Christian Beste

ERP indices for response inhibition are related to anxiety-related personality traits.

Anxiety is often associated with impaired cognitive control and avoidance behaviour. The aim of this study was to investigate the effect of anxiety-related personality traits, such as anxiety sensitivity and trait anxiety, on event-related potentials of response inhibition in a standard Go/Nogo-paradigm. We focused on the Nogo-N2 and Nogo-P3 components, which probably represent different sub-processes of response inhibition. The Nogo-N2 was mainly influenced by trait anxiety, while it was slightly affected by anxiety sensitivity. In contrast, the Nogo-P3 was significantly associated with anxiety sensitivity, but was less affected by trait anxiety. Thus, anxious subjects seem to maintain a higher level of cognitive control to prepare and to monitor the outcome of their actions, which is differentially reflected in Nogo-N2 and Nogo-P3 potentials. Our results show that anxiety-related personality traits modulate electrophysiological responses related to cognitive control processes and should be taken into consideration in studies investigating response inhibition.

A causal role of the right inferior frontal cortex in implementing strategies for multi-component behaviour

Everyday activities, such as, for example, driving a car or preparing a meal, require the hierarchical organization and processing of several individual actions. Currently, the neural mechanisms underlying the control of action sequences are not well understood. Here, the authors demonstrate that the right inferior frontal gyrus (rIFG) plays a key role in implementing the strategy used to cascade different actions. Continuous theta burst stimulation (TBS) applied to the rIFG results in a less efficient action cascading strategy, whereas intermittent TBS results in a more efficient strategy, compared with a shamTBS control condition. These effects are confirmed in electrophysiological data showing that activity differences in the rIFG are related to alterations in response selection processes. Overall, these results suggest that the neural dynamics of the rIFG determine the strategy used during some forms of everyday multi-component behaviour.

The Met-allele of the BDNF Val66Met polymorphism enhances task switching in elderly

In this study we examined the relevance of the functional brain-derived neurotrophic factor (BDNF) Val66Met polymorphism as a modulator of task-switching performance in healthy elderly by using behavioral and event-related potential (ERP) measures. Task switching was examined in a cue-based and a memory-based paradigm. Val/Val carriers were generally slower, showed enhanced reaction time variability and higher error rates, particularly during memory-based task switching than the Met-allele individuals. On a neurophysiological level these dissociative effects were reflected by variations in the N2 and P3 ERP components. The task switch-related N2 was increased while the P3 was decreased in Met-allele carriers, while the Val/Val genotype group revealed the opposite pattern of results. In cue-based task-switching no behavioral and ERP differences were seen between the genotypes. These data suggest that superior memory-based task-switching performance in elderly Met-allele carriers may emerge due to more efficient response selection processes. The results implicate that under special circumstances the Met-allele renders cognitive processes more efficient than the Val/Val genotype in healthy elderly, corroborating recent findings in young subjects.

Mechanisms mediating parallel action monitoring in fronto-striatal circuits.

Flexible response adaptation and the control of conflicting information play a pivotal role in daily life. Yet, little is known about the neuronal mechanisms mediating parallel control of these processes. We examined these mechanisms using a multi-methodological approach that integrated data from event-related potentials (ERPs) with structural MRI data and source localisation using sLORETA. Moreover, we calculated evoked wavelet oscillations. We applied this multi-methodological approach in healthy subjects and patients in a prodromal phase of a major basal ganglia disorder (i.e., Huntingtons disease), to directly focus on fronto-striatal networks. Behavioural data indicated, especially the parallel execution of conflict monitoring and flexible response adaptation was modulated across the examined cohorts. When both processes do not co-incide a high integrity of fronto-striatal loops seems to be dispensable. The neurophysiological data suggests that conflict monitoring (reflected by the N2 ERP) and working memory processes (reflected by the P3 ERP) differentially contribute to this pattern of results. Flexible response adaptation under the constraint of high conflict processing affected the N2 and P3 ERP, as well as their delta frequency band oscillations. Yet, modulatory effects were strongest for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined caudate head volume predicted modulations in conflict monitoring, but not working memory processes. The results show how parallel conflict monitoring and flexible adaptation of action is mediated via fronto-striatal networks. While both, response monitoring and working memory processes seem to play a role, especially response selection processes and ACC-basal ganglia networks seem to be the driving force in mediating parallel conflict monitoring and flexible adaptation of actions.

