Corollary Discharge Signals Research Articles

A corollary discharge circuit in human speech

When we vocalize, our brain distinguishes self-generated sounds from external ones. A corollary discharge signal supports this function in animals; however, in humans, its exact origin and temporal dynamics remain unknown. We report electrocorticographic recordings in neurosurgical patients and a connectivity analysis framework based on Granger causality that reveals major neural communications. We find a reproducible source for corollary discharge across multiple speech production paradigms localized to the ventral speech motor cortex before speech articulation. The uncovered discharge predicts the degree of auditory cortex suppression during speech, its well-documented consequence. These results reveal the human corollary discharge source and timing with far-reaching implication for speech motor-control as well as auditory hallucinations in human psychosis.

Predictive Remapping in Neural Networks: A Model Based on Corollary Discharge Signals for Visual Continuity Across Saccades

Predictive Remapping in Neural Networks: A Model Based on Corollary Discharge Signals for Visual Continuity Across Saccades

Decoding Remapped Spatial Information in the Peri-Saccadic Period.

It has been suggested that, prior to a saccade, visual neurons predictively respond to stimuli that will fall in their receptive fields after completion of the saccade. This saccadic remapping process is thought to compensate for the shift of the visual world across the retina caused by eye movements. To map the timing of this predictive process in the brain, we recorded neural activity using electroencephalography during a saccade task. Human participants (male and female) made saccades between two fixation points while covertly attending to oriented gratings briefly presented at various locations on the screen. Data recorded during trials in which participants maintained fixation were used to train classifiers on stimuli in different positions. Subsequently, data collected during saccade trials were used to test for the presence of remapped stimulus information at the post-saccadic retinotopic location in the peri-saccadic period, providing unique insight into when remapped information becomes available. We found that the stimulus could be decoded at the remapped location ∼180 ms post-stimulus onset, but only when the stimulus was presented 100-200 ms before saccade onset. Within this range, we found that the timing of remapping was dictated by stimulus onset rather than saccade onset. We conclude that presenting the stimulus immediately before the saccade allows for optimal integration of the corollary discharge signal with the incoming peripheral visual information, resulting in a remapping of activation to the relevant post-saccadic retinotopic neurons.

Pre-saccadic shifts of attention in individuals diagnosed with schizophrenia.

Pathophysiological theories of schizophrenia (SZ) symptoms posit an abnormality in using predictions to guide behavior. One such prediction is based on imminent movements, via corollary discharge signals (CD) that relay information about planned movement kinematics to sensory brain regions. Empirical evidence suggests a reduced influence of sensorimotor predictions in individuals with SZ within multiple sensory systems, including in the visual system. One function of CD in the visual system is to selectively enhance visual sensitivity at the location of planned eye movements (pre-saccadic attention), thus enabling a prediction of the to-be-foveated stimulus. We expected pre-saccadic attention shifts to be less pronounced in individuals with SZ than in healthy controls (HC), resulting in unexpected sensory consequences of eye movements, which may relate to symptoms than can be explained in the context of altered allocation of attention. We examined this question by testing 30 SZ and 30 HC on a pre-saccadic attention task. On each trial participants made a saccade to a cued location in an array of four stimuli. A discrimination target that was either congruent or incongruent with the cued location was briefly presented after the cue, during saccade preparation. Pre-saccadic attention was quantified by comparing accuracy on congruent trials to incongruent trials within the interval preceding the saccade. Although SZs were less accurate overall, the magnitude of the pre-saccadic attention effect generally did not differ across groups nor show a convincing relationship with symptom severity. We did, however, observe that SZ had reduced pre-saccadic attention effects when the discrimination target (probe) was presented at early stages of saccade planning, when pre-saccadic attention effects first emerged in HC. These findings suggest generally intact pre-saccadic shifts of attention in SZ, albeit slightly delayed. Results contribute to our understanding of altered sensory predictions in people with schizophrenia.

Abnormal Oculomotor Corollary Discharge Signaling as a Trans-diagnostic Mechanism of Psychosis.

