, like in humans, (i) the information conveyed by the stimulus is processed via two parallel routes, one controlled and relatively slow, and one fast and automatic (dual-route architecture) and (ii) the dual-route processing is finished before the start of motor processes. The correspondence between these findings and those reported in humans open new perspectives for neurophysiological investigations of the dual-route architecture in an animal model routinely studied in neuroscience research.

Spatial enhancement of EEG traces by surface Laplacian estimation: comparison between local and global methods.

OBJECTIVE: Surface Laplacian estimation enhances EEG spatial resolution. In this paper, we compare, on empirical grounds, two computationally different estimations of the surface Laplacian. METHODS: Surface Laplacian was estimated from the same monopolar data set with both Hjorth's method [local; Electroenceph Clin Neurophysiol 39 (1975) 526] as modified by MacKay [Electroenceph Clin Neurophysiol 56 (1983) 696] and with spherical spline interpolation [global; Electroenceph Clin Neurophysiol 72 (1989) 184]. RESULTS: The grand averages computed with the two methods proved to be very similar but differed markedly from the monopolar ones. The two different computations were highly correlated, presented low relative errors and allowed to evidence comparable experimental effects. CONCLUSIONS: These results suggest that Hjorth's method and spherical spline interpolation convey similar topographic and chronometric informations. SIGNIFICANCE: We provide empirical evidence that local and global methods of surface Laplacian estimation are equivalent to improve the spatial resolution of EEG traces. Global methods allow to explore the scalp topography and local methods allow to spare time in electrode setting that can be useful for studies on special populations (i.e. children, aged subjects) and for clinical purposes.

Response monitoring without sensory feedback.

OBJECTIVE: The elicitation of an evoked potential, the 'error negativity' (Ne) when subjects commit errors in speeded tasks, is often taken as an index of response monitoring processes. The presence of a Ne-like wave on purely correct trials challenges the current conceptions about the nature of such a monitoring system. Here, we evaluate the possibility that the Ne-like wave on correct trials is merely due to reafferences, and at the same time, we test directly the general opinion according to which the Ne is generated by an internal signal. METHODS: We studied the presence of a Ne-like wave in a completely deafferented patient. The patient performed two reaction time (RT) tasks: a two-responses RT task and a go/no-go task. RESULTS: In this patient, a Ne occurs on errors, on incorrect EMG activations, and on purely correct responses. On errors, the Ne was clearly followed by an error positivity (Pe). CONCLUSIONS: The Ne and the Ne-like wave are not generated by reafferences. This similarity is a further argument to consider that these two waves are of same nature. SIGNIFICANCE: The present data demonstrate that sensory information is not mandatory for the brain to monitor and correct ongoing responses.

Response selection and motor areas: a behavioural and electrophysiological study.

OBJECTIVE: The involvement of the supplementary motor areas (SMAs) and primary motor areas (M1s) in motor processes was studied. METHODS: A between-hand choice and a simple reaction time (RT) task were mixed in a precueing paradigm. Laplacians were estimated by the source derivation method from the electroencephalogram recorded over the SMAs and M1s. RESULTS: RT was shorter in the simple than in the choice RT task. Response-locked averages showed a negative potential over M1 contralateral to the response and a positive wave over M1 ipsilateral. This ipsilateral positivity was much smaller in the simple than in the choice RT task, whereas the contralateral negativity was not different. A negativity preceding the activations of the M1s developed over the SMAs. This negativity was larger in the choice than in the simple RT task. CONCLUSIONS: In light of previous results, the present data confirm that, in between-hand choice tasks, response execution is implemented by an activation of the contralateral M1 and by an inhibition of the ipsilateral M1. SMAs and contralateral M1 appear hierarchically organized, the SMAs being more involved in response preparation and M1s in response execution. The task-dependent inhibition of ipsilateral M1 could reflect an active suppression of the erroneous response in the choice task. SIGNIFICANCE: The task context in which one movement is executed can affect the pattern of activities recorded over cortical motor structures. Cognitive context is of importance for understanding the nature of the motor command.

Selective effects of low-dose dopamine D1 and D2 receptor antagonists on rat information processing.

