The Electrophysiological Correlates of Processing Self- and Externally Generated Sensations

In order to interact effectively with the world, the brain must distinguish between sensations which are caused by one’s own actions and external sensations that are caused by the environment. This may be achieved through an efference copy-based forward model mechanism in which a copy of the motor command is sent to the relevant sensory cortices with a prediction for the action’s sensory outcome. Studies show that neural and behavioural responses to self-initiated sensations are modulated relative to identical but externally presented stimuli. In EEG studies, self-generated auditory stimuli elicit smaller early ERP components (N1 and P2) than identical but externally generated stimuli. Furthermore, pre-movement neural activity (RP and LRP) may encode the action’s sensory consequences. Previous EEG studies have focussed largely on the auditory domain, with inconsistent results coming from experiments with visual stimuli. These studies also lacked optimal control conditions with passive movements and behavioural measures of perception. In this dissertation, three studies with healthy subjects (two published and one submitted to a journal) were carried out to examine questions related to the neural and behavioural correlates of the forward model mechanism. Study I examined the sensory ERPs elicited by visual stimuli that were triggered by active (self-initiated) and passive (involuntary; finger moved by device) movements. Stimulus perception was measured using an intensity judgement task. Visual N1 and P2 ERP amplitudes were reduced in the active condition, indicating suppression of the self-initiated sensory input. There was no effect of movement in the behavioural task. However, suppression of the P2 component was correlated with behavioural suppression. This component might reflect higher-level processes such as conscious evaluation of perceived intensity. In Study II, it was investigated whether RP and LRP encode information related to anticipating action-effect contingency and stimulus modality. When the action was followed immediately by a stimulus, RP differed between active and passive movements approximately 200 ms before the button press. This difference was not there when the sensory consequences were delayed by one second. Conversely, LRP encoded the movement type but not the action-effect contingency. This demonstrates a dissociation between RP and LRP, with RP representing higher-level processes, including anticipation of upcoming stimuli and LRP being related to low-level preparation for the movement execution. MVPA was also used to investigate whether action-effect prediction was represented across the whole scalp. Movement decoding (active vs passive) showed ramping accuracy in all conditions from around -800 ms onwards up to an accuracy of ∼ 85% at the movement. Accuracy was lower in the control than in the visual and auditory conditions approximately 200 ms before the movement. Sensory modality (visual vs auditory) was also decodable for both active and passive conditions. The active condition showed increased accuracy shortly before the movement. The results suggest that pre-movement EEG activity encodes action-feedback prediction. In Study III, in addition to active (executed here with a minimum latency of 700 ms) and passive movements, participants made quick movements (as quickly as possible in response to a tone cue). The active and quick conditions showed reduced N1-P2 amplitudes relative to the passive condition and did not significantly differ from each other. Active and quick also showed comparable LRP amplitudes, which were significantly greater than passive. However, though all three conditions showed a negative shift in RP, the quick condition had lower amplitudes than the active condition, indicating differences in motor preparation. This may be related to additional preparatory processes for executing the movement as quickly as possible after the cue. The results showed that, even though active and quick were prepared differently, this did not ultimately lead to differences in feedback processing. Taken together, this thesis offers a finer-grained specification of the efference copy mechanism. There was robust evidence of neural sensory suppression in the visual domain. For the first time, it was shown that action-feedback processing is similar between active and quick movements that nonetheless differ in movement initiation, intention to move, task demand and preparation time. The studies have also demonstrated the dissociation between RP and LRP, with the novel result that LRP is significantly reduced preceding involuntary movements. Furthermore, across three studies, there was evidence that RP encodes higher-level motor preparation processes, including feedback anticipation, which was specific to the active condition. The thesis also contributed an innovative analysis approach using MVPA, which demonstrated prediction for the action’s outcome before the movement, taking into account patterns of activity across the entire scalp. The studies presented in this thesis enhance our understanding of the efference copy mechanism, with potential implications for future translational work which could contribute to understanding the deficits associated with major symptoms of psychosis

Pre-movement event-related potentials and multivariate pattern of EEG encode action outcome prediction

