Premotor Level Research Articles

Post-activation depression of the Hoffman reflex is not altered by galvanic vestibular stimulation in healthy subjects.

The comprehension of the neural elements interacting in the spinal cord affected by vestibular input will contribute to the understanding of movement execution in normal and pathological conditions. In this context, Hoffman's reflex (H-reflex) has been used to evaluate transient excitability changes on the spinal cord descending pathways. The post-activation depression (P-AD) of the H-reflex consists of evoking consecutive responses (>1 Hz) provoking an amplitude depression, which has been shown to diminish in pathological conditions (i.e., spasticity, diabetic neuropathy). Galvanic Vestibular Stimulation (GVS) is a non-invasive method that activates the vestibular afferents and has been used to study the excitability of the H-reflex applied as a conditioning pulse. To our knowledge, there are no reports evaluating the P-AD during and after GVS. Our primary aim was to determine if GVS alters the P-AD evoked by stimulating the tibial nerve at 0.1, 1, 5, and 10 Hz, recording in the gastrocnemius and soleus muscles. Direct current stimulation of 2.0 ± 0.6 mA with the cathode ipsilateral (Ipsi) or contralateral (Contra) to the H-reflex electrode montage was applied bilaterally over the mastoid process in 19 healthy subjects. The P-AD's immediate post-GVS response (P Ipsi, P Contra) was also analyzed. Secondarily, we analyzed the excitability of the H-reflex during GVS. Responses evoked at 0.1 Hz with GVS, post-GVS, and a Control (no GVS) condition were used for comparisons. Our results show that P-AD persisted in all subjects despite increased excitability induced by GVS: statistical significance was found when comparing P-AD at 1, 5, and 10 Hz with the corresponding condition (Control, Ipsi, P Ipsi, Contra, P Contra) at 0.1 Hz (p < 0.001). Additionally, the increase in excitability produced by GVS was quantified for the first H-reflex of each P-AD stimulation frequency. The percentage change for all GVS conditions surpassed the Control by at least 20%, being statistically significant for Contra compared to Control (p < 0.01). In summary, although GVS increases the excitability of the vestibulospinal pathway at a premotor level, the neural inhibitory mechanism present in P-AD remains unaltered in healthy subjects.

Binocular Encoding in the Damselfly Pre-motor Target Tracking System.

Akin to all damselflies, Calopteryx (family Calopterygidae), commonly known as jewel wings or demoiselles, possess dichoptic (separated) eyes with overlapping visual fields of view. In contrast, many dragonfly species possess holoptic (dorsally fused) eyes with limited binocular overlap. We have here compared the neuronal correlates of target tracking between damselfly and dragonfly sister lineages and linked these changes in visual overlap to pre-motor neural adaptations. Although dragonflies attack prey dorsally, we show that demoiselles attack prey frontally. We identify demoiselle target-selective descending neurons (TSDNs) with matching frontal visual receptive fields, anatomically and functionally homologous to the dorsally positioned dragonfly TSDNs. By manipulating visual input using eyepatches and prisms, we show that moving target information at the pre-motor level depends on binocular summation in demoiselles. Consequently, demoiselles encode directional information in a binocularly fused frame of reference such that information of a target moving toward the midline in the left eye is fused with information of the target moving away from the midline in the right eye. This contrasts with dragonfly TSDNs, where receptive fields possess a sharp midline boundary, confining responses to a single visual hemifield in a sagittal frame of reference (i.e., relative to the midline). Our results indicate that, although TSDNs are conserved across Odonata, their neural inputs, and thus the upstream organization of the target tracking system, differ significantly and match divergence in eye design and predatory strategies. VIDEO ABSTRACT.

