Neural oscillations guiding action during effects imagery.

Goal-directed acting requires the integration of sensory information but can also be performed without direct sensory input. Examples of this can be found in sports and can be conceptualized by feedforward processes. There is, however, still a lack of understanding of the temporal neural dynamics and neuroanatomical structures involved in such processes. In the current study, we used EEG beamforming methods and examined 37 healthy participants in two well-controlled experiments varying the necessity of anticipatory processes during goal-directed action. We found that alpha and beta activity in the medial and posterior cingulate cortex enabled feedforward predictions about the position of an object based on the latest sensorimotor state. On this basis, theta band activity seems more related to sensorimotor representations, while beta band activity would be more involved in setting up the structure of the neural representations themselves. Alpha band activity in sensory cortices reflects an intensified gating of the anticipated perceptual consequences of the to-be-executed action. Together, the findings indicate that goal-directed acting through the anticipation of the predicted state of an effector is based on accompanying processes in multiple frequency bands in midcingulate and sensory brain regions.

TRACK-a new algorithm and open-source tool for the analysis of pursuit-tracking sensorimotor integration processes.

In daily life, sensorimotor integration processes are fundamental for many cognitive operations. The pursuit-tracking paradigm is an ecological and valid paradigm to examine sensorimotor integration processes in a more complex environment than many established tasks that assess simple motor responses. However, the analysis of pursuit-tracking performance is complicated, and parameters quantified to examine performance are sometimes ambiguous regarding their interpretation. We introduce an open-source algorithm (TRACK) to calculate a new tracking error metric, the spatial error, based on the identification of the intended target position for the respective cursor position. The identification is based on assigning cursor and target direction changes to each other as key events, based on the assumptions of similarity and proximity. By applying our algorithm to pursuit-tracking data, beyond replication of known effects such as learning or practice effects, we show a higher precision of the spatial tracking error, i.e., it fits our behavioral data better than the temporal tracking error and thus provides new insights and parameters for the investigation of pursuit-tracking behavior. Our work provides an important step towards fully utilizing the potential of pursuit-tracking tasks for research on sensorimotor integration processes.

The neurophysiology of continuous action monitoring.

Monitoring actions is essential for goal-directed behavior. However, as opposed to short-lasting, and regularly reinstating monitoring functions, the neural processes underlying continuous action monitoring are poorly understood. We investigate this using a pursuit-tracking paradigm. We show that beta band activity likely maintains the sensorimotor program, while theta and alpha bands probably support attentional sampling and information gating, respectively. Alpha and beta band activity are most relevant during the initial tracking period, when sensorimotor calibrations are most intense. Theta band shifts from parietal to frontal cortices throughout tracking, likely reflecting a shift in the functional relevance from attentional sampling to action monitoring. This study shows that resource allocation mechanisms in prefrontal areas and stimulus-response mapping processes in the parietal cortex are crucial for adapting sensorimotor processes. It fills a knowledge gap in understanding the neural processes underlying action monitoring and suggests new directions for examining sensorimotor integration in more naturalistic experiments.

Valence moderates the effect of stimulus-hand proximity on conflict processing and gaze-cueing.

An effective interaction with the environment requires adaptation of one's own behaviour to environmental demands. We do so by using cues from our environment and relating these cues to our body to predict the outcomes of events. The recent literature on embodied cognition suggests that task-relevant stimuli, presented near the hands, receive more attentional capacity and are processed differently than stimuli, presented spatially more distant to our body. It has also been proposed that near-hand processing is beneficial to conflict resolution. In the current study, we tested the assumption of an attentional bias towards the near hand space in the context of our previous work by combining a cueing paradigm (allocation of visual attention) with a conflict processing paradigm (Simon task) in the near vs far hand space. In addition, the relevance of processing was manipulated by using affective (angry vs neutral smileys) gaze cues (i.e., varying the valence of the cues). Our results indicate that (a) the interaction of valence × cue congruency × hand proximity was significant, indicating that the cueing effect was larger for negative valence in the proximal condition. (b) The interaction of valence × Simon compatibility × stimulus-hand proximity interaction was significant, indicating that for negative valence processing, the Simon effect was smaller in the proximal than in the distal stimulus-hand condition. This effect was at least numerically but not significantly reversed in the neutral valence condition. (c) Overall, cue congruency, indicating the correct vs incorrect attention allocation to the target stimulus onset, did not reveal any effect on Simon compatibility × stimulus-hand proximity. Our results suggest that valence, the allocation of attention, and conflict, seem to be decisive factors determining the direction and strength of hand proximity effects.

