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30 Rohde, Buitelaar, Gerlach & Faraone Box 2.2 MEASURES OF BRAIN STRUCTURE AND FUNCTION Neuroimaging has provided a tremendous boost to neuroscience, by enabling a non- invasive study of the brain in health and disease. This chapter describes research into measures of brain structure, activity, and functional network connectivity in individuals with ADHD and control participants. Structural magnetic resonance imaging (sMRI) scans are used predominantly to study aspects of brain grey matter, containing neuronal cell bodies and synapses, and white matter, consisting mostly of the myelinated axons that connect brain areas. sMRI scans allow both for assessing the volume of apriori defined volumes of cortical and subcortical volumes and for bottom-up brainwide analyses of brain voxels (voxel-based morphometry- VBM). Finally, sMRI scans enable to quantify various aspects of the cortex, such as cortical thickness, surface area and gyrification. Diffusion-tensor imaging (DTI) or diffusion-weighted imaging (DWI) scans make it possible to estimate the location, orientation and functional integrity of the brain’s white matter tracts. Functional MRI (fMRI) takes advantage of changes in the magnetic properties of blood passing through the brain as an indicator of the relative activity of a region over time. The blood-oxygen level dependent (BOLD) signal is usually recorded while subjects perform a cognitive task, and then compared to a baseline recording to isolate the task-associated activity. FMRI data may also be used to study brain functional connectivity by calculating the coherence of activation patterns over time between regions. This may be done with task-based fMRI data, as well as with recordings while individuals are not engaged in any specific task, known as resting-state MRI (rsMRI). Studies into functional connectivity have identified several brain networks, collections of regions that are consistently co-activated. The activation of these networks depends on the subjects’ current state of mind. For instance, activity in the executive function network is most prominent when performing a working memory task, and the default mode network becoming more active while mind wandering during resting conditions. 93 Information about brain function can also be obtained by electroencephalography or EEG; this is the physiological method of choice to record all of the electrical activity generated by the brain from electrodes placed on the scalp surface, and allows to study the power of frequency patterns of brain oscillations (delta, 1-4 Hz, theta 4-7 Hz, alpha 7-12 Hz, beta 12-30 Hz , and gamma > 30 Hz). Event-related potentials (ERP) assess the change in electrical activity time-locked to certain cognitive or attentional tasks. Magnetoencephalography , or MEG, is an imaging technique that measures small magnetic fields produced by the electrical activity in the brain. Proton magnetic resonance spectroscopy (MRS) is an imaging technique allowing for in vivo quantification of several neurometabolites in small volumes of the brain. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) use radioactive tracers for targeting different steps in the process of for example dopaminergic neurotransmission.