Author name cluster

Thomas Straube

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

32 papers

1 author row

YNICL Journal 2026 Journal Article

Disrupted thalamocortical functional connectivity and canonical resting-state network integration in posttraumatic stress disorder

Nick Steele
Ahmed Hussain
Delin Sun
Courtney Russell
Ashley A. Huggins
Nicholas D. Davenport
Seth G. Disner
Scott R. Sponheim

The thalamus exhibits widespread connectivity to the entire cortical mantle, yet distinct thalamic subregions possess unique connectivity profiles and functional roles. While the thalamus has been consistently implicated in posttraumatic stress disorder (PTSD), fine-grained investigations examining thalamic subregions and nuclei remain sparse. We examined how resting-state functional connectivity (RSFC) of thalamic nuclei with the cortex and large-scale brain networks may contribute to PTSD using high-resolution functional magnetic resonance imaging (fMRI) data from a multi-site dataset of PTSD cases and controls (n = 397). We show that the pulvinar nuclei exhibit weaker RSFC with sensorimotor and salience regions, while the medial geniculate nucleus (MGN) exhibits stronger RSFC with the sensorimotor cortex in PTSD. Greater PTSD severity correlated with weaker RSFC between both the pulvinar and mediodorsal thalamus and cortical sensory/motor regions in the frontal, parietal, and occipital lobes. We identified that the default mode network of PTSD participants had stronger RSFC with the mediodorsal thalamus, while the salience and somatosensory networks exhibited stronger RSFC with somatomotor thalamic nuclei. Fine-grained thalamic mapping is important for uncovering thalamocortical disruptions in PTSD. Thalamic RSFC shows a shift toward heightened subcortical sensory responsivity and diminished voluntary control and cognitive regulation in PTSD.

YNIMG Journal 2025 Journal Article

Image-based meta- and mega-analysis (IBMMA): A unified framework for large-scale, multi-site, neuroimaging data analysis

Nick Steele
Ashley A. Huggins
Rajendra A. Morey
Ahmed Hussain
Courtney Russell
Benjamin Suarez-Jimenez
Elena Pozzi
Hadis Jameei

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA successfully analyzed a large-n dataset of several thousand participants and revealed findings in brain regions that some traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage. IBMMA has the potential to accelerate discoveries in neuroscience and enhance the clinical utility of neuroimaging findings.

YNIMG Journal 2024 Journal Article

Lack of evidence for predictive utility from resting state fMRI data for individual exposure-based cognitive behavioral therapy outcomes: A machine learning study in two large multi-site samples in anxiety disorders

Kevin Hilbert
Joscha Böhnlein
Charlotte Meinke
Alice V. Chavanne
Till Langhammer
Lara Stumpe
Nils Winter
Ramona Leenings

Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.

YNIMG Journal 2023 Journal Article

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium

Xi Zhu
Yoojean Kim
Orren Ravid
Xiaofu He
Benjamin Suarez-Jimenez
Sigal Zilcha-Mano
Amit Lazarov
Seonjoo Lee

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

YNIMG Journal 2023 Journal Article

The effects of visual perceptual load on detection performance and event-related potentials to auditory stimuli

Laura Brockhoff
Elisa Adriana Elias
Maximilian Bruchmann
Sebastian Schindler
Robert Moeck
Thomas Straube

Load Theory states that perceptual load prevents, or at least reduces, the processing of task-unrelated stimuli. This study systematically examined the detection and neural processing of auditory stimuli unrelated to a visual foreground task. The visual task was designed to create continuous perceptual load, alternated between low and high load, and contained performance feedback to motivate participants to focus on the visual task instead of the auditory stimuli presented in the background. The auditory stimuli varied in intensity, and participants signaled their subjective perception of these stimuli without receiving feedback. Depending on stimulus intensity, we observed load effects on detection performance and P3 amplitudes of the event-related potential (ERP). N1 amplitudes were unaffected by perceptual load, as tested by Bayesian statistics. Findings suggest that visual perceptual load affects the processing of auditory stimuli in a late time window, which is associated with a lower probability of reported awareness of these stimuli.

