Multivariate pattern analysis detects distinct neural representations of fMRI-based lateralized neurofeedback for cognitive reappraisal training in major depressive disorder

NeuroImage, vol. 338, pp. 122119

Abstract

Neurofeedback (NF)-supported cognitive reappraisal training has shown promise for improving emotion regulation in psychiatric disorders. A previous real-time functional magnetic resonance imaging NF (rt-fMRI NF) study in patients with major depressive disorder (MDD) and healthy individuals revealed better self-regulation and more use of reappraisal strategies for left compared to right ventrolateral prefrontal cortex (vlPFC) modulation. However, univariate approaches failed to detect this lateralized effect on the whole-brain level. Multivariate pattern analysis (MVPA) may detect such effects by detecting spatially distributed neural representations beyond cluster-wise activation differences. Here, we applied MVPA to examine whether targeting different hemispheric regions (left vs. right vlPFC) leads to distinct neural representations and corresponding group differences. This secondary data analysis examined rt-fMRI NF data from 37 patients with MDD and 37 healthy controls. A whole-brain searchlight multivariate pattern classification (MVPC) decoded brain activity distinguishing left- and right-vlPFC NF. Representational similarity analysis (RSA)-based pattern consistency, defined as the ratio of mean similarity among pairwise multivoxel patterns within each condition to that of all conditions, was calculated to estimate neural encoding stability in 20 predefined emotion regulation regions. Searchlight MVPC revealed high classification accuracies in key fronto-limbic emotion regulation regions, e.g., inferior frontal gyrus (IFG), insula, and anterior cingulate cortex (ACC), as well as related cognitive and motor control area, such as supplementary motor area (SMA). Pattern consistency during left-vlPFC NF was significantly lower in frontal regions in the MDD compared to the control group. These results demonstrate that multivariate approaches can capture distributed neural differences during NF-guided emotion regulation. Searchlight findings link NF target laterality to the reconfiguration of local representational structure, which may be crucial for cognitive flexibility and executive function. Encoding instability in MDD during left-vlPFC NF may reflect underlying pathophysiology. MVPA offers a valuable tool for detecting novel neural evidence of complex cognitive and affective processes, extending the exploration of neural differences of lateralized NF-guided cognitive reappraisal from activation level to representational decoding.

Authors 8

1. Rao Fu corresponding Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   Dalian University of Technology · RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, 52074, Germany; School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian, 116024, China. Electronic address: rao.fu1@rwth-aachen.de

2. Jorge Iglesias-Fuster

   University of Electronic Science and Technology of China · Cuban Neuroscience Center

   Affiliation as printed

   Department of Cognitive and Social Neurosciences, Brain Mapping Division, Cuban Center for Neuroscience, Havana, 11600, Cuba; China-Cuba Belt and Road Joint Laboratory on Neurotechnology and Brain-Apparatus Communication, University of Electronic Science and Technology of China, Chengdu, 611731, China

3. Jana Zweerings Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, 52074, Germany

4. Micha Keller Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, 52074, Germany

5. Sophie Kühne Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, 52074, Germany

6. Mitchell Valdés-Sosa

   University of Electronic Science and Technology of China · Cuban Neuroscience Center

   Affiliation as printed

   Department of Cognitive and Social Neurosciences, Brain Mapping Division, Cuban Center for Neuroscience, Havana, 11600, Cuba; China-Cuba Belt and Road Joint Laboratory on Neurotechnology and Brain-Apparatus Communication, University of Electronic Science and Technology of China, Chengdu, 611731, China

7. Fengyu Cong

   Dalian University of Technology · University of Jyväskylä

   Affiliation as printed

   School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian, 116024, China; Faculty of Information Technology, University of Jyvaskyla, Jyvaskyla, 40014, Finland; Key Laboratory of Social Computing and Cognitive Intelligence (Dalian University of Technology), Ministry of Education, Dalian, 116024, China

8. Klaus Mathiak Aachen Department of Psychiatry, Psychotherapy and Psychosomatics Faculty of Medicine

   Jülich Aachen Research Alliance · RWTH Aachen University

   Affiliation as printed

   Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, 52074, Germany; Jülich Aachen Research Alliance (JARA) -Translational Brain Medicine, RWTH Aachen University, Aachen, 52074, Germany