Excitatory Transcranial Magnetic Stimulation Research Articles

Blunted anterior midcingulate response to reward in opioid users is normalized by prefrontal transcranial magnetic stimulation.

Abnormalities in goal-directed behavior, mediated by mesocorticolimbic reward function and structure, contribute to worse clinical outcomes including higher risk of treatment dropout and drug relapse in opioid users (OU). In a sham-controlled randomized study design, we measured whether robot-assisted 10Hz transcranial magnetic stimulation (TMS) applied to the prefrontal cortex was able to modulate anterior midcingulate cortex (MCC) electrophysiological response to rewards, in OU and matched healthy controls. We show that OU exhibit a blunted anterior MCC reward response, compared to healthy controls (t(39) = 2.62, p = 0.01, d = 0.84), and that this is normalized following 10-Hz excitatory TMS (t (36) = .82, p = 0.42, d = 0.17). Excitatory TMS modulated the putative reward function of the MCC in OU. Further work with increased sample sizes and TMS sessions is required to determine whether restoring MCC reward function increases reward-directed behaviors, which may enhance treatment success through the maintenance of treatment goals.

Enhancing ventrolateral prefrontal cortex activation mitigates social pain and modifies subsequent social attitudes: Insights from TMS and fMRI

Social pain, a multifaceted emotional response triggered by interpersonal rejection or criticism, profoundly impacts mental well-being and social interactions. While prior research has implicated the right ventrolateral prefrontal cortex (rVLPFC) in mitigating social pain, the precise neural mechanisms and downstream effects on subsequent social attitudes remain elusive. This study employed transcranial magnetic stimulation (TMS) integrated with fMRI recordings during a social pain task to elucidate these aspects. Eighty participants underwent either active TMS targeting the rVLPFC (n = 41) or control stimulation at the vertex (n = 39). Our results revealed that TMS-induced rVLPFC facilitation significantly reduced self-reported social pain, confirming the causal role of the rVLPFC in social pain relief. Functional connectivity analyses demonstrated enhanced interactions between the rVLPFC and the dorsolateral prefrontal cortex, emphasizing the collaborative engagement of prefrontal regions in emotion regulation. Significantly, we observed that negative social feedback led to negative social attitudes, whereas rVLPFC activation countered this detrimental effect, showcasing the potential of the rVLPFC as a protective buffer against adverse social interactions. Moreover, our study uncovered the impact role of the hippocampus in subsequent social attitudes, a relationship particularly pronounced during excitatory TMS over the rVLPFC. These findings offer promising avenues for improving mental health within the intricate dynamics of social interactions. By advancing our comprehension of the neural mechanisms underlying social pain relief, this research introduces novel intervention strategies for individuals grappling with social distress. Empowering individuals to modulate rVLPFC activation may facilitate reshaping social attitudes and successful reintegration into communal life.

Exploring research trends and focal points in the application of transcranial magnetic stimulation for enhancing motor function in post-stroke patients: A bibliometric and content analytical approach

BackgroundMotor impairment is a significant health concern among post-stroke patients. Transcranial magnetic stimulation (TMS) is considered as an emerging rehabilitation therapy for various neurological conditions, and the effects of excitatory TMS on post-stroke have received much attention in past decade. However, the future hotspots and content analysis on the growth trends have not been studied. This bibliometric and content analysis aimed to study the global developmental history and current status of TMS for motor function of post-stroke from January 2004 to July 2023. MethodsLiterature published on Scopus database from January 2004 to July 2023 were searched. Extracted data was analysed using the R studio and VOS viewer for author's publication, institutions, sources, keyword co-occurrence and world network analysis. Keyword cluster analysis, co-citation analysis for references and content analysis were also performed. We screened top 10 most cited or collaborative areas for publications, institutions and sources in the field of TMS associated with motor function of post-stroke. ResultsIn this study, a comprehensive analysis of 267 publications was conducted, revealing a substantial surge in research output throughout 2022. China emerged as the leading contributor, with 409 publications, followed by the United States with 211 publications. Notably, Harvard Medical School stood out as one of the most prolific institutions, accounting for 34 publications (13.12 %). Among researchers, Abo M garnered the highest publication count, with 9 articles (14.5 %). The Word cloud showed that motor function, repetitive transcranial magnetic stimulation (rTMS) and upper limb have been the focus of recent attention. Burst keywords on thematic evolution and topic trend shows that quality of life scale, network parameters, cognition, lower limb motor function are the future trends. ConclusionThis bibliometric study describes that TMS has shown promising results in improving motor function of upper extremity in stroke patients, the long-term effects and durability of these improvements are still being investigated. Future research might focus on understanding the optimal duration and frequency of TMS sessions for sustained motor recovery and exploring strategies to maintain gains achieved through TMS over extended periods of time. Future studies can investigate the changes in the lower limb motor function.

Pre-frontal stimulation does not reliably increase reward responsiveness.

Depression is the leading cause of disability worldwide and its effects can be fatal, with over 800,000 people dying by suicide each year. Neuromodulatory treatments such as transcranial magnetic stimulation (TMS) are being used to treat depression. Despite its endorsement by two regulatory bodies: NICE (2016) and the FDA (2008), there are major questions about the treatment efficacy and biological mechanisms of TMS. Ahn etal.'s (2013) justified the use of TMS in a clinical context in an important study indicating that excitatory TMS increases reward responsiveness. A pseudo-replication of this study by Duprat etal., (2016) also found a similar effect of active TMS, but only with the addition of an exploratory covariate to the analyses-trait reward responsiveness. Here we replicate Ahn etal.'s (2013) key study, and to test the reliability of the effects, and their dependency on trait reward responsiveness as described by Duprat etal., (2016). Using excitatory and sham TMS, we tested volunteers using the probabilistic learning task to measure their reward responsiveness both before and after stimulation. We also examined affect (positive, negative) following stimulation. Irrespective of TMS, the task was shown to be sensitive to reward responsiveness. However, we did not show TMS to be effective in increasing reward responsiveness and we did not replicate Ahn etal., (2013) or Duprat etal., (2016)'s key findings for TMS efficacy, where we provide evidence favouring the null. Moreover, exploratory analyses suggested following active stimulation, positive affect was reduced. Given our findings, we question the basic effects, which support the use of TMS for depression, particularly considering potential deleterious effects of reduced positive affect in patients with depression.

Feasibility of a Combined Neuromodulation and Yoga Intervention for Mild Traumatic Brain Injury and Chronic Pain: Protocol for an Open-label Pilot Trial.

BackgroundMild traumatic brain injury (mTBI) and chronic pain often co-occur and worsen rehabilitation outcomes. There is a need for improved multimodal nonpharmacologic treatments that could improve outcomes for both conditions. Yoga is a promising activity-based intervention for mTBI and chronic pain, and neuromodulation through transcranial magnetic stimulation is a promising noninvasive, nonpharmacological treatment for mTBI and chronic pain. Intermittent theta burst stimulation (iTBS) is a type of patterned, excitatory transcranial magnetic stimulation. iTBS can induce a window of neuroplasticity, making it ideally suited to boost the effects of treatments provided after it. Thus, iTBS may magnify the impacts of subsequently delivered interventions as compared to delivering those interventions alone and accordingly boost their impact on outcomes.ObjectiveThe aim of this study is to (1) develop a combined iTBS+yoga intervention for mTBI and chronic pain, (2) assess the intervention’s feasibility and acceptability, and (3) gather preliminary clinical outcome data on quality of life, function, and pain that will guide future studies.MethodsThis is a mixed methods, pilot, open-labeled, within-subject intervention study. We will enroll 20 US military veteran participants. The combined iTBS+yoga intervention will be provided in small group settings once a week for 6 weeks. The yoga intervention will follow the LoveYourBrain yoga protocol—specifically developed for individuals with TBI. iTBS will be administered immediately prior to the LoveYourBrain yoga session. We will collect preliminary quantitative outcome data before and after the intervention related to quality of life (TBI-quality of life), function (Mayo-Portland Adaptability Index), and pain (Brief Pain Inventory) to inform larger studies. We will collect qualitative data via semistructured interviews focused on intervention acceptability after completion of the intervention.ResultsThis study protocol was approved by Edward Hines Jr Veterans Administration Hospital Institutional Review Board (Hines IRB 1573116-4) and was prospectively registered on ClinicalTrials.gov (NCT04517604). This study includes a Food and Drug Administration Investigational Device Exemption (IDE: G200195). A 2-year research plan timeline was developed. As of March 2022, a total of 6 veterans have enrolled in the study. Data collection is ongoing and will be completed by November 2022. We expect the results of this study to be available by October 2024.ConclusionsWe will be able to provide preliminary evidence of safety, feasibility, and acceptability of a novel combined iTBS and yoga intervention for mTBI and chronic pain—conditions with unmet treatment needs.Trial RegistrationClinicalTrials.gov NCT04517604; https://www.clinicaltrials.gov/ct2/show/NCT04517604International Registered Report Identifier (IRRID)DERR1-10.2196/37836

Better modulation for risk decision-making after optimized magnetic stimulation.

Traditional repetitive transcranial magnetic stimulation can only produce a significant but weak effect on the cortex while theta burst stimulation (TBS), a patterned accelerated form of stimulation, can produce a stronger poststimulation effect, which may improve decision-making abilities. We designed a comparative assessment of the effect of intermittent TBS (iTBS), 20Hz, in two risk decision-making tasks on healthy controls. Participants were randomized and assigned to the iTBS (n=29), 20Hz (n=29), or sham (n=29) groups. The effects of the different methods of left dorsolateral prefrontal cortex stimulation on risk decision-making functions were compared based on subjects' performance in the Game of Dice Task (GDT) and Risky Gains Task (RGT). The main indicators were positive and negative feedback utilization rates of GDT and RGT. Both iTBS and 20 Hz stimulation resulted in significant improvements upon negative feedback in the GDT, with increases in safe options and reductions in risky options; iTBS stimulation increased subjects' use of positive feedback in the GDT and RGT (all p<0.05). Furthermore, the iTBS group had a stronger feedback risk reduction effect than the 20Hz or sham group following RGT negative feedback (p<0.05). Individuals would integrate positive and negative information more efficiently, leading to them making rational choices after excitatory transcranial magnetic stimulation. Moreover, iTBS has a stronger risk reduction effect following negative feedback than the 20Hz stimulation did. In summary, iTBS might have clinical value in decision promotion.

Modulating functional connectivity between medial frontopolar cortex and amygdala by inhibitory and excitatory transcranial magnetic stimulation.

The prefrontal-limbic network in the human brain plays a major role in social cognition, especially cognitive control of emotion. The medial frontopolar cortex (mFP; Brodmann Area 10) and the amygdala are part of this network and display correlated neuronal activity in time, as measured by functional magnetic resonance imaging (fMRI). This functional connectivity is dynamic, sensitive to training, and affected in mental disorders. However, the effects of neurostimulation on functional connectivity within this network have not yet been systematically investigated. Here, we investigate the effects of both low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) to the right mFP on functional connectivity between mFP and amygdala, as measured with resting state fMRI (rsfMRI). Three groups of healthy participants received either low-frequency rTMS (1 Hz; N = 18), sham TMS (1 Hz, subthreshold; N = 18) or high-frequency rTMS (20 Hz; N = 19). rsfMRI was acquired before and after (separate days). We hypothesized a modulation of functional connectivity in opposite directions compared to sham TMS through adjustment of the stimulation frequency. Groups differed in functional connectivity between mFP and amygdala after stimulation compared to before stimulation (low-frequency: decrease, high-frequency: increase). Motion or induced changes in neuronal activity were excluded as confounders. Results show that rTMS is effective for increasing and decreasing functional coherence between prefrontal and limbic regions. This finding is relevant for social and affective neuroscience as well as novel treatment approaches in psychiatry.

Differential effects of trancranial magnetic stimulation and electroconvulsive stimulation on adult hippocampal neurogenesis in mice

The neurogenic theory of electroconvulsive therapy (ECT) states that the induction of hippocampal neurogenesis is one of the biological mechanisms responsible for ECT’s antidepressant effects. Hippocampal neurogenesis has been shown to be required for antidepressant effect, is negatively regulated by stress, and electroconvulsive stimulation very potently increases neurogenesis. To confirm and further elucidate specific changes in hippocampal neurogenesis, we examined the timeline of neurogenesis following ECS in an animal model, and expanded the theory to include neurogenesis changes following excitatory transcranial magnetic stimulation (eTMS, 10 Hz) and intermittent theta burst stimulation (iTBS). In mice, we used bromodeoxyuridine (BrdU) to label neurons born two days prior to a single ECS, eTMS or iTBS treatment. Numbers of surviving BrdU+ cells, and proliferating PCNA+ cells, were examined 1, 3, and 7 days following neurostimulation. We found that just one session of ECS increased the number of BrdU positive cells significantly immediately starting on day 1 and declining back to baseline on day 3 and 7. Proliferating PCNA+ cell levels were similar to shams on day 1, peaked on day 3, and declined to basal levels on day 7. The data indicates that there is a delayed and transient increase in neuronal proliferation following ECS, and a loss of earlier-born cells that may be due to neuronal death to counteract the proliferating cell increase. In contrast, eTMS had no effect on levels of neurogenesis across time, suggesting that it does not exert its effects through increasing neurogenesis. Finally, iTBS immediately increased neurogenesis but the number of newborn cells declined over 7 days to levels comparable to sham and eTMS animals. Collectively, we found that different neurostimulation techniques have distinct effects on hippocampal neurogenesis. Ongoing work is examining the effects of chronic neurostimulation on neurogenesis levels and the morphology of newborn neurons.

Excitatory TMS modulates memory representations

ABSTRACTBrain stimulation technologies have seen increasing application in basic science investigations, specifically toward the goal of improving memory function. However, proposals concerning the neural mechanisms underlying cognitive enhancement often rely on simplified notions of excitation. As a result, most applications examining the effects of transcranial magnetic stimulation (TMS) on functional neuroimaging measures have been limited to univariate analyses of brain activity. We present here analyses using representational similarity analysis (RSA) and encoding-retrieval similarity (ERS) analysis to quantify the effect of TMS on memory representations. To test whether an increase in local excitability in PFC can have measurable influences on upstream representations in earlier temporal memory regions, we compared 1 and 5Hz stimulation to the left dorsolateral PFC (DLPFC). We found that 5Hz rTMS, relative to 1Hz, had multiple effects on neural representations: 1) greater representational similarity during both encoding and retrieval in ventral stream regions, 2) greater ERS in the hippocampus, and, critically, 3) increasing ERS in MTL was correlated with increasing univariate activity in DLPFC, and greater functional connectivity for hits than misses between these regions. These results provide the first evidence of rTMS modulating semantic representations and strengthen the idea that rTMS may affect the reinstatement of previously experienced events in upstream regions.

Commentary: Cumulative effects of anodal and priming cathodal tDCS on pegboard test performance and motor cortical excitability.

Commentary: Cumulative effects of anodal and priming cathodal tDCS on pegboard test performance and motor cortical excitability.

Inhibition of the cortex using transcranial magnetic stimulation in psychiatric populations: current and future directions

Several lines of evidence suggest that deficits in γ-aminobutyric acid (GABA) inhibitory neurotransmission are implicated in the pathophysiology of schizophrenia, bipolar disorder, major depressive disorder and obsessive-compulsive disorder. Cortical inhibition refers to a neurophysiological process, whereby GABA inhibitory interneurons selectively attenuate pyramidal neurons. Transcranial magnetic stimulation (TMS) represents a noninvasive technique to measure cortical inhibition, excitability and plasticity in the cortex. These measures were traditionally specific to the motor cortex, which is an important limitation when nonmotor neurophysiological processes are of primary interest. Recently, TMS has been combined with electro encephalography (EEG) to derive such measurements directly from the cortex. This review focuses on neurophysiological studies related to inhibitory and excitatory TMS paradigms, linking dysfunctional GABAergic neurotransmission to disease states. We review evidence that suggests cortical inhibition deficits among psychiatric populations and demonstrate how each disorder has a specific neurophysiological response to treatment. We conclude by discussing the future directions of TMS combined with EEG, demonstrating the potential to identify biological markers of neuropsychiatric disorders.

Neurophysiological Correlates of Borderline Personality Disorder: A Transcranial Magnetic Stimulation Study

Cortical inhibition deficits have been demonstrated in several disorders with deficits in impulsive control (e.g., attention-deficit/hyperactivity disorder [ADHD], tic disorder, Tourette syndrome) by using transcranial magnetic stimulation (TMS). With borderline personality disorder (BPD), we investigated another disorder associated with high impulsivity by TMS. We hypothesized that BPD patients display decreased cortical inhibition and/or increased cortical excitation as assessed with TMS. Different inhibitory and excitatory TMS parameters were investigated in 19 unmedicated female BPD patients and 19 healthy control subjects matched for sex, age, handedness, and body height. Additionally, the results were controlled for ADHD symptomatology. A reduced cortical silent period (CSP) duration was found in BPD patients compared with healthy control subjects in the right cortex. Even after controlling for ADHD symptoms, this result remained significant. These findings support an association between BPD and cortical inhibition deficits as indexed through TMS. The results are discussed considering basic neurobiological mechanisms that may explain our findings of decreased intracortical inhibition in BPD patients.