Resting Motor Threshold Research Articles

Increased Amygdala Activation during Symptom Provocation Predicts Response to Combined Repetitive Transcranial Magnetic Stimulation and Exposure Therapy in Obsessive-Compulsive Disorder in a Randomized Controlled Trial.

Repetitive transcranial magnetic stimulation (rTMS), combined with exposure and response prevention (ERP), is a promising treatment modality for treatment-refractory obsessive-compulsive disorder (OCD). Yet, not all patients respond sufficiently to this treatment. We investigated whether brain activation during a symptom provocation task could predict treatment response. Sixty-one adults with OCD (22 male/ 39 female) underwent symptom provocation with OCD- and fear-related visual stimuli during fMRI prior to an 8-week combined rTMS and ERP treatment regimen. Participants received one of the three following rTMS treatments as part of a randomized controlled trial: (1) 10Hz rTMS (110% resting motor threshold (RMT)) to the left dorsolateral prefrontal cortex (DLPFC); (2) 10Hz rTMS (110% RMT) to the left pre-supplementary motor area (preSMA); or (3) 10Hz control rTMS (60% RMT) to the vertex. Multiple regression and correlation were used to examine the predictive value of task-related brain activation for treatment response in the following ROIs: dorsomedial prefrontal cortex, amygdala, DLPFC, and preSMA. The different treatment groups responded equally to treatment. Higher pre-treatment task-related activation of the right amygdala to OCD-related stimuli showed a positive association with treatment response in all groups. Exploratory whole-brain analyses showed positive associations between activation in multiple task-relevant regions and treatment response. Only dorsal anterior cingulate cortex activation to fear-related stimuli showed a negative association with treatment outcome. Higher pre-treatment right amygdala activation during symptom provocation predicts better treatment response to combined rTMS and ERP in OCD.

The cerebral and cognitive changes after intermittent theta burst stimulation (iTBS) treatment for depression: study protocol for a randomized double-blind sham-controlled trial.

The therapeutic use of intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex (LDLPFC) is a relatively new but promising treatment option for depression. There is a need for more knowledge on the mechanisms involved in its antidepressant effects. This is a single-centre, prospective, randomized, double-blind, placebo-controlled trial with two arms, iTBS and sham iTBS. Adult outpatients with unipolar major depressive disorder of at least moderate severity will undergo cognitive assessment with an N-back task (0-back and 2-back), functional and structural magnetic resonance imaging and assessment of depression severity before and after brain stimulation. Neuronavigated iTBS or sham stimulation will be targeted at the LDPFC once a day for 10 consecutive workdays. ITBS will be delivered with the parameters 120% of resting motor threshold, triplet 50Hz bursts repeated at 5Hz; 2s on and 8s off, 600 pulses per session with a total duration of 3min 9s. The severity of depression will be measured with the Montogomery Aasberg Depression Rating Scale and the Beck Depression Inventory - second edition. In the iTBS group relative to sham, we expect significant antidepressant effects and improved N-back performance, associated with increased integrity in white matter tracts functionally connected with the LDLPFC and emotion regulation areas within the rostral anterior cingulate cortices, alongside potential increases in cortical thickness in these regions. On functional imaging, we expect to observe increased brain activity in the LDPFC during the performance of the N-back condition with higher cognitive load (2-back) in the iTBS group relative to sham. iTBS is a promising, time-efficient, and considered a safe treatment option for depression according to existing evidence. This trial aims to assess the neurocognitive impact of a 2-week, once-daily iTBS compared to sham iTBS, targeting the LDLPFC in depressed adult outpatients. The study investigates the relationships between changes in cerebral measures and cognitive performance on an N-back task in relation to the antidepressant effect following iTBS. This trial delves into the neurocognitive mechanisms of iTBS in depression, potentially offering novel scientific insights into its treatment effects and mechanisms of action. ClinicalTrials.gov NCT06534684. Retrospectively registered on August 1st 2024.

The effect of fampridine on working memory: a randomized controlled trial based on a genome-guided repurposing approach.