YNIMG Journal 2022 Journal Article

A comparison of methods to harmonize cortical thickness measurements across scanners and sites

Delin Sun
Gopalkumar Rakesh
Courtney C. Haswell
Mark Logue
C. Lexi Baird
Erin N. O'Leary
Andrew S. Cotton
Hong Xie

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1, 340 cases with posttraumatic stress disorder (PTSD) (6. 2–81. 8 years old) and 2, 057 trauma-exposed controls without PTSD (6. 3–85. 2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ 2(3) = 63. 704, p < 0. 001) as well as case-control differences in age-related cortical thinning (Χ 2(3) = 12. 082, p = 0. 007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ 2(3) = 9. 114, p = 0. 028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0. 001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0. 001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0. 001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0. 001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0. 001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

YNIMG Journal 2022 Journal Article

Differential effects of prediction error and adaptation along the auditory cortical hierarchy during deviance processing

Insa Schlossmacher
Jacky Dilly
Ina Protmann
David Hofmann
Torge Dellert
Marie-Luise Roth-Paysen
Robert Moeck
Maximilian Bruchmann

Neural mismatch responses have been proposed to rely on different mechanisms, including prediction error-related activity and adaptation to frequent stimuli. However, the hierarchical cortical structure of these mechanisms is unknown. To investigate this question, we recorded hemodynamic responses while participants (N = 54) listened to an auditory oddball sequence as well as a suited control condition. In addition to effects in sensory processing areas (Heschl's gyrus, superior temporal gyrus (STG)), we found several distinct clusters that indexed deviance processing in frontal and parietal regions (anterior cingulate cortex/supplementary motor area (ACC/SMA), inferior parietal lobule (IPL), anterior insula (AI), inferior frontal junction (IFJ)). Comparing responses to the control stimulus with the deviant and standard enabled us to delineate the contributions of prediction error- or adaptation-related brain activation, respectively. We observed significant effects of adaptation in Heschl's gyrus, STG and ACC/SMA, while prediction error-related activity was observed in STG, IPL, AI and IFJ. Additional dynamic causal modeling confirmed the superiority of a hierarchical processing structure compared to a flat structure. Thus, we found that while prediction-error related processes increased with the hierarchical level of the brain area, adaptation declined. This suggests that the relative contribution of different mechanisms in deviance processing varies across the cortical hierarchy.

YNIMG Journal 2022 Journal Article

Early and late electrophysiological correlates of gradual perceptual awareness in- and outside the Attentional Blink window

Marie-Luise Roth-Paysen
Anne Bröcker
Maximilian Bruchmann
Thomas Straube

There is an ongoing debate on the neural correlates of consciousness (NCC) in the attentional blink (AB). Theoretical accounts propose that NCC during the attentional blink occur late in the processing hierarchy and that this quality is specific to the AB. We investigated this question by recording event-related potentials during an AB experiment with faces as T2. We analyzed ERPs to T2 stimuli inside (short lag) and outside (long lag) the AB window after carefully calibrating T2 stimuli to ensure equal visibility ratings across lags. We found that the N170, the visual awareness negativity (VAN), and the P3b showed an increased amplitude for seen compared to unseen face stimuli regardless of stimulus lag and that all these components scale linearly with subjective visibility. These findings suggest similar early and late mechanisms of graded perceptual awareness within and outside the AB across perceptual (N170, VAN) and post-perceptual (P3b) processing stages.

YNIMG Journal 2022 Journal Article

Effects of awareness and task relevance on neurocomputational models of mismatch negativity generation

Insa Schlossmacher
Felix Lucka
Antje Peters
Maximilian Bruchmann
Thomas Straube

Detection of regularities and their violations in sensory input is key to perception. Violations are indexed by an early EEG component called the mismatch negativity (MMN) - even if participants are distracted or unaware of the stimuli. On a mechanistic level, two dominant models have been suggested to contribute to the MMN: adaptation and prediction. Whether and how context conditions, such as awareness and task relevance, modulate the mechanisms of MMN generation is unknown. We conducted an EEG study disentangling influences of task relevance and awareness on the visual MMN. Then, we estimated different computational models for the generation of single-trial amplitudes in the MMN time window. Amplitudes were best explained by a prediction error model when stimuli were task-relevant but by an adaptation model when task-irrelevant and unaware. Thus, mismatch generation does not rely on one predominant mechanism but mechanisms vary with task relevance of stimuli.

YNIMG Journal 2022 Journal Article

Neural correlates of consciousness in an attentional blink paradigm with uncertain target relevance

Torge Dellert
Sophie Krebs
Maximilian Bruchmann
Sebastian Schindler
Antje Peters
Thomas Straube

Several event-related potentials (ERPs) have been proposed as neural correlates of consciousness (NCC), most prominently the early visual awareness negativity (VAN) and the late P3b component. Highly influential support for the P3b comes from studies utilizing the attentional blink (AB), where conscious perception of a first visual target (T1) impairs reporting a second target (T2) presented shortly afterwards. Recent no-report studies using other paradigms suggest that the P3b component may reflect post-perceptual processes associated with decision-making rather than awareness. However, no-report studies are limited in their awareness assessment, and their conclusions have not been tested in an AB paradigm. The present study (N = 38) addressed these issues using a novel AB paradigm, which reduced decision-making processes by omitting a discrimination task on T2 stimuli and rendering their relevance uncertain. Nevertheless, awareness was assessed trial by trial. Comparing ERPs in response to seen versus unseen T2 stimuli revealed a VAN but no enhanced P3b regardless of whether they were marked as distinct from distractor stimuli or not. Our results corroborate the VAN and challenge the P3b as NCC despite rigorous trial-by-trial assessment of conscious perception. Thus, they support the idea that awareness emerges during early sensory processing.

