Event segmentation in ADHD: neglect of social information and deviant theta activity point to a mechanism underlying ADHD.

Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently diagnosed psychiatric conditions in children and adolescents. Although the symptoms appear to be well described, no coherent conceptual mechanistic framework integrates their occurrence and variance and the associated problems that people with ADHD face. Aims: The current study proposes that altered event segmentation processes provide a novel mechanistic framework for understanding deficits in ADHD. Methods: Adolescents with ADHD and neurotypically developing (NT) peers watched a short movie and were then asked to indicate the boundaries between meaningful segments of the movie. Concomitantly recorded electroencephalography (EEG) data were analysed for differences in frequency band activity and effective connectivity between brain areas. Results: Compared with their NT peers, the ADHD group showed less dependence of their segmentation behaviour on social information, indicating that they did not consider social information to the same extent as their unaffected peers. This divergence was accompanied by differences in EEG theta band activity and a different effective connectivity network architecture at the source level. Specifically, NT adolescents primarily showed error signalling in and between the left and right fusiform gyri related to social information processing, which was not the case in the ADHD group. For the ADHD group, the inferior frontal cortex associated with attentional sampling served as a hub instead, indicating problems in the deployment of attentional control. Conclusions: This study shows that adolescents with ADHD perceive events differently from their NT peers, in association with a different brain network architecture that reflects less adaptation to the situation and problems in attentional sampling of environmental information. The results call for a novel conceptual view of ADHD, based on event segmentation theory.

Neural connectivity patterns explain why adolescents perceive the world as moving slow.

That younger individuals perceive the world as moving slower than adults is a familiar phenomenon. Yet, it remains an open question why that is. Using event segmentation theory, electroencephalogram (EEG) beamforming and nonlinear causal relationship estimation using artificial neural network methods, we studied neural activity while adolescent and adult participants segmented a movie. We show when participants were instructed to segment a movie into meaningful units, adolescents partitioned incoming information into fewer encapsulated segments or episodes of longer duration than adults. Importantly, directed communication between medial frontal and lower-level perceptual areas and between occipito-temporal regions in specific neural oscillation spectrums explained behavioral differences between groups. Overall, the study reveals that a different organization of directed communication between brain regions and inefficient transmission of information between brain regions are key to understand why younger people perceive the world as moving slow.

Neurophysiological effective network connectivity supports a threshold-dependent management of dynamic working memory gating.

To facilitate goal-directed actions, effective management of working memory (WM) is crucial, involving a hypothesized WM "gating mechanism." We investigate the underlying neural basis through behavioral modeling and connectivity assessments between neuroanatomical regions linked to theta, alpha, and beta frequency bands. We found opposing, threshold-dependent mechanisms governing WM gate opening and closing. Directed beta band connectivity in the parieto-frontal and parahippocampal-occipital networks was crucial for threshold-dependent WM gating dynamics. Fronto-parahippocampal connectivity in the theta band was also notable for both gating processes, although weaker than that in the beta band. Distinct roles for theta, beta, and alpha bands emerge in maintaining information in WM and shielding against interference, whereby alpha band activity likely acts as a "gatekeeper" supporting processes reflected by beta and theta band activity. The study shows that the decision criterion for WM gate opening/closing relies on concerted interplay within neuroanatomical networks defined by beta and theta band activities.

The Ability to Voluntarily Regulate Theta Band Activity Affects How Pharmacological Manipulation of the Catecholaminergic System Impacts Cognitive Control.

BACKGROUND: The catecholaminergic system influences response inhibition, but the magnitude of the impact of catecholaminergic manipulation is heterogeneous. Theoretical considerations suggest that the voluntary modulability of theta band activity can explain this variance. The study aimed to investigate to what extent interindividual differences in catecholaminergic effects on response inhibition depend on voluntary theta band activity modulation. METHODS: A total of 67 healthy adults were tested in a randomized, double-blind, cross-over study design. At each appointment, they received a single dose of methylphenidate or placebo and performed a Go/Nogo task with stimuli of varying complexity. Before the first appointment, the individual's ability to modulate theta band activity was measured. Recorded EEG data were analyzed using temporal decomposition and multivariate pattern analysis. RESULTS: Methylphenidate effects and voluntary modulability of theta band activity showed an interactive effect on the false alarm rates of the different Nogo conditions. The multivariate pattern analysis revealed that methylphenidate effects interacted with voluntary modulability of theta band activity at a stimulus processing level, whereas during response selection methylphenidate effects interacted with the complexity of the Nogo condition. CONCLUSIONS: The findings reveal that the individual's theta band modulability affects the responsiveness of an individual's catecholaminergic system to pharmacological modulation. Thus, the impact of pharmacological manipulation of the catecholaminergic system on cognitive control most likely depends on the existing ability to self-modulate relevant brain oscillatory patterns underlying the cognitive processes being targeted by pharmacological modulations.

