The Effects of High-Frequency rTMS Over the Left Dorsolateral Prefrontal Cortex on Reward Responsiveness

BackgroundHigh-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.ObjectiveWe attempted to investigate whether HF-rTMS over the dorsolateral prefrontal cortex (DLPFC) would modulate reward responsiveness using a probabilistic reward task.MethodsEighteen 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.ResultsParticipants 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.ConclusionHF-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.     

Repetitive Transcranial Magnetic Stimulation With H-Coil Coupled With Cycling for Improving Lower Limb Motor Function After Stroke: An Exploratory Study

Background/ObjectivesRepetitive transcranial magnetic stimulation (rTMS) has been recognized as a promising intervention for the treatment of post-stroke motor deficits. Here, we explore safety, feasibility, and potential effectiveness of high-frequency rTMS (HF-rTMS) delivered with the Hesed coil (H-coil) during active cycling on paretic lower extremity (LE) motor function in chronic stroke.Materials and MethodsTwelve subjects with a first-ever stroke were recruited in this double-blind, placebo controlled, crossover study. Eleven sessions of HF-rTMS (40 2s-trains of 20 Hz at 90% resting leg motor threshold) were delivered over the LE motor areas using the H-coil during active cycling for three weeks. Each subject underwent both real and sham rTMS treatments separated by a four-week washout period, in a random sequence. Vital signs were recorded before and after each rTMS session. Any discomfort related to stimulation and side effects were recorded. LE function was also evaluated with Fugl-Meyer assessment (FMA-LE), spasticity was assessed with modified-Ashworth scale and measures of gait speed and endurance (10-meter and 6-min walk tests, respectively) were recorded.ResultsNo participant reported serious adverse effects. During real rTMS, 4 of 12 subjects reported mild side effects including transitory dizziness and muscle twitches on shoulder, so that intensity of stimulation initially set at 90% of RMT was reduced to 80% of RMT on average in these four subjects. Only real treatment was associated with a significant and sustained improvement in FMA-LL (67% responders vs. 9% of the sham). Spasticity significantly ameliorated only after the real rTMS. Real treatment did not offer advantages on walking timed measures when compared with sham.ConclusionsThis exploratory study suggests that bilateral HF-rTMS combined with cycling is safe and potentially effective in ameliorating paretic LE motor function and spasticity, rather than gait speed or endurance, in chronic stroke.     

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.     

The effects of high frequency rTMS on negative attentional bias are influenced by baseline state anxiety

High frequency (HF) repetitive Transcranial Magnetic Stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been shown to induce an attentional bias towards threatening information in healthy adults, associated with decreased activation in the right DLPFC and increased activation in the right amygdala. Additionally, it has been shown that healthy individuals with higher state anxiety portray similar negative attentional biases and cortico-subcortical activation patterns to those induced by HF-rTMS of the right DLPFC. Therefore, the aim of this study is to investigate whether inter-individual differences in state anxiety levels prior to the administration of HF-rTMS of the right DLPFC might be related to the degree to which rTMS induces such a negative attentional bias in healthy volunteers. We administered HF-rTMS of the right DLPFC to a group of 28 healthy female individuals. In line with previous research, a single session of HF-rTMS of the right DLPFC induced an attentional bias towards threatening information. Moreover, self-report measures of state anxiety (STAI-State) prior to stimulation correlated positively with the magnitude of the induced attentional bias. More specifically, we found that healthy individuals who scored higher on self-reports of state anxiety acquired more attentional bias towards negative information after HF-rTMS. Therefore, the effects of a single placebo-controlled rTMS session of the right DLPFC is consistent with the effects of a disrupted prefrontal-amygdala circuitry. The effects on attentional bias are largest in those participants reporting higher state anxiety scores, possibly because underlying amygdala activation is highest.     