YNICL Journal 2022 Journal Article

Neural correlates of fear conditioning are associated with treatment-outcomes to behavioral exposure in spider phobia – Evidence from magnetoencephalography

Kati Roesmann
Julius Toelle
Elisabeth Johanna Leehr
Ida Wessing
Joscha Böhnlein
Fabian Seeger
Hanna Schwarzmeier
Niklas Siminski

BACKGROUND: Models of anxiety disorders and the rationale of exposure therapy (ET) are grounded on classical fear conditioning. Yet, it is unclear whether lower fear ratings of conditioned safety versus threat cues and corresponding neural markers of safety-learning and/or fear inhibition assessed before treatment would predict better outcomes of behavioral exposure. METHODS: Sixty-six patients with spider phobia completed pre-treatment clinical and experimental fear conditioning assessments, one session of virtual reality ET, a post-treatment clinical assessment, and a 6-month follow-up assessment. Tilted Gabor gratings served as conditioned stimuli (CS) that were either paired (CS+) or remained unpaired (CS-) with an aversive phobia-related and phobia-unrelated unconditioned stimulus (UCS). CS+/CS- differences in fear ratings and magnetoencephalographic event-related fields (ERFs) were related to percentual symptom reductions from pre- to post-treatment, as assessed via spider phobia questionnaire (SPQ), behavioral avoidance test (BAT), and remission status at 6-month follow-up. RESULTS: We observed no associations between pre-treatment CS+/CS- differences in fear ratings and any treatment outcome. CS+/CS- differences in source estimations of ERFs revealed that higher CS- activity in bilateral dorsolateral prefrontal cortex (dlPFC) was related with SPQ- and BAT-reductions. Associations between CS+/CS- differences and treatment outcomes were also observed in left ventromedial prefrontal cortex (vmPFC) regions, which additionally revealed associations with the follow-up remission status. CONCLUSIONS: Results provide initial evidence that neural pre-treatment CS+/CS- differences may hold predictive information regarding outcomes of behavioral exposure. Our findings highlight a key role of neural responses to safety cues with potentially inhibitory effects on affect-generating structures during fear conditioning.

YNIMG Journal 2021 Journal Article

Dissociating neural correlates of consciousness and task relevance during auditory processing

Insa Schlossmacher
Torge Dellert
Maximilian Bruchmann
Thomas Straube

In recent years, several ERP components have been identified as potential neural correlates of consciousness (NCC), including early negativities and late positivities. Based on experiments in the visual modality, it has recently been shown that awareness is often confounded with reporting it, possibly overestimating the NCC. It is unknown whether similar constraints also exist in the auditory modality. In order to address this gap, we presented spoken words in a sustained inattentional deafness paradigm. Electrophysiological responses were obtained in three physically identical experimental conditions that differed only with respect to the participants' instructions. Participants were either left uninformed or informed about the presence of spoken words while confronted with an auditory distractor task (U/I condition), informed about the words while exposed to the same task as before (I condition), or requested to respond to the now task-relevant speech stimuli (TR condition). After completion of the U/I condition, only informed participants reported awareness of the words. In ERPs, awareness of words in the U/I and I condition was accompanied by an anterior auditory awareness negativity (AAN). Only when stimuli were task-relevant, i.e., during the TR condition, late positivities emerged. Taken together, these results indicate that early negativities but not late positivities index awareness across sensory modalities. Thus, they provide evidence for a recurrent processing framework, which highlights the importance of early sensory processing in conscious perception.

YNICL Journal 2019 Journal Article

Phasic amygdala and BNST activation during the anticipation of temporally unpredictable social observation in social anxiety disorder patients

Benedikt Figel
Leonie Brinkmann
Christine Buff
Carina Y. Heitmann
David Hofmann
Maximilian Bruchmann
Michael P.I. Becker
Martin J. Herrmann

Anticipation of potentially threatening social situations is a key process in social anxiety disorder (SAD). In other anxiety disorders, recent research of neural correlates of anticipation of temporally unpredictable threat suggests a temporally dissociable involvement of amygdala and bed nucleus of the stria terminalis (BNST) with phasic amygdala responses and sustained BNST activation. However, the temporal profile of amygdala and BNST responses during temporal unpredictability of threat has not been investigated in patients suffering from SAD. We used functional magnetic resonance imaging (fMRI) to investigate neural activation in the central nucleus of the amygdala (CeA) and the BNST during anticipation of temporally unpredictable aversive (video camera observation) relative to neutral (no camera observation) events in SAD patients compared to healthy controls (HC). For the analysis of fMRI data, we applied two regressors (phasic/sustained) within the same model to detect temporally dissociable brain responses. The aversive condition induced increased anxiety in patients compared to HC. SAD patients compared to HC showed increased phasic activation in the CeA and the BNST for anticipation of aversive relative to neutral events. SAD patients as well as HC showed sustained activity alterations in the BNST for aversive relative to neutral anticipation. No differential activity during sustained threat anticipation in SAD patients compared to HC was found. Taken together, our study reveals both CeA and BNST involvement during threat anticipation in SAD patients. The present results point towards potentially SAD-specific threat processing marked by elevated phasic but not sustained CeA and BNST responses when compared to HC.

YNIMG Journal 2018 Journal Article

Early brain responses to affective faces: A simultaneous EEG-fMRI study

Miriam Müller-Bardorff
Maximilian Bruchmann
Martin Mothes-Lasch
Pienie Zwitserlood
Insa Schlossmacher
David Hofmann
Wolfgang Miltner
Thomas Straube

The spatio-temporal neural basis of earliest differentiation between emotional and neutral facial expressions is a matter of debate. The present study used concurrent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) in order to investigate the ‘when’ and ‘where’ of earliest prioritization of emotional over neutral expressions. We measured event-related potentials (ERPs) and blood oxygen dependent (BOLD) signal changes in response to facial expressions of varying emotional intensity and different valence categories. Facial expressions were presented superimposed by two horizontal bars and participants engaged in a focal bars task (low load, high load), in order to manipulate the availability of attentional resources during face perception. EEG data revealed the earliest expression effects in the P1 range (76–128 ms) as a parametric function of stimulus arousal independent of load conditions. Conventional fMRI data analysis also demonstrated significant modulations as a function of stimulus arousal, independent of load, in amygdala, superior temporal sulcus, fusiform gyrus and lateral occipital cortex. Correspondingly, EEG-informed fMRI analysis revealed a significant positive correlation between single-trial P1 amplitudes and BOLD responses in amygdala and lateral posterior occipital cortex. Our results are in line with the hypothesis of the amygdala as fast responding relevance detector and corresponding effects in early visual face processing areas across facial expressions and load conditions.

YNIMG Journal 2018 Journal Article

Inter-individual differences in trait anxiety shape the functional connectivity between the bed nucleus of the stria terminalis and the amygdala during brief threat processing

Leonie Brinkmann
Christine Buff
Katharina Feldker
Paula Neumeister
Carina Y. Heitmann
David Hofmann
Maximilian Bruchmann
Martin J. Herrmann

An influential framework suggests that the central nucleus of the amygdala (CeA) is involved in phasic responses to threat, while the bed nucleus of the stria terminalis (BNST) mediates sustained anxiety. However, this model has been questioned, proposing that the role of the BNST is not limited to sustained threat contexts. Rather, amygdala and BNST also seem to work in concert in the processing of discrete and briefly presented threat-related stimuli, likely dependent on inter-individual differences in anxiety. A direct test of this assumption with sufficient experimental power is missing in human research and the degree to which individual differences in trait anxiety moderate phasic responses and functional connectivity of amygdala and BNST during threat processing remains unclear. The current event-related functional magnetic resonance imaging (fMRI) study investigated activation and connectivity of amygdala and BNST, as well as modulating effects of trait anxiety, during processing of briefly presented threat-related relative to neutral standardized pictures in 93 psychiatrically healthy individuals. Both amygdala and BNST activation was increased during presentation of threat-related relative to neutral pictures. Furthermore, functional connectivity between BNST and amygdala in response to threat was positively associated with trait anxiety. These findings suggest that amygdala and BNST form a functional unit during phasic threat processing whereby their connectivity is shaped by inter-individual differences in trait anxiety.

YNICL Journal 2017 Journal Article

Brain activation to task-irrelevant disorder-related threat in social anxiety disorder: The impact of symptom severity

Carina Yvonne Heitmann
Katharina Feldker
Paula Neumeister
Leonie Brinkmann
Elisabeth Schrammen
Pienie Zwitserlood
Thomas Straube

Unintentional and uncontrollable processing of threat has been suggested to contribute to the pathology of social anxiety disorder (SAD). The present study investigated the neural correlates of processing task-irrelevant, highly ecologically valid, disorder-related stimuli as a function of symptom severity in SAD. Twenty-four SAD patients and 24 healthy controls (HC) performed a feature-based comparison task during functional magnetic resonance imaging, while task-irrelevant, disorder-related or neutral scenes were presented simultaneously at a different spatial position. SAD patients showed greater activity than HC in response to disorder-related versus neutral scenes in brain regions associated with self-referential processing (e.g. insula, precuneus, dorsomedial prefrontal cortex) and emotion regulation (e.g. dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus). Symptom severity was positively associated with amygdala activity, and negatively with activation in dorsal anterior cingulate cortex and dlPFC in SAD patients. Additional correlation analysis revealed that amygdala-prefrontal coupling was positively associated with symptom severity. A network of brain regions is thus involved in SAD patients' processing of task-irrelevant, complex, ecologically valid, disorder-related scenes. Furthermore, increasing symptom severity in SAD patients seems to reflect a growing imbalance between neural mechanisms related to stimulus-driven bottom-up and regulatory top-down processes resulting in dysfunctional regulation strategies.

YNICL Journal 2017 Journal Article

Initial and sustained brain responses to threat anticipation in blood-injection-injury phobia

Leonie Brinkmann
Hendrik Poller
Martin J. Herrmann
Wolfgang Miltner
Thomas Straube

Blood-injection-injury (BII) phobia differs from other subtypes of specific phobia in that it is associated with elevated disgust-sensitivity as well as specific autonomic and brain responses during processing of phobia-relevant stimuli. To what extent these features play a role already during threat anticipation is unclear. In the current fMRI experiment, 16 female BII phobics and 16 female healthy controls anticipated the presentation of phobia-specific and neutral pictures. On the behavioral level, anxiety dominated the anticipatory period in BII phobics relative to controls, while both anxiety and disgust were elevated during picture presentation. By applying two different models for the analysis of brain responses to anticipation of phobia-specific versus neutral stimuli, we found initial and sustained increases of activation in anterior cingulate cortex (ACC), insula, lateral and medial prefrontal cortex (PFC), thalamus and visual areas, as well as initial activation in the amygdala for BII phobics as compared to healthy controls. These results suggest that BII phobia is characterized by activation of a typical neural defense network during threat anticipation, with anxiety as the predominant emotion.

YNIMG Journal 2017 Journal Article

No differential effects to facial expressions under continuous flash suppression: An event-related potentials study

Insa Schlossmacher
Markus Junghöfer
Thomas Straube
Maximilian Bruchmann

In recent years continuous flash suppression (CFS) has become a popular “blinding” technique for the investigation of nonconscious affective processing since it elicits potent and long-lasting suppression of conscious visual perception. While the majority of studies provides some positive evidence for nonconscious affective processing, there are also studies reporting their absence. Several methodological variations may give rise to this discrepancy: with respect to the experimental paradigm these variations pertain to the likelihood of residual stimulus visibility on the level of individual participants and single trials. Concerning the statistical analysis they relate to the procedures applied to assess whether detection performance is at chance level and whether the outcome measure does or does not depend on the affective stimulus category. In the present study we determined individual eye dominance and individual stimulus contrast in pretests, measured objective and subjective awareness online and applied Bayesian statistics to estimate the likelihood for the null hypothesis. Event-related potentials (ERPs) were measured while participants were subjected to fearful, happy, and neutral faces in a conscious as well as in a nonconscious CFS condition. In the conscious condition, expected emotion effects were observed in the ERP components N170/EPN and LPP. However, despite high statistical power, no effects of emotional expression were found in the nonconscious condition and the absence of nonconscious affective processing under the tested conditions was substantially more likely than its presence. We discuss whether CFS disrupts affective processing completely if thoroughly applied or whether positive and negative findings should be integrated under a two-threshold framework of nonconscious processing.

YNICL Journal 2017 Journal Article

Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder

Janna Marie Bas-Hoogendam
Henk van Steenbergen
J. Nienke Pannekoek
Jean-Paul Fouche
Christine Lochner
Coenraad J. Hattingh
Henk R. Cremers
Tomas Furmark

Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples. An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n =174) and healthy control (HC)-participants (n =213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.

YNIMG Journal 2016 Journal Article

Look who's judging—Feedback source modulates brain activation to performance feedback in social anxiety

Jutta Peterburs
Carolin Sandrock
Wolfgang H.R. Miltner
Thomas Straube

It is as yet unknown if behavioral and neural correlates of performance monitoring in socially anxious individuals are affected by whether feedback is provided by a person or a computer. This fMRI study investigated modulation of feedback processing by feedback source (person vs. computer) in participants with high (HSA) (N=16) and low social anxiety (LSA) (N=16). Subjects performed a choice task in which they were informed that they would receive positive or negative feedback from a person or the computer. Subjective ratings indicated increased arousal and anxiety in HSA versus LSA, most pronounced for social and negative feedback. FMRI analyses yielded hyperactivation in ventral medial prefrontal cortex (vmPFC)/anterior cingulate cortex (ACC) and insula for social relative to computer feedback, and in mPFC/ventral ACC for positive relative to negative feedback in HSA as compared to LSA. These activation patterns are consistent with increased interoception and self-referential processing in social anxiety, especially during processing of positive feedback. Increased ACC activation in HSA to positive feedback may link to unexpectedness of (social) praise as posited in social anxiety disorder (SAD) psychopathology. Activation in rostral ACC showed a reversed pattern, with decreased activation to positive feedback in HSA, possibly indicating altered action values depending on feedback source and valence. The present findings corroborate a crucial role of mPFC for performance monitoring in social anxiety.

YNIMG Journal 2016 Journal Article

Parametric modulation of reward sequences during a reversal task in ACC and VMPFC but not amygdala and striatum

Michael P.I. Becker
Alexander M. Nitsch
Johannes Hewig
Wolfgang H.R. Miltner
Thomas Straube

Several regions of the frontal cortex interact with striatal and amygdala regions to mediate the evaluation of reward-related information and subsequent adjustment of response choices. Recent theories discuss the particular relevance of dorsal anterior cingulate cortex (dACC) for switching behavior; consecutively, ventromedial prefrontal cortex (VMPFC) is involved in mediating exploitative behaviors by tracking reward values unfolding after the behavioral switch. Amygdala, on the other hand, has been implied in coding the valence of stimulus-outcome associations and the ventral striatum (VS) has consistently been shown to code a reward prediction error (RPE). Here, we used fMRI data acquired in humans during a reversal task to parametrically model different sequences of positive feedback in order to unravel differential contributions of these brain regions to the tracking and exploitation of rewards. Parameters from an Optimal Bayesian Learner accurately predicted the divergent involvement of dACC and VMPFC during feedback processing: dACC signaled the first, but not later, presentations of positive feedback, while VMPFC coded trial-by-trial accumulations in reward value. Our results confirm that dACC carries a prominent confirmatory signal during processing of first positive feedback. Amygdala coded positive feedbacks more uniformly, while striatal regions were associated with RPE.

YNICL Journal 2016 Journal Article

Specifically altered brain responses to threat in generalized anxiety disorder relative to social anxiety disorder and panic disorder

Christine Buff
Leonie Brinkmann
Paula Neumeister
Katharina Feldker
Carina Heitmann
Bettina Gathmann
Tanja Andor
Thomas Straube

BACKGROUND: Despite considerable effort, the neurobiological underpinnings of hyper-responsive threat processing specific to patients suffering from generalized anxiety disorder (GAD) remain poorly understood. The current functional magnetic resonance imaging (fMRI) study aims to delineate GAD-specific brain activity during immediate threat processing by comparing GAD patients to healthy controls (HC), to social anxiety disorder (SAD) and to panic disorder (PD) patients. METHOD: Brain activation and functional connectivity patterns to threat vs. neutral pictures were investigated using event-related fMRI. The sample consisted of 21 GAD, 21 PD, 21 SAD and 21 HC. RESULTS: GAD-specific elevated activity to threat vs. neutral pictures was found in cingulate cortex, dorsal anterior insula/frontal operculum (daI/FO) and posterior dorsolateral prefrontal cortex (dlPFC). Defining these effects as seed regions, we detected GAD-specific increased functional connectivity to threat vs. neutral pictures between posterior dlPFC and ventrolateral prefrontal cortex, between cingulate cortex and amygdala, between cingulate cortex and anterior insula, as well as decreased functional connectivity between daI/FO and mid-dlPFC. CONCLUSION: The findings present the first evidence for GAD-specific neural correlates of hyper-responsive threat processing, possibly reflecting exaggerated threat sensitivity, maladaptive appraisal and attention-allocation processes.

YNIMG Journal 2014 Journal Article

Effects of social context on feedback-related activity in the human ventral striatum

Doerte Simon
Michael P.I. Becker
Martin Mothes-Lasch
Wolfgang H.R. Miltner
Thomas Straube

It is now well established that activation of the ventral striatum (VS) encodes feedback related information, in particular, aspects of feedback validity, reward magnitude, and reward probability. More recent findings also point toward a role of VS in encoding social context of feedback processing. Here, we investigated the effect of social observation on neural correlates of feedback processing. To this end, subjects performed a time estimation task and received positive, negative, or uninformative feedback. In one half of the experiment subjects thought that an experimenter closely monitored their face via a camera. We successfully replicated an elevated VS response to positive relative to negative feedback. Further, our data demonstrate that this reward-related activation of the VS is increased during observation by others. Using uninformative feedback as reference condition, we show that specifically VS activation during positive feedback was modulated by observation manipulation. Our findings support accounts which posit a role of VS in integrating social context into the processing of feedback and, in doing so, signaling its social relevance.

YNIMG Journal 2012 Journal Article

Awareness modulates responses of the amygdala and the visual cortex to highly arousing visual threat

Marius Hoffmann
Judith Lipka
Martin Mothes-Lasch
Wolfgang H.R. Miltner
Thomas Straube

It is still a matter of debate under which conditions the neural processing of emotional stimuli can occur without conscious awareness. Using functional magnetic resonance imaging, we investigated brain responses to highly arousing threat-related versus neutral pictures which were presented very briefly during two backward-masking conditions resulting in either subliminal or supraliminal stimulus processing. Signal detection analysis confirmed the successful experimental manipulation of awareness that effectively prevented stimulus recognition during the subliminal condition. Participants showed stronger responses of the amygdala and extrastriate visual cortex during the supraliminal, but not during the subliminal condition. These results suggest that the processing of highly arousing visual threat requires conscious awareness during backward masking. This contradicts the assumption of pervasive neural responses to emotional stimuli.

YNIMG Journal 2012 Journal Article

Processing of angry voices is modulated by visual load

Martin Mothes-Lasch
Wolfgang H.R. Miltner
Thomas Straube

Visual perceptual load has been shown to modulate brain activation to emotional facial expressions. However, it is unknown whether cross-modal effects of visual perceptual load on brain activation to threat-related auditory stimuli also exist. The current fMRI study investigated brain responses to angry and neutral voices while subjects had to solve an easy or a demanding visual task. Although the easy visual condition was associated with increased activation in the right superior temporal region to angry vs. neutral prosody, this effect was absent during the demanding task. Thus, our results show that cross-modal perceptual load modulates the activation to emotional voices in the auditory cortex and that high visual load prevents the increased processing of emotional prosody.

YNIMG Journal 2011 Journal Article

Attention to aversive emotion and specific activation of the right insula and right somatosensory cortex

Thomas Straube
Wolfgang H.R. Miltner

The evaluation of emotional stimuli is based on different levels of information processing, ranging from rather automatic processes to focused attention to the emotional relevance of stimuli. The role of specific brain areas for these processes is a matter of debate. In this event-related fMRI study, we varied the information processing mode of participants exposed to aversive and neutral pictures. Based on four different tasks, participants' attentional focus onto the emotional quality of the stimuli and the own emotional involvement was increased systematically across tasks. Regardless of task, stronger activation to threatening vs. neutral pictures was found in several regions such as the amygdala, anterior insula, anterior cingulate cortex, primary somatosensory cortex and medial prefrontal cortex. However, there was a parametric increase of activation with increasing attention to one's own emotion specifically in the right posterior insula and right primary and secondary somatosensory cortex, i. e. in areas implicated in self-awareness of a person's own body. These findings are in accordance with theories suggesting a crucial role of the perception of bodily states for emotional experiences.

YNIMG Journal 2010 Journal Article

Increased amygdala activation to averted versus direct gaze in humans is independent of valence of facial expression

Thomas Straube
Bernd Langohr
Stephanie Schmidt
Hans-Joachim Mentzel
Wolfgang H.R. Miltner

A recent study in monkeys showed that averted gaze displayed by conspecifics activates the amygdala regardless of the valence of facial expression (angry, neutral, appeasing). In contrast to this result, previous findings on amygdala activation to gaze information in humans have been mainly interpreted in terms of threat-related processing of facial signals. In the present event-related functional magnetic resonance imaging study with humans, we investigated brain responses to angry, happy, and neutral faces with either direct or averted gaze. Averted versus direct gaze induced increased amygdala responses regardless of facial expression. This finding suggests a critical role of the amygdala in gaze processing independently of the valence of facial expression. Furthermore, the effect of gaze on amygdalar responses seems to be preserved across nonhuman and human primates.

YNIMG Journal 2009 Journal Article

Dynamic activation of the anterior cingulate cortex during anticipatory anxiety

Thomas Straube
Stephanie Schmidt
Thomas Weiss
Hans-Joachim Mentzel
Wolfgang H.R. Miltner

Based on theoretical models, we investigated the dynamics of brain activation during anticipatory anxiety using functional magnetic resonance imaging and a combined parametric/correlational design. Subjects (16 females) anticipated the application of electrical shocks of varying intensity resulting in four different threat levels. The parametric analysis revealed an inverted U-function of activation in the ventral anterior cingulate cortex (ACC) depending on the level of threat. Furthermore, the correlation analysis showed that the association between anxiety and brain activation in the pregenual ACC was, as a tendency, positive during moderate threat but clearly negative during strong threat. Moreover, during strong threat, a positive correlation between anxiety and activation was observed in the dorsal ACC, somatosensory cortex, motor cortex, and hippocampus. These findings suggest threat dependent dynamics of brain activation in the ACC; with increased attentional avoidance during moderate threat and a switch to hypervigilant action readiness in the most anxious subjects during strong threat.

YNIMG Journal 2008 Journal Article

Brain activation upon selective stimulation of cutaneous C- and Aδ-fibers

Thomas Weiss
Thomas Straube
Joachim Boettcher
Holger Hecht
Dorothee Spohn
Wolfgang H.R. Miltner

Thermal and nociceptive cutaneous stimuli activate the brain via two types of nerve fibers, slightly myelinated Aδ-fibers with moderate conduction velocity and unmyelinated C-fibers with slow conduction velocity. Differences in central processing upon selective stimulation of these two fiber types in healthy human subjects still remain poorly understood. By means of event-related functional magnetic resonance imaging the present study investigated brain activation in response to stimulation of Aδ- and C-fibers in healthy subjects. We used the stimulation of tiny skin areas to perform a selective stimulation upon cutaneous C-fibers. Besides similar activation in several brain areas in response to both kinds of stimulation, we observed pronounced brain activation to selective C-fiber stimulation as compared to Aδ-fiber stimulation in the right frontal operculum and anterior insula. Based on a putative function of these structures we suggest that the C-fiber system might be engaged in homeostatic and interoceptive functions in a manner other than the Aδ-fiber system, producing a signal of greater emotional salience.

YNIMG Journal 2007 Journal Article

Time course of amygdala activation during aversive conditioning depends on attention

Thomas Straube
Thomas Weiss
Hans-Joachim Mentzel
Wolfgang H.R. Miltner

The time course of amygdala activation during aversive conditioning is a matter of debate. While some researchers reported rapid habituation, others found stable or no amygdalar responses to conditioned stimuli at all. In the present event-related fMRI study, we investigated whether the activity of the amygdala during aversive conditioning depends on attentional conditions. Subjects underwent aversive delay conditioning by pairing an electrical shock (unconditioned aversive stimulus) with a visual conditioned stimulus (CS+). For each singular presentation of the CS+ or a nonconditioned visual stimulus (CS−), subjects attended in random order to features that either differed between both stimuli (identification task) or that did not differ (distraction task). For the identification task trials, increased responses of the left amygdala to CS+ versus CS− were rapidly established but absent at the end of the conditioning trials. In contrast, under the distraction condition, amygdala activation to CS+ versus CS− was present during the late but not the early phase of conditioning. The results suggest that the time course of amygdala activity during aversive associative learning is strongly modulated by an interaction of attention and time.

YNIMG Journal 2007 Journal Article

Waiting for spiders: Brain activation during anticipatory anxiety in spider phobics

Thomas Straube
Hans-Joachim Mentzel
Wolfgang H.R. Miltner

Anticipatory anxiety during expectation of phobogenic stimuli is an integral part of abnormal behaviour in phobics. The neural basis of anticipatory anxiety in specific phobia is unknown. Using functional magnetic resonance imaging (fMRI), we explored brain activation in subjects with spider phobia and in non-phobic subjects, while participants anticipated the presentation of either neutral or phobogenic visual stimuli. Subjective ratings indicated that anticipation of phobia-related stimuli was associated with increased anxiety in phobics but not in healthy subjects. FMRI results showed increased activation of the dorsal anterior cingulate cortex (ACC), insula, thalamus, and visual areas in phobics compared to controls during anticipation of phobia-relevant versus anticipation of neutral stimulation. Furthermore, for this contrast, we found also increased activation of the bed nucleus of the stria terminalis (BNST). This particular finding supports models, which propose, based on animal experiments, a critical involvement of the BNST in anticipatory anxiety. Finally, correlation analysis revealed that subjective anxiety of phobics correlated significantly with activation in rostral and dorsal ACC and the anterior medial prefrontal cortex. Thus, activation in different ACC regions and the medial prefrontal cortex seems to be specifically associated with the severity of experienced anticipatory anxiety in subjects with spider phobia.

YNIMG Journal 2006 Journal Article

Effects of cognitive-behavioral therapy on brain activation in specific phobia

Thomas Straube
Madlen Glauer
Stefan Dilger
Hans-Joachim Mentzel
Wolfgang H.R. Miltner

Little is known about the effects of successful psychotherapy on brain function in subjects with anxiety disorders. The present study aimed to identify changes in brain activation following cognitive-behavioral therapy (CBT) in subjects suffering from specific phobia. Using functional magnetic resonance imaging (fMRI), brain activation to spider videos was measured in 28 spider phobic and 14 healthy control subjects. Phobics were randomly assigned to a therapy-group (TG) and a waiting-list control group (WG). Both groups of phobics were scanned twice. Between scanning sessions, CBT was given to the TG. Before therapy, brain activation did not differ between both groups of phobics. As compared to control subjects, phobics showed greater responses to spider vs. control videos in the insula and anterior cingulate cortex (ACC). CBT strongly reduced phobic symptoms in the TG while the WG remained behaviorally unchanged. In the second scanning session, a significant reduction of hyperactivity in the insula and ACC was found in the TG compared to the WG. These results propose that increased activation in the insula and ACC is associated with specific phobia, whereas an attenuation of these brain responses correlates with successful therapeutic intervention.