Rehabilitative training drives plasticity in the ipsilesional (injured) motor cortex that is believed to support recovery of motor function after either stroke or traumatic brain injury (TBI). In addition, adaptive plasticity in the contralesional (uninjured) motor cortex has been well-characterized in the context of stroke. While similar rehabilitation-dependent plasticity in the intact hemisphere may occur after TBI, this has yet to be thoroughly explored. In this study, we investigated the effects of TBI and forelimb training on reorganization of movement representations in the intact motor cortex. Rats were trained to proficiency on the isometric pull task and then received a controlled cortical impact (CCI) in the left motor cortex to impair function of the trained right forelimb. After TBI, animals underwent forelimb training on the pull task for 2 months. At the end of training, intracortical microstimulation was used to document the organization of the intact motor cortex (the contralesional hemisphere). TBI significantly decreased the cortical area eliciting movements of the impaired forelimb in untrained animals. In the absence of TBI, training significantly increased forelimb map area, compared with in untrained controls. However, training of the impaired forelimb after TBI was insufficient to increase forelimb map area. These findings are consistent with other studies showing impaired rehabilitation-dependent plasticity after TBI and provide a novel characterization of TBI on rehabilitation-dependent plasticity in contralesional motor circuits.
Get full access to this article
View all access options for this article.
References
1.
FaulM., XuL., WaldM., and CoronadoV. (2010). Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths 2002–2006. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control: Atlanta, GA.
2.
PickelsimerE.E., SelassieA.W., SampleP.L., W. HeinemannA., GuJ.K., and VeldheerL.C. (2007). Unmet service needs of persons with traumatic brain injury. J. Head Trauma Rehabil., 22, 1–13.
3.
ThurmanD.J., AlversonC., DunnK.A., GuerreroJ., and SniezekJ.E. (1999). Traumatic brain injury in the United States: a public health perspective. J. Head Trauma Rehabil., 14, 602–615.
4.
SelassieA.W., ZaloshnjaE., LangloisJ.A., MillerT., JonesP., and SteinerC. (2008). Incidence of long-term disability following traumatic brain injury hospitalization, United States, 2003. J. Head Trauma Rehabil., 23, 123–131.
5.
LangloisJ.A., Rutland-BrownW., and WaldM.M. (2006). The epidemiology and impact of traumatic brain injury: a brief overview. J. Head Trauma Rehabil., 21, 375–378.
6.
KoppB., KunkelA., MunickelW., VillringerK., TaubE., and FlorH. (1999). Plasticity in the motor system related to therapy induced improvement of movement after stroke. Neuroreport, 10, 807–810.
7.
KleimJ.A. and JonesT.A. (2008). Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage. J. Speech. Lang. Hear. Res., 51, S225–S239.
8.
CombsH.L., JonesT.A., KozlowskiD.A., and AdkinsD.L. (2015). Combinatorial motor training results in functional reorganization of remaining motor cortex after controlled cortical impact in rats. J. Neurotrauma, 33, 741–747.
9.
FridmanE.A., HanakawaT., ChungM., HummelF., LeiguardaR.C., and CohenL.G. (2004). Reorganization of the human ipsilesional premotor cortex after stroke. Brain, 127, 747–758.
10.
DelvauxV., AlagonaG., GérardP., De PasquaV., PennisiG., and de NoordhoutA.M. (2003). Post-stroke reorganization of hand motor area: a 1-year prospective follow-up with focal transcranial magnetic stimulation. Clin. Neurophysiol., 114, 1217–1225.
11.
CalauttiC., LeroyF., GuincestreJ.Y., and BaronJ.C. (2003). Displacement of primary sensorimotor cortex activation after subcortical stroke: a longitudinal PET study with clinical correlation. Neuroimage, 19, 1650–1654.
12.
PineiroR., PendleburyS., Johansen-BergH., and MatthewsP.M. (2001). Functional MRI detects posterior shifts in primary sensorimotor cortex activation after stroke: evidence of local adaptive reorganization?. Stroke, 32, 1134–1139.
13.
WeillerC., CholletF., FristonK.J., WiseR.J.S., and FrackowiakR.S.J. (1992). Functional reorganization of the brain in recovery from striatocapsular infarction in man. Ann. Neurol., 31, 463–472.
14.
BiernaskieJ., SzymanskaA., WindleV., and CorbettD. (2005). Bi-hemispheric contribution to functional motor recovery of the affected forelimb following focal ischemic brain injury in rats. Eur. J. Neurosci., 21, 989–999.
15.
HagemannG., RedeckerC., Neumann-HaefelinT., FreundH.J., and WitteO.W. (1998). Increased long-term potentiation in the surround of experimentally induced focal cortical infarction. Ann. Neurol., 44, 255–258.
16.
DijkhuizenR.M., RenJ., MandevilleJ.B., WuO., OzdagF.M., MoskowitzM.A., RosenB.R., and FinklesteinS.P. (2001). Functional magnetic resonance imaging of reorganization in rat brain after stroke. Proc. Natl. Acad. Sci. U. S. A., 98, 12766–12771.
17.
DijkhuizenR.M., SinghalA.B., MandevilleJ.B., WuO., HalpernE.F., FinklesteinS.P., RosenB.R., and LoE.H. (2003). Correlation between brain reorganization, ischemic damage, and neurologic status after transient focal cerebral ischemia in rats: a functional magnetic resonance imaging study. J. Neurosci., 23, 510–517.
18.
LotzeM., MarkertJ., SausengP., HoppeJ., PlewniaC., and GerloffC. (2006). The role of multiple contralesional motor areas for complex hand movements after internal capsular lesion. J. Neurosci., 26, 6096–6102.
19.
Johansen-BergH., RushworthM.F.S., BogdanovicM.D., KischkaU., WimalaratnaS., and MatthewsP.M. (2002). The role of ipsilateral premotor cortex in hand movement after stroke. Proc. Natl. Acad. Sci. U. S. A., 99, 14518–14523.
20.
RossiniP.M., CaltagironeC., Castriota-ScanderbegA., CicinelliP., Del GrattaC., DemartinM., PizzellaV., TraversaR., and RomaniG.L. (1998). Hand motor cortical area reorganization in stroke: a study with fMRI, MEG and TCS maps. Neuroreport, 9, 2141–2146.
21.
TurtonA., WroeS., TrepteN., FraserC., and LemonR.N. (1996). Contralateral and ipsilateral EMG responses to transcranial magnetic stimulation during recovery of arm and hand function after stroke. Electroencephalogr. Clin. Neurophysiol. Mot. Control, 101, 316–328.
22.
HondaM., NagamineT., FukuyamaH., YonekuraY., KimuraJ., and ShibasakiH. (1997). Movement-related cortical potentials and regional cerebral blood flow change in patients with stroke after motor recovery. J. Neurol. Sci., 146, 117–126.
23.
MuellbacherW., ArtnerC., and MamoliB. (1999). The role of the intact hemisphere in recovery of midline muscles after recent monohemispheric stroke. J. Neurol., 246, 250–256.
24.
JonesT.A., LiputD.J., MareshE.L., DonlanN., ParikhT.J., MarloweD., and KozlowskiD.A. (2012). Use-dependent dendritic regrowth is limited after unilateral controlled cortical impact to the forelimb sensorimotor cortex. J. Neurotrauma, 29, 1455–1468.
25.
PruittD.T., SchmidA.N., DanaphongseT.T., FlanaganK.E., MorrisonR.A., KilgardM.P., RennakerR.L., and HaysS.A. (2016). Forelimb training drives transient map reorganization in ipsilateral motor cortex. Behav. Brain Res., 313, 10–16.
PruittD.T., SchmidA.N., KimL.J., AbeC.M., TrieuJ.L., ChouaC., HaysS.A., KilgardM.P., and RennakerR.L. (2015). Vagus nerve stimulation delivered with motor training enhances recovery of function after traumatic brain injury. J. Neurotrauma, 33, 871–879.
28.
RodriguezL.C., PalmerK., MontagnerF., and RodriguesD.C. (2015). A novel chlorhexidine-releasing composite bone cement: characterization of antimicrobial effectiveness and cement strength. J. Bioact. Compat. Polym., 30, 34–47.
29.
HaysS.A., KhodaparastN., SloanA.M., HulseyD.R., PantojaM., RuizA.D., KilgardM.P., and RennakerR.L. (2013). The isometric pull task: a novel automated method for quantifying forelimb force generation in rats. J. Neurosci. Methods, 212, 329–337.
