Excitatory rTMS Research Articles

Investigating the effects of excitatory and inhibitory somatosensory rTMS on somatosensory functioning in the acute and subacute phases of stroke: a preliminary double-blind and randomized trial.

Repetitive transcranial magnetic stimulation (rTMS) targeting the primary somatosensory cortex (S1) has a potential effect on somatosensory functioning following a stroke. However, S1-rTMS was combined with peripheral therapies in previous trials. Moreover, these studies have commonly targeted the ipsilesional S1 with excitatory rTMS paradigms. This double-blind, randomized trial (registration number: ChiCTR2200059098) investigated two forms of paradigms, that is ipsilesional excitatory and contralesional inhibitory rTMS, as a stand-alone treatment in post-stroke somatosensation. Patients in the acute and subacute phases of stroke were randomly assigned to either contralesional 1-Hz or ipsilesional 10-Hz rTMS group and received 10 daily sessions of treatment in two consecutive weeks. Results indicate that the contralesional inhibitory and ipsilesional excitatory stimulation were equally effective in improving somatosensory functioning. Moreover, this effect was most prominent in deep sensations and subjective sensations. Using single-pulse EMG recordings, our data also revealed an increased MEP amplitude in the ipsilesional motor cortex following ipsilesional excitatory treatment. This preliminary study demonstrates the primary somatosensory cortex as an effective rTMS target in somatosensory recovery following stroke. https://www.chictr.org.cn/showproj.html?proj=166474, ChiCTR2200059098.

Feasibility and Tolerability of Daily Theta Burst Stimulation in Autistic Youth with Intellectual Disabilities and Minimally Speaking Status: A Pilot Double-Blind Randomized Sham-Controlled Trial.

Scarce clinical trials involving autistic people with intellectual disability (ID) and minimally speaking (MS) status have been a substantial unmet research need in the field. Although earlier studies have demonstrated the feasibility and beneficial potentials of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in intellectually able autistic people, the feasibility and tolerability of applying rTMS in autistic people with ID/MS has never been studied. We conducted the world-first 4-week randomized, double-blind, sham-controlled pilot trial to investigate the feasibility, tolerability, and safety of intermittent theta burst stimulation (iTBS, a variant of excitatory rTMS) over the left DLPFC in autistic youth with ID/MS. 25 autistic youth with ID/MS (aged 8-30 years) were randomized to a 20-session 4-week daily iTBS (n = 13) vs. sham stimulation (n = 12) with follow-up 4 and 8 weeks, respectively, after the last stimulation. A retention rate was 100% in our study. Adverse events of local pain (38%) and dizziness (8%) were only noted in the active group. All adverse events were mild and transient. There were no seizures, new behavioral problems, or other severe/serious adverse events noted. No participants dropped out due to adverse events. With a small sample size, we did not find any beneficial signal of DLPFC iTBS. Our pilot data suggest regular daily TBS treatment for four weeks is feasible, well tolerated and safe in autistic youth with ID/MS. Future randomized controlled trials with sufficiently powered samples are needed to investigate the beneficial potential of rTMS/TBS for autistic people with ID/MS.

Comparison of Bilateral Versus Unilateral 5 Hz or 1 Hz Repetitive Transcranial Magnetic Stimulation in Subacute Stroke: Assessment of Motor Function in a Randomized Controlled Study.

Repetitive transcranial magnetic stimulation (rTMS) can enhance brain plasticity after stroke. At low frequencies, rTMS has an inhibitory effect, whereas at high frequencies, it has an excitatory effect. Combining both frequencies in bilateral stimulation is a new rTMS protocol under investigation, especially in the subacute stage. Fifty-five patients with subacute stroke were divided into four groups according to the rTMS protocol delivered: bilateral, inhibitory, excitatory, and control groups. All groups received concomitant task-oriented physiotherapy. Pretreatment to posttreatment assessment was performed twice, immediately after sessions and 1 month later. Volitional motor control was evaluated by Fugl-Meyer and Wolf motor function tests, and for spasticity, the Ashworth scale was used. All groups showed significant improvement. Bilateral, inhibitory, and excitatory groups showed same efficacy, but the bilateral protocol was superior in spasticity. No correlations were found between improvement and stroke duration and site except for spasticity. Bilateral rTMS shows a comparable effect to inhibitory and excitatory rTMS in improving motor disability in subacute stroke. However, it is superior for spasticity.

