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Background: The mechanism by which high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) improves swallowing function by regulating intestinal flora remains unexplored. We aimed to evaluate this using fecal metabolomics and 16S rRNA sequencing. Methods: A Post-stroke dysphagia (PSD) rat model was established by middle cerebral artery occlusion. The magnetic stimulation group received HF-rTMS from the 7th day post-operation up to 14th day post-surgery. Swallowing function was assessed using a videofluoroscopic swallowing study (VFSS). Hematoxylin-eosin (H&E) staining was used to assess histopathological changes in the intestinal tissue. Intestinal flora levels were evaluated by sequencing the 16S rRNA V3-V4 region. Metabolite changes within the intestinal flora were evaluated by fecal metabolomics using liquid chromatography-tandem mass spectrometry. Results: VFSS showed that the bolus area and pharyngeal bolus speed were significantly decreased in PSD rats, while the bolus area increased and pharyngeal transit time decreased after HF-rTMS administration (p < 0.05). In the PSD groups, H&E staining revealed damaged surface epithelial cells and disrupted cryptal glands, whereas HF-rTMS reinforced the integrity of the intestinal epithelial cells. 16S rRNA sequencing indicated that PSD can disturb the intestinal flora and its associated metabolites, whereas HF-rTMS can significantly regulate the composition of the intestinal microflora. Firmicutes and Lactobacillus abundances were lower in the PSD group than in the baseline group at the phylum and genus levels, respectively; however, both increased after HF-rTMS administration. Levels of ceramides (Cer), free fatty acids (FA), phosphatidylethanolamine (PE), triacylglycerol (TAG), and sulfoquinovosyl diacylglycerol were increased in the PSD group. The Cer, FA, and DG levels decreased after HF-rTMS treatment, whereas the TAG levels increased. Peptococcaceae was negatively correlated with Cer, Streptococcus was negatively correlated with DG, and Acutalibacter was positively correlated with FA and Cer. However, these changes were effectively restored by HF-rTMS, resulting in recovery from dysphagia. Conclusion: These findings suggest a synergistic role for the gut microbiota and fecal metabolites in the development of PSD and the therapeutic mechanisms underlying HF-rTMS. [ABSTRACT FROM AUTHOR]

In this study, a single high‐frequency repetitive transcranial magnetic stimulation (HF‐rTMS) session was applied over the left dorsolateral prefrontal cortex (DLPFC) after a moderate‐to‐intense stressor to investigate whether left DLPFC stimulation could regulate cortisol concentration after stress induction. Participants were randomly divided into three groups (stress‐TMS, stress, and placebo‐stress). Stress was induced in both the stress‐TMS and stress groups using the Trier Social Stress Test (TSST). The placebo‐stress group received a placebo TSST. In the stress‐TMS group, a single HF‐rTMS session was applied over the left DLPFC after TSST. Cortisol was measured across the different groups, and each group's responses to the stress‐related questionnaire were recorded. After TSST, both the stress‐TMS and stress groups reported increased self‐reported stress, state anxiety, negative affect, and cortisol concentration compared with the placebo‐stress group, indicating that TSST successfully induced a stress response. Compared with the stress group, the stress‐TMS group exhibited reduced cortisol levels at 0, 15, 30, and 45 min after HF‐rTMS. These results suggest that left DLPFC stimulation after stress induction might accelerate the stress recovery. Previous studies found that left dorsolateral prefrontal cortex (DLPFC) stimulation using rTMS could help individuals cope with upcoming stress more effectively. However, stressful life events can be unpredictable. The present findings revealed that activating the left DLPFC after stress induction could inhibit cortisol secretion. This efficient stress intervention after stressful events can be achieved by non‐invasive brain stimulation. [ABSTRACT FROM AUTHOR]

