Functional magnetic resonance imaging (FMRI) based on the blood oxygen-level dependent (BOLD) signal has revolutionized cognitive neuroscience. However, the FMRI BOLD signal is an indirect measure of neural activity dependent on fluctuations in the oxygenation level of blood that is neither a direct measure of neural activity nor the hemodynamics responding to that activity. There is accumulating evidence that the indirect nature of the BOLD signal can provide inaccurate estimates of neural activity when comparing groups or individuals with differences in neurovascular coupling. This means that the BOLD signal may provide inaccurate estimates of neural activation in contrasts for typical and atypical development, psychiatric and neurological disorders, and response to psychoactive or pharmacological agents. The BOLD signal may systematically under- or over-estimate neural activity at rest or in response to task or challenge factors in one group or the other. To increase the validity of FMRI, it will be critical to understand how the additional factors modulating the BOLD signal vary across contrasts. This project seeks to meet this challenge by applying a newly developed quantitative FMRI (QFMRI) technology that, unlike other methods of QFMRI, uses standard MRI approaches that do not require the inhalation of special gases (e.g., CO2) and thus are capable of being used in a variety of settings and populations just as traditional BOLD FMRI is used today. Here, we will evaluate the advantages of QFMRI across typical development, an area that has strong evidence for inaccurate estimates of neural activity based on the BOLD signal. This project will use a dual-echo arterial spin labeling (ASL) to obtain baseline cerebral blood flow (CBF) and CBF and BOLD changes during performance on four perceptual processing tasks (visual, auditory, face, and object processing) in three developmental groups: children (8-9 years), adolescents (14-15 years) and young adults (20-30 years). In addition, we will obtain a measure of the cerebral metabolism rate of oxygen (CMRO2) in the baseline state using the newly developed GESSE technique for measuring R2'? (scaling parameter M).
In Aim 1, we will use our direct measure of M to define neural activity in our tasks more precisely across development. This will allow us to characterize the validity of the BOLD method in developmental studies.
In Aim 2, we will investigate the relationship of our QFMRI estimates of the physiological measures of neural activity with structural brain measures including cortical thickness, area, volume, and whole brain volume. The findings from this study of typical development will have broad implications in all areas of basic and clinical neuroscience, and may provide metrics allowing researchers to adjust prior findings of BOLD signal developmental trajectories to correct for potential underestimates of neural activity in children and adolescents based on the BOLD signal alone.
AlthoughFMRIBOLDstudieshavebeeninstrumentalinbuildingourunderstandingofbrain-behavior relationships,thereisincreasingevidencethattheFMRIBOLDmaynotprovidevalidestimatesofneuronal activitybetweenpopulationsdifferinginage,psychiatricorneurologicalstatus,orpharmacologicalstatus,to namejustafew.ThisprojectwillusenewlydevelopedquantitativeFMRItechniquesusingstandardMR imagingprocedurestodeterminewithunprecedentedprecisiontheseparateeffectsofcerebralbloodflow (CBF),thecerebralmetabolicrateofoxygen(CMRO2),andthebrainoxygenextractionfraction(OEF)by measuringthebaselinestateandfractionalchangesinCBFandBOLDacrossvariousperceptualtasksin children,adolescents,andadults.Wewilldemonstrateapotentialsolutiontothevalidityproblemsin estimatingneuralactivityfromBOLDimagingacrossgroups.