Improvement and impairment of visually guided behavior through LTP- and LTD-like exposure-based visual learning.

Cellular studies have focused on long-term potentiation (LTP) and long-term depression (LTD) to understand requirements for persistent changes in synaptic connections. Whereas LTP is induced through high-frequency intermittent stimulation, low-frequency stimulation evokes LTD. Because of the ubiquitous efficacy of these protocols, they are considered fundamental mechanisms underlying learning. Here we adapted LTP/LTD-like protocols to visual stimulation to alter human visually guided behavior. In a change-detection task, participants reported luminance changes against distracting orientation changes. Subsequently, they were exposed to passive visual high- or low-frequency stimulation of either the relevant luminance or irrelevant orientation feature. LTP-like high-frequency protocols using luminance improved ability to detect luminance changes, whereas low-frequency LTD-like stimulation impaired performance. In contrast, LTP-like exposure of the irrelevant orientation feature impaired performance, whereas LTD-like orientation stimulation improved it. LTP-like effects were present for 10 days, whereas LTD-like effects lasted for a shorter period of time. Our data demonstrate that instead of electrically stimulating synapses, selective behavioral changes are evoked in humans by using equivalently timed visual stimulation, suggesting that both LTD- and LTP-like protocols control human behavior but that the direction of changes is determined by the feature incorporated into the stimulation protocol.

Response inhibition in Huntington's disease : A study using ERPs and sLORETA

Huntingtons disease (HD) is an autosomal dominant inherited neurodegenerative disorder, with neurodegeneration mainly affecting the striatum. We investigated executive functions related to response inhibition in (HD) and healthy controls by means of event-related potentials (ERP) in a simple Go/Nogo-task. In Nogo as opposed to Go trials two fronto-central ERP components are elicited: the Nogo-N2 and Nogo-P3. These components are supposed to depend on (medial) prefrontal regions, especially the anterior cingulate cortex (ACC). The results show that the Nogo-N2 did not differ between the groups, while the Nogo-P3 demonstrated a strong attenuation in the HD-group, which also showed more false alarms in the Nogo-condition. Using sLORETA it is shown that this attenuation was related to the medial frontal cortex, especially the ACC, and superior frontal cortex areas. Moreover, the attenuation was related to the underlying genetic disease load (CAG-index). The decline in inhibition is likely mediated via a dysfunction in the ACC, which is known to be dysfunctional in HD. Moreover, the results may be interpreted that the decline in response inhibition in HD is gene-associated. The differentially affected Nogo-components suggest that they rely on different neuronal circuits, even within the ACC. For HD this suggests that this structure is not entirely dysfunctional.

Translating neurobehavioural endpoints of developmental neurotoxicity tests into in vitro assays and readouts

The developing nervous system is particularly vulnerable to chemical insults. Exposure to chemicals can result in neurobehavioural alterations, and these have been used as sensitive readouts to assess neurotoxicity in animals and man. Deconstructing neurobehaviour into relevant cellular and molecular components may allow for detection of specific neurotoxic effects in cell-based systems, which in turn may allow an easier examination of neurotoxic pathways and modes of actions and eventually inform the regulatory assessment of chemicals with potential developmental neurotoxicity. Here, current developments towards these goals are reviewed. Imaging genetics (CB) provides new insights into the neurobiological correlates of cognitive function that are being used to delineate neurotoxic mechanisms. The gaps between in vivo neurobehaviour and real-time in vitro measurements of neuronal function are being bridged by ex vivo measurements of synaptic plasticity (RW). An example of solvent neurotoxicity demonstrates how an in vivo neurological defect can be linked via the N-methyl-d-aspartate (NMDA)-glutamate receptor as a common target to in vitro readouts (AB). Axonal and dendritic morphology in vitro proved to be good correlates of neuronal connectivity and neurobehaviour in animals exposed to polychlorinated biphenyls and organophosphorus pesticides (PJL). Similarly, chemically induced changes in neuronal morphology affected the formation of neuronal networks on structured surfaces. Such network formation may become an important readout for developmental neurotoxicity in vitro (CvT), especially when combined with human neurons derived from embryonic stem cells (ML). We envision that future in vitro test systems for developmental neurotoxicity will combine the above approaches with exposure information, and we suggest a strategy for test system development and cell-based risk assessment.

