Blood Oxygenation Level-dependent Percent Research Articles

Increased pain unpleasantness and pain-related fMRI activation in the periaqueductal gray in Alzheimer's disease.

Pain continues to be underrecognized and undertreated in people with Alzheimer's disease (AD). The periaqueductal gray (PAG) is essential to pain processing and modulation yet is damaged by AD. While evidence exists of altered neural processing of pain in AD, there has not been a focused investigation of the PAG during pain in people with AD. To investigate the role of the PAG in sensory and affective pain processing for people living with AD. Participants from a larger study completed pain psychophysics assessments and then a perceptually-matched heat pain task (warmth, mild, and moderate pain) during a functional MRI scan. In this cross-sectional study, we examined blood oxygenation level-dependent (BOLD) responses in the PAG and other pain-related regions in participants with AD (n = 18) and cognitively intact older adults (age- and sex-matched, n = 18). Associations of BOLD percent signal change and psychophysics were also examined. There were significant main effects of AD status on the temperature needed to reach each perception of warmth or pain, where people with AD reached higher temperatures. Furthermore, participants with AD rated mild and moderate pain as more unpleasant than controls. PAG BOLD activation was greater in AD relative to controls during warmth and mild pain percepts. No significant differences were found for moderate pain or in other regions of interest. Greater PAG activation during mild pain was associated with higher affective/unpleasantness ratings of mild pain in participants with AD but not in controls. Results suggest a role for the PAG in altered pain responses in people with AD. The PAG is the primary source of endogenous opioid pain inhibition in the neuroaxis, thus, altered PAG function in AD suggests possible changes in descending pain inhibitory circuits. People with AD may have a greater risk of suffering from pain compared to cognitively intact older adults.

Gradient-echo and spin-echo blood oxygenation level-dependent functional MRI at ultrahigh fields of 9.4 and 15.2 Tesla.

PurposeSensitivity and specificity of blood oxygenation level–dependent (BOLD) functional MRI (fMRI) is sensitive to magnetic field strength and acquisition methods. We have investigated gradient‐echo (GE)‐ and spin‐echo (SE)‐BOLD fMRI at ultrahigh fields of 9.4 and 15.2 Tesla.MethodsBOLD fMRI experiments responding to forepaw stimulation were performed with 3 echo times (TE) at each echo type and B 0 in α‐chloralose–anesthetized rats. The contralateral forelimb somatosensory region was selected for quantitative analyses.ResultsAt 9.4 T and 15.2 T, average baseline T 2 * (n = 9) was 26.6 and 17.1 msec, whereas baseline T 2 value (n = 9) was 35.7 and 24.5 msec, respectively. Averaged stimulation‐induced ΔR 2 * was –1.72 s–1 at 9.4 T and –3.09 s–1 at 15.2 T, whereas ΔR 2 was –1.19 s–1 at 9.4 T and –1.97 s–1 at 15.2 T. At the optimal TE of tissue T 2 * or T 2, BOLD percent changes were slightly higher at 15.2 T than at 9.4 T (GE: 7.4% versus 6.4% and SE: 5.7% versus 5.4%). The ΔR 2 * and ΔR 2 ratio of 15.2 T to 9.4 T was 1.8 and 1.66, respectively. The ratio of the macrovessel‐containing superficial to microvessel‐dominant parenchymal BOLD signal was 1.73 to 1.76 for GE‐BOLD versus 1.13 to 1.19 for SE‐BOLD, indicating that the SE‐BOLD contrast is less sensitive to macrovessels than GE‐BOLD.ConclusionSE‐BOLD fMRI improves spatial specificity to microvessels compared to GE‐BOLD at both fields. BOLD sensitivity is similar at the both fields and can be improved at ultrahigh fields only for thermal‐noise–dominant ultrahigh‐resolution fMRI.

Evaluation of tumour vascular distribution and function using immunohistochemistry and BOLD fMRI with carbogen inhalation

