Excitatory and inhibitory processes in primary motor cortex during the foreperiod of a warned reaction time task are unrelated to response expectancy

Reaction time (RT) is shortened when a warning signal precedes the response signal, a finding attributed to response preparation during the foreperiod between the warning and response signals. In a previous experiment, we delivered transcranial magnetic stimulation (TMS) during the short constant foreperiod of a warned RT task and found simultaneous suppression of motor evoked potential (MEP) amplitude and reduction of short-interval intracortical inhibition (SICI) on warned trials (Sinclair and Hammond in Exp Brain Res 186:385–392, 2008). To investigate the extent to which these phenomena are associated with response preparation we measured MEP amplitude and SICI during the foreperiod of a warned RT task in which three different warning signals specified the probability (0, 0.5, or 0.83) of response signal presentation. MEP amplitude was suppressed (Experiment 1) and SICI reduced (Experiment 2) equally in all of the warned conditions relative to when TMS was delivered in the inter-trial interval (ITI) suggesting that the modulation of primary motor cortex excitability during the foreperiod does not depend on momentary response expectancy induced by the warning signal. The reduction of SICI and suppression of MEP amplitude can be explained by assuming that a warning signal induces automatic motor cortical activation which is balanced by a competing inhibition to prevent premature response. A composite measure which weighted both speed and accuracy of response was positively correlated with the MEP amplitude during both the foreperiod and the ITI, suggesting that high motor cortical excitability is associated with optimized preparatory strategies for fast and accurate response.     

The Effect of an Acoustic Warning Stimulus Upon the Electrically Elicited Blink Reflex in Humans

In a warned Go/No-Go reaction time experiment blink reflexes were elicited electrically immediately before, at, and shortly after the onset of a low intensity acoustic warning stimulus. This provided the opportunity to study the mutual effects of two stimuli of different modalities arriving at the facial nucleus. The warning stimulus was followed after 3 s by an acoustic response stimulus. Sixteen subjects participated in the experiment. They were informed by the response stimulus if a response (a voluntary blink of the right eye) was required. R1 magnitude was increased from 10 ms to 100 ms after warning stimulus onset, with a pronounced peak at 50 ms. The bilateral late component R2 was enhanced when the reflex eliciting stimulus preceded the warning stimulus. Between 20 ms and 30 ms after warning stimulus onset, R2 returned to control level, whereas an eliciting stimulus presented 40 ms or later after warning stimulus onset produced a pronounced inhibition. R2 latency was facilitated immediately after warning stimulus onset. It was concluded that the mutual effects of stimuli of different modalities can be interpreted only if the moment of arrival at the motor nucleus is taken into consideration.     

Modulation of electrically elicited blink reflex components by visual and acoustic prestimuli in man

The effects of a prestimulus on the electrically elicited blink reflex components were investigated in 20 healthy subjects. In the first group of 10 subjects (warned group), electric shocks were delivered in isolation or preceded, at an interstimulus interval (ISI) of 0.1 s, 1 s, or 10 s, by a visual or acoustic warning stimulus. In the second group of 10 subjects (unwarned group), the electric shocks were delivered either in isolation or preceded, at the same ISI, by visual or acoustic stimuli having no warning value. The modulation of the three blink reflex components was then analysed. Compared to the baseline condition, the R1 oligosynaptic component was enhanced at 0.1 s and 1 s ISI, in the warned group with the visual prestimulus, but only at 0.1 s after a visual and acoustic prestimulus in the unwarned group. On the contrary, the polysynaptic responses showed a different course: R2 was significantly reduced at the 0.1 s interval in the warned group with both the prestimuli, and only with the visual prestimulus in the unwarned group. The R3 was inhibited at all three intervals with the visual prestimulus, and at the 0.1 s and 1 s with the acoustic one in the warned group, and only at 0.1 s in the unwarned group, both after visual and acoustic prestimuli. The decrement in R2 and R3 observed with the shortest interval was probably related to the prepulse inhibition of startle reflex. Furthermore, only R3 was still inhibited at longer intervals, when the sustained processes of attention may have influenced this component. Perhaps this combination of events represents, in the warned group, the best preparation for voluntary reflex reaction.     

