Influences of 12-Week Physical Activity Interventions on TMS Measures of Cortical Network Inhibition and Upper Extremity Motor Performance in Older Adults-A Feasibility Study

Keith M McGregor, Bruce Crosson, Kevin Mammino, Javier Omar, Paul S García, Joe R Nocera, Keith M McGregor, Bruce Crosson, Kevin Mammino, Javier Omar, Paul S García, Joe R Nocera

Abstract

Objective: Data from previous cross-sectional studies have shown that an increased level of physical fitness is associated with improved motor dexterity across the lifespan. In addition, physical fitness is positively associated with increased laterality of cortical function during unimanual tasks; indicating that sedentary aging is associated with a loss of interhemispheric inhibition affecting motor performance. The present study employed exercise interventions in previously sedentary older adults to compare motor dexterity and measure of interhemispheric inhibition using transcranial magnetic stimulation (TMS) after the interventions. Methods: Twenty-one community-dwelling, reportedly sedentary older adults were recruited, randomized and enrolled to a 12-week aerobic exercise group or a 12-week non-aerobic exercise balance condition. The aerobic condition was comprised of an interval-based cycling "spin" activity, while the non-aerobic "balance" exercise condition involved balance and stretching activities. Participants completed upper extremity dexterity batteries and estimates of VO2max in addition to undergoing single (ipsilateral silent period-iSP) and paired-pulse interhemispheric inhibition (ppIHI) in separate assessment sessions before and after study interventions. After each intervention during which heart rate was continuously recorded to measure exertion level (load), participants crossed over into the alternate arm of the study for an additional 12-week intervention period in an AB/BA design with no washout period. Results: After the interventions, regardless of intervention order, participants in the aerobic spin condition showed higher estimated VO2max levels after the 12-week intervention as compared to estimated VO2max in the non-aerobic balance intervention. After controlling for carryover effects due to the study design, participants in the spin condition showed longer iSP duration than the balance condition. Heart rate load was more strongly correlated with silent period duration after the Spin condition than estimated VO2. Conclusions: Aging-related changes in cortical inhibition may be influenced by 12-week physical activity interventions when assessed with the iSP. Although inhibitory signaling is mediates both ppIHI and iSP measures each TMS modality likely employs distinct inhibitory networks, potentially differentially affected by aging. Changes in inhibitory function after physical activity interventions may be associated with improved dexterity and motor control at least as evidence from this feasibility study show.

Keywords: TMS; aging; interhemispheric inhibition; motor control; neuroimaging; physical fitness.

Figures

Figure 1
Figure 1
Repeated measures Bland-Altman plot of VO2max estimate comparisons between interventions sessions as plotted in JMP12. Ordinate axis denotes difference score between treatments, while abscissa denotes. The central axis (in red) is offset to depict the mean value between interventions A+B/2. Thus, vertical gain (from red axis) indicates greater improvement in VO2 in Intervention A, while rightward gain indicates greater improvement after crossover. Circles represent Spin participant in Spin first condition while boxes represent participants in balance first (Between groups comparison—means represented by dotted lines: t = 5.29, p < 0.01).
Figure 2
Figure 2
Repeated measures Bland-Altman plot of HRload comparisons between interventions sessions as plotted in JMP12. Ordinate axis denotes difference score between treatments, while abscissa denotes. The central axis (in red) is offset to depict the mean value between interventions A+B/2. Thus, vertical gain (from red axis) indicates higher HRload in Intervention A, while rightward gain indicates greater improvement after crossover. Circles represent Spin participants while boxes represent Balance participants (Between groups comparison—means represented by dotted lines: t = 2.17, p < 0.04).
Figure 3
Figure 3
Repeated measures Bland-Altman plot of ipsilateral silent period (iSP) comparisons between interventions sessions as plotted in JMP12. Ordinate axis denotes difference measurement difference between treatments, while abscissa denotes average of both treatments. The central axis (in red) is offset to depict the mean value between interventions A+B/2. Thus, vertical gain (from red axis) indicates higher iSP in Intervention A, while rightward gain indicates greater improvement after crossover. Circles represent Spin participant in Spin first condition while boxes represent participants in balance first (Between groups comparison—means represented by dotted lines: t = 2.11, p < 0.05).

References

    1. Altman D. G., Bland J. M. (1983). Measurement in medicine: the analysis of method comparison studies. Statistician 32, 307–317. 10.2307/2987937
    1. Beekley M. D., Brechue W. F., Garzarella L., Werber-Zion G., Pollock M. L. (2004). Cross-validation of the ymca submaximal cycle ergometer test to predict VO2max. Res. Q. Exerc. Sport 75, 337–342. 10.1080/02701367.2004.10609165
    1. Chang W. H., Fried P. J., Saxena S., Jannati A., Gomes-Osman J., Kim Y. H., et al. . (2016). Optimal number of pulses as outcome measures of neuronavigated transcranial magnetic stimulation. Clin. Neurophysiol. 127, 2892–2897. 10.1016/j.clinph.2016.04.001
    1. Chen R. (2004). Interactions between inhibitory and excitatory circuits in the human motor cortex. Exp. Brain Res. 154, 1–10. 10.1007/s00221-003-1684-1
    1. Coppi E., Houdayer E., Chieffo R., Spagnolo F., Inuggi A., Straffi L., et al. . (2014). Age-related changes in motor cortical representation and interhemispheric interactions: a transcranial magnetic stimulation study. Front. Aging Neurosci. 6:209. 10.3389/fnagi.2014.00209
    1. Davidson T., Tremblay F. (2013). Age and hemispheric differences in transcallosal inhibition between motor cortices: an ispsilateral silent period study. BMC Neurosci. 14:62. 10.1186/1471-2202-14-62
    1. Di Lazzaro V., Pilato F., Dileone M., Profice P., Ranieri F., Ricci V., et al. . (2007). Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: a TMS study. Clin. Neurophysiol. 118, 2207–2214. 10.1016/j.clinph.2007.07.005
    1. Diaz-Buschmann I., Jaureguizar K. V., Calero M. J., Aquino R. S. (2014). Programming exercise intensity in patients on beta-blocker treatment: the importance of choosing an appropriate method. Eur. J. Prev. Cardiol. 21, 1474–1480. 10.1177/2047487313500214
    1. Doherty T. J., Vandervoort A. A., Brown W. F. (1993). Effects of ageing on the motor unit: a brief review. Can. J. Appl. Physiol. 18, 331–358. 10.1139/h93-029
    1. Ferbert A., Priori A., Rothwell J. C., Day B. L., Colebatch J. G., Marsden C. D. (1992). Interhemispheric inhibition of the human motor cortex. J. Physiol. 453, 525–546. 10.1113/jphysiol.1992.sp019243
    1. Fleming M. K., Newham D. J. (2017). Reliability of transcallosal inhibition in healthy adults. Front. Hum. Neurosci. 10:681. 10.3389/fnhum.2016.00681
    1. Fujiyama H., Hinder M. R., Summers J. J. (2013). Functional role of left PMd and left M1 during preparation and execution of left hand movements in older adults. J. Neurophysiol. 110, 1062–1069. 10.1152/jn.00075.2013
    1. Gao F., Edden R. A. E., Li M., Puts N. A. J., Wang G., Liu C., et al. . (2013). Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels. Neuroimage 78, 75–82. 10.1016/j.neuroimage.2013.04.012
    1. Garvey M. A., Ziemann U., Becker D. A., Barker C. A., Bartko J. J. (2001). New graphical method to measure silent periods evoked by transcranial magnetic stimulation. Clin. Neurophysiol. 112, 1451–1460. 10.1016/S1388-2457(01)00581-8
    1. Giovannelli F., Borgheresi A., Balestrieri F., Zaccara G., Viggiano M. P., Cincotta M., et al. . (2009). Modulation of interhemispheric inhibition by volitional motor activity: an ipsilateral silent period study. J. Physiol. 587, 5393–5410. 10.1113/jphysiol.2009.175885
    1. Godin G., Shephard R. J. (1997). Godin leisure-time exercise questionnaire. Med. Sci. Sports Exerc. 29, 36–38. 10.1097/00005768-199706001-00009
    1. Gomes-Osman J., Cabral D. F., Hinchman C., Jannati A., Morris T. P., Pascual-Leone A. (2017). The effects of exercise on cognitive function and brain plasticity - a feasibility trial. Restor. Neurol. Neurosci. 35, 547–556. 10.3233/RNN-170758
    1. Hanna-Pladdy B., Mendoza J. E., Apostolos G. T., Heilman K. M. (2002). Lateralised motor control: hemispheric damage and the loss of deftness. J. Neurol. Neurosurg. Psychiatry 73, 574–577. 10.1136/jnnp.73.5.574
    1. Heise K. F., Niehoff M., Feldheim J. F., Liuzzi G., Gerloff C., Hummel F. C. (2014). Differential behavioral and physiological effects of anodal transcranial direct current stimulation in healthy adults of younger and older age. Front. Aging Neurosci. 6:146. 10.3389/fnagi.2014.00146
    1. Heise K. F., Zimerman M., Hoppe J., Gerloff C., Wegscheider K., Hummel F. C. (2013). The aging motor system as a model for plastic changes of GABA-mediated intracortical inhibition and their behavioral relevance. J. Neurosci. 33, 9039–9049. 10.1523/JNEUROSCI.4094-12.2013
    1. Hill B. D., Barkemeyer C. A., Jones G. N., Santa Maria M. P., Minor K. S., Browndyke J. N. (2010). Validation of the coin rotation test: a simple, inexpensive, and convenient screening tool for impaired psychomotor processing speed. Neurologist 16, 249–253. 10.1097/NRL.0b013e3181b1d5b0
    1. Irlbacher K., Brocke J., Mechow J. V., Brandt S. A. (2007). Effects of GABA(A) and GABA(B) agonists on interhemispheric inhibition in man. Clin. Neurophysiol. 118, 308–316. 10.1016/j.clinph.2006.09.023
    1. Jung P., Ziemann U. (2006). Differences of the ipsilateral silent period in small hand muscles. Muscle Nerve 34, 431–436. 10.1002/mus.20604
    1. Kenward M. G., Roger J. H. (2010). The use of baseline covariates in crossover studies. Biostatistics 11, 1–17. 10.1093/biostatistics/kxp046
    1. Kleim J. A., Chan S., Pringle E., Schallert K., Procaccio V., Jimenez R., et al. . (2006). BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat. Neurosci. 9, 735–737. 10.1038/nn1699
    1. Kuo Y. L., Dubuc T., Boufadel D. F., Fisher B. E. (2017). Measuring ipsilateral silent period: effects of muscle contraction levels and quantification methods. Brain Res. 1674, 77–83. 10.1016/j.brainres.2017.08.015
    1. Lenzi D., Conte A., Mainero C., Frasca V., Fubelli F., Totaro P., et al. . (2007). Effect of corpus callosum damage on ipsilateral motor activation in patients with multiple sclerosis: a functional and anatomical study. Hum. Brain Mapp. 28, 636–644. 10.1002/hbm.20305
    1. Levin O., Fujiyama H., Boisgontier M. P., Swinnen S. P., Summers J. J. (2014). Aging and motor inhibition: a converging perspective provided by brain stimulation and imaging approaches. Neurosci. Biobehav. Rev. 43, 100–117. 10.1016/j.neubiorev.2014.04.001
    1. Li J. Y., Lai P. H., Chen R. (2013). Transcallosal inhibition in patients with callosal infarction. J. Neurophysiol. 109, 659–665. 10.1152/jn.01044.2011
    1. Lulic T., El-Sayes J., Fassett H. J., Nelson A. J. (2017). Physical activity levels determine exercise-induced changes in brain excitability. PLoS ONE 12:e0173672. 10.1371/journal.pone.0173672
    1. Maddock R. J., Casazza G. A., Fernandez D. H., Maddock M. I. (2016). Acute modulation of cortical glutamate and GABA content by physical activity. J. Neurosci. 36, 2449–2457. 10.1523/JNEUROSCI.3455-15.2016
