Peripheral blood pressure changes induced by dobutamine do not alter BOLD signals in the human brain.
ABSTRACT In extending the use of functional MRI to neuropharmacology, a primary area of concern is that peripheral blood pressure changes induced by pharmacological agents could independently produce a change in the blood oxygenation level-dependent (BOLD) signal, resulting in difficulties distinguishing or interpreting drug-induced neural activations. In the present study, we utilized intravenous dobutamine, a beta-adrenergic receptor agonist, to increase the mean arterial blood pressure (MABP), while examining the effects of MABP changes on the BOLD signal in cocaine-dependent participants. Dobutamine infusion significantly increased the MABP from 93 +/- 8 mm Hg to 106 +/- 12 mm Hg (P < 0.0005), but did not produce a significant global BOLD signal. Yet, a few voxels in the anterior cingulate showed BOLD signal changes that paralleled the changes in blood pressure (BP). Our observations support the conclusion that following the infusion of psychoactive agents, brain BOLD signals accurately reflect neuronal activity, even in the face of relatively large peripheral cardiovascular effects that transiently increase systemic BP.
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ABSTRACT: Hypertension is associated with mild decrements in cognition. In addition, regional cerebral blood flow responses during memory processing are blunted in parietal and thalamic areas among untreated hypertensive adults, who, compared with normotensive subjects, manifest greater correlation in blood flow response across task-related brain regions. Here, we test whether pharmacological treatment of hypertension normalizes regional cerebral blood flow responses and whether it does so differentially according to drug class. Treatment with lisinopril, an angiotensin-converting enzyme blocker, known to enhance vasodilative responsivity, was compared with treatment with atenolol, a beta-blocker. Untreated hypertensive volunteers (n=28) were randomly assigned and treated for 1 year. Whole brain and regional cerebral flow responses to memory processing and acutely administered acetazolamide, a vasodilator, were assessed pretreatment and posttreatment. Peripheral brachial artery dilation during reactive hyperemia was also measured. Quantitative blood flow measures showed no difference in the magnitude of regional cerebral blood flow responses pretreatment and posttreatment to either memory tasks or acetazolamide injection. Brachial artery flow-mediated dilation increased with treatment. No differences between medications were observed. In brain regions active in memory processing, however, regional cerebral blood flow responses were more highly correlated after treatment. Specificity of cerebral blood flow to different regions appears to decline with treatment of hypertension. This greater correlation among active brain regions, which is present as well in untreated hypertensive relative to normotensive volunteers, may represent compensation in the face of less region-specific responsivity in individuals with hypertension.Hypertension 07/2008; 52(1):65-71. DOI:10.1161/HYPERTENSIONAHA.108.110262 · 7.63 Impact Factor
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ABSTRACT: This review and meta-analysis aims at summarizing and integrating the human neuroimaging studies that report periaqueductal gray (PAG) involvement; 250 original manuscripts on human neuroimaging of the PAG were identified. A narrative review and meta-analysis using activation likelihood estimates is included. Behaviors covered include pain and pain modulation, anxiety, bladder and bowel function and autonomic regulation. Methods include structural and functional magnetic resonance imaging, functional connectivity measures, diffusion weighted imaging and positron emission tomography. Human neuroimaging studies in healthy and clinical populations largely confirm the animal literature indicating that the PAG is involved in homeostatic regulation of salient functions such as pain, anxiety and autonomic function. Methodological concerns in the current literature, including resolution constraints, imaging artifacts and imprecise neuroanatomical labeling are discussed, and future directions are proposed. A general conclusion is that PAG neuroimaging is a field with enormous potential to translate animal data onto human behaviors, but with some growing pains that can and need to be addressed in order to add to our understanding of the neurobiology of this key region.NeuroImage 12/2011; 60(1):505-22. DOI:10.1016/j.neuroimage.2011.11.095 · 6.13 Impact Factor
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ABSTRACT: Prior research points to the importance of psychostimulants in improving self-control. However, the neural substrates underlying such improvement remain unclear. Here, in a pharmacological functional MRI study of the stop signal task, we show that methylphenidate (as compared with placebo) robustly decreased stop signal reaction time (SSRT), an index of improved control, in cocaine-dependent patients (a population in which inhibitory control is impaired). Methylphenidate-induced decreases in SSRT were positively correlated with inhibition-related activation of left middle frontal cortex (MFC) and negatively with activation of the ventromedial prefrontal cortex (vmPFC) in whole brain linear regressions. Inhibition-related MFC but not vmPFC activation distinguished individuals with short and long SSRT in 36 demographically matched healthy individuals, whereas vmPFC but not MFC activation, along with improvement in SSRT, was correlated with a previously implicated biomarker of methylphenidate response (systolic blood pressure). These results implicate a specific neural (i.e., vmPFC) mechanism whereby stimulants improve inhibitory control. Altered ventromedial prefrontal activation and increased blood pressure may represent useful CNS and peripheral biomarkers in individualized treatment with methylphenidate for patients with cocaine dependence.Proceedings of the National Academy of Sciences 08/2010; 107(32):14455-9. DOI:10.1073/pnas.1002467107 · 9.81 Impact Factor