Cortical thickness is related to working memory performance after non-invasive brain stimulation.

Non-invasive brain stimulation (NIBS) probing the dorsolateral prefrontal cortex (DLPFC) has been shown to have little effect on working memory. The variability of NIBS responses might be explained by inter-subject brain anatomical variability. We investigated whether baseline cortical brain thickness of regions of interest was associated with working memory performance after NIBS by performing a secondary analysis of previously published research. Structural magnetic resonance imaging data were analyzed from healthy subjects who received transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and placebo. Twenty-two participants were randomly assigned to receive all the interventions in a random order. The working memory task was conducted after the end of each NIBS session. Regions of interest were the bilateral DLPFC, medial prefrontal cortex, and posterior cingulate cortex. Overall, 66 NIBS sessions were performed. Findings revealed a negative significant association between cortical thickness of the bilateral dorsolateral prefrontal cortex and reaction time for both tDCS (left: P=0.045, right: P=0.037) and iTBS (left: P=0.007, right: P=0.007) compared to placebo. A significant positive association was found for iTBS and posterior cingulate cortex (P=0.03). No association was found for accuracy. Our findings provide the first evidence that individual cortical thickness of healthy subjects might be associated with working memory performance following different NIBS interventions. Therefore, cortical thickness could explain - to some extent - the heterogeneous effects of NIBS probing the DLPFC.

Cortical thickness is related to working memory performance after non-invasive brain stimulation

Non-invasive brain stimulation (NIBS) probing the dorsolateral prefrontal cortex (DLPFC) has been shown to have little effect on working memory. The variability of NIBS responses might be explained by inter-subject brain anatomical variability. We investigated whether baseline cortical brain thickness of regions of interest was associated with working memory performance after NIBS by performing a secondary analysis of previously published research. Structural magnetic resonance imaging data were analyzed from healthy subjects who received transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and placebo. Twenty-two participants were randomly assigned to receive all the interventions in a random order. The working memory task was conducted after the end of each NIBS session. Regions of interest were the bilateral DLPFC, medial prefrontal cortex, and posterior cingulate cortex. Overall, 66 NIBS sessions were performed. Findings revealed a negative significant association between cortical thickness of the bilateral dorsolateral prefrontal cortex and reaction time for both tDCS (left: P=0.045, right: P=0.037) and iTBS (left: P=0.007, right: P=0.007) compared to placebo. A significant positive association was found for iTBS and posterior cingulate cortex (P=0.03). No association was found for accuracy. Our findings provide the first evidence that individual cortical thickness of healthy subjects might be associated with working memory performance following different NIBS interventions. Therefore, cortical thickness could explain - to some extent - the heterogeneous effects of NIBS probing the DLPFC.

[Non-invasive brain stimulation techniques in psychiatric disorders: influential factors and combination of interventions]. / Niet-invasieve hersenstimulatie bij psychiatrische stoornissen: beïnvloedende factoren en combinatie van interventies.

BACKGROUND: The causal influence of cortico-subcortical connectivity by means of brain stimulation seems to be an effective biological treatment in psychiatric patients. AIM: To review the working mechanisms and moderating factors of two non-invasive brain stimulation techniques (NIBS), namely repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). METHOD: We reviewed the current literature on the use of nibs in neuropsychiatric disorders. RESULTS: First of all, stimulation parameters (location of the stimulation, intensity and duration of the stimulation, number of sessions) are important for the effect of nibs. Secondly, it is important to consider the non-specific neuroplasticity that results from NIBS. Thirdly, recent studies suggest that NIBS should be combined with neurobehavioral interventions, namely cognitive interventions, for the purpose of modulating specific neural processes (i.e. specific neuroplasticity). CONCLUSION: If we want to improve the NIBS treatment in neuropsychiatric patients, we need to consider the factors that influence the patients' response to treatment with rTMS and tDCS.

Cognitive control therapy and transcranial direct current stimulation for depression: a randomized, double-blinded, controlled trial.

