title: Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?
abstract: An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first- (single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-of-interest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success.
authors.affiliation: Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland; Medical Image Processing Laboratory, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. Electronic address: kirsten.emmert@unige.ch.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Emmert
authors.affiliation: Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland; Medical Image Processing Laboratory, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Rotem
authors.initials: R
authors.lastname: Kopel
authors.affiliation: Department of Mechanical Engineering, University of Texas at Austin, Austin, TX, USA.
authors.forename: James
authors.initials: J
authors.lastname: Sulzer
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland; Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Annette B
authors.initials: AB
authors.lastname: Brühl
authors.affiliation: Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Berman
authors.affiliation: MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: David E J
authors.initials: DEJ
authors.lastname: Linden
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Silvina G
authors.initials: SG
authors.lastname: Horovitz
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Breimhorst
authors.affiliation: Institute of Medical Psychology and Behavioral Neurobiology, University of Tuebingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Caria
authors.affiliation: Institute of Medical Psychology and Behavioral Neurobiology, University of Tuebingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Frank
authors.affiliation: Department of Psychology, Swansea University, Swansea, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Johnston
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Long
authors.affiliation: Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany; Department for Neuroimaging, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Paret
authors.affiliation: Laboratory for Neurology and Imaging of Cognition, Department of Neurosciences, University of Geneva, Switzerland.
authors.forename: Fabien
authors.initials: F
authors.lastname: Robineau
authors.affiliation: Institute of Medical Psychology and Behavioral Neurobiology, University of Tuebingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Veit
authors.affiliation: Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany; Department of Neuroradiology, University of Würzburg, Würzburg, Germany; FMRIB Centre, University of Oxford, Oxford, UK; Department of Radiology, Bamberg Hospital, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bartsch
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, The Netherlands; Radboud University Medical Centre, Department of Cognitive Neuroimaging, Nijmegen, The Netherlands; Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Beckmann
authors.affiliation: Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland; Medical Image Processing Laboratory, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Van De Ville
authors.affiliation: Affidea Centre de Diagnostique Radiologique de Carouge CDRC, Geneva, Switzerland; Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden; Department of Neuroradiology, University Hospital Freiburg, Germany; Faculty of Medicine of the University of Geneva, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Haller
mesh_terms: D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058765:Neurofeedback / Q000379:methods* / Q000502:physiology*
keywords: Brain regulation; Neurofeedback; Real-time fMRI