The objective of this study was to determine the relationship between descending motor pathway reorganization and abnormal coordination, defined as a reduced set of muscle coactivation patterns between shoulder and elbow muscles in hemiparetic chronic stroke subjects, using transcranial magnetic stimulation (TMS). Specifically, we wanted to 1) determine the relationship...
The polymerization of the microtubule-associated protein, tau, into insoluble filaments is common to Alzheimer's disease (AD) and in a variety of dementias. The conformational change required for tau to transition from soluble monomers to filamentous AD pathology involves the extreme N-terminus of tau coming into contact with other regions of...
Following dopaminergic denervation in Parkinson's Disease, firing patterns in several basal ganglia neuron populations are pathologically altered. In the globus pallidus (GP), this manifests as a loss of autonomous, rhythmic, high-frequency pacemaking and an appearance of correlated, oscillatory bursting. This oscillatory bursting is best disrupted through high-frequency stimulation of affected...
Neurofibrillary tangle (NFT) formation in Alzheimer's disease (AD) and tauopathies occurs when tau protein adopts secondary structure and self-aggregates within neurons. Accompanying NFT maturation are post-translational modifications to tau; hyperphosphorylation, truncation and conformational changes occur in a highly sequential manner. In contrast, granulovacuolar degeneration bodies (GVDs) are a second type...
Stem cells show great promise as cellular replacement and drug delivery therapies for a number of neurological disorders. This dissertation examines embryonic and adult types of stem cells, their plasticity, and mechanisms governing their development (Chapters 1-5). Our studies illustrate that leukemia inhibitory factor (LIF) signaling and bone morphogenetic protein...
The goal of this study was to investigate the properties of the retinal ganglion cell receptive field at low light levels. There has been considerable interest in whether the surround of a ganglion cell receptive field disappears and the center expands in size under scotopic conditions. The previous data from...
The goal of this dissertation was to examine the influence of motivational incentives on visual spatial attention in patients with probable Alzheimer's Disease (PRAD), patients with mild cognitive impairment (MCI) and healthy age-matched control subjects (EC). Specifically, I compared the ability of monetary incentives to influence behavioral and neural performance...
Information processing in the striatum is crucial for voluntary movement control and associative learning and in the normal condition is subject to balanced dopaminergic and cholinergic modulation. However, in Parkinson's disease (PD) striatal dopamine (DA) level falls because of degeneration of DA neurons in the substantia nigra pars compacta and...
Primary Progressive Aphasia (PPA) is an aphasic dementia syndrome caused by neurodegenerative disease in which linguistic abilities are selectively disrupted in the relative absence of other cognitive deficits in early stages. The studies presented in this thesis were designed to examine the integrity of word and object processing by contrasting...
A comprehensive understanding of human memory requires both cognitive and neural descriptions of memory processes along with a conception of how memory processing drives behavioral responses and subjective experiences. Noninvasive neuroimaging techniques have greatly extended our understanding of the functional characteristics of human memory, and how neural events give rise...