William E. Rogers

A library of cortical morphology analysis tools to study development, aging and genetics of cerebral cortex.

Sharing of analysis techniques and tools is among the main driving forces of modern neuroscience. We describe a library of tools developed to quantify global and regional differences in cortical anatomy in high resolution structural MR images. This library is distributed as a plug-in application for popular structural analysis software, BrainVisa (BV). It contains tools to measure global and regional gyrification, gray matter thickness and sulcal and gyral white matter spans. We provide a description of each tool and examples for several case studies to demonstrate their use. These examples show how the BV library was used to study cortical folding process during antenatal development and recapitulation of this process during cerebral aging. Further, the BV library was used to perform translation research in humans and non-human primates on the genetics of cerebral gyrification. This library, including source code and self-contained binaries for popular computer platforms, is available from the NIH-Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC) resource (http://www.nitrc.org/projects/brainvisa_ext).

An Experimental and Theoretical Framework for Manufacturing Prosthetic Sockets for Transtibial Amputees

Selective laser sintering (SLS) is a powerful manufacturing technology that does not require part-specific tooling or significant human intervention and provides the ability to easily generate parts with complex geometric designs. The present work focuses on developing a manufacturing framework using this technology to produce subject-specific transtibial amputee prosthetic sockets made of Duraform PA, which is a nylon-based material. The framework includes establishing an overall socket design (using the patellar-tendon bearing approach), performing a structural analysis using the finite element method (FEM) to ensure structural reliability during patient use, and validating the results by comparing the model output with experimental data. The validation included quantifying the failure conditions for the socket through a series of bending moment and compression tests. In the case study performed, the FEM results were within 3% of the experimental failure loads for the socket and were considered satisfactory

Motor unit action potential components and physiologic duration

Motor unit action potentials (MUAPs) recorded from the same motor unit at two distances along the biceps brachii muscle with monopolar needle electrodes at high amplifier gains (20 μV/division) and averaged 2000–3000 times reveal total potential durations of 39.6 ± 4.6 ms. In addition, the terminal segment for each of these two MUAPs contained a late far‐field potential with a mean duration of 23.8 ± 4.1 ms. Computer simulations of MUAPs suggest that this long‐duration positive far‐field mirrors the true morphology of the intracellular action potential (IAP), which is monophasic positive, possessing a terminal repolarization phase approaching 30 ms. This investigation suggests that the MUAPs physiologic duration is directly proportional to the muscle fiber length and the IAPs duration, which becomes manifest as a positive far‐field potential when the IAP encounters the musculotendinous junction and slowly dissipates. The leading/trailing dipole model is used to explain qualitatively this studys quantitative clinical and computer simulation findings.

Anatomical Global Spatial Normalization

Anatomical global spatial normalization (aGSN) is presented as a method to scale high-resolution brain images to control for variability in brain size without altering the mean size of other brain structures. Two types of mean preserving scaling methods were investigated, “shape preserving” and “shape standardizing”. aGSN was tested by examining 56 brain structures from an adult brain atlas of 40 individuals (LPBA40) before and after normalization, with detailed analyses of cerebral hemispheres, all gyri collectively, cerebellum, brainstem, and left and right caudate, putamen, and hippocampus. Mean sizes of brain structures as measured by volume, distance, and area were preserved and variance reduced for both types of scale factors. An interesting finding was that scale factors derived from each of the ten brain structures were also mean preserving. However, variance was best reduced using whole brain hemispheres as the reference structure, and this reduction was related to its high average correlation with other brain structures. The fractional reduction in variance of structure volumes was directly related to ρ2, the square of the reference-to-structure correlation coefficient. The average reduction in variance in volumes by aGSN with whole brain hemispheres as the reference structure was approximately 32%. An analytical method was provided to directly convert between conventional and aGSN scale factors to support adaptation of aGSN to popular spatial normalization software packages.

