Lateral prefrontal anodal transcranial direct current stimulation augments resolution of auditory perceptual-attentional conflicts.

Successful action control requires the ability to attend to relevant sensory signals in the environment. This, however, can be complicated when different sensory inputs compete for the brain's limited resources. Under such conditions, sensory processes interact with top-down attention to selectively process goal-relevant stimuli, while inhibiting irrelevant or distracting sensory signals. In the current study, we set out to provide causal mechanistic insights for whether and how prefrontal regions are involved in resolving attentional-perceptual conflicts. To this end, we applied atDCS and examined neurophysiological processes of selective auditory perception. To evaluate whether atDCS differentially affects intermingled neurophysiological subprocesses involved during conflict resolution, we decomposed the EEG data using residue iteration decomposition (RIDE). We show that the right prefrontal regions are causally involved in resolving attentional-perceptual conflicts and that atDCS increases the efficacy to do so. The data show that dissociable neurophysiological signals are specifically affected by atDCS. Conflict resolution processes that involve inhibition of competing stimuli and response evaluation and are associated with right middle frontal gyrus (BA46) seem to become intensified by atDCS during the resolution of attentional-perceptual conflicts. After stimulation the early stimulus processing level was also less prone to sensory conflicts, but this alone could not explain the increased behavioral efficacy associated with atDCS. These observed effects likely reflect changes in neuronal gain control mechanisms. Taken together, results of this study may have implications for treating attentional hyperactivity disorder, for which pharmacological intervention is currently the common therapeutic approach.

The system-neurophysiological basis for how methylphenidate modulates perceptual-attentional conflicts during auditory processing.

The ability to selectively perceive and flexibly attend to relevant sensory signals in the environment is essential for action control. Whereas neuromodulation of sensory or attentional processing is often investigated, neuromodulation of interactive effects between perception and attention, that is, high attentional control demand when the relevant sensory information is perceptually less salient than the irrelevant one, is not well understood. To fill this gap, this pharmacological-electroencephalogram (EEG) study applied an intensity-modulated, focused-attention dichotic listening paradigm together with temporal EEG signal decomposition and source localization analyses. We used a double-blind MPH/placebo crossover design to delineate the effects of methylphenidate (MPH)-a dopamine/norepinephrine transporter blocker-on the resolution of perceptual-attentional conflicts, when perceptual saliency and attentional focus favor opposing ears, in healthy young adults. We show that MPH increased behavioral performance specifically in the condition with the most pronounced conflict between perceptual saliency and attentional focus. On the neurophysiological level, MPH effects in line with the behavioral data were observed after accounting for intraindividual variability in the signal. More specifically, MPH did not show an effect on stimulus-related processes but modulated the onset latency of processes between stimulus evaluation and responding. These modulations were further shown to be associated with activation differences in the temporoparietal junction (BA40) and the superior parietal cortex (BA7) and may reflect neuronal gain modulation principles. The findings provide mechanistic insights into the role of modulated dopamine/norepinephrine transmitter systems for the interactions between perception and attention.

Dopamine Modulates the Efficiency of Sensory Evidence Accumulation During Perceptual Decision Making.

Background: Perceptual decision making is the process through which available sensory information is gathered and processed to guide our choices. However, the neuropsychopharmacological basis of this important cognitive function is largely elusive. Yet, theoretical considerations suggest that the dopaminergic system may play an important role. Methods: In a double-blind, randomized, placebo-controlled study design, we examined the effect of methylphenidate in 2 dosages (0.25 mg/kg and 0.5 mg/kg body weight) in separate groups of healthy young adults. We used a moving dots task in which the coherency of the direction of moving dots stimuli was manipulated in 3 levels (5%, 15%, and 35%). Drift diffusion modelling was applied to behavioral data to capture subprocesses of perceptual decision making. Results: The findings show that only the drift rate (v), reflecting the efficiency of sensory evidence accumulation, but not the decision criterion threshold (a) or the duration of nondecisional processes (Ter), is affected by methylphenidate vs placebo administration. Compared with placebo, administering 0.25 mg/kg methylphenidate increased v, but only in the 35% coherence condition. Administering 0.5 mg/kg methylphenidate did not induce modulations. Conclusions: The data suggest that dopamine selectively modulates the efficacy of evidence accumulation during perceptual decision making. This modulation depends on 2 factors: (1) the degree to which the dopaminergic system is modulated using methylphenidate (i.e., methylphenidate dosage) and (2) the signal-to-noise ratio of the visual information. Dopamine affects sensory evidence accumulation only when dopamine concentration is not shifted beyond an optimal level and the incoming information is less noisy.