Brain oscillation-synchronized stimulation of the left dorsolateral prefrontal cortex in depression using real-time EEG-triggered TMS

BackgroundRepetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an effective treatment for major depressive disorder (MDD), but response rates are low and effect sizes small. Synchronizing TMS pulses with instantaneous brain oscillations can reduce variability and increase efficacy of TMS-induced plasticity.ObjectiveTo study whether brain oscillation-synchronized rTMS is feasible, safe and has neuromodulatory effects when targeting the DLPFC of patients with MDD.MethodsUsing real-time EEG-triggered TMS we conducted a pseudo-randomized controlled single-session crossover trial of brain oscillation-synchronized rTMS of left DLPFC in 17 adult patients with antidepressant-resistant MDD. Stimulation conditions in separate sessions were: (1) rTMS triggered at the negative EEG peak of instantaneous alpha oscillations (alpha-synchronized rTMS), (2) a variation of intermittent theta-burst stimulation (modified iTBS), and (3) a random alpha phase control condition.ResultsTriggering TMS at the negative peak of instantaneous alpha oscillations by real-time analysis of the electrode F5 EEG signal was successful in 15 subjects. Two subjects reported mild transient discomfort at the site of stimulation during stimulation; no serious adverse events were reported. Alpha-synchronized rTMS, but not modified iTBS or the random alpha phase control condition, reduced resting-state alpha activity in left DLPFC and increased TMS-induced beta oscillations over frontocentral channels.ConclusionsAlpha-synchronized rTMS of left DLPFC is feasible, safe and has specific single-session neuromodulatory effects in patients with antidepressant-resistant MDD. Future studies need to further elucidate the mechanisms, optimize the parameters and investigate the therapeutic potential and efficacy of brain oscillation-synchronized rTMS in MDD.     

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

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.     

Localized Potentiation of Sleep Slow-Wave Activity Induced by Prefrontal Repetitive Transcranial Magnetic Stimulation in Patients with a Major Depressive Episode

BackgroundThe effects of repetitive transcranial magnetic stimulation (rTMS) on sleep structure in major depression are currently unknown.ObjectiveTo determine the effects of prefrontal rTMS on sleep electroencephalography (EEG) in major depression.MethodsIn this open-label pilot study, twelve male patients with relatively mild depression, who had been medication-resistant, underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC). Polysomnographic (PSG) data were recorded over four nights: Adaptation, Baseline, Post-1 (after the fifth rTMS session), and Post-2 (after the tenth rTMS session). Discrete Fourier Transform (DFT) band power analyses were performed to quantify delta and sigma band activities during Stages II–IV, and determine time courses of these activities between Baseline and Post-1 (first five sessions) and between Post-1 and Post-2 (last five sessions).ResultsPost-hoc tests based on a three-way ANOVA model indicated significant delta power increase at F3 (t₁₁ = ?2.762, P = 0.018) during the first five sessions; however, sigma power was unchanged. No significant band power changes were observed during the second half. Stages II–IV (percent total sleep time) increased significantly during the first half (t₁₂ = ?2.43, P = 0.033). No other significant changes in sleep parameters or clinical correlations were observed.ConclusionsThe first five sessions of high frequency rTMS to the left DLPFC increase slow-wave activity (SWA) at F3, possibly reflecting locally enhanced synaptic plasticity induced by rTMS. This increased activity was not observed during the last half, possibly due to a homeostatic regulation mechanism intrinsic to SWA.     

The influence of high-frequency repetitive transcranial magnetic stimulation on endogenous estrogen in patients with disorders of consciousness

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been proposed as a promising therapeutic intervention for neurological disorders. However, the precise mechanisms of rTMS in neural excitability remains poorly understood. Estradiol is known to have strong influence on cortical excitability. This study aimed to determine whether high-frequency (HF) rTMS influences endogenous estradiol in male patients with disorders of consciousness (DOC).MethodsA randomized controlled trial was conducted with a total of 57 male patients with DOC. Eventually, 50 patients completed the study. Twenty-five patients underwent real rTMS, and 25 patients underwent sham rTMS, which were delivered over the dorsolateral prefrontal cortex. The primary outcome measure was the change in serum estradiol from baseline to after 10 sessions of HF-rTMS. The improvement in the total score of the JFK Coma Recovery Scale-Revised (CRS-R) was also assessed.ResultsChanges in estradiol levels and CRS-R scores from pre-to post-treatment were significantly different between the active rTMS and sham stimulation conditions. A significant enhancement of CRS-R scores in the patients receiving rTMS stimulation was observed compared to the sham group. Serum estradiol levels in patients following HF-rTMS were significantly higher than their baseline levels, whereas no significant changes were found in the sham group from pre-to post-stimulation. The rise in estradiol levels was greater in responders than in non-responders. The changes in estradiol levels were significantly positively correlated with the improvement in CRS-R scores.ConclusionThese preliminary findings indicate that serum estradiol levels are affected by HF-rTMS and positively related to clinical responses in male patients with DOC. The elevation of estradiol levels may lay a physiological foundation for successful rTMS treatment for DOC patients by increasing cortical excitability.     

