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Heike Tost

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12 papers

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YNIMG Journal 2022 Journal Article

Directed coupling in multi-brain networks underlies generalized synchrony during social exchange

Edda Bilek
Peter Zeidman
Peter Kirsch
Heike Tost
Andreas Meyer-Lindenberg
Karl Friston

Advances in social neuroscience have made neural signatures of social exchange measurable simultaneously across people. This has identified brain regions differentially active during social interaction between human dyads, but the underlying systems-level mechanisms are incompletely understood. This paper introduces dynamic causal modeling and Bayesian model comparison to assess the causal and directed connectivity between two brains in the context of hyperscanning (h-DCM). In this setting, correlated neuronal responses become the data features that have to be explained by models with and without between-brain (effective) connections. Connections between brains can be understood in the context of generalized synchrony, which explains how dynamical systems become synchronized when they are coupled to each another. Under generalized synchrony, each brain state can be predicted by the other brain or a mixture of both. Our results show that effective connectivity between brains is not a feature within dyads per se but emerges selectively during social exchange. We demonstrate a causal impact of the sender's brain activity on the receiver of information, which explains previous reports of two-brain synchrony. We discuss the implications of this work; in particular, how characterizing generalized synchrony enables the discovery of between-brain connections in any social contact, and the advantage of h-DCM in studying brain function on the subject level, dyadic level, and group level within a directed model of (between) brain function.

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YNIMG Journal 2021 Journal Article

Generative network models of altered structural brain connectivity in schizophrenia

Xiaolong Zhang
Urs Braun
Anais Harneit
Zhenxiang Zang
Lena S. Geiger
Richard F. Betzel
Junfang Chen
Janina I. Schweiger

Alterations in the structural connectome of schizophrenia patients have been widely characterized, but the mechanisms remain largely unknown. Generative network models have recently been introduced as a tool to test the biological underpinnings of altered brain network formation. We evaluated different generative network models in healthy controls (n=152), schizophrenia patients (n=66), and their unaffected first-degree relatives (n=32), and we identified spatial and topological factors contributing to network formation. We further investigated how these factors relate to cognition and to polygenic risk for schizophrenia. Our data show that among the four tested classes of generative network models, structural brain networks were optimally accounted for by a two-factor model combining spatial constraints and topological neighborhood structure. The same wiring model explained brain network formation across study groups. However, relatives and schizophrenia patients exhibited significantly lower spatial constraints and lower topological facilitation compared to healthy controls. Further exploratory analyses point to potential associations of the model parameter reflecting spatial constraints with the polygenic risk for schizophrenia and cognitive performance. Our results identify spatial constraints and local topological structure as two interrelated mechanisms contributing to regular brain network formation as well as altered connectomes in schizophrenia and healthy individuals at familial risk for schizophrenia. On an exploratory level, our data further point to the potential relevance of spatial constraints for the genetic risk for schizophrenia and general cognitive functioning, thereby encouraging future studies in following up on these observations to gain further insights into the biological basis and behavioral relevance of model parameters.

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YNIMG Journal 2019 Journal Article

Bidirectional signal exchanges and their mechanisms during joint attention interaction – A hyperscanning fMRI study

Gadi Goelman
Rotem Dan
Gabriela Stößel
Heike Tost
Andreas Meyer-Lindenberg
Edda Bilek

Social interactions are essential to our daily life. We tested the hypothesis that social interactions during joint attention (JA) require bidirectional communication, each with a different mechanism. We used a novel multivariate functional connectivity analysis, which enables obtaining directed pathways between four regions at each time-frequency point, with hyper-scanning MRI data of real-time JA interaction. Constructing multiple “4-regional directed pathways” and counting the number of times, regions engaged in feedforward or feedback processes in the ‘sender’ or the ‘receiver brains, we obtained the following. (1) There were more regions in feedforward than in feedback processes (125 versus 99). (2) The right hemisphere was more involved in feedforward (74 versus 33), while the left hemisphere in feedback (66 versus 51). (3) The dmPFC was more engaged in feedforward (73 versus 44) while the TPJ in both (49 versus 45). (4) The dmPFC was more involved in the sending processes (i. e. initiation of feedforward and feedback) while the TPJ in the receiving processes. (5) JA interaction was involved with high MRI frequencies (0. 04–0. 1 Hz), while continues interactions by low MRI frequencies (0. 01–0. 04 Hz). (6) Initiation and responding to JA (i. e. IJA and RJA) evolved with composite neural systems: similar systems for pathways that included the dmPFC, vmPFC and the STS, and different systems for pathways that included the TPJ, vmPFC, PCC and the STS. These findings have important consequences in the basic understanding of social interaction and could help in diagnose and follow-up of social impairments.

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YNICL Journal 2018 Journal Article

No association between cardiometabolic risk and neural reactivity to acute psychosocial stress

Florian Lederbogen
Elisabeth Ulshöfer
Annika Peifer
Phöbe Fehlner
Edda Bilek
Fabian Streit
Michael Deuschle
Heike Tost

Background Exaggerated reactivity to acute psychosocial stress is associated with an increased risk of cardiovascular and metabolic disease. A dysfunction of the cortico-limbic network coordinating the peripheral adaptation to acute stress exposure may constitute a brain mechanism underlying this association. We opted to characterize the changes of this network associated with acute psychosocial stress exposure in individuals with low and high cardiometabolic risk (CMR). Methods In 57 subjects without overt cardiac or cerebral disease, the Framingham risk score and presence/absence of type 2 diabetes or metabolic syndrome defined CMR. Psychosocial stress was induced during functional magnetic resonance imaging (fMRI) of brain activity by an established social threat paradigm. Measurements of heart rate, blood pressure and saliva cortisol quantified the peripheral stress reaction. Regression analyses for the anterior cingulate cortex, hippocampus, amygdala, insula and regulatory prefrontal regions evaluated the association of stress-associated brain activation and CMR. Results Psychosocial stress exposure was associated with an increased activity of a brain network including anterior and posterior cingulate cortex, putamen, insula, parahippocampus and right hippocampus. Psychosocial stress-associated brain activation did neither covary with Framingham risk score nor differ between groups with low or high CMR. Conclusion Exposure to acute psychosocial stress induces the activation of a well-defined cortico-limbic network. However, we did not find an association between CMR and this network's stress reactivity.

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YNIMG Journal 2014 Journal Article

Amygdala habituation: A reliable fMRI phenotype

Michael M. Plichta
Oliver Grimm
Katrin Morgen
Daniela Mier
Carina Sauer
Leila Haddad
Heike Tost
Christine Esslinger

Amygdala function is of high interest for cognitive, social and psychiatric neuroscience, emphasizing the need for reliable assessments in humans. Previous work has indicated unsatisfactorily low within-subject reliability of amygdala activation fMRI measures. Based on basic science evidence for strong habituation of amygdala response to repeated stimuli, we investigated whether a quantification of habituation provides additional information beyond the usual estimate of the overall mean activity. We assessed the within-subject reliability of amygdala habituation measures during a facial emotion matching paradigm in 25 healthy subjects. We extracted the amygdala signal decrement across the course of the fMRI run for the two test–retest measurement sessions and compared reliability estimates with previous findings based on mean response amplitude. Retest-reliability of the session-wise amygdala habituation was significantly higher than the evoked amygdala mean amplitude (intraclass correlation coefficients (ICC)=0. 53 vs. 0. 16). To test the task-specificity of this finding, we compared the retest-reliability of amygdala habituation across two different tasks. Significant amygdala response decrement was also seen in a cognitive task (n-back working memory) that did not per se activate the amygdala, but was totally unreliable in that context (ICC~0. 0), arguing for task-specificity. Together the results show that emotion-dependent amygdala habituation is a robust and considerably more reliable index than the mean amplitude, and provides a robust potential endpoint for within-subject designs including pharmaco-fMRI studies.

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YNICL Journal 2014 Journal Article

Larger amygdala volume in first-degree relatives of patients with major depression

Nina Romanczuk-Seiferth
Lydia Pöhland
Sebastian Mohnke
Maria Garbusow
Susanne Erk
Leila Haddad
Oliver Grimm
Heike Tost

OBJECTIVE: Although a heritable contribution to risk for major depressive disorder (MDD) has been established and neural alterations in patients have been identified through neuroimaging, it is unclear which brain abnormalities are related to genetic risk. Studies on brain structure of high-risk subjects - such as individuals carrying a familial liability for the development of MDD - can provide information on the potential usefulness of these measures as intermediate phenotypes of MDD. METHODS: 63 healthy first-degree relatives of patients with MDD and 63 healthy controls underwent structural magnetic resonance imaging. Regional gray matter volumes were analyzed via voxel-based morphometry (VBM). RESULTS: Whole-brain analysis revealed significantly larger gray matter volume in the bilateral amygdala in first-degree relatives of patients with MDD. Furthermore, relatives showed significantly larger gray matter volume in anatomical structures found relevant to MDD in previous literature, specifically in the bilateral hippocampus and amygdala as well as the left dorsolateral prefrontal cortex (DLPFC). Bilateral DLPFC volume correlated positively with the experience of negative affect. CONCLUSIONS: Larger gray matter volume in healthy relatives of MDD patients point to a possible vulnerability mechanism in MDD etiology and therefore extend knowledge in the field of high-risk approaches in MDD.

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YNIMG Journal 2014 Journal Article

Replication of brain function effects of a genome-wide supported psychiatric risk variant in the CACNA1C gene and new multi-locus effects

Susanne Erk
Andreas Meyer-Lindenberg
David E.J. Linden
Thomas Lancaster
Sebastian Mohnke
Oliver Grimm
Franziska Degenhardt
Peter Holmans

Variation in the CACNA1C gene has consistently been associated with psychosis in genome wide association studies. We have previously shown in a sample of n=110 healthy subjects that carriers of the CACNA1C rs1006737 risk variant exhibit hippocampal and perigenual anterior cingulate dysfunction (pgACC) during episodic memory recall. Here, we aimed to replicate our results, by testing for the effects of the rs1006737 risk variant in a new large cohort of healthy controls. We furthermore sought to refine these results by identifying the impact of a CACNA1C specific, gene-wide risk score in the absence of clinical pathology. An independent sample of 179 healthy subjects genotyped for rs1006737 underwent functional magnetic resonance imaging (fMRI) while performing an associative episodic memory task and underwent psychological testing similar to the discovery sample. The effect of gene-wide risk scores was analyzed in the combined sample of 289 subjects. We replicated our discovery findings of hippocampal and pgACC dysfunction in carriers of the rs1006737 risk variant. Additionally, we observed diminished activation of the dorsolateral prefrontal cortex, in the replication sample. Our replicated results as well as this new effect were also observable in the combined sample. Moreover, the same system-level phenotypes were significantly associated with the individual gene-based genetic risk score. Our findings suggest that altered hippocampal and frontolimbic function is associated with variants in the CACNA1C gene. Since CACNA1C variants have been associated repeatedly with psychosis at a genome-wide level, and preclinical data provide convergent evidence for the relevance of the CACNA1C gene for hippocampal and frontolimbic plasticity and adaptive regulation of stress, our data suggest a potential pathophysiological mechanism conferred by CACNA1C variants that may mediate risk for symptom dimensions shared among bipolar disorder, major depression, and schizophrenia.

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YNIMG Journal 2014 Journal Article

Test–retest reliability of fMRI-based graph theoretical properties during working memory, emotion processing, and resting state

Hengyi Cao
Michael M. Plichta
Axel Schäfer
Leila Haddad
Oliver Grimm
Michael Schneider
Christine Esslinger
Peter Kirsch

The investigation of the brain connectome with functional magnetic resonance imaging (fMRI) and graph theory analyses has recently gained much popularity, but little is known about the robustness of these properties, in particular those derived from active fMRI tasks. Here, we studied the test–retest reliability of brain graphs calculated from 26 healthy participants with three established fMRI experiments (n-back working memory, emotional face-matching, resting state) and two parcellation schemes for node definition (AAL atlas, functional atlas proposed by Power et al.). We compared the intra-class correlation coefficients (ICCs) of five different data processing strategies and demonstrated a superior reliability of task-regression methods with condition-specific regressors. The between-task comparison revealed significantly higher ICCs for resting state relative to the active tasks, and a superiority of the n-back task relative to the face-matching task for global and local network properties. While the mean ICCs were typically lower for the active tasks, overall fair to good reliabilities were detected for global and local connectivity properties, and for the n-back task with both atlases, smallworldness. For all three tasks and atlases, low mean ICCs were seen for the local network properties. However, node-specific good reliabilities were detected for node degree in regions known to be critical for the challenged functions (resting-state: default-mode network nodes, n-back: fronto-parietal nodes, face-matching: limbic nodes). Between-atlas comparison demonstrated significantly higher reliabilities for the functional parcellations for global and local network properties. Our findings can inform the choice of processing strategies, brain atlases and outcome properties for fMRI studies using active tasks, graph theory methods, and within-subject designs, in particular future pharmaco-fMRI studies.

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YNIMG Journal 2012 Journal Article

Brain connectivity in psychiatric imaging genetics

Heike Tost
Edda Bilek
Andreas Meyer-Lindenberg

In the past decade, imaging genetics has evolved into a highly successful neuroimaging discipline with a variety of sophisticated research tools. To date, several neural systems mechanisms have been identified that mediate genetic risk for mental disorders linked to common candidate and genome-wide-supported variants. In particular, the examination of intermediate connectivity phenotypes has recently gained increasing popularity. This paper gives an overview of the scientific methods and evidence that link indices of neural network organization to the genetic susceptibility for mental illness with a focus on the effects of candidate genes and genome-wide supported risk variants on brain structure and function.

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YNIMG Journal 2012 Journal Article

Genetic variation in CYP2D6 impacts neural activation during cognitive tasks in humans

Julia C. Stingl
Christine Esslinger
Heike Tost
Edda Bilek
Peter Kirsch
Barbara Ohmle
Roberto Viviani
Henrik Walter

The drug metabolizing cytochrome P450 2D6 enzyme (CYP2D6) is highly expressed in brain and potentially involved in neurotransmitter biotransformation. Here, we report the effect of the CYP2D6 genotype on brain activation during a working memory and an emotional face matching task measured with fMRI. Subjects were taken from an ongoing large scale multicenter imaging genetic study. CYP2D6 genotyping of the alleles *2, *3, *4, *5, *6, *9, *10, *17, *35, *41 and the duplication was performed in N =114 healthy drug free individuals. All individuals had completed two tasks in functional brain imaging: an n-back working memory task and an implicit emotional face matching task. Contrast images were analyzed in second-level random effects models with CYP2D6 enzyme activity levels as regressor of interest and age, sex and scanning site as covariates. In the working memory task, a significant effect of CYP2D6 genotype was found in the fusiform gyrus and the precuneus. In the emotional face matching task, an effect was detected in the cuneus. No significant activation results were found in the thalamus. A conjunction analysis confirmed a significant joint effect of the CYP2D6 association in both regions. In both tasks activation increased with increasing CYP2D6 activity. In conclusion, we confirmed a central nervous system effect of CYP2D6 activity in a large independent sample using a different imaging modality, and provide evidence that basic cognitive processes related to such as alertness may be impacted.