To evaluate oxygenation changes in rat subcutaneous C6 gliomas using blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) combined with non-haemodynamic response function (non-HRF) analysis. BOLD fMRI were performed during carbogen inhalation in 20 Wistar rats bearing gliomas. Statistical maps of spatial oxygenation changes were computed by a dedicated non-HRF analysis algorithm. Three types of regions of interest (ROIs) were defined: (1) maximum re-oxygenation zone (ROImax), (2) re-oxygenation zones that were less than the maximum re-oxygenation (ROInon-max), and (3) zones without significant re-oxygenation (ROInone). The values of percent BOLD signal change (PSC), percent enhancement (ΔSI), and significant re-oxygenation (T) were extracted from each ROI. Tumours were sectioned for histology using the fMRI scan orientation and were stained with haematoxylin and eosin and CD105. The number of microvessels (MVN) in each ROI was counted. Differences and correlations among the values for T, PSC, ΔSI, and MVN were determined. After carbogen inhalation, the PSC significantly increased in the ROImax areas (p<0.01) located in the tumour parenchyma. No changes occurred in any of the ROInone areas (20/20). Some changes occurred in a minority of the ROInon-max areas (3/60) corresponding to tumour necrosis. MVN and PSC (R=0.59, p=0.01) were significantly correlated in the ROImax areas. In the ROInon-max areas, MVN was significantly correlated with PSC (R=0.55, p=0.00) and ΔSI (R=0.37, p=0.00). Statistical maps obtained via BOLD fMRI with non-HRF analysis can assess the re-oxygenation of gliomas.

Working memory-related neural activity predicts future smoking relapse.

Brief abstinence from smoking impairs cognition, particularly executive function, and this has a role in relapse to smoking. This study examined whether working memory-related brain activity predicts subsequent smoking relapse above and beyond standard clinical and behavioral measures. Eighty treatment-seeking smokers completed two functional magnetic resonance imaging sessions (smoking satiety vs 24 h abstinence challenge) during performance of a visual N-back task. Brief counseling and a short-term quit attempt followed. Relapse during the first 7 days was biochemically confirmed by the presence of the nicotine metabolite cotinine. Mean percent blood oxygen level-dependent (BOLD) signal change was extracted from a priori regions of interest: bilateral dorsolateral prefrontal cortex (DLPFC), medial frontal/cingulate gyrus, posterior cingulate cortex (PCC), and ventromedial prefrontal cortex. Signal from these brain regions and additional clinical measures were used to model outcome status, which was then validated with resampling techniques. Relapse to smoking was predicted by increased withdrawal symptoms, decreased left DLPFC and increased PCC BOLD percent signal change (abstinence vs smoking satiety). Receiver operating characteristic analysis demonstrated 81% area under the curve using these predictors, a significant improvement over the model with clinical variables only. The combination of abstinence-induced decreases in left DLPFC activation and reduced suppression of PCC may be a prognostic marker for poor outcome, specifically early smoking relapse.

Task-modulated coactivation of vergence neural substrates.

While functional magnetic resonance imaging (fMRI) has identified which regions of interests (ROIs) are functionally active during a vergence movement (inward or outward eye rotation), task-modulated coactivation between ROIs is less understood. This study tested the following hypotheses: (1) significant task-modulated coactivation would be observed between the frontal eye fields (FEFs), the posterior parietal cortex (PPC), and the cerebellar vermis (CV); (2) significantly more functional activity and task-modulated coactivation would be observed in binocularly normal controls (BNCs) compared with convergence insufficiency (CI) subjects; and (3) after vergence training, the functional activity and task-modulated coactivation would increase in CIs compared with their baseline measurements. A block design of sustained fixation versus vergence eye movements stimulated activity in the FEFs, PPC, and CV. fMRI data from four CI subjects before and after vergence training were compared with seven BNCs. Functional activity was assessed using the blood oxygenation level dependent (BOLD) percent signal change. Task-modulated coactivation was assessed using an ROI-based task-modulated coactivation analysis that revealed significant correlation between the FEF, PPC, and CV ROIs. Prior to vergence training, the CIs had a reduced BOLD percent signal change compared with BNCs for the CV (p<0.05), FEFs, and PPC (p<0.01). The BOLD percent signal change increased within the CV, FEF, and PPC ROIs (p<0.001) as did the task-modulated coactivation between the FEFs and CV as well as the PPC and CV (p<0.05) when comparing the CI pre- and post-training datasets. Results from the Convergence Insufficiency Symptom Survey were correlated to the percent BOLD signal change from the FEFs and CV (p<0.05).