State-Dependent Modulation of Locomotion by GABAergic Spinal Sensory Neurons

The cerebrospinal fluid (CSF) constitutes an interface through which chemical cues can reach and modulate the activity of neurons located at the epithelial boundary within the entire nervous system. Here, we investigate the role and functional connectivity of a class of GABAergic sensory neurons contacting the CSF in the vertebrate spinal cord and referred to as CSF-cNs. The remote activation of CSF-cNs was shown to trigger delayed slow locomotion in the zebrafish larva, suggesting that these cells modulate components of locomotor central pattern generators (CPGs). Combining anatomy, electrophysiology, and optogenetics in vivo, we show that CSF-cNs form active GABAergic synapses onto V0-v glutamatergic interneurons, an essential component of locomotor CPGs. We confirmed that activating CSF-cNs at rest induced delayed slow locomotion in the fictive preparation. In contrast, the activation of CSF-cNs promptly inhibited ongoing slow locomotion. Moreover, selective activation of rostral CSF-cNs during ongoing activity disrupted rostrocaudal propagation of descending excitation along the spinal cord, indicating that CSF-cNs primarily act at the premotor level. Altogether, our results demonstrate how a spinal GABAergic sensory neuron can tune the excitability of locomotor CPGs in a state-dependent manner by projecting onto essential components of the excitatory premotor pool.

Seeing biological actions in 3D: An fMRI study.

Precise kinematics or body configuration cannot be recovered from visual input without disparity information. Yet, no imaging study has investigated the role of disparity on action observation. Here, we investigated the interaction between disparity and the main cues of biological motion, kinematics and configuration, in two fMRI experiments. Stimuli were presented as point‐light figures, depicting complex action sequences lasting 21 s. We hypothesized that interactions could occur at any of the three levels of the action observation network, comprising occipitotemporal, parietal and premotor cortex, with premotor cortex being the most likely location. The main effects of kinematics and configuration confirmed that the biological motion sequences activated all three levels of the action observation network, validating our approach. The interaction between configuration and disparity activated only premotor cortex, whereas interactions between kinematics and disparity occurred at all levels of the action observation network but were strongest at the premotor level. Control experiments demonstrated that these interactions could not be accounted for by low level motion in depth, task effects, spatial attention, or eye movements, including vergence. These results underscore the role of premotor cortex in action observation, and in imitating others or responding to their actions. Hum Brain Mapp 37:203–219, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Hybrid model of the context dependent vestibulo-ocular reflex: implications for vergence-version interactions.

The vestibulo-ocular reflex (VOR) is an involuntary eye movement evoked by head movements. It is also influenced by viewing distance. This paper presents a hybrid nonlinear bilateral model for the horizontal angular vestibulo-ocular reflex (AVOR) in the dark. The model is based on known interconnections between saccadic burst circuits in the brainstem and ocular premotor areas in the vestibular nuclei during fast and slow phase intervals of nystagmus. We implemented a viable switching strategy for the timing of nystagmus events to allow emulation of real nystagmus data. The performance of the hybrid model is evaluated with simulations, and results are consistent with experimental observations. The hybrid model replicates realistic AVOR nystagmus patterns during sinusoidal or step head rotations in the dark and during interactions with vergence, e.g., fixation distance. By simply assigning proper nonlinear neural computations at the premotor level, the model replicates all reported experimental observations. This work sheds light on potential underlying neural mechanisms driving the context dependent AVOR and explains contradictory results in the literature. Moreover, context-dependent behaviors in more complex motor systems could also rely on local nonlinear neural computations.

Near-optimal decoding of transient stimuli from coupled neuronal subpopulations.

Coupling between sensory neurons impacts their tuning properties and correlations in their responses. How such coupling affects sensory representations and ultimately behavior remains unclear. We investigated the role of neuronal coupling during visual processing using a realistic biophysical model of the vertical system (VS) cell network in the blow fly. These neurons are thought to encode the horizontal rotation axis during rapid free-flight maneuvers. Experimental findings suggest that neurons of the VS are strongly electrically coupled, and that several downstream neurons driving motor responses to ego-rotation receive inputs primarily from a small subset of VS cells. These downstream neurons must decode information about the axis of rotation from a partial readout of the VS population response. To investigate the role of coupling, we simulated the VS response to a variety of rotating visual scenes and computed optimal Bayesian estimates from the relevant subset of VS cells. Our analysis shows that coupling leads to near-optimal estimates from a subpopulation readout. In contrast, coupling between VS cells has no impact on the quality of encoding in the response of the full population. We conclude that coupling at one level of the fly visual system allows for near-optimal decoding from partial information at the subsequent, premotor level. Thus, electrical coupling may provide a general mechanism to achieve near-optimal information transfer from neuronal subpopulations across organisms and modalities.

High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition.

Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such.

Psychological refractory period in introverts and extraverts

The present study was designed to explore extraversion-related differences in the psychological refractory period (PRP). PRP refers to a bottleneck of information processing that becomes evident when participants are required to respond to two signals (S1 and S2) presented in rapid succession. If this capacity limit of premotor information processing is essential for differences in speed of information processing between introverts and extraverts, magnitude of the PRP effect should vary as a function of extraversion. Due to the failure of previous attempts to establish extraversion-related differences in the PRP effect, we also obtained lateralized readiness potentials (LRPs). For this purpose, 63 introverted and 63 extraverted female participants were tested with a standard PRP design. Extraverts responded faster to S2 and exhibited shorter stimulus-locked LRP latencies compared to introverts. Although a general PRP effect could be shown at the behavioral and psychophysiological level, there was no indication for any extraversion-related differences in PRP. Thus, extraversion-related differences in speed of information processing at the premotor level appear unlikely to originate from individual differences in the capacity limits underlying the PRP phenomenon. Furthermore, our findings provide converging evidence for the notion that extraversion-related individual differences in processing speed depend on specific task demands.

Saccade and vergence eye movements: a review of motor and premotor commands

Neuropsychology examines the relationship between cognitive activity and corresponding cerebral conditions. At one end, psychophysics meticulously describes the details of behavior. At the other, physiology records brain cell activity during cognitive tasks. Bridging the two, neuropsychology establishes the neural correlate of behaviour when correlation methods are used, and extends to the critical neural substrate when a causal relationship can be established. Here we revisit the Hering-versus-Helmholtz controversy on binocular coordination from the psychophysician's description of combined saccade-vergence eye movements to the neurophysiological recording of motor and premotor neurons of the oculomotor neural circuitry. Whilst neo-Heringian psychophysicians and physiologists have accumulated arguments for separate saccade and vergence systems, at both the behavioral and the neural premotor levels, neo-Helmholtzians have also provided evidence for monocular programmed eye movements and commands at the premotor level. Bridging the two, we conclude that Hering and Helmholtz were both right. Importantly, the latter's viewpoint brings to the fore the importance of adaptive processes throughout life, in view of the neurobiological constraints emphasized by the former.

The Horizontal Angular Vestibulo-Ocular Reflex: A Nonlinear Mechanism for Context-Dependent Responses

Studies of the vestibulo-ocular reflex (VOR) have revealed that this type of involuntary eye movement is influenced by viewing distance. This paper presents a bilateral model for the horizontal angular VOR in the dark based on realistic physiological mechanisms. It is shown that by assigning proper nonlinear neural computations at the premotor level, the model is capable of replicating target-distance-dependent VOR responses that are in agreement with geometrical requirements. Central premotor responses in the model are also shown to be consistent with experimental observations. Moreover, the model performance after simulated unilateral canal plugging also reproduces experimental observations, an emerging property. Such local nonlinear computations could similarly generate context-dependent behaviors in other more complex motor systems.

Binocular coordination of saccades during reading in children with clinically assessed poor vergence capabilities

Prior studies have pointed toward a link between the saccadic and vergence systems, coordinating binocular saccadic movements. Recent studies have shown that vergence deficits in children induce poor binocular coordination during saccades, but none of them have studied ocular motility in children during a daily task such as reading. The present study tests whether vergence deficits in children perturb binocular coordination of saccades and fixation during reading. Our second objective was to explore whether vergence training could improve the quality of binocular coordination. Twelve patients (from 7.3 to 13.4 years old) complaining from vertigo but without vestibular and neurological pathology underwent orthoptic tests and were selected for our study when they presented vergence deficits. Eye movements were recorded during a reading task with a Mobile EyeBrain® Tracker video-oculography system. Data were compared to twelve age-matched controls with normal orthoptic values. While there was no statistically significant difference in saccade amplitudes between the two groups (p=0.29), patients showed higher disconjugacy during and after the saccades compared to controls (p<0.001). After orthoptic training, six patients out of the first 12 examined came back for a second oculomotor test. All showed a significant improvement of their binocular saccade coordination. We suggest that the larger disconjugacy during reading observed in patients before training could be due to poor vergence as initially assessed by orthoptic examination. Such findings support the hypothesis of a tight relationship between the saccadic and vergence systems for controlling the binocular coordination of saccades. The improvement reported after orthoptic training is in line with the hypothesis of an adaptative interaction on a premotor level between the saccadic and vergence system.

