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Aims:Current evidence suggests that high frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) of the left dorsolateral prefrontal cortex (DLPFC) might be a promising treatment strategy for depression. However, due to rather modest clinical results, the efficacy of rTMS in depressed patients is still under debate. As melancholic depression seems to affect psychomotor activity, in this study, we wanted to evaluate whether HF-rTMS treatment affects psychomotor activity. We also wanted to examine whether the severity of psychomotor retardation could predict clinical outcome.Method:Our group consisted of twenty antidepressant-free unipolar depressed patients of the melancholic subtype. All were considered at least stage II treatment resistant. Depression severity was assessed with the Hamilton Depression Rating Scale (HDRS) and psychomotor symptoms with the Depressive Retardation Rating Scale (DRRS). All received 10 sessions of HF-rTMS delivered on the left DLPFC.Results:Forty percent of the patients showed a reduction of at least 50% on their initial HDRS score and were defined as HF-rTMS responders.The severity of psychomotor retardation, as measured with the DDRS, did not predict clinical outcome. HF-rTMS treatment resulted in significant decreases in DDRS scores for responders as well as for non-responders. However: the better the clinical outcome, the higher the observed level of psychomotor improvement.Conclusion:Our results suggest that HF-rTMS might act on the ‘psychomotor’ level and this might add some further information as to why this kind of treatment can be beneficial for severely depressed patients of the melancholic subtype.

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Introduction Brain imaging studies have revealed that individual differences in the neural response during implicit (unintended) processing the emotional content of affective stimuli are related to differences in the personality trait 'harm avoidance' (HA) [1,2]. This trait is related to the emotions of anxiety and inhibitted behavior. Given that implicitly or explicitly (intended) processing emotional stimuli have been found to activate the brain differently, we have performed an fMRI study to explore the difference in neural response during explicitly processing emotional stimuli between low, average and high HA individuals. This study was focused to the amygdalae given their key role in emotional processes in the brain. Materials and methods 33 healthy female volunteers (age range: 19-27 years) were asked to rate the valence of positive (hapy smiling baby faces) and negative (crying baby faces with a dermatological condition) emotional stimuli during an fMRI scan. All participants had seen all stimuli prior to the fMRI study. All participants completed the Temperament and Character Inventory questionnaire [3]. Based on their HA scores they were categorized into a low (range: 0-10, 10 participants), an average (range: 11-15, 16 participants) and a high (range: 16-25, 7 participants) HA group. The amygdalae responses were recorded in a 5mm radius spherical region-of-interest (ROI) positioned at the maximal amygdalae responses to the positive and the negative stimuli respectively. A two way ANOVA with group (low-average-high) as a between subject factor and emotional valence (positive-negative) as a within subject factor, was performed for the left and right amygdala seperately. We searched for the main effects of group to find differences in emotional processing between our groups independent of valence and the interaction effects to find differences in emotional processing between the groups depending on the valence of the stimuli. Results Our results revealed only a significant main effect of group in the right amygdala. Post-hoc tests revealed a higher right amygdala response to the emotional stimuli in the average compared to the low HA participants (fig. 1). A whole brain analysis (fig. 2) revealed a main effect of group in the right visual cortex, the right fusiform gyrus, the right temporal cortex, the middle and posterior cingulate gyrus, the right frontal eye field, the right caudate nucleus, the right olfactory and the right ventrolateral prefrontal cortex. Interaction effects were found in the left temporal pole, the anterior cingulate cortex and the left ventrolateral prefrontal cortex. Figure 3 presents the results of the post-hoc tests. Discussion Our results revealed differences in neural processing between the groups in brain regions involved in the perception and the analysis of facial expressions and analyzing the other's emotional state. In the prefrontal cortex differences in the neural response were found between the groups suggesting differences in the attentional and cognitive control related to differences in HA scores. The right amygdala, which is involved in the fast and automatic detection of any emotional content in a stimulus, was found to be different between low and average HA females. Remarkebly, no differences in response times between the groups were found. In conclusion, individual differences in HA score leads to differences in the neural response, including the right amygdala during explicitly rating of the valence of affective stimuli. References [1] Baeken et al, 2009. Brain Res. 1296, 94-103, [2] Baeken et al, 2010. Neurosci. Lett. 478, 97-101, [3] Cloninger, 1993. Arch. Gen. Psychiatry 50, 975-990

