Elsevier

Experimental Neurology

Volume 277, March 2016, Pages 27-34
Experimental Neurology

Research Paper
Differential frequency modulation of neural activity in the lateral cerebellar nucleus in failed and successful grasps

https://doi.org/10.1016/j.expneurol.2015.12.007Get rights and content

Highlights

  • We recorded local field potentials of the lateral cerebellar nucleus during reaching.

  • Modulation was apparent in the beta (12–30 Hz) and low gamma (40–50 Hz) bands.

  • Beta band modulation was increased in unsuccessful trials compared to successful.

  • This increased modulation was present even before the target was reached.

Abstract

The olivo-cerebellar system has an essential role in the detection and adaptive correction of movement errors. While there is evidence of an error signal in the cerebellar cortex and inferior olivary nucleus, the deep cerebellar nuclei have been less thoroughly investigated. Here, we recorded local field potential activity in the rodent lateral cerebellar nucleus during a skilled reaching task and compared event-related changes in neural activity between unsuccessful and successful attempts. Increased low gamma (40–50 Hz) band power was present throughout the reach and grasp behavior, with no difference between successful and unsuccessful trials. Beta band (12–30 Hz) power, however, was significantly increased in unsuccessful reaches, compared to successful, throughout the trial, including during the epoch preceding knowledge of the trial's outcome. This beta band activity was greater in unsuccessful trials of high-performing days, compared to unsuccessful trials of low-performing days, indicating that this activity may reflect an error prediction signal, developed over the course of motor learning. These findings suggest an error-related discriminatory oscillatory hallmark of movement in the deep cerebellar nuclei.

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.

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