Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Evoked-Gamma Frequency Oscillations in Autism Spectrum Disorder (ASD).

INTRODUCTION: It has been reported that individuals with Autism Spectrum Disorder (ASD) have abnormal reactions to the sensory environment and visuo-perceptual abnormalities. Electrophysiological research has provided evidence that gamma band activity (30-80 Hz) is a physiological indicator of the co-activation of cortical cells engaged in processing visual stimuli and integrating different features of a stimulus. A number of studies have found augmented and indiscriminative gamma band power at early stages of visual processing in ASD; this may be related to decreased inhibitory processing and an increase in the ratio of cortical excitation to inhibition. Low frequency or 'slow' (≤1HZ) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits. METHODS: We wanted to test the hypothesis of gamma band abnormalities at early stages of visual processing in ASD by investigating relative evoked (i.e. ~ 100 ms) gamma power in 25 subjects with ASD and 20 age-matched controls using Kanizsa illusory figures. Additionally, we wanted to assess the effects of 12 sessions of bilateral 'slow' rTMS to the dorsolateral prefrontal cortex (DLPFC) on evoked gamma activity using a randomized controlled design. RESULTS: In individuals with ASD evoked gamma activity was not discriminative of stimulus type, whereas in controls early gamma power differences between target and non-target stimuli were highly significant. Following rTMS individuals with ASD showed significant improvement in discriminatory gamma activity between relevant and irrelevant visual stimuli. We also found significant improvement in the responses on behavioral questionnaires (i.e., irritability, repetitive behavior) as a result of rTMS. CONCLUSION: We proposed that 'slow' rTMS may have increased cortical inhibitory tone which improved discriminatory gamma activity at early stages of visual processing. rTMS has the potential to become an important therapeutic tool in ASD treatment and has shown significant benefits in treating core symptoms of ASD with few, if any side effects.

Expanded pediatric cardiovascular simulator for research and training.

A mock circulation system has been developed to approximate key anatomic features and simulate the pressures and flows of an infant. Pulsatile flow is generated by 10 cc pulsatile ventricles (Utah infant ventricular assist device). Systemic vasculature is mimicked through the use of 3/8" ID bypass tubing with two flexible reservoirs to provide compliance. Vascular resistance, including pulmonary, aortic, and major branches, is controlled via a series of variable pinch clamps. The coronary branch has a dynamic resistor so that the majority of flow occurs during diastole. The system is instrumented to measure key pressures and flows. Right atrial pressure, left atrial pressure, pulmonary artery pressure, and mean aortic pressure are measured with high-fidelity pressure catheters (Millar Instruments, Houston, TX). Flows are measured by transit time ultrasonic flow probes (Transonic Systems, Ithaca, NY) in the pulmonary artery, aorta, coronary artery, and brachiocephalic artery along with assist device flow. The system can be tuned to create the hemodynamic values of a pediatric patient under normal or heart failure conditions. Once tuned to the desired hemodynamic conditions, the loop may be used to test the performance of various circulatory support systems including the intra-aortic balloon pump, left and right ventricular assist devices, or cardiopulmonary support systems such as extracorporeal membrane oxygenation.

In vitro characterization and performance testing of the ension pediatric cardiopulmonary assist system.

In the last 40 years, mechanical circulatory support devices have become an effective option for the treatment of end-stage heart failure in adults. Few possibilities, however, are available for pediatric cardiopulmonary support. Ension Inc. (Pittsburgh, PA) is developing a pediatric cardiopulmonary assist system (pCAS) intended to address the limitations of existing devices used for this patient population. The pCAS device is an integrated unit containing an oxygenator and pump within a single casing, significantly reducing the size and blood-contacting surface area in comparison to current devices. Prototype pCAS devices produce appropriate flows and pressures while minimizing priming volume and preparation time. The pCAS was tested on a mock circulation designed to approximate the hemodynamic parameters of a small infant using a 10-Fr. extracorporeal membrane oxygenation inflow cannula and an 8-Fr. extracorporeal membrane oxygenation outflow cannula. Revision 4 of the device provided a flow rate of 0.42 L/min at 6,500 RPM. Revision 5, featuring improved impeller and diffuser designs, provided a flow rate of 0.57 L/min at 5,000 RPM. The performance tests indicate that for this cannulae combination, the pCAS pump is capable of delivering sufficient flows for patients <5 kg.