Working memory (WM), a key component of cognitive functions, is often impaired in psychiatric disorders such as schizophrenia. Through a genome-guided drug repurposing approach, we identified fampridine, a potassium channel blocker used to improve walking in multiple sclerosis, as a candidate for modulating WM. In a subsequent double-blind, randomized, placebo-controlled, crossover trial in 43 healthy young adults (ClinicalTrials.gov, NCT04652557), we assessed fampridine's impact on WM (3-back d-prime, primary outcome) after 3.5 days of repeated administration (10 mg twice daily). Independently of baseline cognitive performance, no significant main effect was observed (Wilcoxon P = 0.87, r = 0.026). However, lower baseline performance was associated with higher working memory performance after repeated intake of fampridine compared to placebo (rs = -0.37, P = 0.014, n = 43). Additionally, repeated intake of fampridine lowered resting motor threshold (F(1,37) = 5.31, P = 0.027, R2β = 0.01), the non-behavioral secondary outcome, indicating increased cortical excitability linked to cognitive function. Fampridine's capacity to enhance WM in low-performing individuals and to increase brain excitability points to its potential value for treating WM deficits.

Navigated Transcranial Magnetic Stimulation and Diffusion Tensor Imaging Tractography in Insular Glioma Surgery.

The surgical resection of insular gliomas is associated with a high rate of postoperative morbidity as they grow close to descending motor fibers and lenticulostriate arteries. It is believed that intraoperative perforator infarctions are the determining factor for patients' postoperative outcome, while the majority of patients with intraoperative ischemic events do not develop postoperative motor deficits. This study aims to evaluate whether navigated transcranial magnetic stimulation (nTMS) and nTMS-based fiber tracking could be valuable for the preoperative assessment of patients with insular gliomas. Thirty-two patients with insular gliomas were presurgically examined by nTMS. The resting motor threshold and cortical representation areas of legs, hands, and face were identified on both hemispheres. Motor evoked potential positive stimulation points were then used as a region of interest for diffusion tensor imaging tractographies. Somatotopic fiber tracking was performed enabling analyses of the spatial relation between tumor and cortico-spinal tract (CST) as well as the extraction of fiber tract integrity, measured by fractional anisotropy and the apparent diffusion coefficient. The performance of nTMS mappings of the motor cortex and reconstruction of descending motor fibers for legs, hands, and facial functioning was successful in all patients. Higher preoperative resting motor threshold ratios and a distance between tumor and CST of <3 mm were associated with a permanent deterioration in motor function (P = .029 and P = .007). Shorter distances between CST and tumorous tissue were correlated with lowered peritumoral fractional anisotropy values, suggesting alterations in fiber tract integrity. Lower interhemispheric peritumoral fractional anisotropy ratios showed an association with new postoperative motor deficits (P = .017). nTMS-based diffusion tensor imaging tractography enables somatotopic tract visualization and provides a valuable tool for preoperative planning, intraoperative orientation, and individual risk stratification. Thus, it may be beneficial to increase safety in insular glioma resection surgery.

Evaluating Repetitive Transcranial Magnetic Stimulation for Neuropsychiatric Symptoms in Long COVID: A Case Series.

To describe the immediate clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) in treating long COVID symptoms. Long COVID currently impacts approximately 5.3% of US adults, presenting with persistent fatigue, depression, anxiety, cognitive impairments, and social function decline. Repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex has improved these symptoms in some studies. Five patients (ages 52-63 years, 3 female patients) underwent accelerated rTMS using intermittent theta burst stimulation (600 pulses over 3 minutes 20 seconds, 80%-120% of resting motor threshold) to the left dorsolateral prefrontal cortex. The treatment consisted of twice-daily sessions over 20-30 treatments. Outcomes were measured using the Patient-Reported Outcomes Measurement and Information System (PROMIS) questionnaires, assessing fatigue, depression, anxiety, cognitive function, and social function at baseline and immediately posttreatment. One patient discontinued immediately due to intolerable scalp pain. Posttreatment PROMIS scores showed the following: fatigue decreased from 74.5 to 61.8, depression from 60.3 to 51.5, and anxiety from 62.0 to 54.0. Scores increased for cognitive (26.8 to 32.3) and social (31.0 to 32.5) function. These changes, although not statistically significant, indicate a trend toward symptom reduction. Subjectively, 3 of 4 patients who completed the rTMS course reported improvements. This case series suggests that rTMS may offer symptomatic relief in long COVID patients. Although the observed improvements in PROMIS were not statistically significant, even minimal improvements are clinically significant for patients enduring prolonged suffering. These preliminary findings are encouraging and underscore the need for further research with larger cohorts to validate the efficacy of rTMS in long COVID symptom relief.

Increased cerebellar vermis volume following repetitive transcranial magnetic stimulation in drug-resistant epilepsy: a voxel-based morphometry study.

Voxel-based morphometry (VBM) was applied to explore structural changes induced by repetitive transcranial magnetic stimulation (rTMS) and the relationship with clinical outcomes. Moreover, the relationship between each segmented regional gray matter (GM) volume was investigated to identify circuits involved in the rTMS treatment process in patients with drug-resistant epilepsy (DRE). Nineteen patients with DRE were finally included in the analysis. A session of rTMS was applied for 5 consecutive days. Participants received either 1,000 or 3,000 pulses, at a frequency of 0.5 Hz and the intensity was set at 90% of the individual's resting motor threshold. VBM analysis was performed to explore regional GM volume changes 2 months after rTMS application. The regional volume change was correlated with seizure reduction rate. Relationships between changes in GM volume in each anatomically parcellated region were analyzed using a fully-automated segmentation pipeline. Compared to the baseline, seizure frequency was reduced, and quality of life was improved after rTMS treatment. Regional volume was increased in the cerebellar vermis 2 months after rTMS application. The increased cerebellar vermis volume correlated with the reduced seizure frequency. Regional volume changes in the cerebellar vermis were correlated with changes in the subcortical and cortical GM regions including the thalamus, caudate, and frontal cortex. These results indicate that rTMS treatment effectively reduced seizure frequency in patients with DRE. Increased volume in the cerebellar vermis and activations of the cerebello-thalamo-cortical circuit may be a crucial mechanism underlying the effectiveness of rTMS application in patients with DRE.

Preoperative nTMS analysis: a sensitive tool to detect imminent motor deficits in brain tumor patients.

One of the challenges in surgery of tumors in motor eloquent areas is the individual risk assessment for postoperative motor disorder. Previously a regression model was developed that permits estimation of the risk prior to surgery based on topographical and neurophysiological data derived from investigation with nTMS (navigated Transcranial Magnetic Stimulation). This study aims to analyze the impact of including additional neurophysiological TMS parameters into the established risk stratification model for motor outcome after brain tumor surgery. Biometric and clinical data of 170 patients with glioma in motor eloquent areas were collected prospectively. In addition, the following nTMS parameters were collected bihemispherically prior to surgery: resting motor threshold (RMT), recruitment curve (RC), cortical silent period (CSP) and a nTMS based fibertracking to measure the tumor tract distance (TTD). Motor function was quantified by Medical Research Council Scale (MRCS) preoperatively, seven days and three months postoperatively. Association between nTMS parameters and postoperative motor outcome was investigated in bivariate and multivariable analyses. The bivariate analysis confirmed the association of RMT ratio with the postoperative motor outcome after seven days with higher rates of worsening in patients with RMT ratio > 1.1 compared to patients with RMT ratio ≤ 1.1 (31.6% vs. 15.1%, p = 0.009). Similarly, an association between a pathological CSP ratio and a higher risk of new postoperative motor deficits after seven days was observed (35.3% vs. 16.7% worsening, p = 0.025). A pathological RC Ratio was associated postoperative deterioration of motor function after three months (42.9% vs. 16.2% worsening, p = 0.004). In multiple regression analysis, none of these associations were statistically robust. The current results suggest that the RC ratio, CSP ratio and RMT ratio individually are sensitive markers associated with the motor outcome 7days and 3months after tumor resection in a presumed motor eloquent location. They can therefore supply valuable information during preoperative risk-benefit-balancing. However, underlying neurophysiological mechanisms might be too similar to make the parameters meaningful in a combined model.

The corticospinal tract in multiple sclerosis: correlation between cortical excitability and magnetic resonance imaging measures.

