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1.
Transcranial Magnetic Stimulation in Succinic Semialdehyde Dehydrogenase Deficiency: A Measure of Maturational Trajectory of Cortical Excitability.
Tsuboyama, M, Liu, J, Kaye, H, DiBacco, M, Pearl, PL, Rotenberg, A
Journal of child neurology. 2021;(13-14):1169-1176
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Abstract
BACKGROUND Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a disorder of GABA degradation with use-dependent downregulation of postsynaptic GABAA/B receptors. We aim to measure the resulting cortical excitation: inhibition ratio using transcranial magnetic stimulation. METHODS In this single-center observational study, 18 subjects with SSADHD and 8 healthy controls underwent transcranial magnetic stimulation. Resting motor threshold, cortical silent period, and long-interval intracortical inhibition were measured in both groups. Resting motor threshold in focal epilepsy patients from an institutional transcranial magnetic stimulation database were also included. RESULTS SSADHD subjects had higher resting motor threshold than healthy controls but lower relative to focal epilepsy patients. Resting motor threshold decreased with age in all groups. Cortical silent period was longer in SSADHD subjects than in healthy controls. No difference was detected in long-interval intracortical inhibition between the 2 groups. CONCLUSION Findings suggest abnormal corticospinal tract physiology in SSADHD, but with preserved developmental trajectory for corticospinal tract maturation. Defining features of these transcranial magnetic stimulation metrics in SSADHD will be better elucidated through this ongoing longitudinal study.
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TMS-EEG signatures of glutamatergic neurotransmission in human cortex.
Belardinelli, P, König, F, Liang, C, Premoli, I, Desideri, D, Müller-Dahlhaus, F, Gordon, PC, Zipser, C, Zrenner, C, Ziemann, U
Scientific reports. 2021;(1):8159
Abstract
Neuronal activity in the brain reflects an excitation-inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (dextromethorphan, an NMDA receptor antagonist; perampanel, an AMPA receptor antagonist) and an L-type voltage-gated calcium channel blocker (nimodipine) on transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) potentials (TEPs) and TMS-induced oscillations (TIOs) in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled crossover design. Single-pulse TMS was delivered to the hand area of left primary motor cortex. Dextromethorphan increased the amplitude of the N45 TEP, while it had no effect on TIOs. Perampanel reduced the amplitude of the P60 TEP in the non-stimulated hemisphere, and increased TIOs in the beta-frequency band in the stimulated sensorimotor cortex, and in the alpha-frequency band in midline parietal channels. Nimodipine and placebo had no effect on TEPs and TIOs. The TEP results extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA receptor-mediated glutamatergic excitation. In contrast, AMPA receptor-mediated glutamatergic neurotransmission contributes to propagated activity reflected in the P60 potential and midline parietal induced oscillations. This pharmacological characterization of TMS-EEG responses will be informative for interpreting TMS-EEG abnormalities in neuropsychiatric disorders with pathological excitation-inhibition balance.
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Intermittent Theta Burst Stimulation (iTBS) for Treatment of Chronic Post-Stroke Aphasia: Results of a Pilot Randomized, Double-Blind, Sham-Controlled Trial.
Szaflarski, JP, Nenert, R, Allendorfer, JB, Martin, AN, Amara, AW, Griffis, JC, Dietz, A, Mark, VW, Sung, VW, Walker, HC, et al
Medical science monitor : international medical journal of experimental and clinical research. 2021;:e931468
Abstract
BACKGROUND Research indicates intermittent theta burst stimulation (iTBS) is a potential treatment of post-stroke aphasia. MATERIAL AND METHODS In this double-blind, sham-controlled trial (NCT01512264) participants were randomized to receive 3 weeks of sham (G₀), 1 week of iTBS/2 weeks of sham (G₁), 2 weeks of iTBS/1 week of sham (G₂), or 3 weeks of iTBS (G₃). FMRI localized residual language function in the left hemisphere; iTBS was applied to the maximum fMRI activation in the residual language cortex in the left frontal lobe. FMRI and aphasia testing were conducted pre-treatment, at ≤1 week after completing treatment, and at 3 months follow-up. RESULTS 27/36 participants completed the trial. We compared G0 to each of the individual treatment group and to all iTBS treatment groups combined (G₁₋₃). In individual groups, participants gained (of moderate or large effect sizes; some significant at P<0.05) on the Boston Naming Test (BNT), the Semantic Fluency Test (SFT), and the Aphasia Quotient of the Western Aphasia Battery-Revised (WAB-R AQ). In G₁₋₃, BNT, and SFT improved immediately after treatment, while the WAB-R AQ improved at 3 months. Compared to G₀, the other groups showed greater fMRI activation in both hemispheres and non-significant increases in language lateralization to the left hemisphere. Changes in IFG connectivity were noted with iTBS, showing differences between time-points, with some of them correlating with the behavioral measures. CONCLUSIONS The results of this pilot trial support the hypothesis that iTBS applied to the ipsilesional hemisphere can improve aphasia and result in cortical plasticity.