Repetitive transcranial magnetic stimulation (rTMS) has been introduced as a therapeutic tool for depression. Although a reduction of depressive symptoms in patients after rTMS-treatment has been reported, the interaction with the brain still remains unclear. In this study we performed an fMRI-experiment just before and 1 hour after one rTMS-session on healthy female volunteers in a sham-controlled single-blind study design. During the fMRI-experiment, the volunteers had to look at pictures of attractive, aversive and blurred baby faces used as positive, negative and neutral stimuli respectively. They were asked to empathize with the emotional content as much as possible. For all fMRI-experiments the contrast maps ''positive versus neutral" and "negative versus neutral" were calculated. For both contrasts, we performed a 2-way repeated measures ANOVA with group (active, sham) and repetition (before, after) as variables. We found interactions in the prefrontal and cingulate gyri. These regions are known to be involved in processing emotions and controlling social-emotional behaviors. Introduction: In depression, repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been introduced as a therapeutic tool. In this therapy, patients receive an rTMS-session once a day during 10 days. Although a reduction of depressive symptoms has been reported after treatment [1], only a few studies investigated the corresponding interactions of rTMS with the brain [2,3,4]. In these studies, they focused on metabolic changes [2] after a complete treatment or effects on a memory [3] or a cued reaction time (Posner) [4] task after 1 rTMS-session. Although depression is a mood disorder, we didn't find any study investigating the interaction of rTMS on emotional brain processing in depression. As a first step to investigate the interaction of rTMS with emotional processing in the brain, we performed an fMRI-experiment on healthy volunteer's just before and 1 hour after one rTMS-session. Material and methods: 19 non-depressed female volunteers (25?5 years) who conformed to the current guidelines for MRI and rTMS research were included. 10 underwent active high frequency rTMS-stimulation (10Hz, 40 trains of 3.9s duration, intertrain interval=26.1s) over the left DLPFC while 9 underwent sham stimulation. Just before and 1 hour after the rTMS-session, an fMRI-experiment consisting of the presentation of 20s duration blocks of attractive (4 blocks with 4 pictures each), aversive (4 blocks with 4 pictures each) and blurred (5 blocks with 4 pictures each) baby faces as positive, negative and neutral stimuli respectively, were performed. All volunteers were asked to focus on their emotions during the experiment. We measured 127 EPI volumes (TR/TE=3000/35ms, 18 slices, matrix size=64x64) with a Philips 1.5T Achieva MRI scanner. Preprocessing in SPM5 consisted of a rigid body registration as realignment step, an affine transformation to the MNI-template as normalization stepand a smoothing step with an isotropic 8mm Gaussian kernel were performed. A multi-linear regression analysis of each fMRI-experiment was performed using the general linear model in SPM5. For each fMRI-session, contrast maps "positive versus neutral" and "negative versus neutral", named positive and negative respectively, were calculated. All maps were organized according to 3 variables: repetition (before, after), group (active, sham) and valence (positive, negative). To investigate treatment effects, a 2-way repeated measures ANOVA "repetition x group" and paired T-tests between repetitions for each group were performed in SPM5 for each valence. Results: The ANOVA results were investigated with F-statistical maps while the results of the paired T-tests were investigated with T-statistical maps, significance corresponding to an uncorrected pNo main effect of group was found for either valence. We found main effects of repetition in the prefrontal gyrus bilateral (left: F28.52; right: F=24.01), the left anterior cingulate (F=25.23), the left insula (F=17.35), the right parahippocampus (F=24.28) and the right caudate head (F=18.08) for the positive valence. For the negative valence we found main effects in the prefrontal gyrus bilateral (left: F=26.19; right: F=18.04), the left parahippocampus (F=24.50), the left putamen (F=18.83), the right anterior cingulate (F=17.45) and the caudate head bilateral (left: F=26.53; right: F=17.88). These regions are known to be involved in recognition of facial emotions and memory processes [5]. When looking at the interaction results we found interactions in the temporal gyrus bilateral, the prefrontal gyrus bilateral (left: F=28.01; right: F=21.12), the cingulate gyrus bilateral (left: F=19.32; right: F=17.85), the left hippocampus (F=18.92) the right parahippocampus (F=15.69) and the right thalamus (F=22.40) for the positive valence. The paired T-test showed that in the sham group, the activity in these regions was decreased after the rTMS-session which was not seen in the active group. Moreover, there was an increased activity after the active rTMS-session in the left prefrontal gyrus. For the negative valence, we found interactions at the left temporal gyrus (F=20.04), the left hippocampus (F=16.96), the cingulate gyrus bilateral (left: F=15.63; right: F=20.38), the right precuneus (F=19.63) and the right claustrum (F=52.96). The paired T-test showed that the activity in the cingulate gyrus bilateral decreased after an active rTMS-session and not after a sham session. In the prefrontal regions the activity decreased for both groups. Conclusions: Although previous studies with mood questionnaires on volunteers were unable to demonstrate any subjective mood change after one rTMS-session [6], we were able to find effects of the rTMS-stimulation on the emotional processing in the brain. It is possible that these different results are due to a limited sensitivity of the questionnaires to small subjective mood changes. Nevertheless, it would be speculative to interpret our results in terms of real changes in mood states or social behavior, at this point. The observed interactions in the prefrontal and cingulate gyri are of interest as these regions are known to be involved in controlling social-emotional behaviors [7]. Compared to normal subjects, depressed patients showed an increased activity in the limbic and prefrontal regions when looking at negative stimuli [8] while they showed a lower neural response in these regions to positive faces [9]. Our results are in line with earlier papers reporting that antidepressive treatments may influence neural activity in these regions [3,8,9]. References: [1] Schutter D.J. (2008): Psychological medicine; 30:1-11 [2] Luborzewski A. (2007): Journal of Psychiatric Research; 41:606-615 [3] Solé-Padullés C. (2006): Cerebral Cortex; 16 :1487-1493 [4] Rounis E. (2006): The Journal of Neuroscience; 26:9626-9638 [5] Ranganath C. (2006): Neuroscience; 139:277-289 [6] Baeken C. (2008): Clinical Neurophysiology; 119:568-575 [7] Kesler M.L. (2001): Cognitive brain research; 11:213-226 [8] Fu C.H.Y. (2004): Archives of General Psychiatry; 61:877-889 [9] Fu C.H.Y. (2007): American Journal of Psychiatry; 164:599-607

Introduction In our previous study [1], in response to aversive stimuli less amygdala activity was found in correlation to the personality trait 'Harm Avoidance' (HA) in females while watching passively to blocks with positive or negative affective pictures. However, high HA means stronger negative reactions and paying more attention towards aversive stimuli, resulting in more amygdala activity [2]. To explain this discrepancy, we hypothesized that our volunteers anticipated to the negative stimuli either by shifting their attention away from the pictures or by suppressing their emotional reaction. In an attempt to test this hypothesis, we repeated the fMRI experiment but now we restricted the possibility to anticipate by presenting the pictures in random order and asking to evaluate the valence of the shown pictures. Materials and methods We included 33 non-depressed female volunteers (22±3 years) and quantified their personality with the temperament and character inventory (TCI). During the MRI, they had to evaluate pictures of happy smiling baby faces as positive and unhappy crying baby faces with a severe dermatological condition as negative affective pictures. The associated brain activity was measured with a standard EPI sequence (dynamic resolution: 3s) at a 1.5T MRI scanner. Based on the individual response maps and for each affective condition, we performed a multiple regression analysis with all personality traits and age as regressors on circular ROI's (radius: 5mm) defined on the maximum response in the amygdalae, subregions of the PFC known to regulate the amygdalae response and the visual cortex. Results Using a significance threshold of p Discution and conclusions Although statistically weak, restricting the posibility to anticipate to the presented stimuli seems to result in the expected behavior for the amygdala activity in relation to HA (figure 3). In an attempt to control the emotional reaction, more PFC activity was seen. In conclusion, the high harm avoidand females in our experiments tried to avoid or suppress strong emotional reactions to negative stimuli. References [1] Baeken C. et al. (2009): Brain Research; 1296:94-103 [2] Most S. et al. (2006): NeuroImage; 31:1016-1027

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) applied over the dorsolateral prefrontal cortex (DLPFC) is a new treatment procedure that holds promise of more insight into the pathophysiology of depression because the DLPFC may play an important role in the interplay between emotional and attentional information processing. We sought to investigate whether acute neurocognitive effects of rTMS are related to antidepressant outcomes. METHODS: Between January 2005 and May 2007, we examined the effects of a single session compared with 2 weeks of rTMS over the left DLPFC on cognition and mood in therapy-resistant patients with depression. We used a crossover placebo-controlled double-blind design and differentiated rTMS treatment responders and nonresponders. We used a task-switching paradigm to measure cognitive function. RESULTS: After 2 weeks of high-frequency rTMS over the left DLPFC, depressive symptoms improved in more than half (53%) of our therapy-resistant population. After a single session, mood did not improve but attentional control was increased solely within our group of treatment responders. LIMITATIONS: Our results should be interpreted as preliminary because our sample was small and because the cognitive task we used has not been tested for validity and reliability. In addition, despite minimal stimulation of the DLPFC during sham stimulation, it is possible that the stimulation was partially active. Finally, benzodiazepines may have had impairing effects on the attentional task. CONCLUSION: Cognitive reactivity after a single session of rTMS may hold promise as a predictor of beneficial treatment outcomes. Moreover, within the group of responders, attentional control appears to play an important role in the progress of mood disorders.

BACKGROUND: [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB) is currently the mostly used radiotracer for positron emission tomography (PET) quantitative studies of the serotonin transporter (SERT) in the human brain but has never been validated in dogs. The first objective was therefore to evaluate normal [(11)C]DASB distribution in different brain regions of healthy dogs using PET. The second objective was to provide less invasive and more convenient alternative methods to the arterial sampling-based kinetic analysis. RESULTS: A dynamic acquisition of the brain was performed during 90 min. The PET images were coregistered with the magnetic resonance images taken prior to the study in order to manually drawn 20 regions of interest (ROIs). The highest radioactivity concentration of [(11)C]DASB was observed in the hypothalamus, raphe nuclei and thalamus and lowest levels in the parietal cortex, occipital cortex and cerebellum. The regional radioactivity in those 20 ROIs was quantified using the multilinear reference tissue model 2 (MRTM2) and a semi-quantitative method. The values showed least variability between 40 and 60 min and this time interval was set as the optimal time interval for [(11)C]DASB quantification in the canine brain. The correlation (R(2)) between the MRTM2 and the semi-quantitative method using the data between 40 and 60 min was 99.3 % (two-tailed p-value

Autisme is een ontwikkelingsstoornis die zich kenmerkt door tekortkomingen op het vlak van communicatie en sociale interactie, alsook door de aanwezigheid van beperkte en zich herhalende, stereotiepe patronen van gedrag en/of interesses. Een recente toename in het diagnosticeren van autismespectrumstoornissen (ASS) bij volwassenen brengt deze problematiek onder de aandacht. Mogelijke verklaringen en hypothesen voor de vastgestelde stijging in prevalentie worden toegelicht aan de hand van een literatuurstudie.

Background Prior research in substance dependence has suggested potential anti-craving effects of repetitive transcranial magnetic stimulation (rTMS) when applied to the dorsolateral prefrontal cortex (DLPFC). However, no single sham-controlled session studies applied to the right DLPFC have been carried-out in recently detoxified alcohol-dependent patients. Furthermore, no studies examined the effect of a single HF-rTMS session on craving in these patients’ natural habitat. Methods To further investigate the effect of high-frequency (HF)-rTMS of the right DLPFC on alcohol craving, we performed a prospective, single-blind, sham-controlled study involving 36 hospitalized patients with alcohol dependence syndrome. After successful detoxification, patients were allocated receiving one active or one sham HF-rTMS session. The obsessive–compulsive drinking scale (OCDS) was administered to evaluate the extent of craving just before and after the HF-rTMS session (on Friday), on Saturday and Sunday during the weekend at home, and on Monday when the patient returned to the hospital. Results One single blind sham-controlled HF-rTMS session applied to the right DLPFC did not result in changes in craving (neither immediately after the stimulation session, nor in patients’ natural environment during the weekend). Conclusions One HF-rTMS stimulation session applied to the right DLPFC had no significant effects on alcohol craving in alcohol dependent patients. One such session could have been too short to alter alcohol craving in a sample of alcohol dependent patients.

We present a case of a patient with severe treatment resistant depression who relapsed while being treated with vagus nerve stimulation. We describe that he was safely treated with unilateral ECT concomitantly with the VNS.

A young man, 23 years old, with a clinically isolated syndrome (CIS), presented violent thoughts during a neurological consultation. He was diagnosed with Asperger Syndrome based on a psychiatric and (neuro)psychological examination. Possible risk factors for acting-out and the implications for treatment, if CIS would evolve to MS, are discussed based on a review of the literature.

Introduction: In the therapy of depression, repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has been introduced. Crucial in rTMS-treatment is the accurate positioning of the rTMS-coil over the stimulation area. Standard methods for coil positioning are derived from the Talairach atlas and do not take in account any individual anatomical information. In this study we compared an individualized method based on a 3D MRI of the head, the "3D-MRI system" to the standard method. Methods: 40 healthy female subjects (25±6 years) who conformed the current guidelines for rTMS and MRI research where included. In the standard method, the "5-cm rule", the DLPFC is defined as 5 cm rostral to a point in the motor cortex identified by stimulating the brain with a Magstim rTMS- stimulator and looking for the maximum response recorded with EMG over the right musculus abductor pollicis brevis. For the 3D-MRI system the subjects underwent a T1-weighted MRI (3D-TFE, 1x1x1 mm resolution) of the head using a Philips 1.5T Intera scanner. All post processing was done on a Philips ViewForum console. We located the DLPFC visually on the 3D surface rendering of the brain based on the known gyral morphology. The corresponding coil position was found by making the projection on the skin. For an accurate determination of the coil position on a patient's head, we drew an axis from left ear to right ear through the coil position and one from nose to atlas. The crossing of both axes is defined as "top". We measured the distances from top to the coil position, to the right ear and to the nose on the 3D surface rendering of the head. To compare both methods, we measured the distance between both coil positions on the patients head. Results: The individual stimulation points were scattered widelly about the 5-cm point. There is an average shift of 27±14 mm between both. In most subjects, the standard method positioned the DLPFC too rostrally. Conclusions: We showed that the current positioning method used in rTMS- studies easily fail to target the DLPFC. An inaccurate positioning of the rTMS-coil over the DLPFC can be a reason for the heterogeneous outcome of rTMS-treatments. In order to improve the efficacy of this technique, we should use coil positioning techniques witch take the individual anatomy in account by making the combination with MRI. References: [1] Herwig U. (2001): Biol Psychiatry; 50: 58-61

