Faculty Bibliography

Shape analysis has become of increasing interest to the neuroimaging community due to its potential to precisely locate morphological changes between healthy and pathological structures. This manuscript presents a comprehensive set of tools for the computation of 3D structural statistical shape analysis. It has been applied in several studies on brain morphometry, but can potentially be employed in other 3D shape problems. Its main limitations is the necessity of spherical topology.The input of the proposed shape analysis is a set of binary segmentation of a single brain structure, such as the hippocampus or caudate. These segmentations are converted into a corresponding spherical harmonic description (SPHARM), which is then sampled into a triangulated surfaces (SPHARM-PDM). After alignment, differences between groups of surfaces are computed using the Hotelling T(2) two sample metric. Statistical p-values, both raw and corrected for multiple comparisons, result in significance maps. Additional visualization of the group tests are provided via mean difference magnitude and vector maps, as well as maps of the group covariance information.The correction for multiple comparisons is performed via two separate methods that each have a distinct view of the problem. The first one aims to control the family-wise error rate (FWER) or false-positives via the extrema histogram of non-parametric permutations. The second method controls the false discovery rate and results in a less conservative estimate of the false-negatives.

The emergence of open-source libraries and development tools in the last decade has changed the process of academic software development in many ways. In medical image processing and visualization this change is especially evident, also because open source projects are actively furthered by grant funding institutions. This manuscript presents the use of such development tools and libraries at the UNC Neuro-Image Analysis Laboratory for open source applications and tools. We have also experienced in our research that the development of open source in academics raises the issue of access to unpublished methodology. The strategy at our laboratory is to combine all in-house libraries and applications into a single repository that consists of two parts: a fully open source part that is distributed under a Berkley-style license and a private, closed source part with unpublished tools and methods. Access to the open source part is unrestricted, whereas the private parts can only be downloaded via cvs user login. This setup solved our issues regarding unpublished methodology, as migration from the private to the open source part is very simple. Overall our experience with this development environment within the academic setting is very positive.

Work in progress towards modeling shape statistics of multi-object complexes is presented. Constraints defined by the set of objects such as a compact representation of object shape relationships and correlation of shape changes might have advantages for automatic segmentation and group discrimination. We present a concept for statistical multi-object modeling and discuss the major challenges which are a reduction to a small set of descriptive features, calculation of mean and variability via curved statistics, the choice of aligning sets of multiple objects, and the problem of describing the statistics of object pose and object shape and their interrelationship. Shape modeling and analysis is demonstrated with an application to a longitudinal autism study, with shape modeling of sets of 10 subcortical structures in a population of 20 subjects.

Learning and memory depend on signaling molecules that affect synaptic efficacy. The cytoskeleton has been implicated in regulating synaptic transmission but its role in learning and memory is poorly understood. Fear learning depends on plasticity in the lateral nucleus of the amygdala. We therefore examined whether the cytoskeletal-regulatory protein, myosin light chain kinase, might contribute to fear learning in the rat lateral amygdala. Microinjection of ML-7, a specific inhibitor of myosin light chain kinase, into the lateral nucleus of the amygdala before fear conditioning, but not immediately afterward, enhanced both short-term memory and long-term memory, suggesting that myosin light chain kinase is involved specifically in memory acquisition rather than in posttraining consolidation of memory. Myosin light chain kinase inhibitor had no effect on memory retrieval. Furthermore, ML-7 had no effect on behavior when the training stimuli were presented in a non-associative manner. Anatomical studies showed that myosin light chain kinase is present in cells throughout lateral nucleus of the amygdala and is localized to dendritic shafts and spines that are postsynaptic to the projections from the auditory thalamus to lateral nucleus of the amygdala, a pathway specifically implicated in fear learning. Inhibition of myosin light chain kinase enhanced long-term potentiation, a physiological model of learning, in the auditory thalamic pathway to the lateral nucleus of the amygdala. When ML-7 was applied without associative tetanic stimulation it had no effect on synaptic responses in lateral nucleus of the amygdala. Thus, myosin light chain kinase activity in lateral nucleus of the amygdala appears to normally suppress synaptic plasticity in the circuits underlying fear learning, suggesting that myosin light chain kinase may help prevent the acquisition of irrelevant fears. Impairment of this mechanism could contribute to pathological fear learning