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Bethel Park, PA, United States
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Diekhof E.K.,August Research Systems | Falkai P.,August Research Systems | Gruber O.,August Research Systems
Neuropsychologia | Year: 2011

Converging evidence suggests a specific role for the orbitofrontal cortex (OFC) in processing of reinforcer value and stimulus hedonicity. However, in a recent study posterior parts of the OFC were also activated in the absence of physical reward or positive reinforcement, namely when affectively neutral stimuli were perceived as salient and required an immediate adjustment of behaviour. This suggests that the OFC may be similarly responsive to different types of behaviourally significant events irrespective of their affective valence or the associated response demands. The present functional neuroimaging study aimed at testing this hypothesis. By systematically varying the exact nature of the behavioural significance of experimental stimuli we were able to directly compare neural responses to significant events that signalled the chance to gain a monetary reward for correct performance with brain activation related to salient, but affectively neutral events that occurred unexpectedly and required a rapid adjustment of behaviour towards these events. The observed commonalities in orbitofrontal activation for different types of significant events, which occurred independent of the hedonic value or the actual response requirements, confirmed the hypothesis that the OFC may be more generally involved in evaluating the behavioural relevance of salient environmental stimuli and is not restricted to the processing of reward and positive incentive value. Our findings thus further underscore the putative role of the OFC in the prioritisation of attentional selection and behavioural control. © 2011 Elsevier Ltd.

Henseler I.,Max Planck Institute for Human Cognitive and Brain Sciences | Henseler I.,August Research Systems | Kruger S.,August Research Systems | Dechent P.,University of Gottingen | Gruber O.,August Research Systems
NeuroImage | Year: 2011

Some situations require us to be highly sensitive to information in the environment, whereas in other situations, our attention is mainly focused on internally represented information. It has been hypothesized that a control system located in the rostral prefrontal cortex (PFC) acts as gateway between these two forms of attention. Here, we examined the neural underpinnings of this 'gateway system' using fMRI and functional connectivity analysis. We designed different tasks, in which the demands for attending to external or internal information were manipulated, and tested 1) whether there is a functional specialization within the rostral PFC along a medial-lateral dimension, and 2) whether these subregions can influence attentional weighting processes by specifically interacting with other parts of the brain. Our results show that lateral aspects of the rostral PFC are preferentially activated when attention is directed to internal representations, whereas anterior medial aspects are activated when attention is directed to sensory events. Furthermore, the rostrolateral subregion was preferentially connected to regions in the prefrontal and parietal cortex during internal attending, whereas the rostromedial subregion was connected to the basal ganglia, thalamus, and sensory association cortices during external attending. Finally, both subregions interacted with another important prefrontal region involved in cognitive control, the inferior frontal junction, in a task-specific manner, depending on the current attentional demands. These findings suggest that the rostrolateral and rostromedial part of the anterior PFC have dissociable roles in attentional control, and that they might, as part of larger networks, be involved in dynamically adjusting the contribution of internal and external information to current cognition. © 2011 Elsevier Inc.

Melcher T.,August Research Systems | Born C.,Saarland University | Gruber O.,August Research Systems
Neuroscience Research | Year: 2011

In this event-related fMRI study, we sought to investigate the influence of negative affect on the processing of two kinds of cognitive interference: Stroop-interference and oddball interference. For our purpose, we adopted an oddball variant of the Stroop task in which Stroop-interference and oddball interference conditions were created by presenting incongruent and rarely occurring word meanings, respectively. Immediately preceding the target stimuli, we presented pictures of the International Affective Picture System which were either emotionally negative and arousing or emotionally neutral, providing two affective conditions under which the cognitive task was administered. Both the behavioral and the neuroimaging data exhibited an interaction effect between emotional and cognitive condition. First, the emotion induction selectively impaired behavioral performance on interference trials while behavioral measures on non-interference trials were roughly identical in both emotional conditions. Second, in the negative emotional condition there was incremental interference-related activation in control-related regions (fronto-parietal cortices). Taken together, findings suggest that negative affect specifically disturbs the neural control processes that in a neutral affective state allow to select task-relevant information and to shield its processing from task-irrelevant distraction. Accordingly, agents in a negative affective state have to exert enhanced control efforts to resolve cognitive interference. Additional connectivity analyses revealed that a negative coupling between lateral PFC on the one hand and amygdala and OFC on the other is related to enhanced interference resolution which can be tentatively interpreted as evidence that emotional regulation is an integrated part of an agent's efforts to preserve cognitive performance in affective situations. © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society.

Pfister R.,August Research Systems | Pfister R.,University of Würzburg | Melcher T.,August Research Systems | Melcher T.,University of Basel | And 3 more authors.
Neuroscience | Year: 2014

How does our mind produce physical, goal-directed action of our body? For about 200. years, philosophers and psychologists hypothesized the transformation from mind to body to rely on the anticipation of an action's sensory consequences. Whereas this hypothesis received tremendous support from behavioral experiments, the neural underpinnings of action control via such ideomotor effect anticipations are virtually unknown. Using functional magnetic resonance imaging, the present study identified the inferior parietal cortex and the parahippocampal gyrus as key regions for this type of action control - setting the stage for a neuroscientific framework for explaining action control by ideomotor effect anticipations and thus enabling a synthesis of psychological and neuroscientific approaches to human action. © 2013 IBRO.

Genzel L.,Max Planck Institute of Psychiatry | Genzel L.,University of Edinburgh | Dresler M.,Max Planck Institute of Psychiatry | Cornu M.,Max Planck Institute of Psychiatry | And 8 more authors.
Biological Psychiatry | Year: 2015

Background Overnight memory consolidation is disturbed in both depression and schizophrenia, creating an ideal situation to investigate the mechanisms underlying sleep-related consolidation and to distinguish disease-specific processes from common elements in their pathophysiology.Methods We investigated patients with depression and schizophrenia, as well as healthy control subjects (each n = 16), under a motor memory consolidation protocol with functional magnetic resonance imaging and polysomnography.Results In a sequential finger-tapping task associated with the degree of hippocampal-prefrontal cortex functional connectivity during the task, significantly less overnight improvement was identified as a common deficit in both patient groups. A task-related overnight decrease in activation of the basal ganglia was observed in control subjects and schizophrenia patients; in contrast, patients with depression showed an increase. During the task, schizophrenia patients, in comparison with control subjects, additionally recruited adjacent cortical areas, which showed a decrease in functional magnetic resonance imaging activation overnight and were related to disease severity. Effective connectivity analyses revealed that the hippocampus was functionally connected to the motor task network, and the cerebellum decoupled from this network overnight.Conclusions While both patient groups showed similar deficits in consolidation associated with hippocampal-prefrontal cortex connectivity, other activity patterns more specific for disease pathology differed.

Trost S.,August Research Systems | Gruber O.,August Research Systems
Neuropsychobiology | Year: 2012

Objective: Recent functional neuroimaging studies have provided evidence that human verbal working memory is represented by two complementary neural systems, a left lateralized premotor-parietal network implementing articulatory rehearsal and a presumably phylogenetically older bilateral anterior-prefrontal/ inferior-parietal network subserving non-articulatory maintenance of phonological information. In order to corroborate these findings from functional neuroimaging, we performed a targeted behavioural study in patients with very selective and circumscribed brain lesions to key regions suggested to support these different subcomponents of human verbal working memory. Methods: Within a sample of over 500 neurological patients assessed with high-resolution structural magnetic resonance imaging, we identified 2 patients with corresponding brain lesions, one with an isolated lesion to Broca's area and the other with a selective lesion bilaterally to the anterior middle frontal gyrus. These 2 patients as well as groups of age-matched healthy controls performed two circuit-specific verbal working memory tasks. In this way, we systematically assessed the hypothesized selective behavioural effects of these brain lesions on the different subcomponents of verbal working memory in terms of a double dissociation. Results: Confirming prior findings, the lesion to Broca's area led to reduced performance under articulatory rehearsal, whereas the non-articulatory maintenance of phonological information was unimpaired. Conversely, the bifrontopolar brain lesion was associated with impaired non-articulatory phonological working memory, whereas performance under articulatory rehearsal was unaffected. Conclusion: The present experimental neuropsychological study in patients with specific and circumscribed brain lesions confirms the hypothesized double dissociation of two complementary brain systems underlying verbal working memory in humans. In particular, the results demonstrate the functional relevance of the anterior prefrontal cortex for non-articulatory maintenance of phonological information and, in this way, provide further support for the evolutionary-based functional-neuroanatomical model of human working memory. Copyright © 2012 S. Karger AG, Basel.

Wolf C.,August Research Systems | Linden D.E.J.,University of Cardiff
Genes, Brain and Behavior | Year: 2012

Because living systems depend on their environment, the evolution of environmental adaptability is inseparable from the evolution of life itself. In animals and humans, environmental adaptability extends further to adaptive behavior. It has recently emerged that individual adaptability depends on the interaction of adaptation mechanisms at diverse functional levels. This interaction enables the integration of genetic, epigenetic and environmental factors for coordinated regulation of adaptations. In this review, we first present the basis for the regulation of adaptation mechanisms across functional levels. We then focus on neuronal activity-regulated adaptation mechanisms that involve the regulation of genes, noncoding DNA (ncDNA), ncRNAs and proteins to change the structural and functional properties of neurons. Finally, we discuss a selection of these important neuronal activity-regulated molecules and their effects on brain structure and function and on behavior. Most of the evidence so far is based on sampling of animal tissue or post-mortem studies in humans. However, we also present techniques that combine genetic with behavioral and neurophysiological measures in humans (e.g. genetic imaging) and discuss their potential and limitations. We argue that we need to understand how neuronal activity-dependent adaptation mechanisms integrate genetic, epigenetic and experience-dependent signals in order to explain individual variations in behavior and cognitive performance. © 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Henseler I.,August Research Systems | Falkai P.,August Research Systems | Gruber O.,August Research Systems
Journal of Psychiatric Research | Year: 2010