Treatment expectations and clinical outcomes following repetitive transcranial magnetic stimulation for treatment-resistant depression

BackgroundPatient expectations, including both positive (placebo) and negative (nocebo) effects, influence treatment outcomes, yet their impact on acute repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) is unclear. MethodsIn this single-center retrospective chart review, 208 TRD patients completed the Stanford Expectation of Treatment Scale (SETS) before starting open-label rTMS treatment. Patients were offered two excitatory rTMS protocols (deep TMS or intermittent theta-burst stimulation), which stimulated the left dorsolateral prefrontal cortex. A minimum of 20 once daily treatments were provided, delivered over 4–6 weeks. Primary outcomes were 1) remission, measured by a post-treatment score of <8 on the Hamilton Depression Rating Scale (HAMD-17), and 2) premature discontinuation. The change in HAMD-17 scores over time was used as a secondary outcome. Physicians were blinded to SETS scores. Logistic and linear regression, adjusting for covariates, assessed SETS and HAMD-17 relationships. ResultsOf 208 patients, 177 had baseline and covariate data available. The mean positivity bias score (positive expectancy minus negative expectancy subscale averages) was 0.48 ± 2.21, indicating the cohort was neutral regarding the expectations of their treatment on average. Higher positive expectancy scores were significantly associated with greater odds of remission (OR = 1.90, p = 0.003) and greater reduction in HAMD-17 scores (β = 1.30, p = 0.005) at the end of acute treatment, after adjusting for covariates. Negative expectancy was not associated with decreased odds of remission (p = 0.2) or treatment discontinuation (p = 0.8). ConclusionsHigher pre-treatment positive expectations were associated with greater remission rates with open-label rTMS in a naturalistic cohort of patients with TRD.

The stratified effects of repetitive transcranial magnetic stimulation in upper limb motor impairment recovery after stroke: a meta-analysis.

The recovery of upper extremity motor impairment after stroke remains a challenging task. The clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS), which is believed to aid in the recovery process, is still uncertain. A systematic search was conducted in Medline (Ovid), Cochrane and Embase electronic databases from March 28, 2014, to March 28, 2023. The inclusion criteria consisted of randomized controlled trials that assessed the effects of rTMS on the recovery of upper limb motor impairment among stroke patients. Various measurements, including the Fugl Meyer Assessment Upper Extremity Scale (FMA-UE), Brunnstrom recovery stage, Action Research Arm Test (ARAT), and Barthel index, were evaluated both before and after the intervention. Nineteen articles with 865 patients were included. When considering only the rTMS parameters, both inhibitory and excitatory rTMS improved FMA-UE (MD = 1.87, 95% CI = [0.88]-[2.86], p < 0.001) and Barthel index (MD = 9.73, 95% CI = [4.57]-[14.89], p < 0.001). When considering only the severity of upper limb hemiplegia, both less severe (MD = 1.56, 95% CI = [0.64]-[2.49], p < 0.001) and severe (MD = 2.05, 95% CI = [1.09]-[3.00], p < 0.001) hemiplegia benefited from rTMS based on FMA-UE. However, when considering the rTMS parameters, severity of hemiplegia and stroke stages simultaneously, inhibitory rTMS was found to be significantly effective for less severe hemiplegia in the acute and subacute phases (MD = 4.55, 95% CI = [2.49]-[6.60], p < 0.001), but not in the chronic phase based on FMA-UE. For severe hemiplegia, inhibitory rTMS was not significantly effective in the acute and subacute phases, but significantly effective in the chronic phase (MD = 2.10, 95% CI = [0.75]-[3.45], p = 0.002) based on FMA-UE. Excitatory rTMS was found to be significantly effective for less severe hemiplegia in the acute and subacute phases (MD = 1.93, 95% CI = [0.58]-[3.28], p = 0.005) based on FMA-UE. The improvements in Brunnstrom recovery stage and ARAT need further research. The effectiveness of rTMS depends on its parameters, severity of hemiplegia, and stroke stages. It is important to consider all these factors together, as any single grouping method is incomplete.

An experimental examination of neurostimulation and cognitive restructuring as potential components for Misophonia interventions

Misophonia is a disorder of decreased tolerance to certain aversive, repetitive common sounds, or to stimuli associated with these sounds. Two matched groups of adults (29 participants with misophonia and 30 clinical controls with high emotion dysregulation) received inhibitory neurostimulation (1 Hz) over a personalized medial prefrontal cortex (mPFC) target functionally connected to the left insula; excitatory neurostimulation (10 Hz) over a personalized dorsolateral PFC (dlPFC) target; and sham stimulation over either target. Stimulations were applied while participants were either listening or cognitively downregulating emotions associated with personalized aversive, misophonic, or neutral sounds. Subjective units of distress (SUDS) and psychophysiological measurements (e.g., skin conductance response [SCR] and level [SCL]) were collected.Compared to controls, participants with misophonia reported higher distress (∆SUDS = 1.91–1.93, ps < 0.001) when listening to and when downregulating misophonic distress. Both types of neurostimulation reduced distress significantly more than sham, with excitatory rTMS providing the most benefit (Cohen's dSUDS = 0.53; dSCL = 0.14). Excitatory rTMS also enhanced the regulation of emotions associated with misophonic sounds in both groups when measured by SUDS (dcontrol = 1.28; dMisophonia = 0.94), and in the misophonia group alone when measured with SCL (d = 0.20). Both types of neurostimulation were well tolerated. Engaging in cognitive restructuring enhanced with high-frequency neurostimulation led to the lowest misophonic distress, highlighting the best path forward for misophonia interventions.

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...

Effects of repetitive transcranial magnetic stimulation over the contralesional dorsal premotor cortex on upper limb function in severe ischaemic stroke: study protocol for a randomised controlled trial

IntroductionRepetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment widely recommended to promote hand motor recovery after ischaemic stroke. However, the therapeutic efficacy of rTMS over the motor cortex in...

Differential approach to stroke aphasia and primary progressive aphasia using transcranial magnetic stimulation: A systematic review.

Language disorders can occur as a consequence of stroke or neurodegenerative disorders, among other causes. Post‑stroke aphasia (PSA) and primary progressive aphasia (PPA) are syndromes that, despite having common features, differ in the brain mechanisms that cause their symptoms. These differences in the underlying functional neuroanatomical changes may influence the way they are addressed by different non‑invasive brain stimulation techniques and, in particular, by repetitive transcranial magnetic stimulation (rTMS). The aim of this systematic review is to evaluate the efficacy of rTMS in the treatment of PSA and PPA, as well as the differences in the approach to these disorders using rTMS. To this end, a total of 36 articles were found in the Web of Science, Scopus, and PubMed. The results obtained suggest that whereas in PSA, the selection of the stimulation paradigm is based on bi‑hemispheric functional reorganisation models with a tendency towards the application of inhibitory rTMS in the contralateral right hemisphere, in PPA, the application of excitatory rTMS in functionally compromised areas seems to show promising changes. It is concluded that rTMS is a potential treatment in the therapy of both disorders, although differences in the underlying brain mechanisms differentiate the rTMS approach in each case.

Upregulation of the parietal cortex improves freezing of gait in Parkinson's disease

BACKGROUND The posterior parietal cortex (PPC) is a key brain area for visuospatial processing and locomotion. It has been repetitively shown to be involved in the neural correlates of freezing of gait (FOG), a common symptom of Parkinson's disease (PD). However, current neuroimaging modalities do not allow to precisely determine the role of the PPC during real FOG episodes. OBJECTIVES The purpose of this study was to modulate the PPC cortical excitability using repetitive transcranial magnetic stimulation (rTMS) to determine whether the PPC contributes to FOG or compensates for dysfunctional neural networks to reduce FOG. METHODS Fourteen participants with PD who experience freezing took part in a proof of principle study consisting of three experimental sessions targeting the PPC with inhibitory, excitatory, and sham rTMS. Objective FOG outcomes and cortical excitability measurements were acquired before and after each stimulation protocol. RESULTS Increasing PPC excitability resulted in significantly fewer freezing episodes and percent time frozen during a FOG-provoking task. This reduction in FOG most likely emerged from the trend in PPC inhibiting the lower leg motor cortex excitability. CONCLUSION Our results suggest that the recruitment of the PPC is linked to less FOG, providing support for the beneficial role of the PPC upregulation in preventing FOG. This could potentially be linked to a reduction of the cortical input burden on the basal ganglia prior to FOG. Excitatory rTMS interventions targeting the PPC may have the potential to reduce FOG.

