Heike Tost

National Institutes of Health, 베서스다, Maryland, United States

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Publications (127)

  • Carolin Moessnang · Axel Schäfer · Edda Bilek · [...] · Heike Tost
    [Show abstract] [Hide abstract] ABSTRACT: The debilitating effects of social dysfunction in many psychiatric disorders prompt the need for systems-level biomarkers of social abilities that can be applied in clinical populations and longitudinal studies. A promising neuroimaging approach is the animated shapes paradigm based on so-called Frith-Happé animations (FHAs) which trigger spontaneous mentalizing with minimal cognitive demands. Here, we presented FHAs during functional magnetic resonance imaging to 46 subjects and examined the specificity and sensitivity of the elicited social brain responses. Test-retest reliability was additionally assessed in 28 subjects within a two-week interval. Specific responses to spontaneous mentalizing were observed in key areas of the social brain with high sensitivity and independently from the variant low-level kinematics of the FHAs. Mentalizing-specific responses were well replicable on the group level, suggesting good-to-excellent cross-sectional reliability (intraclass correlation coefficients [ICCs]: .40-.99; dice overlap at Puncorr<.001: .26-1.0). Longitudinal reliability on the single-subject level was more heterogeneous (ICCs of .40-.79; dice overlap at Puncorr<.001: .05-.43). Posterior temporal sulcus activation was most reliable, including a robust differentiation between subjects across sessions (72% of voxels with ICC>.40). These findings encourage the use of FHAs in neuroimaging research across developmental stages and psychiatric conditions, including the identification of biomarkers and pharmacological interventions.
    Article · Jul 2016 · Social Cognitive and Affective Neuroscience
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    [Show abstract] [Hide abstract] ABSTRACT: A physically active lifestyle has been related to positive health outcomes and high life expectancy, but the underlying psychological mechanisms maintaining physical activity are rarely investigated. Tremendous technological progress yielding sophisticated methodological approaches, i.e., ambulatory assessment, have recently enabled the study of these mechanisms in everyday life. In practice, accelerometers allow to continuously and objectively monitor physical activity. The combination with e-diaries makes it feasible to repeatedly assess mood states in real-time and real life and to relate them to physical activity. This state-of-the-art methodology comes with several advantages, like bypassing systematic distortions of retrospective methods, avoiding distortions seen in laboratory settings, and revealing an objective physical activity assessment. Most importantly, ambulatory assessment studies enable to analyze how physical activity and mood wax and wane within persons over time in contrast to existing studies on physical activity and mood which mostly investigated between-person associations. However, there are very few studies on how mood dimensions (i.e., feeling well, energetic and calm) drive non-exercise activity (NEA; such as climbing stairs) within persons. Recent reviews argued that some of these studies have methodological limitations, e.g., scarcely representative samples, short study periods, physical activity assessment via self-reports, and low sampling frequencies. To overcome these limitations, we conducted an ambulatory assessment study in a community-based sample of 106 adults over one week. Participants were asked to report mood ratings on e-diaries and to wear an accelerometer in daily life. We conducted multilevel analyses to investigate whether mood predicted NEA, which was defined as the mean acceleration within the 10-minute interval directly following an e-diary assessment. Additionally, we analyzed the effects of NEA on different time frames following the e-diary prompts in an exploratory manner. Our results revealed that valence significantly and positively predicted NEA within persons (p=.001). Feeling more energetic was associated with significantly increased NEA (p
    Full-text Article · Jun 2016 · Frontiers in Psychology
  • [Show abstract] [Hide abstract] ABSTRACT: Importance: Although deficits in emotional processing are prominent in schizophrenia, it has been difficult to identify neural mechanisms related to the genetic risk for this highly heritable illness. Prior studies have not found consistent regional activation or connectivity alterations in first-degree relatives compared with healthy controls, suggesting that a more comprehensive search for connectomic biomarkers is warranted. Objectives: To identify a potential systems-level intermediate phenotype linked to emotion processing in schizophrenia and to examine the psychological association, task specificity, test-retest reliability, and clinical validity of the identified phenotype. Design, setting, and participations: The study was performed in university research hospitals from June 1, 2008, through December 31, 2013. We examined 58 unaffected first-degree relatives of patients with schizophrenia and 94 healthy controls with an emotional face-matching functional magnetic resonance imaging paradigm. Test-retest reliability was analyzed with an independent sample of 26 healthy participants. A clinical association study was performed in 31 patients with schizophrenia and 45 healthy controls. Data analysis was performed from January 1 to September 30, 2014. Main outcomes