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Functional Neuroimaging 1 Fundamentals Of FUNCTIONAL NEUROIMAGING 1 FUNDAMENTALS OF FUNCTIONAL NEUROIMAGING Stephan Geuter1 Martin A. Lindquist2 Tor D. Wager1,3* 1University of Colorado Boulder, Institute of Cognitive Science 2Johns Hopkins University, Department of Biostatistics 3University of Colorado Boulder, Department of Psychology and Neuroscience Summary: 21303 words (text, without references) 26058 total words (with references) 3 tables 11 figures Running head: FUNCTIONAL NEUROIMAGING * Address correspondence to: Dr. Tor D. Wager Department of Psychology and Neuroscience University of Colorado Boulder 345 UCB Boulder, CO 80309 E-mail: tor.wager@ colorado.edu. FUNCTIONAL NEUROIMAGING 2 Acknowledgments We would like to thank Jessica Andrews-Hanna for helpful comments on the manuscript. Parts of this chapter are adapted from Wager. T. D., Hernandez, L., and Lindquist, M.A. (2009). Essentials of functional neuroimaging. In: G. G. Berntson and J. T. Cacioppo (Eds.), Handbook of Neuroscience for the Behavioral Sciences. (pp. 152-97). Hoboken, NJ: John Wiley & Sons. FUNCTIONAL NEUROIMAGING 3 I. Introduction ................................................................................................................. 5 II. Overview of Neuroimaging Techniques .................................................................... 6 Measures available on MR and PET scanners .................................................... 7 Structural images ............................................................................................ 7 Diffusion weighted imaging (DWI) ................................................................ 8 Functional MRI ............................................................................................... 8 Measures of brain activity using PET ............................................................. 9 Measures of functional neurochemistry using PET ...................................... 11 Comparison of PET and fMRI .......................................................................... 12 Spatial limitations of PET and fMRI ............................................................ 13 Temporal resolution and trial structure ......................................................... 15 Acquisition artifacts ...................................................................................... 16 Combining Techniques: fMRI, EEG, TMS, Genetics ...................................... 17 III. fMRI measures: Signal acquisition and physiology .............................................. 20 MR physics and BOLD basics .......................................................................... 20 BOLD Physiology ............................................................................................. 21 Practical considerations (acquisition) ............................................................... 23 IV. Using fMRI to make inferences about brain and mind ......................................... 25 Interpretation of fMRI studies .......................................................................... 25 Forward inference and reverse inference ...................................................... 25 From regions to patterns: Enhanced potential for inference ......................... 27 Dissociation logic .......................................................................................... 28 Interpretation of overlapping brain signals ................................................... 29 Comparison of univariate and multivariate techniques .................................... 30 FUNCTIONAL NEUROIMAGING 4 Designs for fMRI studies .................................................................................. 32 Experimental designs .................................................................................... 32 Block designs ................................................................................................ 33 Event-related fMRI ....................................................................................... 34 Optimized experimental designs ................................................................... 36 Resting state .................................................................................................. 37 Non-experimental designs ............................................................................ 40 Practical considerations (design, power) .......................................................... 41 V. Fundamentals of fMRI signal processing and analysis ......................................... 44 Preprocessing .................................................................................................... 44 General linear model ......................................................................................... 48 Localizing task-related activations with the GLM ........................................ 48 Single-subject GLM model basics ................................................................ 50 Mixed and fixed effects. ............................................................................... 53 Thresholding and multiple comparisons ........................................................... 54 FWE correction ............................................................................................. 56 FDR control .................................................................................................. 58 Anatomical localization and inference .............................................................. 58 Connectivity analyses in fMRI ......................................................................... 62 VI. Conclusions ................................................................................................................ 64 VII. References ............................................................................................................ 64 VIII. Figure Captions ................................................................................................... 77 FUNCTIONAL NEUROIMAGING 5 I. INTRODUCTION Functional neuroimaging techniques have become a central research tool for psychologists, cognitive scientists and neuroscientists. The use of neuroimaging data from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies is central to the fields of cognitive neuroscience, affective neuroscience, social cognitive neuroscience, neuroeconomics, and related disciplines. FMRI and PET data are being combined with data on human performance, psychophysiology, genetics, and computational models of performance and neural function in increasingly sophisticated ways. The result is enhanced models of human brain function in relation to thought, emotion, and behavior, which can be used to both understand the mind and guide applied research on performance enhancement and clinical assessment and treatment. The best such models are informed by the rich histories of cognitive psychology and psychophysiology, and—due largely to the integration of neuroimaging data—are increasingly grounded in brain physiology. This grounding permits stronger and more specific connections with the neurosciences and biomedical sciences, allowing behavioral scientists to leverage a vast and growing literature on brain systems developed in these fields. All neuroscience methods have limitations, and neuroimaging is no exception. The current trend is towards increasingly multidisciplinary approaches that use multiple methodologies to overcome some of the limitations of each method used in isolation. For example, currently available techniques allow electroencephalography (EEG) and fMRI data to be collected simultaneously (Goldman et al., 2000), which provides improved temporal precision, among other benefits. Neuroimaging data are also being combined with transcranial magnetic stimulation, combining the ability of neuroimaging to observe brain activity with the ability of TMS to manipulate brain function and examine causal effects (Bohning et al., 1997). The rapid pace of development and interdisciplinary nature of the neuro- behavioral sciences presents an enormous challenge to researchers. Moving this kind of science forward requires a collaborative team with expertise in psychology, neuroanatomy, neurophysiology, physics, biomedical engineering, statistics, signal FUNCTIONAL NEUROIMAGING 6 processing, and other disciplines. Having a successful team requires that individuals push beyond the boundaries of their disciplines and develop expertise in multiple areas, so that there is enough overlap that the team can work well together. Hence, the goal of this chapter is to review the basic techniques involved in the acquisition and analysis of neuroimaging data—and some recent developments—in enough detail to highlight the most important issues and concerns. We also intend to provide an overall roadmap of study design and analysis options and some of their limitations. The various aspects of PET and fMRI methodology are organized here into four sections. Section II deals with what several neuroimaging techniques measure, including a comparison of PET and fMRI. Section III covers the basics of fMRI data acquisition and the relationship between brain activity and observed fMRI signals. Section IV describes how fMRI data are used to make psychological inferences and how inference relates to study designs. We emphasize two kinds of inferences: forward inferences about brain activity given a psychological experimental manipulation, and reverse inferences about psychology given patterns of brain
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