D. Murphy

Deficient Activity in the Neural Systems That Mediate Self-regulatory Control in Bulimia Nervosa

CONTEXT Disturbances in neural systems that mediate voluntary self-regulatory processes may contribute to bulimia nervosa (BN) by releasing feeding behaviors from regulatory control. OBJECTIVE To study the functional activity in neural circuits that subserve self-regulatory control in women with BN. DESIGN We compared functional magnetic resonance imaging blood oxygenation level-dependent responses in patients with BN with healthy controls during performance of the Simon Spatial Incompatibility task. SETTING University research institute. PARTICIPANTS Forty women: 20 patients with BN and 20 healthy control participants. Main Outcome Measure We used general linear modeling of Simon Spatial Incompatibility task-related activations to compare groups on their patterns of brain activation associated with the successful or unsuccessful engagement of self-regulatory control. RESULTS Patients with BN responded more impulsively and made more errors on the task than did healthy controls; patients with the most severe symptoms made the most errors. During correct responding on incongruent trials, patients failed to activate frontostriatal circuits to the same degree as healthy controls in the left inferolateral prefrontal cortex (Brodmann area [BA] 45), bilateral inferior frontal gyrus (BA 44), lenticular and caudate nuclei, and anterior cingulate cortex (BA 24/32). Patients activated the dorsal anterior cingulate cortex (BA 32) more when making errors than when responding correctly. In contrast, healthy participants activated the anterior cingulate cortex more during correct than incorrect responses, and they activated the striatum more when responding incorrectly, likely reflecting an automatic response tendency that, in the absence of concomitant anterior cingulate cortex activity, produced incorrect responses. CONCLUSIONS Self-regulatory processes are impaired in women with BN, likely because of their failure to engage frontostriatal circuits appropriately. These findings enhance our understanding of the pathogenesis of BN by pointing to functional abnormalities within a neural system that subserves self-regulatory control, which may contribute to binge eating and other impulsive behaviors in women with BN.

Repetitive Transcranial Magnetic Stimulator with Controllable Pulse Parameters

The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10-310 µs and positive/negative phase amplitude ratio of 1-56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation up to 82% and 57% and decreases coil heating up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications and could lead to clinical applications with potentially enhanced potency.

Controllable pulse parameter transcranial magnetic stimulator with enhanced circuit topology and pulse shaping

OBJECTIVE This work aims at flexible and practical pulse parameter control in transcranial magnetic stimulation (TMS), which is currently very limited in commercial devices. APPROACH We present a third generation controllable pulse parameter device (cTMS3) that uses a novel circuit topology with two energy-storage capacitors. It incorporates several implementation and functionality advantages over conventional TMS devices and other devices with advanced pulse shape control. cTMS3 generates lower internal voltage differences and is implemented with transistors with a lower voltage rating than prior cTMS devices. MAIN RESULTS cTMS3 provides more flexible pulse shaping since the circuit topology allows four coil-voltage levels during a pulse, including approximately zero voltage. The near-zero coil voltage enables snubbing of the ringing at the end of the pulse without the need for a separate active snubber circuit. cTMS3 can generate powerful rapid pulse sequences (< 10 ms inter pulse interval) by increasing the width of each subsequent pulse and utilizing the large capacitor energy storage, allowing the implementation of paradigms such as paired-pulse and quadripulse TMS with a single pulse generation circuit. cTMS3 can also generate theta (50 Hz) burst stimulation with predominantly unidirectional electric field pulses. The cTMS3 device functionality and output strength are illustrated with electrical output measurements as well as a study of the effect of pulse width and polarity on the active motor threshold in ten healthy volunteers. SIGNIFICANCE The cTMS3 features could extend the utility of TMS as a research, diagnostic, and therapeutic tool.

Skilled Bimanual Training Drives Motor Cortex Plasticity in Children With Unilateral Cerebral Palsy.