The temporal dynamics of how the brain structures natural scenes.

Individuals organize the evolving stream of events in their environment by partitioning it into discrete units. Event segmentation theory (EST) provides a cognitive explanation for the process of this partitioning. Critically, the underlying time-resolved neural mechanisms are not understood, and thus a central conceptual aspect of how humans implement this central ability is missing. To gain better insight into the fundamental temporal dynamics of event segmentation, EEG oscillatory activity was measured while participants watched a narrative video and partitioned the movie into meaningful segments. Using EEG beamforming methods, we show that theta, alpha, and beta band activity in frontal, parietal, and occipital areas, as well as their interactions, reflect critical elements of the event segmentation process established by EST. In sum, we see a mechanistic temporal chain of processes that provides the neurophysiological basis for how the brain partitions and structures continuously evolving scenes and points to an integrated system that organizes the various subprocesses of event segmentation. This study thus integrates neurophysiology and cognitive theory to better understand how the human brain operates in rather variable and unpredictable situations. Therefore, it represents an important step toward studying neurophysiological dynamics in ecologically valid and naturalistic settings and, in doing so, addresses a critical gap in knowledge regarding the temporal dynamics of how the brain structures natural scenes.

Interplay between alpha and theta band activity enables management of perception-action representations for goal-directed behavior.

Goal-directed behavior requires integrated mental representations of perceptions and actions. The neurophysiological underpinnings of these processes, however, are not yet understood. It is particularly undetermined, which oscillatory activities in which brain regions are involved in the management of perception-action representations. We examine this question with a focus on response inhibition processes and show that the dynamics of perception-action representations reflected in theta band activity (TBA) are particularly evident in the supplementary motor area and the occipito-temporal cortex. Mental representations coded in alpha band activity (ABA) during perception-action integration are associated with the occipito-temporal cortex. Crucially, perception-action representations are exchanged between theta and alpha frequency bands. The results imply that ABA functions as dynamic top-down control over binding, retrieval and reconfiguration processes during response inhibition, which in turn are reflected by TBA. Our study thus highlights how the interplay of oscillatory activity enables the management of perception-action representations for goal-directed behavior.

Perception-action integration during inhibitory control is reflected in a concomitant multi-region processing of specific codes in the neurophysiological signal.

The integration of perception and action has long been studied in psychological science using overarching cognitive frameworks. Despite these being very successful in explaining perception-action integration, little is known about its neurophysiological and especially the functional neuroanatomical foundations. It is unknown whether distinct brain structures are simultaneously involved in the processing of perception-action integration codes and also to what extent demands on perception-action integration modulate activities in these structures. We investigate these questions in an EEG study integrating temporal and ICA-based EEG signal decomposition with source localization. For this purpose, we used data from 32 healthy participants who performed a 'TEC Go/Nogo' task. We show that the EEG signal can be decomposed into components carrying different informational aspects or processing codes relevant for perception-action integration. Importantly, these specific codes are processed independently in different brain structures, and their specific roles during the processing of perception-action integration differ. Some regions (i.e., the anterior cingulate and insular cortex) take a 'default role' because these are not modulated in their activity by demands or the complexity of event file coding processes. In contrast, regions in the motor cortex, middle frontal, temporal, and superior parietal cortices were not activated by 'default' but revealed modulations depending on the complexity of perception-action integration (i.e., whether an event file has to be reconfigured). Perception-action integration thus reflects a multi-region processing of specific fractions of information in the neurophysiological signal. This needs to be taken into account when further developing a cognitive science framework detailing perception-action integration.