and measures: Conventional amygdala activity and seeded connectivity measures, graph-based global and local network connectivity measures, Spearman rank correlation, intraclass correlation, and gray matter volumes. Results: Among the 152 volunteers included in the relative-control sample, 58 were unaffected first-degree relatives of patients with schizophrenia (mean [SD] age, 33.29 [12.56]; 38 were women), and 94 were healthy controls without a first-degree relative with mental illness (mean [SD] age, 32.69 [10.09] years; 55 were women). A graph-theoretical connectivity approach identified significantly decreased connectivity in a subnetwork that primarily included the limbic cortex, visual cortex, and subcortex during emotional face processing (cluster-level P corrected for familywise error = .006) in relatives compared with controls. The connectivity of the same subnetwork was significantly decreased in patients with schizophrenia (F = 6.29, P = .01). Furthermore, we found that this subnetwork connectivity measure was negatively correlated with trait anxiety scores (P = .04), test-retest reliable (intraclass correlation coefficient = 0.57), specific to emotional face processing (F = 17.97, P < .001), and independent of gray matter volumes of the identified brain areas (F = 1.84, P = .18). Replicating previous results, no significant group differences were found in face-related amygdala activation and amygdala-anterior cingulate cortex connectivity (P corrected for familywise error =.37 and .11, respectively). Conclusions and relevance: Our results indicate that altered connectivity in a visual-limbic subnetwork during emotional face processing may be a functional connectomic intermediate phenotype for schizophrenia. The phenotype is reliable, task specific, related to trait anxiety, and associated with manifest illness. These data encourage the further investigation of this phenotype in clinical and pharmacologic studies.
    Article · May 2016 · JAMA Psychiatry
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    [Show abstract] [Hide abstract] ABSTRACT: Species-conserved (intermediate) phenotypes that can be quantified and compared across species offer important advantages for translational research and drug discovery. Here, we investigate the utility of network science methods to assess the pharmacological alterations of the large-scale architecture of brain networks in rats and humans. In a double-blind, placebo-controlled, cross-over study in humans and a placebo-controlled two-group study in rats, we demonstrate that the application of ketamine leads to a topological reconfiguration of large-scale brain networks towards less-integrated and more-segregated information processing in both the species. As these alterations are opposed to those commonly observed in patients suffering from depression, they might indicate systems-level correlates of the antidepressant effect of ketamine.
    Full-text Article · Apr 2016 · Translational Psychiatry
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    Full-text Dataset · Apr 2016
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    Full-text Dataset · Apr 2016
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    Full-text Dataset · Apr 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Genetic risk for schizophrenia is associated with impairments in the initiation and performance of executive control of cognition and action. The nature of these impairments and of the neural dysfunction that underlies them has been extensively investigated using experimental psychology and neuroimaging methods. In this article, we review schizophrenia-associated functional connectivity and activation abnormalities found in subjects performing experimental tasks that engage different aspects of executive function, such as working memory, cognitive control, and response inhibition. We focus on heritable traits associated with schizophrenia risk (intermediate phenotypes or endophenotypes) that have been revealed using imaging genetics approaches. These data suggest that genetic risk for schizophrenia is associated with dysfunction in systems supporting the initiation and application of executive control in neural circuits involving the anterior cingulate and dorsolateral prefrontal cortex. This article discusses current findings and limitations and their potential relevance to symptoms and disease pathogenesis.
    Article · Mar 2016
  • Stefanie Brassen · Heike Tost · Fabian Höhn · [...] · Dieter F. Braus
    Article · Mar 2016 · Neuroscience Letters
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Psychiatric research is increasingly interested in the influence of social and environmental contexts on human health. According to recent findings, specific impacts of urban upbringing relate to the heightened prevalence of mental disorders. Although this is a major societal problem, it remains unknown which environmental components (e.g., psychosocial stressors, rare nature exposure) are responsible. Method: We introduce Ambulatory Assessment (AA) as a methodological approach to investigate contextual influences. GPS-triggered electronic diaries are suitable to capture data in everyday life, gathering information on both context and mental states to assess dynamic processes in real-life and real-time. Result: A longitudinal study at the Central Institute for Mental Health in Mannheim combines AA, fMRI and epigenetic approaches to investigate environmental factors influencing mental health. The findings might be incorporated in urban planning to reduce mental disorders.
