Lateralization of cervical spinal cord activity during an isometric upper extremity motor task with functional magnetic resonance imaging
Introduction
In humans, the execution of skilled voluntary movements results primarily from descending excitatory inputs from the contralateral cortical motor areas through the crossing fibers of the corticospinal tract to the motoneurons in the anterior horn of the spinal cord ipsilateral to the movement (Jenny and Inukai, 1983, Lemon and Griffiths, 2005). Shortly after the introduction of the blood oxygen level dependent contrast (BOLD), studies demonstrating the feasibility of using functional magnetic resonance imaging (fMRI) to non-invasively detect motor-related brain activity were published (Bandettini et al., 1992, Joliot et al., 1999, Kim et al., 1993, Kwong et al., 1992, van Gelderen et al., 1995). The characteristic finding from these studies was the robust lateralization of the activity to the contralateral motor and sensory cortices, which is consistent with our understanding of the brain regions involved in the execution of voluntary skilled movements (Cincotta and Ziemann, 2008).
Following the success of the early brain fMRI studies, several independent groups have attempted to use fMRI to detect motor-related spinal cord activity. The development of spinal cord fMRI, however, has been slower than brain fMRI due to several technical difficulties with the imaging of the spinal cord and the analysis of functional spinal cord images (Fratini et al., 2014, Stroman et al., 2014). Despite these challenges, the field has continued to progress, and spinal cord fMRI has been used to detect motor-related activity during several different motor tasks including repetitive finger flexion and extension (Bouwman et al., 2008, Yoshizawa et al., 1996), repetitive squeezing of a ball (Giulietti et al., 2008, Stroman et al., 1999, Stroman et al., 2001, Stroman and Ryner, 2001), repetitive fist clenching (Backes et al., 2001, Ng et al., 2006), repetitive elbow flexion and extension (Madi et al., 2001), repetitive wrist extension and flexion (Madi et al., 2001), repetitive finger abduction and adduction (Madi et al., 2001), holding weights in a flexed arm position (Madi et al., 2001), repetitive tongue movements to activate the infrahyoid muscles (Komisaruk et al., 2002), pedaling (Kornelsen and Stroman, 2004, Kornelsen and Stroman, 2007), repetitive thumb to finger apposition (Maieron et al., 2007, Ng et al., 2008, Vahdat et al., 2015), and repetitive finger tapping (Govers et al., 2007, Xie et al., 2009).
As in the brain, lateralization of the activity to the ipsilateral motor (anterior horn) and sensory (posterior horn) areas of the spinal cord during the execution of skilled voluntary movements should be expected with spinal cord fMRI. However, the lateralization of spinal cord activity has not been reliably shown in the previous motor studies. In fact, only a few of the spinal cord fMRI motor studies quantitatively assessed the laterality of the activity (Bouwman et al., 2008, Govers et al., 2007, Maieron et al., 2007, Ng et al., 2008, Stroman et al., 1999, Xie et al., 2009, Yoshizawa et al., 1996). Of these studies, only three statistically assessed the degree of laterality across the subjects, and only Maieron et al. (2007) detected significant lateralization of the activity to the ipsilateral hemicord across the subjects (Bouwman et al., 2008, Maieron et al., 2007, Ng et al., 2008).
The shortfall of reported lateralization of the spinal cord activity in the previous studies may be due to the complexity of the motor tasks employed (e.g., repetitive thumb to finger apposition). The motor tasks required the coordinated reciprocal activation and relaxation of multiple muscle groups and likely produced an influx of neural activity from multiple cutaneous, joint, and muscle afferents. Thus, the resulting fMRI signal in the spinal cord was likely a complex summation of multiple motor, interneuronal, and sensory processes, which may have impeded the detection of task-related signal changes and the localization of activity within the spinal cord. In contrast, a less complex isometric motor task may allow for more robust signal detection in the spinal cord as the motoneuron activity and sensory inputs should remain more stable over a block of activation.
The purpose of this study was to use an isometric left- and right-sided wrist flexion task in order to minimize the complexity of the neural signal and robustly detect and localize the fMRI signal in the spinal cord. In order to determine that the signal being detected was physiological in origin and not artifactual, we tested whether the activation rate exceeded the false positive rate, examined the anatomical specificity of the activity, and determined the reliability of the signal. Additional advancements with this study included the use of reduced field-of-view imaging and spatial normalization to a standard template (Cohen-Adad et al., 2014, Rieseberg et al., 2002).
Section snippets
Participants
Eleven healthy volunteers (5 male and 6 female; average age ± one standard deviation (SD) 27.7 ± 1.9 years) were studied. Subjects reported no neurological or musculoskeletal diseases or contraindications to MRI. Each subject provided written informed consent, and the entire study protocol was approved by Northwestern University's Institutional Review Board.
