Neural representations of statistical and rule-based predictions in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is a disorder characterised by motor and vocal tics, which may represent habitual actions as a result of enhanced learning of associations between stimuli and responses (S-R). In this study, we investigated how adults with GTS and healthy controls (HC) learn two types of regularities in a sequence: statistics (non-adjacent probabilities) and rules (predefined order). Participants completed a visuomotor sequence learning task while EEG was recorded. To understand the neurophysiological underpinnings of these regularities in GTS, multivariate pattern analyses on the temporally decomposed EEG signal as well as sLORETA source localisation method were conducted. We found that people with GTS showed superior statistical learning but comparable rule-based learning compared to HC participants. Adults with GTS had different neural representations for both statistics and rules than HC adults; specifically, adults with GTS maintained the regularity representations longer and had more overlap between them than HCs. Moreover, over different time scales, distinct fronto-parietal structures contribute to statistical learning in the GTS and HC groups. We propose that hyper-learning in GTS is a consequence of the altered sensitivity to encode complex statistics, which might lead to habitual actions.

Resting network architecture of theta oscillations reflects hyper-learning of sensorimotor information in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics. It is associated with enhanced processing of stimulus-response associations, including a higher propensity to learn probabilistic stimulus-response contingencies (i.e. statistical learning), the nature of which is still elusive. In this study, we investigated the hypothesis that resting-state theta network organization is a key for the understanding of superior statistical learning in these patients. We investigated the graph-theoretical network architecture of theta oscillations in adult patients with Gilles de la Tourette syndrome and healthy controls during a statistical learning task and in resting states both before and after learning. We found that patients with Gilles de la Tourette syndrome showed a higher statistical learning score than healthy controls, as well as a more optimal (small-world-like) theta network before the task. Thus, patients with Gilles de la Tourette syndrome had a superior facility to integrate and evaluate novel information as a trait-like characteristic. Additionally, the theta network architecture in Gilles de la Tourette syndrome adapted more to the statistical information during the task than in HC. We suggest that hyper-learning in patients with Gilles de la Tourette syndrome is likely a consequence of increased sensitivity to perceive and integrate sensorimotor information leveraged through theta oscillation-based resting-state dynamics. The study delineates the neural basis of a higher propensity in patients with Gilles de la Tourette syndrome to pick up statistical contingencies in their environment. Moreover, the study emphasizes pathophysiologically endowed abilities in patients with Gilles de la Tourette syndrome, which are often not taken into account in the perception of this common disorder but could play an important role in destigmatization.

Perception-Action Integration Is Altered in Functional Movement Disorders.

BACKGROUND: Although functional neurological movement disorders (FMD) are characterized by motor symptoms, sensory processing has also been shown to be disturbed. However, how the integration of perception and motor processes, essential for the control of goal-directed behavior, is altered in patients with FMD is less clear. A detailed investigation of these processes is crucial to foster a better understanding of the pathophysiology of FMD and can systematically be achieved in the framework of the theory of event coding (TEC). OBJECTIVE: The aim was to investigate perception-action integration processes on a behavioral and neurophysiological level in patients with FMD. METHODS: A total of 21 patients and 21 controls were investigated with a TEC-related task, including concomitant electroencephalogram (EEG) recording. We focused on EEG correlates established to reflect perception-action integration processes. Temporal decomposition allowed to distinguish between EEG codes reflecting sensory (S-cluster), motor (R-cluster), and integrated sensory-motor processing (C-cluster). We also applied source localization analyses. RESULTS: Behaviorally, patients revealed stronger binding between perception and action, as evidenced by difficulties in reconfiguring previously established stimulus-response associations. Such hyperbinding was paralleled by a modulation of neuronal activity clusters, including reduced C-cluster modulations of the inferior parietal cortex and altered R-cluster modulations in the inferior frontal gyrus. Correlations of these modulations with symptom severity were also evident. CONCLUSIONS: Our study shows that FMD is characterized by altered integration of sensory information with motor processes. Relations between clinical severity and both behavioral performance and neurophysiological abnormalities indicate that perception-action integration processes are central and a promising concept for the understanding of FMD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Unsigned surprise but not reward magnitude modulates the integration of motor elements during actions.

