Blood Oxygenation Level Dependent Data Research Articles

Default-Mode and Task-Positive Network Activity in Major Depressive Disorder: Implications for Adaptive and Maladaptive Rumination

Major depressive disorder (MDD) has been associated reliably with ruminative responding; this kind of responding is composed of both maladaptive and adaptive components. Levels of activity in the default-mode network (DMN) relative to the task-positive network (TPN), as well as activity in structures that influence DMN and TPN functioning, may represent important neural substrates of maladaptive and adaptive rumination in MDD. We used a unique metric to estimate DMN dominance over TPN from blood oxygenation level-dependent data collected during eyes-closed rest in 17 currently depressed and 17 never-disordered adults. We calculated correlations between this metric of DMN dominance over TPN and the depressive, brooding, and reflective subscales of the Ruminative Responses Scale, correcting for associations between these measures both with one another and with severity of depression. Finally, we estimated and compared across groups right fronto-insular cortex (RFIC) response during initiations of ascent in DMN and in TPN activity. In the MDD participants, increasing levels of DMN dominance were associated with higher levels of maladaptive, depressive rumination and lower levels of adaptive, reflective rumination. Moreover, our RFIC state-change analysis showed increased RFIC activation in the MDD participants at the onset of increases in TPN activity; conversely, healthy control participants exhibited increased RFIC response at the onset of increases in DMN activity. These findings support a formulation in which the DMN undergirds representation of negative, self-referential information in depression, and the RFIC, when prompted by increased levels of DMN activity, initiates an adaptive engagement of the TPN.

Time series fMRI measures detect changes in pontine raphé following acute tryptophan depletion

Serotonin is synthesized from its precursor, tryptophan, by brainstem raphé neurons and their synaptic terminals in limbic regions. The omission of tryptophan from an Acute Tryptophan Depletion (ATD) diet transiently diminishes serotonin synthesis, alters raphé activity, and mimics symptoms of depression. Raphé functional magnetic resonance imaging (fMRI) poses challenges using signal-averaging analyses. Time-series properties of fMRI blood oxygenation level dependent (BOLD) signals may hold promise, so we analyzed raphé signals for changes with the ATD diet. Eleven remitted (previously depressed) patients were awake with eyes-closed during seven-minute resting scans with 0.5 s −1 sampling. BOLD signal time-series data were frequency-filtered using wavelet transforms, yielding three octave-width frequency bands from 0.25 to 0.03 s −1 and an unbounded band below 0.03 s −1. Spectral power, reflecting signal information, increased in pontine raphé at high frequencies (0.25 to 0.125 s −1) during ATD (compared to control, balanced, diet, P < 0.004) but was unchanged at other frequencies. Functional connectivity, the correlation between time-series data from pairs of regions, weakened between pontine raphé and anterior thalamus at low frequencies during ATD ( P < 0.05). This preliminarily supports using fMRI time-series features to assess pontine raphé function. Whether, and how, high frequency activity oscillations interfere with low frequency signaling requires further study.

Cognitive processing and functional interactions within hippocampal-neocortical networks during a spatial working memory task in humans

Cognitive processing and functional interactions within hippocampal-neocortical networks during a spatial working memory task in humans

Deficits in Functional Connectivity of Hippocampal and Frontal Lobe Circuits After Traumatic Axonal Injury

To examine the functional connectivity of hippocampal and selected frontal lobe circuits in patients with traumatic axonal injury (TAI). Observational study. An inpatient traumatic brain injury unit. Imaging and neurocognitive assessments were conducted in an outpatient research facility. Twenty-five consecutive patients with brain injuries consistent with TAI and acute subcortical white matter abnormalities were studied as well as 16 healthy volunteers of similar age and sex. Echo-planar and high-resolution T1-weighted images were acquired using 3-T scanners. Regions of interest (ROI) were drawn bilaterally for the hippocampus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex and were used to extract time series data. Blood oxygenation level-dependent data from each ROI were used as reference functions for correlating with all other brain voxels. Interhemispheric functional connectivity was assessed for each participant by correlating homologous regions using a Pearson correlation coefficient. Patient functional and neurocognitive outcomes were assessed approximately 6 months after injury. Interhemispheric functional connectivity, spatial patterns of functional connectivity, and associations of connectivity measures with functional and neurocognitive outcomes. Patients showed significantly lower interhemispheric functional connectivity for the hippocampus and ACC. Controls demonstrated stronger and more focused functional connectivity for the hippocampi and ACC, and a more focused recruitment of the default mode network for the dorsolateral prefrontal cortex ROI. The interhemispheric functional connectivity for the hippocampus was correlated with delayed recall of verbal information. Traumatic axonal injury may affect interhemispheric neural activity, as patients with TAI show disrupted interhemispheric functional connectivity. More careful investigation of interhemispheric connectivity is warranted, as it demonstrated a modest association with outcome in chronic TBI.

