Bipolar disorder (BD) affects over 1% of the population and is characterized by deficits in response inhibition. Response inhibition, a crucial component of executive functions, involves the ability to suppress or withhold a planned or ongoing response that is no longer required or appropriate in a given context. Response inhibition may be dissociated into three subcomponents: interference inhibition, action withholding, and action cancellation. These subcomponents are assessed using the hybrid response inhibition (HRI) task. Previous research has shown that inhibitory control is strongly lateralized to the right hemisphere. Specifically, the right inferior frontal gyrus (rIFG) is a key node underpinning response inhibition and might be amenable to neuromodulation using repetitive transcranial magnetic stimulation (rTMS). This proof-of-concept study aimed to investigate the effects of rTMS targeting the rIFG on response inhibition in individuals with BD and controls.

We investigated HRI performance scores in individuals with BD (n = 12) and sex-/age-matched controls (n = 12) immediately before and after intermittent theta-burst stimulation (iTBS) and continuous TBS to modulate cortical excitability of the rIFG.

The response inhibition subcomponent “action withholding” was significantly improved in the HRI task following iTBS in the BD group. No other significant effects were observed in the results.

Our study is the first to show that iTBS to the rIFG neuromodulated a specific subcomponent of response inhibition in BD. Further research investigating the potential therapeutic effect of neuromodulation of the rIFG in BD is warranted.

Binge-eating disorder (BED) is characterized by highly distressing episodes of loss-of-control over-eating. We have examined the use of repetitive transcranial magnetic stimulation (rTMS) for the treatment of people with BED and associated obesity. Such non-invasive brain stimulation (NIBS) techniques are used therapeutically in several psychiatric conditions and there is an associated scientific rationale.

Sixty participants were randomly allocated to receive 20 sessions of neuronavigated 10 Hz rTMS administered to the left dorsolateral prefrontal cortex (dlPFC) or sham treatment. Primary outcomes were the frequency of binge eating episodes (BEE) and the ‘urge to eat’ (craving) evaluated at baseline and end-of-treatment (8 weeks post-randomization). Secondary outcomes included body mass index (BMI), hunger, general and specific eating disorder psychopathology. Follow-up analyses were conducted for most outcomes at 16 weeks post-randomization. Multilevel models were used to evaluate group, time, and group-by-time interactions for the association between rTMS exposure and outcomes.

The real rTMS group (compared with sham treatment), showed a significantly greater decrease in the number of BEE at the end of treatment (Estimated Mean [EM]: 2.41 95% CI: 1.84–3.15 versus EM: 1.45 95% CI: 1.05–1.99, p = 0.02), and at follow-up (EM: 3.79 95% CI: 3–4.78 versus EM: 2.45 95% CI: 1.88–3.17, p = 0.02; group × time interaction analysis p = 0.02). No group differences were found for other comparisons.

rTMS was associated with reduced BEE during and after treatment: it suggests rTMS is a promising intervention for BED.

The literature on cortical excitability, inhibitory and facilitatory properties of the brain in patients with primary dystonia is not well elucidated. We aimed to study the changes in these neurophysiological parameters in patients with dystonia using transcranial magnetic stimulation (TMS).

Patients with primary dystonia of presumed genetic etiology (n = 36) and an equal number of healthy controls (HC) (n = 36) were recruited from May 2021 to September 2022. TMS was done using single and paired pulse paradigms. The left motor cortex was stimulated, and responses were recorded from the contralateral first dorsal interosseus muscle. Resting motor threshold (RMT), central motor conduction time, contralateral silent period (cSP), ipsilateral silent period (iSP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were recorded. All patients underwent whole exome sequencing.

The mean age of patients was 36.6 ± 13.5 years. There was a significant reduction of cSP (79.5 ± 33.8 vs 97.5 ± 25.4, p = 0.02) and iSP (42.3 ± 13.5 vs 53.8 ± 20.8, p = 0.003) in patients compared to HC. SICI was significantly enhanced in patients (0.38 ± 0.23) compared to HC (0.51 ± 0.24, p = 0.006). RMT was higher (42.1 ± 7.9 vs 37.1 ± 6.4%, p = 0.032) with enhanced SICI (0.36 ± 0.21 vs 0.56 ± 0.25, p = 0.004) in patients with generalized dystonia (n = 20) compared to HC. The genetically determined subgroup (n = 13) had significantly enhanced SICI compared to HC (0.23 ± 0.15 vs 0.51 ± 0.23, p = 0.001).

