title: Deep brain stimulation of the lateral cerebellar nucleus produces frequency-specific alterations in motor evoked potentials in the rat in vivo.
abstract: The cerebral cortex is tightly and reciprocally linked to the cerebellum and the ascending dentato-thalalmo-cortical pathway influences widespread cortical regions. Using a rodent model of middle cerebral artery stroke, we showed previously that chronic, 20 Hz stimulation of the contralateral lateral cerebellar nucleus (LCN) improved motor recovery, while 50 Hz stimulation did not. Using motor evoked potentials (MEP) elicited by intracortical microstimulation, we now show the effect of LCN stimulation on motor cortex excitability as a function of pulse frequency in propofol-anesthetized rats. MEPs were recorded serially, at 15-s intervals, with cerebellar stimulation delivered in 10-min blocks at rates of 20, 30, 40, 50 or 100 Hz. Stimulation at 20, 30, 40 or 50 Hz enhanced the average MEP response across the block, with the maximal overall increase observed during 30 Hz stimulation. However, the effect varied as a function of both repeated trials within the block and LCN stimulation frequency, such that 40 Hz and 50 Hz stimulation showed a reduced effect over time. Stimulation at 100 Hz produced a transient increase in MEP amplitude in some animals; however the overall effect across the block was a trend towards reduced cortical excitability. These results suggest that direct stimulation of the LCN can yield frequency-dependent changes in cortical excitability and may provide a therapeutic approach to modulating cortical activity for the treatment of strokes or other focal cortical lesions, movement disorders and epilepsy.
authors.affiliation: Department of Neuroscience (NC-30), Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Baker
authors.forename: Daniel
authors.initials: D
authors.lastname: Schuster
authors.forename: Jessica
authors.initials: J
authors.lastname: Cooperrider
authors.forename: Andre G
authors.initials: AG
authors.lastname: Machado
mesh_terms: D000818:Animals; D002529:Cerebellar Nuclei / Q000502:physiology*; D003265:Contingent Negative Variation / Q000502:physiology; D046690:Deep Brain Stimulation; D004566:Electrodes; D004576:Electromyography / Q000379:methods; D019054:Evoked Potentials, Motor / Q000502:physiology*; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
references.citation: Curr Biol. 2004 Nov 9;14(21):1907-15
references.pmid: 15530391
references.citation: Brain Res. 2009 Jul 14;1280:107-16
references.pmid: 19445910
references.citation: Exp Brain Res. 1976 Mar 15;24(5):495-507
references.pmid: 1253863
references.citation: Stroke. 2006 Jun;37(6):1471-6
references.pmid: 16675743
references.citation: J Neurophysiol. 2003 Jan;89(1):634-9
references.pmid: 12522208
references.citation: Top Stroke Rehabil. 2008 Mar-Apr;15(2):160-72
references.pmid: 18430685
references.citation: J Neurosurg. 2008 Apr;108(4):707-14
references.pmid: 18377250
references.citation: J Neurophysiol. 2003 Jun;89(6):3205-14
references.pmid: 12783955
references.citation: Stroke. 2009 May;40(5):1926-31
references.pmid: 19359643
references.citation: J Neurol Neurosurg Psychiatry. 1994 Jan;57(1):108-10
references.pmid: 8301289
references.citation: Brain. 1950 Jun;73(2):125-40
references.pmid: 14791783
references.citation: Brain Stimul. 2008 Jul;1(3):151-63
references.pmid: 20633382
references.citation: Nat Neurosci. 1998 May;1(1):64-8
references.pmid: 10195111
references.citation: Neurol Res. 2003 Dec;25(8):780-8
references.pmid: 14669519
references.citation: Neurosci Lett. 2004 May 6;361(1-3):106-10
references.pmid: 15135905
references.citation: J Neurophysiol. 2008 Sep;100(3):1498-512
references.pmid: 18596180
references.citation: Brain Res. 1975 May 2;88(2):233-41
references.pmid: 1148824
references.citation: Brain. 1999 Oct;122 ( Pt 10):1919-31
references.pmid: 10506093
references.citation: Exp Brain Res. 1982;47(3):365-80
references.pmid: 6889975
references.citation: Neurosurgery. 1987 Jan;20(1):193-5
references.pmid: 3808262
references.citation: J Neurosci Res. 2006 Feb 1;83(2):177-80
references.pmid: 16385580
references.citation: J Neurophysiol. 2000 Jul;84(1):585-90
references.pmid: 10899231
references.citation: Trans Am Neurol Assoc. 1973;98:192-6
references.pmid: 4206369
references.citation: J Comp Neurol. 1978 Apr 1;178(3):495-517
references.pmid: 19626723
references.citation: Acta Neurochir (Wien). 1995;136(1-2):75-81
references.pmid: 8748831
references.citation: Neurorehabil Neural Repair. 2007 Jan-Feb;21(1):14-24
references.pmid: 17172550
references.citation: Neuroscientist. 2003 Feb;9(1):64-75
references.pmid: 12580341
references.citation: Brain Res. 1971 Mar 19;27(1):97-109
references.pmid: 4251989
references.citation: Neurol Res. 2003 Dec;25(8):801-10
references.pmid: 14669522
references.citation: Physiol Rev. 1974 Oct;54(4):957-1006
references.pmid: 4370744
references.citation: Neurosurgery. 1987 Jan;20(1):195-7
references.pmid: 3808263
references.citation: Neuron. 2007 Oct 25;56(2):209-25
references.pmid: 17964241
references.citation: Lancet Neurol. 2003 Aug;2(8):493-502
references.pmid: 12878437
references.citation: Exp Brain Res. 1998 Mar;119(2):179-90
references.pmid: 9535568
references.citation: Neurosci Lett. 1981 Mar 10;22(2):137-44
references.pmid: 7231805
references.citation: Brain Res. 1983 May;286(3):267-97
references.pmid: 6189562
references.citation: Cogn Behav Neurol. 2006 Mar;19(1):41-7
references.pmid: 16633018
references.citation: J Comp Neurol. 1981 Apr 1;197(2):217-36
references.pmid: 7276233
references.citation: Brain Res. 1975 Nov 7;98(1):73-92
references.pmid: 1175060
references.citation: Clin Neurol Neurosurg. 2004 Sep;106(4):318-29
references.pmid: 15297008
references.citation: Appl Neurophysiol. 1983;46(1-4):57-61
references.pmid: 6608318
references.citation: Neuroscience. 2002;111(4):863-70
references.pmid: 12031409
references.citation: Stroke. 2006 Aug;37(8):2115-22
references.pmid: 16809569
references.citation: J Neurol. 2001 Apr;248(4):315-21
references.pmid: 11374097
references.citation: Exp Brain Res. 2004 Dec;159(4):418-24
references.pmid: 15558250
references.citation: J Neural Transm (Vienna). 2009 Apr;116(4):423-9
references.pmid: 19238517
references.citation: J Physiol. 1979 Dec;297(0):559-80
references.pmid: 119847
references.citation: Stroke. 2000 Jun;31(6):1210-6
references.pmid: 10835434
references.citation: J Neurol Neurosurg Psychiatry. 1984 Aug;47(8):769-74
references.pmid: 6381652
references.citation: Brain. 2005 Mar;128(Pt 3):490-9
references.pmid: 15634731
references.citation: Brain. 1979 Mar;102(1):127-46
references.pmid: 106923
references.citation: Stroke. 2006 Nov;37(11):2850-3
references.pmid: 17008618