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.

Repetitive Transcranial Magnetic Stimulation in Post-stroke Aphasia: Comparative Evaluation of Inhibitory and Excitatory Therapeutic Protocols: Narrative Review.

Aphasia is a serious consequence of stroke resulting in difficulties in using language for communication with negative effects on patients' quality of life. The use of non-invasive repetitive transcranial magnetic stimulation (rTMS) is a novel approach in aphasia therapy, based on the knowledge gained by functional imaging technics of the brain. This review evaluates the effectiveness of rTMS on aphasia therapy according to the results of English language studies that have been published in the databases PubMed/Medline, Scopus, and Web of Science from 2011 to 2021. Twenty-seven studies were included in the review with 672 participants. The studies mainly concern the application of inhibitory rTMS on the right inferior frontal gyrus (rIFG) in the subacute and chronic phase, as well as excitatory rTMS of the unaffected language areas of the left cerebral hemisphere in the chronic phase after stroke. Most of the studies concluded that there was statistically significant improvement in various parameters of language including confrontation naming, repetition, and aphasia quotient. Three studies published results that doubt the effectiveness of rTMS. rTMS is a safe therapeutic method for aphasia treatment in the subacute and chronic phases after stroke. Its effectiveness is immediate as well as distant with a gradually decreasing therapeutic effect. Moreover, rTMS may supplement speech and language therapy as a priming factor. The most recognized method at this point in time is the application of suppressive rTMS on the right inferior frontal gyrus in combination with speech and language therapy.

Excitatory Repetitive Transcranial Magnetic Stimulation Over the Ipsilesional Hemisphere for Upper Limb Motor Function After Stroke: A Systematic Review and Meta-Analysis

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a promising therapy to promote recovery of the upper limb after stroke. According to the regulation of cortical excitability, rTMS can be divided into excitatory rTMS and inhibitory rTMS, and excitatory rTMS includes high-frequency rTMS (HF-rTMS) or intermittent theta-burst stimulation (iTBS). We aimed to evaluate the effects of excitatory rTMS over the ipsilesional hemisphere on upper limb motor recovery after stroke.MethodsDatabases of PubMed, Embase, ISI Web of Science, and the Cochrane Library were searched for randomized controlled trials published before 31 December 2021. RCTs on the effects of HF-rTMS or iTBS on upper limb function in patients diagnosed with stroke were included. Two researchers independently screened the literature, extracted the data, and assessed quality. The meta-analysis was performed by using Review Manager Version 5.4 software.ResultsFifteen studies with 449 participants were included in this meta-analysis. This meta-analysis found that excitatory rTMS had significant efficacy on upper limb motor function (MD = 5.88, 95% CI, 3.32–8.43, P < 0.001), hand strength (SMD = 0.53, 95% CI, 0.04–1.01, P = 0.03), and hand dexterity (SMD = 0.76, 95% CI, 0.39–1.14, P < 0.001). Subgroup analyses based on different types of rTMS showed that both iTBS and HF-rTMS significantly promoted upper limb motor function (iTBS, P < 0.001; HF-rTMS, P < 0.001) and hand dexterity (iTBS, P = 0.01; HF-rTMS, P < 0.001) but not hand strength (iTBS, P = 0.07; HF-rTMS, P = 0.12). Further subgroup analysis based on the duration of illness demonstrated that applying excitatory rTMS during the first 3 months (<1 month, P = 0.01; 1–3 months, P = 0.001) after stroke brought significant improvement in upper limb motor function but not in the patients with a duration longer than 3 months (P = 0.06). We found that HF-rTMS significantly enhanced the motor evoked potential (MEP) amplitude of affected hemisphere (SMD = 0.82, 95% CI, 0.32–1.33, P = 0.001).ConclusionOur study demonstrated that excitatory rTMS over the ipsilesional hemisphere could significantly improve upper limb motor function, hand strength, and hand dexterity in patients diagnosed with stroke. Both iTBS and HF-rTMS which could significantly promote upper limb motor function and hand dexterity, and excitatory rTMS were beneficial to upper limb motor function recovery only when applied in the first 3 months after stroke. HF-rTMS could significantly enhance the MEP amplitude of the affected hemisphere. High-quality and large-scale randomized controlled trials in the future are required to confirm our conclusions.Clinical Trial Registrationwww.crd.york.ac.uk/prospero/, identifier: CRD42022312288.