Patients with primary dystonia have altered cortical excitability and inhibition with significantly reduced silent period and enhanced intracortical inhibition suggestive of impaired GABAergic neurotransmission.

Opioid use disorder (OUD) is a devastating condition with frequent suicidality, contributing to overdose deaths. Theta burst stimulation (TBS) to the dorsolateral prefrontal cortex (DLPFC) is used to treat major depressive disorder (MDD) and is effective in treating suicidal ideation. We piloted a randomized, double-blind, sham-controlled trial of bilateral rTMS for patients with OUD and MDD experiencing suicidality.

Sequential bilateral TBS was delivered guided by structural neuroimaging: continuous TBS to the right then intermittent TBS to the left DLPFC, daily (20 treatments). The primary objective was to determine the feasibility of this population. The primary clinical outcome was the scale for suicidal ideation (SSI), secondary outcomes included depressive symptoms and opioid cue-induced craving. ClinicalTrials.gov: NCT04785456.

Eighty-seven individuals were pre-screened. The most common reasons for ineligibility included being unreachable by the study team, difficulty with scheduling/travel requirements, and medical/psychiatric instability. Six participants (5:1 M:F) were enrolled (3/arm), four had a fentanyl use history; two completed per protocol (1/arm). Of the participants with follow-up data, SSI scores decreased in 2/3 in the sham arm and 2/2 in the active arm; depression and opioid craving scores decreased in all participants.

We present the first data piloting a structural neuroimaging-guided, multi-session rTMS treatment course in outpatients with suicidality and OUD in the current North American context. Recruitment and retention were the main challenges given the highly unstable medical and psychosocial context of this patient population. Future trials should consider a suitable environment to improve the feasibility of delivering this treatment.

This study aimed to evaluate a novel rTMS protocol for treatment-resistant depression (TRD), using an EEG 10–20 system guided dual-target accelerated approach of right lateral orbitofrontal cortex (lOFC) inhibition followed by left dorsolateral prefrontal cortex (dlPFC) excitation, along with comparing 20 Hz dlPFC accelerated TMS v. sham.

Seventy five patients participated in this trial consisting of 20 sessions over 5 consecutive days comparing dual-site (cTBS of right lOFC followed sequentially by 20 Hz rTMS of left dlPFC), active control (sham right lOFC followed by 20 Hz rTMS of left dlPFC) and sham control (sham for both targets). Resting-state fMRI was acquired prior to and following treatment.

Hamilton Rating Scale for Depression (HRSD-24) scores were similarly significantly improved at 4 weeks in both the Dual and Single group relative to Sham. Planned comparisons immediately after treatment highlighted greater HRSD-24 clinical responders (Dual: 47.8% v. Single:18.2% v. Sham:4.3%, χ2 = 13.0, p = 0.002) and in PHQ-9 scores by day 5 in the Dual relative to Sham group. We further showed that accelerated 20 Hz stimulation targeting the left dlPFC (active control) is significantly better than sham at 4 weeks. Dual stimulation decreased lOFC-subcallosal cingulate functional connectivity. Greater baseline lOFC-thalamic connectivity predicted better therapeutic response, while decreased lOFC-thalamic connectivity correlated with better response.

Our novel accelerated dual TMS protocol shows rapid clinically relevant antidepressant efficacy which may be related to state-modulation. This study has implications for community-based accessible TMS without neuronavigation and rapid onset targeting suicidal ideation and accelerated discharge from hospital.

We aimed to evaluate the effect of yoga on motor and non-motor symptoms and cortical excitability in patients with Parkinson’s disease (PD).

We prospectively evaluated 17 patients with PD at baseline, after one month of conventional care, and after one month of supervised yoga sessions. The motor and non-motor symptoms were evaluated using the Unified Parkinson’s disease Rating Scale (motor part III), Hoehn and Yahr stage, Montreal Cognitive Assessment, Hamilton depression rating scale, Hamilton anxiety rating scale, non-motor symptoms questionnaire and World Health Organization quality of life questionnaire. Transcranial magnetic stimulation was used to record resting motor threshold, central motor conduction time, ipsilateral silent period (iSP), contralateral silent period (cSP), short interval intracortical inhibition (SICI), and intracortical facilitation.

The mean age of the patients was 55.5 ± 10.8 years, with a mean duration of illness of 4.0 ± 2.5 years. The postural stability of the patients significantly improved following yoga (0.59 ± 0.5 to 0.18 ± 0.4, p = 0.039). There was a significant reduction in the cSP from baseline (138.07 ± 27.5 ms) to 4 weeks of yoga therapy (116.94 ± 18.2 ms, p = 0.004). In addition, a significant reduction in SICI was observed after four weeks of yoga therapy (0.22 ± 0.10) to (0.46 ± 0.23), p = 0.004).

Yoga intervention can significantly improve postural stability in patients with PD. A significant reduction of cSP and SICI suggests a reduction in GABAergic neurotransmission following yoga therapy that may underlie the improvement observed in postural stability.

CTRI/2019/02/017564

We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer’s disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment.

Systematic review, Meta-Analysis

We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023.

RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included.

Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423).

The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer’s Disease Assessment Scale–Cognitive Subscale (SMD = −0.96 [−1.32, −0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity.

The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.

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.

Response inhibition − or the ability to withhold a suboptimal response − relies on the efficacy of fronto-striatal networks, and is impaired in neuropsychiatric disorders including addiction. Cortical paired associative stimulation (cPAS) is a form of transcranial magnetic stimulation (TMS) which can strengthen neuronal connections via spike-timing-dependent plasticity mechanisms. Here, we used cPAS targeting the fronto-striatal inhibitory network to modulate performance on a response inhibition measure in chronic alcohol use.

Fifty-five participants (20 patients with a formal alcohol use disorder (AUD) diagnosis (26–74 years, 6[30%] females) and 20 matched healthy controls (HCs) (27–73 years, 6[30%] females) within a larger sample of 35 HCs (23–84 years, 11[31.4%] females) underwent two randomized sessions of cPAS 1-week apart: right inferior frontal cortex stimulation preceding right presupplementary motor area stimulation by either 4 ms (excitation condition) or 100 ms (control condition), and were subsequently administered the Stop Signal Task (SST) in both sessions.

HCs showed decreased stop signal reaction time in the excitation condition (t(19) = −3.01, p = 0.007, [CIs]:−35.6 to −6.42); this facilitatory effect was not observed for AUD (F(1,31) = 9.57, p = 0.004, CIs: −68.64 to −14.11). Individually, rates of SST improvement were substantially higher for healthy (72%) relative to AUD (13.6%) groups (OR: 2.33, p = 0.006, CIs:−3.34 to −0.55).

In line with previous findings, cPAS improved response inhibition in healthy adults by strengthening the fronto-striatal network through putative long-term potentiation-like plasticity mechanisms. Furthermore, we identified a possible marker of impaired cortical excitability, and, thus, diminished capacity for cPAS-induced neuroplasticity in AUD with direct implications to a disorder-relevant cognitive process.

Conventional treatment methods have limited effectiveness in addressing late-life depression (LLD) that does not respond well. While a new approach called priming repetitive transcranial magnetic stimulation (rTMS) has shown promise in treating depression in adults, its effectiveness in LLD has not been explored. This study aimed to investigate the impact of priming rTMS on LLD.

This study investigated the effectiveness of priming rTMS in 31 patients with LLD who did not improve after an adequate trial of antidepressants. Patients were randomly assigned to receive either active priming rTMS or sham priming rTMS. Active priming rTMS was delivered over the right dorsolateral prefrontal cortex for 10 sessions, lasting 31 minutes each, over a period of 2 weeks.

The group receiving active priming rTMS demonstrated greater improvements in scores on the Hamilton Rating Scale for Depression (p < 0.037; partial η2 0.141) and the Geriatric Depression Rating Scale (p < 0.045; partial η2 0.131) compared to the sham priming group, with a mild effect size. At the end of the second and fourth weeks, the priming rTMS group achieved a response rate of 50%, while the sham priming group had response rates of 26.7% and 6.7%, respectively. No adverse effects requiring intervention were observed.

Priming rTMS is well-tolerated for the treatment of LLD and not only reduces the severity of depression but also maintains the achieved response over time.

Sensory-motor decoupling at the cortical level involving cholinergic circuitry has also been reported in Parkinson’s Disease (PD). Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been used previously to probe cortical cholinergic circuits in well-characterised subgroups of patients with PD. In the current study, we compared SAI in a cohort of PD patients at various stages of disease and explored correlations between SAI and various clinical measures of disease severity.