It seems natural that motor responses unfold smoothly and that we are able to easily concatenate different components of movements to achieve goal-directed actions. Theoretical frameworks suggest that different motor features have to be bound to each other to achieve a coherent action. Yet, the nature of the "glue" (i.e., bindings) between elements constituting a motor sequence and enabling a smooth unfolding of motor acts is not well understood. We examined in how far motor feature bindings are affected by reward magnitude or the effects of an unsigned surprise signal. We show that the consistency of action file binding strength is modulated by unsigned surprise, but not by reward magnitude. On a conceptual and theoretical level, the results provide links between frameworks, which have until now not been brought into connection. In particular, theoretical accounts stating that only the unexpectedness (surprisingness) is essential for action control are connected to meta-control accounts of human action control.

A neurophysiological perspective on the integration between incidental learning and cognitive control.

Adaptive behaviour requires interaction between neurocognitive systems. Yet, the possibility of concurrent cognitive control and incidental sequence learning remains contentious. We designed an experimental procedure of cognitive conflict monitoring that follows a pre-defined sequence unknown to participants, in which either statistical or rule-based regularities were manipulated. We show that participants learnt the statistical differences in the sequence when stimulus conflict was high. Neurophysiological (EEG) analyses confirmed but also specified the behavioural results: the nature of conflict, the type of sequence learning, and the stage of information processing jointly determine whether cognitive conflict and sequence learning support or compete with each other. Especially statistical learning has the potential to modulate conflict monitoring. Cognitive conflict and incidental sequence learning can engage in cooperative fashion when behavioural adaptation is challenging. Three replication and follow-up experiments provide insights into the generalizability of these results and suggest that the interaction of learning and cognitive control is dependent on the multifactorial aspects of adapting to a dynamic environment. The study indicates that connecting the fields of cognitive control and incidental learning is advantageous to achieve a synergistic view of adaptive behaviour.

Modality-specific and modality-independent neural representations work in concert in predictive processes during sequence learning.

Probabilistic sequence learning supports the development of skills and enables predictive processing. It remains contentious whether visuomotor sequence learning is driven by the representation of the visual sequence (perceptual coding) or by the representation of the response sequence (motor coding). Neurotypical adults performed a visuomotor sequence learning task. Learning occurred incidentally as it was evidenced by faster responses to high-probability than to low-probability targets. To uncover the neurophysiology of the learning process, we conducted both univariate analyses and multivariate pattern analyses (MVPAs) on the temporally decomposed EEG signal. Univariate analyses showed that sequence learning modulated the amplitudes of the motor code of the decomposed signal but not in the perceptual and perceptual-motor signals. However, MVPA revealed that all 3 codes of the decomposed EEG contribute to the neurophysiological representation of the learnt probabilities. Source localization revealed the involvement of a wider network of frontal and parietal activations that were distinctive across coding levels. These findings suggest that perceptual and motor coding both contribute to the learning of sequential regularities rather than to a neither-nor distinction. Moreover, modality-specific encoding worked in concert with modality-independent representations, which suggests that probabilistic sequence learning is nonunitary and encompasses a set of encoding principles.

Theta Activity Dynamics during Embedded Response Plan Processing in Tourette Syndrome.

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder. Because motor signs are the defining feature of GTS, addressing the neurophysiology of motor processes is central to understanding GTS. The integration of voluntary motor processes is subject to so-called "binding problems", i.e., how different aspects of an action are integrated. This was conceptualized in the theory of event coding, in which 'action files' accomplish the integration of motor features. We examined the functional neuroanatomical architecture of EEG theta band activity related to action file processing in GTS patients and healthy controls. Whereas, in keeping with previous data, behavioral performance during action file processing did not differ between GTS and controls, underlying patterns of neural activity were profoundly different. Superior parietal regions (BA7) were predominantly engaged in healthy controls, but superior frontal regions (BA9, BA10) in GTS indicated that the processing of different motor feature codes was central for action file processing in healthy controls, whereas episodic processing was more relevant in GTS. The data suggests a cascade of cognitive branching in fronto-polar areas followed by episodic processing in superior frontal regions in GTS. Patients with GTS accomplish the integration of motor plans via qualitatively different neurophysiological processes.

Deterministic and probabilistic regularities underlying risky choices are acquired in a changing decision context.

Predictions supporting risky decisions could become unreliable when outcome probabilities temporarily change, making adaptation more challenging. Therefore, this study investigated whether sensitivity to the temporal structure in outcome probabilities can develop and remain persistent in a changing decision environment. In a variant of the Balloon Analogue Risk Task with 90 balloons, outcomes (rewards or balloon bursts) were predictable in the task's first and final 30 balloons and unpredictable in the middle 30 balloons. The temporal regularity underlying the predictable outcomes differed across three experimental conditions. In the deterministic condition, a repeating three-element sequence dictated the maximum number of pumps before a balloon burst. In the probabilistic condition, a single probabilistic regularity ensured that burst probability increased as a function of pumps. In the hybrid condition, a repeating sequence of three different probabilistic regularities increased burst probabilities. In every condition, the regularity was absent in the middle 30 balloons. Participants were not informed about the presence or absence of the regularity. Sensitivity to both the deterministic and hybrid regularities emerged and influenced risk taking. Unpredictable outcomes of the middle phase did not deteriorate this sensitivity. In conclusion, humans can adapt their risky choices in a changing decision environment by exploiting the statistical structure that controls how the environment changes.

Processing of embedded response plans is modulated by an interplay of frontoparietal theta and beta activity.

Even simple actions like opening a door require integration/binding and flexible reactivation of different motor elements. Yet, the neural mechanisms underlying the processing of such "embedded response plans" are largely elusive, despite theoretical frameworks, such as the theory of event coding, describing the involved cognitive processes. In a sample of n = 40 healthy participants, we combine time-frequency decomposition and various beamforming methods to examine the neurophysiological dynamics of such action plans, with special emphasis on the interplay of theta and beta frequency activity during the processing of these plans. We show that the integration and rule-guided reactivation of embedded response plans is modulated by a complex interplay of theta and beta activity. Pretrial beta-band activity (BBA) is related to different functional neuroanatomical structures that are activated in a consecutive fashion. Enhanced preparatory activity is positively associated with higher binding-related BBA in the precuneus/parietal areas, indicating that activity in the precuneus/parietal cortex facilitates the execution of an embedded action sequence. Increased preparation subsequently leads to reduced working memory retrieval demands. A cascading pattern of interactions between pretrial and within-trial activity indicates the importance of preparatory brain activity. The study shows that there are multiple roles of beta and theta oscillations associated with different functional neuroanatomical structures during the integration and reactivation of motor elements during actions.NEW & NOTEWORTHY Even simple actions like opening a door require integration/binding and flexible reactivation of different motor elements. Yet, the neural mechanisms underlying the processing of such "embedded response plans" are largely elusive. The study shows that there are multiple roles of beta and theta oscillations associated with different functional neuroanatomical structures during the integration and reactivation of motor elements during actions.

Protocol to decode representations from EEG data with intermixed signals using temporal signal decomposition and multivariate pattern-analysis.

The electroencephalogram (EEG) is one of the most widely used techniques in cognitive neuroscience. We present a protocol showing how to combine a temporal signal decomposition approach (RIDE, Residue iteration decomposition) with multivariate pattern analysis (MVPA) to obtain insights into the temporal stability of representations coded in distinct informational fractions of the EEG signal. In this protocol, we describe pre-processing of human EEG data, followed by the set-up and use of MATLAB-based toolboxes for RIDE and MVPA analysis. For complete details on the use and execution of this protocol, please refer to Petruo et al. (2021).

On the Role of Memory Representations in Action Control: Neurophysiological Decoding Reveals the Reactivation of Integrated Stimulus-Response Feature Representations.

Efficient response selection is essential to flexible, goal-directed behavior. Prominent theoretical frameworks such as the Theory of Event Coding and Binding and Retrieval in Action Control have provided insights regarding the dynamics of perception-action integration processes. According to Theory of Event Coding and Binding and Retrieval in Action Control, encoded representations of stimulus-response bindings influence later retrieval processes of these bindings. However, this concept still lacks conclusive empirical evidence. In the current study, we applied representational decoding to EEG data. On the behavioral level, the findings replicated binding effects that have been established in previous studies: The task performance was impaired when an event file had to be reconfigured. The EEG-decoding results showed that retrieval processes of stimulus-response bindings could be decoded using the representational content developed after the initial establishment of these stimulus-response bindings. We showed that stimulus-related properties became immediately reactivated when re-encountering the respective stimulus-response association. These reactivations were temporally stable. In contrast, representations of stimulus-response mappings revealed a transient pattern of activity and could not successfully be decoded directly after stimulus-response binding. Information detailing the bindings between stimuli and responses were also retrieved, but only after having been loaded into a memory system. The current study supports the notion that stimulus-response integration and memory processes are intertwined at multiple levels.

Multi-level decoding of task sets in neurophysiological data during cognitive flexibility.

Cognitive flexibility is essential to achieve higher level goals. Cognitive theories assume that the activation/deactivation of goals and task rules is central to understand cognitive flexibility. However, how this activation/deactivation dynamic is implemented on a neurophysiological level is unclear. Using EEG-based multivariate pattern analysis (MVPA) methods, we show that activation of relevant information occurs parallel in time at multiple levels in the neurophysiological signal containing aspects of stimulus-related processing, response selection, and motor response execution, and relates to different brain regions. The intensity with which task sets are activated and processed dynamically decreases and increases. The temporal stability of these activations could, however, hardly explain behavioral performance. Instead, task set deactivation processes associated with left orbitofrontal regions and inferior parietal regions selectively acting on motor response task sets are relevant. The study shows how propositions from cognitive theories stressing the importance task set activation/deactivation during cognitive flexibility are implemented on a neurophysiological level.

Increased scale-free and aperiodic neural activity during sensorimotor integration-a novel facet in Tourette syndrome.

Tourette syndrome is a common neurodevelopmental disorder defined by multiple motor and phonic tics. Tics in Tourette syndrome resemble spontaneously occurring movements in healthy controls and are therefore sometimes difficult to distinguish from these. Tics may in fact be mis-interpreted as a meaningful action, i.e. a signal with social content, whereas they lack such information and could be conceived a surplus of action or 'motor noise'. These and other considerations have led to a 'neural noise account' of Tourette syndrome suggesting that the processing of neural noise and adaptation of the signal-to-noise ratio during information processing is relevant for the understanding of Tourette syndrome. So far, there is no direct evidence for this. Here, we tested the 'neural noise account' examining 1/f noise, also called scale-free neural activity as well as aperiodic activity, in n = 74 children, adolescents and adults with Tourette syndrome and n = 74 healthy controls during task performance using EEG data recorded during a sensorimotor integration task. In keeping with results of a previous study in adults with Tourette syndrome, behavioural data confirmed that sensorimotor integration was also stronger in this larger Tourette syndrome cohort underscoring the relevance of perceptual-action processes in this disorder. More importantly, we show that 1/f noise and aperiodic activity during sensorimotor processing is increased in patients with Tourette syndrome supporting the 'neural noise account'. This implies that asynchronous/aperiodic neural activity during sensorimotor integration is stronger in patients with Tourette syndrome compared to healthy controls, which is probably related to abnormalities of GABAergic and dopaminergic transmission in these patients. Differences in 1/f noise and aperiodic activity between patients with Tourette syndrome and healthy controls were driven by high-frequency oscillations and not lower-frequency activity currently discussed to be important in the pathophysiology of tics. This and the fact that Bayesian statistics showed that there is evidence for the absence of a correlation between neural noise and clinical measures of tics, suggest that increased 1/f noise and aperiodic activity are not directly related to tics but rather represents a novel facet of Tourette syndrome.

Access to Procedural Memories After One Year: Evidence for Robust Memory Consolidation in Tourette Syndrome.

Tourette syndrome is a childhood-onset neurodevelopmental disorder characterized by motor and vocal tics. On the neural level, tics are thought to be related to the disturbances of the cortico-basal ganglia-thalamo-cortical loops, which also play an important role in procedural learning. Several studies have investigated the acquisition of procedural information and the access to established procedural information in TS. Based on these, the notion of procedural hyperfunctioning, i.e., enhanced procedural learning, has been proposed. However, one neglected area is the retention of acquired procedural information, especially following a long-term offline period. Here, we investigated the 5-hour and 1-year consolidation of two aspects of procedural memory, namely serial-order and probability-based information. Nineteen children with TS between the ages of 10 and 15 as well as 19 typically developing gender- and age-matched controls were tested on a visuomotor four-choice reaction time task that enables the simultaneous assessment of the two aspects. They were retested on the same task 5 hours and 1 year later without any practice in the offline periods. Both groups successfully acquired and retained the probability-based information both when tested 5 hours and then 1 year later, with comparable performance between the TS and control groups. Children with TS did not acquire the serial-order information during the learning phase; hence, retention could not be reliably tested. Our study showed evidence for short-term and long-term retention of one aspect of procedural memory, namely probability-based information in TS, whereas learning of serial-order information might be impaired in this disorder.

Lower-level associations in Gilles de la Tourette syndrome: Convergence between hyperbinding of stimulus and response features and procedural hyperfunctioning theories.

Gilles de la Tourette syndrome (GTS) can be characterized by enhanced cognitive functions related to creating, modifying and maintaining connections between stimuli and responses (S-R links). Specifically, two areas, procedural sequence learning and, as a novel finding, also event file binding, show converging evidence of hyperfunctioning in GTS. In this review, we describe how these two enhanced functions can be considered as cognitive mechanisms behind habitual behaviour, such as tics in GTS. Moreover, the presence of both procedural sequence learning and event file binding hyperfunctioning in the same disorder can be treated as evidence for their functional connections, even beyond GTS. Importantly though, we argue that hyperfunctioning of event file binding and procedural learning are not interchangeable: they have different time scales, different sensitivities to potential impairment in action sequencing and distinguishable contributions to the cognitive profile of GTS. An integrated theoretical account of hyperbinding and hyperlearning in GTS allows to formulate predictions for the emergence, activation and long-term persistence of tics in GTS.

Perception-action integration in young age-A cross-sectional EEG study.

Humans differ in their capacity for integrating perceived events and related actions. The "Theory of event coding" (TEC) conceptualizes how stimuli and actions are cognitively bound into a common functional representation (or "code"), known as the "event file". To date, however, the neural processes underlying the development of event file coding mechanisms across age are largely unclear. We investigated age-related neural changes of event file coding from late childhood to early adulthood, using EEG signal decompositions methods. We included a group of healthy participants (n = 91) between 10 and 30 years, performing an event file paradigm. Results of this study revealed age-related effects on event file coding processes both at the behavioural and the neurophysiological level. Performance accuracy data showed that event file unbinding und rebinding processes become more efficient from late childhood to early adulthood. These behavioural effects are reflected by age-related effects in two neurophysiological subprocesses associated with the superior parietal cortex (BA7) as revealed in the analyses using EEG signal decomposition. The first process entails mapping and association processes between stimulus and response; whereas, the second comprises inhibitory control subprocesses subserving the selection of the relevant motor programme amongst competing response options.

Adaptation to recent outcomes attenuates the lasting effect of initial experience on risky decisions.

