Effects Of rTMS Research Articles

The Effect of Scalp Acupuncture and rTMS on Neuromotor Function in Photothrombotic Stroke Rat Model

The Effect of Scalp Acupuncture and rTMS on Neuromotor Function in Photothrombotic Stroke Rat Model

Neural effects of TMS trains on the human prefrontal cortex

How does a train of TMS pulses modify neural activity in humans? Despite adoption of repetitive TMS (rTMS) for the treatment of neuropsychiatric disorders, we still do not understand how rTMS changes the human brain. This limited understanding stems in part from a lack of methods for noninvasively measuring the neural effects of a single TMS train—a fundamental building block of treatment—as well as the cumulative effects of consecutive TMS trains. Gaining this understanding would provide foundational knowledge to guide the next generation of treatments. Here, to overcome this limitation, we developed methods to noninvasively measure causal and acute changes in cortical excitability and evaluated this neural response to single and sequential TMS trains. In 16 healthy adults, standard 10 Hz trains were applied to the dorsolateral prefrontal cortex in a randomized, sham-controlled, event-related design and changes were assessed based on the TMS-evoked potential (TEP), a measure of cortical excitability. We hypothesized that single TMS trains would induce changes in the local TEP amplitude and that those changes would accumulate across sequential trains, but primary analyses did not indicate evidence in support of either of these hypotheses. Exploratory analyses demonstrated non-local neural changes in sensor and source space and local neural changes in phase and source space. Together these results suggest that single and sequential TMS trains may not be sufficient to modulate local cortical excitability indexed by typical TEP amplitude metrics but may cause neural changes that can be detected outside the stimulation area or using phase or source space metrics. This work should be contextualized as methods development for the monitoring of transient noninvasive neural changes during rTMS and contributes to a growing understanding of the neural effects of rTMS.

Stably and reliably targeting parietal-hippocampal function connectivity for personalized transcranial magnetic stimulation: A pilot study

ObjectiveTo assess the variability and repeatability of transcranial magnetic stimulation (TMS) target identified by functional connectivity (FC) between the hippocampus and parietal lobes after repeated (multi-run) or a single (one-run) resting-state functional magnetic resonance imaging (fMRI), and to introduce a stable and reliable FC-based target positioning method. MethodsTen runs resting-state fMRI scans were conducted. The FC between the hippocampus and the parietal lobes using each run and the mean FC using multi-run was calculated, respectively. With that, the coordinate of the parietal region with the strongest FC in the aforementioned results was separately set as one- and multi-run targets. The variability and repeatability of the one- and multi-run targets were compared. Finally, five days of rTMS over one- and multi-run targets were performed. Memory tests and Electroencephalography (EEG) was used to assess the effects of rTMS. ResultsThe variability of one- and multi-run targets was 12.96 ± 1.19 mm and 5.33 ± 4.39 mm, respectively. The repeatability of multi-run targets was increased by 22.5 times compared to one-run targets. Compared with one-run targets, rTMS over multi-targets showed more significant results in memory performance, which reduced the event-related potential (ERP) amplitude of the parietal region during memory recollection and improved the FC between the parietal and frontal cortices. We noted significant correlations between changes in memory performance and changes in EEG features. ConclusionStimulation target identified by multiple runs of resting-state fMRI is more stable and reliable than one identified by one run of resting-state fMRI for personalized rTMS.

Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

Resting-state EEG connectivity recorded before and after rTMS treatment in patients with treatment-resistant depression

Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy and tolerability in Major Depressive Disorder (MDD). However, the underlying mechanisms of its antidepressant effects remain unclear. This open-label study investigated electroencephalography (EEG) functional connectivity markers associated with response and the antidepressant effects of rTMS. Resting-state EEG data were collected from 28 participants with MDD before and after a four-week rTMS course. Source-space functional connectivity between 38 cortical regions was compared using an orthogonalised amplitude approach. Depressive symptoms significantly improved following rTMS, with 43% of participants classified as responders. While the study's functional connectivity findings did not withstand multiple comparison corrections, exploratory analyses suggest an association between theta band connectivity and rTMS treatment mechanisms. Fronto-parietal theta connectivity increased after treatment but did not correlate with antidepressant response. Notably, low baseline theta connectivity was associated with greater response. However, due to the exploratory nature and small sample size, further replication is needed. The findings provide preliminary evidence that EEG functional connectivity, particularly within the theta band, may reflect the mechanisms by which rTMS exerts its therapeutic effects.

A systematic review and meta-analysis of neuromodulation therapies for substance use disorders

While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge’s g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.

Repetitive Transcranial Magnetic Stimulation With and Without Text4Support for the Treatment of Resistant Depression: Protocol for a Patient-Centered Multicenter Randomized Controlled Pilot Trial.

Treatment-resistant depression (TRD) is the inability of a patient with major depressive disorder (MDD) to accomplish or achieve remission after an adequate trial of antidepressant treatments. Several combinations and augmentation treatment strategies for TRD exist, including the use of repetitive transcranial magnetic stimulation (rTMS), and new therapeutic options are being introduced. Text4Support, a text message-based form of cognitive behavioral therapy that allows patients with MDD to receive daily supportive text messages for correcting or altering negative thought patterns through positive reinforcement, may be a useful augmentation treatment strategy for patients with TRD. It is however currently unknown if adding the Text4Support intervention will enhance the response of patients with TRD to rTMS treatment. This study aims to assess the initial comparative clinical effectiveness of rTMS with and without the Text4Support program as an innovative patient-centered intervention for the management of patients diagnosed with TRD. This study is a multicenter, prospective, parallel-design, 2-arm, rater-blinded randomized controlled pilot trial. The recruitment process is scheduled to last 12 months. It will involve active treatment for 6 weeks, observation, and a follow-up period of 6 months for participants in the study arms. In total, 200 participants diagnosed with TRD at rTMS care clinics in Edmonton, Alberta, and rTMS clinics in Halifax, Nova Scotia will be randomized to 1 of 2 treatment arms (rTMS sessions alone or rTMS sessions plus Text4Support intervention). Participants in each group will be made to complete evaluation measures at baseline, and 1, 3, and 6 months. The primary outcome measure will be the mean change in the scores of the Patient Health Questionnaire-9 (PHQ-9). The secondary outcome measures will involve the scores of the 7-item Generalized Anxiety Disorders Scale (GAD-7), Columbia-Suicide Severity Rating Scale (CSSRS), and World Health Organization-Five Well-Being Index (WHO-5). Patient data will be analyzed with descriptive statistics, repeated measures, and correlational analyses. Qualitative data will be analyzed using the thematic analysis framework. The results of the study are expected to be available 18 months from the start of recruitment. We hypothesize that participants enrolled in the rTMS plus Text4Support intervention treatment arm of the study will achieve superior outcomes compared with the outcomes of participants enrolled in the rTMS alone arm. The application of the combination of rTMS and Text4Support has not been investigated previously. Therefore, we hope that this study will provide a concrete base of data to evaluate the practical application and efficacy of using the novel combination of these 2 treatment modalities. PRR1-10.2196/46830.

The Efficacy of Transcranial Magnetic Stimulation in the Treatment of Obsessive-Compulsive Disorder: An Umbrella Review of Meta-Analyses.

Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used for treating obsessive-compulsive disorder (OCD). Although several meta-analyses have explored its effectiveness and safety, there is no umbrella review specifically focused on rTMS for OCD. This umbrella review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and analyzed relevant meta-analyses on rTMS for OCD. Twenty-three articles were identified from PubMed, and after screening, 12 meta-analyses were included in the review. The studies analyzed in the meta-analyses ranged from 10 to 27, with total participants ranging from 282 to 791. The most commonly studied regions were the dorsolateral prefrontal cortex (DLPFC), supplementary motor area (SMA), and orbito-frontal cortex (OFC). The majority of the meta-analyses consistently supported the effectiveness of rTMS in reducing OCD symptoms when applied to the DLPFC and SMA. Encouraging results were also observed when targeting the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) through deep transcranial magnetic stimulation (dTMS). However, there was a high level of heterogeneity in the findings of nine out of 12 meta-analyses. In conclusion, existing evidence suggests that rTMS targeting the DLPFC and SMA consistently reduces OCD symptoms, but targeting the mPFC and ACC through dTMS shows variable results. However, the high heterogeneity in the study findings indicates a need for further research and standardization in the field.

COGNITIVE GAIN WITH REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION IN POST-STROKE MOTOR TARGET

We aimed to verify the effects of rTMS on cognition in stroke patients after stimulation of the primary motor cortex (M1). We selected 20 stroke patients from a Rehabilitation Center.They were divided into two groups: (RM1) - Right primary motor cortex and (LM1) - Left primary motor cortex. They had 20 sessions of 20 minutes each and were evaluated using the Montreal Cognitive Assessment (MOCA).The MOCA test demonstrated a significant increase in total scores for the LM1 group comparing pre-and post-intervention periods [(19.55 ± 4.93) X (22.45 ± 5.32)] (p=0.006), and for the RM1 group was not statistically significant [(18.56 ± 3.05) X (20.00 ± 3.39)] (p= 0.51). The subtests that increased the overall performance in LM1 were "attention" [(3.27 ± 1.62) x (4.45 ± 1.29)] (p=0.030), "memory" [(2.27 ± 1.79) x (3.36 ± 1.86)] p= (0.026), and "abstraction" [(1.00 ± 0.89) x (1.36 ± 0.81)] (p=0.045). In RM1, the subtest "naming" showed a statistically significant increase [(2.44 ± 0.53) X (2.89 ± 0.33)] (p=0.046). This study concluded that rTMS increases general cognitive performance with repercussions in attention, memory, and abstraction when stimulated in LM1. Stimulation in RM1 increased performance in "naming" with effects on the rehabilitation process of the patients.

Electroencephalography microstates as novel functional biomarkers for insomnia disorder

BackgroundInsomnia disorder (ID) is one of the most common mental disorders. Research on ID focuses on exploring its mechanism of disease, novel treatments and treatment outcome prediction. An emerging technique...

P1: Dosing and treatment outcomes of rTMS for treatment-resistant depressed older adults in a naturalistic outpatient clinic population.

Introduction:Repetitive transcranial magnetic stimulation (rTMS) is an effective, safe, and well-tolerated option for treatment-resistant depression (TRD). The minimal medical and cognitive side effects are advantages of rTMS for all patients. However, the majority of rTMS studies in older adults are notable for underdosing rTMS relative to the corresponding FDA-protocol, as noted by recent international meta-analyses. This study utilizes the standardized rTMS FDA protocol and compares the response rates between older adult and non-older adult patients in a TRD clinic in Atlanta, Georgia with depressive symptoms as the primary outcome and anxiety symptoms as the secondary outcome.Methods:This retrospective chart review of patients who received rTMS between March 2017 to June 2022 used descriptive statistics to compare treatment parameters and dropout rates between older adult and non-older adult patients. A 2 x 3 repeated-measures analysis of variance (ANOVA) analyzed changes in self-reported depression and anxiety symptom severity throughout treatment course (baseline, treatment midpoint, and final treatment) between the two groups.Results:Eighty-nine patients were included for analysis: Group 1: >55 years old (n= 42; M= 66.48, sd= 6.16; 71% female), and Group 2: <55 years old (n = 47; M= 37.40, sd= 9.13; 60% female). All patients received at least 3000 pulses per session, with 85.71% of patients completing the FDA protocol in Group 1 and 85.11% of patients completing in Group 2. A >50% improvement in depression scores at the end of treatment were seen in 38.1% of patients in Group 1 and 31.9% of patients in Group 2. Both groups demonstrated significant within-group reductions of depression throughout treatment (ps < .001). A smaller subset of patients completed an anxiety questionnaire. Forty percent in Group 1 (n=24) and 33.3% in Group 2 (n=25) showed a >50% improvement in anxiety scores by end of treatment. Both groups demonstrated significant within-group reductions of anxiety throughout treatment (ps < .001). The between groups’ difference for change in depression and anxiety scores was not statistically significant.Conclusion:With FDA protocol dosing, older and non-older patients have consistent response and tolerability. While overall response rates were slightly lower than reported standardized clinical trials, our real-world sample highlights the effectiveness of rTMS for patients, including adults over 55, treated in an unselected, naturalistic outpatient sample.

Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) Combined with Psychological Interventions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

(1) Background: Psychological interventions are effective in alleviating neuropsychiatric symptoms, though results can vary between patients. Repetitive transcranial magnetic stimulation (rTMS) has been proven to improve clinical symptoms and cognition. It remains unclear whether rTMS can augment the efficacy of psychological interventions. (2) Methods: We examined the effects of rTMS combined with psychological interventions on clinical, functional, and cognitive outcomes from randomized controlled trials conducted in healthy and clinical populations. We searched PubMed, EMBASE, Cochrane Library, and PsycINFO databases up to April 2023. (3) Results: Twenty-seven studies were ultimately included. Compared to sham rTMS combined with psychological interventions, active rTMS combined with psychological interventions significantly improved overall clinical symptoms (k = 16, SMD = 0.31, CIs 0.08 to 0.54, p < 0.01). We found that 10 or more sessions of rTMS combined with cognitive behavioural therapy significantly improved clinical outcomes overall (k = 3, SMD = 0.21, CIs 0.05 to 0.36, Z = 2.49, p < 0.01). RTMS combined with cognitive training (CT) significantly improved cognition overall compared to sham rTMS combined with CT (k = 13, SMD = 0.28, CIs 0.15 to 0.42, p < 0.01), with a significant effect on global cognition (k = 11, SMD = 0.45, CIs 0.21 to 0.68, p < 0.01), but not on the other cognitive domains. (4) Conclusion: The current results provide preliminary support for the augmentation effects of active rTMS on clinical and cognitive outcomes across diverse populations. Future clinical trials are required to confirm these augmentation effects for specific psychological interventions in specific clinical populations.

Case Report: Effect of rTMS on urinary incontinence in major vascular neurocognitive disorder

Background: Many efforts had been made to combat the symptoms of incontinence over the past decades, yet difficulties still remain. To stimulate the cortical urination center might theoretically be useful for regulating urination process. In this case of urinary incontinence with major vascular neurocognitive disorder, repetitive transcranial magnetic stimulation (rTMS) on the bilateral paracentral lobule was applied and therapeutic effect was obvious. Case report: A 67-year-old female farmer suffered from urinary incontinence over two weeks. She was diagnosed with major vascular neurocognitive disorder. The patient received rTMS on the bilateral paracentral lobule. Stimulation was administered at 20 Hz with 25 stimulation trains of 30 stimuli each with a 30-second intertrain interval. After a 5-day course of rTMS intervention, the patient reported full awareness of her urination, but her neurocognitive decline had not improved at all. Conclusions: rTMS on bilateral paracentral lobule could be used for treating urinary incontinence in major vascular neurocognitive disorder patients.

A posterior-alpha ageing network is differentially associated with antidepressant effects of venlafaxine and rTMS

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, but chances for remission largely decrease with each failed treatment attempt. It is therefore desirable to assign a given patient to the most promising individual treatment option as early as possible. We used a polygenic score (PGS) informed electroencephalography (EEG) data-driven approach to identify potential predictors for MDD treatment outcome. Post-hoc we conducted exploratory analyses in order to understand the results in depth. First, an EEG independent component analysis produced 54 functional brain networks in a large heterogeneous cohort of psychiatric patients (n = 4,045; 5–84 yrs.). Next, the network that was associated to PGS for antidepressant-response (PRS-AR) in an independent sample (n = 722) was selected: an age-related posterior alpha network that explained >60 % of EEG variance, and was highly stable over recording time. Translational analyses were performed in two other independent datasets to examine if the network was predictive of psychopharmacotherapy (n = 535) and/or repetitive transcranial magnetic stimulation (rTMS) and concomitant psychotherapy (PT; n = 186) outcome. The network predicted remission to venlafaxine (p = 0.015), resulting in a normalized positive predicted value (nPPV) of 138 %, and rTMS + PT – but in opposite direction for women (p = 0.002) relative to men (p = 0.018) – yielding a nPPV of 131 %. Blinded out-of-sample validations for venlafaxine (n = 29) and rTMS + PT (n = 36) confirmed the findings for venlafaxine, while results for rTMS + PT could not be replicated. These data suggest the existence of a relatively stable EEG posterior alpha aging network related to PGS-AR that has potential as MDD treatment predictor.

RTMS regulates homotopic functional connectivity in the SCD and MCI patients

ObjectiveImpaired interhemispheric connectivity and corpus callosum atrophy have been linked to cognitive impairment in Alzheimer’s disease (AD). Existing evidence indicates that repetitive transcranial magnetic stimulation (rTMS) targeting the bilateral precuneus may enhance cognitive function in AD. This study aims to investigate the effects of precuneus rTMS on cognitive function, as well as alterations in interhemispheric functional connectivity (FC) and its structural basis in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI).MethodsA total of 14 patients with SCD and 16 patients with MCI were enrolled in this study and received 10 Hz rTMS intervention on the bilateral precuneus for 2 weeks. Neurocognitive scales, structural and functional magnetic resonance imaging were collected at enrollment and after the rTMS intervention. Interhemispheric FC was assessed using mirror homotopic functional connectivity (VMHC), while the structural equation modeling (SEM) was employed to analyze the relationship between corpus callosum volume, interhemispheric connectivity, and cognitive function after rTMS intervention.ResultsThe precuneus rTMS not only enhanced episodic memory in SCD, but also improved multiple cognitive domains in MCI. Post-rTMS intervention, decreased VMHC values in the lingual cortex, middle occipital gyrus, putamen, and fusiform gyrus were observed in SCD, and an increased VMHC value in the postcentral gyrus along with reduced VMHC value in the cerebellum and putamen in MCI. After intervention, more brain regions show decreased FC in SCD and MCI patients, suggesting that precuneus rTMS may protect cerebral cortical plasticity by reducing excessive functional compensation, and thus improve cognitive function. The SEM indicated that the corpus callosum serves as the structural foundation for rTMS regulation of interhemispheric FC to further improve cognitive function.Conclusion10 Hz rTMS in the bilateral precuneus could be a promising strategy to improve cognitive function in patients with SCD and MCI. Our study implies that improvements in cognition brought about by precuneus rTMS may result from the remodeling of interhemispheric FC, with the corpus callosum possibly acting as the anatomical basis for functional modulation.

Repetitive transcranial magnetic stimulation (rTMS) triggers dose-dependent homeostatic rewiring in recurrent neuronal networks.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to induce neuronal plasticity in healthy individuals and patients. Designing effective and reproducible rTMS protocols poses a major challenge in the field as the underlying biomechanisms of long-term effects remain elusive. Current clinical protocol designs are often based on studies reporting rTMS-induced long-term potentiation or depression of synaptic transmission. Herein, we employed computational modeling to explore the effects of rTMS on long-term structural plasticity and changes in network connectivity. We simulated a recurrent neuronal network with homeostatic structural plasticity among excitatory neurons, and demonstrated that this mechanism was sensitive to specific parameters of the stimulation protocol (i.e., frequency, intensity, and duration of stimulation). Particularly, the feedback-inhibition initiated by network stimulation influenced the net stimulation outcome and hindered the rTMS-induced structural reorganization, highlighting the role of inhibitory networks. These findings suggest a novel mechanism for the lasting effects of rTMS, i.e., rTMS-induced homeostatic structural plasticity, and highlight the importance of network inhibition in careful protocol design, standardization, and optimization of stimulation.

Comparing the effectiveness of CBT and low-frequency rTMS in reducing symptom severity and depression and improving working memory in adults with OCD: a clinical trial

Objective This study aims to compare the effectiveness of cognitive-behavioral therapy (CBT) and low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) in reducing symptom severity and depression and improving working memory in adults with obsessive–compulsive disorder (OCD). Methods This is a randomized clinical trial conducted on 24 adults with OCD, randomly assigned into two groups of CBT (n = 12, received CBT with exposure and response prevention (ERP) individually at 20 sessions) and rTMS (n = 12, received LF (1-Hz) rTMS over the right dorsolateral prefrontal cortex (DLPFC) at 10 sessions). They completed the Yale-Brown Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, and two N-Back tasks before, immediately, and 1 month after interventions. Results Results showed a significant difference between the two methods in reducing the severity of OCD symptoms (p < 0.05) and depression (p = 0.002) immediately after interventions where the CBT with ERP was more effective, but no significant difference was found in terms of working memory (p > 0.05). No significant difference was found between groups in any study variables 1 month after interventions. Conclusion Individual CBT with ERP is superior to LF rTMS for reducing the severity of symptoms and depression in OCD patients. However, there is no difference between them in improving working memory.

