TMS and neocortical neurons: an integrative review on the micro-macro connection in neuroplasticity.

Tian D, Izumi S. TMS and neocortical neurons: an integrative review on the micro-macro connection in neuroplasticity. Jpn J Compr Rehabil Sci 2023; 14: 1-9. Neuroplasticity plays a pivotal role in neuroscience and neurorehabilitation as it bridges the organization and reorganization properties of the brain. Among the numerous neuroplastic protocols, transcranial magnetic stimulation (TMS) is a well-established non-invasive protocol to induce plastic changes in the brain. Here, we review the findings of four plasticity-inducing TMS protocols in the human motor cortex with relatively evident mechanisms: conventional repetitive TMS (rTMS), theta-burst stimulation (TBS), quadripulse stimulation (QPS) and paired associative stimulation (PAS). Based on the reviewed evidence and a preliminary TMS neurocytological model proposed in our previous report, we further integrate the neurophysiological evidence and plasticity rules of these protocols to present an updated micro-macro connection model between neocortical neurons and the neurophysiological evidence in TMS. This prototypical model will guide further efforts to understand the neural circuit of the motor cortex, the mechanisms of TMS, and the advance of neuroplasticity technologies and their outcomes.

Different effects of I-wave periodicity repetitive TMS on motor cortex interhemispheric interaction.

Background: Activity of the neural circuits in the human motor cortex can be probed using transcranial magnetic stimulation (TMS). Changing TMS-induced current direction recruits different cortical neural circuits. I-wave periodicity repetitive TMS (iTMS) substantially modulates motor cortex excitability through neural plasticity, yet its effect on interhemispheric interaction remains unclear. Objective: To explore the modulation of interhemispheric interaction by iTMS applied in different current directions. Materials and Methods: Twenty right-handed healthy young volunteers (aged 27.5 ± 5.0 years) participated in this study with three visits. On each visit, iTMS in posterior-anterior/anterior-posterior direction (PA-/AP-iTMS) or sham-iTMS was applied to the right hemisphere, with corticospinal excitability and intracortical facilitation of the non-stimulated left hemisphere evaluated at four timepoints. Ipsilateral silent period was also measured at each timepoint probing interhemispheric inhibition (IHI). Results: PA- and AP-iTMS potentiated cortical excitability concurrently in the stimulated right hemisphere. Corticospinal excitability of the non-stimulated left hemisphere increased 10 min after both PA- and AP-iTMS intervention, with a decrease in short-interval intracortical facilitation (SICF) observed in AP-iTMS only. Immediately after the intervention, PA-iTMS tilted the IHI balance toward inhibiting the non-stimulated hemisphere, while AP-iTMS shifted the balance toward the opposite direction. Conclusions: Our findings provide systematic evidence on the plastic modulation of interhemispheric interaction by PA- and AP-iTMS. We show that iTMS induces an interhemispheric facilitatory effect, and that PA- and AP-iTMS differs in modulating interhemispheric inhibition.

Interhemispheric Facilitatory Effect of High-Frequency rTMS: Perspective from Intracortical Facilitation and Inhibition.

The activity of excitatory and inhibitory neural circuits in the motor cortex can be probed and modified by transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS), noninvasively. At present, not only has a consensus regarding the interhemispheric effect of high frequency rTMS not been reached, but the attributes of these TMS-related circuits are also poorly understood. To address this question comprehensively, we integrated a single- and paired-pulse TMS evaluation with excitatory 20-Hz rTMS intervention in order to probe the interhemispheric effect on the intracortical circuits by high-frequency rTMS. In the rest state, after 20-Hz rTMS, a significant increase of single-pulse MEP and paired-pulse intracortical facilitation (ICF) in the non-stimulated hemisphere was observed with good test-retest reliability. Intracortical inhibition (measured by the cortical silent period) in the unstimulated hemisphere also increased after rTMS. No significant time-course change was observed in the sham-rTMS group. The results provide the evidence that 20-Hz rTMS induced a reliable interhemispheric facilitatory effect. Findings from the present study suggest that the glutamatergic facilitatory system and the GABAergic inhibitory system may vary synchronously.

Transcranial Magnetic Stimulation and Neocortical Neurons: The Micro-Macro Connection.

Understanding the operation of cortical circuits is an important and necessary task in both neuroscience and neurorehabilitation. The functioning of the neocortex results from integrative neuronal activity, which can be probed non-invasively by transcranial magnetic stimulation (TMS). Despite a clear indication of the direct involvement of cortical neurons in TMS, no explicit connection model has been made between the microscopic neuronal landscape and the macroscopic TMS outcome. Here we have performed an integrative review of multidisciplinary evidence regarding motor cortex neurocytology and TMS-related neurophysiology with the aim of elucidating the micro-macro connections underlying TMS. Neurocytological evidence from animal and human studies has been reviewed to describe the landscape of the cortical neurons covering the taxonomy, morphology, circuit wiring, and excitatory-inhibitory balance. Evidence from TMS studies in healthy humans is discussed, with emphasis on the TMS pulse and paradigm selectivity that reflect the underlying neural circuitry constitution. As a result, we propose a preliminary neuronal model of the human motor cortex and then link the TMS mechanisms with the neuronal model by stimulus intensity, direction of induced current, and paired-pulse timing. As TMS bears great developmental potential for both a probe and modulator of neural network activity and neurotransmission, the connection model will act as a foundation for future combined studies of neurocytology and neurophysiology, as well as the technical advances and application of TMS.

Modulation of Interhemispheric Inhibition between Primary Motor Cortices Induced by Manual Motor Imitation: A Transcranial Magnetic Stimulation Study.

Imitation has been proven effective in motor development and neurorehabilitation. However, the relationship between imitation and interhemispheric inhibition (IHI) remains unclear. Transcranial magnetic stimulation (TMS) can be used to investigate IHI. In this study, the modification effects of IHI resulting from mirror neuron system (MNS) activation during different imitations are addressed. We measured IHI between homologous primary motor cortex (M1) by analyzing the ipsilateral silent period (iSP) evoked by single-pulse focal TMS during imitation and analyzed the respective IHI modulation during and after different patterns of imitation. Our main results showed that throughout anatomical imitation, significant time-course changes of iSP duration through the experiment were observed in both directions. iSP duration declined from the pre-imitation time point to the post-imitation time point and did not return to baseline after 30 min rest. We also observed significant iSP reduction from the right hemisphere to the left hemisphere during anatomical and specular imitation, compared with non-imitative movement. Our findings indicate that using anatomical imitation in action observation and execution therapy promotes functional recovery in neurorehabilitation by regulating IHI.