Sham cTBS Research Articles

Neural Correlates of Reactive Inhibition in Gambling Disorder: An FMRI Study with Transcranial Magnetic Stimulation (TMS)

Gambling Disorder (GD) is a condition characterized by a persistent and recurrent pattern of problematic gambling behavior. Despite significant advances in understanding the neurobiological correlates of Gambling Disorder phenomenological manifestation, there are still several unanswered questions regarding the pathophysiological mechanisms underlying GD. There is substantial evidence from fMRI studies on the role of pre-SMA stimulation in psychiatric conditions with impairments in response inhibition such as behavioral addictions on enhancing the activity of the brain circuitry involving the right inferior (IFG) and middle frontal gyrus (MFG) (two cortical areas are differentially associated with two distinct aspects of control inhibition). In this study we utilized task-related functional Magnetic Resonance Imaging (fMRI) to explore the impact of continuous Theta-Burst Stimulation (cTBS) on the pre-Supplementary Motor Area (pre-SMA) in patients with Gambling Disorder (GD). Four GD patients underwent cTBS on bilateral pre-SMA, administered with the MagVenture MagPro R30 stimulator with add-on theta-burst option (MagVenture INC.) using a Cool D-B80 figure-of-eight coil. cTBS consists of bursts of 3 pulses separated by 20 ms (i.e., 50 Hz) delivered repeatedly at theta frequency on the pre-SMA bilaterally. Changes in Functional Connectivity (FC) were assessed before and after Real or Sham treatment using CONN functional connectivity toolbox and Statistical Parametric Mapping (SPM). The study aimed to determine whether cTBS influences the functional connectivity between pre-SMA and right prefrontal areas, specifically the right Inferior Frontal Gyrus (rIFG) and right Middle Frontal Gyrus (rMFG), and whether these changes correlate with treatment outcomes. Results indicated that real cTBS treatment increased functional connectivity between pre-SMA and both rIFG and rMFG, suggesting enhanced control inhibition. This was associated with a reduction in Gambling Disorder symptom severity, assessed with the Pathological Gambling version of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS) and the Gambling Urges Questionnaire (GUQ), indicating a treatment response. Conversely, sham cTBS did not elicit the same positive FC changes in the reactive control inhibition network, aligning with behavioral measures. The study highlighted the potential of cTBS on pre-SMA in modulating inhibitory control circuit. Overall, this preliminary investigation provides a foundation for future investigations into the neurobiological mechanisms underlying GD and the potential efficacy of TMS interventions.

Polysomnographically mediated cognitive improvements in individuals with insomnia symptoms following continuous theta-burst stimulation of the default mode network

IntroductionInsomnia is associated with mild cognitive impairment, although the mechanisms of this impairment are not well-understood. Timing of slow-wave and rapid eye movement sleep may help explain cognitive impairments common in insomnia. This investigation aimed to determine whether cognitive changes following continuous theta-burst stimulation (cTBS) are attributable to active stimulation, polysomnographic parameters of sleep, or both.MethodData presented here are part of a pilot clinical trial aiming to treat insomnia by targeting a node in the default mode network using an inhibitory 40-s (cTBS). A double-blind counterbalanced sham-controlled crossover design was conducted. Participants (N = 20) served as their own controls on two separate in-laboratory visits—one with active cTBS and the other with sham cTBS. Each visit included cognitive assessments before and after stimulation and following a night of sleep in the lab monitored with polysomnography.ResultsSlow wave sleep duration influenced working memory in the active cTBS condition, with shorter duration predicting improvements in working memory post sleep (B = −0.003, p = 0.095). Onset latency to rapid eye movement sleep predicted subsequent working memory, regardless of treatment condition (B = −0.001, p = 0.040). Results suggest that changes in attention and processing speed were primarily due to slow wave sleep onset (B = −0.001, p = 0.017) and marginally predicted by slow wave sleep duration (B = 0.002, p = 0.081) and sleep efficiency (B = 0.006, p = 0.090).ConclusionsFindings emphasize the important role that timing of slow-wave and rapid eye movement sleep have on information processing. Future work using larger sample sizes and more stimulation sessions is needed to determine optimal interactions between timing and duration of slow wave and rapid eye movement throughout the sleep period.Clinical trial registrationThis study is registered on ClinicalTrials.gov (NCT04953559). https://clinicaltrials.gov/study/NCT04953559?locStr=Arizona&country=United%20States&state=Arizona&cond=insomnia&intr=tms%20&rank=1

Immediate Effects of Preconditioning Intermittent Theta Burst Stimulation on Lower Extremity Motor Cortex Excitability in Healthy Participants.

Previous studies have found that inhibitory priming with continuous theta burst stimulation (cTBS) can enhance the effect of subsequent excitatory conditioning stimuli with intermittent theta burst stimulation (iTBS) in the upper limbs. However, whether this combined stimulation approach elicits a comparable compensatory response in the lower extremities remains unclear. This study aimed to investigate how cTBS preconditioning modulated the effect of iTBS on motor cortex excitability related to the lower limb in healthy individuals. Using a randomised cross-over design, a total of 25 healthy participants (19 females, mean age = 24.80 yr) were recruited to undergo three different TBS protocols (cTBS + iTBS, sham cTBS + iTBS, sham cTBS + sham iTBS) in a random order. Each TBS intervention was administered with one-week intervals. cTBS and iTBS were administered at an intensity of 80% active motor threshold (AMT) delivering a total of 600 pulses. Before intervention (T0), immediately following intervention (T1), and 20 min after intervention (T2), the corticomotor excitability was measured for the tibialis anterior muscle of participants' non-dominant leg using a Magneuro100 stimulator and matched double-cone coil. The average amplitude of the motor-evoked potential (MEP) induced by applying 20 consecutive monopulse stimuli at an intensity of 130% resting motor threshold (RMT) was collected and analysed. Compare with T0 time, the MEP amplitude (raw and normalised) at T1 and T2 showed a statistically significant increase following the cTBS + iTBS protocol (p < 0.01), but no significant differences were observed in amplitude changes following other protocols (sham cTBS + iTBS and sham cTBS + sham iTBS) (p > 0.05). Furthermore, no statistically significant difference was found among the three protocols at any given time point (p > 0.05). Preconditioning the lower extremity motor cortex with cTBS prior to iTBS intervention can promptly enhance its excitability in healthy participants. This effect persists for a minimum duration of 20 min. No: ChiCTR2300069315. Registered 13 March, 2023, https://www.chictr.org.cn.

Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites

BackgroundWhile theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome. MethodsThirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3–4 days posttreatment (T1) and 10–11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses. ResultsAlthough the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients. LimitationsThe modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10–11 days, whereas similar studies usually follow up for at least one month. ConclusionMore research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome.

Continuous Theta-Burst Stimulation on the Left Posterior Inferior Frontal Gyrus Perturbs Complex Syntactic Processing Stability in Mandarin Chinese

Abstract The structure of human language is inherently hierarchical. The left posterior inferior frontal gyrus (LpIFG) is proposed to be a core region for constructing syntactic hierarchies. However, it remains unclear whether LpIFG plays a causal role in syntactic processing in Mandarin Chinese and whether its contribution depends on syntactic complexity, working memory, or both. We addressed these questions by applying inhibitory continuous theta-burst stimulation (cTBS) over LpIFG. Thirty-two participants processed sentences containing embedded relative clauses (i.e., complex syntactic processing), syntactically simpler coordinated sentences (i.e., simple syntactic processing), and non-hierarchical word lists (i.e., word list processing) after receiving real or sham cTBS. We found that cTBS significantly increased the coefficient of variation, a representative index of processing stability, in complex syntactic processing (esp., when subject relative clause was embedded) but not in the other two conditions. No significant changes in d′ and reaction time were detected in these conditions. The findings suggest that (a) inhibitory effect of cTBS on the LpIFG might be prominent in perturbing the complex syntactic processing stability but subtle in altering the processing quality; and (b) the causal role of the LpIFG seems to be specific for syntactic processing rather than working memory capacity, further evidencing their separability in LpIFG. Collectively, these results support the notion of the LpIFG as a core region for complex syntactic processing across languages.

Personalised functional imaging-guided multitarget continuous theta burst stimulation for post-stroke aphasia: study protocol for a randomised controlled trial

IntroductionContinuous theta burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), targeting the language network in the right hemisphere of post-stroke aphasia (PSA) patients shows promising results in...

Lack of effects of eight-week left dorsolateral prefrontal theta burst stimulation on white matter macro/microstructure and connection in autism.

Whether brain stimulation could modulate brain structure in autism remains unknown. This study explored the impact of continuous theta burst stimulation (cTBS) over the left dorsolateral prefrontal cortex (DLPFC) on white matter macro/microstructure in intellectually able children and emerging adults with autism. Sixty autistic participants were randomized (30 active) and received active or sham cTBS for eight weeks twice per week, 16 total sessions using a double-blind (participant-, rater-, analyst-blinded) design. All participants received high-angular resolution diffusion MR imaging at baseline and week 8. Twenty-eight participants in the active group and twenty-seven in the sham group with good imaging quality entered the final analysis. With longitudinal fixel-based analysis and network-based statistics, we found no significant difference between the active and sham groups in changes of white matter macro/microstructure and connections following cTBS. In addition, we found no association between baseline white matter macro/microstructure and autistic symptom changes from baseline to week 8 in the active group. In conclusion, we did not find a significant impact of left DLPFC cTBS on white matter macro/microstructure and connections in children and emerging adults with autism. These findings need to be interpreted in the context that the current intellectually able cohort in a single university hospital site limits the generalizability. Future studies are required to investigate if higher stimulation intensities and/or doses, other personal factors, or rTMS parameters might confer significant brain structural changes visible on MRI in ASD.

The effect of continuous theta burst stimulation on antipsychotic-induced weight gain in first-episode drug-naive individuals with schizophrenia: a double-blind, randomized, sham-controlled feasibility trial

Antipsychotic intake may induce weight gain in drug-naive individuals with schizophrenia, leading to poor compliance in clinical management. However, there is still a lack of effective approaches to treat or prevent this side-effect. Therefore, we conducted this pilot study to investigate the effect of continuous theta burst stimulation (cTBS), a non-invasive magnetic stimulation technique, on preventing olanzapine-induced weight gain. Thirty-nine first-episode drug-naive individuals with schizophrenia were randomly assigned to receive either the active or sham cTBS intervention for 25 sessions (5 times per day for 5 consecutive days). The primary outcomes were changes in body weight and body mass index (BMI). Secondary outcomes included psychiatric symptoms, eating behavior scales, behavior tasks, and metabolic measures. For the result, the body weight and BMI increased significantly in the sham group but not in the active group, with a significant group effect. The active group exhibited a selective increase in the cognitive restraint domain in the Three-Factor Eating Questionnaire (TFEQ-CR) and a decrease in stop-signal reaction time compared to the sham group. The effect of cTBS on body weight was mediated by TFEQ-CR. Our findings demonstrated the feasibility that cTBS intervention could be a potential method for preventing olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients through enhancing cognitive restraint to food. Trial registration: clinical trial registered with clinicaltrials.gov (NCT05086133).

A neuroimaging study of brain activity alterations in treatment-resistant depression after a dual target accelerated transcranial magnetic stimulation.

In this study, we designed a new transcranial magnetic stimulation (TMS) protocol using a dual-target accelerated transcranial magnetic stimulation (aTMS) for patients with treatment resistant depression (TRD). There are 58 TRD patients were recruited from the Second People's Hospital of Guizhou Province, who were, respectively, received dual-target (real continuous theta burst stimulation (cTBS) at right orbitofrontal cortex (OFC) and real repetitive transcranial magnetic stimulation (rTMS) at left dorsolateral prefrontal cortex (DLPFC)), single- target (sham cTBS at right OFC and real rTMS at left DLPFC), and sham stimulation (sham cTBS at right OFC and sham rTMS at left DLPFC). Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired before and after aTMS treatment to compare characteristics of brain activities by use of amplitude of low-frequency fluctuations (ALFF), fractional low-frequency fluctuations (fALFF) and functional connectivity (FC). At the same time, Hamilton Depression Scale-24 (HAMD24) were conducted to assess the effect. HAMD24 scores reduced significantly in dual group comparing to the single and sham group. Dual-target stimulation decreased not only the ALFF values of right fusiform gyrus (FG) and fALFF values of the left superior temporal gyrus (STG), but also the FC between the right FG and the bilateral middle frontal gyrus (MFG), left triangular part of inferior frontal gyrus (IFG). Higher fALFF value in left STG at baseline may predict better reaction for bilateral arTMS. Dual-targe stimulation can significantly change resting-state brain activities and help to improve depressive symptoms.

Continuous Theta-Burst Stimulation of the Contralesional Primary Motor Cortex for Promotion of Upper Limb Recovery After Stroke: A Randomized Controlled Trial.

Despite improvements in acute stroke therapies and rehabilitation strategies, many stroke patients are left with long-term upper limb motor impairment. We assessed whether an inhibitory repetitive transcranial magnetic stimulation treatment paradigm started within 3 weeks after stroke onset promotes upper limb motor recovery. We performed a single-center randomized, sham-controlled clinical trial. Patients with ischemic stroke or intracerebral hemorrhage and unilateral upper limb motor impairment were randomized to 10 daily sessions of active or sham continuous theta-burst stimulation (cTBS) of the contralesional primary motor cortex combined with standard upper limb therapy, started within 3 weeks after stroke onset. The primary outcome was the change in the Action Research Arm Test score from baseline (pretreatment) at 3 months after stroke. Secondary outcomes included the score on the modified Rankin Scale at 3 months and the length of stay at the rehabilitation center. Statistical analyses were performed using mixed models for repeated measures. We enrolled 60 patients between April 2017 and February 2021, of whom 29 were randomized to active cTBS and 31 to sham cTBS. One patient randomized to active cTBS withdrew consent before the intervention and was excluded from the analyses. The mean difference in the change in Action Research Arm Test score from baseline at 3 months poststroke was 9.6 points ([95% CI, 1.2-17.9]; P=0.0244) in favor of active cTBS. Active cTBS was associated with better scores on the modified Rankin Scale at 3 months (OR, 0.2 [95% CI, 0.1-0.8]; P=0.0225) and with an 18 days shorter length of stay at the rehabilitation center than sham cTBS ([95% CI, 0.0-36.4]; P=0.0494). There were no serious adverse events. Ten daily sessions of cTBS of the contralesional primary motor cortex combined with upper limb training, started within 3 weeks after stroke onset, promote recovery of the upper limb, reduce disability and dependence and leads to earlier discharge from the rehabilitation center. URL: https://trialsearch.who.int/; Unique identifier: NTR6133.

0684 Effects of Transcranial Magnetic Stimulation (TMS) on Treatment of Intrusive Thinking in Insomniac Populations

Abstract Introduction Patients with clinical insomnia commonly report intrusive thinking (IT) as a common contributor to delayed sleep onset. Evidence suggests that the default mode network (DMN) may contribute to this intrusive thinking. Therefore, we employed continuous theta burst (cTBS) repetitive transcranial magnetic stimulation (rTMS) to modulate DMN activation, and thus reduce IT before sleep. Methods In a counterbalanced cross-over design, active or sham cTBS was administered to 20 participants with clinical insomnia, 8 males (Mage=31.63, SD=6.74) and 12 females (Mage=23.75, SD=4.29), with sessions separated by at least 5 days. To assess intrusive thoughts prior to sleep, participants took the Glasgow Content of Thoughts Inventory (GCTI). We utilized the subscale of the GCTI measuring sleep and wakefulness. Higher scores indicate more persistent intrusive thoughts. We conducted a mixed ANOVA to examine effects of sham and active cTBS conditions on intrusive thoughts. Results There was a medium effect size (ηp2 =.087) but no significant variance (p&amp;gt;.05) in average IT scores between participants sham cTBS (M=19.100, SD=5.349) and active cTBS (M=18.200, SD=4.502) Post-TMS sessions. There was a significant interaction between sex, TMS, and administration (F(1,18)= 4.697; ηp2=.207; p=.044). We then conducted a simple effects analysis between males and females. There was no significant effect of cTBS condition on reported intrusive thinking post-TMS administration (F(1,7)= .628; ηp2=.082; p=.454). However, there was a significant interaction of cTBS condition on intrusive thoughts post-TMS administration for females (F(1,11)= 5.894; ηp2=.349; p=.034). Post-hoc pairwise comparison revealed that females reported significantly greater intrusive thinking post-TMS administration (M=20.167, SD=5.68) compared to pre-TMS administration (M=17.5, SD=5.73) during their sham cTBS session (p=.042). This was not present post-TMS administration during active cTBS (p&amp;gt;.05). Conclusion There was a decrease in intrusive thoughts relating to sleep and wakefulness in females, but not males, following active TMS. Interestingly, we also observed an increase in intrusive thoughts for the sham condition, suggesting that participants may have developed expectations of improvement and been sensitized to these cognitions when sleep was not improved. These findings are encouraging suggesting that cTBS may improve IT, although preliminary data suggest this may differ between males and females. Support (if any) W81XWH2010173

0066 Continuous Theta Burst Transcranial Magnetic Stimulation for Insomnia and its Effects on Verbal Recall Performance

Abstract Introduction In this project, we studied the efficacy of focused inhibitory stimulation using continuous theta burst stimulation (cTBS) repetitive transcranial magnetic stimulation (rTMS) on an easily accessible region of the default mode network (DMN). As reported elsewhere, we found that cTBS improved brain connectivity and objectively measured sleep. However, there is little known about the side effects of rTMS in the treatment of insomnia, so here we evaluated the effects on verbal memory recall. Methods Twenty adults with clinical insomnia completed this study (Mage=26.90, SD=6.56). Participants conducted two overnight visits during the study; one where they received active cTBS and one where they received a sham cTBS prior to sleep. Participants completed the California Verbal Learning Test (CVLT) before stimulation and again completed the recall portion following a night of laboratory monitored sleep. We analyzed CVLT recall performance with a repeated measures ANOVA with factors of condition (active cTBS vs. sham cTBS) and session (Short Recall, Long Recall, Cued Recall, and Recognition). Results Contrary to our hypothesis, our analyses indicate there was no significant effects on recall performance due to active cTBS. There was no main effect of condition on recall scores post-TMS administration (F(1, 18)=1.162, p=.220, ηp2 = 0.082). There was no interaction effect of active or sham cTBS on recall performance (F(4, 15)=.828, p=.528, ηp2=0.181). Posthoc pairwise comparisons demonstrated that there was no significant difference post-TMS administration between active cTBS and sham cTBS conditions on long recall, cued recall, or recognition (p&amp;gt;.05). There was no significant difference post-TMS administration on short-term recall performance. Participants scored lower on short term recall after receiving active cTBS (M=12.632; SD=2.910) than after sham cTBS administration (M=13.42 ;SD=2.545) (p=.048). Conclusion Compared to sham, active cTBS was not associated with any significant difference in long-term recall performance after TMS administration. While the results demonstrate there are short term effects to recall after administration, recall scores bounce back shortly after. While participants didn’t necessarily improve with active cTBS, it is beneficial to know there are no long-term harmful effects of active cTBS on recall as side effect of insomnia treatment. Support (if any) W81XWH2010173

0416 Preliminary Study of the Effects of Continuous Theta Burst Stimulation of the Default Mode Network on Subjective Sleepiness

Abstract Introduction Repetitive transcranial Magnetic Stimulation (rTMS) is a noninvasive intervention commonly used to treat clinical depression by modulating brain activity in specific regions. We investigated rTMS of the default mode network (DMN) as a potential treatment for insomnia. The DMN is associated with internally focused cognition and rumination. Therefore, we expected that modulation of this network would improve sleep. As reported elsewhere, this trial showed that active cTBS to the DMN improved polysomnographically (PSG) measured sleep. Here, we hypothesized that participants who were treated with active continuous theta burst stimulation (cTBS) rTMS over the DMN versus sham cTBS would report reduced subjective sleepiness following post-treatment sleep. Methods Twenty adults with clinical insomnia completed this study (Mage=26.90, SD=6.56). Participants completed two overnight visits; one where they received active cTBS treatment and one where they received sham TMS treatment. We analyzed the Karolinska Sleepiness Scale (KSS), which was administered six times throughout each visit. KSS 1-3 were administered prior to treatment and KSS 4-6 were post TMS treatment. We used a repeated measures ANOVA to analyze effects of TMS on reported daytime sleepiness. Results There was no main effect of condition on sleepiness score F(1,18 )=1.165, p=0.295, ηp 2=0.061. There was a significant interaction effect of condition and pre/post intervention on reported subjective sleepiness F(1,18)=3.079, p=0.013, ηp 2 = 0.146, although follow-up analyses did not reveal significant differences. Nonetheless, there was a continuous negative trend toward reduced sleepiness for post TMS administration after overnight sleep in active cTBS (M = 4.8, SD = 1.96) compared to the sham cTBS session (M = 5.2, SD = 1.91) (p = 0.366). Conclusion As reported elsewhere, this trial of a single administration of cTBS showed improved PSG sleep. Here we saw that there was no significant change in subjective sleepiness following a night of sleep with or without the trial of cTBS, but there was a nonsignificant trend toward declining sleepiness for the active cTBS group relative to the sham condition. This preliminary study is encouraging and suggests that further research into this approach is warranted. Support (if any) W81XWH2010173

0186 Continuous Theta Burst Transcranial Magnetic Stimulation and Signal Detection Performance on a Military Go/No-Go Task

Abstract Introduction Repetitive transcranial Magnetic Stimulation (rTMS) is an emerging non-pharmacological treatment method utilized to treat multiple clinical diagnoses to include anxiety, depression, and now insomnia. As part of a larger project, we showed that a single rTMS stimulation with continuous theta burst stimulation (cTBS) to the default mode network (DMN) was associated with improved sleep. However, there is little known about potential effects on attention and vigilance because of cTBS to the DMN. We hypothesized that active cTBS would have no significant impact on signal detection tasks post-TMS administration. Methods Twenty adults with clinical insomnia completed this study (Mage=26.90, SD=6.56). Participants completed two overnight visits in total; one where they received active cTBS and one where they received sham cTBS over an easily accessible node of the DMN (left angular gyrus). We analyzed signal detection performance utilizing a Go-No-Go (GNG) task. Three variables were calculated as a result: hit rate, correct rejection rate, and false alarm rate. Higher scores on hit rate and correct rejection rate indicate higher correct responses. Higher scores on false alarm rate indicates a higher number of incorrect responses. We conducted a repeated measures ANOVA with factors of condition, administration, and reversal. Results There was no main effect of condition on GNG hit rate (F(1,17)=1.365, p=.259, ηp2 =.074), GNG false alarm rate (F(1,17)=.210, p=.091, ηp2 =.244), or GNG correct rejection rate (F(1, 17)=1.677, p=.213, ηp2 =.090). We also found there were no significant interaction effects of TMS condition on performance on reversal conditions for GNG hit rate (F(1,17)=0.45, p=.834, ηp2 =.003), GNG false alarm rate (F(1,17)=1.572, p=.227, ηp2 =.085), or GNG correct rejection rate (F(1, 17)=1.510, p=.236, ηp2 =.082). Posthoc pairwise comparisons demonstrated that participants did not significantly differ on GNG hit rate, false alarm rate, or correct rejection rate between their active cTBS and sham cTBS session (p&amp;gt;.05). Conclusion Active cTBS was not significantly associated with any decline in response inhibition or signal detection. It is helpful for future recipients to know they are not adversely affected in attention or vigilance after receiving cTBS rTMS of the DMN for treatment of insomnia. Support (if any) W81XWH2010173

