Research PaperDifferential frequency modulation of neural activity in the lateral cerebellar nucleus in failed and successful grasps
Introduction
The cerebellum is known to play an integral role in both motor learning and kinematics; however, the specific role of the lateral cerebellar nucleus (LCN), or dentate nucleus, in adaptive motor control remains unclear. The dentate is reciprocally connected to contralateral premotor, motor, and associative cortices via the ventrolateral and mesial thalamic nuclei (Allen et al., 1978, Brodal, 1978), with limited projections from the periphery. Recent data suggest that Purkinje single cell spiking in the cerebellar cortex, which inhibits the deep cerebellar nuclei, is associated with failure or success of a trial (Greger and Norris, 2005, Roitman et al., 2009) and can predict performance errors (Kitazawa et al., 1998, Popa et al., 2012). If there is a predictive signal upstream of the LCN at the level of the cerebellar cortex, it follows that a distinctive modulatory signal may be processed in the LCN itself. In the current experimentation, we tested the hypothesis that local field potential (LFP) activity within the LCN could distinguish between successful and unsuccessful reaches during a skilled motor task. Such findings have important physiological implications, as LCN LFPs during reaching and grasp have not been studied to date. Furthermore, these findings represent an important technical milestone by advancing ongoing translational work in chronic stimulation of the LCN as a treatment for post-injury motor rehabilitation (Cooperrider et al., 2014, Machado et al., 2013) towards a closed-loop stimulation therapy, wherein stimulation is triggered by a neural signal.
Section snippets
Animals
Male Long–Evans rats (200–225 g) were housed in standard caging on a 12:12 h light/dark cycle and food-restricted (12 g of food/day) during experimental testing with unrestricted access to water. Behavioral testing was performed during the dark phase of the light cycle under controlled red lighting. Animal use was approved by the Institutional Animal Care and Use Committee of Cleveland Clinic.
Microelectrode array (MEA) implantation
Each animal was implanted unilaterally with a single five-electrode tungsten MEA (Fig. 1; Model
Animals
Seven animals completed this study. Histology confirmed the positioning of the MEA in the LCN for all five electrodes of the array in six of the seven animals (Fig. 1). Only three electrodes could be confirmed for the final animal. Thus, data from 33 electrodes were used in the analysis.
Reaching analysis
Video analysis revealed that the mean time of reach initiation occurred at − 322 ± 16 ms (mean ± SEM, Fig. 2) for HIT and − 328 ± 16 ms for MISS trials and did not differ between trial types (p = 0.28). MISS trials resulted
Discussion
We investigated how the spectral profile of the rat LCN is differentially modulated during successful and unsuccessful performance of a reach and grasp task. To our knowledge, this is the first analysis of LCN LFP activity in a behaving animal model. We observed significant modulation across two frequency bands during the task: low gamma (40–50 Hz) and beta (12–30 Hz). Low gamma band power increased throughout the entirety of the reaching task independent of the trial type, suggesting that
Conflict of interest
A.G.M. and K.B.B. have distribution rights related to intellectual property in Enspire DBS, Cardionomics and ATI. A.G.M. is a consultant to Spinal Modulation and Functional Neuromodulation.
Acknowledgments
This research was funded by NIH grant R01 HD061363.
References (35)
- et al.
Oscillatory activity in forelimb muscles of behaving monkeys evoked by microstimulation in the cerebellar nuclei
Neurosci. Lett.
(2004) - et al.
Multiple single unit recording in the cortex of monkeys using independently moveable microelectrodes
J. Neurosci. Methods
(1999) - et al.
Timing in the cerebellum: oscillations and resonance in the granular layer
Neuroscience
(2009) - et al.
Mode of operation of the cerebellum in the dynamic loop control of movement
Brain Res.
(1972) - et al.
Purkinje cell activity during motor learning
Brain Res.
(1977) - et al.
The role of the cerebello-thalamo-cortical pathway in skilled movement
Prog. Neurobiol.
(1995) - et al.
Chronic electrical stimulation of the contralesional lateral cerebellar nucleus enhances recovery of motor function after cerebral ischemia in rats
Brain Res.
(2009) - et al.
Nonparametric statistical testing of EEG- and MEG-data
J. Neurosci. Methods
(2007) - et al.
Gamma-range corticomuscular coherence during dynamic force output
NeuroImage
(2007) - et al.
The structure of skilled forelimb reaching in the rat: a proximally driven movement with a single distal rotatory component
Behav. Brain Res.
(1990)