What is non-invasive brain stimulation, including Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS)?

What is Non-Invasive Brain Stimulation (NIBS)?

Non-invasive brain stimulation (NIBS) is an umbrella term for techniques that modulate neural activity in targeted brain regions without requiring surgery or anesthesia, primarily including Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), both of which have established safety profiles and induce controllable synaptic changes that promote brain plasticity. 1

Core NIBS Modalities

Transcranial Magnetic Stimulation (TMS)

• TMS delivers repetitive magnetic pulses at varying rates, intensities, and frequencies to induce changes in stimulated neurons and remotely in interconnected brain regions. 1
• The technique works through electromagnetic induction, where magnetic fields generate electrical currents in cortical tissue. 1
• TMS can generate lasting alterations in cortical excitability through mechanisms akin to long-term potentiation and depression. 1
• Six TMS devices currently have FDA approval, with five approved for medication-refractory depression and one for presurgical motor and speech mapping. 2

Transcranial Direct Current Stimulation (tDCS)

• tDCS delivers weak currents (0.5-2.0 mA, typically 1-2 mA) to the cortex via two polarizing electrodes (anodal and cathodal) to modulate cortical excitability. 1, 3
• Anodal stimulation generally increases cortical excitability while cathodal stimulation decreases it. 3
• The technique has Level B evidence supporting its use as an adjunct to physical therapy for motor rehabilitation after stroke. 3

Additional NIBS Techniques

• Other established NIBS methods include transcranial alternating current stimulation (tACS), random noise stimulation (RNS), and transcranial ultrasound stimulation (TUS). 1
• These techniques are less commonly used but represent emerging approaches for neuromodulation. 1

Mechanisms of Action

Neural Entrainment and Plasticity

• NIBS operates through neural entrainment, where rhythmic brain activity adjusts due to interactions with external rhythmic events, involving synchronization or frequency changes. 4
• Repeated stimulation leads to synaptic plasticity through spike-timing-dependent plasticity (STDP), reflecting lasting effects via long-term potentiation and depression. 1, 4
• The aftereffects of rhythmic NIBS protocols, when tuned to the dominant oscillatory frequency, may produce desired outcomes through successful online entrainment as a prerequisite for generating synaptic plasticity. 1

State-Dependent Effects

• NIBS modulates neuronal activity through synergistic interaction with endogenous brain activity, making the response state-dependent and variable between individuals and moments. 1
• The technique works by modulating resonance—the ability of neurons to respond selectively to inputs at preferred frequencies. 1

Clinical Applications

Stroke Rehabilitation

• Over 30 years of research has established that both tDCS and rTMS can optimize rehabilitation outcomes for motor impairment, aphasia, dysphagia, and neglect at various phases of stroke recovery. 1
• Current stroke rehabilitation guidelines provide Level A evidence for low-frequency rTMS for hand function and Level B evidence for tDCS in motor rehabilitation. 1
• NIBS should not be applied as standalone treatment but combined with intensive physical therapy to enhance behavioral therapy effects. 5

Mental Health Disorders

• TMS shows significant positive effects for generalized anxiety disorder (SMD = -1.8) and obsessive-compulsive disorder (SMD = -0.66) without significant heterogeneity in specific protocols. 6
• tDCS demonstrates efficacy for substance use disorder symptoms (SMD = -0.73) and for improving attention and working memory in schizophrenia. 6
• TMS is FDA-approved for medication-refractory depression, representing the most widely accepted clinical indication to date. 2

Addiction Medicine

• Three meta-analyses show preliminary but promising results with tES/TMS in addiction medicine, though the field requires more rigorous methodology. 1
• NIBS for substance use disorders is based on preclinical neuroscience demonstrating links between neural circuits and drug-consuming behavior. 1

Safety Profile and Contraindications

Established Safety

• Both tDCS and rTMS have established safety profiles when used with appropriate patient selection and defined treatment parameters. 1, 7
• The techniques are technically simple, require no surgery, and have significant beneficial effects. 8

Absolute Contraindications

• Exclude patients with seizure history, metallic implants in the head, pacemakers, or those taking medications that lower seizure threshold. 3, 5
• Safety guidelines regarding teenagers or children should be carefully respected when delivering TMS or tES in younger populations. 1

Current Limitations and Research Needs

Methodological Challenges

• Over 70% of published trials have sample sizes under 50 patients, with less than one-third reporting adequate power analyses. 3
• Substantial heterogeneity exists in electrode montages, stimulation durations, and sham procedures, limiting evidence synthesis. 3
• The tremendous variability in methods and outcome measures across trials makes reproducibility and interpretation difficult. 1

Critical Research Priorities

• Future research must focus on increased understanding of NIBS mechanisms, improved methodological rigor, standardization of outcome measures, and individualized protocols based on EEG biomarkers. 1
• Optimization of protocols should be based on the nature (peak frequency and individual power spectrum) and state (oscillatory synchronization and phase) of the individual oscillatory system. 1
• All stimulation parameters, electrode size/placement, lesion characteristics, and paired rehabilitation details must be reported using standardized checklists. 3

Emerging Technologies

Advanced Approaches

• Feedback-controlled stimulation that adapts in real-time to maximize desired effects on neuronal network dynamics represents a promising advancement. 1
• Development includes efforts to deliver higher field strength with higher spatial precision to deeper brain structures through automated closed-loop stimulation. 1
• New algorithms for stimulation artifact removal are under active development to enable simultaneous recording and stimulation. 1