Neurophysiological effects of repetitive transcranial magnetic stimulation (rTMS) in treatment resistant depression

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) is effective for treatment resistant depression (TRD), but little is known about rTMS’ effects on neurophysiological markers. We previously identified neurophysiological markers in depression (N45 and N100) of GABA receptor mediated inhibition. Here, we indexed TMS-electroencephalographic (TMS-EEG) effects of rTMS.MethodsTMS-EEG data was analyzed from a double blind 2:1 randomized active (10 Hz left/bilateral):sham rTMS TRD trial. Participants underwent TMS-EEG over left dorsolateral prefrontal cortex (DLPFC) before and after 6 weeks of rTMS. 30 had useable datasets. TMS-evoked potentials (TEP) and components (N45, N100, P60) were examined with global mean field analysis (GMFA) and locally in DLPFC regions of interest.ResultsThe N45 amplitude differed between active and sham groups over time, N100 amplitude did not. N45 (t = 2.975, p = 0.007) and N100 amplitudes (t = 2.177, p = 0.042) decreased after active rTMS, demonstrating alterations in cortical inhibition. TEP amplitudes decreased after active rTMS in left (t = 4.887, p < 0.001) and right DLPFC (t = 4.403, p < 0.001) not sham rTMS, demonstrating alterations in cortical excitability.ConclusionsOur results provide important new knowledge regarding rTMS effects on TMS-EEG measures in TRD, suggesting rTMS reduces neurophysiological markers of inhibition and excitability.SignificanceThese findings uncover potentially important neurophysiological mechanisms of rTMS action.     

The effect of one left-sided dorsolateral prefrontal cortical HF-rTMS session on emotional brain processes in women

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.We carried out a sham-controlled single-blind crossover study using fMRI, we examined in 20 right-handed healthy female volunteers whether a single high frequency (HF)-rTMS session applied to the left dorsolateral prefrontal cortex (DLPFC) could influence emotional processing while focussing on blocks of positively and negatively valenced baby faces. A single HF-rTMS session selectively influenced the processing of positively and negatively valenced baby faces. In essence, our results indicate that the effects of one left-sided HF-rTMS sessions results in improved processing of positive emotions and reduced negative emotional processing in never depressed female subjects.     

High-frequency rTMS over the dorsolateral prefrontal cortex on chronic and provoked pain: A systematic review and meta-analysis

BackgroundHigh-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated mixed effects on chronic and provoked pain.Objectives/MethodsIn this study, a meta-analysis was conducted to characterise the potential analgesic effects of high-frequency rTMS over the DLPFC on both chronic and provoked pain.ResultsA total of 626 studies were identified in a systematic search. Twenty-six eligible studies were included for the quantitative review, among which 17 modulated chronic pain and the remaining investigated the influence on provoked pain. The left side DLPFC was uniformly targeted in the chronic pain studies. While our data identified no overall effect of TMS across chronic pain conditions, there was a significant short-term analgesia in neuropathic pain conditions only (SMD = −0.87). In terms of long-lasting analgesia, there was an overall pain reduction in the midterm (SMD = −0.53, 24.6 days average) and long term (SMD = −0.63, 3 months average) post DLPFC stimulation, although these effects were not observed within specific chronic pain conditions. Surprisingly, the number of sessions was demonstrated to have no impact on rTMS analgesia. In the analysis of provoked pain, our data also indicated a significant analgesic effect following HF-rTMS over the DLPFC (SMD = −0.73). Importantly, we identified a publication bias in the studies of provoked pain but not for chronic pain conditions.ConclusionsOverall, our findings support that HF-DLPFC stimulation is able to induce an analgesic effect in chronic pain and in response to provoked pain. These results highlight the potential of DLPFC-rTMS in the management of certain chronic pain conditions and future directions are discussed to enhance the potential long-term analgesic effects.     