Reduced intracortical inhibition during the foreperiod of a warned reaction time task

Reaction time (RT) is shortened when the response signal is preceded by a warning signal, a finding that has been attributed to response preparation during the foreperiod between the warning and response signals. Research suggests an increased excitability of cortical movement representations associated with response preparation during the foreperiod of a warned RT task (Davranche et al. in Eur J Neurosci 25:3766–3774, 2007). However when the foreperiod duration is short and constant, the motor evoked potential (MEP) amplitude elicited by transcranial magnetic stimulation (TMS) during the foreperiod is suppressed (Touge et al. in Clin Neurophysiol 111:1216–1226, 1998), suggesting a competing inhibitory process. Three experiments measured MEP amplitude and intracortical inhibition during the foreperiod of a warned RT task in which the response was a flexion of the right index finger. Experiments 1 and 2 measured short-interval intracortical inhibition (SICI) with paired TMS pulses separated by inter-stimulus intervals (ISIs) of 3 (SICI₃) and 1.5 ms (SICI_1.5), respectively. Experiment 3 measured long-interval intracortical inhibition (LICI) with paired TMS pulses with an ISI of 100 ms (LICI₁₀₀). In all experiments MEP amplitude was smaller in the warned condition than in the unwarned condition. There was less SICI₃ in the warned condition than in the unwarned condition (Experiment 1) whereas SICI_1.5 was similar in both conditions (Experiment 2). There was less LICI₁₀₀ in the warned condition than in the unwarned condition (Experiment 3). The intracortical inhibitory processes measured here cannot explain the suppression of MEP amplitude in the warned condition. We propose that the suppression of MEP amplitude is the result of an inhibitory mechanism, which acts on primary motor cortex to prevent premature response during the foreperiod.     

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. Received: 6 November 1997 / Accepted: 2 June 1998     

Effects of a Warning Stimulus on Reflex Elicitation and Reflex Inhibition

Human subjects (n = 14) were given a discriminated reaction time task in which the imperative stimulus (IS), a puff of air to the face, was both a signal for a voluntary response and an elicitor of a reflex eyeblink. On one-half of the trials IS was preceded with a lead time of 100 msec by a stimulus (DS) which both inhibited the reflex blink and served as a signal to refrain from the voluntary response. On one-half of the trials within each DS-IS and IS-alone condition a warning stimulus (WS) led IS by 3000 msec. WS produced a decrease in HR and a faster RT, and WS-IS trials gave greater reflex amplitudes than IS-alone trials. Eyeblinks were inhibited by DS and reflex inhibition was more pronounced following the warning stimulus. These data suggest that warning stimuli initiate an attentional process oriented to significant stimuli, thus enhancing both the eliciting and inhibiting functions of these stimuli.     

Binocular locus of prior time information effect in schizophrenia

Schizophrenics and alcoholic controls estimated the duration of a single dark dot, which followed an auditory warning signal of variable duration that functioned as foreperiod duration. The effect of foreperiod duration on time estimation was an increasing one for both schizophrenics and alcoholics alike. Elimination of such foreperiod effect by prior time information in terms of correlation between pitch of the warning signal and foreperiod duration, was shown to be unique to schizophrenics. However, this prior time information effect was demonstrated only when the dot was viewed binocularly, not when viewed monocularly. This binocular locus of time expectancy in schizophrenia reflects the tendency toward spatialization of prior time information.     

The increased foreperiod duration to attain the neutral optimal preparation from sitting to standing

The purpose of the present experiment was to investigate the effects of a neutral preparation during the foreperiod on motor and postural programming processes in a voluntary upper limb movement. The foreperiod duration (300, 500, 700 and 900 ms) and the postural condition (sitting vs standing) were manipulated using a neutral preparation (no advanced information during the preparatory signal). Thirteen subjects performed a raising arm movement with 1 kg load at the wrist. Premotor time, latency of the anticipatory postural adjustments and the vertical torque were calculated. A previous experiment showed that the optimal foreperiod duration (i.e. leading to the shortest premotor time) increased from sitting to standing in a selective preparation (Cuisinier et al. in Brain Res Bull 66(2):163–170, 2005). The present experiment replicated this finding in a neutral preparation. It was found that (1) this optimal foreperiod duration still increased from 500 ms in sitting to 700 ms in standing in a neutral preparation, (2) this increased optimal foreperiod duration resulted from a greater level of alertness necessary to control a more constrained posture in standing than in sitting, and (3) the existence of a temporal modulation in the central organization of the postural and focal commands was according to the foreperiod duration.     

