title: LTP-like changes induced by paired associative stimulation of the primary somatosensory cortex in humans: source analysis and associated changes in behaviour.
abstract: Paired associative stimulation (PAS), which combines repetitive peripheral nerve stimulation with transcranial magnetic stimulation (TMS), may induce neuroplastic changes in somatosensory cortex (S1), possibly by long-term potentiation-like mechanisms. We used multichannel median nerve somatosensory evoked potential (MN-SSEP) recordings and two-point tactile discrimination testing to examine the location and behavioural significance of these changes. When TMS was applied to S1 near-synchronously to an afferent signal containing mechanoreceptive information, MN-SSEP changes (significant at 21-31 ms) could be explained by a change in a tangential source located in Brodmann area 3b, with their timing and polarity suggesting modification of upper cortical layers. PAS-induced MN-SSEP changes between 28 and 32 ms were linearly correlated with changes in tactile discrimination. Conversely, when the near-synchronous afferent signal contained predominantly proprioceptive information, PAS-induced MN-SSEP changes (20-29 ms) were shifted medially, and tactile performance remained stable. With near-synchronous mechanoreceptive stimulation subtle differences in the timing of the two interacting signals tended to influence the direction of tactile performance changes. PAS performed with TMS delivered asynchronously to the afferent pulse did not change MN-SSEPs. Hebbian interaction of mechanoreceptive afferent signals with TMS-evoked activity may modify synaptic efficacy in superficial cortical layers of Brodmann area 3b and is associated with timing-dependent and qualitatively congruent behavioural changes.
authors.affiliation: Human Cortical Physiology and Motor Control Laboratory, Department of Neurology, University of Wuerzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Litvak
authors.forename: Daniel
authors.initials: D
authors.lastname: Zeller
authors.forename: Robert
authors.initials: R
authors.lastname: Oostenveld
authors.forename: Eric
authors.initials: E
authors.lastname: Maris
authors.forename: Ayala
authors.initials: A
authors.lastname: Cohen
authors.forename: Axel
authors.initials: A
authors.lastname: Schramm
authors.forename: Reinhard
authors.initials: R
authors.lastname: Gentner
authors.forename: Menashe
authors.initials: M
authors.lastname: Zaaroor
authors.forename: Hillel
authors.initials: H
authors.lastname: Pratt
authors.forename: Joseph
authors.initials: J
authors.lastname: Classen
mesh_terms: D000328:Adult; D000344:Afferent Pathways / Q000033:anatomy & histology / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D005073:Evoked Potentials, Somatosensory / Q000502:physiology*; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D012684:Sensory Thresholds / Q000502:physiology; D013003:Somatosensory Cortex / Q000033:anatomy & histology / Q000502:physiology*; D014110:Touch / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods