Functional magnetic resonance imaging: Basic …

1 Developmental Science 5:3 (2002), pp 301 309 Blackwell Publishers Ltd. 2002, 108 Cowley Road, Oxford OX4 1JF, UK and 350 Main Street, Malden, MA 02148, USA. UNCORRECTED PROOF Blackwell Publishers Ltd Functional magnetic resonance imaging : Basic principles of and application to developmental science Casey, 1 Matthew Davidson 1 and Bruce Rosen 2 1. Sackler Institute for Developmental Psychobiology, Weill Medical College of Cornell University, USA 2. NMR Institute, MGH, Harvard University, USA Abstract Functional magnetic resonance imaging (fMRI) has quickly become the preferred technique for imaging normal brain activity,especially in the typically developing child.

2 This technique takes advantage of specific magnetic properties and physiologicalprocesses to generate images of brain activity. These images can be interpreted as a function of group or individual based dif-ferences to explore developmental patterns and/or cognitive abilities. In this paper we present an overview of the Basic principlesof fMRI and a discussion of what is currently known about the physiological bases of the resulting signal. We also report findingsfrom developmental fMRI studies that examine the development of cognitive and neural systems underlying attention andmemory.

3 Behavioral performance and age-related neural changes are examined independently in an attempt to disentangledevelopmental differences from individual variability in performance. Introduction One of the most exciting methodologies to evolvetoward the end of the twentieth century is that of func-tional magnetic resonance imaging (fMRI). This meth-odology began with nuclear magnetic resonance (NMR)and continued with magnetic resonance imaging (MRI)as described by Kennedy et al. in this special issue. MRIbecame especially important to cognitive and develop-mental psychologists when the Functional capabilitieswere discovered and developed.

4 Whereas MRI is usedto produce structural images of subject brains usefulfor anatomical and morphometric studies the functionalcomponent allows an in vivo measure of brain Functional methodology measures changes in oxy-gen levels of the blood in the brain. These changes pre-sumably reflect changes in neural activity that areaccompanied by changes in blood flow. The fMRI method capitalizes on magnetic differencesbetween oxygenated and deoxygenated blood. In short,hemoglobin in the blood becomes strongly paramagneticin its deoxygenated state.

5 Deoxygenated hemoglobin cantherefore be used as a naturally occurring contrast agent,with highly oxygenated brain regions producing a largermagnetic resonance (MR) signal than less oxygenatedareas. Thus, during brain activation, localized increasesin blood flow increase blood oxygenation and conse-quently reduce deoxygenated hemoglobin, causing theMR signal to increase. It is assumed that these local-ized increases in blood oxygenation reflect increases inneuronal activity. This method, blood-oxygenation-level-dependent (BOLD) imaging , eliminates the need forexogenous contrast agents, including radioactive isotopes(Kwong, Belliveau, Chesler, Goldberg, Weisskoff, Poncelet,Kennedy, Hoppel, Cohen & Turner, 1992; Ogawa, Lee,Snyder & Raichle, 1990; Turner, Le Bihan, Moonen,Despres & Frank, 1991).

6 Physiological bases of fMRI Even with the enormous interest and widespread use ofthis methodology, the relation between the MR signaland physiological mechanisms underlying this signal arenot well understood. BOLD imaging relies on sensitivityto changes in oxygen levels within the circulating human brain uses roughly 20% of the oxygenneeded by the body even though it makes up less than2% of total body mass. Oxygen is used in breaking downglucose to supply the brain with energy. However, bloodflow and glucose consumption far exceed the increasesin oxygen consumption.

7 This results in increasedamounts of oxygen in the blood that can be detectedwith fMRI. What is not clear is how blood oxygenationlevels relate to neuronal activity. One model has been put forth in relation to glutamate, Address for correspondence: Casey, Sackler Institute, Weill Medical College of Cornell University, 1300 York Avenue, Box 140, New York,NY 10021, USA; e-mail: 302 Casey, Matthew Davidson and Bruce Rosen Blackwell Publishers Ltd. 2002 UNCORRECTED PROOF the primary excitatory neurotransmitter in the glutamate has been released and stimulates thepostsynaptic receptors it must be removed from thesynaptic cleft to prevent continued stimulation (whichmay lead to excitotoxicity).

8 Glutamate reuptake occursin non-neuronal cells called astrocytes, where glutamateis converted into glutamine and then returned to theneuron and recycled. The processing of glutamate is theresult of glycolysis breakdown of glucose obtainedfrom the blood (and/or astrocytes) without oxygen. Soblood oxygen level is thought to increase after excitatoryneurotransmission because of an increase in processingof glutamate in astrocytes (Magistretti, Pellerin, Roth-man & Shulman, 1999; Shulman, Hyder & Rothman,2001).

9 This model appears to work well for glutamate,but it is less clear how the BOLD signal is related tochanges in other neurotransmitters, including inhibitorysubstances like -aminobutyric acid (GABA). It is alsonot clear why or how blood flow increases occur duringneuronal activity, although many speculate that it is dueto a need for glucose or oxygen (Powers, Hirsch & Cryer,1996; Mintun, Lundstrom, Snyder, Vlassenko, Shulman& Raichle, 2001).Pioneering work by Logothetis and colleagues (2001)has taken us a step forward in understanding the rela-tionship between the BOLD signal and neuronal activity(also see Raichle, 2001; Bandettini & Ungerleider, 2001).

10 Logothetis recorded electrical activity of neurons in thevisual cortex of the monkey in conjunction with results showed a spatially restricted increase in theBOLD signal that corresponded with an increase inneural activity, suggesting a fairly direct relationshipbetween neural activity and fMRI signal. This relation-ship had only been inferred up to this point but theseresults provide important confirmation of the fMRItechnique. The BOLD signal does indeed reflect neuronalactivity (Logothetis, Pauls, Augath, Trinath & Oelter-mann, 2001).