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

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.

Dissociated large-scale functional connectivity networks of the precuneus in medication-naïve first-episode depression

“…The strong negative relationship between DMN activity and SMA activity in depression observed in our study at resting state fits well with the important clinical symptoms of psychomotor retardation often seen in MDD. This notion is also supported by a diffusion tensor imaging study that found an association between alterations in the white matter pathways involving the motor cortex and psychomotor retardation (Bracht et al, 2012). This is further supported by an integrative review showing that manipulating the sensorimotor system could modulate depressive symptoms by influencing moodregulatory circuits (Canbeyli, 2010).…”

Psychomotor retardation is linked to frontal alpha asymmetry in major depression

“…Psychomotor retardation is a core feature of MDD, spanning from disrupted fine and gross motor behavior to reduced processing speed (Schrijvers et al, 2008a;Sobin and Sackeim, 1997). The neurobiological underpinnings of motor dysfunction in MDD are yet to be fully explained, but current evidence indicates disrupted anatomical and functional connectivity in brain networks involving fronto-parietal cortical areas and subcortical regions such as basal ganglia (Bracht et al, 2012;Liberg et al, 2014;Walther et al, 2012a). In a previous study conducted in our lab, AL was positively associated (in both MDD patients and healthy controls) with resting state cerebral blood flow (CBF) in bilateral rostral prefrontal cortex (BA 10).…”

“…The neural correlates of motor activity disturbances in depression have been investigated mostly by means of magnetic resonance imaging (MRI) techniques, showing deficits in structural and functional connectivity between frontal cortical regions and basal ganglia (Bracht et al, 2012;Liberg et al, 2014;Walther et al, 2012aWalther et al, , 2012b. EEG studies addressing the issue are few and mainly investigating the spectral EEG characteristics or the link between action monitoring and psychomotor retardation (Nieber and Schlegel, 1992;Schrijvers et al, 2008bSchrijvers et al, , 2009).…”

Psychosis Is Mutable over Time: A Longitudinal Psychopathology Study

“…This leads us to suggest that studies involving dynamic neurobiological markers should be repeated several times for each patient and then linked to psychopathology. To use the motor domain as an example, such an approach might resolve the question whether a dysfunction of cortico-basal ganglia pathways can at times be compensated by cortical brain regions, as has been suggested [27], or whether different mechanisms are involved. The research focus should be functional, and neurophysiology and neuroimaging may help to clarify pathogenesis.…”