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YNIMG Journal 2012 Journal Article

Microstructure of a three-way anatomical network predicts individual differences in response inhibition: A tractography study

Andrea V. King
Julia Linke
Achim Gass
Michael G. Hennerici
Heike Tost
Cyril Poupon
Michèle Wessa

Response inhibition is thought to depend critically on the inferior frontal gyrus, pars opercularis (IFGoper), presupplementary motor area (preSMA) and basal ganglia, including the subthalamic nucleus (STN), but the differential contribution of structural connections within this network to response inhibition remains unclear. Using diffusion tensor imaging and probabilistic fiber tractography, we investigated the relative associations between local white matter microstructure and stop-signal response inhibition in fronto-basal ganglia tracts delineated by probabilistic tractography. In a tract-of-interest approach, we identify significant associations with fractional anisotropy (FA) in fibers connecting the right STN region to both preSMA/SMA and IFGoper and in bilateral tracts connecting preSMA/SMA to IFGoper and the striatum. In addition, significant associations with radial diffusivity (RD) were found in fibers connecting the right preSMA/SMA to striatum and in bilateral tracts between IFGoper and STN region. In our whole-brain analysis, additional significant clusters were identified in the corpus callosum, optic radiation, inferior fronto-occipital tract and white matter of the precentral gyrus. To investigate the relative importance of regional white matter characteristics to response inhibition performance, we performed a step-wise multiple regression analysis that yielded FA in tracts connecting preSMA/SMA to the STN region and striatum, respectively, and RD in fibers connecting IFGoper to the STN region as best predictors of response inhibition performance (42% explained variance). These findings point to a specific contribution of white matter pathways connecting distinct basal ganglia structures with both medial frontal and ventrolateral prefrontal regions to response inhibition.

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YNIMG Journal 2012 Journal Article

Test–retest reliability of evoked BOLD signals from a cognitive–emotive fMRI test battery

Michael M. Plichta
Adam J. Schwarz
Oliver Grimm
Katrin Morgen
Daniela Mier
Leila Haddad
Antje B.M. Gerdes
Carina Sauer

Even more than in cognitive research applications, moving fMRI to the clinic and the drug development process requires the generation of stable and reliable signal changes. The performance characteristics of the fMRI paradigm constrain experimental power and may require different study designs (e. g. , crossover vs. parallel groups), yet fMRI reliability characteristics can be strongly dependent on the nature of the fMRI task. The present study investigated both within-subject and group-level reliability of a combined three-task fMRI battery targeting three systems of wide applicability in clinical and cognitive neuroscience: an emotional (face matching), a motivational (monetary reward anticipation) and a cognitive (n-back working memory) task. A group of 25 young, healthy volunteers were scanned twice on a 3T MRI scanner with a mean test–retest interval of 14. 6days. FMRI reliability was quantified using the intraclass correlation coefficient (ICC) applied at three different levels ranging from a global to a localized and fine spatial scale: (1) reliability of group-level activation maps over the whole brain and within targeted regions of interest (ROIs); (2) within-subject reliability of ROI-mean amplitudes and (3) within-subject reliability of individual voxels in the target ROIs. Results showed robust evoked activation of all three tasks in their respective target regions (emotional task=amygdala; motivational task=ventral striatum; cognitive task=right dorsolateral prefrontal cortex and parietal cortices) with high effect sizes (ES) of ROI-mean summary values (ES=1. 11–1. 44 for the faces task, 0. 96–1. 43 for the reward task, 0. 83–2. 58 for the n-back task). Reliability of group level activation was excellent for all three tasks with ICCs of 0. 89–0. 98 at the whole brain level and 0. 66–0. 97 within target ROIs. Within-subject reliability of ROI-mean amplitudes across sessions was fair to good for the reward task (ICCs=0. 56–0. 62) and, dependent on the particular ROI, also fair-to-good for the n-back task (ICCs=0. 44–0. 57) but lower for the faces task (ICC=−0. 02–0. 16). In conclusion, all three tasks are well suited to between-subject designs, including imaging genetics. When specific recommendations are followed, the n-back and reward task are also suited for within-subject designs, including pharmaco-fMRI. The present study provides task-specific fMRI reliability performance measures that will inform the optimal use, powering and design of fMRI studies using comparable tasks.

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