0649 Sex Differences in the Effects of TMS on Depression

Abstract Introduction As part of a larger study to examine the effects of repetitive transcranial magnetic stimulation (rTMS) over a single node of the default mode network (DMN) on sleep quality, we also examined secondary effects on depression. We hypothesized that rTMS would be more effective in females, rather than males, due to previously established higher rates of depression in the female population. Methods We administered continuous theta burst stimulation (cTBS) rTMS or sham stimulation, in a counterbalanced order separated by at least 5 days, over the left inferior parietal node of the DMN in 20 participants with clinical insomnia, 8 males (Mage=31.6, SD=6.7) and 12 females (Mage=23.8, SD=4.3). Beck Depression Inventory (BDI) scores obtained immediately before and after the stimulation sessions were compared using mixed (condition x time x sex) ANOVA to determine the effectiveness of rTMS in reducing symptoms of depression between the sexes. Results Overall, there was a large effect size (ηp2=0.207, p=0.077) in BDI scores between scores after the sham cTBS TMS session (M=12.47, SD=2.54) and scores after the active cTBS TMS session (M=10.00, SD=2.01). However, when separating for sex, males did not show a statistically significant reduction in depressive symptoms for the active session compared to the sham session (ηp2=0.08, F(1,6)=19.00, p=0.508). While the treatment did not significantly change depressive symptoms in females, large effect size was observed (ηp2=0.261, F(1,7)=18.06, p=0.16), suggesting potential efficacy of the treatment. Post-hoc pairwise comparisons reveal a greater change in depression symptom scores for active vs sham cTBS TMS in women (M=-4.00, SD=2.00), than men (M=-0.71, SD=1.43). Conclusion An intervention using cTBS rTMS to improve sleep also led to a trend toward reduced depression, that was more evident among women. As reported elsewhere, this treatment significantly improved polysomnographic sleep, and the present preliminary results suggest that it may also be useful for modestly improving depressive mood, but further research will be necessary due to the limited sample size. It is not clear whether the trends toward mood among women was due simply to higher baseline depression scores in that group, but the findings suggest that additional work is warranted. Support (if any) W81XWH2010173

Continuous Theta-Burst Stimulation of the Primary Motor Cortex Induces Specific Influence on Novel Vocabulary Acquisition in Different Learning Environments

The primary motor cortex takes part in various stages of language learning accompanied by human motor activity. However, previous studies of causal relationships between the activation of primary motor cortex and efficiency of language tasks reveal contradictory results, likely due to diverging learning environments and specific movement patterns required by different experimental designs. The goal of this research was to comprehensively investigate the effect of continuous theta-burst magnetic stimulation (cTBS) of the primary motor cortex on the acquisition of new words while modulating the learning environment and the motor response during the learning process. Following cTBS of the primary motor cortex or control conditions (sham and active control cTBS), the subjects (n = 96) completed a novel word learning task, which involved associating visually presented objects with spoken word forms using a virtual reality (VR) or conventional computer monitor environment. In each environment, the subjects were exposed to eight novel words embedded into questions about visual stimulus properties in order to prompt novel associations. Responses to these questions could be performed either by distal or by proximal hand movements. The outcome of the word acquisition was measured using a free recall task immediately after the training and on the next day. The results showed significant differences in the success of recalling new words immediately after the learning session and on the next day only in those subjects who received cTBS of the primary motor cortex; furthermore, this effect was specific to proximal movements in both learning environments. The results suggest that the motor cortex is directly involved in acquiring novel vocabulary during active interaction with the learning material.

Precuneus stimulation alters abstract verbal memory encoding

The present study investigated the role of the precuneus in memory encoding of abstract and concrete words, with the combination of functional Magnetic Resonance Imaging (fMRI) and continuous Theta Burst Stimulation (cTBS) techniques. The memory encoding process was scanned in the fMRI to detect the regions of interest for the difference in memory formation of these two types of words. The real and sham cTBS stimulations were applied over the left precuneus. The fMRI results showed that the left precuneus was deactivated for the memory encoding of both types of words, with concrete words inducing significantly more deactivation. The cTBS stimulation over the left precuneus significantly reduced the reaction time of retrieval of abstract words but not concrete words. It is concluded that precuneus plays a role in modulating the abstract but not the concrete verbal memory encoding. • This study examines the role of precuneus in verbal episodic memory with combination of fMRI and cTBS. • The precuneus was deactivated for the episodic memory encoding of abstract and concrete words. • The precuneus was deactivated significantly less for the episodic encoding of abstract words than that of the concrete words. • The cTBS stimulation over precuneus significantly reduced the reaction time of retrieval of abstract words instead of concrete words.