Stimulus-Response Compatibility in Huntington's Disease: A Cognitive-Neurophysiological Analysis

The basal ganglia are assumed to be of importance in action/response selection, but results regarding the importance are contradictive. We investigate these processes in relation to attentional processing using event-related potentials (ERPs) in Huntingtons disease (HD), an autosomal genetic disorder expressed by degeneration of the basal ganglia, using a flanker task. A symptomatic HD group, a presymptomatic HD group (pHD), and healthy controls were examined. In the behavioral data, we found a general response slowing in HD while the compatibility effect was the same for all groups. The ERP data show a decrease of the N1 on the flanker in HD and pHD; this suggests deficient attentional processes. The N1 on the target was unaffected, suggesting that the attentional system in HD is not entirely deficient. The early lateralized readiness potential (LRP), reflecting automatic response activation due to the flankers, was unchanged, whereas the late LRP, reflecting controlled response selection due to the target information, was delayed in HD. Thus levels of action-selection processes are differentially affected in HD with automatic processes seeming to be more robust against neurodegeneration. The N2, usually associated with conflict processing, was reduced in the HD but not in the pHD and the control groups. Because the N2 was related to the LRP and reaction times in all groups, the N2 may generally not be related to conflict but rather to controlled response selection, which is impaired in HD. Overall, the results suggest alterations in attentional control, conflict processing, and controlled response selection in HD but not in automatic response selection.

Error Processing in Huntington's Disease

Background Huntingtons disease (HD) is a genetic disorder expressed by a degeneration of the basal ganglia inter alia accompanied with dopaminergic alterations. These dopaminergic alterations are related to genetic factors i.e., CAG-repeat expansion. The error (related) negativity (Ne/ERN), a cognitive event-related potential related to performance monitoring, is generated in the anterior cingulate cortex (ACC) and supposed to depend on the dopaminergic system. The Ne is reduced in Parkinsons Disease (PD). Due to a dopaminergic deficit in HD, a reduction of the Ne is also likely. Furthermore it is assumed that movement dysfunction emerges as a consequence of dysfunctional error-feedback processing. Since dopaminergic alterations are related to the CAG-repeat, a Ne reduction may furthermore also be related to the genetic disease load. Methodology/Principle Findings We assessed the error negativity (Ne) in a speeded reaction task under consideration of the underlying genetic abnormalities. HD patients showed a specific reduction in the Ne, which suggests impaired error processing in these patients. Furthermore, the Ne was closely related to CAG-repeat expansion. Conclusions/Significance The reduction of the Ne is likely to be an effect of the dopaminergic pathology. The result resembles findings in Parkinsons Disease. As such the Ne might be a measure for the integrity of striatal dopaminergic output function. The relation to the CAG-repeat expansion indicates that the Ne could serve as a gene-associated “cognitive” biomarker in HD.

The ontogenesis of language lateralization and its relation to handedness.

Dominance of the left hemisphere for many aspects of speech production and perception is one of the best known examples of functional hemispheric asymmetries in the human brain. Classic theories about its ontogenesis assume that it is determined by the same ontogenetic factors as handedness because the two traits are correlated to some extent. However, the strength of this correlation depends on the measures used to assess the two traits, and the neurophysiological basis of language lateralization is different from that of handedness. Therefore, we argue that although the two traits show partial pleiotropy, there is also a substantial amount of independent ontogenetic influences for each of them. This view is supported by several recent genetic and neuroscientific studies that are reviewed in the present article.