Timing‐dependent plasticity in human primary somatosensory cortex

Abstract

Animal experiments suggest that cortical sensory representations may be remodelled as a consequence of changing synaptic efficacy by timing-dependent associative neuronal activity. Here we describe a timing-based associative form of plasticity in human somatosensory cortex. Paired associative stimulation (PAS) was performed by combining repetitive median nerve stimulation with transcranial magnetic stimulation (TMS) over the contralateral postcentral region. PAS increased exclusively the amplitude of the P25 component of the median nerve-evoked somatosensory-evoked potential (MN-SSEP), which is probably generated in the superficial cortical layers of area 3b. SSEP components reflecting neuronal activity in deeper cortical layers (N20 component) or subcortical regions (P14 component) remained constant. PAS-induced enhancement of P25 amplitude displayed topographical specificity both for the recording (MN-SSEP versus tibial nerve-SSEP) and the stimulation (magnetic stimulation targeting somatosensory versus motor cortex) arrangements. Modulation of P25 amplitude was confined to a narrow range of interstimulus intervals (ISIs) between the MN pulse and the TMS pulse, and the sign of the modulation changed with ISIs differing by only 15 ms. The function describing the ISI dependence of PAS effects on somatosensory cortex resembled one previously observed in motor cortex, shifted by approximately 7 ms. The findings suggest a simple model of modulation of excitability in human primary somatosensory cortex, possibly by mechanisms related to the spike-timing-dependent plasticity of neuronal synapses located in upper cortical layers.

Modulation of somatosensory evoked potentials using transcranial magnetic intermittent theta burst stimulation

“…Long lasting effects on cortical excitability have also been described after repeated pairings of a TMS pulse with somatosensory input, a procedure termed paired associative stimulation (PAS) (Wolters et al, 2005).…”

“…In contrast, Wolters et al (2005) used a paired associative method of conditioning the cortex. Repeated pairings of median nerve stimulation with a TMS pulse over sensory cortex increased the SEP if the interstimulus interval was N20 latency; there was no effect if the TMS stimulus was given over M1.…”

Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients

“…This is not surprising, because PAS specifically targeted the motor tracts. It remains to be seen whether long-term PAS protocols can be developed to also target the sensory tracts 28 in SCI patients.…”

State-Dependent and Timing-Dependent Bidirectional Associative Plasticity in the Human SMA-M1 Network

“…This rationale is based on short-latency, likely mono-synaptic excitatory input from SMA-proper to M1 corticospinal neurons (peaking at 2 ms and 4 -6 ms) in monkey intracortical microstimulation experiments (Tokuno and Nambu, 2000) and paired-coil experiments from our group, which showed MEP facilitation if stimulation of SMA-proper preceded a TMS test pulse over M1 by 6 ms (N. Arai, M.-K. Lu, Y. Ugawa, and U. Ziemann, unpublished data). The ISIs of Ϫ3.2 ms and ϩ10 ms were selected because conventional PAS experiments pairing electrical peripheral nerve stimulation with TMS of the contralateral M1 or primary somatosensory cortex had demonstrated a steep transition from a maximum long-term facilitation to maximum depression within a time window of 15-20 ms (Wolters et al, 2003(Wolters et al, , 2005. If this time window also applied to PAS-induced plasticity in the SMA-M1 network, then these intervals, which are intermediate to Ϫ6 ms and ϩ15 ms, should be less effective in inducing long-term MEP change.…”