Functional magnetic resonance inverse imaging of human visuomotor systems using eigenspace linearly constrained minimum amplitude (eLCMA) beamformer

Recently proposed dynamic magnetic resonance (MR) inverse imaging (InI) is a novel parallel imaging reconstruction technique capable of improving the temporal resolution of blood–oxygen level-dependent (BOLD) contrast functional MRI (fMRI) to the order of milliseconds at the cost of moderate spatial resolution. Volumetric InI reconstructs spatial information from projection data by solving ill-posed inverse problems using simultaneous acquisitions from a RF coil array. Previously a spatial filtering technique based on linearly constrained minimum variance (LCMV) beamformer was suggested to localize the hemodynamic changes of dynamic InI data with improved spatial resolution and sensitivity. Here we report an advancement of the spatial filtering method, which combines the eigenspace projection of the measured data and the L1-norm minimization of the spatial filters' output noise amplitude, to further improve the detection power of BOLD contrast fMRI data. Using numerical simulation and in vivo data, we demonstrate that this eigenspace linearly constrained minimum amplitude (eLCMA) beamformer can reconstruct spatiotemporal hemodynamic signals with high statistical significance values and high spatial resolution in event-related two-choice reaction time visuomotor experiments.

Adolescents At Risk for Alcohol Abuse Demonstrate Altered Frontal Lobe Activation During Stroop Performance

Children and adolescents, family history positive (FH+) for alcoholism, exhibit differences in brain structure and functional activation when compared to family history negative (FH-) counterparts. Given that frontal brain regions, and associated reciprocal connections with limbic structures, undergo the most dramatic maturational changes during adolescence, the objective of this study was to compare functional brain activation during a frontally mediated test of response inhibition in 32 adolescents separated into low-risk (FH-) and high-risk (FH+) groups. Functional magnetic resonance (fMRI) blood oxygen level-dependent data were acquired at 1.5 Tesla during performance of Stroop Color Naming, Word Reading, and Interference. Preprocessing and statistical analyses, covaried for age, were conducted in SPM99 using a search territory that included superior, middle, and inferior frontal gyri (trigone region), anterior cingulate gyrus (CG), and left and right amygdala. Significantly greater activation in the fronto-limbic search territory was observed in FH+ relative to FH- subjects during Stroop Interference. In addition, a significant regression between brain activation and family history density was observed, with a greater density being associated with increased activation in regions including middle frontal gyrus (BA9) and CG (BA24). These data demonstrate a significant influence of FH status on brain activation during the performance of a response inhibition task, perhaps reflecting a neurobiological vulnerability associated with FH status that may include reduced neuronal efficiency and/or recruitment of additional neuronal resources. These findings are important given that the adolescent developmental period is already associated with reduced inhibitory capacity, even prior to the onset of alcohol use.

Multisite reliability of cognitive BOLD data

Investigators perform multi-site functional magnetic resonance imaging studies to increase statistical power, to enhance generalizability, and to improve the likelihood of sampling relevant subgroups. Yet undesired site variation in imaging methods could off-set these potential advantages. We used variance components analysis to investigate sources of variation in the blood oxygen level-dependent (BOLD) signal across four 3-T magnets in voxelwise and region-of-interest (ROI) analyses. Eighteen participants traveled to four magnet sites to complete eight runs of a working memory task involving emotional or neutral distraction. Person variance was more than 10 times larger than site variance for five of six ROIs studied. Person-by-site interactions, however, contributed sizable unwanted variance to the total. Averaging over runs increased between-site reliability, with many voxels showing good to excellent between-site reliability when eight runs were averaged and regions of interest showing fair to good reliability. Between-site reliability depended on the specific functional contrast analyzed in addition to the number of runs averaged. Although median effect size was correlated with between-site reliability, dissociations were observed for many voxels. Brain regions where the pooled effect size was large but between-site reliability was poor were associated with reduced individual differences. Brain regions where the pooled effect size was small but between-site reliability was excellent were associated with a balance of participants who displayed consistently positive or consistently negative BOLD responses. Although between-site reliability of BOLD data can be good to excellent, acquiring highly reliable data requires robust activation paradigms, ongoing quality assurance, and careful experimental control.

Decreased ventral striatal activity with impulse control disorders in Parkinson's disease

A range of impulse control disorders (ICDs) are reported to occur in Parkinson's disease (PD). However, alterations in brain activity at rest and during risk taking occurring with ICDs in PD are not well understood. We used both arterial spin labeling perfusion functional magnetic resonance imaging (fMRI) to directly quantify resting cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) fMRI to measure neural responses to risk taking during performance on the Balloon Analogue Risk Task (BART). Eighteen PD patients, either with a diagnosis of one or more ICDs (N = 9) or no lifetime ICD history (N = 9), participated. BOLD fMRI data demonstrated that PD patients without an ICD activate the mesocorticolimbic pathway during risk taking. Compared with non-ICD patients, ICD patients demonstrated significantly diminished BOLD activity in the right ventral striatum during risk taking and significantly reduced resting CBF in the right ventral striatum. ICDs in PD are associated with reduced right ventral striatal activity at rest and diminished striatal activation during risk taking, suggesting that a common neural mechanism may underlie ICDs in individuals with PD and those without PD. Thus, treatments for ICDs in non-PD patients warrant consideration in PD patients with ICDs.

Retinotopic mapping with spin echo BOLD at 7T

For blood oxygenation level-dependent (BOLD) functional MRI experiments, contrast-to-noise ratio (CNR) increases with increasing field strength for both gradient echo (GE) and spin echo (SE) BOLD techniques. However, susceptibility artifacts and nonuniform coil sensitivity profiles complicate large field-of-view fMRI experiments (e.g., experiments covering multiple visual areas instead of focusing on a single cortical region). Here, we use SE BOLD to acquire retinotopic mapping data in early visual areas, testing the feasibility of SE BOLD experiments spanning multiple cortical areas at 7T. We also use a recently developed method for normalizing signal intensity in T 1-weighted anatomical images to enable automated segmentation of the cortical gray matter for scans acquired at 7T with either surface or volume coils. We find that the CNR of the 7T GE data (average single-voxel, single-scan stimulus coherence: 0.41) is almost twice that of the 3T GE BOLD data (average coherence: 0.25), with the CNR of the SE BOLD data (average coherence: 0.23) comparable to that of the 3T GE data. Repeated measurements in individual subjects find that maps acquired with 1.8-mm resolution at 3T and 7T with GE BOLD and at 7T with SE BOLD show no systematic differences in either the area or the boundary locations for V1, V2 and V3, demonstrating the feasibility of high-resolution SE BOLD experiments with good sensitivity throughout multiple visual areas.

Intra‐renal oxygenation in rat kidneys during water loading: Effects of cyclooxygenase (COX) inhibition and nitric oxide (NO) donation

To evaluate intra-renal oxygenation by blood oxygenation level dependent (BOLD) MRI in rat kidneys during water loading and to investigate if the NO donating moiety in naproxcinod could compensate for the effect of cyclooxygenase (COX) inhibition of naproxen. Nineteen male Sprague Dawley rats were divided into three groups and dosed with vehicle, naproxen or naproxcinod by gavage for two weeks. On the day of the experiment, hypotonic saline with glucose was infused intravenously to induce water diuresis. BOLD MRI data to monitor renal oxygenation and timed urine samples for estimation of prostaglandins (PGs) and urine flow were obtained. The data in this study is consistent with previous experience in humans in that pre-treatment with naproxen abolished the improvement in medullary oxygenation during water loading. In addition, the inhibition of PGs by naproxcinod reached similar levels as naproxen but maintained the improvement in oxygenation in renal medulla during water loading. This suggests that naproxcinod may have less nephrotoxicity and that the NO donating moiety partially compensates for the hemodynamic effects of prostaglandin inhibition by naproxen.

