Publications (83) View all
-
Article: Acute Shift in Glutamate-Concentrations Following Experimentally Induced Panic with Cholecystokinin-Tetrapeptide - A 3T-MRS Study in Healthy Subjects.
[show abstract] [hide abstract]
ABSTRACT: According to preclinical studies, glutamate has been implicated in the pathogenesis of anxiety. In order to elucidate the role of glutamate in anxiety and panic in humans, brain glutamate+glutamine (Glx) levels were measured during CCK-4 induced panic using magnetic resonance spectroscopy (MRS). Eighteen healthy subjects underwent CCK-4 challenge. MR spectra were obtained from the anterior cingulate cortex (ACC) using a single voxel point resolved spectroscopy method (PRESS) and analyzed using LCModel. A combined fitting of glutamine and glutamate (Glx) was performed. Panic was assessed using the Acute Panic Inventory (API) and Panic Symptom Scale (PSS) scores. Moreover, hypothalamic-pituitary-adrenal (HPA) axis stimulation was monitored throughout the challenge. There was a significant panic response following CCK-4 as revealed by a marked increase in both panic scores (API: F[1,17]=149.41; p<0.0001; PSS: F[1,17]=88.03; p<0.0001) and a significant increase in heart rate (HR: F[1,17]=72.79; p<0.0001). MRS measures showed a significant increase of brain glutamate+glutamine/creatine (Glx/Cr) levels peaking at 5-10 minutes after challenge (F[1,17]=15.94; p=0.001). There was also a significant increase in CCK-4 related cortisol release (F[6,11]=8.68; p=0.002). Finally, significant positive correlations were found between baseline Glx/Cr and both APImax (r=.598; p=0.009) and the maximum heart rate during challenge HRmax (r=.519; p=0.027). Our results suggest that CCK-4 induced panic is accompanied by a significant glutamate increase in the bilateral ACC. The results add to the hypothesis of a disturbance of the inhibitory-excitatory equilibrium and suggest that apart from static alterations also rapid and dynamic neurochemical changes might be relevant for the neural control of panic attacks.Neuropsychopharmacology accepted article preview online, 5 March 2013; doi:10.1038/npp.2013.61.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2013; · 6.99 Impact Factor -
Article: Functional connectivity profile of the human inferior frontal junction: involvement in a cognitive control network
[show abstract] [hide abstract]
ABSTRACT: Background: The human inferior frontal junction area (IFJ) is critically involved in three main component processes of cognitive control (working memory, task switching and inhibitory control). As it overlaps with several areas in established anatomical labeling schemes, it is considered to be underreported as a functionally distinct location in the neuroimaging literature. While recent studies explicitly focused on the IFJ s anatomical organization and functional role as a single brain area, it is usually not explicitly denominated in studies on cognitive networks. However based on few analyses in small datasets constrained by specific a priori assumptions on its functional specialization, the IFJ has been postulated to be part of a cognitive control network. Goal of this meta-analysis was to establish the IFJ's connectivity profile on a high formal level of evidence by aggregating published implicit knowledge about its co-activations. We applied meta-analytical connectivity modeling (MACM) based on the activation likelihood estimation (ALE) method without specific assumptions regarding functional specialization on 180 (reporting left IFJ activity) and 131 (right IFJ) published functional neuroimaging experiments derived from the BrainMap database. This method is based on coordinates in stereotaxic space, not on anatomical descriptors. Results: The IFJ is significantly co-activated with areas in the dorsolateral and ventrolateral prefrontal cortex, anterior insula, medial frontal gyrus / pre-SMA, posterior parietal cortex, occipitotemporal junction / cerebellum, thalamus and putamen as well as language and motor areas. Results are corroborated by an independent resting-state fMRI analysis. Conclusions: These results support the assumption that the IFJ is part of a previously described cognitive control network. They also highlight the involvement of subcortical structures in this system. A direct line is drawn from works on the functional significance of brain activity located at the IFJ and its anatomical definition to published results related to distributed cognitive brain systems. The IFJ is therefore introduced as a convenient starting point to investigate the cognitive control network in further studies.BMC Neuroscience 10/2012; · 3.04 Impact Factor -
Article: Effect of Cognitive-Behavioral Therapy on Neural Correlates of Fear Conditioning in Panic Disorder.