Background. Intensive bimanual therapy can improve hand function in children with unilateral spastic cerebral palsy (USCP). We compared the effects of structured bimanual skill training versus unstructured bimanual practice on motor outcomes and motor map plasticity in children with USCP. Objective. We hypothesized that structured skill training would produce greater motor map plasticity than unstructured practice. Methods. Twenty children with USCP (average age 9.5; 12 males) received therapy in a day camp setting, 6 h/day, 5 days/week, for 3 weeks. In structured skill training (n = 10), children performed progressively more difficult movements and practiced functional goals. In unstructured practice (n = 10), children engaged in bimanual activities but did not practice skillful movements or functional goals. We used the Assisting Hand Assessment (AHA), Jebsen-Taylor Test of Hand Function (JTTHF), and Canadian Occupational Performance Measure (COPM) to measure hand function. We used single-pulse transcranial magnetic stimulation to map the representation of first dorsal interosseous and flexor carpi radialis muscles bilaterally. Results. Both groups showed significant improvements in bimanual hand use (AHA; P < .05) and hand dexterity (JTTHF; P < .001). However, only the structured skill group showed increases in the size of the affected hand motor map and amplitudes of motor evoked potentials (P < .01). Most children who showed the most functional improvements (COPM) had the largest changes in map size. Conclusions. These findings uncover a dichotomy of plasticity: the unstructured practice group improved hand function but did not show changes in motor maps. Skill training is important for driving motor cortex plasticity in children with USCP.

Repetitive transcranial magnetic stimulator with controllable pulse parameters (cTMS)

We describe a novel transcranial magnetic stimulation (TMS) device that uses a circuit topology incorporating two energy-storage capacitors and two insulated-gate bipolar transistors (IGBTs) to generate near-rectangular electric field E-field) pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable-pulse-parameter TMS (cTMS) device can induce E-field pulses with phase widths of 5–200 µs and positive/negative phase amplitude ratio of 1–10. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation by 78–82% and 55–57% and decreases coil heating by 15–33% and 31–41%, respectively. We demonstrate repetitive TMS (rTMS) trains of 3,000 pulses at frequencies up to 50 Hz with E-field pulse amplitude and width variability of less than 1.7% and 1%, respectively. The reduced power consumption and coil heating, and the flexible pulse parameter adjustment offered by cTMS could enhance existing TMS paradigms and could enable novel research and clinical applications with potentially enhanced potency.

Transcranial Magnetic Stimulation Device With Reduced Acoustic Noise

Transcranial magnetic stimulation (TMS) is widely used for noninvasive activation of neurons in the brain for research and clinical applications. The strong, brief magnetic pulse generated in TMS is associated with a loud (>100 dB) clicking sound that can impair hearing and that activates auditory circuits in the brain. We introduce a two-pronged solution to reduce TMS noise by redesigning both the pulse waveform and the coil structure. First, the coil current pulse duration is reduced which shifts a substantial portion of the pulse acoustic spectrum above audible frequencies. Second, the mechanical structure of the stimulation coil is designed to suppress the emergence of the sound at the source, diminish down-mixing of high-frequency sound into the audible range, and impede the transmission of residual sound to the coil surface but dissipate it away from the casing. A prototype coil driven with ultrabrief current pulses (down to 45-μs biphasic duration) is demonstrated to reduce the peak sound pressure level by more than 25 dB compared to a conventional TMS configuration, resulting in loudness reduction by more than 14-fold. These results motivate improved mechanical design of TMS coils as well as design of TMS pulse generators with shorter pulse durations and increased voltage limits with the objective of reducing TMS acoustic noise while retaining the neurostimulation strength.

Impulse Noise of Transcranial Magnetic Stimulation: Measurement, Safety, and Auditory Neuromodulation

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Quiet transcranial magnetic stimulation: Status and future directions

