Induction of plasticity in the human motor cortex by paired associative stimulation

Abstract

Current models of motor cortical plasticity, developed in studies on experimental animals, emphasize the importance of the conjoint activity of somatosensory afferents and intrinsic motor cortical circuits. The hypothesis that an enduring change in excitability in the cortical output circuitry can be induced in the human motor cortex by a paired-stimulation protocol was tested. Low-frequency median nerve stimulation was paired with transcranial magnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB). This protocol induced an increase in the amplitudes of the motor evoked potentials (MEPs) in the resting APB as well as a prolongation of the silent period measured in the precontracted APB following TMS; amplitudes of MEPs measured in voluntary contraction remained unchanged. Experiments testing the excitability of spinal motoneurons using F-wave studies and electrical stimulation of the brainstem suggested that the site of the plastic changes was within the motor cortex. The increases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation in that they were present when events elicited by afferent and magnetic stimulation were synchronous at the level of the motor cortex. Plasticity induced by paired stimulation evolved rapidly (within 30 min), was persistent (minimum duration 30-60 min) yet reversible, and was topographically specific. This combination of features and the similarity to properties of induced enduring changes in synaptic efficacy, as elucidated in animal studies, leads us to propose that the induced plasticity may represent a signature of associative long-term potentiation of cortical synapses or closely related neuronal mechanisms in the human cortex.

Altered paired associative stimulation‐induced plasticity in NMDAR encephalitis

“…Furthermore, 15 min after the protocol, 10 MEP were performed for follow‐up analyses. As described before,8, 10 we used paired stimulation of the ulnar nerve (electrical stimulation with 300% of individual sensory threshold) and the hotspot of the ipsilateral FDI over the motor cortex. The interstimulus interval was set at 25 msec, which has been proven to be robust for inducing increased cortical excitability 8.…”

“…In humans, LTP‐like cortical plasticity can be assessed using peripheral electric stimulation and subsequent TMS. This so‐called PAS8 is now a widely used protocol to noninvasively investigate rapid‐onset cortical plasticity in healthy subjects and neurological patients 9, 10, 11, 12. Importantly, it has been shown to predominantly reflect NMDAR function,8, 13, 14 whereas MEP and motor threshold (MT) are relatively independent from NMDAR function 4, 8, 13, 15, 16, 17…”

Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex

“…The plastic changes arising from PAS are quantified indirectly by comparing the size of the motor evoked potential (MEP) evoked with TMS before and after PAS (Stefan et al, 2000). The duration of the PASinduced change in MEP amplitude persists for up to 30-90 minutes after stimulation (Stefan et al, 2000;Wischnewski & Schutter, 2015).…”

“…Although several variants of PAS have been developed, the repeated pairing of the stimuli is invariably predictable and rhythmic. For example, in the seminal study that first described PAS, Stefan et al (2000) delivered ninety…”

“…LTPlike changes can be induced in humans using non-invasive brain stimulation. Paired associative stimulation (PAS) repeatedly pairs a peripheral electrical nerve stimulus targeting an intrinsic hand muscle with transcranial magnetic stimulation (TMS) over the motor cortical region representing that muscle (Stefan, Kunesch, Cohen, Benecke, & Classen, 2000). When the timing of these two stimuli is adjusted such that the afferent volley arising from the electrical nerve stimulus arrives in the motor cortex just before a TMS pulse depolarizes the M A N U S C R I P T…”