Aphasia, phonological and phonetic voicing within the consonantal system: preservation of phonological oppositions and compensatory strategies

A great number of studies in aphasiology have reported devoicing of voiced consonants in patients who have particular difficulty with the phonetic processing of speech. Recently, other studies have made attempts to account for these difficulties not only in negative terms of ‘deficit’ but also, positively, as a palliative strategy which patients would resort to in order to compensate, at least partly, for their deficit.The aim of this chapter is to contribute to the ongoing debate about devoicing phenomena in aphasia. We carried out a multiple-case study in which we acoustically analysed consonants distinguished by the voiced–voiceless contrast in order to determine, for each patient: (a) the nature of their deficit: whether it is phonological (pre-motor level of speech processing) or phonetic (motor level); and (b) the existence of possible palliative strategies. Results obtained from anarthria and Broca’s aphasia speech output indicate that the subjects differ in a statistically significant way (p<.05) between the VOT values according to whether the target consonant is voiced or voiceless. This can be interpreted, in the patients under study, as a deficit at the level of planning and/or implementation of the voicing feature without impairment, at a deeper level of processing, of the phonological encoding. These results also show that the subjects resort to alternative acoustic cues such as (i) Voice Termination Time (VTT), (ii) total duration of the segment, (iii) number of noise bursts or (iv) duration of the preceding vowel to mark the phonological opposition of voicing, therefore suggesting that they are making use of palliative strategies to compensate for their deficit.

Electrophysiological evidence for the effect of prior probability on response preparation

We investigated whether prior probability (PP) information modulates preparatory processes at a central premotor level or at a peripheral motor level. We provided parametrically graded probability information during the foreperiod of a precuing paradigm. The Contingent Negative Variation (CNV) and the Lateralized Readiness Potential (LRP) were used as indicators for premotor and motor preparation during the foreperiod, respectively. The CNV amplitude was parametrically modulated by PP. In contrast, the LRP amplitude during the foreperiod differed from baseline only when the precue was reliable. The interval between precue and LRP onset was shortened when probability information was delivered in contrast to noninformative advance information. Furthermore, a source analysis for the foreperiod revealed a dipole in the anterior cingulate cortex. Together, our results suggest that PP modulates preparatory processes at a central premotor level.

Perceptual biases for rhythm: The Mismatch Negativity latency indexes the privileged status of binary vs non-binary interval ratios

Objective Rhythm perception appears to be non-linear as human subjects are better at discriminating, categorizing and reproducing rhythms containing binary vs non-binary (e.a. 1:2 vs 1:3) as well as metrical vs non-metrical (e.a. 1:2 vs 1:2.5) interval ratios. This study examined the representation of binary and non-binary interval ratios within the sensory memory, thus yielding a truly sensory, pre-motor, attention-independent neural representation of rhythmical intervals. Methods Five interval ratios, one binary, flanked by four non-binary ones, were compared on the basis of the MMN they evoked when contrasted against a common standard interval. Results For all five intervals, the larger the contrast was, the larger the MMN amplitude was. The binary interval evoked a significantly much shorter (by at least 23 ms) MMN latency than the other intervals, whereas no latency difference was observed between the four non-binary intervals. Conclusions These results show that the privileged perceptual status of binary rhythmical intervals is already present in the sensory representations found in echoic memory at an early, automatic, pre-perceptual and pre-motor level. Significance MMN latency can be used to study rhythm perception at a truly sensory level, without any contribution from the motor system.