A dissociable functional relevance of theta- and beta-band activities during complex sensorimotor integration.

Sensorimotor integration processes play a central role in daily life and require that different sources of sensory information become integrated: i.e. the information related to the object being under control of the agent (i.e. indicator) and the information about the goal of acting. Yet, how this is accomplished on a neurophysiological level is contentious. We focus on the role of theta- and beta-band activities and examine which neuroanatomical structures are involved. Healthy participants (n = 41) performed 3 consecutive pursuit-tracking EEG experiments in which the source of visual information available for tracking was varied (i.e. that of the indicator and the goal of acting). The initial specification of indicator dynamics is determined through beta-band activity in parietal cortices. When information about the goal was not accessible, but operating the indicator was required nevertheless, this incurred increased theta-band activity in the superior frontal cortex, signaling a higher need for control. Later, theta- and beta-band activities encode distinct information within the ventral processing stream: Theta-band activity is affected by the indicator information, while beta-band activity is affected by the information about the action goal. Complex sensorimotor integration is realized through a cascade of theta- and beta-band activities in a ventral-stream-parieto-frontal network.

Unraveling astrocyte behavior in the space brain: Radiation response of primary astrocytes.

Introduction: Exposure to space conditions during crewed long-term exploration missions can cause several health risks for astronauts. Space radiation, isolation and microgravity are major limiting factors. The role of astrocytes in cognitive disturbances by space radiation is unknown. Astrocytes' response toward low linear energy transfer (LET) X-rays and high-LET carbon (12C) and iron (56Fe) ions was compared to reveal possible effects of space-relevant high-LET radiation. Since astronauts are exposed to ionizing radiation and microgravity during space missions, the effect of simulated microgravity on DNA damage induction and repair was investigated. Methods: Primary murine cortical astrocytes were irradiated with different doses of X-rays, 12C and 56Fe ions at the heavy ion accelerator GSI. DNA damage and repair (γH2AX, 53BP1), cell proliferation (Ki-67), astrocytes' reactivity (GFAP) and NF-κB pathway activation (p65) were analyzed by immunofluorescence microscopy. Cell cycle progression was investigated by flow cytometry of DNA content. Gene expression changes after exposure to X- rays were investigated by mRNA-sequencing. RT-qPCR for several genes of interest was performed with RNA from X-rays- and heavy-ion-irradiated astrocytes: Cdkn1a, Cdkn2a, Gfap, Tnf, Il1ß, Il6, and Tgfß1. Levels of the pro inflammatory cytokine IL-6 were determined using ELISA. DNA damage response was investigated after exposure to X-rays followed by incubation on a 2D clinostat to simulate the conditions of microgravity. Results: Astrocytes showed distinct responses toward the three different radiation qualities. Induction of radiation-induced DNA double strand breaks (DSBs) and the respective repair was dose-, LET- and time-dependent. Simulated microgravity had no significant influence on DNA DSB repair. Proliferation and cell cycle progression was not affected by radiation qualities examined in this study. Astrocytes expressed IL-6 and GFAP with constitutive NF-κB activity independent of radiation exposure. mRNA sequencing of X-irradiated astrocytes revealed downregulation of 66 genes involved in DNA damage response and repair, mitosis, proliferation and cell cycle regulation. Discussion: In conclusion, primary murine astrocytes are DNA repair proficient irrespective of radiation quality. Only minor gene expression changes were observed after X-ray exposure and reactivity was not induced. Co-culture of astrocytes with microglial cells, brain organoids or organotypic brain slice culture experiments might reveal whether astrocytes show a more pronounced radiation response in more complex network architectures in the presence of other neuronal cell types.