    1. Mathiowetz V., Weber K., Kashman N., Volland G. (1985). Adult norms for the nine hole peg test of finger dexterity. Occup. Ther. J. Res. 5, 24–38. 10.1177/153944928500500102
    1. McDonnell M. N., Orekhov Y., Ziemann U. (2007). Suppression of LTP-like plasticity in human motor cortex by the GABAB receptor agonist baclofen. Exp. Brain Res. 180, 181–186. 10.1007/s00221-006-0849-0
    1. McGregor K., Heilman K., Nocera J., Patten C., Manini T., Crosson B., et al. . (2012). Aging, aerobic activity and interhemispheric communication. Brain Sci. 2, 634–648. 10.3390/brainsci2040634
    1. McGregor K. M., Nocera J. R., Sudhyadhom A., Patten C., Manini T. M., Kleim J. A., et al. . (2013). Effects of aerobic fitness on aging-related changes of interhemispheric inhibition and motor performance. Front. Aging Neurosci. 5:66. 10.3389/fnagi.2013.00066
    1. McGregor K. M., Zlatar Z., Kleim E., Sudhyadhom A., Bauer A., Phan S., et al. . (2011). Physical activity and neural correlates of aging: a combined TMS/fMRI study. Behav. Brain Res. 222, 158–168. 10.1016/j.bbr.2011.03.042
    1. Meyer B. U., Röricht S., Von Einsiedel H. G., Kruggel F., Weindl A. (1995). Inhibitory and excitatory interhemispheric transfers between motor cortical areas in normal humans and patients with abnormalities of the corpus callosum. Brain 118, 429–440. 10.1093/brain/118.2.429
    1. Mooney R. A., Cirillo J., Byblow W. D. (2017). GABA and primary motor cortex inhibition in young and older adults: a multimodal reliability study. J. Neurophysiol. 118, 425–433. 10.1152/jn.00199.2017
    1. Nathan P. W., Smith M., Deacon P. (1996). Vestibulospinal, reticulospinal and descending propriospinal nerve fibres in man. Brain 119, 1809–1833. 10.1093/brain/119.6.1809
    1. Nocera J. R., McGregor K. M., Hass C. J., Crosson B. (2015). Spin exercise improves semantic fluency in previously sedentary older adults. J. Aging Phys. Act. 23, 90–94. 10.1123/JAPA.2013-0107
    1. Oldfield R. C. (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113. 10.1016/0028-3932(71)90067-4
    1. Opie G. M., Ridding M. C., Semmler J. G. (2015). Age-related differences in pre- and post-synaptic motor cortex inhibition are task dependent. Brain Stimul. 8, 926–936. 10.1016/j.brs.2015.04.001
    1. Petitjean M., Ko J. Y. L. (2013). An age-related change in the ipsilateral silent period of a small hand muscle. Clin. Neurophysiol. 124, 346–353. 10.1016/j.clinph.2012.07.006
    1. Phillips C., Baktir M. A., Srivatsan M., Salehi A. (2014). Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Front. Cell Neurosci. 20:170 10.3389/fncel.2014.00170
    1. Reitan R. M., Wolfson D. (2013). Theoretical, methodological, and validational bases of the halstead-reitan neuropsychological test battery, in Comprehensive Handbook of Psychological Assessment: Intellectual and Neuropsychological Assessment, Vol. 1 eds Goldstein G., Beers S. R., Hersen M. (Hoboken, NJ: John Wiley & Sons, Inc.). 10.1002/9780471726753.ch8
    1. Roig M., Skriver K., Lundbye-Jensen J., Kiens B., Nielsen J. B. (2012). A single bout of exercise improves motor memory. PLoS ONE 7:e44594. 10.1371/journal.pone.0044594
    1. Rozycka A., Liguz-Lecznar M. (2017). The space where aging acts: focus on the GABAergic synapse. Aging Cell. 16, 634–643. 10.1111/acel.12605
    1. Sale M. V., Semmler J. G. (2005). Age-related differences in corticospinal control during functional isometric contractions in left and right hands. J. Appl. Physiol. 99, 1483–1493. 10.1152/japplphysiol.00371.2005
