Myelination, the elaboration of myelin surrounding neuronal axons, is essential for normal brain function. The development of the myelin sheath enables rapid synchronized communication across the neural systems responsible for higher order cognitive functioning. Despite this critical role, quantitative visualization of myelination in vivo is not possible with current neuroimaging techniques including diffusion tensor and structural magnetic resonance imaging (MRI). Although these techniques offer insight into structural maturation, they reflect several different facets of development, e.g., changes in axonal size, density, coherence, and membrane structure; lipid, protein, and macromolecule content; and water compartmentalization. Consequently, observed signal changes are ambiguous, hindering meaningful inferences between imaging findings and metrics of learning, behavior or cognition. Here we present the first quantitative study of myelination in healthy human infants, from 3 to 11 months of age. Using a ...

Our previous studies have established the utility of Mn-enhanced MRI (MEMRI) for detecting aggregate sound-evoked activity within the inferior colliculus (IC) of hearing and deaf mice. The present goal was to determine the spatial resolution of MEMRI by examining sound frequency-dependent patterns of activity in the mouse IC. Electrophysiological recordings have established the tonotopic map in mouse IC using threshold stimulation. However, there is little information on the spatial pattern of activity for suprathreshold stimulation. Following Mn injections, mice were exposed to one of the following acoustic stimuli in the free field at 65-89 dB SPL: wideband (1-59 kHz), high frequency band pass (20-50 kHz), or pure tones (16 or 40 kHz). Wideband stimulation elicited a diffuse pattern of IC enhancement covering most of the central nucleus, and this spatial pattern became more confined to the ventral-caudal IC with high frequency band pass stimulation. The spatial pattern resolved into a clear ventral-cauda...

Functional magnetic resonance imaging (fMRI) studies in humans have hitherto failed to demonstrate activity changes in the direct vicinity of transcranial magnetic stimulation (TMS) that cannot be attributed to re-afferent somatosensory feedback or a spread of excitation. In order to investigate the underlying activity changes at the site of stimulation as well as in remote connected regions we applied short trains of high-intensity (110% of resting motor threshold) and low-intensity (90% of active motor threshold) repetitive TMS (rTMS; 3 Hz, 10 s duration) over the presumed location of the left dorsal premotor cortex (PMd) during fMRI. Signal increases in the direct vicinity of the stimulated PMd were observed during rTMS at 110% RMT. However, positive BOLD MRI responses were observed with rTMS at both 90% and 110% RMT in connected brain regions such as right PMd, bilateral PMv, supplementary motor area, somatosensory cortex, cingulate motor area, left posterior temporal lobe, cerebellum, and caudate nucl...

Aim Noninvasive observation and visualization of cellular and molecular events are important for understanding of brain function. Manganese-enhanced MRI (MEMRI) has recently been applied for various kinds of modalities such as for tract tracing, neuroarchitecture, neurotransmitter-induced neural activation (PhAIM), and functional MRI (AIM). These MEMRIs rely on many kinds of molecular and physiologic functions such as Ca channel opening, chemical-induced activation, and transport in the brain. The aim of this study was to reveal morphological and functional architecture of the hippocampus and develop new visualization methods that combine the use of the different modalities of MEMRI. Methods Three types of MEMRI were performed using SD rats. 1) Neuroarchitectural MEMRI (n=5): 75 mg/kg MnCl2 was IV administrated. 2) AIM MRI with (n=5) or without (n=5) whisker stimulation: The BBB was disrupted by mannitol injection. Whiskers were stimulated with 2Hz during the MnCl2 infusion. 3) PhAIM MRI for glutamate (n=5...

A persistent question in cognitive neuroscience is whether localized brain regions, or a collection of brain regions, support the representation of different knowledge domains. Using previously published data available in the National fMRI Data Center database (http://www.fmridc.org), the present study explored whether brain regions that respond preferentially to one domain relative to another can be considered neural modules. The domains of interest were the representation of action knowledge, object knowledge and word form. We defined modularity by operationally defining two properties of modular systems (Fodor, 1983) -- domain specificity and mandatory processing. A brain region exhibited domain-specificity if it significantly responded to the domain of interest (e.g. retrieving action knowledge) relative to other domains (e.g. retrieving object knowledge) and a baseline task (e.g. matching visual noise patterns), and the other domain and baseline task did not produce statistically different responses. ...

