Unveiling the Multifaceted Networks of the Left DLPFC by Connectivity-Based Parcellation
Poster No:
1726
Submission Type:
Abstract Submission
Authors:
Lya Paas Oliveros1,2, Timm Poeppl3,4, Niels Reuter2, Felix Hoffstaedter1,2, Kaustubh Patil1,2, Sarah Kreuzer3, Simon Eickhoff1,2, Veronika Müller1,2
Institutions:
1Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf, Düsseldorf, Germany, 2Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich, Jülich, Germany, 3Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany, 4Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Medical Faculty, RWTH Aachen University, Aachen, Germany
First Author:
Lya Paas Oliveros
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Co-Author(s):
Timm Poeppl
Department of Psychiatry and Psychotherapy, University of Regensburg|Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Medical Faculty, RWTH Aachen University
Regensburg, Germany|Aachen, Germany
Department of Psychiatry and Psychotherapy, University of Regensburg|Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Medical Faculty, RWTH Aachen University
Regensburg, Germany|Aachen, Germany
Niels Reuter
Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Jülich, Germany
Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Jülich, Germany
Felix Hoffstaedter
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Kaustubh Patil
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Sarah Kreuzer
Department of Psychiatry and Psychotherapy, University of Regensburg
Regensburg, Germany
Department of Psychiatry and Psychotherapy, University of Regensburg
Regensburg, Germany
Simon Eickhoff
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Veronika Müller
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf|Institute of Neuroscience and Medicine (INM-7: Brain and Behaviour), Research Center Jülich
Düsseldorf, Germany|Jülich, Germany
Introduction:
The left dorsolateral prefrontal cortex (lDLPFC) is the standard target for repetitive transcranial magnetic stimulation (rTMS) to ameliorate treatment-resistant depression (TRD) [1]. However, the non-response rate for rTMS remains approximately 50% [4]. Evidence increasingly suggests that connectivity of the stimulation site, particularly its functional anti-correlation with the subgenual cingulate cortex (SGC) [2,3], determines the clinical efficacy of rTMS. There is also evidence that activity in other regions relevant to the pathophysiology of depression, such as amygdala and insula [5,6], is likely to be modulated by rTMS and should be considered when identifying the optimal rTMS hotspot. In this study, we applied regional connectivity-based parcellation (rCBP) to identify the functional lDLPFC subdivisions that hold maximal connectivity to depression-relevant regions.
Methods:
We defined the lDLPFC as a region of interest (ROI) around previously reported rTMS coordinates [3,7], excluding motor areas, resulting in an ROI of 4,232 voxels (33,856 mm3). We computed rCBP [8,9] on the lDLPFC using resting-state functional connectivity (RSFC) derived from two resting-state fMRI sessions in the ICA-FIX denoised HCP-YA dataset (391 unrelated participants: 28.7 ± 3.8 [22–36] years, 48.3% females). The time series were additionally smoothed (5mm FWHM), corrected for global WM and CSF signals, and band-pass-filtered (0.01–0.08 Hz). At the individual level, we performed k-means clustering (256 initializations and a maximum of 10,000 iterations) to examine nine levels of granularity [k = 2–10]. The group-specific parcellation was obtained via hierarchical clustering with complete linkage and Hamming distance, then relabeling each subject and using the mode label across all subjects. For granularities without parcel splits, seed-to-target RSFC (Bonferroni-corrected at p < 0.05) was computed between each cluster and the bilateral SGC, amygdala, and insula. This approach identified the clusters within each granularity exhibiting the maximal functional anti-correlation with bilateral SGC and amygdala, as well as the maximal positive correlation with bilateral insula.
Results:
The lDLPFC revealed an anterior-to-posterior division, already evident at k = 2 (Figure 1), where the two clusters displayed opposing connectivity patterns with SGC, insula, and amygdala. As granularity increased, a ventral-to-dorsal axis emerged within the anterior and posterior subdivisions (Figure 1). For the seed-to-target RSFC analyses, we focused only on granularities with continuous parcels [k = 2, 3, 6, 8, 9]. Notably, the central cluster in the anterior section of the nine-cluster solution (cluster 6 of k = 9; Figure 1) showed the strongest functional anti-correlation with SGC (z = –0.132) and amygdala (z = –0.049), as well as the strongest positive correlation with insula (z = 0.161). By aggregating the lDLPFC clusters across these granularities with the strongest connectivity to SGC, amygdala, and insula, we generated a spatial probabilistic map highlighting the areas within lDLPFC to target and avoid with rTMS (Figure 2A). It is to be noted that the target- and avoid-stimulation sites display antagonistic connectivity profiles, and the no-go zone is tightly connected with the default-mode network (Figure 2B).
Conclusions:
The anterior-to-posterior division of the lDLPFC aligns with previous findings linking anterior lDLPFC regions to stronger anti-correlations with SGC [3,10]. Here, we identified a subregion located in the center of the anterior lDLPFC that exhibits maximal functional connectivity not only with SGC but also with other depression-relevant areas. This localization should be considered in clinical practice for optimal rTMS targeting. Future research should investigate long-range connectivity profiles of these regions as part of broader brain networks and put the relevance of these findings in context with clinical efficacy measures in depression.
Brain Stimulation:
TMS 2
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Task-Independent and Resting-State Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping 1
Keywords:
Affective Disorders
Cortex
FUNCTIONAL MRI
Psychiatric Disorders
Transcranial Magnetic Stimulation (TMS)
Other - Dorsolateral prefrontal cortex; Connectivity-based parcellation; Depression
1|2Indicates the priority used for review
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