RESUMEN

The hippocampus is a fundamental cortical structure in the memory process of encoding, retaining, and recalling information. Transcranial Magnetic Stimulation (TMS) following a Paired Associative Stimulation (PAS) enhances nervous system excitability and promotes cortical plasticity mechanisms by synchronizing two stimuli in the same neural pathway. However, PAS has not been shown to improve memorization capacity yet. Here, we present an innovative protocol stemming from the PAS paradigm, which combines single-pulse TMS to the hippocampus with endogenous hippocampal activity during a working memory (WM) task. 96 volunteers were randomized across one experimental group and three parallel groups (motor cortex stimulation, sham stimulation, and no stimulation) in a single session. This combined-stimuli configuration resulted in an increased memorization capacity in the WM task, which was dependent on the stimulated brain location and subjects' basal memory performance. These results are potentially significant for clinical research on memory dysfunction and its related neurological disorders. Future research on paired associative or combined stimulation is required to unveil stimulation-derived neural mechanisms that enhance the ability to memorize.

Asunto(s)

Plasticidad Neuronal , Estimulación Magnética Transcraneal , Humanos , Encéfalo , Potenciales Evocados Motores/fisiología , Hipocampo , Plasticidad Neuronal/fisiología , Estimulación Magnética Transcraneal/métodos

RESUMEN

OBJECTIVE: Cortico-cortical paired associative stimulation (ccPAS) is a form of dual-site transcranial magnetic stimulation (TMS) entailing a series of single-TMS pulses paired at specific interstimulus intervals (ISI) delivered to distant cortical areas. The goal of this article is to systematically review its efficacy in inducing plasticity in humans focusing on stimulation parameters and hypotheses of underlying neurophysiology. METHODS: A systematic review of the literature from 2009-2023 was undertaken to identify all articles utilizing ccPAS to study brain plasticity and connectivity. Six electronic databases were searched and included. RESULTS: 32 studies were identified. The studies targeted connections within the same hemisphere or between hemispheres. 28 ccPAS studies were in healthy participants, 1 study in schizophrenia, and 1 in Alzheimer's disease (AD) patients. 2 additional studies used cortico-cortical repetitive paired associative stimulation (cc-rPAS) in generalized anxiety disorder (GAD) patients. Outcome measures include electromyography (EMG), behavioral measures, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). ccPAS seems to be able to modulate brain connectivity depending on the ISI. CONCLUSIONS: ccPAS can be used to modulate corticospinal excitability, brain activity, and behavior. Although the stimulation parameters used across studies reviewed in this paper are varied, ccPAS is a promising approach for basic research and potential clinical applications. SIGNIFICANCE: Recent advances in neuroscience have caused a shift of interest from the study of single areas to a more complex approach focusing on networks of areas that orchestrate brain activity. Consequently, the TMS community is also witnessing a change, with a growing interest in targeting multiple brain areas rather than a single locus, as evidenced by an increasing number of papers using ccPAS. In light of this new enthusiasm for brain connectivity, this review summarizes existing literature and stimulation parameters that have proven effective in changing electrophysiological, behavioral, or neuroimaging-derived measures.

Asunto(s)

Corteza Motora , Humanos , Potenciales Evocados Motores/fisiología , Estimulación Magnética Transcraneal/métodos , Encéfalo/diagnóstico por imagen , Plasticidad Neuronal/fisiología

RESUMEN

Transcranial Magnetic Stimulation (TMS) can be used to modulate cortico-spinal excitability following a paired associative stimulation (PAS) protocol. Movement-related cortical stimulation (MRCS) is a PAS protocol based on the synchronization of a single-pulse TMS with a movement task. However, plasticity and motor performance potentiation due to MRCS has been related exclusively to single-movement tasks. In order to unveil the effects of an MRCS protocol in complex movements, we applied PAS synchronized with a movement-related dynamic task (MRDT) with a customized video game. In 22 healthy subjects, we measured the reaction time (RT), trajectory error (TE), and the number of collected and avoided items when playing the custom video game to evaluate the task motor performance. Moreover, we assessed the recruitment curve of Motor Evoked Potentials (MEPs) with five different intensities to evaluate the motor corticospinal excitability. MEPs were recorded in Abductor Pollicis Brevis (APB) and Abductor Digiti Minimi (ADM), before, right after, and 30 min after the PAS intervention, in an active versus sham experimental design. The MRCS PAS intervention resulted in RT reduction, and motor corticospinal excitability was modulated, reflected as significant MEP amplitude change at 110% RMT intensity in ADM and at 130% RMT intensity in APB. RTs and ADM MEP amplitudes correlated positively in specific time and intensity assessments. We conclude that the proposed PAS protocol facilitated RT performance in a complex task. This phenomenon might be useful to develop neurorehabilitation strategies with complex movements, similar to activities of daily living.