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1.  Area-dependent time courses of brain activation during video-induced symptom provocation in social anxiety disorder 
Previous functional imaging studies using symptom provocation in patients with social anxiety disorder (SAD) reported inconsistent findings, which might be at least partially related to different time-dependent activation profiles in different brain areas. In the present functional magnetic resonance imaging study, we used a novel video-based symptom provocation design in order to investigate the magnitude and time course of activation in different brain areas in 20 SAD patients and 20 healthy controls.
The disorder-related videos induced increased anxiety in patients with SAD as compared to healthy controls. Analyses of brain activation to disorder-related versus neutral video clips revealed amygdala activation during the first but not during the second half of the clips in patients as compared to controls. In contrast, the activation in the insula showed a reversed pattern with increased activation during the second but not during the first half of the video clips. Furthermore, a cluster in the anterior dorsal anterior cingulate cortex showed a sustained response for the entire duration of the videos.
The present findings suggest that different regions of the fear network show differential temporal response patterns during video-induced symptom provocation in SAD. While the amygdala is involved during initial threat processing, the insula seems to be more involved during subsequent anxiety responses. In accordance with cognitive models of SAD, a medial prefrontal region engaged in emotional-cognitive interactions is generally hyperactivated.
PMCID: PMC4052290  PMID: 24921039
Social anxiety disorder; Symptom provocation; Functional magnetic resonance imaging (fMRI); Amygdala; Insula; Medial prefrontal cortex
2.  Pain-related and negative semantic priming enhances perceived pain intensity 
‘Priming’ an individual by exposing them to pictures or words before a painful stimulus can significantly affect their subsequent pain experience. This study aimed to determine whether this priming effect is only associated with negative primes, or whether pain-related primes have the same, or increased, effects.
Negative affective and pain-related cues, such as pictures or words, have been shown to act as primes and enhance the perceived intensity of subsequent painful events. For pain-related semantic primes, it remains unclear whether this effect depends on negative valence itself or, specifically, on the pain-relatedness of the words.
To investigate the effect of pain-related, negative affective (pain-unrelated) and neutral semantic primes on the perception of subsequent noxious target stimuli.
Pain ratings in response to noxious electrical stimulation of light and moderate intensity were examined in 39 healthy subjects after subjects were exposed to semantic primes of different meaning and valence (pain-related, negative, positive and neutral adjectives) presented with different interstimulus intervals (0 ms, 500 ms and 1500 ms).
Increased pain ratings of noxious stimuli were observed following pain-related and negative compared with neutral primes.
The results support the motivational priming theory for semantic stimuli, indicating that affectively negative semantic primes increase subjective pain intensity. However, a specific pain-related priming effect was not reliably demonstrated. Additionally, it is shown that experimental parameters (ie, stimulus intensity and interstimulus interval) modify the extent of negative and pain-related semantic priming.
Verbal priming plays a role for the perception of noxious stimuli in a time-dependent manner.
PMCID: PMC4028655  PMID: 24716197
Affective words; Electrical stimulation; Pain ratings; Pain words; Semantic priming
3.  Impaired Representation of Time in Schizophrenia Is Linked to Positive Symptoms and Cognitive Demand 
PLoS ONE  2013;8(6):e67615.
Time processing critically relies on the mesencephalic dopamine system and striato-prefrontal projections and has thus been suggested to play a key role in schizophrenia. Previous studies have provided evidence for an acceleration of the internal clock in schizophrenia that may be linked to dopaminergic pathology. The present study aimed to assess the relationship between altered time processing in schizophrenia and symptom manifestation in 22 patients and 22 controls. Subjects were required to estimate the time needed for a visual stimulus to complete a horizontal movement towards a target position on trials of varying cognitive demand. It was hypothesized that patients – compared to controls – would be less accurate at estimating the movement time, and that this effect would be modulated by symptom manifestation and task difficulty. In line with the notion of an accelerated internal clock due to dopaminergic dysregulation, particularly patients with severe positive symptoms were expected to underestimate movement time. However, if altered time perception in schizophrenia was better explained in terms of cognitive deficits, patients with severe negative symptoms should be specifically impaired, while generally, task performance should correlate with measures of processing speed and cognitive flexibility. Patients underestimated movement time on more demanding trials, although there was no link to disease-related cognitive dysfunction. Task performance was modulated by symptom manifestation. Impaired estimation of movement time was significantly correlated with PANSS positive symptom scores, with higher positive symptom scores associated with stronger underestimation of movement time. The present data thus support the notion of a deficit in anticipatory and predictive mechanisms in schizophrenia that is modulated both by symptom manifestation and by cognitive demand.
PMCID: PMC3695031  PMID: 23826328
4.  Automatic Neural Processing of Disorder-Related Stimuli in Social Anxiety Disorder: Faces and More 
It has been proposed that social anxiety disorder (SAD) is associated with automatic information processing biases resulting in hypersensitivity to signals of social threat such as negative facial expressions. However, the nature and extent of automatic processes in SAD on the behavioral and neural level is not entirely clear yet. The present review summarizes neuroscientific findings on automatic processing of facial threat but also other disorder-related stimuli such as emotional prosody or negative words in SAD. We review initial evidence for automatic activation of the amygdala, insula, and sensory cortices as well as for automatic early electrophysiological components. However, findings vary depending on tasks, stimuli, and neuroscientific methods. Only few studies set out to examine automatic neural processes directly and systematic attempts are as yet lacking. We suggest that future studies should: (1) use different stimulus modalities, (2) examine different emotional expressions, (3) compare findings in SAD with other anxiety disorders, (4) use more sophisticated experimental designs to investigate features of automaticity systematically, and (5) combine different neuroscientific methods (such as functional neuroimaging and electrophysiology). Finally, the understanding of neural automatic processes could also provide hints for therapeutic approaches.
PMCID: PMC3662886  PMID: 23745116
SAD; automaticity; face; fMRI; EEG; emotion
5.  Amygdala activation to threat under attentional load in individuals with anxiety disorder 
Previous studies in healthy subjects have shown that strong attentional distraction prevents the amygdala from responding to threat stimuli. Here, we investigated the effects of attentional load on amygdala activation to threat-related stimuli in individuals suffering from an anxiety disorder.
During functional magnetic resonance imaging, spider-phobicand healthy control subjects were presented with phobia-related and neutral stimuli while performing a distraction task with varying perceptual load (high vs low).
Our data revealed a pattern of simultaneously increased amygdala and visual cortical activation to threat vs neutral pictures in phobic individuals, compared with controls, occurring regardless of attentional load.
These results suggest that, in contrast to studies in healthy subjects, amygdala activation to clinically relevant threat stimuli is more resistant to attentional load.
PMCID: PMC3384227  PMID: 22738024

Results 1-5 (5)