Neural mechanisms underlying successful and deficient multi-component behavior in early adolescent ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder affecting cognitive control. These functions are important to achieve goals when different actions need to be executed in close succession. This type of multi-component behavior, which often further requires the processing of information from different modalities, is important for everyday activities. Yet, possible changes in neurophysiological mechanisms have not been investigated in adolescent ADHD. We examined N = 31 adolescent ADHD patients and N = 35 healthy controls (HC) in two Stop-Change experiments using either uni-modal or bi-modal stimuli to trigger stop and change processes. These stimuli were either presented together (SCD0) or in close succession of 300 milliseconds (SCD300). Using event-related potentials (ERP), EEG data decomposition and source localization we analyzed neural processes and functional neuroanatomical correlates of multicomponent behavior. Compared to HCs, ADHD patients had longer reaction times and higher error rates when Stop and Change stimuli were presented in close succession (SCD300), but not when presented together (SCD0). This effect was evident in the uni-modal and bi-modal experiment and is reflected by neurophysiological processes reflecting response selection mechanisms in the inferior parietal cortex (BA40). These processes were only detectable after accounting for intra-individual variability in neurophysiological data; i.e. there were no effects in standard ERPs. Multi-component behavior is not always deficient in ADHD. Rather, modulations in multi-component behavior depend on a critical temporal integration window during response selection which is associated with functioning of the inferior parietal cortex. This window is smaller than in HCs and independent of the complexity of sensory input.

On the effects of multimodal information integration in multitasking.

There have recently been considerable advances in our understanding of the neuronal mechanisms underlying multitasking, but the role of multimodal integration for this faculty has remained rather unclear. We examined this issue by comparing different modality combinations in a multitasking (stop-change) paradigm. In-depth neurophysiological analyses of event-related potentials (ERPs) were conducted to complement the obtained behavioral data. Specifically, we applied signal decomposition using second order blind identification (SOBI) to the multi-subject ERP data and source localization. We found that both general multimodal information integration and modality-specific aspects (potentially related to task difficulty) modulate behavioral performance and associated neurophysiological correlates. Simultaneous multimodal input generally increased early attentional processing of visual stimuli (i.e. P1 and N1 amplitudes) as well as measures of cognitive effort and conflict (i.e. central P3 amplitudes). Yet, tactile-visual input caused larger impairments in multitasking than audio-visual input. General aspects of multimodal information integration modulated the activity in the premotor cortex (BA 6) as well as different visual association areas concerned with the integration of visual information with input from other modalities (BA 19, BA 21, BA 37). On top of this, differences in the specific combination of modalities also affected performance and measures of conflict/effort originating in prefrontal regions (BA 6).

Sensory processes modulate differences in multi-component behavior and cognitive control between childhood and adulthood.

Many everyday tasks require executive functions to achieve a certain goal. Quite often, this requires the integration of information derived from different sensory modalities. Children are less likely to integrate information from different modalities and, at the same time, also do not command fully developed executive functions, as compared to adults. Yet still, the role of developmental age-related effects on multisensory integration processes has not been examined within the context of multicomponent behavior until now (i.e., the concatenation of different executive subprocesses). This is problematic because differences in multisensory integration might actually explain a significant amount of the developmental effects that have traditionally been attributed to changes in executive functioning. In a system, neurophysiological approach combining electroencephaloram (EEG) recordings and source localization analyses, we therefore examined this question. The results show that differences in how children and adults accomplish multicomponent behavior do not solely depend on developmental differences in executive functioning. Instead, the observed developmental differences in response selection processes (reflected by the P3 ERP) were largely dependent on the complexity of integrating temporally separated stimuli from different modalities. This effect was related to activation differences in medial frontal and inferior parietal cortices. Primary perceptual gating or attentional selection processes (P1 and N1 ERPs) were not affected. The results show that differences in multisensory integration explain parts of transformations in cognitive processes between childhood and adulthood that have traditionally been attributed to changes in executive functioning, especially when these require the integration of multiple modalities during response selection. Hum Brain Mapp 38:4933-4945, 2017. © 2017 Wiley Periodicals, Inc.

Blocking effects in non-conditioned goal-directed behaviour.