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Deep Transcranial Magnetic Stimulation Affects Gut Microbiota Composition in Obesity: Results of Randomized Clinical Trial.
Ferrulli, A, Drago, L, Gandini, S, Massarini, S, Bellerba, F, Senesi, P, Terruzzi, I, Luzi, L
International journal of molecular sciences. 2021;(9)
Abstract
Growing evidence highlights the crucial role of gut microbiota in affecting different aspects of obesity. Considering the ability of deep transcranial magnetic stimulation (dTMS) to modulate the cortical excitability, the reward system, and, indirectly, the autonomic nervous system (ANS), we hypothesized a potential role of dTMS in affecting the brain-gut communication pathways, and the gut microbiota composition in obesity. In a hospital setting, 22 subjects with obesity (5 M, 17 F; 44.9 ± 2.2 years; BMI 37.5 ± 1.0 kg/m2) were randomized into three groups receiving 15 sessions (3 per week for 5 weeks) of high frequency (HF), low frequency (LF) dTMS, or sham stimulation. Fecal samples were collected at baseline and after 5 weeks of treatment. Total bacterial DNA was extracted from fecal samples using the QIAamp DNA Stool Mini Kit (Qiagen, Italy) and analyzed by a metagenomics approach (Ion Torrent Personal Genome Machine). After 5 weeks, a significant weight loss was found in HF (HF: -4.1 ± 0.8%, LF: -1.9 ± 0.8%, sham: -1.3 ± 0.6%, p = 0.042) compared to LF and sham groups, associated with a decrease in norepinephrine compared to baseline (HF: -61.5 ± 15.2%, p < 0.01; LF: -31.8 ± 17.1%, p < 0.05; sham: -35.8 ± 21.0%, p > 0.05). Furthermore, an increase in Faecalibacterium (+154.3% vs. baseline, p < 0.05) and Alistipes (+153.4% vs. baseline, p < 0.05) genera, and a significant decrease in Lactobacillus (-77.1% vs. baseline, p < 0.05) were found in HF. Faecalibacterium variations were not significant compared to baseline in the other two groups (LF: +106.6%, sham: +27.6%; p > 0.05) as well as Alistipes (LF: -54.9%, sham: -15.1%; p > 0.05) and Lactobacillus (LF: -26.0%, sham: +228.3%; p > 0.05) variations. Norepinephrine change significantly correlated with Bacteroides (r2 = 0.734; p < 0.05), Eubacterium (r2 = 0.734; p < 0.05), and Parasutterella (r2 = 0.618; p < 0.05) abundance variations in HF. In conclusion, HF dTMS treatment revealed to be effective in modulating gut microbiota composition in subjects with obesity, reversing obesity-associated microbiota variations, and promoting bacterial species representative of healthy subjects with anti-inflammatory properties.
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Effect of repetitive peripheral magnetic stimulation combined with motor imagery on the corticospinal excitability of antagonist muscles.
Asao, A, Hoshino, Y, Nomura, T, Shibuya, K
Neuroreport. 2021;(10):894-898
Abstract
OBJECTIVE Repetitive peripheral magnetic stimulation (rPMS) combined with motor imagery facilitates the corticospinal excitability of the agonist muscles. However, the effects of rPMS combined with motor imagery on the corticospinal excitability of the antagonist muscles are unclear. This is an important aspect for applying rPMS in neurorehabilitation for sensorimotor dysfunction. Therefore, we investigated the real-time changes of corticospinal excitability of antagonist muscles during rPMS combined with motor imagery. METHODS Fourteen healthy volunteers underwent four different experimental conditions: rest, rPMS, motor imagery, and rPMS combined with motor imagery (rPMS + motor imagery). In the rPMS and rPMS + motor imagery conditions, rPMS (25 Hz, 1600 ms/train, 1.5× of the motor threshold) was delivered to the dorsal side of the forearm. In motor imagery and rPMS + motor imagery, the participant imagined wrist extension movements. Transcranial magnetic stimulation was delivered to record motor-evoked potentials of the antagonist muscle during experimental interventions. RESULTS The motor-evoked potential (normalized by rest condition) values indicated no difference between rPMS, motor imagery, and rPMS + motor imagery. CONCLUSION These results suggest that rPMS combined with motor imagery has no effect on the corticospinal excitability of the antagonist muscles and highlight the importance of investigating the effects of rPMS combined with motor imagery at the spinal level.