BACKGROUND: Based on findings that major depressive disorder (MDD) is associated to decreased dorsolateral prefrontal cortical (DLPFC) activity; interventions that increase DLPFC activity might theoretically present antidepressant effects. Two of them are cognitive control therapy (CCT), a neurocognitive intervention that uses computer-based working memory exercises, and transcranial direct current stimulation (tDCS), which delivers weak, electric direct currents over the scalp. METHODS: We investigated whether tDCS enhanced the effects of CCT in a double-blind trial, in which participants were randomized to sham tDCS and CCT (n=17) vs. active tDCS and CCT (n=20). CCT and tDCS were applied for 10 consecutive workdays. Clinicaltrials.gov identifier: NCT01434836. RESULTS: Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up, with a response rate of approximately 25%. Older patients and those who presented better performance in the task throughout the trial (possibly indicating greater engagement and activation of the DLPFC) had greater depression improvement in the combined treatment group. LIMITATIONS: Our exploratory findings should be further confirmed in prospective controlled trials. DISCUSSION: CCT and tDCS combined might be beneficial for older depressed patients, particularly for those who have cognitive resources to adequately learn and improve task performance over time. This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy.

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.

Reduced intra-individual reaction time variability during a Go-NoGo task in detoxified alcohol-dependent patients after one right-sided dorsolateral prefrontal HF-rTMS session.

AIMS: As alcohol dependency is characterized by severe executive function deficits, we examined the influence of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex (DLPFC) on executive functioning in recently detoxified alcohol-dependent patients. METHODS: In this randomized, single blind, sham (placebo)-controlled, crossover study, we included 50 detoxified alcohol-dependent patients. We examined the effect of a single right DLPFC HF-rTMS session on commission errors, mean reaction times (RTs) and intra-individual reaction time variability (IIRTV) during a Go-NoGo task (50% Go/50% NoGo condition) in 29 alcohol-dependent patients. Patients completed this cognitive task immediately before and immediately after the stimulation session. In order to avoid carry-over effects between stimulation sessions, a 1-week inter-session interval was respected. Because rTMS treatment has been shown to affect subjective craving, all patients were also assessed with the Obsessive Compulsive Drinking Scale (OCDS). RESULTS: After both stimulation conditions, we observed a significant decrease of commission errors, without differences between active and sham HF-rTMS stimulation. No significant difference was observed between active and sham stimulation on mean RT. However, only active stimulation resulted in a significant decrease in IIRTV. No effects of stimulation were found for the craving measurements. CONCLUSION: Our findings suggest that in recently detoxified alcohol-dependent patients, one right-sided HF-rTMS session stabilizes cognitive performance during executive control tasks, implying that active stimulation reduces patients' proneness to attentional lapses.

Impact of one HF-rTMS session on fine motor function in right-handed healthy female subjects: a comparison of stimulation over the left versus the right dorsolateral prefrontal cortex.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool to investigate neural conduction in motor processes. Most rTMS research has been conducted by targeting the primary motor cortex. Several studies have also found increased psychomotor speed after rTMS of the dorsolateral prefrontal cortex (DLPFC). However, these studies were mainly performed in psychiatric patients, only targeting the left DLPFC, and often without sham control. Moreover, psychomotor speed is mostly measured based on tasks that also require higher executive functions. METHODS: Here, we examined the lateralized effect of one sham-controlled high-frequency rTMS session applied to the left or right DLPFC on fine motor function in 36 healthy right-handed females, using the Fitts' paradigm. RESULTS: We found a significant improvement in psychomotor speed only after actively stimulating the right DLPFC. CONCLUSION: Our results support the assumption of a right prefrontal neural network implicated in visuomotor behavior and performance processes, and that the improvement in psychomotor speed is not a secondary effect of decreased mood.

No influence of one right-sided prefrontal HF-rTMS session on alcohol craving in recently detoxified alcohol-dependent patients: results of a naturalistic study.

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.

The effect of one left-sided dorsolateral prefrontal sham-controlled HF-rTMS session on approach and withdrawal related emotional neuronal processes.

OBJECTIVE: Although repetitive Transcranial Magnetic Stimulation (rTMS) is frequently used to examine emotional changes in healthy volunteers, it remains largely unknown how rTMS is able to influence emotion. METHODS: In this sham-controlled, single-blind crossover study using fMRI, we examined in 20 right-handed healthy females whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces. RESULTS: While positive information was being processed, we observed after one active HF-rTMS session enhanced neuronal activity in the left superior frontal cortex and right inferior parietal cortex. After sham HF-rTMS, we found significant decreases in neuronal activity in the left superior frontal cortex, the left inferior prefrontal cortex, as well as in the right posterior cingulate gyrus. When negative information was processed, one active stimulation attenuated neuronal activity in the right insula only. CONCLUSIONS: Our findings suggest that during the processing of positive information one active session enhanced the ability to empathize with the depicted emotional stimuli, while during the processing of negative information it resulted in decreased psychophysiological reactions. SIGNIFICANCE: These results provide new information on the working mechanism of left-sided HF-rTMS.

Baseline 'state anxiety' influences HPA-axis sensitivity to one sham-controlled HF-rTMS session applied to the right dorsolateral prefrontal cortex.

Although negative results have been reported, an important aspect of the physiology of repetitive transcranial magnetic stimulation (rTMS) could be related to the endocrinological response of the hypothalamic-pituitary-adrenal (HPA) axis, such as cortisol secretion. Because endocrinological responses are influenced by anxiety states, this could influence the effect of rTMS in healthy individuals. In this sham-controlled, "single blind" crossover study, we examined whether one session of HF-rTMS could affect the HPA-system, when taking into account individual state anxiety scores based on the State-Trait Anxiety Inventory (STAI). Twenty-four healthy rTMS naïve females received one sham-controlled high frequency (HF)-rTMS session delivered on the right dorsolateral prefrontal cortex (DLPFC). The Profile of Mood States (POMS) questionnaire, together with salivary cortisol samples, was collected before, just after and 30 min post HF-rTMS. To examine whether state anxiety could influence endocrinological outcome measurements, we administered the STAI-state just before each HF-rTMS experiment started. Based on the POMS questionnaire, no mood changes were observed. Without taking individual state anxiety scores into account, one sham-controlled right-sided HF-rTMS session did not influence the HPA-system. When taking into account individual STAI-state scores, we found that healthy women scoring higher on the STAI-state displayed a significantly more sensitive HPA-system, resulting in salivary cortisol concentration increases after real HF-rTMS, compared to those scoring lower on this anxiety scale. Our results indicate that healthy women scoring high on state anxiety display a more sensitive HPA-system when receiving one right-sided HF-rTMS session. Our findings suggest that the incorporation of individual anxiety states in experimental rTMS research could add further information about its neurobiological influences on the HPA-system.

Right prefrontal HF-rTMS attenuates right amygdala processing of negatively valenced emotional stimuli in healthy females.

Repetitive transcranial magnetic stimulation (rTMS) studies investigating brain imaging correlates of emotion modulation in healthy volunteers can improve our understanding of the 'affective' impact of this application. In this fMRI study, we focused on lateralized amygdala functioning when processing salient emotional visual stimuli after one high-frequency (HF)-rTMS session. In a 'uniform sample' of 20 right-handed, non-depressed, healthy female subjects we examined whether one HF-rTMS session applied to the left (n=10) or right (n=10) dorsolateral prefrontal cortex (DLPFC) would influence amygdala responses to positively and negatively valenced baby faces. Subjects were given no other instructions than to focus on the emotion the visual stimuli elicited during scanning. One HF-rTMS session did not result in a conscious mood change. Whereas one left-sided HF-rTMS session did not affect amygdala processing of the positive or negative stimuli, after a single right-sided HF-rTMS session we found a significant right amygdala activity attenuation during the processing of negatively valenced baby faces. This finding provides additional evidence supporting the role of the right anterior hemisphere in the processing of negative emotional information, and increases our understanding of HF-rTMS treatment effects in mental disorders.

Reduced left subgenual anterior cingulate cortical activity during withdrawal-related emotions in melancholic depressed female patients.

BACKGROUND: Research regarding the neurocircuitry in mood disorders suggests an important role for affective information processing of the subgenual part of the anterior cingulate cortex (Cg25: Brodmann area 25). OBJECTIVE: In this study, we focused on Cg25 neuronal responses in depressed females using a paradigm in which emotions are elicited without explicit cognitive control, relying on the salient nature of the mood inducing stimuli eliciting approach-related emotions (like happiness) or withdrawal-related emotions (like disgust). METHODS: Twelve treatment-resistant melancholic depressed women and 12 healthy female control subjects were asked to passively view blocks of emotionally valenced baby faces while undergoing functional magnetic resonance imaging (fMRI). RESULTS: Compared to the healthy females, the depressed patients displayed significantly higher bilateral Cg25 neuronal activities in both emotional conditions. In melancholically depressed women, we found significantly less left-sided than right-sided Cg25 neuronal activity during the withdrawal-related emotions, while right-sided Cg25 activity was comparable for both emotional responses. CONCLUSIONS: Our results indicate that in depressed women the left Cg25 modulates intense visceral emotional responses to aversive visual stimuli. This could help explain why the left Cg25 provides a valid target region for antidepressant treatment strategies in unipolar melancholic depression.

