Efference Copy Research Articles

Corollary discharge dysfunction as a possible substrate of abnormal self-experiences in schizophrenia

Corollary discharge dysfunction as a possible substrate of abnormal self-experiences in schizophrenia

Corollary discharge function and speech processing in healthy controls

Corollary discharge function and speech processing in healthy controls

Role of locomotor efference copy in vertebrate gaze stabilization.

Vertebrate locomotion presents a major challenge for maintaining visual acuity due to head movements resulting from the intimate biomechanical coupling with the propulsive musculoskeletal system. Retinal image stabilization has been traditionally ascribed to the transformation of motion-related sensory feedback into counteracting ocular motor commands. However, extensive exploration of spontaneously active semi-intact and isolated brain/spinal cord preparations of the amphibian Xenopus laevis, have revealed that efference copies (ECs) of the spinal motor program that generates axial- or limb-based propulsion directly drive compensatory eye movements. During fictive locomotion in larvae, ascending ECs from rostral spinal central pattern generating (CPG) circuitry are relayed through a defined ascending pathway to the mid- and hindbrain ocular motor nuclei to produce conjugate eye rotations during tail-based undulatory swimming in the intact animal. In post-metamorphic adult frogs, this spinal rhythmic command switches to a bilaterally-synchronous burst pattern that is appropriate for generating convergent eye movements required for maintaining image stability during limb kick-based rectilinear forward propulsion. The transition between these two fundamentally different coupling patterns is underpinned by the emergence of altered trajectories in spino-ocular motor coupling pathways that occur gradually during metamorphosis, providing a goal-specific, morpho-functional plasticity that ensures retinal image stability irrespective of locomotor mode. Although the functional impact of predictive ECs produced by the locomotory CPG matches the spatio-temporal specificity of reactive sensory-motor responses, rather than contributing additively to image stabilization, horizontal vestibulo-ocular reflexes (VORs) are selectively suppressed during intense locomotor CPG activity. This is achieved at least in part by an EC-mediated attenuation of mechano-electrical encoding at the vestibular sensory periphery. Thus, locomotor ECs and their potential suppressive impact on vestibular sensory-motor processing, both of which have now been reported in other vertebrates including humans, appear to play an important role in the maintenance of stable vision during active body displacements.

Neurophysiological mechanisms of gait disturbance in advanced Parkinson's disease patients

AbstractThis review considers pathophysiological mechanisms of posture‐gait disturbances in Parkinson's disease (PD). Clinical studies have shown that posture‐gait disturbance attributes to the dysfunction of the whole neuraxis in addition to the musculoskeletal system. The cerebral cortex, basal ganglia (BG), cerebellum, brainstem, and spinal cord temporally and spatially integrate and coordinate multisensory feedback and efferent copies of the motor command. Therefore, the extensive repertoire of voluntary movements can be coupled with anticipatory and reactive postural adjustments to provide the framework for supporting and stabilizing the goal‐directed gait activity. Redundancies in the system allow adaptation and compensation through reward‐oriented and error‐based learning processes implemented through the BG and cerebellar pathways, respectively. However, the impairment of these systems in PD may considerably compromise the capacity to adapt and lead to maladaptive changes impairing posture‐gait control. When these impairments occur, the risk of falls can significantly increase, and interventions are required to reduce morbidity. The damage in dopamine (DA) neurons is the primary cause of PD. Insufficient DA supply in the striatum disturbs the operation of intrinsic networks in the BG. This also pathologically increases GABAergic BG output to the cerebral cortex and brainstem, resulting in functional disconnection of other structures from the BG. The disconnection makes PD patients disable to achieve habitually acquired automatized gait control. Moreover, Lewy body degeneration in most brain areas, particularly in cholinergic and other monoaminergic systems vulnerable to neurodegeneration, further disturbs posture‐gait control and alters non‐motor symptoms of PD.

Application of the Ratings of Perceived Exertion-Clamp Model to Examine the Effects of Joint Angle on the Time Course of Torque and Neuromuscular Responses During a Sustained, Isometric Forearm Flexion to Task Failure.