The Effects of Different Theta and Beta Neurofeedback Training Protocols on Cognitive Control in ADHD.

Neurofeedback (NF) is an important treatment for attention deficit/hyperactivity disorder (ADHD). In ADHD, cognitive control deficits pose considerable problems to patients. However, NF protocols are not yet optimized to enhance cognitive control alongside with clinical symptoms, partly because they are not driven by basic cognitive neuroscience. In this study, we evaluated different EEG theta and/or beta frequency band NF protocols designed to enhance cognitive control. Participants were n = 157 children and adolescents, n = 129 of them were patients with ADHD (n = 28 typically developing (TD) controls). Patients with ADHD were divided into five groups in the order of referral, with four of them taking part in different NF protocols systematically varying theta and beta power. The fifth ADHD group and the TD group did not undergo NF. All NF protocols resulted in reductions of ADHD symptoms. Importantly, only when beta frequencies were enhanced during NF (without any theta regulation or in combination with theta upregulation), consistent enhancing effects in both response inhibition and conflict control were achieved. The theta/beta NF protocol most widely used in clinical settings revealed comparatively limited effects. Enhancements in beta band activity are key when aiming to improve cognitive control functions in ADHD. This calls for a change in the use of theta/beta NF protocols and shows that protocols differing from the current clinical standard are effective in enhancing important facets of cognitive control in ADHD. Further studies need to examine regulation data within the neurofeedback sessions to provide more information about the mechanisms underlying the observed effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s41465-022-00255-6.

Cognitive science theory-driven pharmacology elucidates the neurobiological basis of perception-motor integration.

An efficient integration of sensory and motor processes is crucial to goal-directed behavior. Despite this high relevance, and although cognitive theories provide clear conceptual frameworks, the neurobiological basis of these processes remains insufficiently understood. In a double-blind, randomized placebo-controlled pharmacological study, we examine the relevance of catecholamines for perception-motor integration processes. Using EEG data, we perform an in-depth analysis of the underlying neurophysiological mechanisms, focusing on sensorimotor integration processes during response inhibition. We show that the catecholaminergic system affects sensorimotor integration during response inhibition by modulating the stability of the representational content. Importantly, catecholamine levels do not affect the stability of all aspects of information processing during sensorimotor integration, but rather-as suggested by cognitive theory-of specific codes in the neurophysiological signal. Particularly fronto-parietal cortical regions are associated with the identified mechanisms. The study shows how cognitive science theory-driven pharmacology can shed light on the neurobiological basis of perception-motor integration and how catecholamines affect specific information codes relevant to cognitive control.

Pre-trial fronto-occipital electrophysiological connectivity affects perception-action integration in response inhibition.

Inhibition of inappropriate behavior is relevant in many everyday situations. Nevertheless, the mechanisms that induce response inhibition based on sensory information and what influences these mechanisms are not entirely understood. We examined neurophysiological processes of perception-action integration in response inhibition and the impact of the pre-trial neurophysiological functional connectivity state in the theta and alpha band on these integration processes. The study was motivated by the Theory of Event Coding framework. Within the trial, fronto-medial theta band activity and occipital alpha band activity revealed an opposing interplay depending on the necessity of (re-)binding event files, i.e., the disintegration and recombination of stimulus-response associations, during response inhibition. When response inhibition required the reconfiguration of event files, this was associated with increased theta band activity but lower alpha band activity, and vice versa for the retrieval of event files. Notably, the most substantial impact of pre-trial connectivity on the within-trial event file binding effect (the difference between conditions that require reconfiguration and those that do not) during response inhibition occurred between fronto-medial areas and areas of the ventral stream in the theta frequency band. This suggests a preparatory top-down control of sensory areas before stimulus presentation. Increased pre-trial connectivity was associated with a decreased event file binding effect in the alpha frequency band and an increased event file binding effect in the theta frequency band during response inhibition. This implies an impact of the pre-trial functional connectivity state on inhibitory gating processes of relevant information and event file (re-)binding during response inhibition. The study shows how perception-action integration during response inhibition is affected by preceding transient neurophysiological connectivity states.

