Ann-Kathrin Stock

DRD1 and DRD2 genotypes modulate processing modes of goal activation processes during action cascading.

Dopamine plays an important role in action selection, but little is known about the influence of different dopamine receptor systems on the subprocesses occurring during the cascading of actions. Because action selection and cascading can be accomplished in a serial manner or a parallel manner, we investigated the potential effects of DRD1 (rs4531) and DRD2 (rs6277) receptor polymorphisms on this dimension. We gathered behavioral and neurophysiological data from healthy human subjects (n = 162) and applied mathematical constraints to quantify their action selection strategy on a serial-parallel continuum. The behavioral results show a more serial and more effective action cascading strategy in homozygous DRD1 G allele carriers, who are assumed to have a higher D1 receptor efficiency than carriers of the A allele. In the group of homozygous DRD2 T-allele carriers, who have a higher striatal density of D2 receptors than C-allele carriers, we found a less effective and more parallel action cascading strategy. These findings suggest that, within the same sample, a higher D1 efficiency seems to shift the action cascading strategy toward a more serial processing mode, whereas the D2 receptors seem to promote a shift in the opposite direction by inducing a more parallel processing mode. Furthermore, the neurophysiological analysis shows that the observed differences are not based on attentional differences or basic inhibition. Instead, processes linking stimulus processing and response execution seem to differentiate between more serial and more parallel processing groups.

Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during action cascading processes

The ever-changing environment we are living in requires us to apply different action control strategies in order to fulfill a task goal. Indeed, when confronted with multiple response options it is fundamental to prioritize and cascade different actions. So far, very little is known about the neuromodulation of action cascading. In this study we assessed the causal role of the gamma-aminobutyric acid (GABA)-ergic and noradrenergic system in modulating the efficiency of action cascading by applying transcutaneous vagus nerve stimulation (tVNS), a new non-invasive and safe method to stimulate the vagus nerve and to increase GABA and norepinephrine concentrations in the brain. A single-blind, sham-controlled, between-group design was used to assess the effect of on-line (i.e., stimulation overlapping with the critical task) tVNS in healthy young volunteers (n=30)-on a stop-change paradigm. Results showed that active, as compared to sham stimulation, enhanced response selection functions during action cascading and led to faster responses when two actions were executed in succession. These findings provide evidence for the important role of the GABA-ergic and noradrenergic system in modulating performance in action cascading.

Latent Toxoplasma gondii infection leads to improved action control.

The parasite Toxoplasma gondii has been found to manipulate the behavior of its secondary hosts to increase its own dissemination which is commonly believed to be to the detriment of the host (manipulation hypothesis). The manipulation correlates with an up-regulation of dopaminergic neurotransmission. In humans, different pathologies have been associated with T. gondii infections but most latently infected humans do not seem to display overt impairments. Since a dopamine plus does not necessarily bear exclusively negative consequences in humans, we investigated potential positive consequences of latent toxoplasmosis (and the presumed boosting of dopaminergic neurotransmission) on human cognition and behavior. For this purpose, we focused on action cascading which has been shown to be modulated by dopamine. Based on behavioral and neurophysiological (EEG) data obtained by means of a stop-change paradigm, we were able to demonstrate that healthy young humans can actually benefit from latent T. gondii infection as regards their performance in this task (as indicated by faster response times and a smaller P3 component). The data shows that a latent infection which is assumed to affect the dopaminergic system can lead to paradoxical improvements of cognitive control processes in humans.

The system neurophysiological basis of backward inhibition

Task switching is regularly required in our everyday life. To succeed in switching, it is important to inhibit the most recently performed task and instead activate the currently relevant task. The process that inhibits a recently performed task when a new task is to be performed is referred to as ‘backward inhibition’ (BI). While the BI effect has been subject to intense research in cognitive psychology, little is known about the neuronal mechanisms that are related to the BI effect and those that relate to differences in the magnitude of the BI effect. In the current study, we examined the system neurophysiological basis of BI processes using event-related potentials (ERPs) and sLORETA by also taking inter-individual differences in the magnitude of the BI into account. The results suggest that BI processes and inter-individual differences in them strongly depend upon attentional selection mechanisms (reflected by N1-ERP modulations in the current task/trial) mediated via networks consisting of extrastriate occipital areas, the temporo-parietal junction and the inferior frontal gyrus. Other processes and mechanisms related to conflict monitoring, response selection, or the updating, organization and implementation of a new task-set (i.e. N2 and P3 processes) were not shown to be modulated by BI processes and differences in their magnitude, as evoked with a common BI paradigm.

The impact of mental workload on inhibitory control subprocesses

The inhibition of inappropriate responses is a function known to rely on prefrontal cortex (PFC) functioning. Similarly, working memory processes are known to rely on the PFC. Even though these processes are usually closely intertwined and the functional neuroanatomy underlying these processes is largely overlapping, the influence of working memory load on inhibitory control process has remained largely elusive. In the current study, we therefore examine how response inhibition processes are modulated by working memory load. For this, we systematically increased the working memory load of participants by integrating mental rotation processes in a Go/NoGo paradigm. To examine the system neurophysiology of these processes in detail, and to examine whether there are differential effects of working memory load on distinct response inhibition subprocesses, we applied event-related potentials (ERPs) in combination with source localization techniques. The data shows that after exceeding a certain threshold, inhibitory control processes are aggravated by working memory load. The neurophysiological data paralleled the behavioral data. However, it suggests that distinguishable response inhibition subprocesses are differentially modulated by working memory load: Changes were evident in the NoGo-P3 amplitude but not in the NoGo-N2 amplitude. On a system level, this distinctive modulation of response inhibition subprocesses was related to differences in neural activity in the left inferior and middle frontal gyri. We show that inhibitory control processes are impaired when the working memory load surpasses a certain threshold. This, however only applies to situations in which the necessity of inhibitory control processes cannot be easily detected on the basis of perceptual factors.

Differential Effects of Motor Efference Copies and Proprioceptive Information on Response Evaluation Processes

It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response.

Effects of Concomitant Stimulation of the GABAergic and Norepinephrine System on Inhibitory Control – A Study Using Transcutaneous Vagus Nerve Stimulation

BACKGROUND Inhibitory control processes are a central executive function. Several lines of evidence suggest that the GABAergic and the norepinephrine (NE) system modulate inhibitory control processes. Yet, the effects of conjoint increases in the GABAergic and NE system activity on inhibitory control have not been examined. OBJECTIVE/HYPOTHESIS We examine the conjoint effects of the GABA and NE system for inhibitory control. METHODS We used transcutaneous vagus nerve stimulation (tVNS), which has been shown to modulate both the GABAergic and NE system. We examine the effects of tVNS in two experimental paradigms examining different aspect of inhibitory control; i.e. a backward inhibition paradigm and a response inhibition paradigm modulating working memory load. RESULTS There were no effects of tVNS on backward inhibition processes, but on response inhibition processes. Yet, these only emerged when working memory processes were needed to control response inhibition. Compared to a sham stimulation, tVNS induced better response inhibition performance (i.e. fewer false alarms). CONCLUSIONS A concomitant modulation of the GABAergic and NE system, as induced by tVNS, affects inhibitory control processes, but only when working memory processes play an important role for inhibitory control. Even though both the GABAergic and the NE system are modulated by tVNS, the results suggest that the modulation of the NE system is most important for the emerging effects.

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 Brocas area (BA44).

High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition

Aside from well‐known physiological effects, high‐dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event‐related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high‐dose alcohol intoxication. Using a within‐subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high‐dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus–response mapping processes during response inhibition. In this context, the NOGO‐P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre‐motor level, was not altered. Based on these results, we demonstrate that alcohol‐induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess‐specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such.

A novel cognitive-neurophysiological state biomarker in premanifest Huntington's disease validated on longitudinal data

In several neurodegenerative diseases, like Huntingtons disease (HD), treatments are still lacking. To determine whether a treatment is effective, sensitive disease progression biomarkers are especially needed for the premanifest phase, since this allows the evaluation of neuroprotective treatments preventing, or delaying disease manifestation. On the basis of a longitudinal study we present a biomarker that was derived by integrating behavioural and neurophysiological data reflecting cognitive processes of action control. The measure identified is sensitive enough to track disease progression over a period of only 6 month. Changes tracked were predictive for a number of clinically relevant parameters and the sensitivity of the measure was higher than that of currently used parameters to track prodromal disease progression. The study provides a biomarker, which could change practice of progression diagnostics in a major basal ganglia disease and which may help to evaluate potential neuroprotective treatments in future clinical trials.