Indirect frontocingulate structural connectivity predicts clinical response to accelerated rtms in major depressive disorder

Deborah C.W. Klooster; Iris N. Vos; Karen Caeyenberghs; Alexander Leemans; Szabolcs David; René M.H. Besseling; Albert P. Aldenkamp; Chris Baeken

doi:10.1503/jpn.190088

Indirect frontocingulate structural connectivity predicts clinical response to accelerated rtms in major depressive disorder

Deborah C.W. Klooster (Corresponding author)
, Iris N. Vos
, Karen Caeyenberghs
, Alexander Leemans
, Szabolcs David
, René M.H. Besseling
, Albert P. Aldenkamp
, Chris Baeken

Research output: Contribution to journal › Article › Academic › peer-review

34 Citations (Scopus)

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its clinical efficacy remains rather modest. One reason for this could be that the propagation of rTMS effects via structural connections from the stimulated area to deeper brain structures (such as the cingulate cortices) is suboptimal.

Methods: We investigated whether structural connectivity — derived from diffusion MRI data — could serve as a biomarker to predict treatment response. We hypothesized that stronger structural connections between the patient-specific stimulation position in the left dorsolateral prefrontal cortex (dlPFC) and the cingulate cortices would predict better clinical outcomes. We applied accelerated intermittent theta burst stimulation (aiTBS) to the left dlPFC in 40 patients with MDD. We correlated baseline structural connectivity, quantified using various metrics (fractional anisotropy, mean diffusivity, tract density, tract volume and number of tracts), with changes in depression severity scores after aiTBS.

Results: Exploratory results (p < 0.05) showed that structural connectivity between the patient-specific stimulation site and the caudal and posterior parts of the cingulate cortex had predictive potential for clinical response to aiTBS.

Limitations: We used the diffusion tensor to perform tractography. A main limitation was that multiple fibre directions within voxels could not be resolved, which might have led to missing connections in some patients.

Conclusion: Stronger structural frontocingular connections may be of essence to optimally benefit from left dlPFC rTMS treatment in MDD. Even though the results are promising, further investigation with larger numbers of patients, more advanced tractography algorithms and classic daily rTMS treatment paradigms is warranted.

Clinical trial registration: http://clinicaltrials.gov/show/NCT01832805

Original language	English
Pages (from-to)	243-252
Number of pages	10
Journal	Journal of Psychiatry and Neuroscience
Volume	45
Issue number	4
DOIs	https://doi.org/10.1503/jpn.190088
Publication status	Published - 1 Jul 2020

Funding

the Ghent University Multidisciplinary Research Partnership, “The integrative neuroscience of behavioral control,” and a grant of the “Fonds Wetenschappelijk Onderzoek Rode Neuzen” (G0F4617N). K. Caeyenberghs is supported by a Career Development Fellowship from the National Health and Medical Research Council and an ACURF Program grant from the Australian Catholic University. The research of S. David and A. Leemans is supported by VIDI Grant 639.072.411 from the Netherlands Organization for Scientific Research (NWO).

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1503/jpn.190088

Cite this

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title = "Indirect frontocingulate structural connectivity predicts clinical response to accelerated rtms in major depressive disorder",

abstract = "Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its clinical efficacy remains rather modest. One reason for this could be that the propagation of rTMS effects via structural connections from the stimulated area to deeper brain structures (such as the cingulate cortices) is suboptimal.Methods: We investigated whether structural connectivity — derived from diffusion MRI data — could serve as a biomarker to predict treatment response. We hypothesized that stronger structural connections between the patient-specific stimulation position in the left dorsolateral prefrontal cortex (dlPFC) and the cingulate cortices would predict better clinical outcomes. We applied accelerated intermittent theta burst stimulation (aiTBS) to the left dlPFC in 40 patients with MDD. We correlated baseline structural connectivity, quantified using various metrics (fractional anisotropy, mean diffusivity, tract density, tract volume and number of tracts), with changes in depression severity scores after aiTBS.Results: Exploratory results (p < 0.05) showed that structural connectivity between the patient-specific stimulation site and the caudal and posterior parts of the cingulate cortex had predictive potential for clinical response to aiTBS.Limitations: We used the diffusion tensor to perform tractography. A main limitation was that multiple fibre directions within voxels could not be resolved, which might have led to missing connections in some patients.Conclusion: Stronger structural frontocingular connections may be of essence to optimally benefit from left dlPFC rTMS treatment in MDD. Even though the results are promising, further investigation with larger numbers of patients, more advanced tractography algorithms and classic daily rTMS treatment paradigms is warranted.Clinical trial registration: http://clinicaltrials.gov/show/NCT01832805",

author = "Klooster, \{Deborah C.W.\} and Vos, \{Iris N.\} and Karen Caeyenberghs and Alexander Leemans and Szabolcs David and Besseling, \{Ren{\'e} M.H.\} and Aldenkamp, \{Albert P.\} and Chris Baeken",

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Indirect frontocingulate structural connectivity predicts clinical response to accelerated rtms in major depressive disorder. / Klooster, Deborah C.W. (Corresponding author); Vos, Iris N.; Caeyenberghs, Karen et al.
In: Journal of Psychiatry and Neuroscience, Vol. 45, No. 4, 01.07.2020, p. 243-252.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

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AU - Klooster, Deborah C.W.

AU - Vos, Iris N.

AU - Caeyenberghs, Karen

AU - Leemans, Alexander

AU - David, Szabolcs

AU - Besseling, René M.H.

AU - Aldenkamp, Albert P.

AU - Baeken, Chris

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its clinical efficacy remains rather modest. One reason for this could be that the propagation of rTMS effects via structural connections from the stimulated area to deeper brain structures (such as the cingulate cortices) is suboptimal.Methods: We investigated whether structural connectivity — derived from diffusion MRI data — could serve as a biomarker to predict treatment response. We hypothesized that stronger structural connections between the patient-specific stimulation position in the left dorsolateral prefrontal cortex (dlPFC) and the cingulate cortices would predict better clinical outcomes. We applied accelerated intermittent theta burst stimulation (aiTBS) to the left dlPFC in 40 patients with MDD. We correlated baseline structural connectivity, quantified using various metrics (fractional anisotropy, mean diffusivity, tract density, tract volume and number of tracts), with changes in depression severity scores after aiTBS.Results: Exploratory results (p < 0.05) showed that structural connectivity between the patient-specific stimulation site and the caudal and posterior parts of the cingulate cortex had predictive potential for clinical response to aiTBS.Limitations: We used the diffusion tensor to perform tractography. A main limitation was that multiple fibre directions within voxels could not be resolved, which might have led to missing connections in some patients.Conclusion: Stronger structural frontocingular connections may be of essence to optimally benefit from left dlPFC rTMS treatment in MDD. Even though the results are promising, further investigation with larger numbers of patients, more advanced tractography algorithms and classic daily rTMS treatment paradigms is warranted.Clinical trial registration: http://clinicaltrials.gov/show/NCT01832805

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ER -

Indirect frontocingulate structural connectivity predicts clinical response to accelerated rtms in major depressive disorder

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