Effects of Catecholaminergic and Transcranial Direct Current Stimulation on Response Inhibition.

BACKGROUND: The principle of gain control determines the efficiency of neuronal processing and can be enhanced with pharmacological or brain stimulation methods. It is a key factor for cognitive control, but the degree of how much gain control may be enhanced underlies a physical limit. METHODS: To investigate whether methylphenidate (MPH) and transcranial direct current stimulation (tDCS) share common underlying mechanisms and cognitive effects, we administered MPH and anodal tDCS (atDCS) over the right inferior frontal gyrus both separately and combined, while healthy adult participants (n = 104) performed a response selection and inhibition task. The recorded EEG data were analyzed with a focus on theta band activity, and source estimation analyses were conducted. RESULTS: The behavioral data show that MPH and atDCS revealed interactive effects on the ability to inhibit responses. Both MPH and atDCS modulated task-related theta oscillations in the supplementary motor area when applied separately, making a common underlying mechanism likely. When both stimulation methods were combined, there was no doubling of effects in the supplementary motor area but a shift to inferior frontal areas in the cortical network responsible for theta-driven processing. CONCLUSIONS: The results indicate that both MPH and atDCS likely share a common underlying neuronal mechanism, and interestingly, they demonstrate interactive effects when combined, which are most likely due to the physical limitations of gain control increases. The current study provides critical groundwork for future combined applications of MPH and non-invasive brain stimulation.

Interactions of catecholamines and GABA+ in cognitive control: Insights from EEG and 1H-MRS.

Catecholamines and amino acid transmitter systems are known to interact, the exact links and their impact on cognitive control functions have however remained unclear. Using a multi-modal imaging approach combining EEG and proton-magnetic resonance spectroscopy (1H-MRS), we investigated the effect of different degrees of pharmacological catecholaminergic enhancement onto theta band activity (TBA) as a measure of interference control during response inhibition and execution. It was central to our study to evaluate the predictive impact of in-vivo baseline GABA+ concentrations in the striatum, the anterior cingulate cortex (ACC) and the supplemental motor area (SMA) of healthy adults under varying degrees of methylphenidate (MPH) stimulation. We provide evidence for a predictive interrelation of baseline GABA+ concentrations in cognitive control relevant brain areas onto task-induced TBA during response control stimulated with MPH. Baseline GABA+ concentrations in the ACC, the striatum, and the SMA had a differential impact on predicting interference control-related TBA in response execution trials. GABA+ concentrations in the ACC appeared to be specifically important for TBA modulations when the cognitive effort needed for interference control was high - that is when no prior task experience exists, or in the absence of catecholaminergic enhancement with MPH. The study highlights the predictive role of baseline GABA+ concentrations in key brain areas influencing cognitive control and responsiveness to catecholaminergic enhancement, particularly in high-effort scenarios.

Neurophysiological processes reflecting the effects of the immediate past during the dynamic management of actions.

In recent years, there has been many efforts to establish a comprehensive theoretical framework explaining the working mechanisms involved in perception-action integration. This framework stresses the importance of the immediate past on mechanisms supporting perception-action integration. The present study investigates the neurophysiological principles of dynamic perception-action bindings, particularly considering the influence of the immediate history on action control mechanisms. For this purpose, we conducted an established stimulus-response binding paradigm during EEG recording. The SR-task measures stimulus-response binding in terms of accuracy and reaction time differences depending on the degree of feature overlap between conditions. Alpha, beta and theta band activity in distinct time domains as well as associated brain regions were investigated applying time-frequency analyses, a beamforming approach as well as correlation analyses. We demonstrate, for the first time, interdependencies of neuronal processes relying on the immediate past. The reconfiguration of an action seems to overwrite immediately preceding processes. The analyses revealed modulations of theta (TBA), alpha (ABA) and beta band activity (BBA) in connection with fronto-temporal structures supporting the theoretical assumptions of the considered conceptual framework. The close interplay of attentional modulation by gating irrelevant information (ABA) and binding and retrieval processes (TBA) is reflected by the correlation of ABA in all pre-probe-intervals with post-probe TBA. Likewise, the role of BBA in maintaining the event file until retrieval is corroborated by BBA preceding the TBA-associated retrieval of perception-action codes. Following action execution, TBA shifted towards visual association cortices probably reflecting preparation for upcoming information, while ABA and BBA continue to reflect processes of attentional control and information selection for goal-directed behavior. The present work provides the first empirical support for concepts about the neurophysiological mechanisms of dynamic management of perception and action.

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.

Alpha and theta band activity share information relevant to proactive and reactive control during conflict-modulated response inhibition.