A great deal of our goal-directed behaviour depends on stimulus-response (S-R) associations, which can be established through conditioning or explicit instructions. For conditioned and reward maximizing behaviour, it has been shown that redundant information will no longer be taken into account once those associations have been formed ("blocking effect"). Following from this, new aspects will not be included in a pre-established association unless they improve behaviour. Opposing this, influential action control theories state that all kinds of information may be taken into account during action selection, thus denying the possibility of blocking redundant "surplus" information from non-conditioned goal-directed behaviour. We probed these contradicting predictions by asking two groups of healthy young adults to perform a redundant and a non-redundant version of a stop-change task in a counter-balanced order. Using behavioural and electrophysiological data, we demonstrate that contradicting current theories, blocking seems to be a general mechanism which also applies to non-conditioned goal-directed behaviour. Specifically, we show that the complexity of response selection processes associated with medial frontal cortical activity is altered by blocking. This was reflected by faster responses and smaller central P3 amplitudes originating in the ACC (BA24/BA32). Preceding attentional processes were not affected. Contradicting current views, our ability to ignore information that hampers an expedient unfolding of goal-directed behaviour is quite limited. Prior experiences have a much larger influence on which input we consider for response formation. This offers a functional explanation for why it can be hard to alter (inefficient) behaviour once it has been established.

The norepinephrine system and its relevance for multi-component behavior.

The ability to execute several actions in a specific temporal order to achieve an overarching goal, a process often termed action cascading or multi-component behavior, is essential for everyday life requirements. We are only at the beginning to understand the neurobiological mechanisms important for these cognitive processes. However, it is likely that the locus coeruleus-norepinephrine (LC-NE) system may be of importance. In the current study we examine the relevance of the LC-NE system for action cascading processes using a system neurophysiological approach combining high-density EEG recordings and source localization to analyze event-related potentials (ERPs) with recordings of pupil diameter as a proximate of LC-NE system activity. N=25 healthy participants performed an action cascading stop-change paradigm. Integrating ERPs and pupil diameter using Pearson correlations, the results show that the LC-NE system is important for processes related to multi-component behavior. However, the LC-NE system does not seem to be important during the time period of response selection processes during multi-component behavior (reflected in the P3) as well as during perceptual and attentional selection (P1 and N1 ERPs). Rather, it seems that the neurophysiological processes in the fore period of a possibly upcoming imperative stimulus to initiate multi-component behavior are correlated with the LC-NE system. It seems that the LC-NE system facilitates responses to task-relevant processes and supports task-related decision and response selection processes by preparing cognitive control processes in case these are required during multi-component behavior rather than modulating these processes once they are operating.

Improvements of sensorimotor processes during action cascading associated with changes in sensory processing architecture-insights from sensory deprivation.

In most everyday situations sensorimotor processes are quite complex because situations often require to carry out several actions in a specific temporal order; i.e. one has to cascade different actions. While it is known that changes to stimuli affect action cascading mechanisms, it is unknown whether action cascading changes when sensory stimuli are not manipulated, but the neural architecture to process these stimuli is altered. In the current study we test this hypothesis using prelingually deaf subjects as a model to answer this question. We use a system neurophysiological approach using event-related potentials (ERPs) and source localization techniques. We show that prelingually deaf subjects show improvements in action cascading. However, this improvement is most likely not due to changes at the perceptual (P1-ERP) and attentional processing level (N1-ERP), but due to changes at the response selection level (P3-ERP). It seems that the temporo-parietal junction (TPJ) is important for these effects to occur, because the TPJ comprises overlapping networks important for the processing of sensory information and the selection of responses. Sensory deprivation thus affects cognitive processes downstream of sensory processing and only these seem to be important for behavioral improvements in situations requiring complex sensorimotor processes and action cascading.

Questioning the role of the frontopolar cortex in multi-component behavior--a TMS/EEG study.

Cognitive control is central to many every day situations. There, we usually have to combine different actions to achieve a task goal. Several lines of research indicated that areas in the prefrontal cortex determine cognitive control in situations requiring multi-component behavior. One of this is the frontopolar cortex (FPC). However, direct non-correlative evidence for this notion is widely lacking. In the current study we test the importance of the FPC for the implementation of action cascading processes in a TMS/EEG study. The data, however, clearly show that the FPC does not modulate behavioral or neurophysiological parameters reflecting action cascading, which is in contrast to the findings of dorsolateral prefrontal cortex. The results are supported by a Bayesian analysis of the data. The results suggest that a possible role of the FPC in multi-component behavior needs to be refined. At least in situations, where multi-component behavior is achieved by stopping and switching processes and does not impose high demands on working memory processes the FPC seems to play no role in the implementation of this major cognitive control function.