It is well established that the dopaminergic system influences simple reaction time (RT) performance. However, the role of this system in more complex information processing remains to be clarified. The present study was aimed at addressing this issue. To this end, we used an inferential method that relies on choice RT procedures and allows one to identify information processing stages in both humans and rats. Long-Evans rats responded to lateral visual cues (left or right). Two task factors, signal intensity and foreperiod duration, were manipulated. Low doses of two pharmacological agents, SCH 23390 (a D1 receptor antagonist; 0.015 and 0.025 micromol/kg) and eticlopride (a D2 receptor antagonist; 0.01 and 0.02 micromol/kg), were administrated systemically. Both drugs increased choice RT: eticlopride interacted with signal intensity on RT, showing that D2 receptors mediate at least the sensory stage of stimulus preprocessing. In addition, eticlopride interacted with signal intensity on omission rate, thereby suggesting an involvement of D2 receptors in attentional processes; and SCH 23390 interacted with foreperiod duration on RT, indicating that D1 receptors specifically mediate the response adjustment stage. The effect of this drug on RT rests entirely in its interaction with foreperiod duration, allowing us to conclude that this D1 antagonist affects the response adjustment stage while sparing all other processing stages.

The influence of time preparation on motor processes assessed by surface Laplacian estimation.

OBJECTIVE: The present study was aimed at testing whether foreperiod duration affects the activity recorded over the primary sensorimotor cortices during the reaction time. METHODS: The foreperiod duration (500 or 2500 ms) was varied across blocks of trials during a between-hand choice reaction time task; surface Laplacians were estimated from EEG recordings by the source derivation method. RESULTS: Reaction time was shorter for the 500 ms foreperiod than for the 2500 ms foreperiod. A contralateral negativity/ipsilateral positivity pattern showed up over the primary sensorimotor cortices. The time between the contralateral negativity onset and the electromyographic onset was shorter for the 500 ms foreperiod than for the 2500 ms foreperiod, which suggests that the foreperiod affects the implementation of the motor command. Furthermore, the interval between the onset of the voluntary electromyographic activity and the mechanical response was shorter for the 500 ms foreperiod than for the 2500 ms foreperiod. CONCLUSIONS: These results indicate that time preparation affects both central and peripheral motor processes.

Error negativity on correct trials: a reexamination of available data.

The error negativity, an EEG wave observed when subjects commit an error in a choice reaction time (RT) task, is often considered as a sign of error detection. Recently, reports of Ne-like waves on correct responses did challenge this interpretation. It has been proposed, however, that these Ne-like waves result either from an artifactual contamination of response-locked activities by stimulus-locked ones, or from an implicit monitoring of the time elapsing during the RT. Our aim was to reprocess published data: (1) to compare the shape and amplitude of EMG-locked and stimulus-locked ERPs on correct trials, and (2) to compare the size of the EMG-locked Ne-like waves obtained on fast and slow trials. The results neither support the artifact hypothesis nor the RT monitoring one. Therefore, it seems that the Ne-like waves observed on correct trials do correspond to a Ne, which suggests that the Ne has a broader significance than just error detection.

An electromyographic investigation of the effect of stimulus-response mapping on choice reaction time.

The activity of the agonist muscles was recorded during the performance of a two-choice visual reaction time (RT) task in which the compatibility of the stimulus-response mapping was manipulated. Correct trials were distinguished according to whether or not the activation of the agonist of the required response was preceded by an activation of the agonist of the nonrequired response. Double activation trials were more numerous for the incompatible than for the compatible mapping. Furthermore, these trials yielded longer RTs than the single muscular activation trials. These results suggest that initial activations of nonrequired responses are more frequently aborted and corrected when the mapping is incompatible than when it is compatible. This finding supports the dimensional overlap model of stimulus-response compatibility (S. Kornblum, T. Hasbroucq, & A. Osman, 1990).

Levodopa-induced drowsiness in healthy volunteers: results of a choice reaction time test combined with a subjective evaluation of sedation.

The aim of the present study was to assess levodopa (L-Dopa)-induced drowsiness in healthy volunteers using two parameters: choice reaction time and a subjective rating of sedation. Sixteen subjects participated in a randomized, double-blinded, crossover study. A single dose of 200 mg L-Dopa or placebo was administered at 9:00 AM. To limit peripheral side effects connected with L-Dopa, subjects were treated with 20 mg domperidone three times daily. Subjective rating of sedation consisted of visual analogue scale. Reaction time was measured by means of responses to two light-emitting diodes. The illumination of one of these diodes constituted the imperative signal. Manual responses were performed on two buttons located under the right and left index fingers. Results demonstrated a positive correlation between sedation level and reaction time (r = 0.70, p = 0.0026). Adverse events of L-Dopa were nausea (four cases) and excitation (one case). Subjects who did not develop adverse events were faster under L-Dopa than under placebo (p = 0.02), whereas subjects who had nausea or excitation were slower. A single dose of L-Dopa either deteriorated or improved choice reaction time in healthy volunteers according to whether it was sedative and whether it generated disruptive adverse events.