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Learning by conditioning is a key ability of animals and humans for acquiring novel behavior necessary for survival in a changing environment. Aberrant conditioning has been considered a crucial factor in the etiology and maintenance of panic disorder with agoraphobia (PD/A). Cognitive-behavioral therapy (CBT) is an effective treatment for PD/A. However, the neural mechanisms underlying the effects of CBT on conditioning processes in PD/A are unknown. METHODS: In a randomized, controlled, multicenter clinical trial in medication-free patients with PD/A who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before and after CBT. Quality-controlled fMRI data from 42 patients and 42 healthy subjects were obtained. RESULTS: After CBT, patients compared to control subjects revealed reduced activation for the conditioned response (CS+ > CS-) in the left inferior frontal gyrus (IFG). This activation reduction was correlated with reduction in agoraphobic symptoms from t1 to t2. Patients compared to control subjects also demonstrated increased connectivity between the IFG and regions of the "fear network" (amygdalae, insulae, anterior cingulate cortex) across time. CONCLUSIONS: This study demonstrates the link between cerebral correlates of cognitive (IFG) and emotional ("fear network") processing during symptom improvement across time in PD/A. Further research along this line has promising potential to support the development and further optimization of targeted treatments.Biological psychiatry 08/2012; · 8.93 Impact Factor -
Article: The mirror neuron system under hypnosis - Brain substrates of voluntary and involuntary motor activation in hypnotic paralysis.
[show abstract] [hide abstract]
ABSTRACT: INTRODUCTION: The neurobiological basis of non-organic movement impairments is still unknown. As conversion disorder and hypnotic states share many characteristics, we applied an experimental design established in conversion disorder to investigate hypnotic paralysis. METHODS: Movement imitation and observation were investigated by functional magnetic resonance imaging (fMRI) in 19 healthy subjects with and without hypnotically induced paralysis of their left hand. Paralysis-specific activation changes were explored in a multivariate model and functional interdependencies of brain regions by connectivity analysis. RESULTS: Hypnotic paralysis during movement imitation induced hypoactivation of the contralateral sensorimotor cortex (SMC) and ipsilateral cerebellum and increased activation of anterior cingulate cortex (ACC), frontal gyrus and insula. No paralysis-specific effects were revealed during movement observation. CONCLUSIONS: Hyperactivation of ACC, middle frontal gyrus (MFG), and insula might reflect attention (MFG), conflict-detection (ACC) and self-representation processes (insula) during hypnotic paralysis. The lack of effects in movement observation suggests that early motor processes are not disturbed due to the transient nature of the hypnotic impairment.Cortex 06/2012; · 6.08 Impact Factor -
Article: Neural correlates of individual performance differences in resolving perceptual conflict.
[show abstract] [hide abstract]
ABSTRACT: Attentional mechanisms are a crucial prerequisite to organize behavior. Most situations may be characterized by a 'competition' between salient, but irrelevant stimuli and less salient, relevant stimuli. In such situations top-down and bottom-up mechanisms interact with each other. In the present fMRI study, we examined how interindividual differences in resolving situations of perceptual conflict are reflected in brain networks mediating attentional selection. Doing so, we employed a change detection task in which subjects had to detect luminance changes in the presence and absence of competing distractors. The results show that good performers presented increased activation in the orbitofrontal cortex (BA 11), anterior cingulate (BA 25), inferior parietal lobule (BA 40) and visual areas V2 and V3 but decreased activation in BA 39. This suggests that areas mediating top-down attentional control are stronger activated in this group. Increased activity in visual areas reflects distinct neuronal enhancement relating to selective attentional mechanisms in order to solve the perceptual conflict. Opposed to good performers, brain areas activated by poor performers comprised the left inferior parietal lobule (BA 39) and fronto-parietal and visual regions were continuously deactivated, suggesting that poor performers perceive stronger conflict than good performers. Moreover, the suppression of neural activation in visual areas might indicate a strategy of poor performers to inhibit the processing of the irrelevant non-target feature. These results indicate that high sensitivity in perceptual areas and increased attentional control led to less conflict in stimulus processing and consequently to higher performance in competitive attentional selection.PLoS ONE 01/2012; 7(8):e42849. · 4.09 Impact Factor
