Present learning theories endorse the importance of synaptic plasticity; experience with a stimulus, problem, or procedure is associated with the progressive diminution in synaptic activity across most connections but increased synaptic efficiency across those that are most relevant for behavioral success. Persons with schizophrenia (SZ) may differ from normal volunteers (NV) by virtue of their inability to enhance synaptic efficiency at critical sites during learning. This visual learning study was designed to assess the ways in which SZ and NV differ in their neural response to visual recognition training. NV (n=6, mean age=29) and SZ (n=6, mean age=35) participated in two event-related functional magnetic resonance imaging studies (er_fMRI). The first was obtained prior to training and the second following completion of four training sessions. The task used a 6 second delay between the onset of the first and second stimulus (black rectangle within a frame) to assess hemodynamic response functions during...

Prior studies have used fMRI to measure the onset of neural activity from a stable baseline with a temporal precision on the order of 100 msec. Many important neural processes, however, reveal themselves as increases in activity that lie on top of another neural response. We attempted to determine whether fMRI could measure the timing of an increase that occurred 200 msec after initial response. Subjects viewed stimuli from three conditions. In our baseline condition, a low contrast flickering checkerboard was presented for 600 msec. We added a 400 msec contrast increment to this stimulus either at a 200 msec delay or immediately upon stimulus presentation; thus in the delay condition the low contrast checkerboard increased its contrast after 200 msec and remained high contrast for 400 msec, while in the immediate condition a high contrast flickering checkerboard reduced its contrast after 400 msec and remained low for 200 msec. We acquired BOLD fMR images every 100 msec (TR) while these conditions were pr...

AD selectively affects mesial temporal lobe regions early in its course. Structural MRI (sMRI) studies have shown that atrophy of the hippocampus (HF) and rostral parahippocampal gyrus (PHG) predicts progression to AD in subjects at risk. In healthy subjects, functional MRI (fMRI) memory tasks activate these regions; it is not yet clear how atrophy and fMRI activation are related in individuals at risk for AD. We studied 22 older participants in a longitudinal study of cognition who had a range of impairment on the Clinical Dementia Rating Sum-of-Boxes score (CDR-SB=0.0-4.5). Subjects underwent 1) sMRI scans on which HF and PHG regions of interest (ROIs) were manually drawn; 2) an fMRI block-design picture-encoding paradigm known to activate these regions. The number of fMRI voxels in each ROI with task-related activity was calculated. As expected, worse cognitive impairment was associated with smaller mesial temporal volumes (significant correlations: CDR-SB & RHF, r = -0.49, p<.03; CDR-SB & LPHG, r = -0....

Parkinson’s disease (PD) is a neurodegenerative disorder characterized pathologically by misfolded and aggregated α-synuclein (α-syn) protein. Decreasing the expression of α-syn therefore has considerable therapeutic potential. However, noninvasive drug...

The perceived subjective visual vertical (SVV) is an important sign of a vestibular otolith tone imbalance in the roll plane. Previous studies suggested that unilateral pontomedullary brainstem lesions cause ipsiversive roll-tilt of SVV, whereas pontomesencephalic lesions cause contraversive roll-tilts of SVV. However, previous data were of limited quality and lacked a statistical approach. We therefore tested roll-tilt of the SVV in 79 human patients with acute unilateral brainstem lesions due to stroke by applying modern statistical lesion–behavior mapping analysis. Roll-tilt of the SVV was verified to be a brainstem sign, and for the first time it was confirmed statistically that lesions of the medial longitudinal fasciculus (MLF) and the medial vestibular nucleus are associated with ipsiversive tilt of the SVV, whereas contraversive tilts are associated with lesions affecting the rostral interstitial nucleus of the MLF, the superior cerebellar peduncle, the oculomotor nucleus, and the interstitial nucl...

A new technique based on diffusion tensor imaging and computational neuroanatomy was developed to efficiently and quantitatively characterize the three-dimensional morphology of the developing brains. The technique was used to analyze the phenotype of conditional Bcl-x knock-out mice, in which the bcl-x gene was deleted specifically in neurons of the cerebral cortex and hippocampus beginning at embryonic day 13.5 as cells became postmitotic. Affected brain regions and associated axonal tracts showed severe atrophy in adult Bcl-x- deficient mice. Longitudinal studies revealed that these phenotypes are established by regressive processes that occur primarily during the first postnatal week, whereas neurogenesis and migration showed no obvious abnormality during embryonic stages. Specific families of white matter tracts that once formed normally during the embryonic stages underwent dramatic degeneration postnatally. Thus, this technique serves as a powerful tool to efficiently localize temporal and spatial m...

Amnesia is the most well known symptom of Alzheimer's disease (AD), and typically the earliest to be noticed, but the disease is soon accompanied by a range of disparate cognitive disruptions such as in linguistic and visuospatial abilities and in overall executive function ([Perry and Hodges, 1999

Non-human primate (NHP) models are critical for understanding typical development and alterations in social attention in neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). The goal of this study was to characterize the developmental t...

In early Alzheimer's disease (AD), the hippocampal region is the area most severely affected by cellular and structural alterations, yet glucose hypometabolism predominates in the posterior association cortex and posterior cingulate gyrus. One prevalent hypothesis to account for this discrepancy is that posterior cingulate hypometabolism results from disconnection from the hippocampus through disruption of the cingulum bundle. However, only partial and indirect evidence currently supports this hypothesis. Thus, using structural magnetic resonance imaging and 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography in 18 patients with early AD, we assessed the relationships between hippocampal atrophy, white matter integrity, and gray matter metabolism by means of a whole-brain voxel-based correlative approach. We found that hippocampal atrophy is specifically related to cingulum bundle disruption, which is in turn highly correlated to hypometabolism of the posterior cingulate cortex but also of the mid...

Introduction: Deletions and duplications of the chromosome 16p11.2 locus are associated with autism spectrum disorders, schizophrenia, cognitive and language deficits. Diffusion tensor imaging (DTI) studies have reported increases and decreases in fract...