Origins of intersubject variability of blood oxygenation level dependent and arterial spin labeling fMRI: implications for quantification of brain activity

Accurate localization of brain activity using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been challenged because of the large BOLD signal within distal veins. Arterial spin labeling (ASL) techniques offer greater sensitivity to the microvasculature but possess low temporal resolution and limited brain coverage. In this study, we show that the physiological origins of BOLD and ASL depend on whether percent change or statistical significance is being considered. For BOLD and ASL fMRI data collected during a simple unilateral hand movement task, we found that in the area of the contralateral motor cortex the centre of gravity (CoG) of the intersubject coefficient of variation (CV) of BOLD fMRI was near the brain surface for percent change in signal, whereas the CoG of the intersubject CV for Z-score was in close proximity of sites of brain activity for both BOLD and ASL. These findings suggest that intersubject variability of BOLD percent change is vascular in origin, whereas the origin of inter-subject variability of Z-score is neuronal for both BOLD and ASL. For longer duration tasks (12 s or greater), however, there was a significant correlation between BOLD and ASL percent change, which was not evident for short duration tasks (6 s). These findings suggest that analyses directly comparing percent change in BOLD signal between pre-defined regions of interest using short duration stimuli, as for example in event-related designs, may be heavily weighted by large-vessel responses rather than neuronal responses.

Neural Mechanisms Underlying Paradoxical Performance for Monetary Incentives Are Driven by Loss Aversion

SummaryEmployers often make payment contingent on performance in order to motivate workers. We used fMRI with a novel incentivized skill task to examine the neural processes underlying behavioral responses to performance-based pay. We found that individuals' performance increased with increasing incentives; however, very high incentive levels led to the paradoxical consequence of worse performance. Between initial incentive presentation and task execution, striatal activity rapidly switched between activation and deactivation in response to increasing incentives. Critically, decrements in performance and striatal deactivations were directly predicted by an independent measure of behavioral loss aversion. These results suggest that incentives associated with successful task performance are initially encoded as a potential gain; however, when actually performing a task, individuals encode the potential loss that would arise from failure.

The interplay of cue modality and response latency in brain areas supporting crossmodal motor preparation: an event-related fMRI study

Crossmodal (auditory, visual) motor facilitation can be defined as a cue in one sensory modality eliciting speeded responses to targets in a different sensory modality. We used event-related functional magnetic resonance imaging (fMRI) to isolate brain activity underlying crossmodal motor preparation. Our predictions were that interactions between input modality and processes underlying response selection would be indexed by distinct spatiotemporal brain dynamics. A crossmodal response selection task was designed in which a central, nonspatial cue indicated the response rule (compatible or incompatible) to a lateralized target. Cues and targets appeared in auditory and visual modalities and were separated by a lengthy delay period in which cue-related brain activity could be dissociated. We found faster reaction times to auditory compared with visual cues. Next, we correlated brain activity with behavioural performance using multivariate spatiotemporal partial least squares. We identified a distinct, significant brain-behaviour pattern in which faster reaction times to auditory cues were correlated with higher blood oxygenation level-dependent percent signal change in medial visual, frontoparietal (inferior parietal lobule, superior frontal gyrus and premotor cortex) and subcortical (thalamus and cerebellum) areas. For visual cues, quicker responses were linked to greater activity in the same frontoparietal and subcortical but not medial visual areas. Our results show that both modality-dependent and modality-independent brain areas with different brain-behaviour relationships are implicated in crossmodal motor preparation.

Magnetic resonance imaging of vascular oxygenation changes during hyperoxia and carbogen challenges in the human retina.

To demonstrate blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) of vascular oxygenation changes in normal, unanesthetized human retinas associated with oxygen and carbogen challenge. MRI was performed with a 3-T human scanner and a custom-made surface-coil detector on normal volunteers. BOLD MRI with inversion recovery was used to suppress the vitreous signal. During MRI measurements, volunteers underwent three episodes of air and 100% oxygen or carbogen (5% CO(2) and 95% O(2)) breathing. Eye movement was effectively managed with eye fixation, synchronized blinks, and postprocessing image coregistration. BOLD time-series images were analyzed using the cross-correlation method. Percent changes due to oxygen or carbogen inhalation versus air were tabulated for whole-retina and different regions of the retina. Robust BOLD responses were detected. BOLD MRI percent change from a large region of interest at the posterior pole of the retina was 5.2 ± 1.5% (N = 9 trials from five subjects) for oxygen inhalation and 5.2 ± 1.3% (N = 11 trials from five subjects) for carbogen inhalation. Group-averaged BOLD percent changes were not significantly different between oxygen and carbogen challenges (P > 0.05). The foveal region had greater BOLD response compared with the optic nerve head region for both challenges. BOLD retinal responses to oxygen and carbogen breathing in unanesthetized humans can be reliably imaged at high spatiotemporal resolution. BOLD MRI has the potential to provide a valuable tool to study retinal physiology and pathophysiology, such as how vascular oxygenation at the tissue level is regulated in the normal retina, and how retinal diseases may affect oxygen response.

