Syncopation (movement antiphase to a pacing stimulus) has proven to engage a more distributed network of cortical and subcortical structures than does synchronization (movement in-phase with the same stimulus). In addition, the networks recruited may be modality specific. For example, left superior temporal gyrus (STG) activity occurs during auditory-motor, but not visuomotor synchronization. The present study used FMRI and behavioral measures to assess whether aspects of the neural networks for synchronization and syncopation are modality specific. A standard block design allowed us to measure levels of the BOLD response from six subjects while they syncopated or synchronized (right hand) with an auditory or visual pacer at 1.33 Hz. Behavioral results confirmed that syncopation is more variable than synchronization. FMRI revealed modality specific activation that nevertheless indexed the coordination pattern: activity in occipital cortex was greater during visuomotor syncopation than synchronization. The ...

While the pathological changes induced by the loss of dopamine innervation in the basal ganglia by Parkinson's disease are well studied, little is known about functional changes in the neural circuitry of this area during normal aging. Accordingly we have analyzed age-associated changes in the basal ganglia of behaviorally characterized, awake rhesus monkeys, using pharmacological MRI to map responses to dopaminergic stimulation. Apomorphine, a mixed D1/D2 dopamine receptor agonist, significantly reduced neural activity in the substantia nigra (SN) of young adult rhesus monkeys, while evoking little change in aged animals. Compared to young animals, both apomorphine and amphetamine (an indirect D1/D2 dopamine receptor agonist) significantly increased activation of the aged rhesus globus pallidus externa (GPe). In addition, the aged animals showed decreased activity in the putamen in response to amphetamine administration. The changes in SN, GPe and putamen activation are consistent with the concept that ba...

It is believed that the olfactory bulb (OB) codes the olfactory information from the periphery into a spatial activity pattern in the glomerular layer. Here we used high-resolution fMRI to examine how the structural features of odorants are represented spatially in the entire rat OB. The whole OB mapping results showed that the areas activated by the three structurally related odorants, iso-amyl acetate, ethyl acetate, and benzyl acetate distributed broadly across the entire OB. Many of the activated regions are shared by all three odorants. The patterns are more similar between the two aliphatic acetates than between the aliphatic and aromatic acetates. Statistical analysis showed that the similarity between the patterns of iso-amyl acetate in different exposures is significantly higher than between the patterns of iso-amyl acetate and ethyl acetate. One major cluster, covering nearly 60 glomeruli (thresholded at p < 0.01) at the latero-ventral region in the anterior end of the OB, was activated by the al...

Fetal grafts show little migration after transplantation into the lesioned brain, whereas transplanted stem cells will migrate from the contralateral hemisphere to a focal ischaemic lesion. To track the migration of grafted cells, conditionally immortalized neural stem cells from the MHP36 cell line were labelled in vitro with the bifunctional contrast agent GRID which can be detected by magnetic resonance imaging (MRI) and fluorescent microscopy. Following 60 minutes of middle cerebral artery occlusion or sham surgery, rat brains were imaged by T1-, T2-, and proton density-weighted MRI in a 4.7T Varian imaging system to obtain pre-grafting coronal images of the stroke lesion. All animals were then transplanted contralaterally with 100,000 labelled stem cells in two deposits. The in vivo migration of grafted stem cells was assessed by scanning both transplanted ischaemic and control rats at 1, 7, and 14 days post-grafting. Fluorescent microscopy validated our in vivo images and indicated that some cells mi...

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....