The neural stability of perception-motor representations affects action outcomes and behavioral adaptation.

Actions can fail - even though this is well known, little is known about what distinguishes neurophysiological processes preceding errors and correct actions. In this study, relying on the Theory of Event Coding, we test the assumption that only specific aspects of information coded in EEG activity are relevant for understanding processes leading to response errors. We examined N = 69 healthy participants who performed a mental rotation task and combined temporal EEG signal decomposition with multivariate pattern analysis (MVPA) and source localization analyses. We show that fractions of the EEG signal, primarily representing stimulus-response translation (event file) processes and motor response representations, are essential. Stimulus representations were less critical. The source localization results revealed widespread activity modulations in structures including the frontopolar, the middle and superior frontal, the anterior cingulate cortex, the cuneus, the inferior parietal cortex, and the ventral stream regions. These are associated with differential effects of the neural dynamics preceding correct/erroneous responses. The temporal-generalization MVPA showed that event file representations and representations of the motor response were already distinct 200 ms after stimulus presentation and this lasted till around 700 ms. The stability of this representational content was predictive for the magnitude of posterror slowing, which was particularly strong when there was no clear distinction between the neural activity profile of event file representations associated with a correct or an erroneous response. The study provides a detailed analysis of the dynamics leading to an error/correct response in connection to an overarching framework on action control.

The effects of noninvasive brain stimulation on heart rate and heart rate variability: A systematic review and meta-analysis.

Noninvasive brain stimulation (NIBS) techniques such as transcranial magnetic stimulation and transcranial direct current stimulation are widely used to test the involvement of specific cortical regions in various domains such as cognition and emotion. Despite the capability of stimulation techniques to test causal directions, this approach has been only sparsely used to examine the cortical regulation of autonomic nervous system (ANS) functions such as heart rate (HR) and heart rate variability (HRV) and to test current models in this regard. In this preregistered (PROSPERO) systematic review and meta-analysis, we aimed to investigate, based on meta-regression, whether NIBS represents an effective method for modulating HR and HRV measures, and to evaluate whether the ANS is modulated by cortical mechanisms affected by NIBS. Here we have adhered to the PRISMA guidelines. In a series of four meta-analyses, a total of 131 effect sizes from 35 sham-controlled trials were analyzed using robust variance estimation random-effects meta-regression technique. NIBS was found to effectively modulate HR and HRV with small to medium effect sizes. Moderator analyses yielded significant differences in effects between stimulation of distinct cortical areas. Our results show that NIBS is a promising tool to investigate the cortical regulation of ANS, which may add to the existing brain imaging and animal study literature. Future research is needed to identify further factors modulating the size of effects. As many of the studies reviewed were found to be at high risk of bias, we recommend that methods to reduce potential risk of bias be used in the design and conduct of future studies.

Tasting rewards. Effects of orosensory sweet signals on human error processing.

Human research has shown interactions between rewards and cognitive control. In animal models of affective neuroscience, reward administration typically involves administering orosensory sugar signals (OSS) during caloric-deprived states. We adopted this procedure to investigate neurophysiological mechanisms of reward-cognitive control interactions in humans. We predicted that OSS would affect neurophysiological and behavioral indices of error processing oppositely, depending on the relative weight of the OSS-induced 'wanting' and 'liking' components of reward. We, therefore, conducted a double-blind, non-nutritive sweetener-controlled study with a within-subject design. Fasted (16 hr) participants (N = 61) performed a modified Flanker task to assess neurophysiological (error-related negativity [Ne/ERN]) and behavioral (post-error adaptations) measures of error processing. Non-contingent to task performance, we repeatedly administered either a sugar (glucose) or non-nutritive sweetener (aspartame) solution, which had to be expulsed after short oral stimulation to prevent post-oral effects. Consistent with our hypothesis on how 'liking' would affect Ne/ERN amplitude, we found the latter to be decreased for sugar compared to aspartame. Unexpectedly, we found post-error accuracy, instead of post-error slowing, to be reduced by sugar relative to aspartame. Our findings suggest that OSS may interact with error processing through the 'liking' component of rewards. Adopting our reward-induction procedure (i.e. administering OSS in a state of high reward sensitivity [i.e. fasting], non-contingent to task performance) might help future research investigating the neural underpinnings of reward-cognitive control interactions in humans.