Impairment of movement initiation and execution but not preparation in idiopathic dystonia

Imaging studies have reported impaired activation of the striatum and their frontal projection sites in dsytonia, areas which are considered to play a role in motor preparation, movement initiation and execution. The aim of this study was to investigate the processes of motor preparation, response initiation and execution in patients with idiopathic torsion dystonia (ITD). We assessed 12 patients with ITD and 12 age-matched controls on a number of reaction time (RT) tasks that differed in degree of motor preparation possible. Subjects performed a visual simple RT (SRT) task, an uncued four-choice reaction time (CRT) task and a fully precued four-choice RT task. A stimulus 1-stimulus 2 (S1-S2) paradigm was used. The warning signal/precue (S1) preceded the imperative stimulus (S2) by either 0 ms (no warning signal or precue) 200 ms, 800 ms, 1,600 ms or 3,200 ms. The patients with ITD had significantly slower RTs and movement times than normals across all RT tasks. The unwarned SRT trials were significantly faster than the uncued CRT trials for both groups. For both groups, precued CRTs were significantly faster than the uncued CRTs. The results show that while response initiation and execution are significantly slower in patients with ITD than normals, movement preparation is not quantitatively or qualitatively different. The results are discussed in relation to previous imaging, behavioural and electrophysiological studies and models of fronto-striatal dysfunction in ITD.     

Slow Cortical Potentials in Subjects With High or Low Scores on a Questionnaire Measuring Physical Anhedonia and Body Image Distortion

Slow cortical potentials, response speed, and peripheral physiological responses were investigated in two experiments with four groups of male subjects. Experiment 1 examined constant foreperiod reaction time in a sound-light-button press sequence with an interstimulus interval of 2 sec. Experiment 2 investigated constant foreperiod reaction time conditions with a sudden change from controllable to uncontrollable offset of an aversive imperative stimulus. There were two visual warning stimuli of 6-sec duration followed by an aversive or neutral imperative stimulus to be terminated by button press within 1 sec. Forty trials of this contingency were followed by 40 trials with 5-sec duration of imperative stimuli irrespective of response speed. Subjects were selected by high or low scores on two questionnaire scales measuring physical anhedonia (PA) and body image distortion (BI). In the first paradigm subjects with high PA scores as compared to low-scoring subjects showed less resolution of left precentral CNV after S2, i.e., a more pronounced postimperative negative component. In the second paradigm a postimperative negative variation (PINV) developed in all groups, but was more pronounced in frontal recordings and in subjects with high PA and BI scores. Results are discussed in the context of electrocortical phenomena observed in psychopathological groups.     

Impaired attention modulation of the blink reflex R3 component in Parkinson's disease: a non-task warning paradigm study.

PURPOSE: the aim of this experimental study was to evaluate the attention modulating actions on the polysynaptic component of blink reflex responses and especially of the R3 component in patients suffering from Parkinson's Disease (PD). To this end, a non-task warning paradigm was adopted. METHODS: attention processing was evaluated by means of a non-task paradigm in 55 patients suffering from PD. Subjects were presented with a visual 'warning' prestimulus and the blink reflex (BR) analyzed with special regard for any modulation of its polysynaptic components (R2-R3). RESULTS: The mean amplitude of the post-warning R3 component (PW-R3c) of 'de novo' PD patients was 62% of the corresponding component following unannounced stimuli, a figure which differs significantly from both treated PD patients (18.9%) and control subjects (15.4%). De novo patients subsequently started on L-dopa therapy exhibited a more pronounced inhibition of the R3 component after warning stimulus, as the PW-R3c percentage decreased. Inversely, treated patients whose therapy was withheld showed decreased inhibition of this component. Regarding R2, the mean PW-R2c in the de novo patients differed slightly from that of the treated patients (P<0.05), but not from that of the control subjects. Such a finding may be attributable to a specific effects on the excitability of the polysynaptic responses. CONCLUSIONS: Attention disorders in PD have been well documented by means of this kind of non-task warning paradigm, which appears to probe the modulation of the BR R3 component, even if the interpretation of this R3 changes suggesting a specific alteration of attention processing must be put forward extremely carefully, because something similar, but less evident, appears also for R2.     

The impact of warning signal intensity on reaction time and components of the contingent negative variation.

Slow EEG potentials were recorded during performance of a simple reaction task in which warning signal intensity was varied from trial to trial under foreperiod durations of 1, 3 and 8 sec. As shown by speed of reaction, the warning signal had an activating effect which increased with its intensity and decreased with foreperiod duration. This effect was related to the amplitude of a slow potential which appears in the EEG shortly after presentation of the warning signal. This potential is interpreted as a component of the orienting response regulating sensitivity to subsequent stimulation, so that reaction time is affected through change in the effective intensity of the imperative signal.     