Multiple sclerosis (MS) is a central nervous system disease involving gray and white matters. Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) could help identify potential markers of disease evolution, disability, and treatment response. This work evaluates the relationship between intracortical inhibition and facilitation, motor cortex lesions, and corticospinal tract (CST) integrity. Consecutive adult patients with progressive MS were included. Sociodemographic and clinical data were collected. MRI was acquired to assess primary motor cortex lesions (double inversion and phase-sensitive inversion recovery) and CST integrity (diffusion tensor imaging). TMS outcomes were obtained: motor evoked potentials (MEP) latency, resting motor threshold, short-interval intracortical facilitation (ICF) and inhibition. Correlation analysis was performed. Twenty-five patients completed the study (13 females, age: 55.60 ± 11.49 years, Expanded Disability Status Score: 6.00 ± 1.25). Inverse correlations were found between ICF mean and each of CST radial diffusivity (RD) (ρ =-0.56; p < 0.01), CST apparent diffusion coefficient (ADC) (ρ=-0.44; p = 0.03), and disease duration (ρ=-0.46; p = 0.02). MEP latencies were directly correlated with disability scores (ρ = 0.55; p < 0.01). High ADC/RD and low ICF have been previously reported in patients with MS. While the former could reflect structural damage of the CST, the latter could hint towards an aberrant synaptic transmission as well as a depletion of facilitatory compensatory mechanisms that helps overcoming functional decline. The findings suggest concomitant structural and functional abnormalities at later disease stages that would be accompanied with a heightened disability. The results should be interpreted with caution mainly because of the small sample size that precludes further comparisons (e.g., treated vs. untreated patients, primary vs. secondary progressive MS). The role of these outcomes as potential MS biomarkers merit to be further explored.

ABNORMAL CORTICAL EXCITABILITY IS ASSOCIATED WITH DECREASED OVERALL SURVIVAL IN PATIENTS WITH GLIOBLASTOMA

Abstract AIMS Navigated transcranial magnetic stimulation (nTMS) is a well-established technique for motor cortex mapping and assessing motor tract integrity in patients with brain tumours. Pre-surgical nTMS mapping in patients with glioma has shown an altered interhemispheric excitability that correlates well with WHO grade. The aim of this study is to correlate the preoperative nTMS findings with overall survival (OS) in patients with motor-eloquent brain tumours operated at our institution. METHOD We conducted a retrospective cohort study using electronic patient records to search for all patients with a motor-eloquent brain tumour resected between 2017 and 2023. We included all adult patients (&amp;gt;18 years) with pre-operative nTMS mapping and a tissue diagnosis. Two nTMS measures of cortical excitability were assessed; cortical excitability score (CES) and the intraM1 excitability score (IMES). Our outcome measure was OS. RESULTS 160 patients fulfilled the inclusion criteria (mean age 48.34 years). The commonest tumour histology was glioblastoma (n=51; 32%). Among patients with diffuse gliomas, IDH was mutated in 59% patients and MGMT was methylated in 61%. Majority of patients (62.5%) underwent gross total resection. Resting motor thresholds (RMTs) for both upper and lower limbs between the tumour and healthy side were not significantly different. Interhemispheric RMT ratio in the upper limbs was abnormal in 60.93% patients and in the LLs was abnormal in 57.14%. A higher CES was related to lower overall survival (p=0.04). A subgroup analysis showed this was particularly the case among patients with a diagnosis of Glioblastoma (p=0.015). When adjusted for cofounding factors EOR, MGMT methylation and age, both CES and IMES were inversely related to OS (p=0.002). CONCLUSION A higher CES and IMES is related with poor overall survival in patients with Glioblastoma even when other cofounding factors affecting OS are considered. This information can be used when counselling patients and planning surgical approach to motor-eloquent tumours.

Reduced auditory perception and brain response with quiet TMS coil

BackgroundElectromagnetic forces in transcranial magnetic stimulation (TMS) coils generate a loud clicking sound that produces confounding auditory activation and is potentially hazardous to hearing. To reduce this noise while maintaining stimulation efficiency similar to conventional TMS coils, we previously developed a quiet TMS double containment coil (qTMS-DCC). ObjectiveTo compare the stimulation strength, perceived loudness, and EEG response between qTMS-DCC and a commercial TMS coil. MethodsNine healthy volunteers participated in a within-subject study design. The resting motor thresholds (RMTs) for qTMS-DCC and MagVenture Cool-B65 were measured. Psychoacoustic titration matched the Cool-B65 loudness to qTMS-DCC pulsed at 80, 100, and 120 % RMT. Event-related potentials (ERPs) were recorded for both coils. The psychoacoustic titration and ERPs were acquired with the coils both on and 6 cm off the scalp, the latter isolating the effects of airborne auditory stimulation from body sound and electromagnetic stimulation. The ERP comparisons focused on a centro-frontal region that encompassed peak responses in the global signal while stimulating the primary motor cortex. ResultsRMT did not differ significantly between the coils, with or without the EEG cap on the head. qTMS-DCC was perceived to be substantially quieter than Cool-B65. For example, qTMS-DCC at 100 % coil-specific RMT sounded like Cool-B65 at 34 % RMT. The general ERP waveform and topography were similar between the two coils, as were early-latency components, indicating comparable electromagnetic brain stimulation in the on-scalp condition. qTMS- DCC had a significantly smaller P180 component in both on-scalp and off-scalp conditions, supporting reduced auditory activation. ConclusionsThe stimulation efficiency of qTMS-DCC matched Cool-B65 while having substantially lower perceived loudness and auditory-evoked potentials.