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Intermittent theta-burst stimulation moderates interaction between increment of N-Acetyl-Aspartate in anterior cingulate and improvement of unipolar depression.
Zavorotnyy, M, Zöllner, R, Rekate, H, Dietsche, P, Bopp, M, Sommer, J, Meller, T, Krug, A, Nenadić, I
Brain stimulation. 2020;(4):943-952
Abstract
BACKGROUND Intermittent theta-burst stimulation (iTBS), a novel repetitive transcranial magnetic stimulation (rTMS) technique, appears to have antidepressant effects when applied over left dorsolateral prefrontal cortex (DLPFC). However, its underlying neurobiological mechanisms are unclear. Proton magnetic resonance spectroscopy (1H-MRS) provides in vivo measurements of cerebral metabolites altered in major depressive disorder (MDD) like N-acetyl-aspartate (NAA) and choline-containing compounds (Cho). We used MRS to analyse effects of iTBS on the associations between the shifts in the NAA and Cho levels during therapy and MDD improvement. METHODS In-patients with unipolar MDD (N = 57), in addition to treatment as usual, were randomized to receive 20 iTBS or sham stimulations applied over left DLPFC over four weeks. Single-voxel 1H-MRS of the anterior cingulate cortex (ACC) was performed at baseline and follow-up. Increments of concentrations, as well as MDD improvement, were defined as endpoints. We tested a moderated mediation model of effects using the PROCESS macro (an observed variable ordinary least squares and logistic regression path analysis modeling tool) for SPSS. RESULTS Improvement of depressive symptoms was significantly associated with decrease of Cho/NAA ratio, mediated by NAA. iTBS had a significant moderating effect enhancing the relationship between NAA change and depression improvement. CONCLUSIONS Our findings suggest a potential neurochemical pathway and mechanisms of antidepressant action of iTBS, which may moderate the improvement of metabolic markers of neuronal viability. iTBS might increase neuroplasticity, thus facilitating normalization of neuronal circuit function.
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Transcranial Magnetic Stimulation as Treatment in Multiple Neurologic Conditions.
Iglesias, AH
Current neurology and neuroscience reports. 2020;(1):1
Abstract
PURPOSE OF REVIEW Transcranial magnetic stimulation (TMS) is a method of Non-Invasive Brain Stimulation that is based on electro-physical principles discovered by Michael Faraday. A TMS device is made of one or two copper coils, positioned superficially to a site of interest in the brain, to non-invasively produce a brief magnetic pulse to an estimated depth from the surface of the scalp with the following axonal depolarization. This axonal depolarization activates cortical and subcortical networks with multiple effects. There are different methods of TMS used, all with different mechanisms of action. TMS is well tolerated with very few side effects. RECENT FINDINGS TMS is now approved for major depression disorder and obsessive-compulsive disorder. There is significant data to consider approval of TMS for many neurological disorders. This is a review of the uses of TMS in diverse neurological conditions, including stroke and spasticity, migraine, and dementia. TMS is a device that utilizes non-invasive brain stimulation, and it has shown promising results with objective clinical and basic science data. Its ability to trigger neuronal plasticity and potentiating synaptic transmission gives it incredible therapeutic potential. There are diverse mechanisms of action, and this could be troublesome in elaborating clinical trials and standardization of therapy.
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High frequency deep transcranial magnetic stimulation acutely increases β-endorphins in obese humans.
Ferrulli, A, Macrì, C, Terruzzi, I, Ambrogi, F, Milani, V, Adamo, M, Luzi, L
Endocrine. 2019;(1):67-74
Abstract
PURPOSE In obesity, metabolic and voluntary factors regulate appetite, and a dysregulation of the reward pathway was demonstrated in all addiction disorders. Deep transcranial magnetic stimulation (dTMS) is already used to modulate cerebral dopamine activation in neuro-psychiatric diseases. We presently assess the acute effect of high frequency (HF) and low frequency (LF) dTMS on the modulation of the main neuropeptides and neurotransmitters involved in the reward pathway in obese subjects. METHODS This study was designed as a double-blind, sham-controlled, randomized clinical trial. Thirty-three obese patients (9 males, 24 females, age 48.1 ± 10.6, BMI 36.4 ± 4.7) were enrolled in the study. All patients were studied during a single dTMS session and blood aliquots were drawn before and after a single dTMS session. Metabolic and neuro-endocrine parameters were evaluated before and after: (1) 18 Hz dTMS (HF, 13 patients); (2) 1 Hz dTMS (LF, 10 patients); (3) Sham treatment (Sham, 10 patients). RESULTS No statistically significant variations in metabolic parameters, systolic and diastolic blood pressure, and heart rate were shown acutely. HF showed a significant increase of β-endorphin compared to other groups (p = 0.048); a significant increase of ghrelin in LF (p = 0.041) was also demonstrated. CONCLUSIONS A single session of HF dTMS treatment determines in obese subjects an acute increase of β-endorphin level, indicating an activation of the reward pathway. The present findings constitute proof of principle for a potential application of this methodology in obesity treatment.