Previous research supports the distinction between proactive and reactive control. Although the dorsolateral prefrontal cortex (DLPFC) has been consistently related to these processes, lateralization of proactive and reactive control is still under debate. We manipulated brain activity to investigate the role of the left and right DLPFC in proactive and reactive cognitive control. Using a single-blind, sham-controlled crossover within-subjects design, 25 young healthy females performed the 'AX' Continuous Performance Task after receiving sham vs active high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to increase left and right DLPFC activity. Reaction times (RTs) and pupillometry were used to assess patterns of proactive and reactive cognitive control and task-related resource allocation, respectively. We observed that, compared to sham, HF-rTMS over the left DLPFC increased proactive control. After right DLPFC HF-rTMS, participants showed slower RTs on AX trials, suggesting more reactive control. However, this latter result was not supported by RTs on BX trials (i.e. the trial that specifically assess reactive control). Pupil measures showed a sustained increase in resource allocation after both active left and right HF-rTMS. Our results with RT data provide evidence on the role of the left DLPFC in proactive control and suggest that the right DLPFC is implicated in reactive control. [ABSTRACT FROM AUTHOR]

Abstract Background High frequency repetitive transcranial magnetic stimulation (HF-rTMS) has gained interest as a neuromodulation treatment technique for alcohol dependence. Single sessions of HF-rTMS have consistently shown to decrease craving for substances. However, the results of randomized controlled clinical trials investigating the effect of multiple HF-rTMS sessions in alcohol dependence on abstinence rates and craving are inconsistent. Furthermore, they lack information on the effect of HF-rTMS on cognition and brain functioning. Methods A single center, single blind, randomized controlled trial with 80 abstinent alcohol dependent subjects in treatment randomized (1:1) to either treatment as usual (TAU) plus ten sessions of active HF-rTMS or TAU plus 10 sessions of placebo/ sham HF-rTMS will be performed. The effects of ten HF-rTMS sessions on craving and neurocognitive functions are obtained. In addition a subset of participants will undergo an MR scanning session before the first and after the last HF-rTMS session in order to investigate the effect of ten HF-rTMS sessions on brain functioning. The primary outcome is the continued abstinence rate after the add-on HF-rTMS treatment. Discussion This study uses a randomized controlled trial to examine the clinical, neurocognitive and brain functioning effects of ten add-on HF-rTMS sessions in alcohol dependent individuals in treatment. If the add-on treatment is effective, this may add to the evidence needed for approval of this additional treatment method for alcohol dependence by regulatory authorities. Trial registration The Netherlands National Trial Register (NTR), NTR5291, 6-July-2015.

Background: The mechanism by which high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) improves swallowing function by regulating intestinal flora remains unexplored. We aimed to evaluate this using fecal metabolomics and 16S rRNA sequencing., Methods: A Post-stroke dysphagia (PSD) rat model was established by middle cerebral artery occlusion. The magnetic stimulation group received HF-rTMS from the 7th day post-operation up to 14th day post-surgery. Swallowing function was assessed using a videofluoroscopic swallowing study (VFSS). Hematoxylin-eosin (H&E) staining was used to assess histopathological changes in the intestinal tissue. Intestinal flora levels were evaluated by sequencing the 16S rRNA V3-V4 region. Metabolite changes within the intestinal flora were evaluated by fecal metabolomics using liquid chromatography-tandem mass spectrometry., Results: VFSS showed that the bolus area and pharyngeal bolus speed were significantly decreased in PSD rats, while the bolus area increased and pharyngeal transit time decreased after HF-rTMS administration (p < 0.05). In the PSD groups, H&E staining revealed damaged surface epithelial cells and disrupted cryptal glands, whereas HF-rTMS reinforced the integrity of the intestinal epithelial cells. 16S rRNA sequencing indicated that PSD can disturb the intestinal flora and its associated metabolites, whereas HF-rTMS can significantly regulate the composition of the intestinal microflora. Firmicutes and Lactobacillus abundances were lower in the PSD group than in the baseline group at the phylum and genus levels, respectively; however, both increased after HF-rTMS administration. Levels of ceramides (Cer), free fatty acids (FA), phosphatidylethanolamine (PE), triacylglycerol (TAG), and sulfoquinovosyl diacylglycerol were increased in the PSD group. The Cer, FA, and DG levels decreased after HF-rTMS treatment, whereas the TAG levels increased. Peptococcaceae was negatively correlated with Cer, Streptococcus was negatively correlated with DG, and Acutalibacter was positively correlated with FA and Cer. However, these changes were effectively restored by HF-rTMS, resulting in recovery from dysphagia., Conclusion: These findings suggest a synergistic role for the gut microbiota and fecal metabolites in the development of PSD and the therapeutic mechanisms underlying HF-rTMS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Chen, Shan, Hong, Ye, Dai, Hu, Zhang, Li and Wen.)