Disruptive compensatory mechanisms in fibromyalgia syndrome and their association with pharmacological agents.

Fibromyalgia syndrome (FMS) is a chronic disorder characterized commonly by widespread musculoskeletal pain and fatigue, predominantly affecting women, with its complexity often leading to underdiagnosis and complicating treatment effectiveness. Transcranial magnetic stimulation (TMS) metrics are potential markers to optimize FMS treatments; however, evidence is limited. Our study aimed to explore the relationship between cortical excitability and inhibition, assessed through TMS markers, and clinical characteristics in patients with FMS. This presented cross-sectional study employed baseline data from a clinical trial with 108 FMS patients, mostly female (88.8%), and mean age of 47.3 years old (SD = 12.06). Our analysis showed that decreased short-intracortical inhibition (SICI) was associated with gabapentinoids use, nicotine history, and increased fatigue levels, suggesting its connection with compensatory mechanisms for non-painful FMS features. Increased motor intracortical facilitation (ICF) was linked with greater pain severity and shorter FMS duration, implying its relationship with a reorganization of sensorimotor pathways due to chronic pain. Additionally, higher resting motor threshold (rMT) was associated with less effective pain modulation (lower conditioned pain modulation [CPM]), indicating a disruption of pain compensatory mechanism. Given the role of SICI in indexing homeostatic brain mechanisms and its association with fatigue, a hallmark characteristic of FMS-induced behavioral changes, these results suggest that FMS likely has a deleterious effect on brain inhibitory function, thus providing a potential novel insight for FMS mechanisms. In addition, it seems that this compensatory mechanism's disruption is enhanced by pharmacological agents such as gabapentioids and nicotine.

Transformation but not generation of motor images is disrupted following stimulation over the left inferior parietal lobe

Motor imagery (MI) involves the generation, maintenance, and transformation of motor images; yet, the neural underpinnings of each stage are not well understood. Here, we investigated the role of the left inferior parietal lobe (IPL) in the stages of MI. Healthy participants (N=20) engaged in a MI task (making judgments about hands presented on a screen; hand laterality judgment task) over two days. Past literature demonstrates the mental rotation of hands in this task involves implicit MI (i.e., where MI occurs spontaneously in the absence of explicit instructions). During the task, active (Day A; 120% resting motor threshold) or sham (Day B; placebo) neuronavigated transcranial magnetic stimulation (TMS) was applied to the left IPL (location determined from past neuroimaging work) on 50% of trials at 250, 500, or 750ms post-stimulus onset, corresponding to different stages of MI. A/B days were randomized across participants. Linear mixed effects (LME) modelling conducted on reaction time and accuracy revealed that longer reaction times were observed when TMS was delivered at 750ms after trial onset, and more greatly for active vs. sham stimulation. This effect was exacerbated for palm- vs. back-view stimuli and for left vs. right hands. Accuracy overall was decreased for active vs. sham stimulation, and to a greater extent for palm- vs. back-view stimuli. Findings suggest that the left IPL is involved in image transformation. Overall this work informs on the neural underpinnings of the stages of MI.

Does Cathodal Preconditioning Enhance the Effects of Subsequent Anodal Transcranial Direct Current Stimulation on Corticospinal Excitability and Grip Strength?

Lewis, A, Rattray, B, and Flood, A. Does cathodal preconditioning enhance the effects of subsequent anodal transcranial direct current stimulation on corticospinal excitability and grip strength? J Strength Cond Res XX(X): 000-000, 2024-Inconsistent effects of transcranial direct current stimulation (tDCS) on corticospinal excitability (CSE) and exercise performance are commonly reported. Cathodal preconditioning, involving cathodal tDCS delivered before anodal tDCS over the same region, may enhance changes in CSE and exercise beyond that resulting from anodal tDCS alone. This study aimed to investigate whether the effects of anodal tDCS on CSE and isometric grip strength can be enhanced by cathodal preconditioning. Thirty-five healthy subjects aged 19-37 years completed a familiarization session followed by 4 stimulation conditions presented in a randomized cross-over design across 4 separate sessions. tDCS doses were applied at 2 mA over the primary motor cortex for 10 minutes. Corticospinal excitability was assessed using 120% of resting motor threshold and an input/output curve of motor evoked potentials of the first dorsal interosseous. Grip strength was evaluated as time to exhaustion (TTE) in a sustained isometric contraction. Relative to conventional sham stimulation, TTE was significantly increased by 15% after conventional anodal tDCS. Corticospinal excitability increased in response to tDCS, but this effect did not differ across conditions. Cathodal preconditioning before anodal stimulation did not increase CSE or grip strength beyond that seen in the other stimulation conditions. Our findings did not reveal any significant impact of stimulation type on CSE. Notably, anodal tDCS led to a significant improvement in grip strength endurance. However, cathodal preconditioning did not seem to increase the effect of subsequent anodal stimulation on CSE nor grip strength.

