What are the guidelines for using transcranial pulse stimulation, including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), for therapeutic purposes?

Guidelines for Transcranial Pulse Stimulation in Therapeutic Applications

Transcranial pulse stimulation techniques, including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), should follow established protocols targeting specific brain regions with appropriate parameters based on the therapeutic indication, with the dorsolateral prefrontal cortex (DLPFC) being the most common target for most applications. 1

Types of Transcranial Stimulation Techniques

• Transcranial Magnetic Stimulation (TMS): Uses electromagnetic induction to generate brief focal electromagnetic pulses that penetrate the skull to stimulate target brain regions, with sufficient magnetic field strength to induce neuronal firing 1
• Repetitive TMS (rTMS): Delivers continuous trains of TMS pulses at specific frequencies, with high-frequency (>5 Hz) typically facilitating and low-frequency (<1 Hz) inhibiting cortical excitability 1
• Theta-Burst Stimulation (TBS): A patterned form of TMS that can be intermittent (iTBS) or continuous (cTBS), with shorter stimulation duration compared to conventional rTMS 1
• Transcranial Direct Current Stimulation (tDCS): Delivers low-intensity electric currents (0.5-2.0 mA) through electrodes placed on the scalp to modulate cortical excitability via polarity-dependent shifts of neuronal membrane potential 1
• Transcranial Alternating Current Stimulation (tACS): Delivers alternating current with sinusoidal or patterned waveforms to modulate power and/or phase of endogenous brain oscillations 1

Stimulation Parameters and Protocols

TMS Parameters

• Frequency: High-frequency rTMS (>5 Hz) facilitates cortical excitability, while low-frequency rTMS (<1 Hz) inhibits it 1
• Common frequencies: 1 Hz, 5 Hz, 10 Hz, 15 Hz, and 20 Hz are most frequently used in clinical applications 1
• Intensity: Typically calibrated to individual motor threshold 2
• Session duration: Varies by protocol but typically involves hundreds of pulses per session 3

tDCS Parameters

• Current intensity: Conventional doses range from 0.5 to 2 mA 1
• Duration: Typically up to 30 minutes per session 1
• Electrode placement: Anodal placement typically enhances excitability, while cathodal placement reduces excitability of the target region 1
• Electrode configuration: Conventional tDCS uses two large electrodes, while "high-definition" tDCS uses arrays of multiple smaller electrodes for more focal stimulation 1

Target Brain Regions

• Dorsolateral Prefrontal Cortex (DLPFC): Most frequently targeted region (77 out of 84 studies), with left DLPFC being the most common target followed by right DLPFC 1
• Other targets: Include frontal pole (FP), temporoparietal junction (TP), inferior frontal gyrus (IFG), superior frontal gyrus (SFG), motor cortex, anterior cingulate cortex (ACC), and insula 1
• Electrode placement: For tDCS, common configurations include:
  • Anodal left DLPFC with cathode on right orbitofrontal region 4
  • Anodal right DLPFC with cathode on left DLPFC 4
  • Anodal motor cortex with cathode on supraorbital region 1

Clinical Applications with Evidence-Based Recommendations

• Depression: Level B recommendation (probable efficacy) for anodal tDCS of the left DLPFC with right orbitofrontal cathode in major depressive episode without drug resistance 4, 3
• Addiction/Craving: Level B recommendation (probable efficacy) for anodal tDCS of the right DLPFC with left DLPFC cathode 4
• Pain: Level B recommendation (probable efficacy) for anodal tDCS of the left primary motor cortex in fibromyalgia; Level C recommendation (possible efficacy) for chronic lower limb neuropathic pain secondary to spinal cord lesion 4
• Stroke rehabilitation: Emerging evidence supports tDCS and rTMS for motor rehabilitation (Level B evidence for tDCS) and hand function (Level A evidence for low-frequency rTMS) 1
• Schizophrenia: Dose-response association for high-frequency TMS on left DLPFC for negative symptoms 3

Safety Considerations

• Conventional tDCS doses: Stimulation intensities up to 2 mA and durations up to 30 minutes are considered safe based on behavioral outcomes and neuroimaging studies in both humans and animals 1
• Common adverse effects: Mild and transient, including skin irritation, headache, and fatigue 5
• Contraindications: Include implanted medical devices, seizure history (particularly for high-frequency TMS), and metal in the head (excluding dental fillings) 5

Implementation Guidelines

• Standardized protocols: Use established protocols for specific conditions as outlined in consensus papers and guidelines 1
• Dose optimization: Consider dose-response relationships, as efficacy often follows bell-shaped curves with specific optimal parameters for different conditions 3
• Combined approaches: Consider combining brain stimulation with pharmacotherapy and behavioral management for optimized treatment efficacy 1
• Rigorous methodology: Implement sham-controlled designs with adequate blinding in research settings 1
• Training requirements: Ensure proper training of professionals and education of patients to avoid inappropriate applications 4

Common Pitfalls and Caveats

• Variability in response: Individual responses to stimulation can vary significantly, requiring careful monitoring and potential parameter adjustments 6
• Home use concerns: While the ease of use and low cost of tDCS devices allow for potential home applications, this raises ethical and legal concerns regarding misuse or overuse 4
• Optimization challenges: The optimal parameters for different conditions remain under investigation, with ongoing research needed to refine protocols 3
• Reproducibility issues: Variability in methods and outcome measures across studies makes reproducibility and interpretation difficult 1

Future Directions

• Personalized approaches: Development of computational models to individualize stimulation protocols based on individual brain anatomy and functional connectivity 5
• Combined interventions: Integration of transcranial stimulation with pharmacological or psychotherapeutic interventions 5
• Closed-loop technologies: Development of systems that adjust stimulation parameters based on real-time neurophysiological feedback 5
• Standardized reporting: Implementation of uniform reporting standards to improve comparability across studies 1