Design and Analysis of Orthogonally Compliant Features for Local Contact Pressure Relief in Transtibial Prostheses

A very attractive advantage of manufacturing prosthetic sockets using solid freeform fabrication is the freedom to introduce design solutions that would be difficult to implement using traditional manufacturing techniques. Such is the case with compliant features embedded in amputee prosthetic sockets to relieve contact pressure at the residual limb-socket interface. The purpose of this study was to present a framework for designing compliant features to be incorporated into transtibial sockets and manufacturing prototypes using selective laser sintering (SLS) and Duraform material. The design process included identifying optimal compliant features using topology optimization algorithms and integrating these features within the geometry of the socket model. Using this process, a compliant feature consisting of spiral beams and a supporting external structure was identified. To assess its effectiveness in reducing residual limb-socket interface pressure, a case study was conducted using SLS manufactured prototypes to quantify the difference in interface pressure while a patient walked at his self-selected pace with one noncompliant and two different compliant sockets. The pressure measurements were performed using thin pressure transducers located at the distal tibia and fibula head. The measurements revealed that the socket with the greatest compliance reduced the average and peak pressure by 22% and 45% at the anterior side distal tibia, respectively, and 19% and 23% at the lateral side of the fibula head, respectively. These results indicate that the integration of compliant features within the socket structure is an effective way to reduce potentially harmful contact pressure and increase patient comfort.

Positive sharp wave and fibrillation potential modeling

A finite muscle fiber simulation program which calculates the extracellular potential for any given intracellular action potential (IAP) was used to model a fibrillation potential and a positive sharp wave. This computer model employs the core conductor model assumptions for an active muscle fiber and allows two distinct types of end effects: a cut or a crush. A “cut end” is defined as a membrane segment with the termination of both active and passive ion channels. The “crush end” is simulated as a focal membrane segment which blocks action potential propagation, and is connected to a region of normal membrane on either side of it so that a normal transmembrane potential is maintained beyond the crush zone. A prototypical positive sharp wave of appropriate amplitude and duration could only be detected extracellularly by using an IAP of the configuration found in denervated rat muscle recorded from a muscle fiber terminating in a crush segment of membrane.

Concurrent TMS to the primary motor cortex augments slow motor learning

Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool, with one FDA approved use. While TMS alone is able to up- (or down-) regulate a targeted neural system, we argue that TMS applied as an adjuvant is more effective for repetitive physical, behavioral and cognitive therapies, that is, therapies which are designed to alter the network properties of neural systems through Hebbian learning. We tested this hypothesis in the context of a slow motor learning paradigm. Healthy right-handed individuals were assigned to receive 5 Hz TMS (TMS group) or sham TMS (sham group) to the right primary motor cortex (M1) as they performed daily motor practice of a digit sequence task with their non-dominant hand for 4 weeks. Resting cerebral blood flow (CBF) was measured by H2(15)O PET at baseline and after 4 weeks of practice. Sequence performance was measured daily as the number of correct sequences performed, and modeled using a hyperbolic function. Sequence performance increased significantly at 4 weeks relative to baseline in both groups. The TMS group had a significant additional improvement in performance, specifically, in the rate of skill acquisition. In both groups, an improvement in sequence timing and transfer of skills to non-trained motor domains was also found. Compared to the sham group, the TMS group demonstrated increases in resting CBF specifically in regions known to mediate skill learning namely, the M1, cingulate cortex, putamen, hippocampus, and cerebellum. These results indicate that TMS applied concomitantly augments behavioral effects of motor practice, with corresponding neural plasticity in motor sequence learning network. These findings are the first demonstration of the behavioral and neural enhancing effects of TMS on slow motor practice and have direct application in neurorehabilitation where TMS could be applied in conjunction with physical therapy.

Towards a Healthy Human Model of Neural Disorders of Movement

A quantitative approach to virtual-lesion physiology is presented which integrates event-related fMRI, image-guided, repetitive, transcranial magnetic stimulation (irTMS), and simultaneous recording of 3-D movement kinematics. By linking motor neuroscience with clinical disorders of motor function, our method allows development of a healthy, human system model of disorders of skilled action.