Both primarily and recently encountered information have been shown to influence experience-based risky decision making. The primacy effect predicts that initial experience will influence later choices even if outcome probabilities change and reward is ultimately more or less sparse than primarily experienced. However, it has not been investigated whether extended initial experience would induce a more profound primacy effect upon risky choices than brief experience. Therefore, the present study tested in two experiments whether young adults adjusted their risk-taking behavior in the Balloon Analogue Risk Task after an unsignaled and unexpected change point. The change point separated early "good luck" or "bad luck" trials from subsequent ones. While mostly positive (more reward) or mostly negative (no reward) events characterized the early trials, subsequent trials were unbiased. In Experiment 1, the change point occurred after one-sixth or one-third of the trials (brief vs. extended experience) without intermittence, whereas in Experiment 2, it occurred between separate task phases. In Experiment 1, if negative events characterized the early trials, after the change point, risk-taking behavior increased as compared with the early trials. Conversely, if positive events characterized the early trials, risk-taking behavior decreased after the change point. Although the adjustment of risk-taking behavior occurred due to integrating recent experiences, the impact of initial experience was simultaneously observed. The length of initial experience did not reliably influence the adjustment of behavior. In Experiment 2, participants became more prone to take risks as the task progressed, indicating that the impact of initial experience could be overcome. Altogether, we suggest that initial beliefs about outcome probabilities can be updated by recent experiences to adapt to the continuously changing decision environment.

Neurophysiological and functional neuroanatomical coding of statistical and deterministic rule information during sequence learning.

Humans are capable of acquiring multiple types of information presented in the same information stream. It has been suggested that at least two parallel learning processes are important during learning of sequential patterns-statistical learning and rule-based learning. Yet, the neurophysiological underpinnings of these parallel learning processes are not fully understood. To differentiate between the simultaneous mechanisms at the single trial level, we apply a temporal EEG signal decomposition approach together with sLORETA source localization method to delineate whether distinct statistical and rule-based learning codes can be distinguished in EEG data and can be related to distinct functional neuroanatomical structures. We demonstrate that concomitant but distinct aspects of information coded in the N2 time window play a role in these mechanisms: mismatch detection and response control underlie statistical learning and rule-based learning, respectively, albeit with different levels of time-sensitivity. Moreover, the effects of the two learning mechanisms in the different temporally decomposed clusters of neural activity also differed from each other in neural sources. Importantly, the right inferior frontal cortex (BA44) was specifically implicated in visuomotor statistical learning, confirming its role in the acquisition of transitional probabilities. In contrast, visuomotor rule-based learning was associated with the prefrontal gyrus (BA6). The results show how simultaneous learning mechanisms operate at the neurophysiological level and are orchestrated by distinct prefrontal cortical areas. The current findings deepen our understanding on the mechanisms of how humans are capable of learning multiple types of information from the same stimulus stream in a parallel fashion.

Dissociation between two aspects of procedural learning in Tourette syndrome: Enhanced statistical and impaired sequence learning.

Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder that primarily affects the cortico-basal ganglia-thalamo-cortical (CBGTC) circuitry and is characterized by motor and vocal tics. Previous studies have found enhancement in procedural memory, which depends on the CBGTC circuitry and plays an important role in the learning and processing of numerous motor, social, and cognitive skills and habits. Based on these studies, procedural hyperfunctioning in TS has been proposed. However, the neurocognitive mechanism underlying such hyperfunctioning is poorly understood. Here, we investigated how two aspects of procedural learning, namely 1) frequency-based statistical learning and 2) order-based sequence learning, are affected in TS. Twenty-one children with TS between the ages of ten and fifteen as well as 21 typically developing controls were tested on a probabilistic sequence learning task that enables the parallel assessment of these two aspects. We found that children with TS showed enhanced sensitivity to statistical information but impaired sequence learning compared to typically developing children. The deconstruction of procedural memory suggests that procedural hyperfunctioning in TS may be supported by enhanced sensitivity to statistical information. These results can provide a potential path for improving therapy methods and skill-oriented educational programs for TS.