Effect of Two Weeks of rTMS on Brain Activity in Healthy Subjects During an n-Back Task: A Randomized Double Blind Study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has shown significant efficiency in the treatment of several psychiatric disorders. In depressive disorders, the dorsolateral prefrontal cortex (DLPFC) is the main target for rTMS, but the effects of this stimulation on cognitive functions and their neural correlates are not well known. Previous works have established that the left DLPFC is reliably activated during the n-back working memory task.ObjectiveThe aim of this randomized double-blind study was to determine the impact of rTMS applied to the DLPFC on brain activity during an n-back task in healthy subjects.MethodsAfter randomization, twenty subjects received either active treatment (10 sessions; 1 session a day; frequency = 10 Hz; intensity = 110% of motor threshold) or placebo treatment (sham coil). Subjects performed an n-back task during two functional magnetic resonance imaging sessions (one before stimulation, and one after 10 active or sham rTMS sessions).ResultsNo significant changes, neither in mood nor in performance in the n-back task, were shown. A significant group-by-time interaction effect was found in the bilateral middle frontal gyrus and in the left caudate nucleus.ConclusionsThese results show that rTMS applied on the left DLPFC had close and remote effects on brain areas involved in working memory.     

Cortical plasticity is correlated with cognitive improvement in Alzheimer’s disease patients after rTMS treatment

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has been widely used in non-invasive treatments for different neurological disorders. Few biomarkers are available for treatment response prediction. This study aims to analyze the correlation between changes in long-term potentiation (LTP)-like cortical plasticity and cognitive function in patients with Alzheimer’s disease (AD) that underwent rTMS treatment.MethodsA total of 75 AD patients were randomized into either 20 Hz rTMS treatment at the dorsolateral prefrontal cortex (DLPFC) group (n = 37) or a sham treatment group (n = 38) for 30 sessions over six weeks (five days per week) with a three-month follow-up. Neuropsychological assessments were conducted using the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment-Cognitive Component (ADAS-Cog). The cortical plasticity reflected by the motor-evoked potential (MEP) before and after high-frequency repetitive TMS to the primary motor cortex (M1) was also examined prior to and after the treatment period.ResultsThe results showed that the cognitive ability of patients who underwent the MMSE and ADAS-Cog assessments showed small but significant improvement after six weeks of rTMS treatment compared with the sham group. The cortical plasticity improvement correlated to the observed cognition change.ConclusionsCortical LTP-like plasticity could predict the treatment responses of cognitive improvements in AD patients receiving rTMS intervention. This warrants future clinical trials using cortical LTP as a predictive marker.     

Repetitive transcranial magnetic stimulation influences mood in healthy male volunteers

The influence of repetitive transcranial magnetic stimulation (rTMS) on mood in healthy people is uncertain, as former studies show divergent results. Previous studies in healthy volunteers focused exclusively on the immediate effect of a single session of rTMS. In contrast the aim of this randomised sham-controlled study was to analyse the influence on mood of a series of 9 High Frequency (HF) rTMS stimulations of the left dorsolateral prefrontal cortex (DLPFC).44 young healthy male volunteers were randomly assigned to receive 9 sessions of active HF-rTMS (n = 22) or sham rTMS (n = 22) over the left DLPFC. Each session in the active group consisted of 15 trains of 25 Hz starting with 100% of motor threshold. Sham stimulation was performed following the same protocol, but using a sham coil. The variables of interest were the Beck Depression Inventory (BDI) and six Visual Analogue Scales (VAS) which quantified “mood”, “enjoyment” and “energy”. We found a significant reduction of the BDI sum score in the active group (GLM, p < 0.001) whereas no significant changes of the BDI sum score were caused by sham stimulation (GLM, p = 0.109). The BDI single item analyses revealed within and between group differences supporting the modifying effect of rTMS on BDI. According to the employed VAS we did not find significant differences caused by active or sham stimulation in five of six VAS. In the VAS labelled lively/gloomy the active group was found to be more “gloomy” (p = 0.0111) immediately after stimulation. Our data show that a 9-day long series of HF-rTMS of the left DLPFC improves mood, analysed by BDI in healthy young men, whereas no significant long-term changes were found in VAS.     

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)

A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.     