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been shown to be effective for cognitive intervention. However, whether HF-rTMS with extremely low intensity could influence cognitive functions is still under investigation. The present study systematically investigated the effects of continuous 40 Hz and 10 Hz rTMS on cognition in young adult mice at extremely low intensity (10 mT and 1 mT) for 11 days (30 min/day). Cognitive functions were assessed using diverse behavioral tasks, including the open field, Y-maze, and Barnes maze paradigms. We found that 40 Hz rTMS significantly impaired exploratory behavior and spatial memory in both 10 mT and 1 mT conditions. In addition, 40 Hz rTMS induced remarkably different effects on exploratory behavior between 10 mT and 1mT, compared to 10 Hz stimulation. Our results indicate that extremely low intensity rTMS can significantly alter cognitive performance depending on intensity and frequency, shedding light on the understanding of the mechanism of rTMS effects. • Gamma frequency rTMS at extremely low intensity has been studied. • rTMS reduced exploratory behavior. • rTMS impaired spatial learning/memory. • Effects of rTMS depended on intensity and frequency. [ABSTRACT FROM AUTHOR]

Three decades of clinical research on repetitive transcranial magnetic stimulation (rTMS) has yielded one clear treatment indication in psychiatry for major depression disorder (MDD). Although the clinical response equals the standard treatment algorithms, the effect sizes on the beneficial outcome remain rather modest. Over the last couple of years, to improve the efficacy in resistant depression, two new avenues have been developed: personalization and intensifying rTMS treatment. For the latter, we retrospectively compared accelerated high-frequency rTMS (arTMS) with accelerated intermittent theta burst stimulation (aiTBS) in the refractory depressed state. Although the clinical efficacy was not significantly different between both protocols, our observations substantiate the potential of the accelerated stimulation to shorten the treatment duration from the depressed state to the response state. Any time gain from the depressed state to the recovered state is in the patients’ interest.

Repetitive transcranial magnetic stimulation (rTMS) is an evidence based neurostimulation modality used to treat patients with Major Depressive Disorder (MDD). In spite that the duration of current a depressive episode has been put forward as a negative predictor for clinical outcome, little is known about the underlying neurobiological mechanisms of this phenomenon. To address this important issue, in a sample of 43 melancholic stage III treatment resistant antidepressant-free refractory MDD patients, we reanalysed regional cerebral glucose metabolism (CMRglc) before high frequency (HF)-rTMS treatment, applied to the left dorsolateral prefrontal cortex (DLPFC). Besides that a lower baseline cerebellar metabolic activity indicated negative clinical response, a longer duration of the depressive episode was a negative indicator for recovery and negatively influenced cerebellar CMRglc. This exploratory 18FDG PET study is the first to demonstrate that the clinical response of HF-rTMS treatment in TRD patients may depend on the metabolic state of the cerebellum. Our observations could imply that for left DLPFC HF-rTMS non-responders other brain localisations for stimulation, more specifically the cerebellum, may be warranted. [ABSTRACT FROM AUTHOR]

