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Background: As part of repetitive negative thinking (RNT), rumination is a maladaptive cognitive response style to stress or negative mood which can increase the risk of depression and may prohibit complete recovery. Cognitive behavioral therapy (CBT) and transcranial direct current stimulation (tDCS) both proved to be effective in decreasing rumination. However, the combined effects of tDCS and CBT interventions on rumination have not yet been explored. The first aim of this pilot study is to investigate whether the combination of tDCS and CBT has an accumulating positive effect on modulating state rumination. The second aim is to assess the feasibility and safety profile of the proposed combined approach. Method: Seventeen adults aged 32-60 years, suffering from RNT, were referred by their primary care professional to participate in an 8-week group intervention for RNT ("Drop It") comprising 8 sessions of CBT. Before each CBT session, patients underwent one double-blinded prefrontal active (2 mA for 20 min) or sham tDCS (anode over F3, cathode over the right supraorbital region) combined with an internal cognitive attention task focused on individual RNT, i.e., online tDCS priming. During each session, the Brief State Rumination Inventory was used to assess state rumination. Results: A mixed effects model analysis revealed no significant differences between the stimulation conditions, weekly sessions, or their interaction in terms of state rumination scores. Conclusion: Overall, the combination of online tDCS priming followed by group CBT was found to be safe and feasible. On the other hand, no significant additional effects of this combined approach on state rumination were established. Although our pilot study may have been too small to find significant clinical effects, future larger RCT studies on combined tDCS-CBT treatment protocols may reevaluate the selection of internal cognitive attention tasks and more objective neurophysiological measurements, consider the optimal timing of the combination (concurrently or sequentially), or may add additional tDCS sessions when following CBT.

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OBJECTIVES: Treatment of repetitive negative thinking (RNT) focuses rather on individual than group cognitive behaviour therapy (CBT) treatment. Additionally, little is known on how clients experienced these interventions. This study investigates clients' experiences on participating in a CBT group intervention targeting RNT (RNT-G). DESIGN: Of the 80 participants, 11 were randomly selected for an in-depth, semi-structured interview after treatment. Interviews focused on what participants experienced as important on group aspects, offered interventions, homework tasks, and possible changes. METHODS: All participants were adults, diagnosed with major depressive disorder and/or generalized anxiety disorder and being currently in mental health care treatment. After transcribing the interviews, analyses were performed according to the guidelines of thematic analysis. RESULTS: Four major themes were identified. First, the group format itself was experienced as an important factor of change. The experiences about the different offered interventions during the group formed a second theme. A third theme related to changes in family or professional life and dealing with RNT as a result of the intervention. Finally, group participation, social interactions, and mental health care treatment were experienced as mutually influencing during the intervention. CONCLUSIONS: The results of this study shed some light on which treatment interventions were perceived as beneficial during the RNT-G and should therefore be emphasized in treatment. Further, they indicate that the treatment in a group format was experienced as helpful by the participants. Finally, a positive mutual influence between the group intervention and the ongoing individual treatment was experienced.

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Repetitive negative thinking (RNT)-such as worry and rumination-is an important transdiagnostic factor in the onset, course, and recurrence of depressive and anxiety disorders. This article describes a psychoeducational cognitive behavioral therapy (CBT)-based group intervention entitled "Drop It" that focuses exclusively on treating RNT in patients with major depressive disorder and/or generalized anxiety disorder. The theoretical concepts and treatment goals of the intervention are outlined. The organization and therapeutic processes of the different sessions are described and illustrated with statements of participants. Special attention is given to how the intervention capitalizes on the group structure and process to maximize the effectiveness of psychoeducation and CBT-based techniques. We also provide practical guidelines for clinicians treating patients with RNT.

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Repetitive negative thinking (RNT) is a core process underlying various psychiatric disorders. 'Uncontrollability of rumination (UOR)' is one the most maladaptive factors of rumination, but little is known on how cognitive behavioral focused RNT psychotherapy may alter brain activity. In a subsample of 47 patients suffering from RNT who also underwent brain imaging (registered RCT trial NCT01983033), we evaluated the effect of cognitive behavioral based group psychotherapy (CBGP) (n = 25) as compared to a delayed treatment control group (DTCG) (n = 22) on frontolimbic brain perfusion with a focus on UOR. This RNT construct was measured using the subscale 'uncontrollability' of the Dutch version of the Rumination on Sadness Scale (LARSS-U). Brain perfusion was assessed with arterial spin labeling (ASL)-fMRI. LARSS-U scale scores significantly decreased in the CBGP cohort whereas no significant changes emerged in the DTCG group. Compared to the DTCG, this decrease on UOR in the CBGP group was related to significant perfusion increases in the left (dorsolateral) prefrontal cortex, part of the executive network. Besides the fact that CBGP significantly reduced RNT, this attenuation of uncontrollable ruminative thoughts was related to brain perfusion increases areas documented to be involved in the top down control of adaptive emotion regulation and the inhibition of ruminative processes.

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The mechanisms by which transcranial direct current stimulation (tDCS) influences emotional processing - and whether this is related to individual vulnerability for psychopathology - are still poorly understood. The present study aimed to investigate if one prefrontal tDCS session modulates mood and neural functional connectivity after being exposed to negative information differently in individuals low or high in perceived criticism (PC), which has been related to vulnerability for psychiatric illness. In a randomized cross-over design, one session of MRI-compatible prefrontal tDCS (neuronavigated placement of the anodal electrode at the left dorsolateral prefrontal cortex and the cathodal electrode at the right supraorbital region; vs. sham) was administered to healthy females, prior to listening to self-referential criticism. PC-dependent (low vs. high PC) changes in mood and resting-state functional connectivity patterns following tDCS and after hearing criticism were explored. After being criticized all females (low and high PC) felt angrier and more depressed, both in the active tDCS or sham tDCS condition. However, in contrast to low PC females, in high PC females prefrontal tDCS reduced connectivity between the left dorsal anterior cingulate cortex and the right dorsomedial prefrontal cortex following criticism. Despite having no differential effects on self-reported mood, prefrontal tDCS reduces medial prefrontal neural connectivity after being criticized in high PC females compared to low PC females. Depending on individual vulnerability for psychopathology, a single tDCS session differentially affects neural processing of negative emotional information, especially in brain regions involved in monitoring, experiencing and appraising/evaluating emotional material.

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Transcranial direct current stimulation (tDCS) is a potential treatment strategy for mood and anxiety disorders, but how this application may influence emotional processes, and whether this is related to individual characteristics, is not well understood. It has been proposed that perceived criticism (PC) may represent a vulnerability factor for the development of such mental illnesses. To decipher whether neural mechanisms of action of tDCS potentially differ depending on PC status (low vs. high), we evaluated mood and brain perfusion before and after applying MRI-compatible tDCS, and after participants were exposed to verbal criticism in the scanner. Experimental design 30 healthy nondepressed females were included in a sham-controlled crossover MRI-compatible tDCS study. Brain perfusion was measured by means of arterial spin labeling (ASL) before and after tDCS applied to the left dorsolateral prefrontal cortex (DLPFC), and after hearing criticism. Before the experiment, all participants provided a rating of PC in their closest environment. Principal observations at the behavioral level, criticism made participants angrier. This was unrelated to the active or sham stimulation. After being criticized, females scoring high on PC had significantly decreased brain perfusion in the pregenual anterior cingulate cortex (pgACC) and medioprefrontal cortex (mPFC), after active tDCS but not sham. The decrease in pgACC/mPFC perfusion points to a significant impact of tDCS in brain areas related to stress responses and self-referential processes, especially in females scoring high on PC, which has been shown to be related to vulnerability for mood and anxiety disorders.

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Transcranial direct current stimulation (tDCS) involves positioning two electrodes at specifically targeted locations on the human scalp. In neuropsychiatric research, the anode is often placed over the left dorsolateral prefrontal cortex (DLPFC), while the cathode is positioned over a contralateral cephalic region above the eye, referred-to as the supraorbital region. Although the 10-20 EEG system is frequently used to locate the DLPFC, due to inter-subject brain variability, this method may lack accuracy. Therefore, we compared in forty participants left DLPFC-localization via the 10-20 EEG system to MRI-guided neuronavigation. In one participant, with individual electrode positions in close proximity to the mean electrode position across subjects, we also investigated whether distinct electrode localizations were associated with different tDCS-induced electrical field distributions. Furthermore, we aimed to examine which neural region is targeted when placing the reference-electrode on the right supraorbital region. Compared to the 10-20 EEG system, MRI-guided neuronavigation localizes the DLPFC-targeting anode more latero-posteriorly, targeting the middle prefrontal gyrus. tDCS-induced electric fields (n = 1) suggest that both localization methods induce significantly different electric fields in distinct brain regions. Considering the frequent application of tDCS as a neuropsychiatric treatment, an evaluation and direct comparison of the clinical efficacy of targeting methods is warranted.

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It has been proposed that a crucial link between cognitive (i.e., self-schemas) and biological vulnerability is prefrontal control. This is because decreased control leads to impaired ability to inhibit ruminative thinking after the activation of negative self-schemas. However, current evidence is mainly correlational. In the current experimental study we tested whether the effect of neurostimulation of the dorsolateral prefrontal cortex (DLPFC) on self-esteem is mediated by momentary ruminative self-referential thinking (MRST) after the induction of negative self-schemas by criticism. We used a single, sham-controlled crossover session of anodal transcranial Direct Current Stimulation (tDCS) applied to the left DLPFC (cathode over the right supraorbital region) in healthy female individuals. After receiving tDCS/sham stimulation, we measured MRST and exposed the participants to critical audio scripts, followed by another MRST measurement. Subsequently, all participants completed two Implicit Relational Assessment Procedures to implicitly measure actual and ideal self-esteem. Our behavioral data indicated a significant decrease in MRST after real but not sham tDCS. Moreover, although there was no immediate effect of tDCS on implicit self-esteem, an indirect effect was found through double mediation, with the difference in MRST from baseline to after stimulation and from baseline to after criticism as our two mediators. The larger the decrease of criticism induced MRST after real tDCS, the higher the level of actual self-esteem. Our results show that tDCS can influence cognitive processes such as rumination, and subsequently self-esteem, but only after the activation of negative self-schemas. Rumination and negative self-esteem characterize different forms of psychopathology, and these data expand our knowledge of the role of the prefrontal cortex in controlling these self-referential processes, and the mechanisms of action of tDCS.

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BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive electrical stimulation technique, assumed to influence cognition and emotional processing. OBJECTIVE: However, it is unclear how tDCS influences spontaneous cognitive processes such as momentary self-referential thoughts on the neuronal level. METHODS: Forty healthy female volunteers participated in a single session sham-controlled crossover tDCS study while being in the MRI scanner. We measured brain perfusion (arterial spin labeling) just before and just after tDCS. Before and after the stimulation procedure, participants were scored on mood (visual analogue scales) and on the Momentary Ruminative Self-focus Inventory (MRSI). We performed a 1.5 mA, 20-min, anodal left dorsolateral prefrontal cortex, cathodal right supraorbital stimulation. RESULTS: One sham-controlled tDCS session did not result in subjective mood changes. However, as compared to before, MRSI scores significantly decreased only after active tDCS. Regression analysis revealed that this reduction in momentary ruminative self-referential thoughts was related to tDCS-related increases in left prefrontal cortical perfusion. tDCS decreased momentary self-referential thoughts, which was associated with increasing perfusion in the left prefrontal cortex. CONCLUSION: Our findings are in line with the hypothesis that tDCS of the DLPFC attenuates ruminative processes.

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Non-invasive neurostimulation or neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) were welcomed as promising tools for investigating cognitive and mood processes in healthy participants as well as in patients suffering from neuropsychiatric conditions. Due to their rather easy application, both modalities have been used to experimentally examine prefrontal cognitive and emotional control. However, it remains unclear whether a single session of such stimulation may affect the mood of participants in a healthy state. We provide a systematic review of studies reporting the effects of a single session of rTMS or tDCS (…-2014) on self-reported mood in healthy participants. Although early studies reported significant effects on self-reported mood in healthy participants, more recent work investigating mood effects after a single rTMS/tDCS session has failed to find any significant changes in self-reported mood. Therefore it appears that a single session of rTMS/tDCS has no impact on mood in the healthy state.

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OBJECTIVE: Previous research has demonstrated that prefrontal activity is related to control over stress responses. However, the causal mechanisms are not well understood. In this study we investigated the possible influence of brain stimulation on the physiological stress response system. Because an increased stress response is known to precipitate psychiatric disorders, further inquiry can have important clinical implications. METHOD: In 38 healthy, right-handed female participants, we examined the effects of a single sham-controlled high-frequency (HF) repetitive Transcranial Magnetic Stimulation (rTMS) session over the left (n = 19) and right (n = 19) dorsolateral prefrontal cortex (DLPFC) on the autonomic nervous system stress response, as measured by heart rate variability (HRV). Stress was transiently induced through evaluative negative feedbacks. RESULTS: Although the induction procedure was efficient in increasing self-reported distress in all groups and conditions, only after real HF-rTMS over the left DLPFC the physiological stress response was diminished, as indicated by a significant increase in HRV. No effects were found in the sham or right side stimulation condition. CONCLUSIONS: These findings demonstrate that increasing brain activity by HF-rTMS over the left DLPFC can help attenuating physiological stress reactions. Results are indicative of the positive effects of rTMS on stress resilience and underscore the possible benefit of HF-rTMS as a transdiagnostic intervention. Finally, the results also show that effects only occur when stimulating the left DLPFC, which is in line with the therapeutic effects of HF-rTMS in affective disorders. (PsycINFO Database Record

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Everyday social evaluations are psychologically potent and trigger self-reflective thoughts and feelings. The present study sought to examine the psychophysiological impact of such evaluations using eye tracking, pupillometry, and heart-rate variability. Fifty-nine healthy adult volunteers received rigged social feedback (criticism and praise) based on their photograph. Gaze data were collected to investigate processes of attentional deployment/allocation toward the self or the evaluator expressing criticism or praise. Whereas voluntary attention was directed to evaluators who expressed praise, attention was drawn to one's own picture after criticism. Pupil dilation and heart-rate variability were larger in response to criticism as compared to praise, suggesting a flexible and adaptive emotion regulatory effort in response to social information that triggers an affective response. Altogether, healthy individuals recruited more regulatory resources to cope with negative (as compared to positive) social feedback, and this processing of social feedback was associated with adjustments in self-focused attention.

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A growing body of work suggests that both depressed and non-depressed individuals display implicit positivity towards the self. In the current study, we examined whether this positivity can be underpinned by two qualitatively distinct propositions related to actual ('I am good') or ideal ('I want to be good') self-esteem. Dysphoric and non-dysphoric participants completed a self-esteem Implicit Association Test (IAT) as well an Implicit Relational Assessment Procedure (IRAP) targeting their actual self-esteem and an IRAP targeting ideal self-esteem. Both groups demonstrated similar and positive IAT effects. A more complex picture emerged with regard to the IRAP effects. Whereas non-dysphorics did not differ in their actual and ideal self-esteem, their dysphoric counterparts demonstrated lower actual than ideal self-esteem. Our results suggest that closer attention to the role of propositional processes in implicit measures may unlock novel insight into the relationship between implicit self-esteem and depression.

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Emotions can occur during an emotion-eliciting event, but they can also arise when anticipating the event. We used pupillary responses, as a measure of effortful cognitive processing, to test whether the anticipation of an emotional stimulus (positive and negative) influences the subsequent online processing of that emotional stimulus. Moreover, we tested whether individual differences in the habitual use of emotion regulation strategies are associated with pupillary responses during the anticipation and/or online processing of this emotional stimulus. Our results show that, both for positive and negative stimuli, pupillary diameter during the anticipation of emotion-eliciting events is inversely and strongly correlated to pupillary responses during the emotional image presentation. The variance in this temporal interplay between anticipation and online processing was related to individual differences in emotion regulation. Specifically, the results show that high reappraisal scores are related to larger pupil diameter during the anticipation which is related to smaller pupillary responses during the online processing of emotion-eliciting events. The habitual use of expressive suppression was not associated to pupillary responses in the anticipation and subsequent online processing of emotional stimuli. Taken together, the current data suggest (most strongly for individuals scoring high on the habitual use of reappraisal) that larger pupillary responses during the anticipation of an emotional stimulus are indicative of a sustained attentional set activation to prepare for an upcoming emotional stimulus, which subsequently directs a reduced need to cognitively process that emotional event. Hence, because the habitual use of reappraisal is known to have a positive influence on emotional well-being, the interplay between anticipation and online processing of emotional stimuli might be a significant marker of this well-being.

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OBJECTIVES: Intensified repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) may result in fast clinical responses in treatment resistant depression (TRD). In these kinds of patients, subgenual anterior cingulate cortex (sgACC) functional connectivity (FC) seems to be consistently disturbed. So far, no de novo data on the relationship between sgACC FC changes and clinical efficacy of accelerated rTMS were available. METHODS: Twenty unipolar TRD patients, all at least stage III treatment resistant, were recruited in a randomized sham-controlled crossover high-frequency (HF)-rTMS treatment study. Resting-state (rs) functional MRI scans were collected at baseline and at the end of treatment. RESULTS: HF-rTMS responders showed significantly stronger resting-state functional connectivity (rsFC) anti-correlation between the sgACC and parts of the left superior medial prefrontal cortex. After successful treatment an inverted relative strength of the anti-correlations was observed in the perigenual prefrontal cortex (pgPFC). No effects on sgACC rsFC were observed in non-responders. CONCLUSIONS: Strong rsFC anti-correlation between the sgACC and parts of the left prefrontal cortex could be indicative of a beneficial outcome. Accelerated HF-rTMS treatment designs have the potential to acutely adjust deregulated sgACC neuronal networks in TRD patients.

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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.

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Transcranial Direct Current Stimulation (tDCS) is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP) as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation), we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right) prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information.

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Although depression is characterised by low self-esteem as measured by questionnaires, research using implicit measures of self-esteem has failed to reveal the expected differences between depressed and non-depressed individuals. In this study, we used an implicit measure which enables the differentiation of ideal self- and actual self-esteem, through the introduction of propositions: "I am" versus "I want to be". We measured implicit relational associations about actual and ideal self in low (N=27) versus high dysphoric (N=29) undergraduates. Our data revealed that dysphoric individuals have a higher ideal self-esteem, and lower actual self-esteem in comparison to healthy participants. The results underscore the need to go beyond simple associations and suggest that the use of individual-specific propositions could enhance our understanding of the implicit measurement of self-esteem. Furthermore, these results underscore the importance of actual versus ideal self-discrepancy theories, which might guide the content of therapeutic interventions.

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