Continuous high-frequency repetitive transcranial magnetic stimulation at extremely low intensity affects exploratory behavior and spatial cognition in mice

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

Memory-related hippocampal brain-derived neurotrophic factor activation pathways from repetitive transcranial magnetic stimulation in the 3xTg-AD mouse line

Alzheimer's disease is associated with a loss of plasticity and cognitive functioning. Previous research has shown that repetitive transcranial magnetic stimulation (rTMS) boosts cortical neurotrophic factors, potentially addressing this loss. The current study aimed to expand these findings by measuring brain-derived neurotrophic factor (BDNF), its downstream hippocampal signaling molecules, and behavioral effects of rTMS on the 3xTg-AD mouse line. 3xTg-AD (n = 24) and B6 wild-type controls (n = 26), aged 12 months, were given 14 days of consecutive rTMS at 10 Hz for 10 min. Following treatment, mice underwent a battery of behavioral tests and biochemical analysis of BDNF and its downstream cascades were evaluated via Western blot and ELISA. Results showed that brain stimulation did improve performance on the Object Place Task and increased hippocampal TrkB, ERK, and PLCγ in 3xTg-AD mice with minimal effects on wild-type mice. There was no significant difference in the levels of AKT and Truncated TrkB (TrkB.T1) between treatment and sham. Thus, rTMS has the potential to provide an efficacious non-invasive therapy for the treatment of Alzheimer's disease through activation of neurotrophic factor signaling.

73 Sleep Onset Latency and Duration in rTMS Treatment in Veterans with Treatment-Resistant Major Depressive Disorder

Objective:This study builds on the work by Rehman et al (2022) who argued that transcranial magnetic stimulation (TMS) treatment not only helps treat depression but also decreases sleep problems such as difficulty falling asleep,staying asleep, and waking too early. The present study further explores differences in sleep onset latency, meaning the time it takes to fall asleep, and duration of sleep per night in the pre and post treatment phases of rTMS. The information regarding major attributes of sleep is critical because recent research shows that about 90% of patients with major depressive disorder (MDD) also struggle with sleep disorders (Li et al., 2022), and sleeping for less than seven hours may eventually lead to sleep deprivation (Hirshkowitz et al., 2015), with increased risk of physical and mental health problems (Sheehan et al, 2019). Sleep onset latency estimates vary from individual to individual but typical sleep latency is considered between 10 to 20 minutes (Jung et al, 2013). As it has been shown that overall sleep problems improve with rTMS, we hypothesized that self-reported sleep onset latency will decrease, and sleep duration will increase.Participants and Methods:All participants met inclusion criteria for MDD diagnosis and completed a full course of TMS treatment (N=470; Mean age=53.45, SD=13.73). The sample was mostly male (81%) and ethnically diverse: 77.7% non-Hispanic White, 13.3% Black Americans, 1.9% Asian, 0.2 % Asian Indian, and 1.9% other ethnicities. Sleep problems were assessed using the following questions at the pre and post treatment stages: the number of minutes it takes to fall asleep and duration of sleep each night.Results:A Wilcoxon matched-pairs signed-rank test was conducted to determine whether there was a difference in sleep onset latency and hours of sleep per night between pre and post intervention. The results indicated a significant difference in time to fall asleep between pre and post treatment (pre-treatment M = 1.19, SD = 0.99, post-treatment M = 0.93, SD = 0.91; z = -5.01, p &lt; .001. In addition, there was a significant increase in the minutes of sleep per night in pre (M = 6.11, SD = 2.07) compared to the post treatment (M = 6.32, SD = 1.77), z = -2.56, p = .010.Conclusions:Reduced sleep is known to negatively impact mood, cognitive ability, work performance, and immune function (Besedovsky et al., 2012; Killgore, 2010; Massar et al, 2019; Vandekerckhove &amp; Wang, 2018). Similarly, longer sleep onset latency can cause an individual to enter the first sleep stage later than expected and complete fewer sleep cycles. The results of the present study show the effectiveness of rTMS in decreasing sleep onset latency and increasing the duration of sleep. Given the comorbidity and bidirectionality between sleep disturbances and mood disorders (Fang et al., 2019; Palagini et al., 2019), further researching treatments such as rTMS to improve sleep as a means to also improve mood is crucial. We propose acquiring knowledge about sleep attributes as an essential part of clinicians’ work early on in the rTMS treatment in order to monitor an individual’s global functioning level in light of improved sleep.