Transcranial magnetic stimulation: the road to clinical therapy for dystonia

Despite many research studies, transcranial magnetic stimulation (TMS) is not yet an FDA-approved clinical therapy for dystonia patients. This review describes the four major challenges that have historically hindered the clinical translation of TMS. The four challenges described are limited types of clinical trial designs, limited evidence on objective behavioral measures, variability in the TMS clinical response, and the extensive TMS parameters to optimize for clinical therapy. Progress has been made to diversify the types of clinical trial design available to clinical researchers, identify evidence-based objective behavioral measures, and reduce the variability in TMS clinical response. Future studies should identify objective behavioral measures for other dystonia subtypes and expand the optimal TMS stimulation parameters for clinical therapy. Our review highlights the key progress made to overcome these barriers and gaps that remain for TMS to develop into a long-lasting clinical therapy for dystonia patients

Double-containment coil with enhanced winding mounting for transcranial magnetic stimulation with reduced acoustic noise

Objective: This work aims to reduce the acoustic noise level of transcranial magnetic stimulation (TMS) coils. TMS requires high currents (several thousand amperes) to be pulsed through the coil, which generates a loud acoustic impulse whose peak sound pressure level (SPL) can exceed 130 dB(Z). This sound poses a risk to hearing and elicits unwanted neural activation of auditory brain circuits. Methods: We propose a new double-containment coil with enhanced winding mounting (DCC), which utilizes acoustic impedance mismatch to contain and dissipate the impulsive sound within an air-tight outer casing. The coil winding is potted in a rigid block, which is mounted to the outer casing by its acoustic nodes that are subject to minimum vibration during the pulse. The rest of the winding block is isolated from the casing by an air gap, and sound is absorbed by foam within the casing. The casing thickness under the winding center is minimized to maximize the coil electric field output. Results: Compared to commercial figure-of-eight TMS coils, the DCC prototype has 10-33 dB(Z) lower SPL at matched stimulation strength, whilst providing 22% higher maximum stimulation strength than equally focal commercial coils. Conclusion: The DCC design greatly reduces the acoustic noise of TMS while increasing the achievable stimulation strength. Significance: The acoustic noise reduction from our coil design is comparable to that provided by typical hearing protection devices. This coil design approach can enhance hearing safety and reduce auditory co-activations in the brain and other detrimental effects of TMS sound.Comment: 8 pages, 5 figure

Module Implementation and Modulation Strategy for Sensorless Balancing in Modular Multilevel Converters

Modules with series and parallel connectivity add new features and operation modes to modular multilevel converters (MMCs). Compared to full- and half-bridges, the series/parallel modules allow sensorless module balancing and reduce conduction loss with the same semiconductor area. However, in high-voltage applications with limited switching rates, the sensorless operation of the series/parallel modules suffers from large charge-balancing currents. This paper introduces a series/parallel module variant with a small port inductor. The port inductor suppresses the charge-balancing current despite low switching rates. We also propose a carrier-based modulation framework and show the importance of the carrier assignment in terms of efficiency and balancing. The proposed module and the modulation method are verified on a lab setup with module switching rates down to 200 Hz. The module voltages are kept within a narrow band with the charge-balancing currents below 5% of the arm current. The experimental results show practicality and advantages of the new series/parallel modules in high-voltage MMC applications

Module Implementation and Modulation Strategy for Sensorless Balancing in Modular Multilevel Converters

Modules with series and parallel connectivity add new features and operation modes to modular multilevel converters (MMCs). Compared to full- and half-bridges, the series/parallel modules allow sensorless module balancing and reduce conduction loss with the same semiconductor area. However, in high-voltage applications with limited switching rates, the sensorless operation of the series/parallel modules suffers from large charge-balancing currents. This paper introduces a series/parallel module variant with a small port inductor. The port inductor suppresses the charge-balancing current despite low switching rates. We also propose a carrier-based modulation framework and show the importance of the carrier assignment in terms of efficiency and balancing. The proposed module and the modulation method are verified on a lab setup with module switching rates down to 200 Hz. The module voltages are kept within a narrow band with the charge-balancing currents below 5% of the arm current. The experimental results show practicality and advantages of the new series/parallel modules in high-voltage MMC applications

Extended Remediation of Sleep Deprived-Induced Working Memory Deficits Using fMRI-Guided Transcranial Magnetic Stimulation

STUDY OBJECTIVES: We attempted to prevent the development of working memory (WM) impairments caused by sleep deprivation using fMRI-guided repetitive transcranial magnetic stimulation (rTMS). Novel aspects of our fMRI-guided rTMS paradigm included the use of sophisticated covariance methods to identify functional networks in imaging data, and the use of fMRI-targeted rTMS concurrent with task performance to modulate plasticity effects over a longer term. DESIGN: Between-groups mixed model. SETTING: TMS, MRI, and sleep laboratory study. PARTICIPANTS: 27 subjects (13 receiving Active rTMS, and 14 Sham) completed the sleep deprivation protocol, with another 21 (10 Active, 11 Sham) non-sleep deprived subjects run in a second experiment. INTERVENTIONS: Our previous covariance analysis had identified a network, including occipital cortex, which demonstrated individual differences in resilience to the deleterious effects of sleep deprivation on WM performance. Five Hz rTMS was applied to left lateral occipital cortex while subjects performed a WM task during 4 sessions over the course of 2 days of total sleep deprivation. MEASUREMENTS AND RESULTS: At the end of the sleep deprivation period, Sham sleep deprived subjects exhibited degraded performance in the WM task. In contrast, those receiving Active rTMS did not show the slowing and lapsing typical in sleep deprivation, and instead performed similarly to non- sleep deprived subjects. Importantly, the Active sleep deprivation group showed rTMS-induced facilitation of WM performance a full 18 hours after the last rTMS session. CONCLUSIONS: Over the course of sleep deprivation, these results indicate that rTMS applied concurrently with WM task performance affected neural circuitry involved in WM to prevent its full impact

Transcranial direct current stimulation (tDCS) of frontal cortex decreases performance on the WAIS-IV intelligence test

Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2mA at each anode for 20 minutes) or active sham tDCS (2mA for 40 seconds), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2mA for 20 minutes). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement