Transcranial Magnetic Stimulation (TMS) in Autism Spectrum Disorders

Index

TMS presents a promising, non-invasive intervention for modulating neurophysiological abnormalities associated with ASD.

ASD is a neurodevelopmental disorder characterized by:
- Difficulties in social communication and interaction
- Restricted, repetitive patterns of behavior, interests, or activities
- Sensory abnormalities
Highly heterogeneous in nature, with varying symptom expression and severity
Prevalence: Approximately 1 in 54 children (CDC, 2020)
Etiology: Multifactorial, involving genetic and environmental factors
Neuropathology:
- Abnormalities in brain development and neuronal migration
- Cortical dysplasias and minicolumnar abnormalities
- Alterations in gray-white matter boundaries

Non-invasive brain stimulation technique
Based on Faraday’s law of electromagnetic induction
Key components:
- Power supply and capacitors
- Stimulating coil (figure-8 or circular)
Process:
- Rapid discharge of current through the coil
- Generation of a time-varying magnetic field
- Induction of electric currents in underlying neural tissue
- Depth of penetration: Approximately 2-3 cm from the scalp
Types:
- Single-pulse TMS
- Paired-pulse TMS
- Repetitive TMS (rTMS)
- Low-frequency (≤1 Hz): Generally inhibitory
- High-frequency (≥5 Hz): Generally excitatory

A. Behavioral Changes
- Reduction in repetitive and stereotypic behaviors
- Improved social responsiveness
- Enhanced error monitoring and correction
- Decreased irritability and hyperactivity
B. Cognitive Functions
- Improved executive functioning
- Enhanced attention and working memory
- Better response inhibition
- Improved visual processing and perceptual binding
C. Neurophysiological Effects
- Modulation of cortical excitability
- Normalization of gamma oscillations
- Altered connectivity patterns (local and long-range)
- Changes in event-related potentials (ERPs)

Target areas:
- Dorsolateral prefrontal cortex (DLPFC)
- Inferior parietal lobule
- Temporoparietal junction
Protocols:
- Low-frequency rTMS (e.g., 1 Hz) to DLPFC
- High-frequency rTMS (e.g., 5-20 Hz) to various regions
- Duration: Typically 2-6 weeks, with daily or alternate-day sessions
- Session length: 20-40 minutes
- Number of pulses: 1000-3000 per session

Cortical inhibitory imbalance in ASD:
- Reduced GABAergic inhibition
- Altered excitatory/inhibitory (E/I) balance
Gamma oscillations (30-80 Hz):
- Associated with cognitive functions often impaired in ASD
- Abnormal in ASD (often increased power and reduced discrimination)
Parvalbumin-positive interneurons:
- Crucial for generating gamma oscillations
- Reduced in number in ASD
TMS effects on neural circuits:
- Modulation of local and long-range connectivity
- Potential normalization of E/I balance
- Alteration of synaptic plasticity

Generally considered safe when applied within established guidelines
Common side effects:
- Headache
- Scalp discomfort
- Transient changes in hearing
Rare but serious risks:
- Seizures (risk < 1% in normal populations)
Effectiveness:
- Promising results in multiple studies
- Variability in individual responses
- Long-term effects still under investigation

Casanova et al. (2020):
- Low-frequency rTMS to DLPFC decreased gamma power
- Increased differentiation between target and non-target stimuli
- Improved executive function and self-monitoring behaviors
Afshari et al. (2024):
- High-frequency rTMS in animal model of ASD
- Reduced oxidative stress and improved biochemical factors
- Increased dendritic spine density in hippocampus
Yang et al. (2023):
- rTMS strengthened long-range feedback connections
- Weakened short-range connections
- Corresponded with improvement in core ASD symptoms
Sokhadze et al. (2018):
- rTMS improved error monitoring (ERN) and post-error reaction time
- Reduced repetitive behaviors and irritability
Ni et al. (2017):
- Theta-burst stimulation to DLPFC and posterior superior temporal sulcus
- Improved social relating and motivation

Large-scale, multi-site clinical trials
Optimization of stimulation parameters:
- Frequency, intensity, duration, and target locations
Combination therapies:
- TMS with behavioral interventions
- TMS with neurofeedback
Personalized medicine approaches:
- Genetic profiling to predict responders
- Neuroimaging-guided targeting
Long-term follow-up studies:
- Durability of effects
- Need for maintenance sessions
Investigation of age-dependent effects:
- Optimal timing for intervention
- Safety and efficacy in younger children
Exploration of novel stimulation paradigms:
- Theta-burst stimulation
- Quadripulse stimulation
- Development of home-based TMS devices for more frequent application

TMS shows promise as a therapeutic intervention for ASD
Targets core pathophysiological features (e.g., E/I imbalance, gamma abnormalities)
Demonstrates improvements in behavior, cognition, and neurophysiology
Further research needed to optimize protocols and understand long-term effects
Potential to become an important tool in the multimodal treatment of ASD

References

Casanova, M. F., Shaban, M., Ghazal, M., El-Baz, A. S., Casanova, E. L., Opris, I., & Sokhadze, E. M. (2020). Effects of transcranial magnetic stimulation therapy on evoked and induced gamma oscillations in children with autism spectrum disorder. Brain Sciences, 10(7), 423. doi:10.3390/brainsci10070423
Afshari, M., Gharibzadeh, S., Pouretemad, H., & Roghani, M. (2024). Promising therapeutic effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in addressing autism spectrum disorder induced by valproic acid. Frontiers in Neuroscience, 18, 1385488. doi:10.3389/fnins.2024.1385488
Yang, Y., Jiang, L., He, R., Song, P., Xu, P., Wang, Y., & Li, F. (2023). Repetitive transcranial magnetic stimulation modulates long-range functional connectivity in autism spectrum disorder. Journal of Psychiatric Research, 160, 187–194. doi:10.1016/j.jpsychires.2023.02.021
Ni, H.-C., Hung, J., Wu, C.-T., Wu, Y.-Y., Chang, C.-J., Chen, R.-S., & Huang, Y.-Z. (2017). The impact of single session intermittent theta-burst stimulation over the dorsolateral prefrontal cortex and posterior superior temporal sulcus on adults with autism spectrum disorder. Frontiers in Neuroscience, 11, 255. doi:10.3389/fnins.2017.00255
Sokhadze EM, Lamina EV, Casanova EL, et al: Exploratory study of rTMS neuomodulation effects on electrocortical functional measures of performance in an oddball test and behavioral symptoms of autism. Front Syst Neurosci 12:20, 2018

2024-12-29 18:09:07

Details: Editor CNKE; Created: 29 December 2024; Last Updated: 29 December 2024; Hits: 60