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The effects of high-frequency repetitive transcranial magnetic stimulation on resting-state functional connectivity in obese adults.
Kim, SH, Park, BY, Byeon, K, Park, H, Kim, Y, Eun, YM, Chung, JH
Diabetes, obesity & metabolism. 2019;(8):1956-1966
Abstract
AIMS: We conducted a 4-week randomized, sham-controlled, single-blind, parallel-group trial to examine the effect of repetitive transcranial magnetic stimulation (rTMS) delivered to the left dorsolateral prefrontal cortex (DLPFC) on functional brain connectivity and body weight in adults with obesity. MATERIALS AND METHODS Of the 45 volunteers with obesity, aged between 18 and 70 years (body mass index [BMI] ≥25 kg/m2 according to the obesity criterion for an Asian population), 36 participants (54.1 ± 11.0 years, BMI 30.2 ± 3.5 kg/m2 , 77.8% female) completed the 4 weeks of follow-up, undergoing two resting state fMRI scans (20 in the real stimulation group and 16 in the sham stimulation group). A total of eight sessions of high-frequency rTMS targeting the left DLPFC were provided over a period of 4 weeks (5-second trains with 25-second inter-train intervals, 10 Hz, 110% motor threshold; 2000 pulses over 20 minutes). RESULTS Participants in the real stimulation group showed significantly greater weight loss from baseline following the eight session of rTMS (-2.53 ± 2.41 kg vs 0.38 ± 1.13 kg, P < 0.01). For intrinsic brain connectivity comparisons, the between-ness centrality values within the right frontoparietal network tended to increase with rTMS, and a significant interaction effect was identified for time (pre vs post) × rTMS (real vs sham) in the right frontoparietal network (P = 0.031, FDR corrected). CONCLUSIONS We observed that rTMS selectively increased resting state functional connectivity within the right frontoparietal network. Our findings suggest that high-frequency rTMS to the left DLPFC might strengthen the frontoparietal network that orchestrates top-down inhibitory control to reduce food intake.
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Multimodal Surgical Treatment of High-Grade Gliomas in the Motor Area: The Impact of the Combination of Navigated Transcranial Magnetic Stimulation and Fluorescein-Guided Resection.
Raffa, G, Scibilia, A, Conti, A, Cardali, SM, Rizzo, V, Terranova, C, Quattropani, MC, Marzano, G, Ricciardo, G, Vinci, SL, et al
World neurosurgery. 2019;:e378-e390
Abstract
BACKGROUND Fluorescein-guided surgery of high-grade gliomas (HGGs) increases the extent of tumor resection but its efficacy has been questioned, especially for tumors located close to functional networks. In these cases, navigated transcranial magnetic stimulation (nTMS) may be used to plan and guide a safe resection. The aim of this study was to assess the impact of these techniques combined with intraoperative neurophysiologic mapping (IONM) to achieve the maximal safe resection of tumors located in the motor area. METHODS We collected data of patients operated using a multimodal combination of sodium fluorescein-guided resection, nTMS motor planning, and IONM for HGGs in the motor area. The nTMS planning accuracy, extent of resection, and postoperative motor and functional status were compared with a matched control group of patients with HGG operated on only by IONM-guided resection. RESULTS Forty-one patients treated by multimodal approach (group A) and 41 controls (group B) were included. The nTMS-based planning reliably identified the tumor/motor pathway spatial relationship (accuracy, 92.68%). We obtained in group A versus controls a higher gross total resection rate (73.17% vs. 51.22%; P = 0.04), and a reduction of cases with new permanent motor deficits (9.75% vs. 29.27%; P = 0.04) or Karnofsky Performance Status worsening (12.19% vs. 31.71%; P = 0.03). CONCLUSIONS This study supports the role of the combination of sodium fluorescein-guided resection and nTMS-based planning for surgery of HGGs close to the motor pathway. This multimodal approach in combination with IONM may lead to customized preoperative planning, increased extent of resection, and improved functional outcome, compared with standard IONM-guided surgery.