Perturbational complexity index in assessing responsiveness to rTMS treatment in patients with disorders of consciousness: a cross-over randomized controlled trial study

BackgroundDisorders of Consciousness (DoC) caused by severe brain injuries represent a challenging clinical entity, which is easy to misdiagnosis and lacks effective treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuroelectric stimulation method that shows promise in improving consciousness for DoC, especially in minimally conscious state (MCS). However, there is little evidence of its effectiveness, especially in RCT studies.MethodsTwenty MCS patients participated in a double-blind, randomized, crossover, sham-controlled clinical study to evaluate the safety and efficacy of rTMS for MCS. Subjects were randomized into two groups: one group received rTMS-active for 10 consecutive days (n = 10), and the other group received rTMS-sham for 10 consecutive days (n = 10). After a 10-day washout period, the two groups were crossed over and received the opposite treatment. the rTMS protocol consisted of 2,000 pulses per day in the left dorsolateral prefrontal cortex (L-DLPFC), sent at 10 Hz. The stimulation intensity was 90% of the resting motor threshold. Coma Recovery Scale Revised (CRS-R), the main evaluation index, was evaluated before and after each phase in a double-blind manner. Meanwhile RS-EEG and TMS-EEG data were acquired and relative alpha power (RAP), and perturbational complexity index based on state transitions (PCIst) were caculated.ResultsOne-way ANOVA revealed significantly higher scores in rTMS-active treatment compared to rTMS-sham across various measures, including CRS-R total score, RAP, PCIst (all P < 0.05). Among the 20 MCS patients, 7 (35%) were identified as responders following rTMS treatment. Compared to rTMS-sham, responder scores for CRS-R, RAP, and PCIst (all P < 0.05) were significantly elevated after rTMS-active treatment. Conversely, there was no significant difference observed in non-responders. Furthermore, post-hoc analysis revealed that baseline PCIst was significantly higher in responders than non-responders. Upon a 6-month follow-up, CRS-R scores significantly increased in all 20 patients (P = 0.026). However, the responder group exhibited a more favorable prognosis compared to the non-responder group (P = 0.031).ConclusionsApplying 10 Hz rTMS to L-DLPFC significantly increased consciousness level in MCS patients. PCIst is a neurophysiological index that has the potential to evaluate and predict therapeutic efficacy.Trial registrationwww.ClinicalTrials.gov, identifier: NCT05187000.

Erratum] Non-invasive brain stimulation in craving disorders: evidence-based umbrella review

INTRODUCTION: The use of brain stimulation in the control of craving disorders is controversial, mainly in relation to the best target, technique, duration, frequency and parameters. Several meta-analyses have been published, and their data should be summarized to support the best evidence-based clinical practice. OBJECTIVE: To provide the best level of evidence for the use of non-invasive brain stimulation (NIBS) in the control of craving disorders. METHODS: Umbrella review registraded on Prospero (CRD42021239577), and conducted according to PRISMA recommendations. The methodological quality and evidence level were assessed through AMSTAR, AMSTAR rank and GRADE. RESULTS: A total of 81 meta-analyses were screened and the final analysis was made on 10 studies including 224 randomized clinical trials (RCTs) enrolling 5,555 patients. The main targets of stimulation were the right, left and bi-hemispheric dorsolateral prefrontal cortices. The studies used anodal tDCS, and high-frequency rTMS. The protocols with the larger effect sizes were anodal tDCS with 2mA, for 30 minutes over the right DLPFC (g=0.45; 95%CI 0.328-0.583; p&lt;0.001), and high-frequency rTMS (10Hz), with 100% of the resting motor threshold, over the left DLPFC (g=1.116; 95%CI 0.597-1.634; p&lt;0.001). The quality of evidence ranged from very low to moderate because of inconsistencies mainly due to sample heterogeneity. CONCLUSION: The results of 10 meta-analyses assessing the efficacy of NIBS in the control of craving disorders are robust regarding the effect sizes and provide evidence that bi-hemispheric tDCS and high-frequency rTMS over the DLPFC are effective in the control of craving disorders. However, the evidence level is from low to moderate.

Modulation of electroencephalogram brain activity dynamics by 10 Hz parietal repetitive transcranial magnetic stimulation: Implications for recovery of the minimally conscious state

Background and objectivesDespite the fact that the parietal cortex is associated with consciousness, the underlying mechanisms of parietal repetitive transcranial magnetic stimulation (rTMS) have not yet been specifically investigated. The present study aims to examine the effects of parietal rTMS on patients with disorders of consciousness (DoC) and identify a novel potential target. MethodsTwenty minimally conscious state (MCS) patients were stochastically assigned to a real or sham rTMS group in a controlled trial. The real rTMS group was administered over the parietal cortex, with a frequency of 10 Hz and a rest motor threshold of 90 %. The sham rTMS group was identical to the real rTMS group without magnetic stimulation over the cortex. Pre- and post-treatment resting-state electrophysiological (EEG) data and coma recovery scale-revised (CRS-R) score were gathered. Microstate analyses were calculated to evaluate the brain activity dynamics. ResultsThe real rTMS treatment improved the CRS-R scores. There were notable alterations in the mean microstate duration (MMD) of microstate B in the real rTMS group. The sham rTMS group did not exhibit such changes in CRS-R score or EEG results, which were not statistically significant. Furthermore, the MMD and RTC of microstate E were found to be negatively correlated with baseline CRS-R scores. ConclusionParietal rTMS can induce behavioral improvement and brain activity dynamics in patients with MCS. EEG microstates can be used as a valuable method to study neurophysiological mechanisms behind MCS. And the parietal cortex represents an alternative for rTMS therapy protocols.

Neurophysiological effects of a combined treatment of lovastatin and minocycline in patients with fragile X syndrome: Ancillary results of the LOVAMIX randomized clinical trial.

Fragile X syndrome (FXS) is the primary hereditary cause of intellectual disability and autism spectrum disorder. It is characterized by exacerbated neuronal excitability, and its correction is considered an objective measure of treatment response in animal models, a marker albeit rarely used in clinical trials. Here, we used an extensive transcranial magnetic stimulation (TMS) battery to assess the neurophysiological effects of a therapy combining two disease-modifying drugs, lovastatin (40 mg) and minocycline (100 mg), administered alone for 8 weeks and in combination for 12 weeks, in 19 patients (mean age of 23.58 ± 1.51) with FXS taking part in the LOVAmix trial. The TMS battery, which included the resting motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, corticospinal silent period, and intracortical facilitation, was completed at baseline after 8 weeks of monotherapy (visit 2 of the clinical trial) and after 12 weeks of dual therapy (visit 4 of the clinical trial). Repeated measure ANOVAs were performed between baseline and visit 2 (monotherapy) and visit 3 (dual therapy) with interactions for which monotherapy the participants received when they began the clinical trial. Results showed that dual therapy was associated with reduced cortical excitability after 20 weeks. This was reflected by a significant increase in the resting-motor threshold after dual therapy compared to baseline. There was a tendency for enhanced short-intracortical inhibition, a marker of GABAa-mediated inhibition after 8 weeks of monotherapy compared to baseline. Together, these results suggest that a combined therapy of minocycline and lovastatin might act on the core neurophysiopathology of FXS. This trial was registered at clinicaltrials.gov (NCT02680379).

Fluctuations in resting motor threshold during electroconvulsive and magnetic seizure therapy