Abstract Smith, RW, Housh, TJ, Anders, JPV, Neltner, TJ, Arnett, JE, Schmidt, RJ, and Johnson, GO. Application of the ratings of perceived exertion-clamp model to examine the effects of joint angle on the time course of torque and neuromuscular responses during a sustained, isometric forearm flexion to task failure. J Strength Cond Res 37(5): 1023–1033, 2023—The present study used the ratings of perceived exertion (RPE)-clamp model during a sustained, isometric forearm flexion task to failure to determine the effects of joint angle on torque and neuromuscular responses. Twelve college-aged women performed two 3-second maximal voluntary isometric contractions at elbow joint angles (EJ) of 75°, 100°, and 125° before sustained, isometric, forearm flexions anchored to RPE = 7 to task failure (defined as RPE > 7, or the torque was reduced to zero) at EJ75, EJ100, and EJ125. The amplitude (AMP) and frequency (MPF) of the electromyographic (EMG) and mechanomyographic (MMG) signals from the biceps brachii were recorded. Repeated-measures ANOVAs and post hoc comparisons were used to examine differences across time and between joint angles for torque and neuromuscular parameters. A p-value ≤0.05 was considered significant. For each joint angle, there was a decrease (p < 0.05) in torque across the sustained, isometric task. Collapsed across joint angle, there were decreases (p < 0.001, = 0.378) in EMG AMP from 30 to 100% time to task failure. No changes were observed, however, for the other neuromuscular responses. The subjects voluntarily reduced torque to maintain RPE = 7 for each joint angle, and we hypothesize that RPE was maintained by afferent feedback from group III/IV motor neurons and corollary discharge (efferent copy of an internal signal that develops from central motor commands). The RPE-Clamp Model may be extended to athletes recovering from injury because a self-selected exercise intensity may be perceived as more enjoyable and promote adherence.

Predictive steering: integration of artificial motor signals in self-motion estimation.

The brain's computations for active and passive self-motion estimation can be unified with a single model that optimally combines vestibular and visual signals with sensory predictions based on efference copies. It is unknown whether this theoretical framework also applies to the integration of artificial motor signals, such as those that occur when driving a car, or whether self-motion estimation in this situation relies on sole feedback control. Here, we examined if training humans to control a self-motion platform leads to the construction of an accurate internal model of the mapping between the steering movement and the vestibular reafference. Participants (n = 15) sat on a linear motion platform and actively controlled the platform's velocity using a steering wheel to translate their body to a memorized visual target (motion condition). We compared their steering behavior to that of participants (n = 15) who remained stationary and instead aligned a nonvisible line with the target (stationary condition). To probe learning, the gain between the steering wheel angle and the platform or line velocity changed abruptly twice during the experiment. These gain changes were virtually undetectable in the displacement error in the motion condition, whereas clear deviations were observed in the stationary condition, showing that participants in the motion condition made within-trial changes to their steering behavior. We conclude that vestibular feedback allows not only the online control of steering but also a rapid adaptation to the gain changes to update the brain's internal model of the mapping between the steering movement and the vestibular reafference.NEW & NOTEWORTHY Perception of self-motion is known to depend on the integration of sensory signals and, when the motion is self-generated, the predicted sensory reafference based on motor efference copies. Here we show, using a closed-loop steering experiment with a direct coupling between the steering movement and the vestibular self-motion feedback, that humans are also able to integrate artificial motor signals, like the motor signals that occur when driving a car.

Perceived Exertion: Revisiting the History and Updating the Neurophysiology and the Practical Applications.

