Release time ：2023-08-25
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Clinical Support Department of Shenzhen Yingchi Technology Co.,Ltd.
Transcranial Magnetic Stimulation (TMS) is increasingly used to explore the neurophysiological mechanisms of neurodevelopmental and neurodegenerative diseases throughout the life cycle and to treat a range of neurological and psychiatric disorders in children, adults and the elderly.
Different stimulation parameters and protocol types were used to explore or modulate specific neurophysiological mechanisms short-term/long-term.
However, the physiological and clinical effects of TMS depend not only on stimulation parameters, but also on how the brain receives and processes the stimulation. The degree and direction of the neurophysiological effects of TMS are influenced by the excitation state of the target cortical area and the degree of structural and functional connectivity of the target network. In childhood development and old age, these neurophysiological states vary considerably throughout the life cycle, such as the maturation of GABaergic and glutaminergic neurons in childhood and adolescence, changes in dopamine and hormones in adolescence, and reduced transmission of dopamine, serotonergic, and cholinergic later in life. As we age, the functional and structural connections of neural networks change. The internal resting brain oscillations change with age, which may affect the cortical receptivity to neural stimulation. Disease and/or injury can affect both the neurophysiological state of the target region and the functional and structural connectivity properties of the network. Careful consideration of how development, aging, and pathophysiology affect the response of these populations to TMS is critical.
In this article, based on Oberman et al.'s "Transcranial Magnetic Stimulation Across the Lifespan: Impact of Developmental and Degenerative Processes" published in "Biological Psychiatry" (IF=10.6) in July 2023, it summarizes the influence of neurodevelopment on TMS detection indicators and rTMS treatment.
①Resting motor threshold (RMT) and MEP: Compared with adults, monopulse TMS of primary motor cortex in children show higher RMT, which may be due to the development of myelin sheath of corticospinal tract. Despite the need for higher stimulation intensity, MEP in children are typically smaller, latency delayed, and polyphasic compared to adults.
②N100 component of TMS-evoked EEG potentials (TEPs): TMS-EEG evaluation of children's skin layer excitability was found, the global mean field power (GMFP) decreased, and the N100 amplitude decreased.
①CSP: One study found that children's CSP was shorter, while other studies did not find age-related changes. Part of the reason for the difference may be that children's and adults' exercise thresholds are different, resulting in different effective stimulus doses.
②SICI: Early studies of pulsed pulses showed a decrease in SICI, while a recent study found that there was no age effect when the interval stimulation time was determined alone.
③LTP-iTBS: Existing studies used single-phase θ burst stimulation (Theta Burst Stimulation, TBS), and reported high inter-individual variability, with no significant age effect for children aged 8-17 years.
Many neurodevelopmental and childhood neuropsychiatric disorders may be characterized by abnormal cortical and subcortical excitability and/or dysfunctional network connectivity. TMS in combination with EMG/EEG has been used to explore these mechanisms to identify potential diagnostic and predictive biomarkers and to intervene with rTMS in combination with other therapeutic approaches.
Pathophysiological theory of ASD suggests that there is an imbalance between excitatory/inhibitory and plasticity/synaptic plasticity mechanisms; However, earlier studies of adolescents and young adults with ASD have found that:
①MT, input-output curves, CSP duration, SICI or ICF: no differences compared to normally developing controls.
②Interhemispheric signal propagation (ISP): TMS-EEG studies have shown that children with ASD show typical developmental features of ISP, a measure of interhemispheric connectivity, with no association between ISP and behavioral symptoms.
③LTP-TBS: TBS has greater and longer-lasting effects on motor cortex excitability in children with ASD. Abnormal changes become more pronounced with age.
④LTP-PAS: LTP-like plasticity in ASD is reduced with PAS, independent of GABAergic SICI indicators.
Various rTMS protocols have been tested in ASD.
①Improve social relationships and reduce repetitive behaviors: low-frequency rTMS stimulates the dorsolateral prefrontal cortex (DLPFC), and iTBS stimulates the posterior superior temporal cortex (pSTS). Higher IQ, better baseline sociocognitive performance, less social impairment, less baseline ASD symptoms, and less attention deficit hyperactivity disorder severity predict better responses to pSTS-stimulated social relationships.
②Improvement of executive function, irritability, hyperactivity and concurrent depression: low-frequency stimulation of the DLPFC.
③Improved sensorimotor integration: 8Hz rTMS stimulates the premotor cortex.
④Improving adaptive behavior: 5Hz rTMS stimulation of right inferior frontal gyrus stimulation combined with movement observation and execution.
Children with ADHD and TS have deficits in response inhibition and motor control.
①RMT, MEP amplitude, CSP: no difference.
②ICF: Early studies have shown that there is no difference. A recent study showed that ICF was enhanced when the stimulation interval was 15 ms and the CSP duration was longer.
③ISP: Consistent with deficits in inhibitory control and dysfunctional network connectivity, ISP latencies and ipsilateral cortical resting-period latencies were prolonged and ISP durations were shortened. ISP duration and latency did not correlate with age or symptom severity.
④SICI: Attenuated, negatively correlated with symptom severity and Motor Impairment Scale scores.
⑤N100: One study found that children with ADHD had smaller TMS-evoked N100 potentials and shorter latencies, but this was not confirmed by subsequent studies. When assessed on the N100 of concurrent tasks, children with ADHD showed diminished modulation of response readiness or motor execution, which decreased with age. A recent study found that rTMS at 1 Hz resulted in an unexpected decrease in TMS-evoked N100 amplitude.
①CSP: Shortened, it was not related to the severity of clinical symptoms.
②RMT: Earlier studies showed no difference, independent of clinical symptom severity. A recent study showed that children with TS have higher RMTS, shallower input-output curves with increasing intensity, and normalize with age.
③SICI: Decreased, and was negatively correlated with the severity of convulsions.
The literature on rTMS treatment for ADHD and TS also varies in terms of protocol and efficacy.
①Improving inattention and hyperactivity/impulsivity in children with ADHD: 1Hz rTMS stimulates the left DLPFC. However, 10Hz stimulation of the right DLPFC did not significantly improve ADHD symptoms compared to sham stimulation.
②Improve the severity of TS symptoms: 1Hz rTMS or cTBS to suppress the auxiliary motor area (SMA).
①ICF: Single-pulse and paired-pulse patterns showed enhanced ICF.
②RMT、CSP: no difference. RMT has a significant age effect. Shorter CSP durations (weakened inhibition) were associated with higher depression scores.
③SICI: A recent study found that SICI decreased before antidepressant treatment and that increases in SICI were associated with improvements in symptom severity at follow-up.
④LICI: There is a significant age effect. Lower LICI(reduced inhibition) is indicative of unresponsiveness to fluoxetine treatment.
⑤N100 and P200: When TMS stimulates DLPFC of depressed adolescents, TMS induced cerebral electrocortical inhibition and increase of N100 and P200, but not in inferior parietal lobule (IPL) or motor cortex. Anhedonia was negatively correlated with P200 amplitude.
⑥N45(Marker of GABA-A neurotransmission): Baseline N45 at frontal lobe sites predicted clinical treatment response, and modulation of N45 potentials on the IPL correlated with the degree of functional connectivity between the DLPFC and the IPL.
Early case reports and small open-label trials have shown promising efficacy of rTMS for the treatment of adolescent depression, with mean reductions in depressive symptoms ranging from 23-71%. Most of the studies mainly mimicked adult studies with 10 Hz rTMS stimulation of the left DLPFC.
1.This content is organized by the Clinical Support Department of Shenzhen Yingchi Technology Co.,Ltd. Criticisms and corrections are welcome. For reprint, please indicate the source.
2.Reference: Oberman, Lindsay M., & Benussi, Alberto.. (2023). Transcranial Magnetic Stimulation Across the Lifespan: Impact of Developmental and Degenerative Processes. Biological psychiatry.
