Impaired consolidation and long-term retention of motor learning after traumatic brain injury
- 1. •Memory deficits are typical after traumatic brain injury (TBI) and may be a result of the stereotypical axonal damage after TBI, impairing the connections between brain regions. •While motor impairments after TBI resolve relatively soon after injury, higher-level motor functions such as learning and memory may be more affected. Motor learning occurs in stages and involves different brain circuitry/regions as learning progresses (Dayan and Cohen 2011). Currently, there is a gap in research involving motor learning after TBI. •Many TBI patients are young, and return to work may be based on their ability to learn novel motor coordination patterns. HYPOTHESIS: Traumatic brain injury affects specific stages of learning a novel motor skill and motor memory. INTRODUCTION METHODS RESULTS CONCLUSIONS •TBI animals learned a motor task as well as controls after 5 days of training, however they did so differently. •Specific stages of motor learning were affected after CCI: • Overnight consolidation was disrupted in both TBI groups. • Long term retention was impaired in the more severe TBI group. •Lesion size was significantly larger in the sTBI group, affecting M1 and premotor areas as well as deforming the hippocampus. •Preliminary observations: GFAP immunoreactivity was higher in the premotor area and in the striatum in the sTBI group, GFAP immunoreactivity in the hippocampus was similar in the lesioned andn non-lesioned hemispheres. •SUMMARY: Overnight consolidation and long term retention are impaired after CCI of the motor cortex. ACKNOWLEDGEMENTS •This work was supported by the Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation, grant # G1703N •Thanks to Marla Ramirez for MRI lesion size analysis. •Thanks to Jeeva Munasinghe for MRI scan development. 1Human Cortical Physiol. and Stroke Neurorehabilitation Section, NINDS, NIH, Bethesda, MD; 2Anatomy, Physiol. and Genet., 3Neurosci., Uniformed Services Univ., Bethesda, MD; 4Landon Center on Aging, Molecular and Integrative Physiol., Kansas Univ. Med. Center, Kansas City, KS *S. C. SCHWERIN1,2, M. SHINDELL2, N. DATTA2, R. NUDO4, S. L. JULIANO2,3, L. G. COHEN1 Impaired Consolidation and Long-Term Retention of Motor Learning after Traumatic Brain Injury Mice: C57Bl6 Groups: *Control (surgically naïve) *more Mild TBI 12 wk old males *Sham (craniotomy only) *more Severe TBI •Handedness: determined prior to injury -Mice food restricted to 90% original body weight -15 min/day, placed in box and trained to reach, 10 reaches with either hand determined handedness •Acclimation: 3 days -1 trial, 1 minute, at 4 RPM -Animals placed back on if fall •Outcome Measure: time to fall or to complete 1 full rotation CCI Coordinates: •Dominant hemisphere , M1 CFA •1.5 mm lateral to Bregma Controlled Cortical Impact Parameters: 100ms dwell time, 15° angle, velocity: 5 m/s •more mild TBI: - impactor diameter: 1.5 mm - depth: 1 mm •more severe TBI: - impactor diameter: 3 mm - depth: 2mm Stoelting Co., IL CCI Tennat KA, et al., 2011 Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 RETENTIONACCLIMATION ROTAROD MRI MRI MRICCI 3DPI 42DPI •Training: began on day 3 after injury -4-40 RPM over 2 minutes -5 trials/day for 5 days -1st trial: 60 sec at 4 RPM before acceleration -2nd-5th trial:10 sec at 4 RPM before acceleration •Retention: tested 5 weeks after training completion -1 trial, with 60 sec at 4 RPM before acceleration Timeline: Motor Training: REFERENCES •Dayan E, Cohen LG. Neuroplasticity subserving motor skill learning. Neuron. 2011 Nov 3;72(3):443-54. •Tennant KA, Adkins DL, Donlan NA, Asay AL, Thomas N, Kleim JA, Jones TA. The organization of the forelimb representation of the C57BL/6 mouse motor cortex as defined by intracortical microstimulation and cytoarchitecture. Cereb Cortex. 2011 Apr;21(4):865-76. •Turtzo LC, Budde MD, Gold E, Lewis BK, Janes L, Watson WD, Frank JA, The Evolution of Traumatic Brain Injury in a Rat Focal Contusion Model by MRI. NMR in Biomedicine, submitted T2 MRI: Injury Quantification * •*Lesion cavity •Hyperintense Region of Edema •Isointense Region Similar analysis methods as Turtzo et al., submitted 0 20 40 60 80 100 120 Control Sham mTBI sTBI HealthyTissueinLesioned Hemisphereexpressedas%of NonlesionedHemisphere Pre 1week 6weeks E mTBI sTBI GFAP F C D1 (T5-T1) Online LearningB T25 Retention Retention * * *** D2-D1 D3-D2 D4-D3 D5-D4 Overnight Consolidation D2T1-D1T5 * * * * * * A Control (13) Sham(7) mTBI(7) sTBI(13) SkillLoss------------SkillGain Time(sec) D mTBI sTBI 1000um 1000um TBI TBI TBI TBI * *
- 2. The views presented here are those of the author and are not to be construed as official or reflecting the views of the Uniformed Services University of the Health Sciences, the Department of Defense or the U.S. Government.