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Bethel Park, PA, United States

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

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. Source

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

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. Source

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 Source

Focke N.K.,University Hospital Freiburg | Trost S.,August Research Systems | Paulus W.,University Hospital Freiburg | Falkai P.,Ludwig Maximilians University of Munich | Gruber O.,August Research Systems
Frontiers in Psychiatry

Voxel-based morphometry (VBM) is a commonly used method to study volumetric variations on a whole brain basis. However, it is often criticized for potential confounds, mainly based on imperfect spatial registration. We therefore aimed to evaluate if VBM and "gold standard" manual volumetry are measuring the same effects with respect to subcortical gray matter volumes. Manual regions-of-interest were drawn in the hippocampus, amygdala, nucleus accumbens, thalamus, putamen, pallidum, and caudate nucleus bilaterally. Resulting volumes were used for a whole brain VBM correlation analysis with Statistical Parametric Mapping (SPM8). The hippocampus, amygdala, putamen, and caudate nucleus were correctly identified by SPM using the contemporary high-dimensional normalization (DARTEL toolbox). This strongly suggests that VBM and manual volumetry both are indeed measuring the same effects with regard to subcortical brain structures. © 2014 Focke, Trost, Paulus, Falkai and Gruber. Source

Diekhof E.K.,August Research Systems | Diekhof E.K.,University of Hamburg | Nerenberg L.,August Research Systems | Falkai P.,August Research Systems | And 3 more authors.
Human Brain Mapping

The ability to resist immediate rewards is crucial for lifetime success and individual well-being. Using functional magnetic resonance imaging, we assessed the association between trait impulsivity and the neural underpinnings of the ability to control immediate reward desiring. Low and high extreme impulsivity groups were compared with regard to their behavioral performance and brain activation in situations, in which they had to forego immediate rewards with varying value to achieve a superordinate long-term goal. We found that highly impulsive (HI) individuals, who successfully compensated for their lack in behavioral self-control, engaged two complementary brain mechanisms when choosing actions in favor of a long-term goal, but at the expense of an immediate reward. First, self-controlled decisions led to a general attenuation of reward-related activation in the nucleus accumbens, which was accompanied by an increased inverse connectivity with the anteroventral prefrontal cortex. Second, HI subjects controlled their desire for increasingly valuable, but suboptimal rewards through a linear reduction of activation in the ventromedial prefrontal cortex (VMPFC). This was achieved by an increased inverse coupling between the VMPFC and the ventral striatum. Importantly, the neural mechanisms observed in the HI group differed from those in extremely controlled individuals, despite similar behavioral performance. Collectively, these results suggest trait-specific neural mechanisms that allow HI individuals to control their desire for immediate reward. © 2011 Wiley Periodicals, Inc. Source

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