Separate Modulations of Human V1 Associated with Spatial Attention and Task Structure

Functional magnetic resonance imaging (fMRI) was used while normal human volunteers engaged in simple detection and discrimination tasks, revealing separable modulations of early visual cortex associated with spatial attention and task structure. Both modulations occur even when there is no change in sensory stimulation. The modulation due to spatial attention is present throughout the early visual areas V1, V2, V3, and VP, and varies with the attended location. The task structure activations are strongest in V1 and are greater in regions that represent more peripheral parts of the visual field. Control experiments demonstrate that the task structure activations cannot be attributed to visual, auditory, or somatosensory processing, the motor response for the detection/discrimination judgment, or oculomotor responses such as blinks or saccades. These findings demonstrate that early visual areas are modulated by at least two types of endogenous signals, each with distinct cortical distributions.

Evidence for frequent divergence impairment in French dyslexic children: deficit of convergence relaxation or of divergence per se?

There is a controversy as to whether dyslexic children present visuo-motor disabilities such as vergence and accommodative problems assessed with orthoptic tests. The purpose of this study is to re-examine this issue in a large population of children. Extensive orthoptic evaluation was made in 57 dyslexic and 46 non-dyslexic ("normal") age-matched children. Convergence and divergence capacities were evaluated at two distances (30 cm and 400 cm). Binocular vision measured with stereo-acuity tests was normal in dyslexics. In contrast, the near point of convergence was significantly more remote in dyslexics; most importantly, divergence at both far and near distance was significantly more reduced in dyslexics (median value 4 pD and 10 pD, respectively, at far and near) than in "normals" (median value 6 pD and 12 pD, at far and near). The existence of the divergence deficit at far distance indicates the presence of deficit of divergence per se, independently from convergence and accommodation relaxation. This result is novel and corroborated by physiological studies indicating distinct control of convergence and divergence, both at the cortical and subcortical premotor level. We conclude that vergence deficits are frequently present in dyslexics, and that dyslexics should be re-educated; training should address distinctively convergence and divergence subsystems.

Sensory and Motor Effects of Etomidate Anesthesia

The effects of anesthesia with etomidate on the cellular mechanisms of sensory processing and sensorimotor coordination have been studied in the active electric sense of the mormyrid fish Gnathonemus petersii. Like many anesthetics, etomidate is known to potentiate GABA(A) receptors, but little is known about the effects on sensory processing at the systems level. A better understanding is necessary for experimental studies of sensory processing, in particular regarding possible effects on the dynamic structure of excitatory and inhibitory receptive fields and to improve the knowledge of the mechanisms of anesthesia in general. Etomidate slowed the electromotor discharge rhythm, probably because of feedback inhibition at the premotor level, but did not alter the structure of the electromotor command. Sensory translation through primary afferents projecting to the cerebellum-like electrosensory lobe (ELL) was not changed. However, central interneurons and projection neurons were hyperpolarized under etomidate, and their spiking activity was reduced. Although the spatial extent and the center/surround organization of sensory receptive fields were not changed, initial excitatory responses were followed by prolonged inhibition. Corollary discharge input to ELL was maintained, and the temporal sequence of excitatory and inhibitory components of this descending signal remained intact. Later inhibitory corollary discharge responses were prolonged by several hundred milliseconds. The result was that excitatory reafferent sensory input was conserved with enhanced precision of timing, whereas background activity was greatly reduced. Anti-Hebbian synaptic plasticity evoked by association of sensory and corollary discharge input was still present under anesthesia, and differences compared with the nonanesthetized condition are discussed.

Interhemispheric transmission of visuomotor information in humans: fMRI evidence.

Normal human subjects underwent functional magnetic resonance imaging (fMRI) while performing a simple visual manual reaction-time (RT) task with lateralized brief stimuli, the so-called Poffenberger's paradigm. This paradigm was employed to measure interhemispheric transmission (IT) time by subtracting mean RT for the uncrossed hemifield-hand conditions, that is, those conditions not requiring an IT, from the crossed hemifield-hand conditions, that is, those conditions requiring an IT to relay visual information from the hemisphere of entry to the hemisphere subserving the response. The obtained difference is widely believed to reflect callosal conduction time, but so far there is no direct physiological evidence in humans. The aim of our experiment was twofold: first, to test the hypothesis that IT of visuomotor information requires the corpus callosum and to identify the cortical areas specifically activated during IT. Second, we sought to discover whether IT occurs mainly at premotor or perceptual stages of information processing. We found significant activations in a number of frontal, parietal, and temporal cortical areas and in the genu of the corpus callosum. These activations were present only in the crossed conditions and therefore were specifically related to IT. No selective activation was present in the uncrossed conditions. The location of the activated callosal and cortical areas suggests that IT occurs mainly, but not exclusively, at premotor level. These results provide clear cut evidence in favor of the hypothesis that the crossed-uncrossed difference in the Poffenberger paradigm depends on IT rather than on a differential hemispheric activation.