Self-initiated movements are accompanied by an efference copy, a motor command sent from motor regions to the sensory cortices, containing a prediction of the movement's sensory outcome. Previous studies have proposed pre-motor event-related potentials (ERPs), including the readiness potential (RP) and its lateralized sub-component (LRP), as potential neural markers of action feedback prediction. However, it is not known how specific these neural markers are for voluntary (active) movements as compared to involuntary (passive) movements, which produce much of the same sensory feedback (tactile, proprioceptive) but are not accompanied by an efference copy. The goal of the current study was to investigate how active and passive movements are distinguishable from premotor electroencephalography (EEG), and to examine if this change of neural activity differs when participants engage in tasks that differ in their expectation of sensory outcomes. Participants made active (self-initiated) or passive (finger moved by device) finger movements that led to either visual or auditory stimuli (100 ms delay), or to no immediate contingency effects (control). We investigated the time window before the movement onset by measuring pre-movement ERPs time-locked to the button press. For RP, we observed an interaction between task and movement. This was driven by movement differences in the visual and auditory but not the control conditions. LRP conversely only showed a main effect of movement. We then used multivariate pattern analysis to decode movements (active vs. passive). The results revealed ramping decoding for all tasks from around −800 ms onwards up to an accuracy of approximately 85% at the movement. Importantly, similar to RP, we observed lower decoding accuracies for the control condition than the visual and auditory conditions, but only shortly (from −200 ms) before the button press. We also decoded visual vs. auditory conditions. Here, task is decodable for both active and passive conditions, but the active condition showed increased decoding shortly before the button press. Taken together, our results provide robust evidence that pre-movement EEG activity may represent action-feedback prediction in which information about the subsequent sensory outcome is encoded

Perception of self- and externally-generated visual stimuli: Evidence from EEG and behaviour

Associated paper: https://doi.org/10.1111/psyp.14295 This repository releases data that were recorded for a project where we asked participants to judge the intensity of auditory and visual stimuli presented following active or passive button presses. The repository contains group level ERP and behavioural data. In separate blocks, participants either pressed a button (active condition), or the button pulled the finger down by means of an electromagnet (passive condition). In each trial, the button press triggered a stimulus, followed by a second stimulus after a 500-1250ms delay. In auditory conditions, the stimuli were 1000Hz tones, while in visual conditions they were 250-pixel grey discs. Participants were asked to judge which of the stimuli was more intense. The first stimulus had a fixed intensity, while the second could have one of five different values. To assess behvavioural performance, we took the proportion of ‘second more intense’ answers and fitted psychometric functions to the data to derive the point of subjective equality (threshold) for each participant. ERPs were derived by time-locking to the button press

Differential effects of self-initiated, externally triggered, and passive movements on action-outcome processing: Insights from sensory and motor-preparatory ERPs

Self-initiated voluntary actions are different from externally triggered or passive movements. However, it remains unclear how these movements differentially affect action feedback processing and how they are prepared. Here we focus on the sensory and motor-preparatory ERPs. Participants made active (self-initiated, 700 ms lower limit), quick (respond to a cue as quickly as possible) and passive (finger moved by device) button presses that triggered visual stimuli. The active and quick conditions elicited lower visual N1-P2 peak-to-peak amplitudes than the passive condition but did not significantly differ from each other. For prestimulus ERPs (lateralized/readiness potential; L/RP), all conditions showed a negative shift in RP, with lower amplitudes in the quick than in the active condition. There were no significant differences between active and passive. For the LRP, the active and quick conditions showed a sharp deflection shortly before the button press. The amplitude of both conditions was significantly lower than passive around 100 ms before the movement. Our results suggest that active and quick movements might involve similar feedback prediction, even though they are prepared differently. They thus offer a finer-grained specification of the efference copy mechanism

Pre-movement event-related potentials and multivariate pattern of EEG encode action outcome prediction

Self-initiated movements are accompanied by an efference copy, a motor command sent from motor regions to the sensory cortices, containing a prediction of the movement's sensory outcome. Previous studies have proposed pre-motor event-related potentials (ERPs), including the readiness potential (RP) and its lateralized sub-component (LRP), as neural signatures of the efference copy. However, it is not known how specific these neural markers are for voluntary (active) movements as compared to involuntary (passive) movements, which produce much of the same sensory feedback (tactile, proprioceptive) but are not accompanied by an efference copy. The goal of the current study was to investigate how active and passive movements are distinguishable from premotor EEG, and to examine if this change of neural activity differs when participants engage in tasks that differ in their expectation of sensory outcomes. Participants made active (self-initiated) or passive (finger moved by device) finger movements that lead to either visual or auditory stimuli (100 ms delay), or to no immediate contingency effects (control). We investigated the time window before the movement onset by measuring pre-movement ERPs time-locked to the button press. For RP, we observed an interaction between task and movement. This was driven by movement differences in the visual and auditory but not the control conditions. LRP conversely only showed a main effect of movement. We then used multivariate pattern analysis (MVPA) to decode movements (active vs. passive). The results revealed ramping decoding for all tasks from around -800 ms onwards up to an accuracy of ∼ 85% at the movement. Importantly, similar to RP, we observed lower decoding accuracies for the control condition than the visual and auditory conditions, but only shortly (from -200 ms) before the button press. Here we provide robust evidence that pre-movement EEG activity may represent the efference copy of voluntary actions in which the information about the subsequent sensory outcome is encoded

Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

<p>Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.</p>