    Article · Jan 2016
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    [Show abstract] [Hide abstract] ABSTRACT: White matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer's disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD. WM hyperintensity volume on fluid-attenuated inversion recovery images of 201 patients with AD (128 carriers and 73 non-carriers of the APOE ε4 risk allele) was determined globally as well as regionally with voxel-based lesion mapping. Clinical, neuropsychological and MRI data were collected from prospective multicenter trials conducted by the German Dementia Competence Network. WM hyperintensity volume was significantly greater in non-carriers of the APOE ε4 allele. Lesion distribution was similar among ε4 carriers and non-carriers. Only ε4 non-carriers showed a correlation between lesion volume and cognitive performance. The current findings indicate an increased prevalence of WM hyperintensities in non-carriers compared with carriers of the APOE ε4 allele among patients with AD. This is consistent with a possibly more pronounced contribution of heterogeneous vascular risk factors to WM damage and cognitive impairment in patients with AD without APOE ε4-mediated risk.
    Full-text Article · Dec 2015 · Alzheimer's Research and Therapy
  • [Show abstract] [Hide abstract] ABSTRACT: The developing human brain is shaped by environmental exposures - for better or worse. Many exposures relevant to mental health are genuinely social in nature or believed to have social subcomponents, even those related to more complex societal or area-level influences. The nature of how these social experiences are embedded into the environment may be crucial. Here we review select neuroscience evidence on the neural correlates of adverse and protective social exposures in their environmental context, focusing on human neuroimaging data and supporting cellular and molecular studies in laboratory animals. We also propose the inclusion of innovative methods in social neuroscience research that may provide new and ecologically more valid insight into the social-environmental risk architecture of the human brain.
    Article · Sep 2015 · Nature Neuroscience
  • [Show abstract] [Hide abstract] ABSTRACT: Convergent evidence implicates regional neural responses to reward anticipation in the pathogenesis of several psychiatric disorders, such as schizophrenia, where blunted ventral striatal responses to positive reward are observed in patients and at-risk populations. in vivo oxygen amperometry measurements in the ventral striatum in awake, behaving rats reveal reward-related tissue oxygen changes that closely parallel BOLD signal changes observed in human fMRI, suggesting that a cross-species approach targeting this mechanism might be feasible in psychopharmacology. The present study explored modulatory effects of acute, subanaesthetic doses of ketamine—a pharmacological model widely used in psychopharmacological research, both preclinically and clinically—on ventral striatum activity during performance of a reward anticipation task in both species, using fMRI in humans and in vivo oxygen amperometry in rats. In a region of interest analysis conducted following a cross-over placebo and ketamine study in human subjects, an attenuated ventral striatal response during reward anticipation was observed following ketamine relative to placebo during performance of a monetary incentive delay task. In rats, a comparable attenuation of ventral striatal signal was found after ketamine challenge, relative to vehicle, in response to a conditioned stimulus that predicted delivery of reward. This study provides the first data in both species demonstrating an attenuating effect of acute ketamine on reward-related ventral striatal [O2] and fMRI signals. These findings may help elucidate a deeper mechanistic understanding of the potential role of ketamine as a model for psychosis, show that cross-species pharmacological experiments targeting reward signalling are feasible, and suggest this phenotype as a promising translational biomarker for the development of novel compounds, assessment of disease status, and treatment efficacy.
    Article · Sep 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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    [Show abstract] [Hide abstract] ABSTRACT: Multivariate pattern analysis can reveal new information from neuroimaging data to illuminate human cognition and its disturbances. Here, we develop a methodological approach, based on multivariate statistical/machine learning and time series analysis, to discern cognitive processing stages from fMRI blood oxygenation level dependent (BOLD) time series. We apply this method to data recorded from a group of healthy adults whilst performing a virtual reality version of the delayed win-shift radial arm maze task. This task has been frequently used to study working memory and decision making in rodents. Using linear classifiers and multivariate test statistics in conjunction with time series bootstraps, we show that different cognitive stages of the task, as defined by the experimenter, namely, the encoding/retrieval, choice, reward and delay stages, can be statistically discriminated from the BOLD time series in brain areas relevant for decision making and working memory. Discrimination of these task stages was significantly reduced during poor behavioral performance in dorsolateral prefrontal cortex (DLPFC), but not in the primary visual cortex (V1). Experimenter-defined dissection of time series into class labels based on task structure was confirmed by an unsupervised, bottom-up approach based on Hidden Markov Models. Furthermore, we show that different groupings of recorded time points into cognitive event classes can be used to test hypotheses about the specific cognitive role of a given brain region during task execution. We found that whilst the DLPFC strongly differentiated between task stages associated with different memory loads, but not between different visual-spatial aspects, the reverse was true for V1. Our methodology illustrates how different aspects of cognitive information processing during one and the same task can be separated and attributed to specific brain regions based on information contained in multivariate patterns of voxel activity.
