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Updated: Mar 29, 2026
Meta-analysis of Voxel-Based Neuroimaging Studies using Seed-based d Mapping with Permutation of Subject Images SDM-PSI
Published on: November 27, 2019
Medial Prefrontal Aberrations in Major Depressive Disorder Revealed by Cytoarchitectonically Informed Voxel-Based
Sebastian Bludau1, Danilo Bzdok1, Oliver Gruber1
1From the Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany; the Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; the Center for Translational Research in Systems Neuroscience and Psychiatry, Clinic for Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany; the Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Nijmegen, the Netherlands; the Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; the Neuroimaging Center (TUM-NIC), Klinikum Rechts der Isar, München, Germany; the Department of Neuroradiology, TU München, München, Germany; the Department of Psychiatry, TU München, München, Germany; the Cécile and Oskar Vogt Institute for Brain Research, Heinrich Heine University, Düsseldorf, Germany; and the Parietal team, INRIA, Neurospin, Gif-sur-Yvette, France; the Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany; and JARA-Translational Brain Medicine, Aachen, Germany.
Objective:
The heterogeneous human frontal pole has been identified as a node in the dysfunctional network of major depressive disorder. The contribution of the medial (socio-affective) versus lateral (cognitive) frontal pole to major depression pathogenesis is currently unclear. The authors performed morphometric comparison of the microstructurally informed subdivisions of human frontal pole between depressed patients and comparison subjects using both uni- and multivariate statistics.
Method:
Multisite voxel- and region-based morphometric MRI analysis was conducted in 73 depressed patients and 73 matched comparison subjects without psychiatric history. Frontal pole volume was first compared between depressed patients and comparison subjects by subdivision-wise classical morphometric analysis. In a second approach, frontal pole volume was compared by subdivision-naive multivariate searchlight analysis based on support vector machines.
Results:
Subdivision-wise morphometric analysis found a significantly smaller medial frontal pole in depressed patients, with a negative correlation of disease severity and duration. Histologically uninformed multivariate voxel-wise statistics provided converging evidence for structural aberrations specific to the microstructurally defined medial area of the frontal pole in depressed patients.
Conclusions:
Across disparate methods, subregion specificity in the left medial frontal pole volume in depressed patients was demonstrated. Indeed, the frontal pole was shown to structurally and functionally connect to other key regions in major depression pathology, such as the anterior cingulate cortex and the amygdala via the uncinate fasciculus. Present and previous findings consolidate the left medial portion of the frontal pole as particularly altered in major depression.