Simultaneous acquisition of gradient echo/spin echo BOLD and perfusion with a separate labeling coil

Arterial spin labeling-based cerebral blood flow imaging complements blood oxygenation level dependent (BOLD) imaging with a measure that is more quantitative and has better specificity to neuronal activation. Relative to gradient echo BOLD, spin echo BOLD has better spatial specificity because it is less biased to large draining veins. Although there have been many studies comparing simultaneously acquired cerebral blood flow data with gradient echo BOLD data in fMRI, there have been few studies comparing cerebral blood flow with SE BOLD and no study comparing all three. We present a pulse sequence that simultaneously acquires cerebral blood flow data with a separate labeling coil, gradient echo BOLD, and spin echo BOLD images. Simultaneous acquisition avoids interscan variability, allowing more direct assessment and comparison of each contrast's relative specificity and reproducibility. Furthermore, it facilitates studies that may benefit from multiple complementary measures.

Testing methodologies for the nonlinear analysis of causal relationships in neurovascular coupling

We investigated the use and implementation of a nonlinear methodology for establishing which changes in neurophysiological signals cause changes in the blood oxygenation level-dependent (BOLD) contrast measured in functional magnetic resonance imaging. Unlike previous analytical approaches, which used linear correlation to establish covariations between neural activity and BOLD, we propose a directed information-theoretic measure, the transfer entropy, which can elucidate even highly nonlinear causal relationships between neural activity and BOLD signal. In this study we investigated the practicality of such an analysis given the limited data samples that can be collected experimentally due to the low temporal resolution of BOLD signals. We implemented several algorithms for the estimation of transfer entropy and we tested their effectiveness using simulated local field potentials (LFPs) and BOLD data constructed to match the main statistical properties of real LFP and BOLD signals measured simultaneously in monkey primary visual cortex. We found that using the advanced methods of entropy estimation implemented and described here, a transfer entropy analysis of neurovascular coupling based on experimentally attainable data sets is feasible.

Blood‐oxygen level dependent MRI measures of cerebrovascular reactivity using a controlled respiratory challenge: Reproducibility and gender differences

To evaluate the reproducibility and gender differences in cerebrovascular reactivity (CVR) measurements obtained using the blood-oxygen level dependent (BOLD) response to controlled changes in end-tidal partial pressure of carbon dioxide (PETCO(2)). We obtained ethical approval to image 19 healthy volunteers (10 men, 9 women) on a 1.5 Tesla (T) MRI scanner twice on two separate days using identical procedures. CVR images were generated by collecting BOLD MRI data during controlled changes in PETCO(2) induced by a sequential gas delivery system. Using the intraclass correlation coefficient (ICC), we demonstrated excellent within-day CVR measures in gray matter (GM) (ICC = 0.92) and white matter (WM) (ICC = 0.88) regions, excellent between-day reproducibility in GM (ICC = 0.81), and good between-day reproducibility in the WM (ICC = 0.66). CVR values between men and women were significantly different in the GM and WM. Men exhibited a 22 +/- 2% greater CVR in GM and a 17 +/- 2% greater CVR in WM compared with females. Our results demonstrate the reliability of BOLD MRI CVR measurements obtained using a controlled cerebrovascular challenge. Using this technique, we also revealed significantly increased BOLD response to CO(2) in males compared with females.

Functional segmentation of the brain cortex using high model order group PICA

Baseline activity of resting state brain networks (RSN) in a resting subject has become one of the fastest growing research topics in neuroimaging. It has been shown that up to 12 RSNs can be differentiated using an independent component analysis (ICA) of the blood oxygen level dependent (BOLD) resting state data. In this study, we investigate how many RSN signal sources can be separated from the entire brain cortex using high dimension ICA analysis from a group dataset. Group data from 55 subjects was analyzed using temporal concatenation and a probabilistic independent component analysis algorithm. ICA repeatability testing verified that 60 of the 70 computed components were robustly detectable. Forty-two independent signal sources were identifiable as RSN, and 28 were related to artifacts or other noninterest sources (non-RSN). The depicted RSNs bore a closer match to functional neuroanatomy than the previously reported RSN components. The non-RSN sources have significantly lower temporal intersource connectivity than the RSN (P < 0.0003). We conclude that the high model order ICA of the group BOLD data enables functional segmentation of the brain cortex. The method enables new approaches to causality and connectivity analysis with more specific anatomical details.

