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Involvement of different neuronal components in the induction of cortical plasticity with associative stimulation.

ABSTRACT: BACKGROUND:Paired associative stimulation (PAS), with stimulus interval of 21.5 or 25?ms, using transcranial magnetic stimulation in the posterior-anterior (PA) current direction, produces a long-term-potentiation-like effect. Stimulation with PA directed current generates both early and late indirect (I)-waves while that in anterior-posterior (AP) current predominantly elicits late I-waves. Short interval intracortical inhibition (SICI) inhibits late I-waves but not early I-waves. OBJECTIVE:To investigate how cortical inhibition modulates the effects of PAS. METHODS:PAS at stimulus interval of 21.5?ms conditioned by SICI (SICI-PAS) was compared to PAS alone with both PA and AP directed currents. RESULTS:PAS with both current directions increased cortical excitability. SICI-PAS increased cortical excitability in the PA but not the AP current direction. CONCLUSIONS:Both early and late I-waves circuits can mediate cortical PAS plasticity under different conditions. Plasticity induction with the late but not the early I-wave circuits is blocked by SICI.

SUBMITTER: Ni Z

PROVIDER: S-EPMC6301109 | biostudies-literature | 2019 Jan - Feb

REPOSITORIES: biostudies-literature

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Involvement of different neuronal components in the induction of cortical plasticity with associative stimulation.

Ni Zhen Z Cash Robin F H RFH Gunraj Carolyn C Bercovici Eduard E Hallett Mark M Chen Robert R

Brain stimulation 20180905 1

<h4>Background</h4>Paired associative stimulation (PAS), with stimulus interval of 21.5 or 25 ms, using transcranial magnetic stimulation in the posterior-anterior (PA) current direction, produces a long-term-potentiation-like effect. Stimulation with PA directed current generates both early and late indirect (I)-waves while that in anterior-posterior (AP) current predominantly elicits late I-waves. Short interval intracortical inhibition (SICI) inhibits late I-waves but not early I-waves.<h4>Ob ...[more]

PMID: 30205951

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Project description:OBJECTIVE:To determine whether neurophysiological mechanisms indicating cortical excitability, long-term potentiation (LTP)-like plasticity, GABAergic and glutamatergic function are altered in patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and whether they can be helpful as markers of diagnostic assessment, disease progression, and potentially therapy response. METHODS:Neurophysiological characterizations of patients with NMDAR encephalitis (n = 34, mean age: 28 ± 11 years; 30 females) and age/gender-matched healthy controls (n = 27, 28.5 ± 10 years; 25 females) were performed using transcranial magnetic stimulation-derived protocols including resting motor threshold, recruitment curve, intracortical facilitation, short intracortical inhibition, and cortical silent period. Paired associative stimulation (PAS) was applied to assess LTP-like mechanisms which are mediated through NMDAR. Moreover, resting state functional connectivity was determined using functional magnetic resonance imaging. RESULTS:PAS-induced plasticity differed significantly between groups (P = 0.0056). Cortical excitability, as assessed via motor-evoked potentials after PAS, decreased in patients, whereas it increased in controls indicating malfunctioning of NMDAR in encephalitis patients. Lower PAS-induced plasticity significantly correlated with the modified Rankin Scale (mRS) (r = -0.41; P = 0.0031) and was correlated with lower functional connectivity within the motor network in NMDAR encephalitis patients (P < 0.001, uncorrected). Other neurophysiological parameters were not significantly different between groups. Follow-up assessments were available in six patients and demonstrated parallel improvement of PAS-induced plasticity and mRS. INTERPRETATION:Assessment of PAS-induced plasticity may help to determine NMDAR dysfunction and disease severity in NMDAR encephalitis, and might even aid as a sensitive, noninvasive, and well-tolerated "electrophysiological biomarker" to monitor therapy response in the future. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov: Identifier: NCT01865578.

Project description:Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cognition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China (approval No. TJ-A20151102) on July 11, 2015.

Project description:Human speech requires that new words are routinely memorized, yet neurocognitive mechanisms of such acquisition of memory remain highly debatable. Major controversy concerns the question whether cortical plasticity related to word learning occurs in neocortical speech-related areas immediately after learning, or neocortical plasticity emerges only on the second day after a prolonged time required for consolidation after learning. The functional spatiotemporal pattern of cortical activity related to such learning also remains largely unknown. In order to address these questions, we examined magnetoencephalographic responses elicited in the cerebral cortex by passive presentations of eight novel pseudowords before and immediately after an operant conditioning task. This associative procedure forced participants to perform an active search for unique meaning of four pseudowords that referred to movements of left and right hands and feet. The other four pseudowords did not require any movement and thus were not associated with any meaning. Familiarization with novel pseudowords led to a bilateral repetition suppression of cortical responses to them; the effect started before or around the uniqueness point and lasted for more than 500 ms. After learning, response amplitude to pseudowords that acquired meaning was greater compared with response amplitude to pseudowords that were not assigned meaning; the effect was significant within 144-362 ms after the uniqueness point, and it was found only in the left hemisphere. Within this time interval, a learning-related selective response initially emerged in cortical areas surrounding the Sylvian fissure: anterior superior temporal sulcus, ventral premotor cortex, the anterior part of intraparietal sulcus and insula. Later within this interval, activation additionally spread to more anterior higher-tier brain regions, and reached the left temporal pole and the triangular part of the left inferior frontal gyrus extending to its orbital part. Altogether, current findings evidence rapid plastic changes in cortical representations of meaningful auditory word-forms occurring almost immediately after learning. Additionally, our results suggest that familiarization resulting from stimulus repetition and semantic acquisition resulting from an active learning procedure have separable effects on cortical activity.

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Involvement of different neuronal components in the induction of cortical plasticity with associative stimulation.

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Involvement of different neuronal components in the induction of cortical plasticity with associative stimulation.

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