The perceived exertion construct creation is a landmark in exercise physiology and sport science. Obtaining perceived exertion is relatively easy, but practitioners often neglect some critical methodological issues in its assessment. Furthermore, the perceived exertion definition, neurophysiological basis, and practical applications have evolved since the perceived exertion construct's inception. Therefore, we revisit the careful work devoted by Gunnar Borg with psychophysical methods to develop the perceived exertion construct, which resulted in the creation of two scales: the rating of perceived exertion (RPE) and the category-ratio 10 (CR10). We discuss a contemporary definition that considers perceived exertion as a conscious perception of how hard, heavy, and strenuous the exercise is, according to the sense of effort to command the limbs and the feeling of heavy breathing (respiratory effort). Thus, other exercise-evoked sensations would not hinder the reported perceived exertion. We then describe the neurophysiological mechanisms involved in the perceived exertion genesis during exercise, including the influence of the peripheral feedback from the skeletal muscles and the cardiorespiratory system (i.e., afferent feedback) and the influence of efferent copies from the motor command and respiratory drive (i.e., corollary discharges), as well as the interaction between them. We highlight essential details practitioners should consider when using the RPE and CR10 scales, such as the perceived exertion definition, the original scales utilization, and the descriptors anchoring process. Finally, we present how practitioners can use perceived exertion to assess cardiorespiratory fitness, individualize exercise intensity prescription, predict endurance exercise performance, and monitor athletes' responses to physical training.

The Generic Inhibitory Function of Corollary Discharge in Motor Intention: Evidence from the Modulation Effects of Speech Preparation on the Late Components of Auditory Neural Responses.

The importance of action-perception loops necessitates efficient computations linking motor and sensory systems. Corollary discharge (CD), a concept in motor-to-sensory transformation, has been proposed to predict the sensory consequences of actions for efficient motor and cognitive control. The predictive computation has been assumed to realize via inhibiting sensory reafference when actions are executed. Continuous control throughout the course of action demands inhibitory function ubiquitously on all potential reafference when sensory consequences are not available before execution. However, the temporal and functional characteristics of CD are unclear. When does CD begin to operate? To what extent does CD inhibit sensory processes? How is the inhibitory function implemented in neural computation? Using a delayed articulation paradigm with three types of auditory probes (speech, nonspeech, and nonhuman sounds) in an electroencephalography experiment with 20 human participants (7 males), we found that preparing to speak without knowing what to say (general preparation) suppressed neural responses to each type of auditory probe, suggesting a generic inhibitory function of CD in motor intention. Moreover, power and phase coherence in low-frequency bands (1-8 Hz) were both suppressed, indicating that inhibition was mediated by dampening response amplitude and adding temporal variance to sensory processes. Furthermore, inhibition was stronger for sounds that humans can produce than nonhuman sounds, hinting that the generic inhibitory function of CD is regulated by the established motor-sensory associations. These results suggest a functional and temporal granularity of corollary discharge that mediates multifaceted computations in motor and cognitive control.

Neurobiological Signatures of Auditory False Perception and Phantom Perception as a Consequence of Sensory Prediction Errors.

Simple SummaryThe principle of Bayesian inference provides a theoretical framework for stable perception in numerous tasks, including sensory–perceptual tasks, sensorimotor, and motor tasks. Efference copy (EC) signals enable organisms to reduce cognitive loading by decreasing the sensory processing of their own actions. In the auditory domain, the sensorimotor prediction error is responsible for false perceptions, such as auditory hallucinations in schizophrenia, while sensory prediction error also leads to auditory phantom perception such as tinnitus. Attenuation of the N1 component in event-related potentials has been suggested as evidence for the integrity of the EC mechanism. The current study investigated the EC mechanism in auditory false perception and phantom perception as a consequence of sensory prediction errors. N1 attenuation failures were present in tinnitus patients with significant hearing impairment and in those with schizophrenia, indicating that phantom perception after sensory deprivation might lead to impairment in the EC mechanism. However, the corresponding neural representation with spatiotemporal patterns presented differently between patients with schizophrenia and tinnitus. Although the present study had several constraints, the results provide a new perspective on neurobiological aspects of abnormal auditory perception resulting from deficits in predictive coding.In this study, we hypothesized that top-down sensory prediction error due to peripheral hearing loss might influence sensorimotor integration using the efference copy (EC) signals as functional connections between auditory and motor brain areas. Using neurophysiological methods, we demonstrated that the auditory responses to self-generated sound were not suppressed in a group of patients with tinnitus accompanied by significant hearing impairment and in a schizophrenia group. However, the response was attenuated in a group with tinnitus accompanied by mild hearing impairment, similar to a healthy control group. The bias of attentional networks to self-generated sound was also observed in the subjects with tinnitus with significant hearing impairment compared to those with mild hearing impairment and healthy subjects, but it did not reach the notable disintegration found in those in the schizophrenia group. Even though the present study had significant constraints in that we did not include hearing loss subjects without tinnitus, these results might suggest that auditory deafferentation (hearing loss) may influence sensorimotor integration process using EC signals. However, the impaired sensorimotor integration in subjects with tinnitus with significant hearing impairment may have resulted from aberrant auditory signals due to sensory loss, not fundamental deficits in the reafference system, as the auditory attention network to self-generated sound is relatively well preserved in these subjects.

Multiple mechanisms mediate the suppression of motion vision during escape maneuvers in flying Drosophila

SummaryDuring voluntary behaviors, animals need to disable any reflexes that could interfere with the intended movements. With the optomotor response, flies stabilize a straight flight path by correcting for unintended deviations sensed as the panoramic motion of the surround. HS cells of the fly are thought to mediate optomotor responses to horizontal motion. During spontaneous flight turns, an efference copy acts on HS cells with the right sign to counteract the visual input elicited by the fly’s own behavior. Here, we investigated, whether looming-elicited turns in flying Drosophila have a similar effect on HS cells. We show that looming stimuli themselves can influence the processing of panoramic motion stimuli in HS cells and that an inhibitory efference copy suppresses excitatory motion responses during turns in both directions, but only in a subset of HS cells. Our findings support the notion that the processing of sensory information is finely tuned to behavioral context.

Shifts in the eye-centered frame of reference may underlie saccades, visual perception, and eye-hand coordination.

Conventional, computational theories limit the understanding of how action and perception are controlled. In an alternative scheme, the nervous system controls the values of physical and neurophysiological parameters that predetermine the choice of the spatial frames of reference (FRs) for action and perception. For example, all possible eye positions, Q, can be considered as comprising a spatial FR in which extraocular muscles (EOMs) stabilize gaze directions. The origin or referent point of this FR is a specific, threshold eye position, R, at which EOMs can be quiescent but activated depending on the difference between Q and R. Starting before eye motion, shifts in R cause displacement of the FR and resetting of the stable equilibrium position to which the eyes are forced to move. Rather than corollary discharge, the depiction of visual images integrated across the entire retina in the shifted spatial FR is responsible for remapping visual receptive fields and visual constancy. These suggestions are illustrated in computer models of saccades in the referent control framework in humans and monkeys. The existence of three types of visual RF remapping during saccades is suggested. Properly scaled, shifts in the R underlying a saccade are transmitted to motoneurons of arm muscles to guide reach-to-grasp motion in the same, eye-centered FR. Some predictions of the proposed control scheme have been verified and new tests are suggested. The scheme is applicable to several eye-hand coordination deficits including micrography in Parkinson's disease and explains why vision helps deafferented subjects diminish movement deficits.

Action-based predictions affect visual perception, neural processing, and pupil size, regardless of temporal predictability

Sensory consequences of one's own action are often perceived as less intense, and lead to reduced neural responses, compared to externally generated stimuli. Presumably, such sensory attenuation is due to predictive mechanisms based on the motor command (efference copy). However, sensory attenuation has also been observed outside the context of voluntary action, namely when stimuli are temporally predictable. Here, we aimed at disentangling the effects of motor and temporal predictability-based mechanisms on the attenuation of sensory action consequences. During fMRI data acquisition, participants (N = 25) judged which of two visual stimuli was brighter. In predictable blocks, the stimuli appeared temporally aligned with their button press (active) or aligned with an automatically generated cue (passive). In unpredictable blocks, stimuli were presented with a variable delay after button press/cue, respectively. Eye tracking was performed to investigate pupil-size changes and to ensure proper fixation. Self-generated stimuli were perceived as darker and led to less neural activation in visual areas than their passive counterparts, indicating sensory attenuation for self-generated stimuli independent of temporal predictability. Pupil size was larger during self-generated stimuli, which correlated negatively with the blood oxygenation level dependent (BOLD) response: the larger the pupil, the smaller the BOLD amplitude in visual areas. Our results suggest that sensory attenuation in visual cortex is driven by action-based predictive mechanisms rather than by temporal predictability. This effect may be related to changes in pupil diameter. Altogether, these results emphasize the role of the efference copy in the processing of sensory action consequences.

