rTMS Protocol Research Articles

Effect of high frequency repetitive transcranial magnetic stimulation (rTMS) on the balance and the white matter integrity in patients with relapsing-remitting multiple sclerosis: A long-term follow-up study

ObjectivesRepetitive Transcranial Magnetic Stimulation (rTMS) is considered as a safe and non-invasive developing technique used as a therapeutic method for patients with Relapsing-Remitting Multiple Sclerosis (RRMS) who suffer from disturbances in gait and balance. The aim of our study is to evaluate the long-term effect of high frequency rTMS as a therapeutic option for truncal ataxia in RRMS patients and to assess its impact on the integrity of the white matter (WMI), measured in the form of anisotropy metrics using diffusion tensor imaging (DTI). MethodsThe study was conducted in two phases: phase I; a randomized, single-blind, sham-controlled phase and phase II was a 12 months longitudinal open-label prospective phase. Phase I of the trial involved the randomization of 43 patients with RRMS and truncal ataxia to either real (n = 20) or sham (n = 19) rTMS (2 participants from each treatment group were excluded from the study; one developed a relapse before treatment, 2 declined to participate, and one did not show up). Phase II involved providing 12 actual treatments cycles to all patients; each cycle length is 4 weeks, repeated four times on a trimonthly basis, forming a total of 48 sessions. DTI was used for assessment of the WMI. All patients performed DTI 3 times: Imaging sessions were conducted at the screening visit, at the end of phase I, and after the last session in phase II for the first, second and third sessions respectively. A figure-of-8-shape coil, employing rTMS protocol and located over the cerebellum, was used. rTMS protocol is formed of 20 trains formed of 50 stimuli with 20 s apart (5 Hz of 80 % of resting Motor Threshold “MT”). The Berg Balance Scale (BBS), Time up and go (TUG) test, and 10-m walk test (10MWT) were first evaluated at the start of each cycle and just after the final rTMS session. ResultsThe genuine rTMS group's 10MWT, TUG, and BBS showed substantial improvement (p < 0.01), which is continued to be improved throughout the study Timeline, with a significant difference observed following the final rTMS session (P< 0.001). A longitudinal increase in FA was observed in both the Cerebello-Thalamo-Cortical (CTC) and Cortico-Ponto-Cerebellar (CPC) bilateral, as indicated by means of Fractional Anisotropy (FA) measures (p < 0.05). ConclusionIn ataxic RRMS patients, high frequency rTMS over the cerebellum has a long-term beneficial impact on both balance and WMI.

Efficacy test for intermittent theta burst stimulation during motor rehabilitation in patients post‐stroke in a tertiary centre in Hong Kong

AbstractAimStroke represents a significant cause of long‐term disability in adults. Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive brain stimulation method known for its potential to enhance motor recovery. Intermittent theta burst stimulation (iTBS), a standardised rTMS protocol initially utilised in patients with depression, has garnered attention in the realm of stroke rehabilitation. This study seeks to establish the efficacy profile of iTBS in motor rehabilitation for patients with subacute or chronic stroke.Patients and methodsThis study is a prospective cohort trial in which eligible patients with stroke were recruited into the iTBS group. Ten sessions of iTBS were conducted, followed by physiotherapy. An equal number of matched controls were recruited into the conventional physiotherapy group. The differences in various scoring systems related to motor performance at 6 months were analysed using independent two‐sample t test.ResultsForty patients were enrolled in the study. At 6 months, iTBS demonstrated a statistically significant improvement compared with conventional physiotherapy across various scoring systems, including motor power grading (47.4% vs 0%, P &lt; .0001), Upper Extremity Fugl–Meyer Assessment (19.8% vs 0.7%, P &lt; .0001), Box and Block Test (25.6% vs 1.7%, P = .007) and Barthel Index (17.8% vs 0.1%, P = .0002). No major adverse events were reported in the iTBS group at 6 months.ConclusioniTBS resulted in significant improvement in motor performance across various domains at 6 months compared with conventional physiotherapy alone. This method proves to be a safe approach for motor rehabilitation.

Effects of a periodic intermittent theta burst stimulation in Alzheimer’s disease

BackgroundPrevious studies have demonstrated that excitatory repetitive transcranial magnetic stimulation (rTMS) can improve the cognitive function of patients with Alzheimer’s disease (AD). Intermittent theta burst stimulation (iTBS) is a novel...