A significant limitation of transcranial magnetic stimulation (TMS) is that the magnetic pulse delivery is associated with a loud clicking sound as high as 140 dB resulting from electromagnetic forces. The loud noise significantly impedes both basic research and clinical applications of TMS. It effectively makes TMS less focal since every click activates auditory cortex, brainstem, and other connected regions, synchronously with the magnetic pulse. The repetitive clicking sound can induce neuromodulation that can interfere with and confound the intended effects at the TMS target. As well, there are known concerns regarding blinding of TMS studies, hearing loss, induction of tinnitus, as well as tolerability. Addressing this need, we are developing a quiet TMS (qTMS) device that incorporates two key concepts: First, the dominant frequency components of the TMS pulse sound (typically 2-5 kHz) are shifted to higher frequencies that are above the human hearing upper threshold of about 20 kHz. Second, the TMS coil is designed electrically and mechanically to generate suprathreshold electric field pulses while minimizing the sound emitted at audible frequencies (<; 20 kHz). The enhanced acoustic properties of the coil are accomplished with a novel, layered coil design. We summarize a proof-of-concept qTMS prototype demonstrating noise loudness reduction by 19 dB(A) with ultrabrief pulses at conventional amplitudes. Further, we outline next steps to accomplish further sound reduction and suprathreshold pulse amplitudes.

The eardrums move when the eyes move: A multisensory effect on the mechanics of hearing

Significance The peripheral hearing system contains several motor mechanisms that allow the brain to modify the auditory transduction process. Movements or tensioning of either the middle ear muscles or the outer hair cells modifies eardrum motion, producing sounds that can be detected by a microphone placed in the ear canal (e.g., as otoacoustic emissions). Here, we report a form of eardrum motion produced by the brain via these systems: oscillations synchronized with and covarying with the direction and amplitude of saccades. These observations suggest that a vision-related process modulates the first stage of hearing. In particular, these eye movement-related eardrum oscillations may help the brain connect sights and sounds despite changes in the spatial relationship between the eyes and the ears. Interactions between sensory pathways such as the visual and auditory systems are known to occur in the brain, but where they first occur is uncertain. Here, we show a multimodal interaction evident at the eardrum. Ear canal microphone measurements in humans (n = 19 ears in 16 subjects) and monkeys (n = 5 ears in three subjects) performing a saccadic eye movement task to visual targets indicated that the eardrum moves in conjunction with the eye movement. The eardrum motion was oscillatory and began as early as 10 ms before saccade onset in humans or with saccade onset in monkeys. These eardrum movements, which we dub eye movement-related eardrum oscillations (EMREOs), occurred in the absence of a sound stimulus. The amplitude and phase of the EMREOs depended on the direction and horizontal amplitude of the saccade. They lasted throughout the saccade and well into subsequent periods of steady fixation. We discuss the possibility that the mechanisms underlying EMREOs create eye movement-related binaural cues that may aid the brain in evaluating the relationship between visual and auditory stimulus locations as the eyes move.

Photovoltaic multilevel inverter with distributed maximum power point tracking and dynamic circuit reconfiguration

This work will present a novel photovoltaic (PV) inverter with integrated short-term storage. The topology combines advantages of microinverter topologies, such as module-specific maximum-power-point tracking, failure-tolerance, safety due to limited voltages, modularity, use of low-cost low-voltage components such as silicon field-effect transistors (FET), and simple expandability, with those of conventional string inverters, such as low control electronics effort and high power conversion efficiency. Our approach substantially deviates from both microinverters, which connect small-scale module-dedicated inverters in parallel to feed into a common ac or dc interlink, and previously introduced modular multilevel converters (MMC) with integrated PV elements, which essentially wire a number of individual inverters in series. In contrast, we incorporate individual PV modules into power modules, which can dynamically reconfigure their series-parallel circuit configuration with their neighbors to generate the output. The individual power modules can use components with relatively low voltage and low cost. Each power module further incorporates a storage based on double-layer capacitors and NiMH batteries which provide a high power density. This short-term storage enables continuous power flow at the output and compensates input-power fluctuations, e.g., due to clouds. This approach provides exceptionally high output quality, beyond levels achievable with conventional two-level string inverters, since the dynamic rewiring between the power modules in mixed series-parallel configurations is operated at the switching speed of the FET switches so that ac sinusoidal output power is generated with fine quantization levels and furthermore pulse-width modulation between these levels is possible. Finally, the dynamic circuit reconfiguration for mixed parallel-series connectivity forms a near-ideal impedance converter that minimizes loss. The paper will validate and analyze the theoretical concept with an eight-module prototype based on state-of-the art low-loss silicon FETs.