BOLD fMRI of visual and somatosensory–motor stimulations in baboons

Baboon, with its large brain size and extensive cortical folding compared to other non-human primates, serves as a good model for neuroscience research. This study reports the implementation of a baboon model for blood oxygenation level-dependent (BOLD) fMRI studies (1.5×1.5×4 mm resolution) on a clinical 3T-MRI scanner. BOLD fMRI responses to hypercapnic (5% CO2) challenge, 10Hz flicker visual, and vibrotactile somatosensory–motor stimulations were investigated in baboons anesthetized sequentially with isoflurane and ketamine. Hypercapnia evoked robust BOLD increases. Paralysis was determined to be necessary to achieve reproducible functional activations within and between subjects under our experimental conditions. With optimized anesthetic doses (0.8–1.0% isoflurane or 6–8mg/kg/h ketamine) and adequate paralysis (vecuronium, 0.2mg/kg), robust activations were detected in the visual (V), primary (S1) and secondary (S2) somatosensory, primary motor (M cortices), supplementary motor area (SMA), lateral geniculate nucleus (LGN) and thalamus (Th). Data were tabulated for 11 trials under isoflurane and 10 trials under ketamine on 5 baboons. S1, S2, M, and V activations were detected in essentially all trials (90–100% of the time, except 82% for S2 under isoflurane and 70% for M under ketamine). LGN activations were detected 64–70% of the time under both anesthetics. SMA and Th activations were detected 36–45% of the time under isoflurane and 60% of the time under ketamine. BOLD percent changes among different structures were slightly higher under ketamine than isoflurane (0.75% versus 0.58% averaging all structures), but none was statistically different (P>0.05). This baboon model offers an opportunity to non-invasively image brain functions and dysfunctions in large non-human primates.

Functional abnormalities in normally appearing athletes following mild traumatic brain injury: a functional MRI study.

Memory problems are one of the most common symptoms of sport-related mild traumatic brain injury (MTBI), known as concussion. Surprisingly, little research has examined spatial memory in concussed athletes given its importance in athletic environments. Here, we combine functional magnetic resonance imaging (fMRI) with a virtual reality (VR) paradigm designed to investigate the possibility of residual functional deficits in recently concussed but asymptomatic individuals. Specifically, we report performance of spatial memory navigation tasks in a VR environment and fMRI data in 15 athletes suffering from MTBI and 15 neurologically normal, athletically active age matched controls. No differences in performance were observed between these two groups of subjects in terms of success rate (94 and 92%) and time to complete the spatial memory navigation tasks (mean = 19.5 and 19.7 s). Whole brain analysis revealed that similar brain activation patterns were observed during both encoding and retrieval among the groups. However, concussed athletes showed larger cortical networks with additional increases in activity outside of the shared region of interest (ROI) during encoding. Quantitative analysis of blood oxygen level dependent (BOLD) signal revealed that concussed individuals had a significantly larger cluster size during encoding at parietal cortex, right dorsolateral prefrontal cortex, and right hippocampus. In addition, there was a significantly larger BOLD signal percent change at the right hippocampus. Neither cluster size nor BOLD signal percent change at shared ROIs was different between groups during retrieval. These major findings are discussed with respect to current hypotheses regarding the neural mechanism responsible for alteration of brain functions in a clinical setting.

Electrodermal Recording and fMRI to Inform Sensorimotor Recovery in Stroke Patients

Background. Functional magnetic resonance imaging (fMRI) appears to be useful for investigating motor recovery after stroke. Some of the potential confounders of brain activation studies, however, could be mitigated through complementary physiological monitoring. Objective. To investigate a sensorimotor fMRI battery that included simultaneous measurement of electrodermal activity in subjects with hemiparetic stroke to provide a measure related to the sense of effort during motor performance. Methods. Bilateral hand and ankle tasks were performed by 6 patients with stroke (2 subacute, 4 chronic) during imaging with blood oxygen level-dependent (BOLD) fMRI using an event-related design. BOLD percent changes, peak activation, and laterality index values were calculated in the sensorimotor cortex. Electrodermal recordings were made concurrently and used as a regressor. Results. Sensorimotor BOLD time series and percent change values provided evidence of an intact motor network in each of these well-recovered patients. During tasks involving the hemiparetic limb, electrodermal activity changes were variable in amplitude, and electrodermal activity time-series data showed significant correlations with fMRI in 3 of 6 patients. No such correlations were observed for control tasks involving the unaffected lower limb. Conclusions. Electrodermal activity activation maps implicated the contralesional over the ipsilesional hemisphere, supporting the notion that stroke patients may require higher order motor processing to perform simple tasks. Electrodermal activity recordings may be useful as a physiological marker of differences in effort required during movements of a subject's hemiparetic compared with the unaffected limb during fMRI studies.