The modified Hoehn and Yahr (H&Y) scale was used to stage disease in 22 patients with PD. Motor and cognitive function were assessed using the MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale) part III and MoCA (Montreal Cognitive Assessment) score, respectively. Objective gait assessment was performed using an electronic walkway (GAITRite®). SAI was measured as the average percentage inhibition of test motor-evoked potentials (MEPs) conditioned by electrical stimulation of the contralateral median nerve at the wrist.

SAI was significantly reduced in patients with advanced PD (H&Y stage 3) compared to early PD patients (H&Y stage 1) on pairwise comparison. The visuospatial executive function and orientation domains of cognition demonstrated significant negative associations with SAI.

Cortical sensory-motor integration is progressively diminished as disease progresses. The observation that a reduction in SAI is associated with a reduction in cognitive function possibly reflects the progressive involvement of cortical cholinergic circuits in PD with increasing motor stage. Future longitudinal studies are necessary to confirm this preliminary result.

Obsessive-compulsive disorder (OCD) is one of the most common neuropsychiatric disorders with lifetime prevalence higher than that of schizophrenia and bipolar disorders. Inadequate response to available pharmacological and psychotherapeutic interventions is common in OCD. Adjunctive brain stimulation methods to address the inadequate treatment response in OCD have found a special interest in research. This study aimed to examine the efficacy of adjunctive deep transcranial magnetic stimulation (dTMS) in ameliorating the symptoms of OCD and the effect of dTMS on activation of brain regions while performing the Stroop task using functional magnetic resonance imaging (fMRI).

A total of 41 patients were assessed for the study out of which 15 OCD patients received 10 sessions of high-frequency dTMS using the H7 coil to target the anterior cingulate cortex and the medial prefrontal cortex over a period of 2 weeks. The Yale-Brown Obsessive-Compulsive Scale, the Hamilton Anxiety Rating Scale, and the Hamilton Depression Rating Scale were used for the pre- and post-stimulation clinical assessment. fMRI was used to measure the activation of brain regions while performing the Stroop task.

There was a significant improvement in the obsessive-compulsive, anxiety, and depressive symptoms after the 2 weeks of the dTMS treatment. A significant decrease in the activation of left caudate nucleus and adjacent white matter was noted while performing the Stroop task after the dTMS treatment.

The study provides preliminary evidence for functional correlates of effectiveness of dTMS as an adjunctive treatment modality for OCD.

Rapid eye movement sleep behaviour disorder (RBD) is considered to be one of the most frequent and important prodromal symptoms of Parkinson’s disease (PD). We aimed to study the neurophysiological abnormalities in patients of PD-RBD and PD without RBD (PD-nRBD) using transcranial magnetic stimulation (TMS).

Twenty patients each of PD-RBD and PD-nRBD were included in the study in addition to 20 age and gender-matched healthy controls. RBD was identified using the RBD screening questionnaire (RBDSQ). All the subjects were evaluated with single and paired-pulse TMS and parameters such as resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were recorded.

The mean age of the controls and PD patients with and without RBD was comparable. There were no significant differences in RMT, CMCT and silent period between the two patient groups. SICI was present in all the three groups with significant inhibition noted in PD-RBD group (p < 0.001). ICF was absent in patients of PD-RBD (0.19 ± 0.11) and PD-nRBD (0.7 ± 0.5) when compared to controls (1.88 ± 1.02) with profound impairment in patients with PD-RBD (p < 0.001). The mean MoCA score was found to be significantly different in all the three groups with a worse score in patients with RBD (23.10 ± 2.55; p < 0.001).

PD-RBD patients have significantly greater inhibition and reduced intracortical facilitation suggesting enhanced GABAergic and reduced glutaminergic transmission. These abnormalities may underlie the different pathophysiological process observed in these patients.

Cooperation is a key component of our lives. When we identify people in need, we are frequently motivated to cooperate by overcoming selfishness. However, we may also become selfish to pursue greater gains by putting ourselves at risk and exploiting others. Such cooperation dilemmas are ubiquitous in real life. Although functional magnetic resonance imaging studies have repeatedly reported the involvement of right temporoparietal junction (rTPJ) in cooperation dilemmas, a causal link between the two has been rarely explored.