Alpha and Theta Bands Dynamics Serve Distinct Functions during Perception-Action Integration in Response Inhibition.

The ability to inhibit responses is central for situational behavior. However, the mechanisms how sensory information is used to inform inhibitory control processes are incompletely understood. In the current study, we examined neurophysiological processes of perception-action integration in response inhibition using the theory of event coding as a conceptual framework. Based on theoretical considerations, we focused on theta and alpha band activity in close connection to the functional neuroanatomical level using EEG beamforming. Moreover, we performed a network-based analysis of theta and alpha band activity. We show a seesaw-like relationship between medial and superior frontal cortex theta band activity and frontoparietal cortex alpha band activity during perception-action integration in response inhibition, depending on the necessity to reconfigure perception-action associations. When perception-action integration was more demanding, because perception-action associations (bindings) have to be reconfigured, there was an increase of theta and a decrease of alpha band activity. Vice versa, when there was no need to reconfigure perception-action bindings, theta band activity was low and alpha band activity was high. However, theta band processes seem to be most important for perception-action integration in response inhibition, because only the sensor-level network organization of theta band activity showed variations depending on the necessity to reconfigure perception-action associations. When no reconfiguration was necessary, the network architecture was more small-world-like, likely enabling efficient processing. When reconfigurations were necessary, the network organization becomes more random. These differences were particularly strong for fractions of the neurophysiological signal supposed to reflect response selection processes.

Feedback-Based Learning of Timing in Attention-Deficit/Hyperactivity Disorder and Neurofibromatosis Type 1.

OBJECTIVE: Patients with Neurofibromatosis Type 1 (NF1) frequently display symptoms resembling those of Attention Deficit/Hyperactivity Disorder (ADHD). Importantly, these disorders are characterised by distinct changes in the dopaminergic system, which plays an important role in timing performance and feedback-based adjustments in timing performance. In a transdiagnostic approach, we examine how far NF1 and ADHD show distinct or comparable profiles of timing performance and feedback-based adjustments in timing. METHOD: We examined time estimation and learning processes in healthy control children (HC), children with ADHD with predominantly inattentive symptoms and those with NF1 using a feedback-based time estimation paradigm. RESULTS: Healthy controls consistently responded closer to the correct time window than both patient groups, were less variable in their reaction times and displayed intact learning-based adjustments across time. The patient groups did not differ from each other regarding the number of in-time responses. In ADHD patients, the performance was rather unstable across time. No performance changes could be observed in patients with NF1 across the entire task. CONCLUSIONS: Children with ADHD and NF1 differ in feedback learning-based adjustments of time estimation processes. ADHD is characterised by behavioural fluctuations during the learning process. These are likely to be associated with inefficiencies in the dopaminergic system. NF1 is characterised by impairments of feedback learning which could be due to various neurotransmitter alterations occurring in addition to deficits in dopamine synthesis. Results show that despite the strong overlap in clinical phenotype and neuropsychological deficits between NF1 and ADHD, the underlying cognitive mechanisms are different.

Neural dynamics of stimulus-response representations during inhibitory control.

The investigation of action control processes is one major field in cognitive neuroscience and several theoretical frameworks have been proposed. One established framework is the "Theory of Event Coding" (TEC). However, only rarely, this framework has been used in the context of response inhibition and how stimulus-response association or binding processes modulate response inhibition performance. Particularly the neural dynamics of stimulus-response representations during inhibitory control are elusive. To address this, we examined n = 40 healthy controls and combined temporal EEG signal decomposition with source localization and temporal generalization multivariate pattern analysis (MVPA). We show that overlaps in features of stimuli used to trigger either response execution or inhibition compromised task performance. According to TEC, this indicates that binding processes in event file representations impact response inhibition through partial repetition costs. In the EEG data, reconfiguration of event files modulated processes in time windows well-known to reflect distinct response inhibition mechanisms. Crucially, event file coding processes were only evident in a specific fraction of neurophysiological activity associated with the inferior parietal cortex (BA40). Within that specific fraction of neurophysiological activity, the decoding of the dynamics of event file representations using temporal generalization MVPA suggested that event file representations are stable across several hundred milliseconds, and that event file coding during inhibitory control is reflected by a sustained activation pattern of neural dynamics.NEW & NOTEWORTHY The "mental representation" of how stimulus input translate into the appropriate response is central for goal-directed behavior. However, little is known about the dynamics of such representations on the neurophysiological level when it comes to the inhibition of motor processes. This dynamic is shown in the current study.