Corollary discharge (CD) signals are "copies" of motor signals sent to sensory areas to predict the corresponding input. They are a posited mechanism enabling one to distinguish actions generated by oneself vs external forces. Consequently, altered CD is a hypothesized mechanism for agency disturbances in psychosis. Previous studies have shown a decreased influence of CD signals on visual perception in individuals with schizophrenia-particularly in those with more severe positive symptoms. We therefore hypothesized that altered CD may be a trans-diagnostic mechanism of psychosis. We examined oculomotor CD (using the blanking task) in 49 participants with schizophrenia or schizoaffective disorder (SZ), 36 bipolar participants with psychosis (BPP), and 40 healthy controls (HC). Participants made a saccade to a visual target. Upon saccade initiation, the target disappeared and reappeared at a horizontally displaced position. Participants indicated the direction of displacement. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of pre-saccadic target to inform perception. Thus, multi-level modeling was used to examine the influence of target displacement and saccade landing site on displacement judgements. SZ and BPP were equally less sensitive to target displacement than HC. Moreover, regardless of diagnosis, SZ and BPP with more severe positive symptoms were more likely to rely on saccade landing site. These results suggest that altered CD may be a trans-diagnostic mechanism of psychosis.

A synaptic corollary discharge signal suppresses midbrain visual processing during saccade-like locomotion

In motor control, the brain not only sends motor commands to the periphery, but also generates concurrent internal signals known as corollary discharge (CD) that influence sensory information processing around the time of movement. CD signals are important for identifying sensory input arising from self-motion and to compensate for it, but the underlying mechanisms remain unclear. Using whole-cell patch clamp recordings from neurons in the zebrafish optic tectum, we discovered an inhibitory synaptic signal, temporally locked to spontaneous and visually driven locomotion. This motor-related inhibition was appropriately timed to counteract visually driven excitatory input arising from the fish’s own motion, and transiently suppressed tectal spiking activity. High-resolution calcium imaging revealed localized motor-related signals in the tectal neuropil and the upstream torus longitudinalis, suggesting that CD enters the tectum via this pathway. Together, our results show how visual processing is suppressed during self-motion by motor-related phasic inhibition. This may help explain perceptual saccadic suppression observed in many species.

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.

Tyraminergic corollary discharge filters reafferent perception in a chemosensory neuron

Interpreting sensory information requires its integration with the current behavior of the animal. However, how motor-related circuits influence sensory information processing is incompletely understood. Here, we report that current locomotor state directly modulates the activity of BAG CO2 sensory neurons in Caenorhabditis elegans. By recording neuronal activity in animals freely navigating CO2 landscapes, we found that during reverse crawling states, BAG activity is suppressed by tyraminergic corollary discharge signaling. We provide genetic evidence that tyramine released from the RIM reversal interneurons extrasynaptically activates the inhibitory chloride channel LGC-55 in BAG. Disrupting this pathway genetically leads to excessive behavioral responses to CO2 stimuli. Moreover, we find that LGC-55 signaling cancels out perception of self-produced CO2 and O2 stimuli when animals reverse into their own gas plume in ethologically relevant aqueous environments. Our results show that sensorimotor integration involves corollary discharge signals directly modulating chemosensory neurons.

Perceptual enhancement and suppression correlate with V1 neural activity during active sensing

Perception in multiple sensory modalities is an active process that involves exploratory behaviors. In humans and other primates, vision results from sensory sampling guided by saccadic eye movements. Saccades are known to modulate visual perception, and a corollary discharge signal associated with saccades appears to establish a sense of visual stability. Neural recordings have shown that saccades also modulate activity widely across the brain. To investigate the neural basis of saccadic effects on perception, simultaneous recordings from multiple neurons in area V1 were made as animals performed a contrast detection task. Perceptual and neural measures were compared when the animal made real saccades that brought a stimulus into V1 receptive fields and when simulated saccades were made (identical retinal stimulation but no eye movement). When real saccades were made and low spatial frequency stimuli were presented, we observed a reduction in both perceptual sensitivity and neural activity compared with simulated saccades; conversely, with higher spatial frequency stimuli, saccades increased visual sensitivity and neural activity. The performance of neural decoders, which used the activity of the population of simultaneously recorded neurons, showed saccade effects on sensitivity that mirrored the frequency-dependent perceptual changes, suggesting that the V1 population activity could support the perceptual effects. A minority of V1 neurons had significant choice probabilities, and the saccades decreased both average choice probability and pairwise noise correlations. Taken together, the findings suggest that a signal related to saccadic eye movements alters V1 spiking to increase the independence of spiking neurons and bias the system toward processing higher spatial frequencies, presumably to enhance object recognition. The effects of saccades on visual perception and noise correlations appear to parallel effects observed in other sensory modalities, suggesting a general principle of active sensory processing.

Oculomotor corollary discharge signaling is related to repetitive behavior in children with autism spectrum disorder.

Corollary discharge (CD) signals are “copies” of motor signals sent to sensory regions that allow animals to adjust sensory consequences of self-generated actions. Autism spectrum disorder (ASD) is characterized by sensory and motor deficits, which may be underpinned by altered CD signaling. We evaluated oculomotor CD using the blanking task, which measures the influence of saccades on visual perception, in 30 children with ASD and 35 typically developing (TD) children. Participants were instructed to make a saccade to a visual target. Upon saccade initiation, the presaccadic target disappeared and reappeared to the left or right of the original position. Participants indicated the direction of the jump. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of the presaccadic target and use it to inform perception. We used multilevel modeling to examine the influence of saccade landing site on trans-saccadic perceptual judgements. We found that, compared with TD participants, children with ASD were more sensitive to target displacement and less reliant on saccade landing site when spatial uncertainty of the post-saccadic target was high. This pattern was driven by ASD participants with less severe restricted and repetitive behaviors. These results suggest a relationship between altered CD signaling and core ASD symptoms.

Corollary discharge promotes a sustained motor state in a neural circuit for navigation.

Animals exhibit behavioral and neural responses that persist on longer timescales than transient or fluctuating stimulus inputs. Here, we report that Caenorhabditis elegans uses feedback from the motor circuit to a sensory processing interneuron to sustain its motor state during thermotactic navigation. By imaging circuit activity in behaving animals, we show that a principal postsynaptic partner of the AFD thermosensory neuron, the AIY interneuron, encodes both temperature and motor state information. By optogenetic and genetic manipulation of this circuit, we demonstrate that the motor state representation in AIY is a corollary discharge signal. RIM, an interneuron that is connected with premotor interneurons, is required for this corollary discharge. Ablation of RIM eliminates the motor representation in AIY, allows thermosensory representations to reach downstream premotor interneurons, and reduces the animal's ability to sustain forward movements during thermotaxis. We propose that feedback from the motor circuit to the sensory processing circuit underlies a positive feedback mechanism to generate persistent neural activity and sustained behavioral patterns in a sensorimotor transformation.

Embodied Predictions, Agency, and Psychosis.

Psychotic symptoms, i.e., hallucinations and delusions, involve gross departures from conscious apprehension of consensual reality; respectively, perceiving and believing things that, according to same culture peers, do not obtain. In schizophrenia, those experiences are often related to abnormal sense of control over one's own actions, often expressed as a distorted sense of agency (i.e., passivity symptoms). Cognitive and computational neuroscience have furnished an account of these experiences and beliefs in terms of the brain's generative model of the world, which underwrites inferences to the best explanation of current and future states, in order to behave adaptively. Inference then involves a reliability-based trade off of predictions and prediction errors, and psychotic symptoms may arise as departures from this inference process, either an over- or under-weighting of priors relative to prediction errors. Surprisingly, there is empirical evidence in favor of both positions. Relatedly, there is evidence for both an enhanced and a diminished sense of agency in schizophrenia. How can this be? We argue that there is more than one generative model in the brain, and that ego- and allo-centric models operate in tandem. In brief, ego-centric models implement corollary discharge signals that cancel out the effects of self-generated actions while allo-centric models compare several hypothesis regarding the causes of sensory inputs (including the self among the potential causes). The two parallel hierarchies give rise to different levels of agency, with ego-centric models subserving “feelings of agency” and allo-centric predictions giving rise to “judgements of agency.” Those two components are weighted according to their reliability and combined, generating a higher-level “sense of agency.” We suggest that in schizophrenia a failure of corollary discharges to suppress self-generated inputs results in the absence of a “feeling of agency” and in a compensatory enhancement of allo-centric priors, which might underlie hallucinations, delusions of control but also, under certain circumstances, the enhancement of “judgments of agency.” We discuss the consequences of such a model, and potential courses of action that could lead to its falsification.

Organization of Corollary Discharge Neurons in Monkey Medial Dorsal Thalamus.