Repetitive Transcranial Magnetic Stimulation (rTMS) in Major Depression.

Major depressive disorder (MDD) is a psychiatric disorder with several effective therapeutic approaches, being antidepressants and psychotherapies the first-line treatments. Nonetheless, due to side effects, limited efficacy, and contraindications for these treatments, alternative treatment options are required. Neurostimulation is a non-pharmacological and non-psychotherapeutic approach that has been under study for diverse neuropsychiatric conditions in the form of electrical or magnetic stimulation of the brain. Repetitive transcranial magnetic stimulation (rTMS) is a neurostimulation method designed to generate magnetic fields and deliver magnetic pulses to stimulate the brain cortex. The magnetic pulses produce electrical currents in the brain which are not intense enough to provoke seizures, differentiating this method from other forms of neurostimulation that produce seizures. Although the exact rTMS mechanisms of action are not completely understood, rTMS seems to cause its beneficial effects through changes in neuroplasticity. Devices and protocols for rTMS are still evolving, becoming more efficient over time. There are still some challenges to be addressed, including further refinement of parameters (coil/device type, location, intensity, frequency, number of sessions, and duration of treatment); treatment cost and burden for patients; and treatment resistance. However, the efficacy, tolerability, and safety of some rTMS protocols have been demonstrated in different double-blind sham-controlled randomized controlled trials and meta-analyses for treatment-resistant depression.

Bilateral rTMS Shows No Advantage in Depression nor in Comorbid Depression and Anxiety: A Naturalistic Study.

The objective was to determine if adding low-frequency right-sided rTMS treatment to the standard high-frequency left-sided treatment (LUL), referred to as sequential bilateral treatment (SBT), confers additional benefit for depression or anxiety outcomes. A retrospective chart review from January 2015 through December 2018 yielded 275 patients, all of whom were treated with a figure-8 coil for a major depressive episode. Their protocol was either LUL or SBL. Outcome measures were the Generalized Anxiety Disorder 7-item scale (GAD-7) and the Patient Health Questionnaire (PHQ-9). There was no significant difference in GAD-7 change scores between patients who had LUL or SBL (4.2 vs 4.8). This was also true when the sample was restricted to only patients who started with high GAD-7 scores. There was likewise no significant difference in PHQ-9 change scores between patients who had LUL or SBL (6.8 vs 5.1). Patients switching from LUL to SBL mid-course had poorer overall outcomes as compared to patients who stayed with the same protocol throughout treatment. This large naturalistic study shows no advantage for SBL treatment any group or condition examined. The results of this study have clinical applicability and sound a cautionary note regarding the use of combination rTMS protocols.

Time perception in stimulant-dependent participants undergoing repetitive transcranial magnetic stimulation

BackgroundThe dopaminergic (DA) system is an important neural system for the modulation of time perception and the timing of motor actions. Dysregulation of the DA system is related to chronic use of stimulant drugs, which lead, among others, to executive dysfunctions. Little is known instead about the potential deficiencies in temporal processing of stimulant-dependent individuals. The present study aimed to investigate temporal processing using a time bisection task with different temporal intervals in chronic cocaine users undergoing repetitive transcranial magnetic stimulation (rTMS). MethodStudy 1: A time bisection task with short temporal intervals range (480/1920 ms) was administered to 18 cocaine use disorder (CocUD) patients and 20 healthy control before and after the intensive phase of rTMS treatment (5 days apart). Study 2: 22 CocUD participants and 23 control participants completed two temporal tasks (time bisection and time reproduction) with long temporal intervals range (1200/2640 ms) at baseline and immediately after the intensive phase of rTMS treatment. ResultsStudy 1: A shift in the psychometric function consistent with temporal overestimation in CocUD patients compared to controls was observed. However, no temporal impairment in CocUD patients at test session was found. Study 2: The analysis of temporal variability indices showed a significant difference between groups at baseline but not at Day 5 due to a significant difference between time points only in the CocUD group. ConclusionsThis study report a temporal overestimation in CocUD patients and a temporal variability reduction after an rTMS protocol in CocUD patients.

Repetitive transcranial magnetic stimulation (rTMS) as a tool for cognitive enhancement in healthy adults: a review study.

As human beings, we have always sought to expand on our abilities, including our cognitive and motor skills. One of the still-underrated tools employed to this end is repetitive transcranial magnetic stimulation (rTMS). Until recently, rTMS was almost exclusively used in studies with rehabilitation purposes. Only a small strand of literature has focused on the application of rTMS on healthy people with the aim of enhancing cognitive abilities such as decision-making, working memory, attention, source memory, cognitive control, learning, computational speed, risk-taking, and impulsive behaviors. It, therefore, seems that the findings in this particular field are the indirect results of rehabilitation research. In this review paper, we have set to investigate such studies and evaluate the rTMS effectuality in terms of how it improves the cognitive skills in healthy subjects. Furthermore, since the most common brain site used for rTMS protocols is the dorsolateral prefrontal cortex (DLPFC), we have added theta burst stimulation (TBS) wave patterns that are similar to brain patterns to increase the effectiveness of this method. The results of this study can help people who have high-risk jobs including firefighters, surgeons, and military officers with their job performance.

EEG microstates as a “real time” feedback for rTMS treatment efficacy in MCI subjects

AbstractBackgroundNew treatments for the Alzheimer’s disease (AD) are evolving. There is a need for cheap, immediate and available treatment feedback biomarker which can demonstrate rapidly treatment success/failure. We used EEG microstates for this purpose while using repetitive Trans Magnetic stimulation (rTMS) treatment. Four types of microstates are identified according to EEG topography. They are characterized by their duration, frequent appearance and the transitions among the different microstates. The possibility of using microstates properties as a biomarker for rTMS treatment efficacy in mild cognitive impairment (MCI) subjects was explored.MethodsWe recruited 14 MCI subject to receive 16 rTMS sessions. EEG microstates were analyzed immediately before and after each treatment. We used 3 rTMS predefined protocols. The preferred protocol, for each patient, was selected using microstates duration. All patients performed a comprehensive neuro‐cognitive evaluation before rTMS treatment. 11 subjects completed a second neuro‐cognitive evaluation after treatment period ended.ResultsMicrostates duration change was noticed before and after each rTMS treatment. Duration variation aided deciding which rTMS protocol is preferred in all participants. Moreover, new rTMS protocol was designed, for 3 patients, using microstates parameters. Cognitive performance was associated with microstate duration (p&lt;0.05).ConclusionsMicrostates duration may serve as a “real time” treatment efficacy biomarker for MCI subjects. Further work should be done in order to validate this method.

Determining the Optimal Stimulation Sessions for TMS-Induced Recovery of Upper Extremity Motor Function Post Stroke: A Randomized Controlled Trial.

To find out the optimal treatment sessions of repetitive transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) for upper extremity dysfunction after stroke during the 6-week treatment and to explore its mechanism using motor-evoked potentials (MEPs) and resting-state functional magnetic resonance imaging (rs-fMRI), 72 participants with upper extremity motor dysfunction after ischemic stroke were randomly divided into the control group, 10-session, 20-session, and 30-session rTMS groups. Low-frequency (1 Hz) rTMS over the contralesional M1 was applied in all rTMS groups. The motor function of the upper extremity was assessed before and after treatment. In addition, MEPs and rs-fMRI data were analyzed to detect its effect on brain reorganization. After 6 weeks of treatment, there were significant differences in the Fugl-Meyer Assessment of the upper extremity and the Wolf Motor Function Test scores between the 10-session group and the 30-session group and between the 20- and 30-session groups and the control group, while there was no significant difference between the 20-session group and the 30-session group. Meanwhile, no significant difference was found between the 10-session group and the control group. The 20-session group of rTMS decreased the excitability of the contralesional corticospinal tract represented by the amplitudes of MEPs and enhanced the functional connectivity of the ipsilesional M1 or premotor cortex with the the precentral gyrus, postcentral gyrus, and cingulate gyrus, etc. In conclusion, the 20-session of rTMS protocol is the optimal treatment sessions of TMS for upper extremity dysfunction after stroke during the 6-week treatment. The potential mechanism is related to its influence on the excitability of the corticospinal tract and the remodeling of corticomotor functional networks.

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.

Somatosensory evoked potentials amplitude is enhanced after non-invasive brain stimulation in chronic ischemic stroke: Preliminary results from a randomised control trial

ObjectiveTo investigate the effects of transcranial electrical and magnetic non-invasive brain stimulation (NIBS) protocols on somatosensory evoked potential (SEP) in chronic ischemic stroke. Methods33 patients were randomly assigned to one of the four treatment groups of the transcranial direct current stimulation (tDCS) and/or repetitive transcranial magnetic stimulation (rTMS) protocol. SEP parameters were recorded before and after ten days of the treatment session. All the statistical analyses were carried out using SPSS version 19. ResultsIt was found that there is a statistically significant improvement in the N20-P22 mean amplitude after treatment sessions in all groups except the group where tDCS and rTMS groups were sham. On paired t-tests, the difference betweeen post and pre-stimulation SEP amplitudes for the real tDCS and real rTMS coupled group was 1.045 ± 0.732 (p value = 0.005). For sham tDCS+real rTMS group, 1.05 ± 0.96 (P = 0.04); for real tDCS+sham rTMS 0.543 ± 0.332 (P = 0.01) and for double sham stimulation, 0.204 ± 0.648 (P = 0.4) respectively ConclusionIn ischemic stroke patients, either or coupled true transcranial tDCS and rTMS was found to be safe and significantly enhanced the amplitude of cortical somatosensory potentials when combined with standard physiotherapy, in the interim analysis of an ongoing randomised controlled trial. Clinical Trial Registry of IndiaCTRI/2019/11/022009 SignificanceThe results of this research indicates the importance of RCTs in developing robust improved NIBS protocols coupled to physiotherapy to enhance the sensory-motor functional recovery following ischemic stroke.

The Effects of Exercise on Synaptic Plasticity in Individuals With Mild Cognitive Impairment: Protocol for a Pilot Intervention Study.

Mild cognitive impairment (MCI) is a syndrome preceding more severe impairment characterized by dementia. MCI affects an estimated 15% to 20% of people older than 65 years. Nonpharmacological interventions including exercise are recommended as part of overall MCI management based on the positive effects of exercise on cognitive performance. Interval training involves brief intermittent bouts of exercise interspersed with short recovery periods. This type of exercise promotes cognitive improvement and can be performed in individuals with MCI. Synaptic plasticity can be assessed in vivo by the neurophysiological response to repetitive transcranial magnetic stimulation (rTMS). A method to assess synaptic plasticity uses an intermittent theta burst stimulation (iTBS), which is a patterned form of rTMS. Individuals with MCI have decreased responses to iTBS, reflecting reduced synaptic plasticity. It is unknown whether interval training causes changes in synaptic plasticity in individuals living with MCI. This research will determine whether interval training performed using a cycle ergometer enhances synaptic plasticity in individuals with MCI. The three aims are to (1) quantify synaptic plasticity after interval training performed at a self-determined intensity in individuals with MCI; (2) determine whether changes in synaptic plasticity correlate with changes in serum brain-derived neurotrophic factor, osteocalcin, and cognition; and (3) assess participant compliance to the exercise schedule. 24 individuals diagnosed with MCI will be recruited for assignment to 1 of the 2 equally sized groups: exercise and no exercise. The exercise group will perform exercise 3 times per week for 4 weeks. Synaptic plasticity will be measured before and following the 4-week intervention. At these time points, synaptic plasticity will be measured as the response to single-pulse TMS, reflected as the percent change in the average amplitude of 20 motor-evoked potentials before and after an iTBS rTMS protocol, which is used to induce synaptic plasticity. In addition, individuals will complete a battery of cognitive assessments and provide a blood sample from the antecubital vein to determine serum brain-derived neurotrophic factor and osteocalcin. The study began in September 2023. The proposed research is the first to assess whether synaptic plasticity is enhanced after exercise training in individuals with MCI. If exercise does indeed modify synaptic plasticity, this will create a new avenue by which we can study and manipulate neural plasticity in these individuals. ClinicalTrials.gov NCT05663918; https://clinicaltrials.gov/study/NCT05663918. PRR1-10.2196/50030.

Pretreatment pupillary reactivity is associated with differential early response to 10 Hz and intermittent theta-burst repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD)

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD). Two common rTMS protocols, 10 Hz and intermittent theta burst stimulation (iTBS), have comparable rates of efficacy in groups of patients. Recent evidence suggests that some individuals may be more likely to benefit from one form of stimulation than the other. The pretreatment pupillary light reflex (PLR) is significantly associated with response to a full course of rTMS using heterogeneous stimulation protocols. ObjectiveTo test whether the relationship between pretreatment PLR and early symptom improvement differed between subjects treated with iTBS or 10 Hz stimulation. MethodsPLR was measured in 52 subjects who received solely 10 Hz (n = 35) or iTBS (n = 17) to left dorsolateral prefrontal cortex (DLPFC) for the first ten sessions of their treatment course. Primary outcome measure was the percent change of Inventory of Depressive Symptomatology – Self Report (IDS-SR) from session 1 to session 10. ResultsThere was a positive association between normalized maximum constriction velocity (nMCV) and early improvement in subjects receiving 10 Hz stimulation (R = 0.48, p = 0.004) and a negative association in subjects receiving iTBS (R = −0.52, p = 0.03). ANOVA revealed a significant interaction between nMCV and the type of initial stimulation (p = 0.001). Among subjects with low nMCV, those initially treated with iTBS showed 2.6 times greater improvement after 10 sessions (p = 0.01) than subjects initially receiving 10 Hz stimulation. ConclusionnMCV may detect physiologic differences between those likely to benefit from 10 Hz or iTBS treatment. Future studies should examine whether PLR could guide prospective treatment selection.

Modulating Visuomotor Sequence Learning by Repetitive Transcranial Magnetic Stimulation: What Do We Know So Far?

Predictive processes and numerous cognitive, motor, and social skills depend heavily on sequence learning. The visuomotor Serial Reaction Time Task (SRTT) can measure this fundamental cognitive process. To comprehend the neural underpinnings of the SRTT, non-invasive brain stimulation stands out as one of the most effective methodologies. Nevertheless, a systematic list of considerations for the design of such interventional studies is currently lacking. To address this gap, this review aimed to investigate whether repetitive transcranial magnetic stimulation (rTMS) is a viable method of modulating visuomotor sequence learning and to identify the factors that mediate its efficacy. We systematically analyzed the eligible records (n = 17) that attempted to modulate the performance of the SRTT with rTMS. The purpose of the analysis was to determine how the following factors affected SRTT performance: (1) stimulated brain regions, (2) rTMS protocols, (3) stimulated hemisphere, (4) timing of the stimulation, (5) SRTT sequence properties, and (6) other methodological features. The primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC) were found to be the most promising stimulation targets. Low-frequency protocols over M1 usually weaken performance, but the results are less consistent for the DLPFC. This review provides a comprehensive discussion about the behavioral effects of six factors that are crucial in designing future studies to modulate sequence learning with rTMS. Future studies may preferentially and synergistically combine functional neuroimaging with rTMS to adequately link the rTMS-induced network effects with behavioral findings, which are crucial to develop a unified cognitive model of visuomotor sequence learning.

Repetitive transcranial magnetic stimulation implementation within residential substance use disorder treatment centers for patients with comorbid depression

PurposeRepetitive transcranial magnetic stimulation (rTMS) is a well-established treatment with efficacy for several psychiatric disorders and has yielded promising yet mixed data showing reductions in craving for substance use. Patients with substance use disorders and comorbid depression may encounter obstacles to receiving rTMS in outpatient settings for treatment of depression. In turn, implementation of rTMS in residential substance use programs would greatly benefit those with comorbid treatment resistant depression. This paper aims to provide recommendations for implementing rTMS within residential substance use treatment centers.Design/methodology/approachUsing PubMed, the authors conducted a narrative review of manuscripts using various combinations of the following search terms: rTMS, depression, substance use and substance use disorder. The authors read manuscripts for their methodology, outcomes and adverse events to synthesize their results, which correspond to their recommendations for patient selection, safely implementing rTMS in residential substance use facilities and optimal rTMS protocols to start with.FindingsAdvantages of this approach include increased compliance, monitoring and access to care. Recommendations to safely incorporate rTMS in residential substance use disorder treatment centers revolve around selection of patients eligible for rTMS, allowing for sufficient time to elapse prior to commencing rTMS, monitoring for signs of recent substance use or withdrawal and using rTMS protocols compatible with the therapeutic programming of a treatment center.Originality/valueThis paper details the challenges and benefits of implementing rTMS for patients with dual diagnosis and provides recommendations to safely do so. To the best of the authors’ knowledge, this is a novel and unpublished endeavor.

After-effects of repetitive transcranial magnetic stimulation with parameter dependence on long-term potentiation-like plasticity and object recognition memory in rats.