Functional segmentation of the brain cortex using high model order group-PICA.

Baseline activity of resting state brain networks (RSN) in a resting subject has become one of the fastest growing research topics in neuroimaging. It has been shown that up to 12 RSNs can be differentiated using an independent component analysis (ICA) of the blood oxygen level dependent (BOLD) resting state data. In this study, we investigate how many RSN signal sources can be separated from the entire brain cortex using high dimension ICA analysis from a group dataset. Group data from 55 subjects was analyzed using temporal concatenation and a probabilistic independent component analysis algorithm. ICA repeatability testing verified that 60 of the 70 computed components were robustly detectable. Forty-two independent signal sources were identifiable as RSN, and 28 were related to artifacts or other noninterest sources (non-RSN). The depicted RSNs bore a closer match to functional neuroanatomy than the previously reported RSN components. The non-RSN sources have significantly lower temporal intersource connectivity than the RSN (P < 0.0003). We conclude that the high model order ICA of the group BOLD data enables functional segmentation of the brain cortex. The method enables new approaches to causality and connectivity analysis with more specific anatomical details.

Inter-subject variability in hypercapnic normalization of the BOLD fMRI response

In the application of hypercapnic normalization to functional magnetic resonance imaging (fMRI) studies, the blood oxygenation level dependent (BOLD) response to a functional stimulus is typically divided by the BOLD response to a hypercapnic challenge. While some prior studies have shown that hypercapnic normalization can reduce inter-subject BOLD variability, other studies have found an increase in inter-subject variability. In this study we used measures of baseline cerebral blood flow (CBF) and the functional BOLD and CBF responses to both visual stimuli and hypercapnia to assess the effect of hypercapnic normalization on inter-subject variability. We found that the functional and hypercapnic BOLD and CBF responses all exhibited a significant inverse dependence on baseline CBF. In contrast, the maximum BOLD response was independent of baseline CBF and was not a major source of inter-subject BOLD variability. Division of the functional BOLD response by the hypercapnic BOLD response increased inter-subject variability in the normalized responses as compared to the original responses, reflecting the presence of a systematic bias term that was inversely dependent on the hypercapnic BOLD response. This systematic bias resulted from a positive intercept term in the linear relationship between the functional and hypercapnic BOLD responses. This positive intercept term reflected a steeper inverse dependence of the hypercapnic CBF response on baseline CBF, as compared to the functional CBF response. In contrast to the results obtained with normalization based on division, normalized responses obtained by using the hypercapnic BOLD response as a covariate were unaffected by the systematic bias and exhibited reduced inter-subject variability. The findings of this study indicate that the positive intercept in the linear relationship between functional and hypercapnic BOLD responses should be carefully considered in the hypercapnic normalization of BOLD fMRI data.

Pain fMRI in rat cervical spinal cord: An echo planar imaging evaluation of sensitivity of BOLD and blood volume-weighted fMRI

Objective measure of pain is valuable in drug discovery research and development of analgesics. Spinal cord is an important relay of the pain pathway, and fMRI offers an excellent opportunity to quantify pain using activation in the spinal cord induced by painful stimuli. fMRI literature of cervical spinal cord with regard to the spatial extent, in both longitudinal and cross-sectional directions, of neuronal activation induced by noxious stimulation is ambiguous. This study investigates the feasibility of developing a robust pain assay using fMRI in the cervical spinal cord in α-chloralose anesthetized rats subjected to transcutaneous noxious electrical stimulation of the forepaw. Blood oxygenation level dependent (BOLD) and blood volume (BV)-weighted fMRI data were acquired without and with intravenous injection of ultra small superparamagnetic iron oxide particles (USPIO), respectively. BOLD data were acquired by gradient-echo (GE) and spin-echo (SE) echo planar imaging (EPI), while BV-weighted fMRI data were acquired only by GE EPI. Cervical spinal cord activity was robustly detected by all three fMRI techniques. The sensitivity of the fMRI signal was highest in GE BV-weighted fMRI followed in order by GE BOLD, and SE BOLD, respectively. Spatially, the fMRI signal extended ∼ 9 mm in the longitudinal direction, covering C 4–C 8 segments, coinciding with the synapse location of afferent terminals from the stimulated site. In the cross-sectional direction, the signal change is localized predominantly to the ipsilateral dorsal region. This study demonstrates that cervical spinal cord fMRI can be performed reliably in anesthetized rats offering it as a potential tool for analgesic drug development.