Introduction: Disturbed interregional functional connectivity has been hypothesized to be a promising marker of schizophrenia. The relationship between working memory (WM) impairment, disturbed functional connectivity, and the characteristic symptoms of schizophrenia, however, remains elusive. Methods: We used functional MRI (fMRI) to investigate in patients with schizophrenia and matched controls the patterns of functional connectivity during the performance of different tasks selectively engaging subcomponent processes of working memory. Results: Compared with controls, patients showed reduced connectivity of the prefrontal cortex with the intraparietal cortex and the hippocampus and abnormal negative interactions between the ventrolateral and dorsolateral prefrontal cortex during the non-articulatory maintenance of phonological information. During the maintenance of visuospatial information, patients presented reduced connectivity between regions in the superior parietal and occipital cortex, as well as enhanced positive connectivity of the frontal eye field with visual processing areas. Discussion: Our findings suggest complex dysregulations within the networks supporting working memory functions in schizophrenia, which manifest as decreased positive and abnormal negative interactions. Correlations between the connection strength and WM performance suggest that these dysregulations may be neurofunctional correlates of the WM deficits seen in schizophrenia. Altered prefronto-hippocampal and parieto-occipital connectivity was further found to be associated with higher positive symptoms, providing a possible explanation for the development of delusions and disorganization symptoms. Conclusion: The present findings can help to better understand the relationship between altered patterns of synchronized brain activity and the cognitive and clinical symptoms of schizophrenia. © 2009 Elsevier Ltd.

Recent genome-wide association studies have identified MAD1L1 (mitotic arrest deficient-like 1) as a susceptibility gene for bipolar disorder and schizophrenia. The minor allele of the single-nucleotide polymorphism (SNP) rs11764590 in MAD1L1 was associated with bipolar disorder. Both diseases, bipolar disorder and schizophrenia, are linked to functional alterations in the reward system. We aimed at investigating possible effects of the MAD1L1 rs11764590 risk allele on reward systems functioning in healthy adults. A large homogenous sample of 224 young (aged 18–31 years) participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All participants performed the ‘Desire-Reason Dilemma’ paradigm investigating the neural correlates that underlie reward processing and active reward dismissal in favor of a long-term goal. We found significant hypoactivations of the ventral tegmental area (VTA), the bilateral striatum and bilateral frontal and parietal cortices in response to conditioned reward stimuli in the risk allele carriers compared with major allele carriers. In the dilemma situation, functional connectivity between prefrontal brain regions and the ventral striatum was significantly diminished in the risk allele carriers. Healthy risk allele carriers showed a significant deficit of their bottom-up response to conditioned reward stimuli in the bilateral VTA and striatum. Furthermore, functional connectivity between the ventral striatum and prefrontal areas exerting top-down control on the mesolimbic reward system was reduced in this group. Similar alterations in reward processing and disturbances of prefrontal control mechanisms on mesolimbic brain circuits have also been reported in bipolar disorder and schizophrenia. Together, these findings suggest the existence of an intermediate phenotype associated with MAD1L1.Neuropsychopharmacology advance online publication, 8 June 2016; doi:10.1038/npp.2016.70. © 2016 American College of Neuropsychopharmacology

Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase I | Award Amount: 69.18K | Year: 2010

August Research Systems, Inc. proposes to establish the feasibility of rapidly deployable, thin-film camouflage coatings for on ground vehicles. The film-based coatings will leverage the robust and expanding vehicle wraps industry, which provides full-vehicle appliqué systems that are digitally printed, self-adhesive, vinyl films that serve as a medium for vivid vehicle graphics, while the underlying vehicle paint is protected. Vehicle wraps offer potential advantages in military use among which are: enabling color-rich, digitally optimized camouflage patterns without the need for paint; the circumvention of a paint operation for refreshing or changing vehicle appearance; a deployable and field-installable coating system that is 0-VOC and free of hazardous air pollutants; protection and life extension of underlying CARC paint; and rapid, cost-effective repair or replacement. However, wrap technology does not address several important military requirements such as non-slip properties, specific camouflage color and gloss characteristics, and near infrared reflectance spectral requirements. This Phase I effort will, through testing and evaluation, quantify the shortcomings of current wrap material and manufacturing technology per military requirements and define innovative approaches for the engineering and production of militarily useful wrap materials for vehicle applications.

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