Repetitive transcranial magnetic stimulation for post-traumatic stress disorder: Lights and shadows.

We have read with interest the publication that describes the available data related to the use of neuromodulation strategies for the treatment of post-traumatic stress disorder (PTSD). Despite treatment advances, however, a substantial proportion of PTSD patients receiving psychological and/or pharmacological treatment do not reach an adequate clinical response. In their paper, the authors draw attention to the current understanding of the use of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for PTSD. Most of the previous studies indeed applied both inhibitory (1 Hz) and excitatory (> 1 Hz, up to 20 Hz) rTMS to the right and/or left dorsolateral prefrontal cortex. Despite larger therapeutic effects observed when high-frequency stimulation was applied, the question of which side and frequency of stimulation is the most successful is still debated. The authors also reported on the after-effect of rTMS related to neuroplasticity and identified the intermittent theta burst stimulation as a technique of particular interest because of it showed the most effective improvement on PTSD symptoms. However, although numerous studies have highlighted the possible beneficial use of rTMS protocols for PTSD, the exact mechanism of action remains unclear. In their conclusions, the authors stated that rTMS has been demonstrated to be effective for the treatment of PTSD symptoms. Nevertheless, we believe that further research with homogeneous samples, standardized protocols, and objective outcome measures is needed to identify specific therapeutic targets and to better define significant changes when active and sham stimulation procedures are compared.

Non-invasive brain stimulation for smoking cessation: a systematic review and meta-analysis.

Non-invasive brain stimulation (NIBS) methods have showed promising results for the treatment of tobacco use disorder, but little is known about the efficacy of NIBS on sustained tobacco abstinence. We aimed to assess its effectiveness for long-term smoking cessation. Systematic review and meta-analysis of randomized controlled trials (RCT). PubMed, Cochrane library, Embase, PsycINFO and clinical trials registries were systematically searched for relevant studies up to May 2021. Relevant studies included adult smokers seeking smoking cessation, included in an RCT using NIBS [specifically repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)], and with follow-up of more than 4 weeks. There were no restrictions on location. Abstinence rates in the active NIBS groups were compared with abstinence rates in sham NIBS or in usual treatment groups, from 4 weeks to 12 months following the quit attempt. Smoking abstinence was measured on an intention-to-treat basis and we used risk ratios (RRs) as measures of effect size. Seven studies were included (n = 699 patients). In all included studies, the control groups were receiving sham NIBS and only data from 3 to 6months were analysable. By pooling the seven included studies, the RR of sustained abstinence of any form of NIBS relative to sham NIBS was 2.39 [95% confidence interval (CI) = 1.26-4.55; I2 = 40%]. Subgroup analyses found that the RR was even higher when excitatory rTMS was used on the left dorsolateral prefrontal cortex (RR = 4.34; 95% CI = 1.69-11.18; I2 = 0%) or when using deep rTMS targeting the lateral prefrontal cortex and insula bilaterally (RR = 4.64; 95% CI = 1.61-13.39; I2 = 0%). A high risk of bias was found in four included studies. We also determined, using grades of recommendation, assessment, development and evaluation, that overall there was a low level of confidence in the results. Non-invasive brain stimulation (NIBS) may improve smoking abstinence rates from 3 to 6months after quitting smoking, compared with sham NIBS or usual treatment.

Low-Frequency vs. Theta Burst Transcranial Magnetic Stimulation for the Treatment of Chronic Non-fluent Aphasia in Stroke: A Proof-of-Concept Study.