HF-rTMS treatment decreases psychomotor retardation in medication-resistant melancholic depression.

Repetitive Transcranial Magnetic Stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising treatment strategy for depression. As one of the key features of melancholic depression is disturbances in psychomotor activity, we wanted to evaluate whether HF-rTMS treatment could influence psychomotor symptoms. Twenty antidepressant-free unipolar melancholic depressed patients, all at least stage III medication-resistant, were studied. All were treated with 10 sessions of High-Frequency (HF)-rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) under MRI guidance. Forty percent of the patients showed a reduction of at least 50% on their initial 17-item Hamilton Depression Rating Score (HDRS) scale and were defined as clinical responders. Regardless of clinical outcome HF-rTMS treatment resulted in significant decreases on the Depressive Retardation Rating Scale (DRRS) scores. Although this was an open study in a relatively small sample, our results suggest that HF-rTMS might act on the 'psychomotor' level and these findings could add some further information as to why this kind of treatment can be beneficial for severely depressed patients of the melancholic subtype.

Impairments in cognitive control persist during remission from depression and are related to the number of past episodes: an event related potentials study.

Recently, cognitive control deficits have been explored as a possible underlying trait abnormality in depression. In this study, cognitive control was investigated in homogeneous samples of never depressed controls, formerly depressed patients who had experienced a maximum of two depressive episodes and formerly depressed patients who had experienced at least three depressive episodes. We measured event related potentials (ERP) during a modified Stroop task in a sample of twenty-five formerly depressed patients and thirteen controls. Using this Stroop task, we manipulated subjects' cognitive control for congruent and incongruent trials. These Stroop manipulations have generally been related to two post-stimulus ERP components related to cognitive control, the N2 and the N450. Behavioural measurements of reaction times and error rates did not indicate a difference in cognitive control between the samples. Left frontal N450 amplitude for the high conflict (HC) condition differentiated the three groups. While a N450 conflict-related modulation was significant in the healthy comparison group, such an effect was significantly reduced in the remitted depressed patients, particularly in the high recurrent group. Importantly, the amplitude of the N450 conflict-related enhancement was inversely correlated with the number of prior episodes. This pattern was not found for the N2 component. These findings suggest that deficits in cognitive control increase with each depressive episode and persist after symptom remission, suggesting that depressive episodes leave a "scar" on cognitive control processes.

The impact of one HF-rTMS session on mood and salivary cortisol in treatment resistant unipolar melancholic depressed patients.

BACKGROUND: Recent studies indicate that medication resistant depressed patients can be successfully treated by a series of sessions of High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS), delivered on the left dorsolateral prefrontal cortex (DLPFC). However, changes in subjectively experienced mood give only limited insight into the underlying physiological responses. Previous studies in depressed patients, as well as in healthy volunteers, have reported a possible impact of HF-rTMS on the hypothalamic-pituitary-adrenal (HPA) axis. OBJECTIVE: We wanted to evaluate the emotional and neurobiological impact of one session of HF-rTMS applied on the left DLPFC in a sample of unipolar treatment resistant depressed patients of the melancholic subtype. METHODS: 20 right-handed antidepressant-free depressed patients were studied using a sham-controlled, 'single' blind, crossover design. We examined subjective mood changes with Visual Analogue Scales (VAS). To examine HF-rTMS effects on the HPA-axis, we analyzed salivary cortisol levels. Mood assessment and salivary cortisol levels were assessed before and immediately after stimulation. To detect any delayed effects, all measurements were also re-assessed 30 min post HF-rTMS. The left DLPFC was determined under MRI guidance. RESULTS: One session of HF-rTMS did not result in any subjectively experienced mood changes. However, salivary cortisol concentrations decreased significantly immediately and 30 min after active HF-rTMS. CONCLUSIONS: Although one session of HF-rTMS on the left DLPFC did not influence mood subjectively in melancholic unipolar depressed patients, we found support for the hypothesis that a single session has a significant impact on the HPA-axis, as measured by salivary cortisol. Our results may provide more insight into the underlying working mechanisms of HF-rTMS in unipolar melancholic depression, and could add further information about endocrinological functioning in affective disorders.

Influence of high-frequency repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex on the inhibition of emotional information in healthy volunteers.

BACKGROUND: Evidence suggests that repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) might be a promising new treatment procedure for depression. However, underlying working mechanisms of this technique are yet unclear. Multiple sessions of rTMS may--apart from the reported antidepressant effects--cause primary improvements in attentional control over emotional information, modulated by changes in cortical brain excitability within stimulated prefrontal regions. METHOD: In two experiments, we examined the temporary effects of high-frequency (HF) rTMS (10 Hz) applied over the left and right DLPFC on the attentional processing of emotional information and self-reported mood within samples of healthy volunteers. RESULTS: The present study showed that one session of HF-rTMS over the right DLPFC produces instant impairments in the ability to inhibit negative information, in line with a characteristic cognitive vulnerability found in depressive pathology, whereas HF-rTMS of the left DLPFC did not lead to significant changes in attentional control. These effects could not be attributed to mood changes. CONCLUSIONS: The findings of the present study may suggest a specific involvement of the right DLPFC in the attentional processing of emotional information.

Left and right High Frequency repetitive Transcranial Magnetic Stimulation of the dorsolateral prefrontal cortex does not affect mood in female volunteers.

OBJECTIVE: High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) has yielded divergent results concerning its effect on mood in normal volunteers. In a former study, we were unable to demonstrate negative mood effects after one session of HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC) in a large group of healthy female volunteers: researchers had focused mainly on negative mood changes, overlooking a possible positive mood induction, while no studies had yet examined mood effects of HF-rTMS delivered on the right prefrontal cortex. In this study, we have tried to replicate our previous HF-rTMS findings on the left DLPFC in a new (large) group of healthy female subjects, and we focused especially on positive mood changes. We also extended our former research by stimulating the right DLPFC in a different but comparable (large) group of healthy female volunteers with the same HF-rTMS parameters. METHODS: In this sham-controlled, single blind, crossover HF-rTMS study, stimulus parameters were an exact copy of our previous healthy volunteer study. To exclude individual anatomical differences, the left and right DLPFC were targeted under magnetic resonance (MRI) guidance. To examine subjective mood changes we used Visual Analogue Scales (VAS), the Profile of Mood States (POMS), and the Positive Affect and Negative Affect Schedule (PANAS), the latter to assure assessment of positive emotions. To detect any delayed mood changes, assessments were also re-administered 30min post-HF-rTMS. RESULTS: We were unable to demonstrate immediate or delayed mood changes after one single active HF-rTMS session on the left or right DLPFC. CONCLUSIONS: Although we took into account several methodological problems which might have confounded previous rTMS mood induction studies, the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence mood in healthy female volunteers was not supported. SIGNIFICANCE: One HF-rTMS session has no effect on subjective mood in healthy female volunteers.

Lack of impact of repetitive High Frequency Transcranial Magnetic Stimulation on mood in healthy female subjects.

BACKGROUND: High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) is currently used as an experimental tool to induce mood changes in normal volunteers and as a treatment option for depression. However, HF-rTMS, mostly performed on the left dorsolateral prefrontal cortex (DLPFC), has yielded divergent results and effects on mood which seem to be oppositely lateralized between these two groups. The inconsistent results that have been reported might be explained by methodological heterogeneity and drawbacks. METHODS: In this sham-controlled, single blind, crossover study, we tried to reproduce previous HF-rTMS findings of a negative mood induction in 28 healthy female subjects. To exclude individual anatomical differences, the left DLPFC was localised under magnetic resonance guidance (MRI). Mood assessment was performed before and just after HF-rTMS with Visual Analogue Scales and the Profile of Mood States. To detect possible delayed mood changes, ratings were also performed 30 min post HF-rTMS. RESULTS: We were unable to demonstrate significant mood changes from baseline after one single active HF-rTMS session on the left DLPFC. CONCLUSIONS: Although this study controlled for several methodological problems, the hypothesis that one single session of HF-rTMS on the left DLPFC has negative mood effects in healthy female volunteers was not supported.