Neuropeptide-mediated facilitation and inhibition of sensory inputs and spinal cord reflexes in the lamprey.

The effects of neuromodulators present in the dorsal horn [tachykinins, neuropeptide Y (NPY), bombesin, and GABAB agonists] were studied on reflex responses evoked by cutaneous stimulation in the lamprey. Reflex responses were elicited in an isolated spinal cord preparation by electrical stimulation of the attached tail fin. To be able to separate modulator-induced effects at the sensory level from that at the motor or premotor level, the spinal cord was separated into three pools with Vaseline barriers. The caudal pool contained the tail fin. Neuromodulators were added to this pool to modulate sensory inputs evoked by tail fin stimulation. The middle pool contained high divalent cation or low calcium Ringer to block polysynaptic transmission and thus limit the input to the rostral pool to that from ascending axons that project through the middle pool. Ascending inputs and reflex responses were monitored by making intracellular recordings from motor neurons and extracellular recordings from ventral roots in the rostral pool. The tachykinin neuropeptide substance P, which has previously been shown to potentiate sensory input at the cellular and synaptic levels, facilitated tail fin-evoked synaptic inputs to neurons in the rostral pool and concentration dependently facilitated rostral ventral root activity. Substance P also facilitated the modulatory effects of tail fin stimulation on ongoing locomotor activity in the rostral pool. In contrast, NPY and the GABAB receptor agonist baclofen, both of which have presynaptic inhibitory effects on sensory afferents, reduced the strength of ascending inputs and rostral ventral root responses. We also examined the effects of the neuropeptide bombesin, which is present in sensory axons, at the cellular, synaptic, and reflex levels. As with substance P, bombesin increased tail fin stimulation-evoked inputs and ventral root responses in the rostral pool. These effects were associated with the increased excitability of slowly adapting mechanosensory neurons and the potentiation of glutamatergic synaptic inputs to spinobulbar neurons. These results show the possible behavioral relevance of neuropeptide-mediated modulation of sensory inputs at the cellular and synaptic levels. Given that the types and locations of neuropeptides in the dorsal spinal cord of the lamprey show strong homologies to that of higher vertebrates, these results are presumably relevant to other vertebrate systems.

Somatosensory-evoked blink response: investigation of the physiological mechanisms.

The somatosensory-evoked blink response (SBR) is a newly identified blink reflex elicited by electrical stimulation of peripheral nerves. The present study was performed to investigate the physiological mechanism underlying the SBR elicited by median nerve stimulation in normal subjects. The peripheral afferents responsible for the SBR included low-threshold cutaneous fibres. In the SBR-positive subjects, the late (R2) component of the blink reflex elicited by supraorbital nerve stimulation and the SBR facilitated each other when both responses were induced at the same time, but they each caused long-lasting inhibition in the other when one stimulus was given as a conditioning stimulus. The extent of inhibition was correlated with the size of the preceding SBR. In the SBR-negative subjects, simultaneous inhibition of R2 was observed when median nerve stimulation was applied as a conditioning stimulus. Brainstem excitability, as evaluated by blink-reflex recovery studies, did not differ between SBR-positive and SBR-negative subjects. Therefore, based on anatomical and physiological findings, it appears that the reflex pathways of the SBR and R2 converge within the brainstem and compete with each other, presumably by presynaptic inhibition at the premotor level, before entering the common blink-reflex pathway. The influence of median nerve stimulation upon tonic contraction of the orbicularis oculi muscle was studied to detect the latent SBR. There was not only a facilitatory period corresponding to the SBR but also an active inhibitory period (exteroceptive suppression), suggesting that the mechanism generating the SBR is not only influenced by blink-reflex volleys but also by active exteroceptive suppression. Thus, the SBR may appear as a result of integration of facilitatory and inhibitory mechanisms within the brainstem.