BackgroundAlthough low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise in the treatment of poststroke aphasia, the efficacy of high-frequency rTMS (HF-rTMS) has yet to be determined.PurposeWe investigated the efficacy of intermittent theta burst stimulation (iTBS) in ameliorating chronic non-fluent aphasia and compared it with that of LF-rTMS.MethodsWe randomly assigned patients with poststroke non-fluent aphasia to an ipsilesional iTBS (n = 29), contralesional 1-Hz rTMS (n = 27), or sham (n = 29) group. Each group received the rTMS protocol executed in 10 daily sessions over 2 weeks. We evaluated language function before and after the intervention by using the Concise Chinese Aphasia Test (CCAT).ResultsCompared with the sham group, the iTBS group exhibited significant improvements in conversation, description, and expression scores (P = 0.0004–0.031), which characterize verbal production, as well as in auditory comprehension, reading comprehension, and matching scores (P < 0.01), which characterize language perception. The 1-Hz group exhibited superior improvements in expression, reading comprehension, and imitation writing scores compared with the sham group (P < 0.05). The iTBS group had significantly superior results in CCAT total score, matching and auditory comprehension (P < 0.05) relative to the 1-Hz group.ConclusionOur study findings contribute to a growing body of evidence that ipsilesional iTBS enhances the language recovery of patients with non-fluent aphasia after a chronic stroke. Auditory comprehension was more preferentially enhanced by iTBS compared with the 1-Hz protocol. Our findings highlight the importance of ipsilesional modulation through excitatory rTMS for the recovery of non-fluent aphasia in patients with chronic stroke.Clinical Trial Registration:[www.ClinicalTrials.gov], identifier [NCT03059225].

Revisiting Hemispheric Asymmetry in Mood Regulation: Implications for rTMS for Major Depressive Disorder.

Hemispheric differences in emotional processing have been observed for over half a century, leading to multiple theories classifying differing roles for the right and left hemisphere in emotional processing. Conventional acceptance of these theories has had lasting clinical implications for the treatment of mood disorders. The theory that the left hemisphere is broadly associated with positively valenced emotions, while the right hemisphere is broadly associated with negatively valenced emotions, drove the initial application of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD). Subsequent rTMS research has led to improved response rates while adhering to the same initial paradigm of administering excitatory rTMS to the left prefrontal cortex (PFC) and inhibitory rTMS to the right PFC. However, accumulating evidence points to greater similarities in emotional regulation between the hemispheres than previously theorized, with potential implications for how rTMS for MDD may be delivered and optimized in the near future. This review will catalog the range of measurement modalities that have been used to explore and describe hemispheric differences, and highlight evidence that updates and advances knowledge of TMS targeting and parameter selection. Future directions for research are proposed that may advance precision medicine and improve efficacy of TMS for MDD.

Repetitive Transcranial Magnetic Stimulation Shows Longitudinal Improvements in Memory in Patients With Treatment-Resistant Depression

BackgroundCognitive dysfunction (CD) is a commonly reported symptom of major depressive disorder (MDD). Patients with treatment-resistant depression (TRD) tend to experience greater rates of CD; however, treatment options are limited. Repetitive transcranial magnetic stimulation (rTMS) is effective in treating affective symptoms in patients with TRD, but its potential effect on CD in TRD has not been established. ObjectivesThis study sought to establish the potential cognitive benefits of rTMS in patients with TRD. Materials and MethodsThis study used data from a noninferiority clinical trial investigating two excitatory rTMS protocols to the left dorsolateral prefrontal cortex in unipolar outpatients with TRD. Cognitive testing was performed at baseline and three months posttreatment in 47 patients and a demographically matched cohort of 22 healthy volunteers. Changes in cognitive performance from baseline to posttreatment were assessed using repeated-measures analysis of variance, using both normative and individualized cognitive scoring methods. ResultsPatients with baseline neurocognitive dysfunction showed significant changes in verbal memory at three months posttreatment when using individualized cognitive scoring. Furthermore, improvement in verbal memory within this subset was associated with improvements in affective symptoms. LimitationsThis analysis was performed on a relatively small sample of patients with TRD who were not prescreened for CD and did not include a clinical comparator group. ConclusionsrTMS may be associated with improvements in verbal memory in patients with TRD who present with global CD and who are clinical responders to the treatment. These findings warrant replication in a larger sample as well as further investigations into the neural mechanisms of cognitive improvement after rTMS.

Modulation of Dorsolateral Prefrontal Cortex Glutamate/Glutamine Levels Following Repetitive Transcranial Magnetic Stimulation in Young Adults With Autism.

