Clinic for Psychiatry, Psychotherapy and Psychosomatics How to plan and prepare a Meta-analysis Claudia Rottschy Felix Hoffstaedter Structural and functional organization of the brain (INM-1) Why Meta-Analyses? Small samples Compared to other fields of cognitive and social science and particularly to clinical research Publication of isolated findings Due to logistic expenses, additional experiments for confirmation and extension of findings are rarely performed Indirect measures of neuronal activity Reliability is influenced and probably limited by biological, technical and methodological confounds Generalisation of context-specific findings Inference on brain function and pathomechanisms based on specific differences in this experimental setting Why Meta-Analyses? BUT There are many studies Recent estimate 15.000 fMRI and PET Paper All report standardised results! Derrfuss & Mar 2009 Neuroimaging of working memory Working memory may be investigated by many paradigms Sternberg, n-back, Delayed match to sample… These paradigms may be performed on various material Verbal items, spatial locations, object properties… Plus, investigators may add aspects like Distractors, cross-model transfer, emotional aspects… 4 Performing meta-analyses -‐ PubMed search Working-memory: [“working memory” OR “short term memory”], “fMRI”, “healthy subjects” - PubMed search on related topics - Review Articles - Reference tracing Performing meta-analyses General Inclusion-/Exclusion criteria Voxel-wise whole brain Analysis No ROI analyses No small volume correction No partial coverage (if evident from methods) Coordinates in MNI or Talairach space Careful, legends not always indicative Good to know standard space of software packages SPM/FSL: MNI / AFNI/BV: Talairach Have coordinates been transformed? Performing meta-analyses Specific Inclusion-/Exclusion criteria Healthy subjects No patients (within group-effect for controls OK) No selected groups (genetics, behavior) Within subject, between-condition effects Normal mapping No intervention (pharmacology, TMS, training etc) Only fMRI Performing meta-analyses Potential Inclusion-/Exclusion criteria Paradigm type This determines what will be represented by the meta-analysis Contrast type Low-level baseline (rest, fixation cross) High-level control task (input, output) Post-hoc classification (remembered vs. forgotten) Design-correlations (e.g., with memory load) Covariate-correlations (e.g., with RT) Interactions (e.g., valence x load) Also determines what the results will represent Meta-analysis on working memory 113 Paper (distinct publications) 1653 subjects (count distinct persons) 189 experiments (contrasts = sets of coordinates) 2662 activations (total number of foci) Organize your data ! Paper Subjects Allen et al 2006 Altamura et al 2007 Altamura et al 2007 Audoin et al 2005 Axmacher et al 2007 Axmacher et al 2007 Axmacher et al 2007 Axmacher et al 2007 Axmacher et al 2009 Bedwell et al 2005 Bedwell et al 2005 Bedwell et al 2005 Beneventi et al 2007 Binder et al 2006 Binder et al 2006 Bunge et al 2001 Cader et al 2006 Cader et al 2006 Cairo et al 2004 Cairo et al 2004 Cairo et al 2004 Cairo et al 2004 Cairo et al 2004 Caldwell et al 2005 Callicott et al 1999 10 18 18 18 23 23 23 23 30 14 14 14 12 12 12 16 16 16 18 18 18 18 18 10 9 Contrast Task>control Task>control activation modulated by load Task>control Task>baseline Task>baseline activation modulated by load activation modulated by load difficult>easy Task>control Task>control Task>control Task>baseline Task>control Task>control difficult>easy Task>control activation modulated by load Task>baseline activation modulated by load activation modulated by load Task>baseline activation modulated by load Task>control activation modulated by load Task Modality (visual) Stimuli Type (letter) n-back Sternberg Sternberg Calculation Sternberg Sternberg Sternberg Sternberg Sternberg Sternberg Sternberg Sternberg n-back n-back n-back Sternberg n-back n-back Sternberg Sternberg Sternberg Sternberg Sternberg Sternberg n-back visual visual visual auditory visual visual visual visual visual visual visual visual visual visual visual visual visual visual visual visual visual visual visual visual visual letter letter letter numbers faces faces faces faces figures letter letter letter shapes letter shapes letter letter letter letter letter letter letter letter letter numbers Rottschy et al., Neuroimage 2012 Meta-analysis on working memory Meta-analysis across 189 working memory experiments → Activations of all included experiments How to quantify convergence? Rottschy et al., Neuroimage 2012 Meta-analysis on working memory Meta-analysis across 189 working memory experiments ALE: Union of the modelled activation likelihood maps Main effect Convergence across all experiments investigating the neuronal correlates of working memory Rottschy et al., Neuroimage 2012 Meta-analysis on working memory Sub-analyses Examine the effects of: §  Tasks / settings §  Specific contrasts or other experimental parameters May allow inference on design effects Do comparisons that are not possible in a single study Verbal vs. non-verbal stimuli More consistent activation for verbal stimuli More consistent activation for non-verbal stimuli Rottschy et al., Neuroimage 2012 n-back vs. Sternberg Significantly higher convergence for activations in n-back tasks vs. Sternberg tasks Rottschy et al., Neuroimage 2012 Meta-‐analysis on voli1onal movements -  PubMed search Volitional movements: Volition; self-initiated; self-paced; internally specified; selection; choice; timing; etc. movements ∩ fMRI; PET Specific Inclusion-/Exclusion criteria manipulation of a volitional aspect resulting in hand movements à  53 papers including 103 experiments Meta-‐analysis on voli1onal movements -  PubMed search Volitional movements: Volition; self-initiated; self-paced; internally specified; selection; choice; timing; etc. movements ∩ fMRI; PET Specific Inclusion-/Exclusion criteria manipulation of a volitional aspect resulting in hand movements à  53 papers including 103 experiments Meta-‐analysis on voli1onal movements Convergent ac1va1on across 103 studies of voli1onal hand movements Eﬀects of movement (+ voli1on; 61exp.) ∩ Eﬀects of voli1on (-‐ movement; 42 exp.) Meta-‐analysis on voli1onal movements Choice (59 exp.) ∩ Timing (39 exp.) Meta-‐analysis on voli1onal movements Task-set: choice (33 exp.) PET; fMRI block-design event-related fMRI Preparation (19 exp.) ∩ ∩ Task-set: timing (32 exp.) Execution (17 exp.) Meta-‐analysis on voli1onal movements Meta-analyses allow to … … base inference on sample sizes hardly to be reached in individual studies … identify those effects that are reproducible across a larger number of publications … integrate many variants of probing a particular construct to test for effects of the experimental design … relate different tasks or topics to each other Aachen Birgit Derntl Kathrin Reetz Göttingen Oliver Gruber Simon Eickhoff Danilo Bzdok Julia Camilleri Edna Cieslik Sarah Genon Robert Langner Claudia Rottschy Veronika Müller Rachel Pläschke Andrew Reid Deepthi Varikuti Düsseldorf Katrin Amunts Alfons Schnitzler Karl Zilles Köln Christian Grefkes Jochen Michely Leo Schilbach