Homeostatic plasticity in human motor cortex demonstrated by two consecutive sessions of paired associative stimulation

Abstract

Long-term potentiation (LTP) and long-term depression (LTD) underlie most models of learning and memory, but neural activity would grow or shrink in an uncontrolled manner, if not guarded by stabilizing mechanisms. The Bienenstock-Cooper-Munro (BCM) rule proposes a sliding threshold for LTP/LTD induction: LTP induction becomes more difficult if neural activity was high previously. Here we tested if this form of homeostatic plasticity applies to the human motor cortex (M1) in vivo by examining the interactions between two consecutive sessions of paired associative stimulation (PAS). PAS consisted of repeated pairs of electrical stimulation of the right median nerve followed by transcranial magnetic stimulation of the left M1. The first PAS session employed an interstimulus interval equalling the individual N20-latency of the median nerve somatosensory-evoked cortical potential plus 2 ms, N20-latency minus 5 ms, or a random alternation between these intervals, to induce an LTP-like increase in motor-evoked potential (MEP) amplitudes in the right abductor pollicis brevis muscle (PAS(LTP)), an LTD-like decrease (PAS(LTD)), or no change (PAS(Control)), respectively. The second PAS session 30 min later was always PAS(LTP). It induced an moderate LTP-like effect if conditioned by PAS(Control), which increased if conditioned by PAS(LTD), but decreased if conditioned by PAS(LTP). Effects on MEP amplitude induced by the second PAS session exhibited a negative linear correlation with those in the first PAS session. Because the two PAS sessions activate identical neuronal circuits, we conclude that 'homosynaptic-like' homeostatic mechanisms in accord with the BCM rule contribute to regulating plasticity in human M1.

Preconditioning tDCS facilitates subsequent tDCS effect on skill acquisition in older adults

“…The current study demonstrated that plastic changes in the corticospinal system largely follow the rule of homeostatic metaplasticity by showing greater corticospinal excitability increases in the C-A group compared to S-A group, which is in agreement with previous studies using tDCS (Christova et al 2015) and other forms of NIBS protocols in healthy young adults (Iyer et al 2003, Muller et al 2007, Murakami et al 2012, Siebner et al 2004). …”

“…It appears that the human motor system is regulated by homeostatic metaplasticity mechanisms (Muller et al 2007, Murakami et al 2012, Siebner et al 2004). According to the Bienenstock-Cooper-Munro (BCM) theory of homeostatic metaplasticity (Bienenstock et al 1982), plasticity at a synapse is bidirectional, resulting in either LTP or LTD.…”

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

“…The intensity of TMS was adjusted to SI 1mV in the resting APB when given without the preceding median nerve stimulus. To produce a long lasting LTP-like increase in MEP amplitude the interstimulus interval was equal to the individual N20-latency of the median nerve somatosensory-evoked cortical potential plus 2 ms (N20 þ 2 ms) (Müller et al, 2007). The mean ( ± SD) interstimulus interval was 21.9 ± 0.6 ms.…”

“…PAS LTP was performed according to a protocol originally described by (Stefan et al, (2000)) and later on slightly modified by our group (Müller et al, 2007;Müller-Dahlhaus et al, 2008). It consisted of 225 pairs of electrical stimulation of the right median nerve at the wrist followed by TMS delivered at a rate of 0.25 Hz (duration: 15 min).…”

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

“…Bipolar electrical stimulation of the right median nerve at the wrist (cathode proximal, constant-current square pulses of 1 ms duration, intensity of three times the perceptual sensory threshold) preceded TMS of the hand area of the left M1 by the individually determined latency of the median nerve somatosensory evoked early cortical potential (N20) plus 2 ms. This interstimulus interval resulted in previous studies in consistent and reproducible LTP-like plasticity, that is, a long-lasting (430 min) on average 1.5-fold increase in MEP amplitude (Müller et al, 2007;Jung and Ziemann, 2009;Heidegger et al, 2010). The TMS intensity was adjusted to elicit on average peak-to-peak MEP amplitudes of 1 mV (MEP 1 mV ) when TMS was given alone.…”