Background Although one of the most frequent diagnosed mental illnesses worldwide, it appears to be challenging to successfully treat major depressive disorder (MDD). Although the phenomenon of treatment-resistant depression (TRD) still remains unclear, the subgenual anterior cingulate cortex (sgACC) has been put forward as a possible neurobiological marker to evaluate clinical effects of a variety of antidepressant treatments, including repetitive transcranial magnetic stimulation (rTMS). Accelerated high-frequency (HF)-rTMS may have the potential to rapidly result in beneficial clinical outcomes in TRD. No studies yet examined the clinical effects of such accelerated stimulation treatment paradigms on sgACC regional glucose metabolism (CMRglc), nor the predictive value of the latter for clinical outcome. Objective First, we investigated the predictive value of baseline sgACC metabolic activity for clinical outcome. Second, we hypothesized that in clinical responders only accelerated HF-rTMS treatment would result in significant metabolic decreases. Methods We recruited right-handed antidepressant-free unipolar melancholic TRD patients to participate in a two-week randomized sham-controlled crossover HF-rTMS treatment study. Stimulation was applied to the left dorsolateral prefrontal cortex (DLPFC). Fifteen patients underwent 18FDG PET (CMRglc) at baseline (T0), after the first week (T1) of accelerated HF-rTMS and at the end of the treatment after the second week (T2). Results Higher baseline sgACC metabolic activity may indicate beneficial clinical outcome to this kind of accelerated HF-rTMS treatment. Moreover, clinical response resulted in a significant decrease in sgACC CMRglc. Non-response did not affect sgACC CMRglc. Conclusions Our results add to the sgACC as a specific neurobiological marker for anti-depressive response in accelerated HF-rTMS treatment paradigms. Such protocols may not only have the ability to result in fast clinical responses but they may also have potential to acutely modulate a dysfunctional sgACC. [ABSTRACT FROM AUTHOR]

Although well-defined predictors of response are still unclear, clinicians refer a variety of depressed patients for a repetitive Transcranial Magnetic Stimulation (rTMS) treatment. It has been suggested that personality features such as Harm Avoidance (HA) and self-directedness (SD) might provide some guidance for a classical antidepressant treatment outcome. However, to date no such research has been performed in rTMS treatment paradigms. In this open study, we wanted to examine whether these temperament and character scores in particular would predict clinical outcome in refractory unipolar depressed patients when a typical high-frequency (HF)-rTMS treatment protocol is applied. Thirty six unipolar right-handed antidepressant-free treatment resistant depressed (TRD) patients, all of the melancholic subtype, received 10 HF-rTMS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). All patients were classified as at least stage III TRD and were assessed with the Temperament and Character Inventory (TCI) before a HF-rTMS treatment. Only the individual scores on SD predicted clinical outcome. No other personality scales were found to be a predictor of this kind of application. Our results suggest that refractory MDD patients who score higher on the character scale SD may be more responsive to the HF-rTMS treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Background: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the prefrontal region has been shown to increase endogenous dopamine release in the striatum, which is closely associated with probabilistic reward learning. Objective: We attempted to investigate whether HF-rTMS over the dorsolateral prefrontal cortex (DLPFC) would modulate reward responsiveness using a probabilistic reward task. Methods: Eighteen healthy volunteers participated in this study using a randomized within-subject crossover design. Each participant received a single session of 10 Hz high-frequency rTMS over the left DLPFC and another session of sham stimulation, with an interval of 1 week between sessions. Nine hundred magnetic stimuli were delivered in three blocks 10 min apart, for a total duration of 30 min. After each stimulation session, participants performed a probabilistic reward task where two different stimuli were rewarded with different probabilities (i.e., rich vs. lean) to produce a response bias toward the more frequently rewarded stimulus. Results: Participants showed faster and more accurate responses toward the rich stimulus than the lean stimulus. Participants developed a greater response bias toward the rich stimulus after HF-rTMS during the early learning trials versus after sham stimulation. No differences in response bias were observed during the later learning trials. Reaction time did not differ between the active HF-rTMS and sham stimulation conditions. Conclusion: HF-rTMS over the left DLPFC increased responsiveness toward rewarding stimuli. This facilitation effect of HF-rTMS might be associated with changes in dopaminergic neurotransmission in the striatum. Our findings contribute to our understanding of the effects HF-rTMS can have on reward learning. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Background: Currently, the underlying neurobiological mechanism as to how repetitive transcranial magnetic stimulation (rTMS) can alter depressive states remains unclear. Animal data suggest that its influence could occur at the neurotransmitter level, such as modulation of the serotonin system. Methods: Twenty-one antidepressant-free medication-resistant unipolar depressed patients, and 21 age- and gender-matched healthy subjects were studied. We examined the neurobiologic impact of 10 high-frequent (HF)-rTMS sessions applied to the left dorsolateral prefrontal cortex (DLPFC) on postsynaptic 5-HT2A receptor binding indices (BI) measured with 123I-5-I-R91150 single photon emission computed tomography (SPECT) only in patients. Results: Compared with the control group, patients displayed significantly less bilateral dorsolateral prefrontal cortical and significantly higher left hippocampal baseline 5-HT2A receptor BI. Successful HF-rTMS treatment correlated positively with 5-HT2A receptor BI in the DLPFC bilaterally and correlated negatively with right hippocampal 5-HT2A receptor uptake values. Conclusions: Our results indicate that HF-rTMS treatment affect the serotonergic system. Our data also suggest that this kind of treatment affects 5-HT2A receptor BI in the DLPFC and in the hippocampus in different ways. [Copyright &y& Elsevier]

Summary: 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 30min 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. [Copyright &y& Elsevier]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: Current evidence concerning the neurocircuitry underlying the interplay between attention and emotion is mainly correlational. We used high-frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) to experimentally manipulate activity within the right or left dorsolateral prefrontal cortex (DLPFC) of healthy women and examined changes in attentional processing of emotional information using an emotional modification of the exogenous cueing task during event-related fMRI. Right prefrontal HF-rTMS resulted in impaired disengagement from angry faces, associated with decreased activation within the right DLPFC, dorsal anterior cingulate cortex (dACC) and left superior parietal gyrus, combined with increased activity within the right amygdala. Left prefrontal HF-rTMS resulted in diminished attentional engagement by angry faces and was associated with increased activity within the right DLPFC, dACC, right superior parietal gyrus and left orbitofrontal cortex. The present observations are in line with reports of a functionally interactive network of cortical-limbic pathways that play a central role in emotion regulation. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Previous studies in healthy volunteers reported a possible impact of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on stress hormones, like cortisol. In this sham-controlled, 'single blind', crossover study, we examined whether HF-rTMS had an effect on the hypothalamic-pituitary-adrenal (HPA) axis, by analysing salivary cortisol levels. Two studies were conducted. First, HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC) was performed in 28 young healthy female volunteers. Second, in a comparable, but different group of 26 healthy females, HF-rTMS was performed on the right DLPFC. Salivary cortisol levels were assessed before, immediately after and 30 min after real and sham HF-rTMS. We found no support for the hypothesis that one single session of HF-rTMS on the left or the right DLPFC has an immediate or delayed impact on the HPA-axis, as measured by salivary cortisol. Although we controlled for several methodological problems in HF-rTMS research, the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence the HPA-axis in healthy volunteers was not supported. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Background: High frequency repetitive transcranial magnetic stimulation (HF-rTMS) has gained interest as a neuromodulation treatment technique for alcohol dependence. Single sessions of HF-rTMS have consistently shown to decrease craving for substances. However, the results of randomized controlled clinical trials investigating the effect of multiple HF-rTMS sessions in alcohol dependence on abstinence rates and craving are inconsistent. Furthermore, they lack information on the effect of HF-rTMS on cognition and brain functioning. Methods: A single center, single blind, randomized controlled trial with 80 abstinent alcohol dependent subjects in treatment randomized (1:1) to either treatment as usual (TAU) plus ten sessions of active HF-rTMS or TAU plus 10 sessions of placebo/ sham HF-rTMS will be performed. The effects of ten HF-rTMS sessions on craving and neurocognitive functions are obtained. In addition a subset of participants will undergo an MR scanning session before the first and after the last HF-rTMS session in order to investigate the effect of ten HF-rTMS sessions on brain functioning. The primary outcome is the continued abstinence rate after the add-on HF-rTMS treatment. Discussion: This study uses a randomized controlled trial to examine the clinical, neurocognitive and brain functioning effects of ten add-on HF-rTMS sessions in alcohol dependent individuals in treatment. If the add-on treatment is effective, this may add to the evidence needed for approval of this additional treatment method for alcohol dependence by regulatory authorities. Trial registration: The Netherlands National Trial Register (NTR), NTR5291, 6-July-2015. [ABSTRACT FROM AUTHOR]