Data acquisition
Imaging was performed with a 3.0 T Siemens (Erlangen, Germany) Prisma magnetic resonance (MR) scanner equipped with a 64-channel head/neck coil
Results
All subjects successfully completed each run of data collection. No images were excluded due to motion artifacts. Motion correction improved the quality of the data as indicated by the increase in the average tSNR over the spinal cord. The average tSNR ± one SD significantly increased from 10.1 ± 1.7 arbitrary units (au) to 15.4 ± 2.1 au with the first phase of motion correction (t = 10.763, p < 0.001) and significantly increased from the first phase of motion correction to 16.2 ± 2.1 au with the second
Discussion
This study demonstrated the feasibility of using fMRI to measure motor-related activity in the cervical spinal cord of healthy subjects at the group and subject level using a left- and right-sided isometric wrist flexion task. The activity exceeded the spatial extent and magnitude of the control analyses, and the activity was anatomically specific and reliable across the runs. The average percent signal change was 0.49 ± 0.18% and 0.43 ± 0.14%, for the left and right contrasts, respectively, which
Conclusion
We were able to robustly detect cervical spinal cord activity at the group and subject level. The activity was lateralized to the ipsilateral hemicord, and the activity was reliable.
Acknowledgments
Research reported in this publication was supported by the National Center For Complementary and Integrative Health under award number F32AT007800 and the National Institute of Child Health and Development under award number T32HD057845. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
References (67)
- et al.
General multilevel linear modeling for group analysis in fMRI
Neuroimage
(2003) - et al.
Spinal cord functional MRI at 3 T: gradient echo echo-planar imaging versus turbo spin echo
Neuroimage
(2008) - et al.
Physiological noise modelling for spinal functional magnetic resonance imaging studies
Neuroimage
(2008) - et al.
Measuring fMRI reliability with the intra-class correlation coefficient
Neuroimage
(2009) - et al.
Mapping of neural activity produced by thermal pain in the healthy human spinal cord and brain stem: a functional magnetic resonance imaging study
Magn. Reson. Imaging
(2011) - et al.
Neurophysiology of unimanual motor control and mirror movements
Clin. Neurophysiol.
(2008) - et al.
Framework for integrated MRI average of the spinal cord white and gray matter: the MNI-Poly-AMU template
Neuroimage
(2014) - et al.
Characterization of the functional response in the human spinal cord: impulse–response function and linearity
Neuroimage
(2008) - et al.
Improved optimization for the robust and accurate linear registration and motion correction of brain images
Neuroimage
(2002) - et al.
FSL
Neuroimage
(2012)
FMRI and PET of self-paced finger movement: comparison of intersubject stereotaxic averaged data
Neuroimage
Assessment of physiological noise modelling methods for functional imaging of the spinal cord
Neuroimage
Precentral projections to different parts of the spinal intermediate zone in therhesus monkey
Brain Res.
Diffusion-weighted echo-planar imaging of the head and neck using 3-T MRI: Investigation into the usefulness of liquid perfluorocarbon pads and choice of optimal fat suppression method
Magn. Reson. Imaging
Power calculation for group fMRI studies accounting for arbitrary design and temporal autocorrelation
Neuroimage
Encoding and decoding in fMRI
Neuroimage
Proton-density-weighted spinal fMRI with sensorimotor stimulation at 0.2 T
Neuroimage
Cervical spinal cord BOLD fMRI study: modulation of functional activation by dexterity of dominant and non-dominant hands
Neuroimage
Zoomed functional imaging in the human brain at 7 Tesla with simultaneous high spatial and high temporal resolution
Neuroimage
Laterality index in functional MRI: methodological issues
Magn. Reson. Imaging
Advances in functional and structural MR image analysis and implementation as FSL
Neuroimage
Functional MRI of motor and sensory activation in the human spinal cord
Magn. Reson. Imaging
Characterization of contrast changes in functional MRI of the human spinal cord at 1.5 T
Magn. Reson. Imaging
The current state-of-the-art of spinal cord imaging: methods
Neuroimage
Robust group analysis using outlier inference
Neuroimage
Temporal autocorrelation in univariate linear modeling of fMRI data
Neuroimage
Multilevel linear modelling for fMRI group analysis using Bayesian inference
Neuroimage
SSFSE sequence functional MRI of the human cervical spinal cord with complex finger tapping
Eur. J. Radiol.
Functional magnetic resonance imaging of motor activation in the human cervical spinal cord
Neuroimage
Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat
J. Neurophysiol.
Functional MR imaging of the cervical spinal cord by use of median nerve stimulation and fist clenching
AJNR Am. J. Neuroradiol.
Time course EPI of human brain function during task activation
Magn. Reson. Med.
Vibratory adaptation of cutaneous mechanoreceptive afferents
J. Neurophysiol.
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