Excitability Changes in Occipital Cortex After Continuous Theta-Burst Stimulation.

Modulation of visual cortical structures by repetitive transcranial magnetic stimulation is rarely observed in literature. In this study; the researchers aimed to investigate the neurophysiological alterations by using continuous theta burst stimulation (cTBS) protocol over the occipital cortex in healthy subjects. Twenty-five (15 female, 10 male) (mean age 29.84±4.7 years) healthy individuals were included in sham and real cTBS occipital stimulation sessions. Before and after each session, neurophysiological studies including phosphene threshold and visual evoked potential (VEP) responses were recorded. The P100 latency values and maximum amplitude values between N75-P100 peaks of 100 responses of 1000 uninterrupted continuous visual stimuli were measured. The VEP habituation and phosphene thresholds were compared in sham and real cTBS sessions. The phosphene threshold values increased to statistically significant levels after the real cTBS session. Visual evoked potential habituation was observed in both sham and real cTBS sessions in individuals without significant differences. Also, no difference between the P100 latencies and N75-P100 amplitude values in the sham and real cTBS sessions was observed. Phosphene threshold measurements demonstrated the modulation of the occipital cortex excitability via cTBS in healthy subjects.

Non-invasive Brain Stimulation and Prism Adaptation in Art Constructive Errors in Painting.

This study aimed to investigate the influence of neglect and the effect of prism adaptation (PA) combined with continuous Theta-burst transcranial magnetic stimulation (cTBS) on the art constructive errors in painting rehabilitation of stroke patients with neglect. Fourteen patients with neglect and art constructive errors in painting secondary to stroke were randomly assigned to the rehabilitation group and received PA combined with the inhibitory protocol of cTBS over the intact parietal cortex; the control group received PA combined with sham cTBS for two weeks in ten daily sessions. Patients were assessed for art constructive errors in painting in figure copying test (FCT), and coloring test (CT) before and after the intervention. Art constructive errors in painting were classified into omission, deformation, size, neglect of warm colors, and perseveration of errors. Neglect was evaluated using the line bisection task (LBT), figure copying test (FCT), and coloring test (CT). All patients showed a significant improvement in art constructive errors in painting (measured using the pattern of painting' errors in FCT and CT), and neglect (measured using LBT, FCT, and CT) (P<0.05). Omission, neglect of warm colors, and deformation were the most frequent errors. Neglect and rehabilitation influence the painting system in stroke patients. Both approaches improved art constructive errors in painting and neglect symptoms.

Theta burst stimulation over left cerebellum does not modulate auditory feedback control of vocal production.

Accumulating evidence has shown significant contributions of the right cerebellum to auditory-motor integration for vocal production. Whether the left cerebellum is likewise involved in vocal motor control, however, remains unclear. By applying neuronavigated continuous and intermittent theta burst stimulation (cTBS/iTBS) over the left cerebellar lobule VII (Crus I), the present event-related potential (ERP) study investigated whether the left cerebellum exerts causal effects in modulating auditory feedback control of vocal pitch production. After receiving cTBS, iTBS, or sham stimulation over the left cerebellum, a group of fifteen young adults produced sustained vowels while hearing their voice unexpectedly shifted in pitch upwards or downwards by 200 cents. The effects of cerebellar stimulation were assessed by measuring the vocal and ERP (N1/P2) responses to pitch perturbations across the conditions. When compared to sham stimulation, cTBS or iTBS over the left cerebellar lobule VII (Crus I) led to no systematic changes in vocal compensations for pitch perturbations in auditory feedback. Also, the cortical N1/P2 responses did not vary significantly across the three stimulation sessions. These findings present the first neurobehavioral evidence suggesting that the left cerebellum is not causally associated with auditory feedback control of vocal production. Together with previously reported causal effects of the right cerebellum in modulating vocal pitch regulation, the present study lends support to the hypothesis that there is a functional lateralization of the cerebellum in vocal motor control though auditory feedback.