Changes in neuronal activity are accompanied by the release of vasoactive mediators that cause microscopic dilation and constriction of the cerebral microvasculature and are manifested in macroscopic blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signals. We used two-photon microscopy to measure the diameters of single arterioles and capillaries at different depths within the rat primary somatosensory cortex. These measurements were compared with cortical depth-resolved fMRI signal changes. Our microscopic results demonstrate a spatial gradient of dilation onset and peak times consistent with "upstream" propagation of vasodilation toward the cortical surface along the diving arterioles and "downstream" propagation into local capillary beds. The observed BOLD response exhibited the fastest onset in deep layers, and the "initial dip" was most pronounced in layer I. The present results indicate that both the onset of the BOLD response and the initial dip depend on cortical depth and can be explained, at least in part, by the spatial gradient of delays in microvascular dilation, the fastest response being in the deep layers and the most delayed response in the capillary bed of layer I.blood flow | cortical layer | hemodynamic | imaging | somatosensory N euroglial activation is accompanied by release of vasoactive mediators that dilate and constrict the surrounding arterioles (1, 2) and capillaries (3, 4). These changes in diameter in turn lead to changes in blood flow throughout the vascular matrix and can be detected on the macroscopic level as a positive blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal when blood flow response exceeds oxygen consumption (5-7). Under the assumption of local neurovascular coupling, the onset of the changes in diameter is determined by the following three factors, any of which may differ as a function of the cortical depth and branching order within the vascular tree: (i) the onset and peak time of the neuronal activity evoking the response; (ii) the time needed to release a vascular messenger [e.g., prostaglandin or NO (8)]; and (iii) the time needed for the target vessel to respond. However, in addition to local neurovascular coupling, vascular responses can propagate within the arteriolar/capillary networks (3, 9, 10). Indeed, propagation of dilation and constriction has been observed on the cortical surface (11-15), in excised cerebral vessels, and in noncerebral preparations (16,17).Previous studies with single-vessel resolution in vivo have been limited to the cortical surface, but recent improvements in twophoton microscopy technology allow direct imaging of singlevessel diameters and flow velocities within a 3D geometry of vascular trees (1,2,18,19). In the present study, we used this technology to examine microvascular responses to sensory stimulation down to 550 μm below the cortical surface in the rat primary somatosensory cortex (SI). We then compared the results with highresolution BOLD fMRI to investigate the extent to which laminar ...

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The blood oxygenation level-dependent (BOLD) responses to visual stimuli, using both a 1-s long single trial stimulus and a 20-s long block stimulus, were measured in a 4-T magnetic field both before and immediately after a 200-mg caffeine dose. In addition, resting levels of cerebral blood flow (CBF) were measured using arterial spin labeling. For the single trial stimulus, the caffeine dose significantly ( p b 0.05) reduced the time to peak (TTP), the time after the peak at which the response returned to 50% of the peak amplitude (TA 50 ), and the amplitude of the poststimulus undershoot in all subjects (N = 5). Other parameters, such as the full-width half-maximum (FWHM) and the peak amplitude, also showed significant changes in the majority of subjects. For the block stimulus, the TTP, TA 50 , and the time for the response to reach 50% of the peak amplitude (T 50 ) were significantly reduced. In some subjects, oscillations were observed in the poststimulus portion of the response with median peak periods of 9.1 and 9.5 s for the single trial and block responses, respectively. Resting CBF was reduced by an average of 24%. The reproducibility of the results was verified in one subject who was scanned on 3 different days. The dynamic changes are similar to those previously reported for baseline CBF reductions induced by hypocapnia and hyperoxia. D

Objective Disturbances in functional connectivity have been suggested to contribute to cognitive and emotion processing deficits observed in bipolar disorder (BD). Functional connectivity between medial prefrontal cortex (mPFC) and other brain regions may be particularly abnormal. The goal of the present study was to characterize the temporal dynamics of the default mode network (DMN) connectivity in BD and examine its association with cognition. Method In a preliminary study, euthymic BD (n=15) and healthy comparison (HC, n=19) participants underwent resting-state functional magnetic resonance imaging, using high-resolution sequences adapted from the Human Connectome Project, and completed neuropsychological measures of processing speed and executive function. A seed-based approach was used to measure DMN correlations in each participant, with regions of interest in the mPFC, posterior cingulate cortex (PCC), and lateral parietal cortex. Subsequently, to characterize temporal dynamics, correlational analyses between the mPFC and other DMN nodes were repeated using a sliding-window correlational analysis with subsets of the time series. Results When averaged across the entire scan, there were no group differences in overall connectivity strength between the mPFC and other regions of the DMN. However, dynamic connectivity between the mPFC and PCC was altered in BD, such that connectivity was less variable (i.e., more rigid) over time. Decreased connectivity variability was associated with slower processing speed and reduced cognitive set-shifting in BD patients. Conclusions Variability in resting-state functional connectivity may be an index of internetwork flexibility that is reduced in BD and a correlate of ongoing cognitive impairment during periods of euthymia.

Arterial spin labeling (ASL) is an MRI perfusion imaging method from which quantitative cerebral blood flow (CBF) can be calculated. We present a multi-TI ASL method (multi-TI integrated ASL) in which variable post-labeling delays and variable TRs are used to improve the estimation of arterial transit time (ATT) and CBF while shortening the scan time by 41% compared to the conventional methods. Variable bolus widths allow for T1 and M0 estimation from raw ASL data. Multi-TI integrated pseudo-continuous ASL images were collected at 7 TI times ranging 100-4300 ms. Voxel-wise T1 and M0 maps were estimated, then CBF and ATT maps were created using the estimated T1 tissue map. All maps were consistent with physiological values reported in the literature. Based on simulations and in vivo comparisons, this method demonstrates higher CBF and ATT estimation efficiency than other ATT acquisition methods and better fit to the perfusion model. It produces CBF maps with reduced sensitivity to errors from ATT and tissue T1 variations. The estimated M0, T1, and ATT maps also have potential clinical utility. The method requires a single scan acquired within a clinically acceptable scan time (under 6 minutes) and with low sensitivity to motion.