A corollary discharge (CD) is a copy of a neuronal command for movement sent to other brain regions to inform them of the impending movement. In monkeys, a circuit from superior colliculus (SC) through medial-dorsal nucleus of the thalamus (MD) to frontal eye field (FEF) carries such a CD for saccadic eye movements. This circuit provides the clearest example of such internal monitoring reaching cerebral cortex. In this report we first investigated the functional organization of the critical MD relay by systematically recording neurons within a grid of penetrations. In two male rhesus macaque monkeys (Macaca mulatta), we found that lateral MD neurons carrying CD signals discharged before saccades to ipsilateral as well as contralateral visual fields instead of just contralateral fields, often had activity over large movement fields, and had activity from both central and peripheral visual fields. Each of these characteristics has been found in FEF, but these findings indicate that these characteristics are already present in the thalamus. These characteristics show that the MD thalamic relay is not passive but instead assembles inputs from the SC before transmission to cortex. We next determined the exact location of the saccade-related CD neurons using the grid of penetrations. The neurons occupy an anterior-posterior band at the lateral edge of MD, and we established this band in stereotaxic coordinates to facilitate future study of CD neurons. These observations reveal both the organizational features of the internal CD signals within the thalamus, and the location of the thalamic relay for those signals.SIGNIFICANCE STATEMENT A corollary discharge (CD) circuit within the brain keeps an internal record of physical movements. In monkeys and humans, one such CD keeps track of rapid eye movements, and in monkeys, a circuit carrying this CD extends from midbrain to cerebral cortex through a relay in the thalamus. This circuit provides guidance for eye movements, contributes to stable visual perception, and when defective, might be related to difficulties that schizophrenic patients have in recognizing their own movements. This report facilitates the comparison of the circuit in monkeys and humans, particularly for comparison of the location of the thalamic relay in monkeys and in humans.

Corollary Discharge Signaling and Repetitive Behavior in Children With Autism Spectrum Disorder

Sensory and motor deficits represent core features of autism spectrum disorder (ASD) and may contribute to restricted and repetitive behaviors (RRBs). Corollary discharge (CD) signals are “copies” of motor signals sent to sensory brain regions that allow organisms to suppress sensory consequences of self-generated action.

Temporal Aspects of Corollary Discharge Functioning in Adults With ASD

Motor and sensory abnormalities are features of autism spectrum disorder (ASD). Recently, we proposed that core symptoms of ASD may result from reduced attenuation of self-generated sensory information. Namely, corollary discharge (CD) signals allowing inhibition of neural responses to self-generated actions may be disturbed in ASD. Despite evidence for temporal processing deficits in ASD, the effects of temporal offset between action and perception are unknown.

Spatial updating of attention across eye movements: A neuro-computational approach.

While we are scanning our environment, the retinal image changes with every saccade. Nevertheless, the visual system anticipates where an attended target will be next and attention is updated to the new location. Recently, two different types of perisaccadic attentional updates were discovered: predictive remapping of attention before saccade onset (Rolfs, Jonikaitis, Deubel, & Cavanagh, 2011) and lingering of attention after saccade (Golomb, Chun, & Mazer, 2008; Golomb, Pulido, Albrecht, Chun, & Mazer, 2010). We here propose a neuro-computational model located in lateral intraparietal cortex based on a previous model of perisaccadic space perception (Ziesche & Hamker, 2011, 2014). Our model can account for both types of updating of attention at a neural-systems level. The lingering effect originates from the late updating of the proprioceptive eye-position signal and the remapping from the early corollary-discharge signal. We put these results in relationship to predictive remapping of receptive fields and show that both phenomena arise from the same simple, recurrent neural circuit. Thus, together with the previously published results, the model provides a comprehensive framework for discussing multiple experimental observations that occur around saccades.

Generalization of learned responses in the mormyrid electrosensory lobe.

Appropriate generalization of learned responses to new situations is vital for adaptive behavior. We provide a circuit-level account of generalization in the electrosensory lobe (ELL) of weakly electric mormyrid fish. Much is already known in this system about a form of learning in which motor corollary discharge signals cancel responses to the uninformative input evoked by the fish's own electric pulses. However, for this cancellation to be useful under natural circumstances, it must generalize accurately across behavioral regimes, specifically different electric pulse rates. We show that such generalization indeed occurs in ELL neurons, and develop a circuit-level model explaining how this may be achieved. The mechanism involves regularized synaptic plasticity and an approximate matching of the temporal dynamics of motor corollary discharge and electrosensory inputs. Recordings of motor corollary discharge signals in mossy fibers and granule cells provide direct evidence for such matching.

Structural Thalamofrontal Hypoconnectivity Is Related to Oculomotor Corollary Discharge Dysfunction in Schizophrenia.