Objectives Magnetic seizure therapy (MST) is more benign than electroconvulsive therapy (ECT) in terms of cognitive impairment. However, whether these two ‘artificial seizures’ facilitate the central motor neural pathway and the motor cortical effects have not been investigated. The study aimed to compare the effects of ECT and MST on motor-evoked potential (MEP) in patients with mental disorders. Methods Forty-nine patients with mental disorders (major depressive disorder, bipolar disorder type II and schizophrenia [SCZ]) received 6 treatment sessions of vertex MST versus 6 bifrontal ECT treatments in a nonrandomized comparative clinical design. Data on the duration of motor seizures were collected for each treatment. MEP latency and the resting motor threshold (rMT) were measured at baseline and after every two treatments. Comparisons were performed between or within the groups. Results Seizure durations were significantly longer in the ECT group compared to the MST group across multiple sessions. Both MST and ECT demonstrated a significant reduction in rMT in the left and right hemispheres after the fourth (T3) and sixth treatments (T4) compared to baseline (T1). However, there were no significant changes in MEP latency within or between the groups throughout the treatment sessions. The only difference was that the rMT in the left cerebral hemisphere was significantly lower after T4 than after the second treatment (T2). There was no difference in rMT between the ECT and MST groups. Conclusions Both ECT and MST facilitate the central motor pathway, with a shared mechanism of increased motor cortex excitability.

People with hip osteoarthritis have reduced quadriceps voluntary activation and altered motor cortex function

AimsCompare quadriceps voluntary activation, corticospinal and intracortical excitability between people with and without hip osteoarthritis (OA). Exploratory objectives include quantifying the association of corticospinal/intracortical excitability with voluntary activation, corticospinal/intracortical excitability with hip related pain, and motor threshold with motor cortex inhibition and facilitation. MethodsCase-control study including participants with clinically and radiologically confirmed hip OA and non-OA controls. Quadriceps voluntary activation was assessed using twitch interpolation via femoral nerve stimulation. Single- and paired-pulse transcranial magnetic stimulation over the motor cortex assessed resting motor threshold (RMT), active motor threshold (AMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and silent period. Generalized linear models assessed outcomes (p ​< ​0.05). ResultsWe included 17 hip OA (76% female) and 24 controls (92% female) with a mean (standard deviation) age of 58.7 (7.9) years. Compared to controls, people with hip OA had reduced quadriceps voluntary activation (β ​= ​-5.29, 95% confidence intervals [CI], -0.79–-9.79) and increased ICF (β ​= ​0.22, 95%CI, 0.01–0.43). People with hip OA did not differ from controls in RMT (β ​= ​−4.76, 95%CI, −14.08–4.56), AMT (β ​= ​−2.13, 95%CI, −7.12-2.86), SICI (β ​= ​−0.02, 95%CI, −0.15-0.006) or silent period (β= 8.72, 95%CI, −24.75–42.20). More facilitation was associated with increased hip pain (β= 24.55, 95%CI, 6.93–42.18), and more inhibition was associated with less voluntary activation (β= 10.50, 95%CI, 2.00–18.99). ConclusionPeople with hip OA demonstrate reduced quadriceps voluntary activation and complex changes in motor cortex excitability compared to controls. These findings suggest that hip OA can alter quadriceps neuromuscular function (facilitation associated with pain, inhibition associated with activation), thus having implications for rehabilitation.

Effects of transcranial magnetic stimulation on sleep quality in fibromyalgia: A double-blind randomized clinical trial

ObjectivesThe aim of the current study was to assess the therapeutic impact of repeated low frequency repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (rDLPFC) on sleep problems in patients with fibromyalgia. MethodsForty two patients with fibromyalgia who had sleep difficulties were randomly assigned to receive either real or sham rTMS treatment. Patients received 20 treatment sessions (5 sessions per week) in which 1200 rTMS pulses were applied over the rDLPFC using a frequency of 1 Hz and an intensity of 120 % of the resting motor threshold. All participants were evaluated at baseline, and then 1 month and 3 months after treatment using the Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep Quality Index (PSQI), Medical Outcomes Study Sleep Scale (MOS-SS) and polysomnography (PSG). ResultsThere were significant time (pre, 1month, and 3 months)X group (real versus sham group) interactions in all 3 clinical rating scales; FIQ (Df = 1.425, F = 237.645, P = 0.001), PSQI (Df = 2, F = 64.005, P = 0.001), MOS-SS (Df = 2, F = 28.938, P = 0.001) due to the fact that the real group improved significantly more over time than the sham group. Similarly, the real group improved more on the PSG parameters than the sham group. The effect sizes were large both in the rating scales and PSG, indicating a substantial clinical improvement. Correlation as an exploratory analysis between the changes (pre - post 3 months) in MOS-SS and PLMs index (/h) showed significant negative correlation (r = −0.643, P = 0.002). Conclusions20 sessions of LF-rTMS over rDLPFC can improve sleep quality in both subjective (PSQI and MOSS) as well as objective (PSG) rating scales.