N-methyl-D-aspartate receptors and information processing: human choice reaction time under a subanaesthetic dose of ketamine.

Ketamine is an N-methyl-D-aspartate antagonist that induces cognitive dysfunctions. The purpose of the present study was to investigate the effects of a subanesthetic dose of ketamine on human information processing, using the additive factor method. During perfusion of a subanesthetic dose of ketamine (0.5 mg/kg over 60 min) or a placebo (randomized double-blind, cross-over design), eight adults (aged 22-33, mean=27) performed a two-choice visual reaction time (RT) task. Signal intensity, stimulus-response mapping, and foreperiod duration were manipulated. The effects of these three variables were found to be additive on RT, indicating that three independent stages - namely, stimulus preprocessing, response selection and motor selection- were manipulated. Ketamine altered RT performance in a specific way: it interacted with foreperiod duration but its effect was additive with those of signal intensity and stimulus-response mapping. These results show that ketamine specifically affects the stage of motor adjustment, which suggests that the glutamatergic system plays an important role in motor processes.

The chronometry of single neuron activity: testing discrete and continuous models of information processing.

The authors propose to study information transmission by comparing the effects of experimental factors on reaction time (RT) with the latency of the changes in activity of single-neurons. An experiment was conducted in which a monkey (Macaca mulatta) performed a tactilo-manual 2-choice RT task and the compatibility of the stimulus-response mapping was manipulated. Task-related neurons were recorded in the monkey's primary somesthetic and motor cortices. The changes in activity of 105 of these neurons were classified either as sensory-like or as motor-like. The sensory-like changes occurred before the motor-like ones. The stimulus-response mapping exerted its entire effect on the RT after the sensory-like changes and before the motor-like ones. These findings suggest that the information was transmitted discretely from the processes affected by the mapping to the processes implemented by the motor-like changes.

The additive factor method in rat information processing.

Sternberg introduced the additive factor method as a tool for discovering and studying in choice reaction time situations in human subjects. Underlying the method is the notion that if information processing consists of successive stages, then different factors affecting different stages must have additive effects on reaction-time measurements. The additive factor method has been extensively used in humans but few attempts have been made to examine whether or not additive reaction time patterns were obtainable in rats. In the present work, the subjects (13 Long-Evans rats) had to press down a lever and to respond to a visual (right or left) stimulus by releasing the lever and introducing the head into a lateral (right or left) operandum. The present findings show an additive pattern of effects of signal luminance and foreperiod duration on the mean reaction time which suggests that we have successfully manipulated two stages of rat information processing - the preprocessing stage and the motor adjustment stage, respectively. Accordingly, the present study sets the basis for the basis for investigating the effects of invasive manipulations (pharmacological and/or lesional) on information processing stages.

Changes in spinal excitability during choice reaction time: the H reflex as a probe of information transmission.

The aim of the present study was to investigate the modulations in amplitude of H reflexes elicited in a hand muscle, the flexor pollicis brevis, during the performance of a choice reaction time (RT) task in which this muscle was directly involved. Ten subjects were to choose between a left- or a right-thumb key-press according to the lateral location of a flash of light. The stimulus-response mapping was either compatible or incompatible. Hoffman reflexes were elicited at different times during the RT by stimulation of the median nerve. Twenty-five milliseconds before the voluntary response, the amplitude of the H reflex suddenly increased when the muscle was involved in the response and decreased symmetrically when the muscle was not involved in the response. Mapping compatibility exerted no detectable influence on the changes in spinal excitability. The latter result supports the assumptions that are at the core of Sternberg's additive factor method.

Is the 'error negativity' specific to errors?

When subjects make an erroneous response in a choice reaction time task, an error negativity, or error-related negativity (N(E)/ERN), peaking at about 100 ms after EMG onset, has been described. This wave is often considered to be absent on correct response trials. We report a small N(E)/ERN wave on correct response trials during a choice reaction time task in which surface Laplacians were estimated by the source derivation method. This wave is well focused at FCz, and its time course is the same for correct responses trials, incorrect sub-threshold EMG activation trials, and error trials. Current source density maps, also indicate a focus at FCz. A second experiment showed the existence of a N(E) at FCz on correct trials during a simple RT task. Rather than an error detection process per se, we propose that the N(E)/ERN reflects either a comparison process leading secondarily to error detection, or an emotional reaction.

