Augmenting LTP-Like Plasticity in Human Motor Cortex by Spaced Paired Associative Stimulation

Abstract

Paired associative stimulation (PASLTP) of the human primary motor cortex (M1) can induce LTP-like plasticity by increasing corticospinal excitability beyond the stimulation period. Previous studies showed that two consecutive PASLTP protocols interact by homeostatic metaplasticity, but animal experiments provided evidence that LTP can be augmented by repeated stimulation protocols spaced by ~30min. Here we tested in twelve healthy selected PASLTP responders the possibility that LTP-like plasticity can be augmented in the human M1 by systematically varying the interval between two consecutive PASLTP protocols. The first PASLTP protocol (PAS1) induced strong LTP-like plasticity lasting for 30-60min. The effect of a second identical PASLTP protocol (PAS2) critically depended on the time between PAS1 and PAS2. At 10min, PAS2 prolonged the PAS1-induced LTP-like plasticity. At 30min, PAS2 augmented the LTP-like plasticity induced by PAS1, by increasing both magnitude and duration. At 60min and 180min, PAS2 had no effect on corticospinal excitability. The cumulative LTP-like plasticity after PAS1 and PAS2 at 30min exceeded significantly the effect of PAS1 alone, and the cumulative PAS1 and PAS2 effects at 60min and 180min. In summary, consecutive PASLTP protocols interact in human M1 in a time-dependent manner. If spaced by 30min, two consecutive PASLTP sessions can augment LTP-like plasticity in human M1. Findings may inspire further research on optimized therapeutic applications of non-invasive brain stimulation in neurological and psychiatric diseases.

The effect of stimulation interval on plasticity following repeated blocks of intermittent theta burst stimulation

“…Previous studies report that plasticity is blocked following 5 minute interval spaced iTBS [20], and facilitated/prolonged with either 10 minute intervals [37] or 3 blocks of 15 minute intervals [38]. Furthermore, repeated blocks of facilitatory paired associative stimulation, another TMS paradigm which induces LTP-like plasticity, prolongs plasticity duration [39]. In contrast, several studies have reported blocking or reversal of plasticity following repeated iTBS intervals at 15 [34], 20 [20] and 25 minutes [36].…”

Increasing motor cortex plasticity with spaced paired associative stimulation at different intervals in older adults

“…As Muller‐Dahlhaus et al . () reported homoeostatic interactions at longer IPIs in young subjects, we expected that older adults would show homoeostatic metaplasticity at the 30‐min interval. However, based on our own previous findings, we expected that metaplastic interactions would be reduced in older adults at the 10‐min interval.…”

“…In particular, a recent study in young subjects has shown that the time interval between priming and test blocks of PAS (i.e. the inter‐PAS interval; IPI) is a key factor in determining the nature of metaplastic interactions, with two consecutive sessions of PAS separated by 30 min being most effective at augmenting LTP‐like plasticity (Muller‐Dahlhaus et al ., ). It is currently unknown whether changing the interval between the priming and test NIBS interventions can augment plasticity induction in older adults, with the possibility that there is a change in the temporal dependency of metaplastic effects in the elderly.…”

Brain–machine interfaces for rehabilitation of poststroke hemiplegia

“…For instance, paired associative stimulation involving the repeated pairing of peripheral nerve stimulation and TMS over M1 operates with spiketiming-dependent plasticity (M€ uller-Dahlhaus et al, 2015), such that increases in corticospinal excitability occur when the neural spikes transmitted through the peripheral nerves and the neural activity elicited by TMS coincide temporally in the cortex (Carson and Kennedy, 2013). In the context of BMI motor rehabilitation training in which regulation of SMR-ERD is linked with sensory feedback, Hebbian (timing dependent) plasticity might strengthen the synaptic links between the compromised afferent and efferent pathways.…”