It has been shown that the blood oxygenation level dependent (BOLD) functional MRI signal at magnetic field strengths of ≤ 1.5T arises predominantly from large vessels, which can be quite distant from the sites of neuronal activity. To improve the spatial localization to the active tissues/capillaries, the use of high field magnets has been proposed. To test this hypothesis, we evaluated the microvascular versus the macrovascular contribution to the BOLD response at high fields (4 and 7T) following visual stimulation in humans. Diffusion-weighted BOLD fMRI was used to selectively attenuate the fast-moving (large-vessel) fMRI signals. Two acquisition schemes were used: a gradient-echo scheme which is sensitive to both large- and small-vessel BOLD effects and a spin-echo scheme which should mitigate large-vessel BOLD effects. A comparison was made between the two sets of results. Diffusion-weighted BOLD fMRI was performed on 24 normal humans with graded flow-crushing gradients (4-7 b values). The visual stim...

Postmortem studies indicate a temporal sequence of primary allocortical and secondary neocortical degeneration during Alzheimer disease (AD) progression. Hippocampus (HC) atrophy correlates with allocortical neuronal degeneration and atrophy of the corpus callosum (CC) reflects loss of intracortical projecting pyramidal neurons in neocortex. First, we wanted to determine the temporal sequence and rate of degeneration of HC and CC in AD. Second, to answer the question, whether rates of atrophy were correlated with rates of cognitive decline and third, whether both markers could be proposed as potential morphological parameters for mapping drug effects on brain structure in longitudinally studied AD patients and healthy control subjects. MRI-derived measures of CC and HC were compared between 27 clinically diagnosed AD patients and 28 age- and gender-matched healthy control subjects. Rates of CC and HC atrophy were determined in 21 AD patients and 10 control subjects studied longitudinally. We found mean rel...

Brain structure size changes with normal aging, but the rate at which different structures change is controversial, likely owing to inferences based on cross-sectional study. We used MRI performed twice, 4 years apart, to compare rate of age-related size change of the corpus callosum, which has been inconsistently observed to thin with age, with change in the lateral ventricles, which incontrovertibly enlarge. Subjects were 215 community dwelling, elderly men (70-82 yr), participants in the NHLBI longitudinal study of cardiovascular risk factors. Contiguous sagittal and coronal images were acquired and realigned to the anterior commissure. A midsagittal image was extracted for semi-automated callosal edge identification; 3 coronal slices were extracted for ventricular outlining. MRIs were processed together and scored blind to subject identity. Percent change in size was significant for callosal and ventricular measures but rate of annual ventricular expansion (2.9%) was significantly greater than rate of ...

To depict the neural representation of the cross-modal transfer of information between the tactile and visual shape representation, we performed 3 Tesla functional MRI with 7 normal volunteers. During the scan, two dimensional shape patterns were simultaneously presented both tactually and visually. Two diagram patterns engraved side-by-side on a plastic tile were explored by the right thumb, while similar patterns were presented through the video-projector. Four different matching tasks were performed as separate sessions: tactile-tactile with eyes closed (TT), tactile-tactile with visual input (TTv), visual-visual with tactile input (VVt), and tactile-visual (TV). Each session was repeated twice. Tactile shape matching task activated the left primary sensorimotor area, bilateral superior and inferior parietal lobule, anterior SMA and bilateral cerebellum. Visual matching (VVt - TT) activated the primary visual cortex, lingual and fusiform gyri bilaterally. Cross-modal area, which was activated by both TV...

The subthalamic nucleus (STh) is a small subcortical structure which is involved in regulating motor as well as cognitive functions. Due to its small size and close proximity to other small subcortical structures, it has been a challenge to localize and visualize it using magnetic resonance imaging (MRI). Currently there are several standard atlases available that are used to localize the STh in functional MRI studies and clinical procedures such as deep brain stimulation (DBS). DBS is an increasingly common neurosurgical procedure that has been successfully used to alleviate motor symptoms present in Parkinson's disease. However, current atlases are based on low sample sizes and restricted age ranges ([Schaltenbrand and Wahren, 1977][1]), and hence the use of these atlases effectively ignores the substantial structural brain changes that are associated with aging. In the present study, ultra-high field 7 tesla (T) magnetic resonance imaging (MRI) in humans was used to visualize and segment the STh in youn...