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7T Mental health: Functional alterations in resting-state within the executive control network and its association with BDI-II and TMT-B in MDD1Institute of Neuroscience and Medicine - 4 (Medical Imaging Physics), Forschungszentrum Juelich GmbH, Jülich, Germany, 2Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, 34JARA – BRAIN – Translational Medicine, Aachen, Germany, 4JARA – BRAIN – Translational Medicine, Aachen, Germany, 5Department of Neurology, RWTH Aachen University, Aachen, Germany, 6Institute of Neuroscience and Medicine, INM-11, Forschungszentrum Jülich GmbH, Jülich, Germany
Synopsis
Executive functioning is reported to be deficient in depression. In this pilot study, functional alterations in MDD patients and their association with mental flexibility and depression severity, particularly within the executive control network, are investigated. Our data contribute to a better understanding of the neurobiological signatures of depression. Further investigation in this area may lead to an improvement in the diagnosis and treatment of MDD patients.
Introduction:
Different cognitive domains, as executive functions, working memory, planning, mental flexibility, and attention are known to be deficient in patients with major depressive disorder (MDD)1. This corresponds with functional and structural neuroimaging studies demonstrating alterations in regions involving various executive functions in depressed patients2. Considering these findings, and utilising the advantages offered by ultrahigh field (UHF) functional imaging at 7 Tesla (7T), in this pilot study, we aim to investigate functional alterations in MDD patients and their associations with mental flexibility and depression severity. To achieve this, we analysed the executive control network (ECN), otherwise known as dorsolateral prefrontal cortex network, during resting state (RS).Methods:
Data Acquisition: The MR data acquisition was performed using 7T MAGNETOM Terra scanner (Siemens Healthineers, Germany) on 20 subjects (10 depressed patients (age : 37 ± 11, 6 females) and 10 age and gender matched healthy control (HC) subjects (age : 38 ± 10)). The structural and functional data were acquired in the same session. Anatomical images were acquired with a T1 weighted MP-RAGE sequence. The matrix size was set to 256x256x192 to achieve a 0.8mm isotropic resolution in the respective field of view (FOV). The RS-fMRI data were acquired using spin echo planar imaging (EPI) using echo and repetition time, TE/TR, of 25ms/2200ms, FOV was 200 x 200 mm2 resulting in a 3.1mm isotropic resolution.fMRI data analysis: The RS-fMRI data were analysed using MATLAB based software packages, SPM12 and DPABI3. Following the required pre-processing steps, fMRI parameters such as degree centrality (DC)4, regional homogeneity (ReHo)5, amplitude of low frequency fluctuations (ALFF)6 and fractional ALFF (fALFF)4 were computed. DC was computed with the Pearson correlation cut-off of 0.25 (p = 0.001). The fALFF and ALFF measures were calculated within the low frequency range of the BOLD fMRI signal between 0.01 and 0.08 Hz. The ReHo connectivity measure was calculated over a cluster of 27 neighbouring voxels. fMRI measures were linearly standardised into Z-values, co-registered to the MNI152 (2×2×2 mm3) standard space and smoothed with a Gaussian kernel size of 3 mm along all directions..
Statistical Analysis: A separate mask of the right and left ECN was obtained from an atlas7. The ECN mainly comprises part of the frontal gyrus, angular gyrus, precuneus, temporal gyrus, thalamus, right caudate and parts of the cerebellum. The fMRI measures of voxels within the ECN masks were extracted, and their mean values were calculated. A Wilcoxon rank-sum test was performed on the mean fMRI measures to determine the functional changes between HC and depressed patients. Depression severity was assessed using BDI-II (Beck Depression Inventory)8 in all depressed patients. The mental flexibility domain of the executive function was evaluated using the TMT-B (Trail Making Test)9 task in 7 depressed patients (4 females) prior to the MR measurements. Further, to find the association between BDI-II and TMT-B with the fMRI functional measures, a Spearman's rank correlation was performed.
Results:
The analysed fMRI images showing DC, ReHo, ALFF and fALFF are depicted in Fig. 1. The Wilcoxon rank-sum test on DC and fALFF measures showed significant differences between depressed patients and HC in RECN (p = 0.03) and LECN (p = 0.03), respectively (Fig. 2). RECN and LECN were not associated with BDI-II and TMT-B scores. However, the left thalamus a subregion within the LECN showed a significant positive correlation between ALFF measure and BDI-II score (rs = 0.64, p = 0.04) (Fig. 3). Similarly, a significant association between TMT-B score and ALFF was found within the right middle frontal gyrus (rs = 0.78, p = 0.04), which is part of RECN.Discussions:
The altered long-range connectivity (DC) changes within the RECN (Fig. 2) is in agreement with previous literature10–14 suggesting functional changes in brain regions regulating executive function in depressed patients. A positive association between poor cognitive flexibility (TMT-B score) and fMRI ALFF measures within the right middle frontal gyrus (rMFG) may be due to attention deficits in MDD patients15 leading to changes in executive functions (mental flexibility in this case). Higher spontaneous fluctuations may be due to a denser neuronal population16 and higher cerebral blood flow17. The positive association between fMRI ALFF measure and the BDI-II score within the left thalamus suggests that such a process underlies an increased disease severity in depressed patients.Conclusions:
This 7T fMRI pilot study suggests that changes in functional parameters within the ECN are associated with executive functions impairments and disease severity in MDD patients. However, further exploration with a greater number of patients and more detailed neuropsychological testing may help to find specific neurobiological signatures of depression using ultra high field (7T) neuroimaging technology. Such data could further improve diagnostic and therapeutic options for MDD patients.Acknowledgements
We thank Dilsa Cemre Altiok Akkoc and Dominik Nießen for their assistance in healthy volunteers data acquisition. We are also thankful to Claire Rick for proofreading the manuscript and to Petra Engels, Elke Bechholz, and Anita Köth for their technical assistance.References
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