Neurons responding to the observation of actions performed by others have been described in the superior temporal sulcus (STS), parietal area PF, and prefrontal area F5 (see Rizzolatti and Craighero, Ann Rev Neurosci., 2004). In the present study we defined the whole cortical circuit underlying action observation, using contrast-enhanced fMRI in awake macaques. Three macaques (Macaca mulatta) were scanned (1.5Tesla; Siemens Sonata; MION) while they viewed video-sequences of grasping actions. These included object directed human hand actions, human actions using tools, actions performed by a robot hand and mimed human actions. As a control either static images or phase-scrambled sequences were presented. Comparing human actions with their static or phase-scrambled controls, revealed activations throughout the lower bank and the middle part of the upper bank of the STS, in the anterior part of the intraparietal sulcus, extending sometimes laterally on the parietal convexity, and in the posterior bank, fundus...

Blood brain barrier (BBB) integrity is lost several neurological conditions in which astrocytes are damaged. We have studied the focal lesions induced by systemic injection of 3-choloropropanediol, a toxicant that induces early astrocytic (but not neuronal) death followed by BBB leakage. Anatomical images of coronal brain sections illustrate the regional selectivity of the lesions, with affected areas including symmetrical brain stem and midbrain nuclei: primarily the inferior colliculi and red nuclei. The MRI intensity in the lesioned areas peaked at 2 days post-injection, correlating with the later BBB breakdown, and diminished thereafter; returning to close to pre-injection levels by 30 days in parallel with the return of astrocytes. T2 measurements of the lesioned areas increased at 2 days indicating increased water content in the lesioned areas, consistent with cellular damage and BBB leakage. T2 was not increased at 6 hours, a time when astrocyte swelling is marked but the vasculature is intact. Inje...

We used functional Magnetic Resonance Imaging (fMRI) to assess motor recovery in a patient with left middle cerebral artery (MCA) stroke. The patient was scanned on three occasions, at one-month intervals using a finger-sequencing paradigm consisting of both overt movement and movement imagery. Each of these finger-to-thumb opposition tasks were carried out in a prescribed sequence and consisted of three conditions, two unimanual and one bimanual. Although the first session showed more ipsilateral sensorimotor cortex activation during movement using the affected hand, later sessions exhibited more contralateral activation, which conforms to the pattern of the vascular response in normal subjects. However, blood flow to ipsilateral parietal cortex increased over sessions, suggesting that the undamaged parietal cortex took over the function of the affected side, even after improved blood flow to the contralateral sensorimotor cortex. Stronger activation was observed in the motor cortex of the lesion side and...

Optical imaging spectroscopy (OIS), laser Doppler flowmetry (LDF) and magnetic resonance imaging (MRI) were used to investigate the hemodynamic response to neural activation in rat barrel cortex. The MRI measurements were made at 3T in a small animal magnet facility (Magnex with MRRS console). Both fMRI measurements of the BOLD signal and cbv-MRI estimates of changes in blood volume (CBV) were obtained concurrently with measurements of CBF using a magnet compatible LDF probe (Perimed) following both electrical stimulation of the whisker pad (16s,1.2mA @5Hz) and hypercapnic challenge (120s @10% CO2). MRI measurements were obtained using a GRE-EPI sequence at a voxel resolution of 470x470x2000µm. Of necessity, cbv-MRI data was collected after BOLD measurements following infusion of the contrast agent AMI-227 (10mgFe/kg ~200µmol Fe/kg). The BOLD and cbv-MRI data from the hypercapnic challenges were used to estimate the baseline scaling term M=TE.A.CBV0.[Hbr]βv0 used in the biophysical model of the BOLD signal...

Introduction: In the brain of premature infants primary intracerebral hemorrhage (ICH) is a common occurrence. It is usually unilateral and deep in the cerebrum near the ganglionic eminence beside the lateral ventricle. Blood can extend into the ventricles causing hydrocephalus. Even small lesions of this type, are associated with poor developmental outcome including cerebral palsy and mental retardation. The purpose of this study was to obtain magnetic resonance images (MRI) of the mouse brain after ICH and to correlate the images with histological evolution. Methods: ICH was induced in one-day-old mice, which are developmentally similar to a 24-26 weeks human fetus, by injection of autologous blood into the striatum. MRI was obtained 15 minutes to 48 hours later. Mice were perfused with 4% paraformaldehyde 8 hours to 28 days later. H&E, immunohistochemical, and TUNEL staining were used to quantify the lesion area, neutrophils, microglia, and cell death at the edge of the hemorrhagic lesion. Results: Hist...