Noninvasive Associative Plasticity Induction in a Corticocortical Pathway of the Human Brain

Abstract

Coincident pairing of presynaptic and postsynaptic activity selectively strengthens synaptic connections, a key mechanism underlying cortical plasticity. Using paired associative transcranial magnetic stimulation (TMS), we demonstrate selective potentiation of physiological connectivity between two human brain regions, ventral premotor cortex (PMv) and primary motor cortex (M1) after repeated paired-pulse TMS of PMv and M1. The effect was anatomically specific: paired stimulation of the presupplementary motor area and M1 did not induce changes in PMv-M1 pathway connectivity. The effect was dependent on stimulation order: repeated stimulation of PMv before M1 led to strengthening of the PMv-M1 pathway, while repeated stimulation of M1 before PMv diminished the strength of the PMv-M1 pathway. The expression of the change in the pathway depended on the cognitive state of the subject at the time of testing: when the subject was tested at rest, paired PMv-M1 stimulation led to an increased inhibitory influence of PMv over M1, but when the subject was tested while engaged in a visuomotor task, PMv-M1 stimulation led to an increased facilitatory influence of PMv over M1. Plasticity evolved rapidly, lasted for at least 1 h, and began to reverse 3 h after intervention.

Improving the Potential of Neuroplasticity

“…They then sought to induce plastic change in this connection by repetitively delivering 90 pairs of pulses (one pair every 10 s) with the same interstimulus interval (ISI) and the same coil positions. Buch et al (2011) found that stimulating PMv and M1 with an ISI of 8 ms significantly potentiated the inhibitory effect in the PMv-M1 paired-pulse paradigm, as the test-MEP size was reduced significantly. The effects of the PAS on functional connectivity were present for up to 1 h after intervention and reverted back to baseline at 3 h.…”

“…Buch et al (2011) asked whether paired associative stimulation (PAS) of interconnected areas of the cortex via noninvasive transcranial magnetic stimulation (TMS) might selectively induce Hebbian-like plasticity in a specific anatomical pathway in humans.…”

“…Buch et al (2011) asked whether paired associative stimulation (PAS) of interconnected areas of the cortex via noninvasive transcranial magnetic stimulation (TMS) might selectively induce Hebbian-like plasticity in a specific anatomical pathway in humans.As introduced by Stefan and colleagues (2000), PAS is a plasticity-inducing protocol that pairs electrical stimulation of a median nerve with a TMS pulse over primary motor cortex (M1). The time interval between stimuli is crucial for induction of either potentiation-or depression-like plasticity effects.…”

“…They demonstrated that it is possible to induce lasting changes in paired-pulse interhemispheric motor inhibition and single-pulse-induced M1-MEP size in humans by using a modified PAS protocol that used two consecutive TMS pulses between left and right M1. To address whether such plasticity between interconnected cortical areas can be pathwayspecific, Buch et al (2011) used an established paired-pulse protocol (with an interstimulus interval of 8 ms) for probing physiological connectivity between ventral premotor cortex (PMv) and M1. A first conditioning TMS pulse is applied over PMv followed by a second test TMS pulse over M1.…”

“…Interestingly, Buch et al (2011) also tested whether the plasticity induced in the pathways depended on the cognitive state of the subject at the time of testing. Previous studies indicated that the effect of this connectivity depends on the cognitive state of the subject (Davare et al, 2009).…”