    Full-text Article · Sep 2015 · Frontiers in Human Neuroscience
  • [Show abstract] [Hide abstract] ABSTRACT: As evidenced by a multitude of studies, abnormalities in Theory of Mind (ToM) and its neural processing might constitute an intermediate phenotype of schizophrenia. If so, neural alterations during ToM should be observable in unaffected relatives of patients as well, since they share a considerable amount of genetic risk. While behaviorally, impaired ToM function is confirmed meta-analytically in relatives, evidence on aberrant function of the neural ToM network is sparse and inconclusive. The present study therefore aimed to further explore the neural correlates of ToM in relatives of schizophrenia. 297 controls and 63 unaffected first-degree relatives of patients with schizophrenia performed a ToM task during functional magnetic resonance imaging. Consistent with the literature relatives exhibited decreased activity of the medial prefrontal cortex. Additionally, increased recruitment of the right middle temporal gyrus and posterior cingulate cortex was found, which was related to subclinical paranoid symptoms in relatives. These results further support decreased medial prefrontal activation during ToM as an intermediate phenotype of genetic risk for schizophrenia. Enhanced recruitment of posterior ToM areas in relatives might indicate inefficiency mechanisms in the presence of genetic risk. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
    Article · Sep 2015 · Social Cognitive and Affective Neuroscience
  • Article · Sep 2015
  • N. Capraz · C. Akdeniz · A. Schaefer · [...] · H. Tost
    Article · Sep 2015
  • [Show abstract] [Hide abstract] ABSTRACT: Improved classification of mental disorders through neurobiological measures will require a set of traits that map to transdiagnostic subgroups of patients and align with heritable, core psychopathological processes at the center of the disorders of interest. A promising candidate is working memory (WM) function, for which deficits have been reported across multiple diagnostic entities including schizophrenia, bipolar disorder, ADHD, autism, and major depressive disorder. Here we review genetic working memory associations and their brain functional correlates from the perspective of identifying patient subgroups across conventional diagnostic boundaries, explore the utility of multimodal investigations integrating functional information at the neural systems level and explore potential limitations as well as future directions for research. © 2015 Wiley Periodicals, Inc.
    Article · Sep 2015 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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    [Show abstract] [Hide abstract] ABSTRACT: The brain is an inherently dynamic system, and executive cognition requires dynamically reconfiguring, highly evolving networks of brain regions that interact in complex and transient communication patterns. However, a precise characterization of these reconfiguration processes during cognitive function in humans remains elusive. Here, we use a series of techniques developed in the field of "dynamic network neuroscience" to investigate the dynamics of functional brain networks in 344 healthy subjects during a working-memory challenge (the "n-back" task). In contrast to a control condition, in which dynamic changes in cortical networks were spread evenly across systems, the effortful working-memory condition was characterized by a reconfiguration of frontoparietal and frontotemporal networks. This reconfiguration, which characterizes "network flexibility," employs transient and heterogeneous connectivity between frontal systems, which we refer to as "integration." Frontal integration predicted neuropsychological measures requiring working memory and executive cognition, suggesting that dynamic network reconfiguration between frontal systems supports those functions. Our results characterize dynamic reconfiguration of large-scale distributed neural circuits during executive cognition in humans and have implications for understanding impaired cognitive function in disorders affecting connectivity, such as schizophrenia or dementia.
    Full-text Article · Aug 2015 · Proceedings of the National Academy of Sciences
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    [Show abstract] [Hide abstract] ABSTRACT: The search for quantifiable biological mediators of genetic risk or 'intermediate phenotypes' is an essential strategy in psychiatric neuroscience and a useful tool for exploring the complex relationships between genes, neural circuits and behaviors. In recent years, the examination of connectivity-based intermediate phenotypes has gained increasing popularity in the study of schizophrenia, a brain disorder that manifests in early adulthood and disturbs a wide range of neural network functions. To date, several potential connectivity phenotypes have been identified that link neuroimaging measures of neural circuit interaction to genetic susceptibility for schizophrenia. This paper briefly reviews recent advances, current limitations and future directions in the search for functional connectivity intermediate phenotypes for schizophrenia across different cognitive domains. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text Article · Aug 2015 · Current opinion in neurobiology

Publication Stats

2k Citations


  • 2011
    • National Institutes of Health
      베서스다, Maryland, United States
  • 2009
    • National Institute of Mental Health (NIMH)
      • Clinical Brain Disorders Branch
      Bethesda, MD, United States
  • 2008
    • Georg-August-Universität Göttingen
      • Department of Clinical Psychology and Psychotherapy
      Göttingen, Lower Saxony, Germany
  • 2005
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany