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Leonie Brinkmann

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5 papers
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5

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

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.

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.