Altered excitatory and inhibitory neurotransmission has been implicated in autism spectrum disorder (ASD). Interventions using repetitive transcranial magnetic stimulation (rTMS) to enhance or inhibit cortical excitability are under study for various targets, though the mechanistic effects of rTMS have yet to be examined in ASD. Here, we examined whether an excitatory rTMS treatment course modulates glutamatergic (Glx) or γ-aminobutyric acid (GABA) metabolite levels in emerging adults with ASD. Twenty-eight participants with ASD and executive function impairment [23.3 ± 4.69 years; seven-female] underwent two magnetic resonance spectroscopy (MRS) scans of the left dorsolateral prefrontal cortex (DLPFC). MRS scans were acquired before and after participants with ASD were randomized to receive a 20-session course of active or sham rTMS to the DLPFC. Baseline MRS data was available for 19 typically developing controls [23.8 ± 4.47 years; six-female]. Metabolite levels for Glx and GABA+ were compared between ASD and control groups, at baseline, and metabolite level change, pre-to-post-rTMS treatment, was compared in ASD participants that underwent active vs. sham rTMS. Absolute change in Glx was greater in the active vs. sham-rTMS group [F(1,19) = 6.54, p = 0.02], though the absolute change in GABA+ did not differ between groups. We also examined how baseline metabolite levels related to pre/post-rTMS metabolite level change, in the active vs. sham groups. rTMS group moderated the relation between baseline Glx and pre-to-post-rTMS Glx change, such that baseline Glx predicted Glx change in the active-rTMS group only [b = 1.52, SE = 0.32, t(18) = 4.74, p < 0.001]; Glx levels increased when baseline levels were lower, and decreased when baseline levels were higher. Our results indicate that an interventional course of excitatory rTMS to the DLPFC may modulate local Glx levels in emerging adults with ASD, and align with prior reports of glutamatergic alterations following rTMS. Interventional studies that track glutamatergic markers may provide mechanistic insights into the therapeutic potential of rTMS in ASD.Clinical Trial Registration: Clinicaltrials.gov (ID: NCT02311751), https://clinicaltrials.gov/ct2/show/NCT02311751?term=ameis&rank=1; NCT02311751.

PREDICTING CLINICAL RESPONSE TO TRANSCRANIAL MAGNETIC STIMULATION IN MAJOR DEPRESSION USING TIME-FREQUENCY EEG SIGNAL PROCESSING

Repetitive transcranial magnetic stimulation (rTMS) is defined as a noninvasive technique of brain stimulation conducted for both diagnostic and therapeutic purposes. rTMS can effectively excite the brain neurons and increase brain plasticity, which becomes particularly useful in psychiatric and neurological fields. Biomarkers that predict clinical outcomes in depression are essential for increasing the precision of treatments and clinical outcomes. The electroencephalogram (EEG) is a noninvasive neurophysiological test that is promising as a biomarker sensitive to treatment effects. The aim of our study was to investigate a novel nonlinear index of the resting state EEG activity as a predictor of clinical outcome and compare its predictive capacity to traditional frequency-based indices. EEG was recorded from 50 patients with treatment resistant depression (TRD) and 24 healthy comparison (HC) subjects. TRD patients were treated with excitatory rTMS to the dorsolateral prefrontal cortex (DLPFC) for 4–6 weeks. EEG signals were first decomposed using the ICA algorithm and the extracted components were then processed by time-frequency analysis. We then go on to compare the participants’ depression severity before, after, and 2 months after finishing the last treatment session using the proposed rTMS therapy. Absolute powers (APs), band powers (BPs), and theta and beta band entropies (BAs), which were extracted from the EEG, are used as features for the classification of changes in patients and normal cases after applying rTMS. Accordingly, we can go beyond the Beck score and clinically classify the EEG signal into two classes: depression and normal. The results demonstrated 78.37%, 74.32%, and 82.43% accuracy for artificial neural network (ANN), [Formula: see text]-nearest neighbor (KNN), and support vector machine (SVM) classifiers, respectively, indicating the superiority of the proposed method to those mentioned in similar studies. Also, the electrophysiological changes are shown to be evident in patients with major depression. Our data show that the time-frequency index yields superior outcome prediction performance compared to the traditional frequency band indices. Our findings warrant further investigation of EEG-based biomarkers in depression.