Keeping the pace: The effect of slow-paced breathing on error monitoring.

Detecting errors is crucial for adapting one's own actions. Moreover, behavior is often optimized by adapting to maladaptive actions, i.e. errors. In this regard, recent studies and models of error monitoring point to an involvement of emotional states in error monitoring. A psychophysiological correlate of the latter is the error negativity or error-related negativity (Ne/ERN), reflecting partly the functional implementation of anterior cingulate cortex functions. In the present study, we aimed to test whether neurophysiological aspects of error monitoring can be altered by a relaxation technique, i.e. slow-paced breathing. Slow-paced breathing has been shown to increase cardiac vagal activity. According to the neurovisceral integration model, cardiac vagal activity is thought to be a marker of the effectiveness of executive functions. We tested the effect of slow-paced breathing on error monitoring, i.e. the Ne/ERN and behavioral adaptation in a modified flanker task, a cognitive task during which performance depends on executive control. The Ne was increased following slow-paced breathing compared to a passive control condition. Furthermore, behavioral results indicate that response variability decreased in the slow-paced breathing condition whereas overall performance remained constant. We conclude that slow-paced breathing improves the ability to focus on the task at hand. Thus, the error monitoring system is being supported in keeping the pace, i.e. tracking responses.

Vom Sinn des Verfahrenskonzepts und der Verfahrensvielfalt ­ und warum das Baukasten-System in der Psychotherapie nicht funktioniert.

Why the concept of distinct psychotherapeutic approaches is indispensable - and why the tool box concept of psychotherapy cannot work Background: In Germany, the official psychotherapy guidelines are oriented towards the model of distinct psychotherapeutic approaches. Within the German health care system this also applies to the training in psychotherapy. Some critics, however, are presently pleading in favour of abolishing the model of distinct psychotherapeutic approaches, which also implies to abolish the concept of the so called "Richtlinienverfahren" in Germany - approaches of psychotherapy which proved to be efficacious and whose costs are reimbursed by the insurance companies. Objective: The arguments put forward such as the heterogeneity of the approaches as well as the proposed alternatives, for example, an "integrative" model of both mental disorders and psychotherapeutic treatment are critically discussed. Results: Both the arguments and proposed alternatives are found to be not convincing, neither from a scientific nor from a psychotherapeutic perspective. From a scientific perspective, there is no evidence for efficacy of a "general" or "integrative" model of psychotherapy - which is in contrast to the Richtlinienverfahren for which evidence for efficacy exists. From a psychotherapeutic perspective psychotherapy cannot be taught, learnt and applied by use of tools or modules without a theoretical orientation. Conclusions: The concept of distinct psychotherapeutic approaches proves to be an in dispensable principal for orientation in psychotherapy, for both therapists and patients.

Rapid development of API nano-formulations from screening to production combining dual centrifugation and wet agitator bead milling.

Various wet ball nanomilling-screening tools for poorly soluble APIs are available which differ in their milling principle, batch size and number of samples. Here, the transferability of results from screening (small to medium-scale) to pharmaceutical production (largescale) was investigated. Wet ball milling in a dual centrifuge (DC) (10-100 mg API, 40 samples in parallel) was used to identify stable nanoformulations. In addition different sized agitator bead mills were used for scale-up to industrial scales. DC-and small-scale agitator milling (AM) resulted in small and virtually identical API-particles. Additionally, similar API-particles were obtained using two different sized agitator bead mills (batch size 1.5 and 30 kg) and applying comparable specific grinding energies (SGE). The SGE used in the trials represents the grinding limit for this API-suspension. Using lower SGEs, AM results in larger API-particles. All used milling tools had no influence on the APIs crystal structure and wear of grinding media (Zr/Y) is low. The study confirmed the importance to choose the right formulation and process parameters, which positively affect grinding efficacy, particle size distribution and wear contamination. The excellent comparability of results obtained from DC-milling and AM significantly reduces the duration for successful and predictable formulation development.