Pushing to the Limits: What Processes during Cognitive Control are Enhanced by Reaction-Time Feedback?

To respond as quickly as possible in a given task is a widely used instruction in cognitive neuroscience; however, the neural processes modulated by this common experimental procedure remain largely elusive. We investigated the underlying neurophysiological processes combining electroencephalography (EEG) signal decomposition (residue iteration decomposition, RIDE) and source localization. We show that trial-based response speed instructions enhance behavioral performance in conflicting trials, but slightly impair performance in nonconflicting trials. The modulation seen in conflicting trials was found at several coding levels in EEG data using RIDE. In the S-cluster N2 time window, this modulation was associated with modulated activation in the posterior cingulate cortex and the superior frontal gyrus. Furthermore, in the C-cluster P3 time window, this modulation was associated with modulated activation in the middle frontal gyrus. Interestingly, in the R-cluster P3 time window, this modulation was strongest according to statistical effect sizes, associated with modulated activity in the primary motor cortex. Reaction-time feedback mainly modulates response motor execution processes, whereas attentional and response selection processes are less affected. The study underlines the importance of being aware of how experimental instructions influence the behavior and neurophysiological processes.

Resting theta activity is associated with specific coding levels in event-related theta activity during conflict monitoring.

Brain electrical activity in the theta frequency band is essential for cognitive control (e.g., during conflict monitoring), but is also evident in the resting state. The link between resting state theta activity and its relevance for theta-related neural mechanisms during cognitive control is still undetermined. Yet, theoretical considerations suggest that there may be a connection. To examine the link between resting state theta activity and conflict-related theta activity, we combined temporal EEG signal decomposition methods with time-frequency decomposition and beamforming methods in N = 86 healthy participants. Results indicate that resting state theta activity is closely associated with the strength of conflict-related neural activity at the level of ERPs and total theta power (consisting of phase-locked and nonphase-locked aspects of theta activity). The data reveal that resting state theta activity is related to a specific aspect of conflict-related theta activity, mainly in superior frontal regions and in the supplemental motor area (SMA, BA6) in particular. The signal decomposition showed that only stimulus-related, but not motor-response-related coding levels in the EEG signal and the event-related total theta activity were associated with resting theta activity. This specificity of effects may explain why the association between resting state theta activity and overt conflict monitoring performance may not be as strong as often assumed. The results suggest that resting state theta activity is particularly important to consider for input integration processes during cognitive control.

Learning Experience Reverses Catecholaminergic Effects on Adaptive Behavior.

BACKGROUND: Catecholamines are important for cognitive control and the ability to adapt behavior (e.g., after response errors). A prominent drug that modulates the catecholaminergic system is methylphenidate. On the basis of theoretical consideration, we propose that the effects of methylphenidate on behavioral adaptation depend on prior learning experience. METHODS: In a double-blind, randomized, placebo-controlled crossover study design, we examined the effect of methylphenidate (0.25 mg/kg) on post error behavioral adaptation processes in a group of n = 43 healthy young adults. Behavioral adaptation processes were examined in a working memory, modulated response selection task. The focus of the analysis was on order effects within the crossover study design to evaluate effects of prior learning/task experience. RESULTS: The effect of methylphenidate/placebo on post-error behavioral adaptation processes reverses depending on prior task experience. When there was no prior experience with the task, methylphenidate increased post-error slowing and thus intensified behavioral adaptation processes. However, when there was prior task experience, (i.e., when the placebo session was conducted first in the crossover design), methylphenidate even decreased post-error slowing and behavioral adaptation. Effect sizes were large and the power of the observed effects was higher than 95%. CONCLUSIONS: The data suggest that catecholaminergic effects on cognitive control functions vary as a function of prior learning/task experience. The data establish a close link between learning/task familiarization and catecholaminergic effects for executive functions, which has not yet been studied, to our knowledge, but is of considerable clinical relevance. Theoretical implications are discussed.