Rehabilitation robotics: pilot trial of a spatial extension for MIT-Manus

BACKGROUND: Previous results with the planar robot MIT-MANUS demonstrated positive benefits in trials with over 250 stroke patients. Consistent with motor learning, the positive effects did not generalize to other muscle groups or limb segments. Therefore we are designing a new class of robots to exercise other muscle groups or limb segments. This paper presents basic engineering aspects of a novel robotic module that extends our approach to anti-gravity movements out of the horizontal plane and a pilot study with 10 outpatients. Patients were trained during the initial six-weeks with the planar module (i.e., performance-based training limited to horizontal movements with gravity compensation). This training was followed by six-weeks of robotic therapy that focused on performing vertical arm movements against gravity. The 12-week protocol includes three one-hour robot therapy sessions per week (total 36 robot treatment sessions). RESULTS: Pilot study demonstrated that the protocol was safe and well tolerated with no patient presenting any adverse effect. Consistent with our past experience with persons with chronic strokes, there was a statistically significant reduction in tone measurement from admission to discharge of performance-based planar robot therapy and we have not observed increases in muscle tone or spasticity during the anti-gravity training protocol. Pilot results showed also a reduction in shoulder-elbow impairment following planar horizontal training. Furthermore, it suggested an additional reduction in shoulder-elbow impairment following the anti-gravity training. CONCLUSION: Our clinical experiments have focused on a fundamental question of whether task specific robotic training influences brain recovery. To date several studies demonstrate that in mature and damaged nervous systems, nurture indeed has an effect on nature. The improved recovery is most pronounced in the trained limb segments. We have now embarked on experiments that test whether we can continue to influence recovery, long after the acute insult, with a novel class of spatial robotic devices. This pilot results support the pursuit of further clinical trials to test efficacy and the pursuit of optimal therapy following brain injury

Macro-meso-microsystems integration in LTCC : LDRD report.

Low Temperature Cofired Ceramic (LTCC) has proven to be an enabling medium for microsystem technologies, because of its desirable electrical, physical, and chemical properties coupled with its capability for rapid prototyping and scalable manufacturing of components. LTCC is viewed as an extension of hybrid microcircuits, and in that function it enables development, testing, and deployment of silicon microsystems. However, its versatility has allowed it to succeed as a microsystem medium in its own right, with applications in non-microelectronic meso-scale devices and in a range of sensor devices. Applications include silicon microfluidic ''chip-and-wire'' systems and fluid grid array (FGA)/microfluidic multichip modules using embedded channels in LTCC, and cofired electro-mechanical systems with moving parts. Both the microfluidic and mechanical system applications are enabled by sacrificial volume materials (SVM), which serve to create and maintain cavities and separation gaps during the lamination and cofiring process. SVMs consisting of thermally fugitive or partially inert materials are easily incorporated. Recognizing the premium on devices that are cofired rather than assembled, we report on functional-as-released and functional-as-fired moving parts. Additional applications for cofired transparent windows, some as small as an optical fiber, are also described. The applications described help pave the way for widespread application of LTCC to biomedical, control, analysis, characterization, and radio frequency (RF) functions for macro-meso-microsystems

Biotechnology development for biomedical applications.

Sandia's scientific and engineering expertise in the fields of computational biology, high-performance prosthetic limbs, biodetection, and bioinformatics has been applied to specific problems at the forefront of cancer research. Molecular modeling was employed to design stable mutations of the enzyme L-asparaginase with improved selectivity for asparagine over other amino acids with the potential for improved cancer chemotherapy. New electrospun polymer composites with improved electrical conductivity and mechanical compliance have been demonstrated with the promise of direct interfacing between the peripheral nervous system and the control electronics of advanced prosthetics. The capture of rare circulating tumor cells has been demonstrated on a microfluidic chip produced with a versatile fabrication processes capable of integration with existing lab-on-a-chip and biosensor technology. And software tools have been developed to increase the calculation speed of clustered heat maps for the display of relationships in large arrays of protein data. All these projects were carried out in collaboration with researchers at the University of Texas M. D. Anderson Cancer Center in Houston, TX

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients

Introduction: Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations. Methods: We studied six samples (N = 365 participants) covering the spectrum of AD and SVD, including genetically defined samples. We calculated diffusion measures from DTI and free water imaging. Simple linear, multivariable random forest, and voxel-based regressions were used to evaluate associations between AD biomarkers (amyloid beta, tau), SVD imaging markers, and diffusion measures. Results: SVD markers were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analysis across all memory clinic samples. Voxel-wise analyses between tau and diffusion measures were not significant. Discussion: In memory clinic patients, the effect of SVD on diffusion alterations largely exceeds the effect of AD, supporting the value of diffusion measures as markers of SVD.Fil: Finsterwalder, Sofia. Ludwig Maximilians Universitat; AlemaniaFil: Vlegels, Naomi. University of Utrecht; Países BajosFil: Gesierich, Benno. Ludwig Maximilians Universitat; AlemaniaFil: Araque Caballero, Miguel Á.. Ludwig Maximilians Universitat; Alemania. German Center for Neurodegenerative Diseases; AlemaniaFil: Weaver, Nick A.. University of Utrecht; Países BajosFil: Franzmeier, Nicolai. Ludwig Maximilians Universitat; AlemaniaFil: Georgakis, Marios K.. Ludwig Maximilians Universitat; AlemaniaFil: Konieczny, Marek J.. Ludwig Maximilians Universitat; AlemaniaFil: Koek, Huiberdina L.. University of Utrecht; Países BajosFil: Karch, Celeste M.. Washington University in St. Louis; Estados UnidosFil: Graff Radford, Neill R.. Mayo Clinic In Jacksonville; Estados UnidosFil: Salloway, Stephen. Butler Hospital; Estados UnidosFil: Oh, Hwamee. University Brown; Estados UnidosFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Chhatwal, Jasmeer P.. Harvard Medical School; Estados UnidosFil: Jessen, Frank. Universitat zu Köln; Alemania. German Center for Neurodegenerative Diseases; AlemaniaFil: Düzel, Emrah. Otto-von-Guericke-Universität Magdeburg; Alemania. German Center for Neurodegenerative Diseases; AlemaniaFil: Dobisch, Laura. Otto-von-Guericke-Universität Magdeburg; Alemania. German Center for Neurodegenerative Diseases; AlemaniaFil: Metzger, Coraline. Otto-von-Guericke-Universität Magdeburg; Alemania. German Center for Neurodegenerative Diseases; AlemaniaFil: Peters, Oliver. German Center for Neurodegenerative Diseases; Alemania. Freie Universität Berlin; AlemaniaFil: Incesoy, Enise I.. Freie Universität Berlin; AlemaniaFil: Priller, Josef. Freie Universität Berlin; Alemania. German Center for Neurodegenerative Diseases; AlemaniaFil: Spruth, Eike J.. Freie Universität Berlin; Alemania. German Center for Neurodegenerative Diseases; AlemaniaFil: Schneider, Anja. German Center for Neurodegenerative Diseases; Alemania. University Hospital Bonn; AlemaniaFil: Fließbach, Klaus. German Center for Neurodegenerative Diseases; Alemania. University Hospital Bonn; AlemaniaFil: Buerger, Katharina. Ludwig Maximilians Universitat; Alemania. German Center for Neurodegenerative Diseases; AlemaniaFil: Janowitz, Daniel. Ludwig Maximilians Universitat; AlemaniaFil: Teipel, Stefan J.. German Center for Neurodegenerative Diseases; Alemania. Rostock University Medical Center; AlemaniaFil: Kilimann, Ingo. German Center for Neurodegenerative Diseases; Alemania. Rostock University Medical Center; AlemaniaFil: Laske, Christoph. German Center for Neurodegenerative Diseases; Alemania. University of Tübingen; Alemani

Segregation of functional networks is associated with cognitive resilience in Alzheimer\u27s disease

Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer\u27s disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal ageing, we tested the hypothesis that higher segregation of the brain\u27s connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer\u27s disease. Using resting-state functional MRI, we assessed both resting-state functional MRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: (i) 108 individuals with autosomal dominantly inherited Alzheimer\u27s disease and 71 non-carrier controls; and (ii) 156 amyloid-PET-positive subjects across the spectrum of sporadic Alzheimer\u27s disease and 184 amyloid-negative controls. In the autosomal dominant Alzheimer\u27s disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer\u27s sample, disease stage was assessed by temporal lobe tau-PET (i.e. composite across Braak stage I and III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer\u27s disease, we found higher functional MRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (P = 0.007). Similarly, for patients with sporadic Alzheimer\u27s disease, higher functional MRI-assessed system segregation was associated with less decrement in global cognition (P = 0.001) and episodic memory (P = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer\u27s disease