Timing-Dependent Modulation of Associative Plasticity by General Network Excitability in the Human Motor Cortex

Abstract

Associative neuroplasticity, which encompasses the modification of synaptic strength by coactivation of two synaptic inputs, has been linked to learning processes. Because unlimited plasticity destabilizes neuronal networks, homeostatic rules were proposed and experimentally proven that control for the amount and direction of plasticity dependent on background network activity. Accordingly, low background activity would enhance facilitatory plasticity, whereas high background activity would inhibit it.However, the impact of background excitability on associative plasticity has not been studied so far in humans. Facilitatory associative plasticity was induced by paired associative stimulation (PAS) in the human motor cortex, whereas background activity was enhanced or diminished by transcranial direct current stimulation (tDCS). When applied before PAS, excitability-enhancing tDCS also boosted the efficacy of PAS, whereas excitability-diminishing tDCS turned it into inhibition. Thus, previous background activity does not influence associative plasticity homeostatically. When tDCS and PAS were applied simultaneously, now in accordance with homeostatic rules of neuroplasticity, reduced background activity resulted in a prolonged excitability enhancement by PAS, whereas enhanced background activity turned it into inhibition. We conclude that background network activity can influence associative plasticity homeostatically. However, only simultaneous modulation of both parameters is in accordance with homeostatic concepts. These findings might be of importance for the development of plasticity-inducing stimulation protocols supporting information processing in humans.

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

“…As a consequence, the LTP-like increase in MEP amplitude of 1.71 ± 0.05 in the PBO condition is one of the largest reported in the literature (Wolters et al, 2003;Stefan et al, 2004;Ziemann et al, 2004;Nitsche et al, 2007). Therefore, one might argue that LTP-like plasticity was saturated already under PBO conditions and could not be enhanced any further.…”

“…The MEP increase is dose dependent, that is, its magnitude and duration scales with the number of stimulus pairs . It saturates at B160-170% (Stefan et al, 2004;Nitsche et al, 2007). The site of MEP increase is in the motor cortex because motor responses elicited by direct electrical stimulation of the corticospinal tract do not change (Stefan et al, 2000), whereas epidural recordings of the descending corticospinal volley at the level of the cervical spinal cord show a significant increase (Di Lazzaro et al, 2009).…”

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

“…The input-output relationship of corticospinal cells in human motor cortex can be shifted to the right or left by cortex polarization through cathodal or anodal transcranial direct current stimulation, respectively (Nitsche and Paulus, 2000). A shift to the right by cathodal stimulation abolished PAS LTP -induced LTP-like plasticity, while a shift to the left by anodal stimulation enhanced it (Nitsche et al, 2007). Similarly, cathodal vs anodal stimulation of rat hippocampal slices respectively suppressed or enhanced subsequent LTP induction (Ranieri et al, 2012).…”

Chronic Enhancement of Serotonin Facilitates Excitatory Transcranial Direct Current Stimulation-Induced Neuroplasticity

“…These noninvasive brain stimulation tools induce prolonged cortical excitability changes (Nitsche et al, 2003b;Paulus, 2000, 2001;Stephan et al, 2000;Ziemann et al, 2008). tDCS induces non-focal plasticity via the primary mechanism of tonic subthreshold modulation of resting membrane potentials (Nitsche et al, 2007. Cathodal tDCS results in neural hyperpolarization and anodal tDCS elicits neural depolarization.…”