Imaging oxygen consumption in forepaw somatosensory stimulation in rats under isoflurane anesthesia.

The cerebral metabolic rate of oxygen (CMRO2) was dynamically evaluated on a pixel-by-pixel basis in isoflurane-anesthetized and spontaneously breathing rats following graded electrical somatosensory forepaw stimulations (4, 6, and 8 mA). In contrast to alpha-chloralose, which is the most widely used anesthetic in forepaw-stimulation fMRI studies of rats under mechanical ventilation, isoflurane (1.1-1.2%) provided a stable anesthesia level over a prolonged period, without the need to adjust the ventilation volume/rate or sample blood gases. Combined cerebral blood flow signals (CBF) and blood oxygenation level-dependent (BOLD) fMRI signals were simultaneously measured with the use of a multislice continuous arterial spin labeling (CASL) technique (two-coil setup). CMRO2 was calculated using the biophysical BOLD model of Ogawa et al. (Proc Natl Acad Sci USA 1992;89:5951-5955). The stimulus-evoked BOLD percent changes at 4, 6, and 8 A were, respectively, 0.5% +/- 0.2%, 1.4% +/- 0.3%, and 2.0% +/- 0.3% (mean +/- SD, N = 6). The CBF percent changes were 23% +/- 6%, 58% +/- 9%, and 87% +/- 14%. The CMRO2 percent changes were 14% +/- 4%, 24% +/- 6%, and 43% +/- 11%. BOLD, CBF, and CMRO2 activations were localized to the forepaw somatosensory cortices without evidence of plateau for oxygen consumption, indicative of partial coupling of CBF and CMRO2. This study describes a useful forepaw-stimulation model for fMRI, and demonstrate that CMRO2 changes can be dynamically imaged on a pixel-by-pixel basis in a single setting with high spatiotemporal resolution.

Origin of negative blood oxygenation level-dependent fMRI signals.

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in spike activity are accompanied by modulation in the blood oxygenation level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed and are thought to reflect a decrease in neural activity. In this study, the source of the negative BOLD signal was investigated using T2*-weighted BOLD and cerebral blood volume (CBV) techniques in isoflurane-anesthetized cats. A positive BOLD signal change was observed in the primary visual cortex (area 18) during visual stimulation, while a prolonged negative BOLD change was detected in the adjacent suprasylvian gyrus containing higher-order visual areas. However, in both regions neurons are known to increase spike activity during visual stimulation. The positive and negative BOLD amplitudes obtained at six spatial-frequency stimuli were highly correlated, and negative BOLD percent changes were approximately one third of the positive changes. Area 18 with positive BOLD signals experienced an increase in CBV, while regions exhibiting the prolonged negative BOLD signal underwent a decrease in CBV. The CBV changes in area 18 were faster than the BOLD signals from the same corresponding region and the CBV changes in the suprasylvian gyrus. The results support the notion that reallocation of cortical blood resources could overcome a local demand for increased cerebral blood flow induced by increased neural activity. The findings of this study imply that caution should be taken when interpreting the negative BOLD signals as a decrease in neuronal activity.

Influence of baseline hematocrit and hemodilution on BOLD fMRI activation

Current understanding of blood oxygenation level dependent (BOLD) fMRI physiology predicts a close relationship between BOLD signal and blood hematocrit level. However, neither this relationship nor its effect on BOLD percent activation (BPA) has been empirically examined in man. To that end, BPA in primary visual cortex in response to photic stimulation was determined in a group of 24 normal subjects. A positive linear relationship between BPA and hematocrit was seen, particularly in men. To evaluate the effect of change in hematocrit on BPA, 9 men were studied before and following isotonic saline hemodilution, resulting in an average 6% reduction in hematocrit and an 8–31% reduction in BPA. No significant change in the number of activated pixels was seen. A model of predicted BPA as a function of hematocrit and vessel size was developed, and results from this model closely mirrored the empiric data. These results suggest that hematocrit significantly influences the magnitude of BPA and that such baseline factors should be accounted for when comparing BOLD data across groups of subjects, particularly in the many instances in which hematocrit may vary systematically. Such instances include several disease states as well as studies involving sex differences, drug administration, stress and other factors. Finally, the robust agreement between predicted and empiric data serves to validate a semiquantitative approach to the analysis of BOLD fMRI data.