Cortico-Cortical White Matter Motor Pathway Microstructure Is Related to Psychomotor Retardation in Major Depressive Disorder

Tobias Bracht,Susanne Schnell,Sebastian Walther,Thomas Dierks,Thomas J Müller,Oliver Höfle,Helge Horn,Roland Wiest,Andrea Federspiel,Werner Strik,Gabriel Alejandro De Erausquin

doi:10.1371/journal.pone.0052238

Abstract

Alterations of brain structure and function have been associated with psychomotor retardation in major depressive disorder (MDD). However, the association of motor behaviour and white matter integrity of motor pathways in MDD is unclear. The aim of the present study was to first investigate structural connectivity of white matter motor pathways in MDD. Second, we explore the relation of objectively measured motor activity and white matter integrity of motor pathways in MDD. Therefore, 21 patients with MDD and 21 healthy controls matched for age, gender, education and body mass index underwent diffusion tensor imaging and 24 hour actigraphy (measure of the activity level) the same day. Applying a probabilistic fibre tracking approach we extracted connection pathways between the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the SMA-proper, the primary motor cortex (M1), the caudate nucleus, the putamen, the pallidum and the thalamus. Patients had lower activity levels and demonstrated increased mean diffusivity (MD) in pathways linking left pre-SMA and SMA-proper, and right SMA-proper and M1. Exploratory analyses point to a positive association of activity level and mean-fractional anisotropy in the right rACC-pre-SMA connection in MDD. Only MDD patients with low activity levels had a negative linear association of activity level and mean-MD in the left dlPFC-pre-SMA connection. Our results point to structural alterations of cortico-cortical white matter motor pathways in MDD. Altered white matter organisation of rACC-pre-SMA and dlPFC-pre-SMA pathways may contribute to movement initiation in MDD.

Highlights

Besides disturbances of mood and affect psychomotor retardation is a key feature of major depressive disorder (MDD) [1]
In MDD associations of cerebral blood flow (CBF) and psychomotor slowing were found in the dorsolateral prefrontal cortex, the anterior cingulate cortex or the orbitofrontal cortex [6,7,8,9,10]
The rostral anterior cingulate cortex (rACC) is involved in reinforcing behaviour and in anhedonia [11] whereas the dorsolateral prefrontal cortex (dlPFC) is essential for goal directed behaviour [12]

Summary

Introduction

Besides disturbances of mood and affect psychomotor retardation is a key feature of major depressive disorder (MDD) [1]. In MDD associations of cerebral blood flow (CBF) and psychomotor slowing were found in the dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex or the orbitofrontal cortex [6,7,8,9,10]. Neurobiological alterations of rACC and dlPFC may contribute to prominent symptoms of MDD such as avolition and anhedonia and result in reduced daily activities [13]. Psychomotor retardation was linked to CBF of the supplemental motor area [10] and to structural alterations and hypodopaminergic states of the basal ganglia [14,15,16]. White matter pathways connect these core regions of the motor system Those cortico-cortical and cortico-basal ganglia connection pathways are of particular interest to understand psychomotor slowing in depression

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Conclusion