title: Reversed timing-dependent associative plasticity in the human brain through interhemispheric interactions.
abstract: Spike timing-dependent plasticity (STDP) has been proposed as one of the key mechanisms underlying learning and memory. Repetitive median nerve stimulation, followed by transcranial magnetic stimulation (TMS) of the contralateral primary motor cortex (M1), defined as paired-associative stimulation (PAS), has been used as an in vivo model of STDP in humans. PAS-induced excitability changes in M1 have been repeatedly shown to be time-dependent in a STDP-like fashion, since synchronous arrival of inputs within M1 induces long-term potentiation-like effects, whereas an asynchronous arrival induces long-term depression (LTD)-like effects. Here, we show that interhemispheric inhibition of the sensorimotor network during PAS, with the peripheral stimulation over the hand ipsilateral to the motor cortex receiving TMS, results in a LTD-like effect, as opposed to the standard STDP-like effect seen for contralateral PAS. Furthermore, we could show that this reversed-associative plasticity critically depends on the timing interval between afferent and cortical stimulation. These results indicate that the outcome of associative stimulation in the human brain depends on functional network interactions (inhibition or facilitation) at a systems level and can either follow standard or reversed STDP-like mechanisms.
authors: Max Planck Institute for Human Cognitive and Brain Sciences and Department of Neurology and Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany. conde@cbs.mpg.de
authors: Virginia
authors: V
authors: Conde
authors: Henning
authors: H
authors: Vollmann
authors: Marco
authors: M
authors: Taubert
authors: Bernhard
authors: B
authors: Sehm
authors: Leonardo G
authors: LG
authors: Cohen
authors: Arno
authors: A
authors: Villringer
authors: Patrick
authors: P
authors: Ragert
mesh_terms: D000293:Adolescent; D000328:Adult; D001244:Association; D005260:Female; D007839:Functional Laterality; D006225:Hand / Q000294:innervation / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology; D013003:Somatosensory Cortex / Q000502:physiology*; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation
keywords: interhemispheric inhibition; paired-associative stimulation; primary motor cortex; primary somatosensory cortex; spike timing-dependent plasticity