Spatial smoothing systematically biases the localization of reward-related brain activity

Neuroimaging methods with enhanced spatial resolution such as functional magnetic resonance imaging (FMRI) suggest that the subcortical striatum plays a critical role in human reward processing. Analysis of FMRI data requires several preprocessing steps, some of which entail tradeoffs. For instance, while spatial smoothing can enhance statistical power, it may also bias localization towards regions that contain more gray than white matter. In a meta-analysis and reanalysis of an existing dataset, we sought to determine whether spatial smoothing could systematically bias the spatial localization of foci related to reward anticipation in the nucleus accumbens (NAcc). An activation likelihood estimate (ALE) meta-analysis revealed that peak ventral striatal ALE foci for studies that used smaller spatial smoothing kernels (i.e. <6mm FWHM) were more anterior than those identified for studies that used larger kernels (i.e. >7mm FWHM). Additionally, subtraction analysis of findings for studies that used smaller versus larger smoothing kernels revealed a significant cluster of differential activity in the left relatively anterior NAcc (Talairach coordinates: -10, 9, -1). A second meta-analysis revealed that larger smoothing kernels were correlated with more posterior localizations of NAcc activation foci (p<0.015), but revealed no significant associations with other potentially relevant parameters (including voxel volume, magnet strength, and publication date). Finally, repeated analysis of a representative dataset processed at different smoothing kernels (i.e., 0-12mm) also indicated that smoothing systematically yielded more posterior activation foci in the NAcc (p<0.005). Taken together, these findings indicate that spatial smoothing can systematically bias the spatial localization of striatal activity. These findings have implications both for historical interpretation of past findings related to reward processing and for the analysis of future studies.

[1]  Jeffrey C. Cooper,et al.  Functional magnetic resonance imaging of reward prediction , 2005, Current opinion in neurology.

[2]  Gregory R. Samanez-Larkin,et al.  Anticipation of monetary gain but not loss in healthy older adults , 2007, Nature Neuroscience.

[3]  Kristen A. Lindquist,et al.  The brain basis of emotion: A meta-analytic review , 2012, Behavioral and Brain Sciences.

[4]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited—Again , 1995, NeuroImage.

[5]  Camelia M. Kuhnen,et al.  Variability in Nucleus Accumbens Activity Mediates Age-Related Suboptimal Financial Risk Taking , 2010, The Journal of Neuroscience.

[6]  Brian Knutson,et al.  Anticipation of Increasing Monetary Reward Selectively Recruits Nucleus Accumbens , 2001, The Journal of Neuroscience.

[7]  Michael J. Martinez,et al.  Bias between MNI and Talairach coordinates analyzed using the ICBM‐152 brain template , 2007, Human brain mapping.

[8]  Edson Oliveira,et al.  The Human Nucleus Accumbens: Where Is It? A Stereotactic, Anatomical and Magnetic Resonance Imaging Study , 2008, Neuromodulation : journal of the International Neuromodulation Society.

[9]  A. Laird,et al.  The Neural Basis of Drug Stimulus Processing and Craving: An Activation Likelihood Estimation Meta-Analysis , 2011, Biological Psychiatry.

[10]  Brian Knutson,et al.  Reward system activation in schizophrenic patients switched from typical neuroleptics to olanzapine , 2008, Psychopharmacology.

[11]  Angela R. Laird,et al.  Co-activation patterns distinguish cortical modules, their connectivity and functional differentiation , 2011, NeuroImage.

[12]  Henrik Walter,et al.  Prediction error as a linear function of reward probability is coded in human nucleus accumbens , 2006, NeuroImage.

[13]  Stefan Kaiser,et al.  Neural reward processing is modulated by approach- and avoidance-related personality traits , 2010, NeuroImage.

[14]  V. Barnett,et al.  Applied Linear Statistical Models , 1975 .

[15]  Brian Knutson,et al.  Dissociation of reward anticipation and outcome with event-related fMRI , 2001, Neuroreport.

[16]  D. Kahneman,et al.  Functional Imaging of Neural Responses to Expectancy and Experience of Monetary Gains and Losses tasks with monetary payoffs , 2001 .

[17]  Jin Fan,et al.  Common and distinct networks underlying reward valence and processing stages: A meta-analysis of functional neuroimaging studies , 2011, Neuroscience & Biobehavioral Reviews.

[18]  Angela R. Laird,et al.  Comparison of the disparity between Talairach and MNI coordinates in functional neuroimaging data: Validation of the Lancaster transform , 2010, NeuroImage.

[19]  A. Smit,et al.  Synapse Formation between Central Neurons Requires Postsynaptic Expression of the MEN1 Tumor Suppressor Gene , 2001, The Journal of Neuroscience.

[20]  Martin A. Lindquist,et al.  Adaptive spatial smoothing of fMRI images , 2010 .

[21]  E Zarahn,et al.  Empirical analyses of BOLD fMRI statistics. II. Spatially smoothed data collected under null-hypothesis and experimental conditions. , 1997, NeuroImage.

[22]  Brian Knutson,et al.  A region of mesial prefrontal cortex tracks monetarily rewarding outcomes: characterization with rapid event-related fMRI , 2003, NeuroImage.

[23]  K. Berridge,et al.  Positive and Negative Motivation in Nucleus Accumbens Shell: Bivalent Rostrocaudal Gradients for GABA-Elicited Eating, Taste “Liking”/“Disliking” Reactions, Place Preference/Avoidance, and Fear , 2002, The Journal of Neuroscience.

[24]  Brian Knutson,et al.  Amphetamine Modulates Human Incentive Processing , 2004, Neuron.

[25]  Emily Bell,et al.  Striatal topography of probability and magnitude information for decisions under uncertainty , 2012, NeuroImage.

[26]  K. Berridge,et al.  The Neuroscience of Natural Rewards: Relevance to Addictive Drugs , 2002, The Journal of Neuroscience.

[27]  Brian Knutson,et al.  Incentive-elicited Striatal Activation in Adolescent Children of Alcoholics , 2022 .

[28]  Angela R. Laird,et al.  Activation likelihood estimation meta-analysis revisited , 2012, NeuroImage.

[29]  B. Abler,et al.  Human reward system activation is modulated by a single dose of olanzapine in healthy subjects in an event-related, double-blind, placebo-controlled fMRI study , 2007, Psychopharmacology.

[30]  Brian Knutson,et al.  Ventral Striatal Activation During Reward Anticipation Correlates with Impulsivity in Alcoholics , 2009, Biological Psychiatry.

[31]  Brian Knutson,et al.  Anticipatory affect: neural correlates and consequences for choice , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[32]  J. O'Doherty,et al.  Reward representations and reward-related learning in the human brain: insights from neuroimaging , 2004, Current Opinion in Neurobiology.

[33]  S. Haber,et al.  The Reward Circuit: Linking Primate Anatomy and Human Imaging , 2010, Neuropsychopharmacology.

[34]  Michael Bauer,et al.  Reward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder , 2008, NeuroImage.

[35]  David Miller,et al.  Bilateral spatial filtering: Refining methods for localizing brain activation in the presence of parenchymal abnormalities , 2006, NeuroImage.

[36]  Brian Knutson,et al.  Reward-Motivated Learning: Mesolimbic Activation Precedes Memory Formation , 2006, Neuron.

[37]  Mark S. Cohen,et al.  Parametric Analysis of fMRI Data Using Linear Systems Methods , 1997, NeuroImage.

[38]  Brian Knutson,et al.  Incentive-Elicited Brain Activation in Adolescents: Similarities and Differences from Young Adults , 2004, The Journal of Neuroscience.

[39]  K. Zilles,et al.  Coordinate‐based activation likelihood estimation meta‐analysis of neuroimaging data: A random‐effects approach based on empirical estimates of spatial uncertainty , 2009, Human brain mapping.

[40]  Michael X. Cohen,et al.  Different neural systems adjust motor behavior in response to reward and punishment , 2007, NeuroImage.

[41]  Brian Knutson,et al.  Neural Responses to Monetary Incentives in Major Depression , 2008, Biological Psychiatry.

[42]  Brian Knutson,et al.  FMRI Visualization of Brain Activity during a Monetary Incentive Delay Task , 2000, NeuroImage.

[43]  S. Quartz,et al.  Neural Differentiation of Expected Reward and Risk in Human Subcortical Structures , 2006, Neuron.

[44]  T. Robbins,et al.  Neurobehavioural mechanisms of reward and motivation , 1996, Current Opinion in Neurobiology.

[45]  Karl J. Friston,et al.  Assessing the significance of focal activations using their spatial extent , 1994, Human brain mapping.

[46]  Nikos K Logothetis,et al.  Interpreting the BOLD signal. , 2004, Annual review of physiology.

[47]  S. Krach,et al.  Anticipation of monetary and social reward differently activates mesolimbic brain structures in men and women. , 2009, Social cognitive and affective neuroscience.

[48]  P. Fox,et al.  Mapping context and content: the BrainMap model , 2002, Nature Reviews Neuroscience.

[49]  Arno Villringer,et al.  Dysfunction of ventral striatal reward prediction in schizophrenia , 2006, NeuroImage.

[50]  P. Dayan,et al.  Differential Encoding of Losses and Gains in the Human Striatum , 2007, The Journal of Neuroscience.

[51]  S. Hyman,et al.  Acute Effects of Cocaine on Human Brain Activity and Emotion , 1997, Neuron.

[52]  G. Glover,et al.  Spiral‐in/out BOLD fMRI for increased SNR and reduced susceptibility artifacts , 2001, Magnetic resonance in medicine.

[53]  N Ramnani,et al.  Instructed delay activity in the human prefrontal cortex is modulated by monetary reward expectation. , 2003, Cerebral cortex.

[54]  Michael H. Kutner Applied Linear Statistical Models , 1974 .

[55]  R. Wise Brain Reward Circuitry Insights from Unsensed Incentives , 2002, Neuron.

[56]  Simon B Eickhoff,et al.  Minimizing within‐experiment and within‐group effects in activation likelihood estimation meta‐analyses , 2012, Human brain mapping.

[57]  Brian Knutson,et al.  Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics , 2007, NeuroImage.

[58]  Angela R. Laird,et al.  BrainMap , 2007, Neuroinformatics.

[59]  Peter Kirsch,et al.  Anticipation of reward in a nonaversive differential conditioning paradigm and the brain reward system: an event-related fMRI study , 2003, NeuroImage.

[60]  Angela R Laird,et al.  Brainmap taxonomy of experimental design: Description and evaluation , 2005, Human brain mapping.

[61]  M. Delgado,et al.  Provided for Non-commercial Research and Educational Use Only. Not for Reproduction, Distribution or Commercial Use. Representation of Subjective Value in the Striatum , 2022 .