Handedness and effective connectivity of the motor system

Highlights

• Handedness has a systematic impact on cortical connectivity.

• Prominent role of SMA on neural coupling strength in right-handers.

• Less asymmetry in effective connectivity in left-handers

Abstract

Handedness denotes the individual predisposition to consistently use the left or right hand for most types of skilled movements. A putative neurobiological mechanism for handedness consists in hemisphere-specific differences in network dynamics that govern unimanual movements.

We, therefore, used functional magnetic resonance imaging and dynamic causal modeling to investigate effective connectivity between key motor areas during fist closures of the dominant or non-dominant hand performed by 18 right- and 18 left-handers. Handedness was assessed employing the Edinburgh-Handedness-Inventory (EHI). The network of interest consisted of key motor regions in both hemispheres including the primary motor cortex (M1), supplementary motor area (SMA), ventral premotor cortex (PMv), motor putamen (Put) and motor cerebellum (Cb).

The connectivity analysis revealed that in right-handed subjects movements of the dominant hand were associated with significantly stronger coupling of contralateral (left, i.e., dominant) SMA with ipsilateral SMA, ipsilateral PMv, contralateral motor putamen and contralateral M1 compared to equivalent connections in left-handers. The degree of handedness as indexed by the individual EHI scores also correlated with coupling parameters of these connections. In contrast, we found no differences between right- and left-handers when testing for the effect of movement speed on effective connectivity.

In conclusion, the data show that handedness is associated with differences in effective connectivity within the human motor network with a prominent role of SMA in right-handers. Left-handers featured less asymmetry in effective connectivity implying different hemispheric mechanisms underlying hand motor control compared to right-handers.

Introduction

Handedness is a fundamental, behavioral characteristic of the motor system that evolves even before birth and stabilizes during early childhood (Fagard, 2013). While to date a formal definition of handedness is missing, it is widely accepted that handedness includes that (i) one hand is consistently preferred for carrying out a particular task, (ii) the same hand is chosen for the majority of tasks to be performed, and (iii) this hand is more proficient than the other in task performance (Hammond, 2002, Serrien et al., 2006). Experimental evidence suggests that this intrinsic behavioral phenomenon is associated with asymmetries in the structural and functional organization of the cerebral cortex (Amunts et al., 1996, Eickhoff et al., 2008, Hammond, 2002). For example, anatomical studies revealed a deeper central sulcus in the dominant compared to the non-dominant hemisphere in both right- and left-handers (Amunts et al., 1996). Furthermore, neuroimaging studies demonstrated an influence of hand dominance on neural activity (Dassonville et al., 1997, Kim et al., 1993, Solodkin et al., 2001, Volkmann et al., 1998). In both right- and left-handers, dominant hand movements were shown to be associated with a greater volume of the hand representation in the contralateral primary motor cortex (M1) (Dassonville et al., 1997, Volkmann et al., 1998). Solodkin and colleagues mapped brain activation patterns in right- and left-handers during single and sequential finger movements and found larger volumes of activation and less hemispheric lateralization in left-handers (Solodkin et al., 2001). The latter finding is compatible with behavioral data demonstrating that hand preference in left-handers is often expressed to a lesser degree than in right-handers (Borod et al., 1984). Finally, transcranial magnetic stimulation (TMS) paradigms provided evidence for handedness-related asymmetries in cortical excitability (Brouwer et al., 2001, Ziemann and Hallett, 2001). Ziemann and Hallett (2001) demonstrated that performing a complex motor task with one hand increases the excitability of the motor cortex contralateral to the inactive hand. This increase was significantly smaller when the task was performed with the dominant (right) as opposed to the non-dominant (left) hand (Ziemann and Hallett, 2001). The authors hypothesized that the dominant (left) motor cortex exerts more inhibitory control upon the contralateral motor cortex controlling the non-dominant left hand than vice versa. Taken together, the neural mechanisms for hand dominance might rest in hemispheric-specific differences of network dynamics that govern unimanual movements.

Accordingly, we here investigated whether the preference to use the right or left hand in everyday life is reflected by systematic differences in network interactions during unimanual movements. As outlined above, structural and functional neuroimaging studies have already addressed the neural correlates of handedness (Amunts et al., 1996, Dassonville et al., 1997, Kloppel et al., 2007, Solodkin et al., 2001, Volkmann et al., 1998). However, to date little is known about hand preference and the dynamics of the motor network. To this end, we addressed in a functional magnetic resonance imaging (fMRI) study the question whether there are differences in neural activity and interregional interaction of key motor regions between right- (n = 18) and left-handers (n = 18). Dynamic causal modeling (DCM) was used to assess effective connectivity, i.e., the causal influence that one area exerts upon activity of another (Friston et al., 2003), during unimanual movements of the dominant and non-dominant hands at different frequencies for a bihemispheric network consisting of key motor areas like M1, supplementary motor area (SMA), ventrolateral premotor cortex (PMv), motor putamen (Put) and motor cerebellum (Cb) (Grefkes et al., 2008, Passingham, 1997, Witt et al., 2008). We hypothesized that higher movement speed evokes a stronger BOLD signal especially in the contralateral primary sensorimotor cortex (Jancke et al., 1998, Sadato et al., 1996). Moreover, we hypothesized that movement-related connections are differentially modulated depending on whether subjects are right-handed or left-handed (Kloppel et al., 2007, Solodkin et al., 2001).