Default motor preparation under conditions of response uncertainty

In a choice reaction time (RT) paradigm, providing partial advance information (a precue) about the upcoming response has been shown to decrease RT, presumably due to preprogramming of the precued parameters. When advance information about a particular aspect of a movement is provided (precued), several different strategies might be used to prepare the motor system during the foreperiod. For example, in studies where response preparation time was manipulated, precues were provided specifying the required arm and direction but movement amplitude was left uncertain. In this case it was shown that a default movement was preprogrammed whose amplitude was intermediate between the alternatives (Favilla et al. in Exp Brain Res 75(2):280-294, 1989, Exp Brain Res 79(3):530-538, 1990; Ghez et al. in Exp Brain Res 115(2):217-233, 1997). However, this strategy did not appear to be used in a RT task since there was an absence of online adjustments to movement. Therefore, it appeared movements were not initiated until all parameters had been correctly specified and programmed by the nervous system (Bock and Arnold in Exp Brain Res 90:(1):209-216, 1992). The present study reinvestigated the notion of a default movement preparation strategy in a choice RT paradigm, employing the triggering effect of a startling acoustic stimulus. On control trials (80 dB imperative stimulus), the movements were initiated toward the correct targets. Providing a startle stimulus (124 dB) resulted in the early initiation of a "default" movement whose amplitude fell in between the potential response alternatives. Thus, the current experiment found behavioral evidence of default intermediate-amplitude movement preparation as a strategy under conditions of response amplitude uncertainty.     

Effects of foreperiod duration on reflexive and voluntary responses to intense noise bursts

The question of whether a common mechanism underlies the facilitation of voluntary and reflexive reactions by a warning stimulus was investigated in two experiments. In both studies, the foreperiod preceding an intense noise burst was manipulated within and between blocks of trials. Previous reaction time experiments have shown that individuals respond fastest at the shortest foreperiod for between-block manipulations and fastest at the longest foreperiod when foreperiod duration is varied unpredictably from trial to trial. In the present research, this pattern was found for voluntary hand-grip responses, but acoustic startle blinks were facilitated at long foreperiods for both within- and between-block manipulations. Invariance of the trisynaptic postauricular reflex across foreperiod conditions was evidence against any general activation of low-level motor pathways by warning stimuli. Analyses of nonreflexive lid movements subsequent to startle blink suggested that inhibition of spontaneous blinking during the foreperiod may have contributed to the unexpected divergence between voluntary reactions and eyeblink reflexes.     

The differences in human spinal motoneuron excitability during the foreperiod of a motor task

Changes in excitability of the spinal motoneuron pool during the foreperiod, which was fixed at 0.8 s, in simple and choice reaction time experiments using ankle dorsiflexion and plantar flexion were studied in fourteen healthy normal subjects by combining the visually guided tracking and H-reflex testing methods. Almost all cases showed a significant facilitation in the soleus H-reflex within the time interval between 100 and 300 ms after a warning signal (Phase I), irrespective of movement direction and task modality. The pretibial H-reflex was also facilitated. On the other hand, variable effects were noted in the later half of the foreperiod, particularly within the 200 ms prior to the response signal (Phase II). Using a simple reaction task with dorsiflexion, six cases showed no changes in the soleus H-reflex, while four others showed statistically significant inhibitory changes and the remaining four showed facilitation. The inhibition and facilitation were often accompanied with very weak and unintended EMG activities in the pretibial and So1 muscles respectively. A similar finding was obtained in the simple plantar flexion task and the choice reaction task with dorsiflexion or plantar flexion. We suggest that the facilitation at Phase I represents a perceptual orienting response to a warning signal and the effects seen in Phase II represent the difference in the waiting attitude of each subject anticipating initiation of the coming task, or the preparatory "set" which primed the spinal motor structure in a biased position.     

Warning signals induce automatic EMG activations and proactive volitional inhibition: evidence from analysis of error distribution in simple RT

Typical simple reaction-time (RT) paradigms usually include a warning signal followed by a variable foreperiod before the presentation of a reaction stimulus. Most current interpretations suggest that the warning stimulus alerts the organism and so results in faster processing of either the sensory or motor components of the task. In this study, electromyography (EMG) was used to detect both covert and overt motor errors in a simple warned RT task. Results show that warning signals may trigger automatic motor activations that are likely to cause false alarms. Distribution analysis reveals that 77% of all errors detected with EMG are erroneous responses to the warning signal. Accordingly, we propose that movement triggering needs to be temporarily inhibited before the stimulus to prevent premature responses during the foreperiod. This proactive inhibition would be responsible for a paradoxical increase in RT for conditions with short foreperiods compared with control conditions in which no warning signal is presented. These results call for a reassessment of the theoretical framework used to interpret the effects of warning signals.     

Heart Rate, Contingent Negative Variation, and Evoked Potentials during Anticipation of Affective Stimulation

Thirteen subjects low in fear of mutilation and 11 subjects high in this fear were exposed to repeated presentations of a 6-sec tone followed by slides depicting a mutilated body or a 6-sec tone of a different frequency paired with a slide of a neutral scene. For both groups, the N140 component of the evoked potential was larger following the signal for gruesome slides. Slow EEG activity displayed two negative waves. Notably, the late CNV wave was present even though a motor response was not required at the end of the foreperiod. Overall, high-fear subjects' early waves tended to be larger preceding neutral scenes than gruesome slides, whereas low-fear subjects showed a trend in the opposite direction. Similar but largely nonsignificant trends were present for the late wave. Heart rate reactions of both groups in the foreperiod included an early deceleration, acceleration, and a late deceleration. Among high-fear subjects both the acceleratory and late deceleratory limbs were greater preceding mutilation than neutral slides. In contrast, low-fear subjects' reactions lacked the acceleratory reaction and did not vary as a function of type of warning signal. These results, therefore, indicate differential autonomic patterns of anticipation of affective stimulation as a function of individual differences in fear.     

Effects of warning-signal duration on the early and late components of the contingent negative variation.

Slow EEG potentials were recorded from three sites on the scalp (Fz, Cz and Pz) during a simple reaction time task in which the duration of the warning signal was either 0.5 or 2 sec. The duration of the foreperiod was held constant, and order of conditions was varied according to a latin square design. As predicted, the longer warning signal evoked increased amplitude of the early component of the contingent negative variation (CNV). These results confirm the interpretation of that wave as an orienting response. In contrast, the duration of the warning signal did not affect the second CNV component or reaction time latency. Additional dissociation between the two CNV components was evident in their distribution on the scalp. The early component was smallest at Pz, whereas the late component attained its lowest amplitude at Fz. Concurrently recorded palmar skin potentials exhibited different polarity and latency from the CNV.     

On ego regression and prior time information effect in schizophrenia

Process schizophrenics, reactive schizophrenics, neurotics, and alcoholics (N = 80) estimated the duration of a dark dot that followed an auditory warning signal of variable duration. The duration of the warning signal constituted foreperiod (FP). The effect of FP duration on time estimation (TE) was an increasing one for all Ss, and schizophrenics were indistinguishable from nonschizophrenics. Similarly, there was no group difference with respect to the effect of preceding foreperiod (PFP). Prior time information (TI) in terms of the correlation between the pitch of the warning signal and FP duration eliminated the effects of FP and FP change for schizophrenics. As for neurotics, such prior TI accentuated the effect of decrease of FP duration and attenuated the effect of increase of FP duration. The multi-level conceptualization of time is proposed in order to establish the distinction between regression in time and regression of time. Neurosis is regarded as involving regression in time; schizophrenia is regarded as involving regression of time.     

Preparatory process for anticipatory postural adjustments: Modulation of leg muscles reflex pathways during preparation for arm movements in standing man

Summary We have investigated, in 6 standing subjects, the time course of amplitude changes in the short latency (40–60 ms) and long latency (60–80 ms) reflex response components of gastrocnemius medialis (GM) and soleus (S) muscles during the preparatory period (time between a warning signal and a response signal) as a function of the precued direction (pull or push) of arm movement. Subjects maintained their standing posture by visual feedback during the 1.5 s preparatory period of a reaction time task. A warning signal gave advance information concerning the voluntary response to be performed which consisted of either a pull or push movement of the right arm. The excitability of the reflex pathways was evaluated by triggering a rapid rotation of the right ankle joint (dorsiflexion) applied randomly at 100, 300 or 500 ms before the response signal for arm movement. Statistical analysis of EMG amplitude (ANOVA) showed that preparatory effects were different for the two synergistic muscles with both short (spinal) and longer latency components of GM showing generalized facilitation and of S showing generalized inhibition. In addition, the longer latency, presumably supraspinal, component of the two muscles was differentially modulated according to directional advance information, showing relative facilitation for pull as compared to push trials. These reflex response modulations were emphasized in faster reaction time (RT) performers at the end of the preparatory period. It is concluded that postural preparatory processes are reflected at the spinal level in global effects and at the supraspinal level in directionally specific effects.