Events coupled with an emotional context seem to be better retained than non-emotional events. The aim of our study was to investigate whether an emotional context could influence the neural substrates of memory associations with novel portrait art stimuli. In the current prospective fMRI study, we have investigated for one specific visual art form (modern artistic portraits with a high degree of abstraction) whether memory is influenced by priming with emotional facial pictures. In total forty healthy female volunteers in the same age range were recruited for the study. Twenty of these women participated in a prospective brain imaging memory paradigm and were asked to memorize a series of similar looking, but different portraits. After randomization, for twelve participants (Group 1), a third of the portraits was emotionally primed with approach-related pictures (smiling baby faces), a third with withdrawal-related pictures (baby faces with severe dermatological conditions), and another third with neutral images. Group 2 consisted of eight participants and they were not primed. Then, during an fMRI session 2 h later, these portraits were viewed in random order intermixed with a set of new (previously unseen) ones, and the participants had to decide for each portrait whether or not they had already been seen. In a separate experiment, a different sample of twenty healthy females (Group 3) rated their mood after being exposed to the same art stimuli, without priming. The portraits did not evoke significant mood changes by themselves, supporting their initial neutral emotional character (Group 3). The correct decision on whether the portraits were Familiar of Unfamiliar led to similar neuronal activations in brain areas implicated in visual and attention processing for both groups (Groups 1 and 2). In contrast, whereas primed participants showed significant higher neuronal activities in the left midline superior frontal cortex (Brodmann area (BA) 6), unprimed volunteers displayed higher right medial frontal cortical (BA 10) activities. Furthermore, specifically in Group 1, correct retrieval of negatively primed portraits evoked increased neuronal activity in the left medial orbitofrontal cortex (BA 11) and in the right (posterior) insula, suggesting enhanced stress-related responses to the memory of withdrawal-related primed modern artistic portraits in this group. Our prospective memory data in healthy females indicate that, to reach a correct retrieval decision, different midline anterior neuronal networks are recruited for portraits that were emotionally primed than for the unprimed ones. Importantly, our results also suggest that the negative emotional context leads to the formation of associations that are reactivated during memory retrieval processes of the initially neutral art portraits. When correctly recognized, the portraits evoke neuronal activities consistent with the withdrawal-related character of the emotional visual stimuli with which they have been associated. Although our results show that abstract portrait art can be associated with emotional primes this doesn't mean that this effect is specific for art images.

We aimed to Examine the safety and effectiveness of HF-rTMS in a treatment-refractory bipolar I patient in a mixed affective episode. Our case illustrates that "combative" HF-rTMS therapy could be a safe and valid treatment alternative for refractory bipolar I patients in mixed episode, not successfully treated with ECT.

Introduction: The temperament trait 'Harm Avoidance' (HA) from Cloninger's biopsychological model of personality [1], has been shown to be indicative for one's sensitivity to develop an anxiety-disorder during lifetime [2]. It has been revealed that people scoring high on harm avoidance show a tendency to respond more intense to aversive stimuli [3]. In this study, we examined the influence of harm avoidance in response to aversive and attractive stimuli in young female brains during an fMRI experiment in which the volunteers were asked to judge the stimuli to the displayed emotion. Given the central role of the amygdalae in emotional processes in the brain and pathological anxiety states [4], we limited our analysis to this region bilateral. Materials and methods: We included 34 non-depressed female volunteers (22±3 years) who conformed to the current guidelines for fMRI research. From reference [5], we used the positive baby face pictures as attractive stimuli and the negative baby face pictures as aversive stimuli. To focus on emotional neuronal processes in particular, the volunteers were asked to judge the valence of the displayed emotion by a right button press for a positive and a left button press for a negative emotion. The pictures were shown in random sequence with 3.78±2.26s inter-trial time. The volunteers were familiarized with all pictures just before the fMRI experiment. We measured 168 EPI images (TR/TE=3000/35ms; 18 slices; matrix=64x64) using a 1.5T Philips MRI scanner. Analysis was done as pointed out in [6] using SPM8, to find the individual activation maps in response to the positive and negative pictures and the contrast maps 'positive - negative'. Based on these individual maps we performed three multiple regression analyses with all seven personality characteristics of Cloninger's model (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, cooperativeness and self-transcendence) and age as regressors. Using the AAL atlas as implemented in the WFU-Pickatlastoolbox for SPM we defined a mask to limit the analysis to the voxels in both amygdalae. Results: Based on Monte Carlo simulations conducted in AlphaSim, we used a voxel significance threshold p5 to have a multiple comparison corrected significance ?Using the Marsbar toolbox we selected the found clusters as ROI's and performed a 1-sampled T-test on the corresponding individual maps with the personality traits and age as covariates to check the significance of the underlying activation. This test revealed only a significant (pFWE-correctedConclusions: Our study showed a higher activation in the right amygdala related to higher scores on harm avoidance in response to aversive pictures in young healthy females. This result supports previous findings of a stronger response to aversive stimuli in individuals scoring high on harm avoidance [3,7]. References: [1] Cloninger. C.R. (1993): Archives of General Psychiatry; 50:975-990 [2] Farmer R.F. et al. (2009): Depression and anxiety; 26:371-381 [3] Most S. et al. (2006): NeuroImage; 31:1016-1027 [4] Kim M.J. et al. (2011): Behavioral Brain Research; 223:403-410 [5] Baeken C. et al. (2010): Behavioral Brain Research; 214:450-455 [6] Calhoun V.D. et al. (2004): NeuroImage; 22:252-257 [7] Reinhardt I. et al. (2010): European Archives of Psychiatry and Clinical Neuroscience; 260:443-453

People with anxiety disorders show an attentional bias for threat (AB), and Attention Bias Modification (ABM) procedures have been found to reduce this bias. However, the underlying processes accounting for this effect remain poorly understood. One explanation suggests that ABM requires the modification of attention control, driven by the recruitment of the dorsolateral prefrontal cortex (DLPFC). In the present double-blind study, we examined whether modifying left DLPFC activation influences the effect of ABM on AB. We used transcranial direct current stimulation (tDCS) to directly modulate cortical excitability of the left DLPFC during an ABM procedure designed to reduce AB to threat. Anodal tDCS increases excitability, whereas cathodal tDCS decreases it. We randomly assigned highly trait-anxious individuals to one of three conditions: 1) ABM combined with cathodal tDCS, 2) ABM combined with anodal tDCS, or 3) ABM combined with sham tDCS. We assessed the effects of these manipulations on both reaction times and eye-movements on a task indexing AB. Results indicate that combining ABM and anodal tDCS over the left DLPFC reduces the total duration that participants’ gaze remains fixated on threat, as assessed using eye-tracking measurement. However, in contrast to previous studies, there were no changes in AB from baseline to post-training for participants that received ABM without tDCS. As the tendency to maintain attention to threat is known to play an important role in the maintenance of anxiety, the present findings suggest that anodal tDCS over the left DLPFC may be considered as a promising tool to reduce the maintenance of gaze to threat. Implications for future translational research combining ABM and tDCS are discussed.

IntroductionRepetitive transcranial magnetic stimulation (rTMS) affects neuronal circuits and neurotransmitter systems in the brain. Recent data suggest that this application could diminish ‘craving’ in patients with alcohol dependence.Objectives and aimsGiven these preliminary data, we examined whether one high frequency (HF)- rTMS session over the right dorsolateral prefrontal cortex (DLPFC) would reduce alcohol craving in alcohol dependent patients in their natural habitat.MethodsAfter detoxification during hospitalization, 22 current alcohol dependent inpatients were included (8 female, 14 male; age = 49.95 ± 8.82y).We used a sham-controlled between-subjects design where after randomization patients received under MRI guidance one right-sided DLPFC active HF-rTMS session or sham. In each high-frequency (20 Hz) stimulation session, patients received 1560 pulses at 110 % MT. The obsessive-compulsive drinking scale (OCDS) was collected at baseline, just before and just after the stimulation session on Friday after detoxification and on the three consecutive days following stimulation in patient's natural habitat.ResultsAlthough the OCDS total score significantly decreased after the detoxification period, one sham-controlled stimulation session did not affect immediate craving measurements. Furthermore, no significant group differences were observed on OCDS total scores when patients were in their natural habitat.ConclusionsAlthough the right DLPFC was targeted under MRI guidance, our preliminary results indicate that one sham-controlled HF-rTMS session does not affect craving in recently detoxified alcohol dependent patients. Besides the limited number of patients it could be possible that only one stimulation session could be insufficient to have a subjective effect on craving.

