Modelling and validating an enhanced transcranial magnetic stimulator for neuroscience and clinical therapies

Transcranial magnetic stimulation (TMS) is a non-invasive technique for stimulating the nervous system. Conventional TMS devices are limited to a small set of predefined pulse shapes. Recent technological developments in TMS devices using switching circuits have allowed more control over the TMS parameters. Our group has introduced a new TMS device, the programmable TMS (pTMS), which uses pulse-width modulation (PWM) to rapidly switch between voltage levels, allowing the approximation of pulses of arbitrary shape. In the first part of this thesis, I validated the PWM method by using computational modelling to compare the neuronal response to stimuli generated by the pTMS device and by a conventional transcranial magnetic stimulator. The computational models predicted highly correlated activation thresholds for both stimulator types, showing that the pTMS can approximate existing pulses. Second, I validated the model and the pTMS by assessing the comparability of the effects of PWM and conventional pulses on motor evoked potentials in a first-in-human validation study. Resting motor thresholds showed a strong correlation between the stimulation pulses, with a consistently lower threshold for the PWM pulses, corroborating the results of the computational model. No significant differences in other motor response measures were found between the pulse types. Third, I exploited the capabilities of the pTMS device by designing and conducting an in-human study where I investigated a previously unfeasible stimulation pattern, monophasic theta burst stimulation (TBS). Comparing the effects of monophasic TBS with conventional biphasic TBS on corticospinal excitability, the monophasic pulses induced larger plasticity effects than biphasic pulses and than an anatomical control. Finally, I explored the sources of variability of resting motor thresholds in a large data set collected across TMS clinics, in particular investigating the effects of time of day. The results indicated that the majority of the observed differences in thresholds across the day were due to differences between clinics, highlighting the need to control for and standardise methods across clinics. In summary, this thesis demonstrates and validates the capabilities of the programmable TMS device, to firstly mimic the stimulation effects of conventional stimulators but importantly to also expand the parameter set to new stimulation protocols with the potential to have stronger effects on the stimulated neurons, and investigates the origins of variance in clinical practice

Radiographic Inspection of Fueled Clads

Five general purpose heat source (GPHS) fueled clads were radiographically inspected at the Idaho National Laboratory (INL). The girth weld region of each clad had previously passed visual examination, ring gauge test, and leak test but showed “positive” indications on the ultrasonic (UT) test. Positive ultrasonic indications are allowable under certain weld conditions; radiographic inspection provides a secondary nonintrusive means of clad inspection and may confirm allowable anomalies from the UT inspection. All the positive UT indications were found to exhibit allowable weld shield fusion or mismatch conditions. No indication of void defects was found. One additional clad (FCO371) was deemed unacceptable for radiographic inspection due to an unknown black substance that obscured the angular origin on the weld so that the angular offset to the UT indication could not be found

Digital unterstütztes Schreiben im inklusiven Schulkontext. Aktuelle Anforderungen in der Lehrer:innenbildung

Die zunehmend schriftliche Kommunikation in Schule und Beruf zeigt den Stellenwert und die Relevanz einer ausgebildeten Schreibkompetenz. (Deutsch-)Lehrer:innen benötigen Wissen über die Weiterentwicklung von Schreibkompetenzen, um Schüler:innen passgenau individuelle Schreiblernsettings anzubieten. Der gezielte Einsatz digitaler Tools ermöglicht dabei, diese Aufgaben im Rahmen des eigenen Könnens, im jeweiligen Tempo und in Zusammenarbeit mit anderen bedarfsorientiert zu bearbeiten. Für einen inklusiven Unterricht mit spezifischen Anforderungen einzelner Schüler:innen eröffnen sich somit neue Potentiale. Das digital unterstützte Schreiben als aktuelle Anforderung an Lehrer:innen sollte somit als fester Bestandteil in allen Phasen der Qualifikation, insbesondere der universitären, gefasst werden. Das Ineinandergreifen der drei Bereiche Schreiben, Inklusion und Digitalisierung und deren Verankerung in einem Seminar der Lehrer:innenbildung thematisiert vorliegender Artikel. (DIPF/Orig.

Numerical modelling of plasticity induced by Quadri-pulse stimulation

Quadri-pulse stimulation (QPS), a type of repetitive transcranial magnetic stimulation (rTMS), can induce a considerable aftereffect on cortical synapses. Human experiments have shown that the type of effect on synaptic efficiency (in terms of potentiation or depression) depends on the time interval between pulses. The maturation of biophysically-based models, which describe the physiological properties of plasticity mathematically, offers a beneficial framework to explore induced plasticity for new stimulation protocols. To model the QPS paradigm, a phenomenological model based on the knowledge of spike timing-dependent plasticity (STDP) mechanisms of synaptic plasticity was utilized where the cortex builds upon the platform of neuronal population modeling. Induced cortical plasticity was modeled for both conventional monophasic pulses and unidirectional pulses generated by the cTMS device, in a total of 117 different scenarios. For the conventional monophasic stimuli, the results of the predictive model broadly follow what is typically seen in human experiments. Unidirectional pulses can produce a similar range of plasticity. Additionally, changing the pulse width had a considerable effect on the plasticity (approximately 20% increase). As the width of the positive phase increases, the size of the potentiation will also increase. The proposed model can generate predictions to guide future plasticity experiments. Estimating the plasticity and optimizing the rTMS protocols might effectively improve the safety implications of TMS experiments by reducing the number of delivered pulses to participants. Finding the optimal stimulation protocol with the maximum potentiation/depression can lead to the design of a new TMS pulse generator device with targeted hardware and control algorithms

Digital Radiography and Computed Tomography (DRCT) Product Improvement Plan (PIP)

The Idaho National Laboratory (INL) has been developing and deploying x-ray inspection systems for chemical weapons containers for the past 12 years under the direction of the Project Manager for Non-Stockpile Chemical Materiel (PMNSCM). In FY-10 funding was provided to advance the capabilities of these systems through the DRCT (Digital Radiography and Computed Tomography) Product Improvement Plan (PIP), funded by the PMNSCM. The DRCT PIP identified three research tasks; end user study, detector evaluation and DRCT/PINS integration. Work commenced in February, 2010. Due to the late start and the schedule for field inspection of munitions at various sites, it was not possible to spend sufficient field time with operators to develop a complete end user study. We were able to interact with several operators, principally Mr. Mike Rowan who provided substantial useful input through several discussions and development of a set of field notes from the Pueblo, CO field mission. We will be pursuing ongoing interactions with field personnel as opportunities arise in FY-11

Abnormal wiring of the connectome in adults with high-functioning autism spectrum disorder

Background: Recent brain imaging findings suggest that there are widely distributed abnormalities affecting the brain connectivity in individuals with autism spectrum disorder (ASD). Using graph theoretical analysis, it is possible to investigate both global and local properties of brain's wiring diagram, i.e., the connectome. Methods: We acquired diffusion-weighted magnetic resonance imaging data from 14 adult males with high-functioning ASD and 19 age-, gender-, and IQ-matched controls. As with diffusion tensor imaging-based tractography, it is not possible to detect complex (e.g., crossing) fiber configurations, present in 60-90 % of white matter voxels; we performed constrained spherical deconvolution-based whole brain tractography. Unweighted and weighted structural brain networks were then reconstructed from these tractography data and analyzed with graph theoretical measures. Results: In subjects with ASD, global efficiency was significantly decreased both in the unweighted and the weighted networks, normalized characteristic path length was significantly increased in the unweighted networks, and strength was significantly decreased in the weighted networks. In the local analyses, betweenness centrality of the right caudate was significantly increased in the weighted networks, and the strength of the right superior temporal pole was significantly decreased in the unweighted networks in subjects with ASD. Conclusions: Our findings provide new insights into understanding ASD by showing that the integration of structural brain networks is decreased and that there are abnormalities in the connectivity of the right caudate and right superior temporal pole in subjects with ASD.Peer reviewe

Effect of community health clubs on child diarrhoea in western Rwanda: cluster-randomised controlled trial

Background Community health clubs are multi-session village-level gatherings led by trained facilitators and designed to promote healthy behaviours mainly related to water, sanitation, and hygiene. They have been implemented in several African and Asian countries but have never been evaluated rigorously. We aimed to evaluate the effect of two versions of the community health club model on child health and nutrition outcomes. Methods We did a cluster-randomised trial in Rusizi district, western Rwanda. We defined villages as clusters. We assessed villages for eligibility then randomly selected 150 for the study using a simple random sampling routine in Stata. We stratified villages by wealth index and by the proportion of children younger than 2 years with caregiverreported diarrhoea within the past 7 days. We randomly allocated these villages to three study groups: no intervention (control; n=50), eight community health club sessions (Lite intervention; n=50), or 20 community health club sessions (Classic intervention; n=50). Households in these villages were enrolled in 2013 for a baseline survey, then re-enrolled in 2015 for an endline survey. The primary outcome was caregiver-reported diarrhoea within the previous 7 days in children younger than 5 years. Analysis was by intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT01836731. Findings At the baseline survey undertaken between May, 2013, and August, 2013, 8734 households with children younger than 5 years of age were enrolled. At the endline survey undertaken between Sept 21, 2015, and Dec 22, 2015, 7934 (91%) of the households were re-enrolled. Among children younger than 5 years, the prevalence of caregiver-reported diarrhoea in the previous 7 days was 514 (14%) of 3616 assigned the control, 453 (14%) of 3196 allocated the Lite intervention (prevalence ratio compared with control 0·97, 95% CI 0·81–1·16; p=0·74), and 495 (14%) of 3464 assigned the Classic intervention (prevalence ratio compared with control 0·99, 0·85–1·15; p=0·87). Interpretation Community health clubs, in this setting in western Rwanda, had no effect on caregiver-reported diarrhoea among children younger than 5 years. Our results question the value of implementing this intervention at scale for the aim of achieving health gains

Rosanna Raymond’s SaVAge K’lub at the eighth Asia Pacific Triennial of Contemporary Art

This visual essay is based on a conversation in June 2016 between artist Rosanna Raymond and academic Karen Jacobs on Raymond’s art work, The SaVAge K’lub, with which she contributed to the eighth Asia Pacific Triennial of Contemporary Art. While this artwork challenges a variety of stereotypical misrepresentations of Pacific people and their arts, it unexpectedly appeared to reinforce certain perceptions too