To investigate a causal role of rTPJ in resolving cooperation dilemmas in ecologically valid settings.

Twenty-two healthy volunteers were examined. We combined repetitive transcranial magnetic stimulation (rTMS) with a snowdrift cooperation dilemma game task (cross-the-traffic intersection version) wherein either cooperation or defection should be chosen. Participants and opponents jointly faced a problem at the intersection where their cooperation could diffuse the situation (stopping/avoiding a car-crash). This conflicted with a choice in the participant’s self-interest which was more rewarding, but risky (not stopping/defection). We also included explicit-cue condition that showed elderly/pregnant passengers in the opponent’s car. Furthermore, we measured participants’ empathic-traits (e.g., perspective-taking) to study personality-cooperation associations.

The cooperation-ratio did not statistically differ between the sham stimulation and inhibitory continuous theta burst stimulation (cTBS) in both the no-cue and with-cue conditions. However, after cTBS, only in the no-cue condition, the strength of the relationship between cooperation-ratios and empathic-traits decreased significantly (p<0.05).

These results contribute to our understandings of rTPJ’s role in spontaneous social cognition, which may be considerably complex and require further examination.

No significant relationships.

Use of combined antidepressive treatment included high-frequency rhythmic transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is one of the ways for overcoming of pharmaco-resistance in depressive patients.

The aim of the study was the search for possible EEG predictors of antidepressive effects of rTMS of the left DLPFC in combined treatment of depression.

30 female in-patients (F31.3, F33.0, F33.1, by ICD-10; 20-50 years, mean age 36.9±10.3) with pharmaco-resistant depression were enrolled in the study. Treatment included antidepressants (mainly SSRI) and a 3-week course of rTMS (20 Hz) of the left DLPFC. Correlations between pre-treatment EEG spectral power values, and post-treatment quantitative clinical assessments of patients were analyzed. Responders/non-responders were determined by standard criteria of 50% decrease in HDRS-17 scale total scores after treatment course.

Responders (23 out of 30) revealed significant (p<0.05) negative correlations between post-treatment HDRS-17 scores and pre-treatment EEG spectral power in theta-2 (6-8 Hz) and alpha-1 (8-9 Hz) frequency sub-bands in the parietal-occipital-posterior temporal leads. Non-responders (7 out of 30) showed negative correlations between the post-treatment HDRS-17 scores and pre-treatment theta-2 EEG spectral power in the frontal-central-temporal regions of the right hemisphere.

Even brief course of rTMS of the left DLPFC enhances the action of antidepressants, and allows overcoming partially the pharmaco-resistance in depressive patients. Baseline values of theta-2 and alpha-1 EEG spectral power may serve as possible predictors of the effects of combined antidepressive therapy including rTMS. The study supported by RBRF grant No.18-01-00029a.

No significant relationships.

Obsessive-Compulsive Disorder (OCD) is an incapacitating Neuropsychiatric condition characterized by the presence of obsessions and/or compulsions. Although the disorder’s phenotype is well described, its pathophysiology remains elusive (Aouizerate et al, 2004). Over the last decade, techniques to noninvasively study the brain’s neurophysiology, such as Transcranial Magnetic Stimulation (TMS), have found widespread use in psychiatric research. For OCD, single- and paired-pule TMS protocols have been used to explore abnormalities in motor cortex excitability and cortical neuroplasticity. Here we propose to systematically review and, where possible, metanalyse existing case-control studies that compared such measures in patients and healthy subjects.

To systematically review and meta-analyse published case-control studies comparing cortical excitability measures, as measured by single- or paired-pulse TMS, in subjects with OCD and healthy controls.

We have conducted a systematic review of published literature (PROSPERO registration CRD42020201764) reporting measures of cortical excitability as measured by single or paired-pulse TMS, in patients with OCD and healthy controls. We searched 4 different electronic libraries (PubMed, Web of Science, EMBASE, PsycINFO). The resulting list of articles was reviewed, separately, by two researchers. Disagreements were discussed and resolved by consensus, until a final list of eligible articles was obtained.

13 studies reporting motor cortex excitability measures were included in our final list. The total number of participants included in our analyses is 615 (349 OCD; 180 healthy subjects; 86 other conditions)

A sufficient number of studies was found to allow for metanalyses, currently ongoing.