The Psychophysiology of Action: A Multidisciplinary Endeavor for Integrating Action and Cognition.

There is a vast amount of literature concerning the integration of action and cognition. Although this broad research area is of great interest for many disciplines like sports, psychology and cognitive neuroscience, only a few attempts tried to bring together different perspectives so far. Our goal is to provide a perspective to spark a debate across theoretical borders and integration of different disciplines via psychophysiology. In order to boost advances in this research field it is not only necessary to become aware of the different areas that are relevant but also to consider methodological aspects and challenges. We briefly describe the most relevant theoretical accounts to the question of how internal and external information processes or factors interact and, based on this, argue that research programs should consider the three dimensions: (a) dynamics of movements; (b) multivariate measures and; (c) dynamic statistical parameters. Only with an extended perspective on theoretical and methodological accounts, one would be able to integrate the dynamics of actions into theoretical advances.

Effects of binge drinking and hangover on response selection sub-processes-a study using EEG and drift diffusion modeling.

Effects of binge drinking on cognitive control and response selection are increasingly recognized in research on alcohol (ethanol) effects. Yet, little is known about how those processes are modulated by hangover effects. Given that acute intoxication and hangover seem to be characterized by partly divergent effects and mechanisms, further research on this topic is needed. In the current study, we hence investigated this with a special focus on potentially differential effects of alcohol intoxication and subsequent hangover on sub-processes involved in the decision to select a response. We do so combining drift diffusion modeling of behavioral data with neurophysiological (EEG) data. Opposed to common sense, the results do not show an impairment of all assessed measures. Instead, they show specific effects of high dose alcohol intoxication and hangover on selective drift diffusion model and EEG parameters (as compared to a sober state). While the acute intoxication induced by binge-drinking decreased the drift rate, it was increased by the subsequent hangover, indicating more efficient information accumulation during hangover. Further, the non-decisional processes of information encoding decreased with intoxication, but not during hangover. These effects were reflected in modulations of the N2, P1 and N1 event-related potentials, which reflect conflict monitoring, perceptual gating and attentional selection processes, respectively. As regards the functional neuroanatomical architecture, the anterior cingulate cortex (ACC) as well as occipital networks seem to be modulated. Even though alcohol is known to have broad neurobiological effects, its effects on cognitive processes are rather specific.

Classifying Response Correctness across Different Task Sets: A Machine Learning Approach.

Erroneous behavior usually elicits a distinct pattern in neural waveforms. In particular, inspection of the concurrent recorded electroencephalograms (EEG) typically reveals a negative potential at fronto-central electrodes shortly following a response error (Ne or ERN) as well as an error-awareness-related positivity (Pe). Seemingly, the brain signal contains information about the occurrence of an error. Assuming a general error evaluation system, the question arises whether this information can be utilized in order to classify behavioral performance within or even across different cognitive tasks. In the present study, a machine learning approach was employed to investigate the outlined issue. Ne as well as Pe were extracted from the single-trial EEG signals of participants conducting a flanker and a mental rotation task and subjected to a machine learning classification scheme (via a support vector machine, SVM). Overall, individual performance in the flanker task was classified more accurately, with accuracy rates of above 85%. Most importantly, it was even feasible to classify responses across both tasks. In particular, an SVM trained on the flanker task could identify erroneous behavior with almost 70% accuracy in the EEG data recorded during the rotation task, and vice versa. Summed up, we replicate that the response-related EEG signal can be used to identify erroneous behavior within a particular task. Going beyond this, it was possible to classify response types across functionally different tasks. Therefore, the outlined methodological approach appears promising with respect to future applications.

Does response selection contribute to inhibition of return?

