Regular articleIpsilateral motor cortex activation on functional magnetic resonance imaging during unilateral hand movements is related to interhemispheric interactions
Introduction
Functional imaging studies in stroke subjects recovering from a hemiparesis often show activation of ipsilateral, unaffected motor cortex during motor tasks with their paretic hand Weiller et al 1992, Marshall et al 2000. Such activation ipsilateral to the hand movement could be related to ipsilateral, uncrossed projections (corticospinal or corticobrain stem descending pathways (Ziemann et al., 1999)) or interhemispheric interactions. Several studies report that in patients with unilateral stroke motor-evoked potentials (MEPs)1 for paretic hand muscles can be obtained by transcranial magnetic stimulation (TMS) of the ipsilateral, unaffected motor cortex more frequently than in normal subjects Trompetto et al 2000, Caramia et al 2000, Alagona et al 2001. However, induction of MEPs in the paretic hand by TMS of the ipsilateral, unaffected motor cortex is inconsistently found and does not indicate favorable outcome in stroke patients Netz et al 1997, Caramia et al 2000, Alagona et al 2001.
Activation of the ipsilateral, unaffected motor cortex in stroke patients during movements of their paretic hand might be related to mechanisms similar to those accounting for activation of the ipsilateral primary motor area during certain more challenging and difficult unimanual motor tasks in normal subjects Roland et al 1980, Kim et al 1993. Positron emission tomography (PET) and functional MRI (fMRI) studies have shown activation of the primary motor area during an ipsilateral, unilateral motor task in normal subjects, although not in all of them Roland et al 1980, Rao et al 1993, Singh et al 1998, Cramer et al 1999, Allison et al 2000. Such ipsilateral activation is more frequently observed when a simple motor task is performed with the nondominant hand (Kawashima et al., 1998). During simple movements with the dominant hand, the activation in the motor cortex is generally limited to the contralateral hemisphere or, if any, sparse in the ipsilateral primary motor cortex Kim et al 1993, Beltramello et al 1998. Performing or learning complex motor tasks with the nondominant hand can also evoke activation of the ipsilateral primary motor cortex in many, although not in all subjects Beltramello et al 1998, Hund-Georgiadis and von Cramon 1999.
fMRI and PET reflect regional changes of cerebral blood flow and provide only indirect measures of synaptic and neuronal activity. Therefore, the neurophysiological mechanisms underlying ipsilateral motor cortex activation during unimanual tasks remain unclear. Interhemispheric transcallosal interactions between both motor areas have been studied in animals using direct electrical cortical stimulation Asanuma and Okamoto 1962, Matsunami and Hamada 1984 and more recently in humans using TMS Ferbert et al 1992, Hanajima et al 2001. These studies show that stimulation of one motor cortex can induce facilitatory and mostly inhibitory effects in the contralateral motor cortex. Therefore, it is possible that activation of the ipsilateral motor cortex on fMRI during unilateral hand movements might be related to interhemispheric interactions. Such interhemispheric interactions might be engaged during complex motor tasks in normal subjects and might account for similar findings in stroke patients.
In the present study we used TMS to address two possible explanations for the activation of the ipsilateral motor cortex during unimanual movements. The activation of the motor cortex ipsilateral to the hand movement could be due to the contribution of ipsilateral descending pathways for unimanual movements. Alternatively, the activation of the ipsilateral motor cortex could be related to interhemispheric, transcallosal interactions. We investigated 10 healthy right-handed subjects using fMRI during unilateral movements of their index finger. During nondominant (left) finger movements, 5 of the 10 subjects showed significant activation on their ipsilateral (left) sensorimotor hand area. Dominant (right) finger movement did not activate the sensorimotor area of the ipsilateral side in any subject. TMS was then used to assess the feasibility of inducing ipsilateral motor-evoked potentials or silent periods as markers of corticospinal projections. Interhemispheric interaction was assessed by paired-pulse TMS (Ferbert et al., 1992).
Section snippets
Subjects
Ten healthy volunteers (7 men and 3 women; 25 to 55 years old; mean age 36.5 ± 12.3 years) were recruited into this study. None of them had any psychiatric or significant past medical history or any contraindications to fMRI or TMS (Wassermann, 1998). Subjects were excluded if they had any pathological findings on their T1 or T2 weighted MRI scanning. All subjects were strongly right-handed according to a hand preference questionnaire (Oldfield, 1971). Importantly, none of the subjects had a
Ipsilateral activation in the functional MRI study
No subject showed significant activation of the ipsilateral (right) sensorimotor cortex during movements of his or her right (dominant) index finger. However, half of subjects showed ipsilateral activation when moving their left (nondominant) index fingers. Fig. 1 shows the fMRI images of all subjects while moving their left index fingers. Five of the 10 subjects showed ipsilateral activation, i.e., the activation of the left primary motor cortex during their left index finger movement
Discussion
Half of our subjects showed IpsiLM1, i.e., activation of their left (ipsilateral) motor cortex when performing a relatively simple motor task with their nondominant (left) hands. In these subjects, TMS of the left motor cortex failed to evoke MEPs or silent periods in the left, ipsilateral hand, and the motor threshold for induction of contralateral MEPs was not different between the right and left hemispheres. Therefore, activation of the ipsilateral motor cortex on fMRI does not seem to be
Acknowledgements
We dedicate this paper to the memory of Dr. Berndt-Ulrich Meyer who, along with his wife, Dr. Simone Röricht, and their two young sons, tragically died in the CrossAir flight accident near Zürich on Saturday, November 24, 2001. This work was conducted at the Harvard–Thorndike General Clinical Research Center, supported by the National Center for Research Resources (MO1 RR01032). In addition, support is acknowledged from the National Institutes of Health (RO1MH57980, RO1MH60734, RO1EY12091), the
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