To investigate the after-effects of 25-Hz repetitive transcranial magnetic stimulation (rTMS) at 60, 100, and 120% resting motor threshold (rMT) on long-term potentiation (LTP) in the rat hippocampus, to clarify the intensity dependence of rTMS, and to determine whether it simultaneously affects learning and memory ability. Five rats were randomly selected from 70 male Wistar rats, and evoked rMT potentials were recorded in response to magnetic stimulation. The remaining 65 rats were randomly assigned to five groups (n = 13), including sham rTMS, 1 Hz 100% rMT, and 25 Hz rTMS groups with 3 subgroups of 60% rMT, 100% rMT, and 120% rMT. Five rats in each group were anesthetized and induced by a priming TMS-test design for population spike (PS) response of the perforant path-dentate gyrus in the hippocampus; the remaining eight rats in each group were evaluated for object recognition memory in the novel object recognition (NOR) task after the different rTMS protocols. Forty-five percent (approximately 1.03 T) of the magnetic stimulator output was confirmed as rMT in the biceps femoris muscle. The PS ratio was ranked as follows: 25 Hz 100% rMT (267.78 ± 25.71%) > sham rTMS (182 ± 9.4%) >1 Hz 100% rMT (102.69 ± 6.64%) > 25 Hz 120% rMT (98 ± 11.3%) > 25 Hz 60% rMT (36 ± 8.5%). Significant differences were observed between the groups, except for the difference between the 25 Hz 120% rMT and the 1 Hz 100% rMT groups (p = 0.446). LTP was successfully induced over the 60-min recording period only in the sham rTMS and 25 Hz 100% rMT groups. Moreover, these two groups spent more time exploring a novel object than a familiar object during the NOR task (p < 0.001), suggesting long-term recognition memory retention. In the between-group analysis of the discrimination index, the following ranking was observed: 25 Hz 100% rMT (0.812 ± 0.158) > sham rTMS (0.653 ± 0.111) > 25 Hz 120% rMT (0.583 ± 0.216) >1 Hz 100% rMT (0.581 ± 0.145) > 25 Hz 60% rMT (0.532 ± 0.220). The after-effect of 25-Hz rTMS was dependent on stimulus intensity and provided an inverted (V-shaped) bidirectional modulation on hippocampal plasticity that involved two forms of metaplasticity. Furthermore, the effects on the recognition memory ability were positively correlated with those on LTP induction in the hippocampus in vivo.

An Evaluation of the Effectiveness of Repetitive Transcranial Magnetic Stimulation (rTMS) for the Management of Treatment-Resistant Depression with Somatic Attributes: A Hospital-Based Study in Oman.

Depressive illnesses in non-Western societies are often masked by somatic attributes that are sometimes impervious to pharmacological agents. This study explores the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for people experiencing treatment-resistant depression (TRD) accompanied by physical symptoms. Data were obtained from a prospective study conducted among patients with TRD and some somatic manifestations who underwent 20 sessions of rTMS intervention from January to June 2020. The Hamilton Rating Scale for Depression (HAMD) was used for clinical evaluation. Data were analysed using descriptive and inferential techniques (multiple logistic regression) in SPSS. Among the 49 participants (mean age: 42.5 ± 13.3), there was a significant reduction in posttreatment HAMD scores compared to baseline (t = 10.819, p < 0.0001, and 95% CI = 8.574-12.488), indicating a clinical response. Approximately 37% of the patients responded to treatment, with higher response rates among men and those who remained in urban areas, had a history of alcohol use, and were subjected to the standard 10 HZ protocol. After adjusting for all extraneous variables, the rTMS protocol emerged as the only significant predictor of response to the rTMS intervention. To our knowledge, this is the first study to examine the effectiveness of rTMS in the treatment of somatic depression.

