Jonathan Remue

Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from subgenual anterior cingulate functional connectivity

Abstract 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.

Intensive HF-rTMS treatment in refractory medication-resistant unipolar depressed patients.

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.

tDCS over the Left Prefrontal Cortex Enhances Cognitive Control for Positive Affective Stimuli

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.

Self-esteem revisited: Performance on the implicit relational assessment procedure as a measure of self- versus ideal self-related cognitions in dysphoria

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.

To Be or Want to Be: Disentangling the Role of Actual versus Ideal Self in Implicit Self-Esteem

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.

One left dorsolateral prefrontal cortical HF-rTMS session attenuates HPA-system sensitivity to critical feedback in healthy females

OBJECTIVE Although left dorsolateral prefrontal cortical (DLPFC) repetitive Transcranial Magnetic Stimulation (rTMS) is used to treat major depression, its underlying neurophysiological working mechanism remains to be determined. Prior research suggested that the clinical effects could be mediated by affecting the hypothalamic-pituitary-adrenal (HPA) system, but experimental studies in healthy individuals did not yield clear results. However, in healthy individuals, the influence of HF-rTMS on the HPA-system may only be detected when it is challenged. METHODS In 30 rTMS naïve healthy females we evaluated the effect of one sham-controlled high frequency (HF)-rTMS session applied to the left DLPFC on the stress hormone cortisol by collecting salivary cortisol samples. In order to increase stress levels, 5min after stimulation, all participants performed the Critical Feedback Task (CFT), during which they were criticized on their performance. To take possible mood influences into account, all participants were also assessed with Visual Analogue Scales (VAS). RESULTS The experimental procedure did not affect mood differently in the real or sham stimulation. Area under the curve (AUCi) analysis showed that one real HF-rTMS session significantly influenced HPA-system sensitivity, as demonstrated by a decrease in cortisol concentrations. The sham procedure yielded no effects. CONCLUSIONS In line with former observations in major depression, one real left DLPFC HF-rTMS session significantly influenced HPA-system sensitivity in experimentally stressed females, resulting in decreases in cortisol levels.

Does a single neurostimulation session really affect mood in healthy individuals? A systematic review

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.

The regulation of positive and negative social feedback: A psychophysiological study

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.

The interplay between the anticipation and subsequent online processing of emotional stimuli as measured by pupillary dilatation: the role of cognitive reappraisal

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.

The effect of a single HF-rTMS session over the left DLPFC on the physiological stress response as measured by heart rate variability.

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