By predicting sensory consequences of actions, humans can distinguish self-generated sensory inputs from those that are elicited externally. This is one mechanism by which we achieve a subjective sense of agency over our actions. Corollary discharge (CD) signals-"copies" of motor signals sent to sensory areas-permit such predictions, and CD abnormalities are a hypothesized mechanism for the agency disruptions in schizophrenia that characterize a subset of symptoms. Indeed, behavioral evidence of altered CD, including in the oculomotor system, has been observed in schizophrenia patients. A pathway projecting from the superior colliculus to the frontal eye fields (FEFs) via the mediodorsal thalamus (MD) conveys oculomotor CD associated with saccadic eye movements in nonhuman primates. This animal work provides a promising translational framework in which to investigate CD abnormalities in clinical populations. In the current study, we examined whether structural connectivity of this MD-FEF pathway relates to oculomotor CD functioning in schizophrenia. Twenty-two schizophrenia patients and 24 healthy control participants of both sexes underwent diffusion tensor imaging, and a large subset performed a trans-saccadic perceptual task that yields measures of CD. Using probabilistic tractography, we identified anatomical connections between FEF and MD and extracted indices of microstructural integrity. Patients exhibited compromised microstructural integrity in the MD-FEF pathway, which was correlated with greater oculomotor CD abnormalities and more severe psychotic symptoms. These data reinforce the role of the MD-FEF pathway in transmitting oculomotor CD signals and suggest that disturbances in this pathway may relate to psychotic symptom manifestation in patients.SIGNIFICANCE STATEMENT People with schizophrenia sometimes experience abnormalities in a sense of agency, which may stem from abnormal sensory predictions about their own actions. Consistent with this notion, the current study found reduced structural connectivity in patients with schizophrenia in a specific brain pathway found to transmit such sensorimotor prediction signals in nonhuman primates. Reduced structural connectivity was correlated with behavioral evidence for impaired sensorimotor predictions and psychotic symptoms.

Dopamine and eye movement control in Parkinson's disease: deficits in corollary discharge signals?

Movement in Parkinson’s disease (PD) is fragmented, and the patients depend on visual information in their behavior. This suggests that the patients may have deficits in internally monitoring their own movements. Internal monitoring of movements is assumed to rely on corollary discharge signals that enable the brain to predict the sensory consequences of actions. We studied early-stage PD patients (N = 14), and age-matched healthy control participants (N = 14) to examine whether PD patients reveal deficits in updating their sensory representations after eye movements. The participants performed a double-saccade task where, in order to accurately fixate a second target, the participant must correct for the displacement caused by the first saccade. In line with previous reports, the patients had difficulties in fixating the second target when the eye movement was performed without visual guidance. Furthermore, the patients had difficulties in taking into account the error in the first saccade when making a saccade toward the second target, especially when eye movements were made toward the side with dominant motor symptoms. Across PD patients, the impairments in saccadic eye movements correlated with the integrity of the dopaminergic system as measured with [123I]FP-CIT SPECT: Patients with lower striatal (caudate, anterior putamen, and posterior putamen) dopamine transporter binding made larger errors in saccades. This effect was strongest when patients made memory-guided saccades toward the second target. Our results provide tentative evidence that the motor deficits in PD may be partly due to deficits in internal monitoring of movements.

Neural Evidence of Hierarchical Cognitive Control during Haptic Processing: An fMRI Study.

Interacting with our immediate surroundings requires constant manipulation of objects. Dexterous manipulation depends on comparison between actual and predicted sensory input, with these predictions calculated by means of lower- and higher-order corollary discharge signals. However, there is still scarce knowledge about the hierarchy in the neural architecture supporting haptic monitoring during manipulation. The present study aimed to assess this issue focusing on the cross talk between lower-order sensory and higher-order associative regions. We used functional magnetic resonance imaging in humans during a haptic discrimination task in which participants had to judge whether a touched shape or texture corresponded to an expected stimulus whose name was previously presented. Specialized haptic regions identified with an independent localizer task did not differ between expected and unexpected conditions, suggesting their lack of involvement in tactile monitoring. When presented stimuli did not match previous expectations, the left supramarginal gyrus (SMG), middle temporal, and medial prefrontal cortices were activated regardless of the nature of the haptic mismatch (shape/texture). The left primary somatosensory area (SI) responded differently to unexpected shapes and textures in line with a specialized detection of haptic mismatch. Importantly, connectivity analyses revealed that the left SMG and SI were more functionally coupled during unexpected trials, emphasizing their interaction. The results point for the first time to a hierarchical organization in the neural substrates underlying haptic monitoring during manipulation with the SMG as a higher-order hub comparing actual and predicted somatosensory input, and SI as a lower-order site involved in the detection of more specialized haptic mismatch.