The reduction of plasticity with age has been shown by many previous papers in animal experiments. This issue can be studied in humans because several non-invasive brain stimulation techniques induce synaptic plasticity in the human brain. We investigated the influence of individuals’ age on the responder rate of the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS). The participants were 107 healthy volunteers: 53 older participants (Mean ± SD 65.0 ± 1.5 years) and 54 younger participants (37.2 ± 8.7). The quadripulse stimulation with 5-ms inter-pulse interval (QPS5) was applied over the primary motor cortex (M1). We measured motor evoked potentials (MEPs) before QPS, and at five time points after QPS for up to 25 min. In each participant, average MEP amplitude (size) ratios were quantified. We first classified participants as responders and non-responders simply by comparing the size ratio with 1.0 for consistency with previous studies, then as “significant responders”, “non-responders”, and “opposite responders” for more detailed analysis by comparing the size ratio with the mean and standard deviation of the MEP size ratios of the sham condition. The degree of LTP-like effects induced by QPS5 was significantly smaller in the older group compared to the younger group. Also, the rates of responders and significant responders were lower in the older group (58 and 47%, respectively) compared to the younger group (80 and 76%, respectively). The age of the participants significantly affected the LTP-like effect induced by QPS5, which suggests that brain plasticity decreases with age.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Di Lazzaro V, Pilato F, Dileone M, Profice P, Oliviero A, Mazzone P, Insola A, Ranieri F, Meglio M, Tonali PA, Rothwell JC (2008) The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex. J Physiol 586:3871–3879
Dickins DS, Sale MV, Kamke MR (2015) Plasticity induced by intermittent theta burst stimulation in bilateral motor cortices is not altered in older adults. Neural Plast 2015:323409
Dumitriu D, Hao J, Hara Y, Kaufmann J, Janssen WG, Lou W, Rapp PR, Morrison JH (2010) Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J Neurosci 30(22):7507–7515
Fathi D, Ueki Y, Mima T, Koganemaru S, Nagamine T, Tawfik A, Fukuyama H (2010) Effects of aging on the human motor cortical plasticity studied by paired associative stimulation. Clin Neurophysiol 121:90–93
Fujiyama H, Hyde J, Hinder MR, Kim SJ, McCormack GH, Vickers JC, Summers JJ (2014) Delayed plastic responses to anodal tDCS in older adults. Front Aging Neurosci 6:115
Gutchess A (2014) Plasticity of the aging brain: new directions in cognitive neuroscience. Science 346:579–582
Hamada M, Terao Y, Hanajima R, Shirota Y, Nakatani-Enomoto S, Furubayashi T, Matsumoto H, Ugawa Y (2008) Bidirectional long-term motor cortical plasticity and metaplasticity induced by quadripulse transcranial magnetic stimulation. J Physiol 586:3927–3947
Hamada M, Murase N, Hasan A, Balaratnam M, Rothwell JC (2013) The role of interneuron networks in driving human motor cortical plasticity. Cereb Cortex 23:1593–1605
Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005) Theta burst stimulation of the human motor cortex. Neuron 45:201–206
Inomata-Terada S, Okabe S, Arai N, Hanajima R, Terao Y, Furubayashi T, Ugawa Y (2007) Effects of high frequency electromagnetic field (EMF) emitted by mobile phones on the human motor cortex. Bioelectromagnetics 28:553–561
López-Alonso V, Cheeran B, Río-Rodríguez D, Fernández-Del-Olmo M (2014) Inter-individual variability in response to non-invasive brain stimulation paradigms. Brain Stimul 7:372–380
Müller-Dahlhaus JF, Orekhov Y, Liu Y, Ziemann U (2008) Interindividual variability and age-dependency of motor cortical plasticity induced by paired associative stimulation. Exp Brain Res 187:467–475
Nakamura K, Groiss SJ, Hamada M, Enomoto H, Kadowaki S, Abe M, Murakami T, Wiratman W, Chang F, Kobayashi S, Hanajima R, Terao Y, Ugawa Y (2016) Variability in response to quadripulse stimulation of the motor cortex. Brain Stimul. doi:10.1016/j.brs.2016.01.008
Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527:633–639
Sawaki L, Yaseen Z, Kopylev L, Cohen LG (2003) Age-dependent changes in the ability to encode a novel elementary motor memory. Ann Neurol 53:521–524
Simeoni S, Hannah R, Sato D, Kawakami M, Rothwell J, Simeoni S, Gigli GL, Sato D, Kawakami M (2016) Effects of quadripulse stimulation on human motor cortex excitability: a replication study. Brain Stimul 9:148–150
Stefan K, Kunesch E, Benecke R, Cohen LG, Classen J (2002) Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation. J Physiol 543:699–708
Tanaka N, Hanajima R, Tsutsumi R, Shimizu T, Shirota Y, Terao Y, Ugawa Y (2015) Influence of zonisamide on the LTP-like effect induced by quadripulse transcranial magnetic stimulation (QPS). Brain Stimul 8:1220–1222
Vallence AM, Goldsworthy MR, Hodyl NA, Semmler JG, Pitcher JB, Ridding MC (2015) Inter- and intra-subject variability of motor cortex plasticity following continuous theta-burst stimulation. Neuroscience 304:266–278
Young-Bernier M, Tanguay AN, Davidson PS, Tremblay F (2014) Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults. Front Aging Neurosci 6:182
This work was supported in part by a research grant from Catecholamine and the Neurological Disorders Symposium (RH), research funds from the Magnetic Health Science Foundation (RH, YT) and by research grants from Research Project Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology [No. 26461308 (RH), No. 25293206 (YU), No. 22390181 (YU, HE), No. 25461322 (HE), No. 22590954 (YT), 15K19496 (RT), 15H05881 (RH, YU), 16H05322 (YU),15H01658 (MH), 15K19476 (MH), and 16H01605 (MH)].
Conflict of interest
About this article
Cite this article
Hanajima, R., Tanaka, N., Tsutsumi, R. et al. The effect of age on the homotopic motor cortical long-term potentiation-like effect induced by quadripulse stimulation. Exp Brain Res 235, 2103–2108 (2017). https://doi.org/10.1007/s00221-017-4953-0
- Transcranial magnetic stimulation
- Cortical plasticity
- Age dependence