The associative brain at work: Evidence from paired associative stimulation studies in humans

Abstract

The original protocol of Paired Associative Stimulation (PAS) in humans implies repetitive cortical and peripheral nerve stimuli, delivered at specific inter-stimulus intervals, able to elicit non-invasively long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity in the human motor cortex. PAS has been designed to drive cortical LTP/LTD according to the Hebbian rule of associative plasticity. Over the last two decades, a growing number of researchers have increasingly used the PAS technique to assess cortical associative plasticity in healthy humans and in patients with movement disorders and other neuropsychiatric diseases. The present review covers the physiology, pharmacology, pathology and motor effects of PAS. Further sections of the review focus on new protocols of "modified PAS" and possible future application of PAS in neuromorphic circuits designed for brain-computer interface.

Toward the establishment of neurophysiological indicators for neuropsychiatric disorders using transcranial magnetic stimulation‐evoked potentials: A systematic review

“…[39][40][41] The PAS paradigm is based on the principle that was found in basic animal research of spike-timingdependent plasticity 118,119 ; specifically, it is a synaptic plasticity mechanism in which synaptic transmission is facilitated when presynaptic input precedes postsynaptic excitation (e.g., ISI of 21.5-25 ms), and transmission is inhibited when postsynaptic excitation precedes presynaptic input (e.g., ISI:~10 ms). [39][40][41] Huber et al examined the association between cortical plasticity as indexed by PAS using ISI of 25 or 10 ms and slow-wave sleep activity that is assumed to be associated with sleep need. They showed that PAS at an ISI of 25 ms led to long-term potentiation (LTP)-like changes in MEP and TEP, while PAS at ISI of 10 ms resulted in long-term depression (LTD)-like changes in MEP and TEP in areas both ipsilateral and contralateral to the stimulation site.…”

“…This paradigm is called 'paired associative stimulation' (PAS), which is thought to be related to cortical plasticity at the stimulation site. [39][40][41] While there have been many TMS-EMG studies targeting M1, TMS-EEG research that extends TMS neurophysiology to the dorsolateral prefrontal cortex (DLPFC) has gradually been implemented. [42][43][44][45][46] Thus, there are several review articles for TMS-EMG for M1, 47,48 but only a few review papers summarizing TMS-EEG research for the non-motor areas, such as the DLPFC.…”

“…Additionally, Garcia Dominguez et al analyzed the LICI TMS-EEG data for the M1 and DLPFC using both discrete Fourier transform, and Hilbert transform methods and demonstrated that the Hilbert transform method could detect more robust LICI inhibition in the time-frequency domain 111. Rogasch et al investigated TEP component variations (N45, P60, and N100) and TMS-evoked oscillations (alpha[8][9][10][11][12], lower beta[13][14][15][16][17][18][19][20], upper beta[21][22][23][24][25][26][27][28][29][30], gamma[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]) over the DLPFC in the LICI paradigm in healthy subjects. They indicated that LICI significantly suppressed all TEP components and TMS-evoked oscillations and that the N100 slope evoked by sp-TMS correlated with the N45 component and beta…”

Spinal associative plasticity in depth: evidence from animal model

“…More recently, a number of modified PAS protocols have been designed and tested in humans such as protocols able to promote plasticity in the spinal cord (Suppa et al . ). Spinal PAS might be in theory applied to harness plasticity for motor recovery in patients with various neurological disorders.…”

“…The original PAS protocol described in humans (Stefan et al 2000) consists of repetitive cortical and peripheral nerve stimuli delivered at specific interstimulus intervals (ISIs), able to elicit long-term potentiation (LTP)-and depression (LTD)like plasticity in the primary motor cortex (M1). More recently, a number of modified PAS protocols have been designed and tested in humans such as protocols able to promote plasticity in the spinal cord (Suppa et al 2017). Spinal PAS might be in theory applied to harness plasticity for motor recovery in patients with various neurological disorders.…”