The amygdalae play an important role in the evaluation and processing of emotionally salient visual stimuli. However, individual differences in personality traits, such as Harm Avoidance (HA), have been reported to influence emotional amygdalae responses. To trigger strong approach and withdrawal-related emotions in 'never depressed' young female subjects under fMRI, we presented them with blocks of happy 'healthy' baby faces and baby faces disfigured by severe dermatological conditions and we integrated the temperament dimension HA into our analysis. No other instructions were given than to watch the images attentively. Only in withdrawal-related emotional experience, we observed a negative correlation between HA and left amygdala activity, suggesting that during passive viewing females scoring higher on HA 'avoid' images with highly aversive content. When investigating the amygdala's emotional role in passive viewing paradigms, personality features such as HA should be taken into account.

Introduction: High-frequency repetitive transcranial magnetic stimulation (HF-rTSM) of the left dorsolateral prefrontal cortex (L-DLPFC) has been introduced to treat mood disorders. The influence of HF-rTMS on emotional processes in the brain is still unclear. In this study we investigated in healthy volunteers the effects present one hour after stimulation using an emotional task during fMRI. Subject selection avoided the confounding effects of age, gender and depressive mood Materials and methods: We included 19 non-depressed female volunteers (25?5 years) who conformed to the current guidelines for rTMS and fMRI research. All of them received an active rTMS (10Hz; 40 trains of 3.9s; intertrain interval=26.1s; 110% motor threshold intensity) and a sham (coil perpendicular to the scalp) session of the L-DLPFC in two separate sessions (separated by at least 1 week). 10 volunteers were chosen at random to receive the active session first, while the other 9 received the sham session first. One hour after each stimulation session, all volunteers completed an event-related fMRI experiment. They were asked to assess the emotional content of the positively and negatively valenced baby face pictures used in [1], by button presses. The pictures were shown in random sequence with 3.78?2.26s inter-trial time. The volunteers were familiarized with all pictures just before the fMRI experiment. We measured 164 EPI images (TR/TE=3000/35ms; 18 slices; matrix=64x64) using a 1.5T Philips MRI scanner. Analysis was done as pointed out in [2] using SPM8, to find the individual activation maps in response to the positive and negative pictures. Results: Based on these activation maps, a 3-by-2 ANOVA (emotion x group x treatment) was performed. With p(uncorrected)Conclusions: Stimulation effects in regions known to play a key role in emotional processes [3] were found one hour after the rTMS session. References: [1] Baeken C.(2010): Behavioral Brain Research;214:450-455 [2] Calhoun V.D.(2004): NeuroImage;22:252-257 [3] Pessoa L.(2010): Nat. Rev. Neurosci.;11:773-783

The amygdalae are key players in the processing of a variety of emotional stimuli. Especially aversive visual stimuli have been reported to attract attention and activate the amygdalae. However, as it has been argued that passively viewing withdrawal-related images could attenuate instead of activate amygdalae neuronal responses, its role under passive viewing conditions remains unclear. Furthermore, because individual sensitivity to stress reactions has been shown to modulate amygdalae processing, the aim of the current event-related fMRI study was to investigate whether individual differences in stress proneness could influence amygdala responses while passively viewing withdrawal and approach-related visual images. We presented 14 healthy female subjects with a random sequence of images of happy ‘healthy’ baby faces (approach-related) and baby faces disfigured by severe dermatological conditions (withdrawal-related). No instructions were given other than to watch the images attentively. We integrated individual perceived stress (PSS) scores in our analysis. The processing of withdrawal-related pictures resulted in less left amygdala activity in females scoring higher on perceived stress. Our findings suggest that stress-sensitive healthy females are less able to fully attend to withdrawal-related visual material and in essence avoid exposure to such images in an effort to reduce strong psychophysiological responses. Although the relatively small number of participants limits drawing firm conclusions, we suggest that in passive viewing emotional brain imaging paradigms, individual information on stress proneness should be included in the interpretation of amygdala neuronal processes.