Effects of copper toxicity on response inhibition processes: a study in Wilson's disease.

Wilson's disease (WD) is a rare genetic disease causing copper deposits in various tissues. Given the specificity of the underlying pathology, it is a good model to investigate the effects of copper toxicity on cognitive functions in humans. If left untreated, WD results in neurodegeneration and organ failure, but irrespective of potential brain damage, the medication might reduce cortical norepinephrine (NE) levels. In line with this, dysexecutive symptoms including increased impulsivity have been reported for WD patients, but the underlying mechanisms have remained elusive. We investigated inhibition and the associated neurophysiological correlates in n = 26 WD patients with mild-to-moderate clinical symptoms and matched healthy controls who completed a Go/Nogo task, while an EEG was recorded. Although the behavioral data do not show increased impulsivity in WD, the neurophysiological data show that evaluative processing of successful inhibition (as reflected by the P3 component) was strongly compromised. This was reflected by a decrease in ACC activity which was positively correlated with the severity of WD symptoms, stressing the importance of copper (toxicity) for neurocognitive functioning and impulsivity. These changes are most likely due to a combination of NE deficiency induced by WD medication as well as WD-induced brain damage. The fact that changes were still evident on a neurophysiological level suggests that neurophysiological correlates of cognitive processes and functions provide a more sensitive index of toxicity and/or treatment efficiency than purely behavioral measures.

Age-related differences in task goal processing strategies during action cascading.

We are often faced with situations requiring the execution of a coordinated cascade of different actions to achieve a goal, but we can apply different strategies to do so. Until now, these different action cascading strategies have, however, not been examined with respect to possible effects of aging. We tackled this question in a systems neurophysiological study using EEG and source localization in healthy older adults and employing mathematical constraints to determine the strategy applied. The results suggest that older adults seem to apply a less efficient strategy when cascading different actions. Compared to younger adults, older adults seem to struggle to hierarchically organize their actions, which leads to an inefficient and more parallel processing of different task goals. On a systems level, the observed deficit is most likely due to an altered processing of task goals at the response selection level (P3 ERP) and related to changes of neural processes in the temporo-parietal junction.

The importance of sensory integration processes for action cascading.

Dual tasking or action cascading is essential in everyday life and often investigated using tasks presenting stimuli in different sensory modalities. Findings obtained with multimodal tasks are often broadly generalized, but until today, it has remained unclear whether multimodal integration affects performance in action cascading or the underlying neurophysiology. To bridge this gap, we asked healthy young adults to complete a stop-change paradigm which presented different stimuli in either one or two modalities while recording behavioral and neurophysiological data. Bimodal stimulus presentation prolonged response times and affected bottom-up and top-down guided attentional processes as reflected by the P1 and N1, respectively. However, the most important effect was the modulation of response selection processes reflected by the P3 suggesting that a potentially different way of forming task goals operates during action cascading in bimodal vs. unimodal tasks. When two modalities are involved, separate task goals need to be formed while a conjoint task goal may be generated when all stimuli are presented in the same modality. On a systems level, these processes seem to be related to the modulation of activity in fronto-polar regions (BA10) as well as Broca's area (BA44).

Binds and bounds of communion: effects of interpersonal values on assumed similarity of self and others.

Assumed similarity refers to ascribing similar attributes to the self and others. Because self-other similarity facilitates communion, people who value communion should be prone to assume self-other similarity; but because self-other similarity also evokes obligation, they may be prone to assume similarity only with others with whom they are or would feel comfortable being interconnected. We tested these hypotheses in 5 studies (total N = 1,709). In Study 1, students indicated their political preferences and estimated other students' preferences. In Studies 2-5, students described their personality and the personalities of the following targets: actual or imagined romantic partners in Study 2; ingroup members (students from the respondents' university) and outgroup members (students from a foreign university) in Studies 3-4; and specific liked and disliked others in Study 5. As hypothesized, people with stronger communal values were more likely to assume self-other similarity with liked others, romantic partners, and ingroup members, but not with disliked others and outgroup members. These effects replicated across different cultures (India, Korea, and the United States) and remained significant when controlling for self-esteem, national identification, and attribute desirability. Although people who valued communion tended to depict themselves and liked and ingroup others in relatively normative (typical) ways, which partially explained assumptions of similarity and indicated that those assumptions were to some extent accurate, communal values continued to predict distinctive self-other similarity or "false consensus" even after controlling for the normative prevalence of attributes.