The effect of self-generated versus externally generated actions on timing, duration, and amplitude of blood oxygen level dependent response for visual feedback processing.

It has been widely assumed that internal forward models use efference copies to create predictions about the sensory consequences of our own actions. While these predictions have frequently been associated with a reduced blood oxygen level dependent (BOLD) response in sensory cortices, the timing and duration of the hemodynamic response for the processing of video feedback of self‐generated (active) versus externally generated (passive) movements is poorly understood. In the present study, we tested the hypothesis that predictive mechanisms for self‐generated actions lead to early and shorter neural processing compared with externally generated movements. We investigated active and passive movements using a custom‐made fMRI‐compatible movement device. Visual video feedback of the active and passive movements was presented in real time or with variable delays. Participants had to judge whether the feedback was delayed. Timing and duration of BOLD impulse response was calculated using a first (temporal derivative [TD]) and second‐order (dispersion derivative [DD]) Taylor approximation. Our reanalysis confirmed our previous finding of reduced BOLD response for active compared to passive movements. Moreover, we found positive effects of the TD and DD in the supplementary motor area, cerebellum, visual cortices, and subcortical structures, indicating earlier and shorter hemodynamic responses for active compared to passive movements. Furthermore, earlier activation in the putamen for active compared to passive conditions was associated with reduced delay detection performance. These findings indicate that efference copy‐based predictive mechanisms enable earlier processing of action feedback, which might have reduced the ability to detect short delays between action and feedback.

Directed information flow during laparoscopic surgical skill acquisition dissociated skill level and medical simulation technology

Virtual reality (VR) simulator has emerged as a laparoscopic surgical skill training tool that needs validation using brain–behavior analysis. Therefore, brain network and skilled behavior relationship were evaluated using functional near-infrared spectroscopy (fNIRS) from seven experienced right-handed surgeons and six right-handed medical students during the performance of Fundamentals of Laparoscopic Surgery (FLS) pattern of cutting tasks in a physical and a VR simulator. Multiple regression and path analysis (MRPA) found that the FLS performance score was statistically significantly related to the interregional directed functional connectivity from the right prefrontal cortex to the supplementary motor area with F (2, 114) = 9, p < 0.001, and R2 = 0.136. Additionally, a two-way multivariate analysis of variance (MANOVA) found a statistically significant effect of the simulator technology on the interregional directed functional connectivity from the right prefrontal cortex to the left primary motor cortex (F (1, 15) = 6.002, p = 0.027; partial η2 = 0.286) that can be related to differential right-lateralized executive control of attention. Then, MRPA found that the coefficient of variation (CoV) of the FLS performance score was statistically significantly associated with the CoV of the interregionally directed functional connectivity from the right primary motor cortex to the left primary motor cortex and the left primary motor cortex to the left prefrontal cortex with F (2, 22) = 3.912, p = 0.035, and R2 = 0.262. This highlighted the importance of the efference copy information from the motor cortices to the prefrontal cortex for postulated left-lateralized perceptual decision-making to reduce behavioral variability.

Approach to impaired corollary discharge in patients with schizophrenia: An analysis of self-induced somatosensory evoked potentials and fields.

BackgroundDifficulty in distinguishing between self-generated actions and those generated by others is a core feature of schizophrenia. This is thought to be underpinned by the failure of corollary discharge. However, few studies have investigated these events using somatosensory evoked potentials (SEPs) and somatosensory evoked magnetic fields (SEFs).MethodsThe study included 15 right-handed patients with schizophrenia and 16 healthy controls. SEP and SEF were elicited by electrical stimuli to the left median nerve at intervals of 1–3 s. In the external condition, stimuli were externally induced by a machine. In the self-condition, stimuli were induced by tapping the participants’ own right index finger. Peak amplitude at C4’ in SEP and root mean square in 10 channels on the right primary somatosensory area in SEF were analyzed.ResultsAlthough there was a significant main effect of condition at N20m, and a significant main effect of condition and group at P30m, no significant interactions of condition and group were found in either N20m or P30m. The post-hoc Wilcoxon signed-rank test revealed that the peak value of P30m in the external condition was significantly higher than that in the self-condition in the healthy control group only. In addition, there was a significant positive correlation between the peak value of P30m in the self-condition and a positive symptom score.ConclusionIn the current study, we did not find abnormalities of corollary discharge in primary sensory areas in patients with schizophrenia. Further investigations with more cases may reveal the possibility of corollary discharge disturbance in the primary sensory cortex.