The effects of repetitive transcranial magnetic stimulation on body weight and food consumption in obese adults: A randomized controlled study

BackgroundAlthough some studies have reported significant reductions in food cravings following the single-session of repetitive transcranial magnetic stimulation (rTMS), there is little research on the effects of multi-session of rTMS on food consumption and body weight in obese subjects.ObjectiveWe conducted 4-week randomized, sham-controlled, single-blind, parallel-group trial to examine the effect of rTMS on body weight in obese adults.MethodsForty-three obese patients (body mass index [BMI] ≥25 kg/m²) aged between 18 and 70 years were randomized to the sham or real treatment group (21 in the TMS group and 22 in the sham treatment group). A total of 8 sessions of rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) was provided over a period of 4 weeks. The primary outcome measure was weight change in kilograms from baseline to 4 weeks. Secondary endpoints included changes in anthropometric measures, cardiovascular risk factors, food intake, and appetite.ResultsParticipants in the rTMS group showed significantly greater weight loss from baseline following the 8 session of rTMS (−2.75 ± 2.37 kg vs. 0.38 ± 1.0 kg, p < 0.01). Consistent with weight loss, there was a significant reduction in fat mass and visceral adipose tissue at week 4 in the rTMS group compared with the control group (p < 0.01). After the 8 sessions of rTMS, the TMS group consumed fewer total kilocalories and carbohydrates per day than the control group (p < 0.05).Conclusions8 sessions of HF rTMS delivered to the left DLPFC were effective in inducing weight loss and decreasing food intake in obese patients.Trial registrationClinical trial registered with the Clinical Trials Registry at http://cris.cdc.go.kr (KCT0002548).     

Induction and quantification of prefrontal cortical network plasticity using 5 Hz rTMS and fMRI

Neuronal plasticity is crucial for flexible interaction with a changing environment and its disruption is thought to contribute to psychiatric diseases like schizophrenia. High‐frequency repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool to increase local excitability of neurons and induce short‐time functional reorganization of cortical networks. While this has been shown for the motor system, little is known about the short‐term plasticity of networks for executive cognition in humans. We examined 12 healthy control subjects in a crossover study with fMRI after real and sham 5 Hz rTMS to the right dorsolateral prefrontal cortex (DLPFC). During scanning, subjects performed an n‐back working memory (WM) task and a flanker task engaging cognitive control. Reaction times during the n‐back task were significantly shorter after rTMS than after sham stimulation. RTMS compared with sham stimulation caused no activation changes at the stimulation site (right DLPFC) itself, but significantly increased connectivity within the WM network during n‐back and reduced activation in the anterior cingulate cortex during the flanker task. Reduced reaction times after real stimulation support an excitatory effect of high‐frequency rTMS. Our findings identified plastic changes in prefrontally connected networks downstream of the stimulation site as the substrate of this behavioral effect. Using a multimodal fMRI‐rTMS approach, we could demonstrate changes in cortical plasticity in humans during executive cognition. In further studies this approach could be used to study pharmacological, genetic and disease‐related alterations. Hum Brain Mapp 35:140–151, 2014. © 2012 Wiley Periodicals, Inc.     

State-Dependent Effects of Prefrontal Repetitive Transcranial Magnetic Stimulation on Emotional Working Memory

BackgroundA growing body of findings illustrates the importance of state-dependency in studies using brain stimulation.ObjectiveWe aimed to investigate the effects of tDCS priming followed by rTMS applied over the right dorsolateral prefrontal cortex (DLPFC) on emotional working memory.MethodsIn a randomized single-blind within-subjects design, participants performed an emotional 3-back task at baseline and after tDCS priming (anodal, cathodal) and subsequent low-frequency rTMS (active, sham) of the right DLPFC. Stimuli consisted of words related to the distinct emotion categories fear and anger as well as neutral words.ResultsTask accuracy increased for fear-related words and decreased for neutral words across stimulation conditions. No general state-dependent effects of prefrontal rTMS on working memory were found. We further showed a detrimental effect of negative emotional content on working memory performance.ConclusionsOur findings support a hemispheric lateralization of emotion processing by demonstrating that the withdrawal-related emotion fear is associated with the right DLPFC and contribute to clarifying the interaction between working memory and emotion.     

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement

IntroductionRepetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness.MethodsWe applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas.ResultsCompared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas.ConclusionsOur results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.     

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.