Inhibition of return (IOR) means delayed responses for targets at a cued compared to targets at an uncued location. It is assumed to reflect delayed reallocation of attention toward a previously attended location. Besides an attentional mechanism, IOR could also be due to a cue-evoked inhibition to respond toward a cued target. In the present study, IOR with simple, compatible, and incompatible choice responses was compared and tracked by means of event-related EEG activity. IOR was amplified with simple responses but did not differ between compatible and incompatible responses. Attention-related ERP correlates were constant across cue target onset asynchronies as were, in part, behavioral effects. Early, rather sensory ERP components varied with time, reflecting sensory or attentional interaction of cue and target processing. None of these effects varied with response requirements, indicating that response selection does not contribute to IOR in manual choice response tasks.

A perspective on neural and cognitive mechanisms of error commission.

Behavioral adaptation and cognitive control are crucial for goal-reaching behaviors. Every creature is ubiquitously faced with choices between behavioral alternatives. Common sense suggests that errors are an important source of information in the regulation of such processes. Several theories exist regarding cognitive control and the processing of undesired outcomes. However, most of these models focus on the consequences of an error, and less attention has been paid to the mechanisms that underlie the commissioning of an error. In this article, we present an integrative review of neuro-cognitive models that detail the determinants of the occurrence of response errors. The factors that may determine the likelihood of committing errors are likely related to the stability of task-representations in prefrontal networks, attentional selection mechanisms and mechanisms of action selection in basal ganglia circuits. An important conclusion is that the likelihood of committing an error is not stable over time but rather changes depending on the interplay of different functional neuro-anatomical and neuro-biological systems. We describe factors that might determine the time-course of cognitive control and the need to adapt behavior following response errors. Finally, we outline the mechanisms that may proof useful for predicting the outcomes of cognitive control and the emergence of response errors in future research.

Sustained posterior contralateral activity indicates re-entrant target processing in visual change detection: an EEG study.

The present study investigated the neural mechanisms that contribute to the detection of visual feature changes between stimulus displays by means of event-related lateralizations of the electroencephalogram (EEG). Participants were instructed to respond to a luminance change in either of two lateralized stimuli that could randomly occur alone or together with an irrelevant orientation change of the same or contralateral stimulus. Task performance based on response times and accuracy was decreased compared to the remaining stimulus conditions when relevant and irrelevant feature changes were presented contralateral to each other (contralateral distractor condition). The sensory response to the feature changes was reflected in a posterior contralateral positivity at around 100 ms after change presentation and a posterior contralateral negativity in the N1 time window (N1pc). N2pc reflected a subsequent attentional bias in favor of the relevant luminance change. The continuation of the sustained posterior contralateral negativity (SPCN) following N2pc covaried with response times within feature change conditions and revealed a posterior topography comparable to the earlier components associated with sensory and attentional mechanisms. Therefore, this component might reflect the re-processing of information based on sustained short-term memory representations in the visual system until a stable target percept is created that can serve as the perceptual basis for response selection and the initiation of goal-directed behavior.

Frontal theta activity reflects distinct aspects of mental fatigue.

Longer lasting performance in cognitively demanding tasks leads to an exhaustion of cognitive resources and to a state commonly described as mental fatigue. More specifically, the allocation and focusing of attention become less efficient with time on task. Additionally, the selection of even simple responses becomes more error prone. With respect to the recorded EEG, mental fatigue has been reported to be associated with an increase in frontal theta and frontal and occipital alpha activity. The present study focused on the time course of changes in behavior and in the EEG to characterize fatigue-related processes. Participants performed a spatial stimulus-response-compatibility task in eight blocks for an overall duration of 4h. Error rates increased continuously with time on task. Total alpha power was larger at the end compared to the beginning of the experiment. However, alpha power increased rapidly and reached its maximal amplitude already after 1h, whereas frontal theta showed a continuous increase with time on task, possibly related to increased effort to keep the performance level high. Time frequency analyses revealed power changes in the theta band induced by task relevant information that might be assigned to a drain of executive control capacities. Thus, frontal theta turned out to be a reliable marker of distinct changes in cognitive processing with increasing fatigue.