Response inhibition is an important instance of cognitive control and can be complicated by perceptual conflict. The neurophysiological mechanisms underlying these processes are still not understood. Especially the relationship between neural processes directly preceding cognitive control (proactive control) and processes underlying cognitive control (reactive control) has not been examined although there should be close links. In the current study, we investigate these aspects in a sample of N = 50 healthy adults. Time-frequency and beamforming approaches were applied to analyze the interrelation of brain states before (pre-trial) and during (within-trial) cognitive control. The behavioral data replicate a perceptual conflict-dependent modulation of response inhibition. During the pre-trial period, insular, inferior frontal, superior temporal, and precentral alpha activity was positively correlated with theta activity in the same regions and the superior frontal gyrus. Additionally, participants with a stronger pre-trial alpha activity in the primary motor cortex showed a stronger (within-trial) conflict effect in the theta band in the primary motor cortex. This theta conflict effect was further related to a stronger theta conflict effect in the midcingulate cortex until the end of the trial. The temporal cascade of these processes suggests that successful proactive preparation (anticipatory information gating) entails a stronger reactive processing of the conflicting stimulus information likely resulting in a realization of the need to adapt the current action plan. The results indicate that theta and alpha band activity share and transfer aspects of information when it comes to the interrelationship between proactive and reactive control during conflict-modulated motor inhibition.

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.

How Intermittent Brain States Modulate Neurophysiological Processes in Cognitive Flexibility.

Cognitive flexibility is an essential facet of everyday life, for example, when switching between different tasks. Neurophysiological accounts on cognitive flexibility have often focused on the task switch itself, disregarding preceding processes and the possible impact of "brain states" before engaging in cognitive flexibility. In a combined working memory/task-switching paradigm, we examined how neuronal processes during cognitive flexibility are interrelated to preceding neuronal processes across time and brain regions in a sample of n = 42 healthy adults. The interrelation of alpha- and theta-band-related processes over brain states ahead and during response selection was investigated on a functional neuroanatomical level using EEG-beamforming. The results showed that response selection processes (reflected by theta-band activity) seem to be strongly connected to "idling" and preparatory brain activity states (in both the theta- and alpha-band). Notably, the superior parietal cortex seems to play a crucial role by assembling alpha-band-related inhibitory processes from the rule- and goal-based actions during "idling" brain states, namely, short-term maintenance of rules (temporal cortex), task-set reconfiguration (superior frontal/precentral regions), and perceptual control (occipital cortex). This information is further relayed to response selection processes associated with theta-band activity. Notably, when the task has to be switched, theta-band activity in the superior frontal gyrus indicates a need for cognitive control in the "idling" brain state, which also seems to be relayed by BA7. The results indicate the importance of brain activity states ahead of response selection processes for cognitive flexibility.

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.

Alcohol-induced deficits in reactive control of response selection and inhibition are counteracted by a seemingly paradox increase in proactive control.

High-dose alcohol intoxication reduces cognitive control, including inhibition. Although inhibition deficits may contribute to the behavioral deficits commonly observed in alcohol use disorder (AUD), many questions about potentially modulating factors have remained unanswered. We examined the effects of experimentally induced high-dose alcohol intoxication (~ 1.1 ‰) on the interplay between controlled vs. automatic response selection and inhibition in healthy young men. A holistic EEG-based theta activity analysis that considered both reactive control during task performance and preceding proactive control processes was run. It revealed a previously unknown seesaw relationship, with decreased reactive control, but paradoxically increased proactive control. Most importantly, alcohol-induced increases in proactive occipital theta band power were associated with reductions in negative alcohol effects on reactive control processes associated with decreased activity in the SMA and medial frontal cortex. Our findings demonstrate that research should not solely focus on immediate effects during task performance. Aside from differential neurobiochemical and neuroanatomical effects of alcohol, it is also conceivable that proactive control may have been recruited in a (secondary) response to compensate for alcohol-induced impairments in reactive control. Against this background, it could be promising to investigate changes in such compensatory mechanisms in pronounced alcohol-associated inhibition deficits, like in AUD patients.

Extra Movements in Healthy People: Challenging the Definition and Diagnostic Practice of Tic Disorders.

The occurrence of motor/vocal tics, that is, "extra movements" and/or "extra vocalizations," is the leading diagnostic criterion for tic disorders. We show that extra movements are common also in healthy controls, so that a surplus of movements per se is not indicative of the presence of a tic disorder. This questions the usefulness of Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for tic disorders in clinical practice. Apparently, it is not solely a surplus of movements that defines tic disorders. Instead, movement characteristics and patterns seem to play a crucial role. ANN NEUROL 2023;93:472-478.

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.

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.

Pretrial Theta Band Activity Affects Context-dependent Modulation of Response Inhibition.

The ability to inhibit a prepotent response is a crucial prerequisite of goal-directed behavior. So far, research on response inhibition has mainly examined these processes when there is little to no cognitive control during the decision to respond. We manipulated the "context" in which response inhibition has to be exerted (i.e., a controlled or an automated context) by combining a Simon task with a go/no-go task and focused on theta band activity. To investigate the role of "context" in response inhibition, we also examined how far theta band activity in the pretrial period modulates context-dependent variations of theta band activity during response inhibition. This was done in an EEG study applying beamforming methods. Here, we examined n = 43 individuals. We show that an automated context, as opposed to a controlled context, compromises response inhibition performance and increases the need for cognitive control. This was also related to context-dependent modulations of theta band activity in superior frontal and middle frontal regions. Of note, results showed that theta band activity in the pretrial period, associated with the right inferior frontal cortex, was substantially correlated with context-dependent modulations of theta band activity during response inhibition. The direction of the obtained correlation provides insights into the functional relevance of a pretrial theta band activity. The data suggest that pretrial theta band activity reflects some form of attentional sampling to inform possible upcoming processes signaling the need for cognitive control.