Investigating distortions in perceptual stability during different self-movements using virtual reality.

Using immersive virtual reality (the HTC Vive Head Mounted Display), we measured both bias and sensitivity when making judgements about the scene stability of a target object during both active (self-propelled) and passive (experimenter-propelled) observer movements. This was repeated in the same group of 16 participants for three different observer-target movement conditions in which the instability of a target was yoked to the movement of the observer. We found that in all movement conditions that the target needed to move with (in the same direction) as the participant to be perceived as scene-stable. Consistent with the presence of additional available information (efference copy) about self-movement during active conditions, biases were smaller and sensitivities to instability were higher in these relative to passive conditions. However, the presence of efference copy was clearly not sufficient to completely eliminate the bias and we suggest that the presence of additional visual information about self-movement is also critical. We found some (albeit limited) evidence for correlation between appropriate metrics across different movement conditions. These results extend previous findings, providing evidence for consistency of biases across different movement types, suggestive of common processing underpinning perceptual stability judgements.

Chemosensation: Corollary discharge filters out self-generated chemical cues

Corollary discharge allows organisms to discriminate external sensory inputs from self-generated cues. However, the underlying synaptic and molecular mechanisms are not well understood. A new study has identified a tyraminergic corollary discharge signal that extrasynaptically modulates chemosensory neurons in Caenorhabditis elegans.

A corollary discharge mediates saccade-related inhibition of single units in mnemonic structures of the human brain

Despite the critical link between visual exploration and memory, little is known about how neuronal activity in the human mesial temporal lobe (MTL) is modulated by saccades. Here, we characterize saccade-associated neuronal modulations, unit-by-unit, and contrast them to image onset and to occipital lobe neurons. We reveal evidence for a corollary discharge (CD)-like modulatory signal that accompanies saccades, inhibiting/exciting a unique population of broad-/narrow-spiking units, respectively, before and during saccades and with directional selectivity. These findings comport well with the timing, directional nature, and inhibitory circuit implementation of a CD. Additionally, by linking neuronal activity to event-related potentials (ERPs), which are directionally modulated following saccades, we recontextualize the ERP associated with saccades as a proxy for both the strength of inhibition and saccade direction, providing a mechanistic underpinning for the more commonly recorded saccade-related ERP in the human brain.

Corollary discharge: Linking saccades and memory circuits in the human brain

A new study has found that, in primates with highly specialized visual systems, a corollary discharge of motor commands to make exploratory saccades arises in the midbrain, propagates to the thalamus, and then reaches hippocampal circuits in the depths of the temporal lobe where it shapes the making of memories.

Evolutionary convergence of a neural mechanism in the cavefish lateral line system.

Animals can evolve dramatic sensory functions in response to environmental constraints, but little is known about the neural mechanisms underlying these changes. The Mexican tetra, Astyanax mexicanus, is a leading model to study genetic, behavioral, and physiological evolution by comparing eyed surface populations and blind cave populations. We compared neurophysiological responses of posterior lateral line afferent neurons and motor neurons across A. mexicanus populations to reveal how shifts in sensory function may shape behavioral diversity. These studies indicate differences in intrinsic afferent signaling and gain control across populations. Elevated endogenous afferent activity identified a lower response threshold in the lateral line of blind cavefish relative to surface fish leading to increased evoked potentials during hair cell deflection in cavefish. We next measured the effect of inhibitory corollary discharges from hindbrain efferent neurons onto afferents during locomotion. We discovered that three independently derived cavefish populations have evolved persistent afferent activity during locomotion, suggesting for the first time that partial loss of function in the efferent system can be an evolutionary mechanism for neural adaptation of a vertebrate sensory system.