    1. Salthouse T. A. (1996). The processing-speed theory of adult age differences in cognition. Psychol. Rev. 103, 403–428. 10.1037/0033-295X.103.3.403
    1. Schmolesky M. T., Webb D. L., Hansen R. A. (2013). The effects of aerobic exercise intensity and duration on levels of brain-derived neurotrophic factor in healthy men. J. Sports Sci. Med. 12, 502–511.
    1. Siebner H. R., Dressnandt J., Auer C., Conrad B. (1998). Continuous intrathecal baclofen infusions induced a marked increase of the transcranially evoked silent period in a patient with generalized dystonia. Muscle Nerve 21, 1209–1212. 10.1002/(SICI)1097-4598(199809)21:9<1209::AID-MUS15>;2-M
    1. Singh A. M., Duncan R. E., Neva J. L., Staines W. R. (2014). Aerobic exercise modulates intracortical inhibition and facilitation in a nonexercised upper limb muscle. BMC Sports Sci. Med. Rehabil. 6:23. 10.1186/2052-1847-6-23
    1. Spirduso W. W. (1975). Reaction and movement time as a function of age and physical activity level. J. Gerontol. 30, 435–440. 10.1093/geronj/30.4.435
    1. Stagg C. J., Bachtiar V., Johansen-Berg H. (2011). The role of GABA in human motor learning. Curr. Biol. 21, 480–484. 10.1016/j.cub.2011.01.069
    1. Szuhany K. L., Bugatti M., Otto M. W. (2015). A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J. Psychiatr. Res. 60, 56–64. 10.1016/j.jpsychires.2014.10.003
    1. Talelli P., Waddingham W., Ewas A., Rothwell J. C., Ward N. S. (2008). The effect of age on task-related modulation of interhemispheric balance. Exp. Brain Res. 186, 59–66. 10.1007/s00221-007-1205-8
    1. Tang S. W., Chu E., Hui T., Helmeste D., Law C. (2008). Influence of exercise on serum brain-derived neurotrophic factor concentrations in healthy human subjects. Neurosci. Lett. 431, 62–65. 10.1016/j.neulet.2007.11.019
    1. Taubert M., Villringer A., Lehmann N. (2015). Endurance exercise as an “Endogenous” neuro-enhancement strategy to facilitate motor learning. Front. Hum. Neurosci. 9:692. 10.3389/fnhum.2015.00692
    1. Tiffin J., Asher E. J. (1948). The Purdue pegboard; norms and studies of reliability and validity. J. Appl. Psychol. 32, 234–247. 10.1037/h0061266
    1. Udupa K., Ni Z., Gunraj C., Chen R. (2010). Effect of long interval interhemispheric inhibition on intracortical inhibitory and facilitatory circuits. J. Physiol. 588(Pt 14), 2633–2641. 10.1113/jphysiol.2010.189548
    1. Voelcker-Rehage C., Godde B., Staudinger U. M. (2010). Physical and motor fitness are both related to cognition in old age. Eur. J. Neurosci. 31, 167–176. 10.1111/j.1460-9568.2009.07014.x
    1. Wischnewski M., Kowalski G. M., Rink F., Belagaje S. R., Haut M. W., Hobbs G., et al. . (2016). Demand on skillfulness modulates interhemispheric inhibition of motor cortices. J. Neurophysiol. 115, 2803–2813. 10.1152/jn.01076.2015
    1. Ziemann U., Ishii K., Borgheresi A., Yaseen Z., Battaglia F., Hallett M., et al. . (1999). Dissociation of the pathways mediating ipsilateral and contralateral motor-evoked potentials in human hand and arm muscles. J. Physiol. 518, 895–906. 10.1111/j.1469-7793.1999.0895p.x
    1. Ziemann U., Reis J., Schwenkreis P., Rosanova M., Strafella A., Badawy R., et al. . (2015). TMS and drugs revisited 2014. Clin. Neurophysiol. 126, 1847–1868. 10.1016/j.clinph.2014.08.028

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