Effect of the irrelevant location of the response signal on choice reaction time: an electromyographic study in humans.

Choice reaction time (RT) is shorter when the stimulus corresponds spatially to the response than when the stimulus does not, even when the stimulus location is irrelevant to the task. We used electromyographic measures to document that this effect is the result of a response conflict. The activity of the prime movers of two alternative responses was recorded during the performance of a visual RT task in which the irrelevant spatial correspondence between the stimuli and the responses was varied. Only the premotor component of RT was affected by the stimulus-response correspondence. Correct trials were distinguished according to whether or not the activation of the prime mover involved in the required response was preceded by an activation of the prime mover involved in the alternative response. Double muscular activation trials were more numerous for noncorresponding than for corresponding stimulus-response associations. Furthermore, these trials yielded longer RTs than the single muscular activation trials.

Cortico-spinal inhibition reflects time but not event preparation: neural mechanisms of preparation dissociated by transcranial magnetic stimulation.

Changes in cortico-spinal excitability related to time and event preparation were investigated by transcranial magnetic stimulation (TMS) of the motor cortex during the foreperiod of a movement-precuing task. Subjects performed a four alternative choice reaction time (RT) task involving a button-press with the index or middle finger (FI) of the left or right hand. Advance information about the to-be-signaled response was provided by a precue, which preceded the response signal by a 1 s foreperiod. The precue either indicated the hand (right or left) or FI (index or middle) with which the response would be executed or was uninformative. TMS was delivered to the left or right cortical hand area at one of five possible times during the foreperiod: -1000, -500, -333, -166 or 0 ms prior to the response signal. Surface EMG activity from a prime mover involved in flexion of the response FIs (Flexor digitorum superficialis) was used to measure the magnitude of the motor evoked potential (MEP) elicited by TMS. Cortico-spinal excitability--as assessed by the magnitude of the MEP evoked in the target muscle contralateral to the stimulated hemisphere--progressively decreased during the foreperiod. The identity of the precued responses, however, had no effect on MEP magnitude. These results suggest that preparation to respond at a particular time inhibited excitability of the cortico-spinal tract, while advance preparation to perform specific responses affected more central structures only.

Serotonin and human information processing: an electromyographic study of the effects of fluvoxamine on choice reaction time.

Previous studies have shown that fluvoxamine, an inhibitor of serotonin reuptake, shortens choice reaction time. The present study, was intended to explore this effect by using two complementary approaches: (i) Sternberg's additive factor method, and (ii) the analysis of the electromyographic activity of a prime mover. Eight healthy subjects who received either a single oral dose of fluvoxamine (100 mg) or a placebo participated in a choice reaction time experiment in which imperative signal intensity, stimulus-response mapping, and response repertoire were manipulated. Previous results were replicated. Moreover, it was shown that fluvoxamine shortens the interval between prime mover activation and overt response. This supports the hypothesis proposed in a previous study that fluvoxamine affects motor processes. A possible mechanism of this effect is discussed.

The time-course of preparatory spinal and cortico-spinal inhibition: an H-reflex and transcranial magnetic stimulation study in man.

In a previous study where reaction-time methods were combined with transcranial magnetic stimulation (TMS) of the motor cortex, cortico-spinal excitability was shown to reflect time preparation. Provided that subjects can accurately estimate time, the amplitude of motor-evoked potentials (MEPs) diminish progressively during the interval separating the warning signal from the response signal (i.e., the foreperiod). On the other hand, several experiments have demonstrated that the amplitude of the Hoffman (H) reflex elicited in prime movers diminishes during the foreperiod of reaction-time tasks. The aim of the present study was to compare the time course of the respective decrements of H-reflex and MEP amplitude during a constant 500-ms foreperiod. The subjects (n=8) participated in two experimental sessions. In one session, H-reflexes were induced in a tonically activated, responding hand muscle, the flexor pollicis brevis, at different times during the foreperiod of a visual-choice reaction-time task. In the other session, motor potentials were evoked in the same muscle by TMS of the motor cortex delivered in the same behavioral conditions and at the same times as in the first session. The results show that both H-reflexes and MEPs diminish in amplitude during the foreperiod, which replicates and extends previous findings. Interestingly, the time constants of the two decrements differed. There was a facilitatory effect of both electrical and magnetic stimulations on the subject's performance: reaction time was shorter for the trials during which a stimulation was delivered than for the no-stimulation trials. This facilitation was maximal when the stimulations were delivered simultaneously with the warning signal and vanished progressively with stimulation time.