A randomized trial comparing beam F3 and 5.5 cm targeting in rTMS treatment of depression demonstrates similar effectiveness

BackgroundThe Beam F3 and 5.5 cm methods are the two most common targeting strategies for localizing the left dorsolateral prefrontal cortex (DLPFC) treatment site in repetitive transcranial magnetic stimulation (rTMS) protocols. This prospective, randomized, double-blind comparative effectiveness trial assesses the clinical outcomes for these two methods in a naturalistic sample of patients with major depressive disorder (MDD) undergoing clinical rTMS treatment. Methods105 adult patients with MDD (mean age = 43.2; range = 18–73; 66% female) were randomized to receive rTMS to the Beam F3 (n = 58) or 5.5 cm (n = 47) target. Between group differences from pre-to post-treatment were evaluated with the Patient Health Questionnaire-9 (PHQ-9) [primary outcome measure], Generalized Anxiety Disorder-7 (GAD-7), and clinician-administered Montgomery-Åsberg Depression Scale (MADRS). Primary treatment endpoint was completion of daily treatment series. ResultsPer-protocol analyses showed no statistically significant differences on any measure between the 5.5 cm and F3 groups (all p ≥ 0.50), including percent improvement (PHQ-9: 39% vs. 39%; GAD-7: 34% vs. 27%; MADRS: 40% vs. 38%), response rate (PHQ-9: 37% vs. 43%; GAD-7: 27% vs. 30%; MADRS: 43% vs. 43%), and remission rate (PHQ-9: 22% vs. 21%; MADRS: 20% vs. 19%). Post hoc analysis of anxiety symptom change while controlling for depression severity suggested more favorable anxiolytic effects with 5.5 cm targeting (p = 0.03). ConclusionsSimilar antidepressant effects were observed with DLFPC rTMS using either the Beam F3 or 5.5 cm targeting method, supporting clinical equipoise in MDD patients with head circumference ≤ 60 cm. Comparison to MRI-based targeting and differential effects on anxiety symptoms require further investigation. Trial registrationClinicalTrials.gov identifier: NCT03378570.

Preliminary Observations of Personalized Repetitive Magnetic Stimulation (PrTMS) Guided by EEG Spectra for Concussion.

There are no FDA-approved treatments for the chronic sequelae of concussion. Repetitive magnetic transcranial stimulation (rTMS) has been explored as a therapy but outcomes have been inconsistent. To address this we developed a personalized rTMS (PrTMS) protocol involving continual rTMS stimulus frequency adjustment and progressive activation of multiple cortical sites, guided by spectral electroencephalogram (EEG)-based analyses and psychological questionnaires. We acquired pilot clinical data for 185 symptomatic brain concussion patients who underwent the PrTMS protocol over an approximate 6 week period. The PrTMS protocol used a proprietary EEG spectral frequency algorithm to define an initial stimulation frequency based on an anteriorly graded projection of the measured occipital alpha center peak, which was then used to interpolate and adjust regional stimulation frequency according to weekly EEG spectral acquisitions. PrTMS improved concussion indices and normalized the cortical alpha band center frequency and peak EEG amplitude. This potentially reflected changed neurotransmitter, cognitive, and perceptual status. PrTMS may be a promising treatment choice for patients with persistent concussion symptoms. This clinical observational study was limited in that there was no control group and a number of variables were not recorded, such as time since injury and levels of depression. While the present observations are indeed preliminary and cursory, they may suggest further prospective research on PrTMS in concussion, and exploration of the spectral EEG as a concussion biomarker, with the ultimate goals of confirmation and determining optimal PrTMS treatment parameters.

The acute effects of repetitive transcranial magnetic stimulation on laminar diffusion anisotropy of neocortical gray matter.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used to treat neuropsychiatric disorders. Inhibitory and excitatory regimens have been both adopted but the exact mechanism of action remains unclear, and investigating their differential effects on laminar diffusion profiles of neocortex may add important evidence. Twenty healthy participants were randomly assigned to receive a low-frequency/inhibitory or high-frequency/excitatory rTMS targeting the left dorsolateral prefrontal cortex (DLPFC). With the brand-new submillimeter diffusion tensor imaging of whole brain and specialized surface-based laminar analysis, fractional anisotropy (FA) and mean diffusion (MD) profiles of cortical layers at different cortical depths were characterized before/after rTMS. Inhibitory and excitatory rTMS both showed impacts on diffusion metrics of somatosensory, limbic, and sensory regions, but different patterns of changes were observed-increased FA with inhibitory rTMS, whereas decreased FA with excitatory rTMS. More importantly, laminar analysis indicated laminar specificity of changes in somatosensory regions during different rTMS patterns-inhibitory rTMS affected the superficial layers contralateral to the DLPFC, while excitatory rTMS led to changes in the intermediate/deep layers bilateral to the DLPFC. These findings provide novel insights into acute neurobiological effects on diffusion profiles of rTMS that may add critical evidence relevant to different protocols of rTMS on neocortex.