Assessment of regional myocardial oxygenation changes in the presence of coronary artery stenosis with balanced SSFP imaging at 3.0T: Theory and experimental evaluation in canines

To examine the dependence of steady-state free-precession (SSFP) -based myocardial blood-oxygen-level-dependent (BOLD) contrast on field strength using theoretical and experimental models. Numerical simulations using a two-pool exchange model and a surgically prepared dog model were used to assess the SSFP-based myocardial BOLD signal changes at 1.5T and 3.0T. Experimental studies were performed in eight canines with pharmacological vasodilation under various levels of left circumflex coronary artery stenosis. Experimentally obtained BOLD signal changes were correlated against microsphere-based true flow changes. Theoretical results showed that, at 3.0T, relative to 1.5T, a threefold increase in oxygen sensitivity can be expected. Experimental studies in canines showed near similar results-a 2.5 +/- 0.2-fold increase in BOLD sensitivity at 3.0T relative to 1.5T (P < 0.05). Based on the scatter gram of BOLD data and microsphere data, it was found that the minimum regional flow difference that can be detected with SSFP-based myocardial BOLD imaging at 1.5T and 3.0T were 2.9 and 1.6, respectively (P < 0.05). This study demonstrated that SSFP-based myocardial BOLD sensitivity is substantially greater at 3.0T compared with 1.5T. The findings here suggest that SSFP-based myocardial BOLD imaging at 3.0T may have the necessary sensitivity to detect the clinically required minimum flow difference of 2.0.

SNR and functional sensitivity of BOLD and perfusion-based fMRI using arterial spin labeling with spiral SENSE at 3 T

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies using parallel imaging to reduce the readout window have reported a loss in temporal signal-to-noise ratio (SNR) that is less than would be expected given a purely thermal noise model. In this study, the impact of parallel imaging on the noise components and functional sensitivity of both BOLD and perfusion-based fMRI data was investigated. Dual-echo arterial spin labeling data were acquired on five subjects using sensitivity encoding (SENSE), at reduction factors (R) of 1, 2 and 3. Direct recording of cardiac and respiratory activity during data acquisition enabled the retrospective removal of physiological noise. The temporal SNR of the perfusion time series closely followed the thermal noise prediction of a radicalR loss in SNR as the readout window was shortened, with temporal SNR values (relative to the R=1 data) of 0.72 and 0.56 for the R=2 and R=3 data, respectively, after accounting for physiological noise. However, the BOLD temporal SNR decreased more slowly than predicted even after accounting for physiological noise, with relative temporal SNR values of 0.80 and 0.63 for the R=2 and R=3 data, respectively. Spectral analysis revealed that the BOLD trends were dominated by low-frequency fluctuations, which were not dominant in the perfusion data due to signal processing differences. The functional sensitivity, assessed using mean F values over activated regions of interest (ROIs), followed the temporal SNR trends for the BOLD data. However, results for the perfusion data were more dependent on the threshold used for ROI selection, most likely due to the inherently low SNR of functional perfusion data.

Differential age effects on cerebral blood flow and BOLD response to encoding: Associations with cognition and stroke risk

Changes in the cerebrovascular system due to age or disease can significantly alter the blood-oxygenation-level-dependent (BOLD) signal and complicate its interpretation. The simultaneous acquisition of arterial spin labeling (ASL) and BOLD data represents a useful technique to more fully characterize the neurovascular underpinnings of functional brain response to cognition. We conducted a functional magnetic resonance imaging (FMRI) study of episodic memory encoding to investigate whether age is related to cerebral blood flow (CBF) and BOLD response in the medial temporal lobe (MTL). Results demonstrated a significant reduction in resting-state CBF in older compared to young adults. Conversely, older adults showed significantly increased CBF but not BOLD response in the MTL during picture encoding relative to young adults. Correlations between CBF response and cognition were demonstrated whereas associations with BOLD were not observed. Stroke risk was associated with both CBF and BOLD response. Results suggest that aging effects on CBF and BOLD responses to encoding are dissociable and that cerebrovascular alterations contribute to findings of age-related differences.