Background Major depression is a worldwide severe mental health problem. Unfortunately, not all depressed patients respond to pharmacotherapy or psychotherapy, even when adhering to treatment guidelines. Even though current guidelines do not in particular advocate repetitive Transcranial Magnetic Stimulation (rTMS) in refractory treatment resistant depression (TRD), using more intensive stimulation parameters might hold promise as a valuable alternative. Objective Consequently, in this randomized sham-controlled crossover study, we wanted to evaluate clinical outcome of intensive HF-rTMS treatment in TRD when applied to the left dorsolateral prefrontal cortex (DLPFC). Methods After a 2-week antidepressant washout, 20 unipolar TRD patients, at least stage III, received 20 sham-controlled high-frequency (HF)-rTMS sessions, in a crossover design. Five daily suprathreshold HF-rTMS sessions were spread over four successive days delivering in total 31,200 stimuli. Results Overall, the procedure resulted in immediate statistical significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham), suggesting possible placebo responses. On the other hand, albeit only 35% (7/20) of the patients showed a 50% reduction of their initial Hamilton Depression rating score at the end of the two-week procedure, all these patients showed a prompt clinical response after real HF-rTMS treatment, not after sham. Furthermore, a shorter duration of the current depressive episode was a predictor for beneficial clinical outcome. Unresponsiveness to former ECT could be indicative for negative clinical outcome in these kinds of patients. Limitations Single center setup with relatively small sample size and no follow-up. Conclusions Our findings indicate that intensive HF-rTMS treatment might have the potential to result in fast clinical response when confronted with a refractory TRD patient.

IntroductionRepetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC) is safe and efficient for treatment-resistant depression (TRD). More intensive rTMS protocols could improve clinical outcome.ObjectivesWe report on an intensive high frequency (HF)-rTMS treatment protocol in patients unresponsive to current treatment strategies.AimsMonitoring effectiveness and tolerability.MethodsPatients were diagnosed with TRD, schizoaffective disorder, bipolar type or bipolar type I disorder, mixed episode. All were unresponsive to adequate therapy (rTMS excluded).HF-rTMS was administrated on the left DLPFC under MRI guidance. In each 20 Hz stimulation session, the patient received 40 trains of 1.9 seconds duration at 120% of the motor threshold. The 20 HF-rTMS sessions were spread over 4 days (5 times/day), yielding a total of 31,200 stimuli.ResultsThere were neither seizures nor important adverse events. The bipolar patient clinically responded (Hamilton Depression Rating Scale (HAMD) from 20 to 9) following treatment day 1. After completing the protocol a week earlier, the TRD patient's HAMD went from 28 to 5. There was a 5 point decrease in the score of the schizoaffective patient. He improved on the brief psychiatric rating subscales blunted affect and emotional withdrawal. No positive symptoms occurred. None of the patients had significant elevations in YMRS scores or in psychomotor activity.Conclusion‘Intensively’ targeting the left DLPFC was tolerated and safe. Our results suggest a strategy of HF-rTMS protocols in non-responders to classical treatment. Larger sham-controlled HF-rTMS studies should substantiate these recent findings.

Two different emotion regulation strategies, cognitive reappraisal and expressive suppression, are strongly associated with increased neural activity in the prefrontal cognitive control network. In this event-related fMRI study, we investigated whether individual differences in habitual reappraisal and suppression tendencies are related to differences in prefrontal cognitive control processes for emotional information. In order to measure cognitive control over inhibiting a dominant response to happy or sad stimuli (in favor of the opposite valence), thirty-one healthy female participants performed the Cued Emotional Conflict Task (CECT). The Emotion Regulation Questionnaire was used to measure individual differences in everyday use of emotion regulation. Results demonstrate that high reappraisers are behaviorally faster and exert more fronto-cingulate activity when inhibiting a response to sad faces (compared to happy faces, FDR corrected). On the other hand, suppression scores are not correlated with performance to CECT trials. Interestingly, suppression scores are associated with higher amygdala activation during the inhibition of a response to sad faces (compared to happy faces). These data suggest that habitual reappraisal is associated with underlying functional cognitive control processes to inhibit a dominant response to negative material. In contrast, the effort to control negative material has negative consequences in individuals who have a tendency to suppress emotions.

Background: The affective personality trait 'harm avoidance' (HA) from Cloninger's psychobiological personality model determines how an individual deals with emotional stimuli. Emotional stimuli are processed by a neural network that include the left and right amygdalae as important key nodes. Explicit, implicit and passive processing of affective stimuli are known to activate the amygdalae differently reflecting differences in attention, level of detailed analysis of the stimuli and the cognitive control needed to perform the required task. Previous studies revealed that implicit processing or passive viewing of affective stimuli, induce a left amygdala response that correlates with HA. In this new study we have tried to extend these findings to the situation in which the subjects were required to explicitly process emotional stimuli. Methods: A group of healthy female participants was asked to rate the valence of positive and negative stimuli while undergoing fMRI. Afterwards the neural responses of the participants to the positive and to the negative stimuli were separately correlated to their HA scores and compared between the low and high HA participants. Results: Both analyses revealed increased neural activity in the left laterobasal (LB) amygdala of the high HA participants while they were rating the positive and the negative stimuli. Conclusions: Our results indicate that the left amygdala response to explicit processing of affective stimuli does correlate with HA.