30.
KhodaparastN., HaysS.A., SloanA.M., HulseyD.R., RuizA., PantojaM., RennakerR.L., and KilgardM.P. (2013). Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke. Neurobiol. Dis., 60, 80–88.
31.
SloanA.M., FinkM.K., RodriguezA.J., LovitzA.M., KhodaparastN., RennakerR.L., and HaysS.A. (2015). A within-animal comparison of skilled forelimb assessments in rats. PLoS One, 10, e0141254.
32.
Brus-RamerM., CarmelJ.B., and MartinJ.H. (2009). Motor cortex bilateral motor representation depends on subcortical and interhemispheric interactions. J. Neurosci., 29, 6196–6206.
33.
AxelsonH.W., WinklerT., FlygtJ., DjupsjöA., HånellA., and MarklundN. (2013). Plasticity of the contralateral motor cortex following focal traumatic brain injury in the rat. Restor. Neurol. Neurosci., 31, 73–85.
34.
PorterB.A., KhodaparastN., FayyazT., CheungR.J., AhmedS.S., VranaW.A., RennakerR.L., and KilgardM.P. (2012). Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex. Cereb. Cortex, 22, 2365–2374.
35.
HulseyD.R., HaysS.A., KhodaparastN., RuizA., DasP., RennakerR.L., and KilgardM.P. (2016). Reorganization of motor cortex by vagus nerve stimulation requires cholinergic innervation. Brain Stimul. 9, 174–181.
36.
KhodaparastN., HaysS.A., SloanA.M., FayyazT., HulseyD.R., RennakerR.L., and KilgardM.P. (2014). Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke. Neurorehabil. Neural Repair, 28, 698–706.
37.
HarrisN.G., ChenS.F., and PickardJ.D. (2013). Cortical reorganization after experimental traumatic brain injury: a functional autoradiography study. J. Neurotrauma, 30, 1137–1146.
38.
BarbayS., GuggenmosD.J., NishibeM., and NudoR.J. (2013). Motor representations in the intact hemisphere of the rat are reduced after repetitive training of the impaired forelimb. Neurorehabil. Neural Repair, 27, 381–384.
39.
DingM.C., WangQ., LoE.H., and StanleyG.B. (2011). Cortical excitation and inhibition following focal traumatic brain injury. J. Neurosci., 31, 14085–14094.
40.
NudoR.J. (2003). Adaptive plasticity in motor cortex: implications for rehabilitation after brain injury. J. Rehabil. Med.7–10.
41.
Bach-y-RitaP. (2003). Theoretical basis for brain plasticity after a TBI. Brain Inj. 17, 643–651.
Johansen-BergH., RushworthM.F.S., BogdanovicM.D., KischkaU., WimalaratnaS., and MatthewsP.M. (2002). The role of ipsilateral premotor cortex in hand movement after stroke. Proc. Natl. Acad. Sci. U. S. A., 99, 14518–14523.
44.
BashirS., VernetM., YooW.K., MizrahiI., TheoretH., and Pascual-LeoneA. (2012). Changes in cortical plasticity after mild traumatic brain injury. Restor. Neurol. Neurosci., 30, 277–282.
45.
SandersM.J., SickT.J., Perez-PinzonM.A., DietrichW.D., and GreenE.J. (2000). Chronic failure in the maintenance of long-term potentiation following fluid percussion injury in the rat. Brain Res. 861, 69–76.
46.
ReevesT.M., LyethB.G., and PovlishockJ.T. (1995). Long-term potentiation deficits and excitability changes following traumatic brain injury. Exp. Brain Res., 106, 248–56.
47.
MiyazakiS., KatayamaY., LyethB.G., JenkinsL.W., DeWittD.S., GoldbergS.J., NewlonP.G., and HayesR.L. (1992). Enduring suppression of hippocampal long-term potentiation following traumatic brain injury in rat. Brain Res. 585, 335–9.
48.
JeffersonS.C., ClaytonE.R., DonlanN.A., KozlowskiD.A., JonesT.A., and AdkinsD.L. (2015). Cortical stimulation concurrent with skilled motor training improves forelimb function and enhances motor cortical reorganization following controlled cortical impact. Neurorehabil. Neural Repair, 30, 155–158.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
