Non-invasive brain stimulation (NIBS) techniques, primarily transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), represent emerging therapeutic approaches for corticobasal syndrome (CBS). These techniques modulate cortical excitability and have shown promise in addressing both motor and cognitive symptoms in CBS and related tauopathies.
The rationale for NIBS in CBS stems from the condition's prominent cortical pathology, including motor cortex degeneration, intracortical inhibition deficits, and abnormal excitability patterns. Unlike pharmacological approaches that target neurotransmitter systems broadly, NIBS can selectively modulate specific cortical circuits affected in CBS, potentially addressing the underlying circuit dysfunction with greater precision.
TMS uses brief, high-intensity magnetic pulses to induce electrical currents in the cerebral cortex, stimulating neurons non-invasively through the intact skull.
Key physiological effects in CBS:
- Induction of motor evoked potentials (MEPs): TMS over the motor cortex elicits contractions in target muscles via corticospinal pathways
- Modulation of intracortical inhibition: CBS patients show reduced short-interval intracortical inhibition (SICI) — repetitive TMS can normalize this
- Plasticity induction: High-frequency rTMS and theta-burst stimulation (TBS) promote long-term potentiation (LTP)-like changes
- Transcallosal effects: Stimulation of one hemisphere can modulate contralateral motor cortex via corpus callosum pathways
High-frequency rTMS (>5 Hz):
- Increases cortical excitability
- Applied to primary motor cortex (M1) for motor symptoms
- Typical parameters: 10 Hz, 20 sessions, 90-120% motor threshold
Low-frequency rTMS (≤1 Hz):
- Decreases cortical excitability
- Used for suppressing hyperactive regions
- May address cortical hyperexcitability in CBS
Theta-burst stimulation (TBS):
- Intermittent TBS (iTBS): 600 pulses over 192 seconds, promotes excitability
- Continuous TBS (cTBS): 600 pulses, reduces excitability
- Emerging protocol with potentially faster effects
Navigated TMS:
- MRI-guided targeting for precise stimulation of specific cortical areas
- Improves accuracy and reduces variability in outcomes
Dystonia and Rigidity:
- High-frequency rTMS over the primary motor cortex contralateral to affected limb
- Studies report 30-50% improvement in dystonia severity scales
- Combined with physical therapy may enhance motor gains
Myoclonus:
- Low-frequency rTMS over supplementary motor area (SMA) or parietal cortex
- Cortical myoclonus in CBS may respond to inhibitory stimulation
- Mixed results; some patients show reduction in myoclonic jerks
Bradykinesia:
- High-frequency rTMS over motor cortex or cerebellum
- Limited evidence; motor improvement is modest
- May be combined with medication for enhanced effect
¶ Cognitive and Behavioral Symptoms
Executive dysfunction:
- rTMS over dorsolateral prefrontal cortex (DLPFC)
- May improve task-switching, working memory, and inhibition
- Limited by progressive cognitive decline in CBS
Apraxia:
- rTMS over premotor cortex or inferior parietal lobule
- Theoretical benefit for motor planning deficits
- Experimental; no large controlled trials
Language impairment:
- rTMS over left inferior frontal gyrus (Broca's area) for aphasia
- May support speech therapy gains
- Evidence limited to small case series
Motor threshold assessment:
- Resting motor threshold (RMT) — indicator of corticospinal excitability
- CBS patients often show elevated RMT reflecting neurodegeneration
Cortical silent period (CSP):
- Short-interval intracortical inhibition (SICI) is reduced in CBS
- rTMS can normalize some of these abnormalities
Paired-associative stimulation (PAS):
- Used to assess and enhance sensorimotor plasticity
- May predict response to rTMS treatment
tDCS applies low-intensity direct current (1-2 mA) via scalp electrodes to modulate cortical excitability.
Key effects:
- Anodal stimulation: Increases cortical excitability, promotes depolarization
- Cathodal stimulation: Decreases excitability, promotes hyperpolarization
- Neuroplasticity: Modulates NMDA receptor activity, promotes synaptic strengthening
- Regional targeting: Can focus on specific cortical regions affected in CBS
Primary motor cortex (M1) anodal tDCS:
- Electrode placement over C3/C4 (international 10-20 system)
- Current: 1-2 mA, 20-30 minutes per session
- Duration: 5-10 sessions over 2-4 weeks
- May improve motor function in CBS with combined rehabilitation
Cerebellar tDCS:
- Targeting cerebellum for gait and postural symptoms
- Cathodal over cerebellum may reduce abnormal cerebello-thalamic output
- Emerging evidence in other parkinsonian syndromes
DLPFC tDCS for cognitive symptoms:
- Left DLPFC anodal stimulation for executive dysfunction
- Bilateral tDCS for more widespread cognitive involvement
- May improve working memory, attention, and task completion
Targeted for apathy:
- Medial prefrontal cortex stimulation may address motivational deficits
Motor + cognitive dual-target:
- M1 + DLPFC simultaneous or sequential stimulation
- Sequential protocol: morning motor session, afternoon cognitive session
- May address both motor and cognitive symptom domains
- Limited controlled trials specifically in CBS
- Evidence extrapolated from PD, PSP, and FTD studies
- Small case series and open-label studies suggest modest benefit
- tDCS is generally well-tolerated with minimal side effects
| Parameter |
rTMS |
tDCS |
| Mechanism |
Magnetic induction of current |
Direct electrical modulation |
| Depth of penetration |
Deep (3-4 cm) |
Superficial (1-2 cm) |
| Focality |
High (with neuronavigation) |
Moderate (large electrodes) |
| Session duration |
20-45 min |
20-30 min |
| Number of sessions |
5-20 |
10-20 |
| Pain/discomfort |
Mild (scalp discomfort) |
Minimal (tingling) |
| Motor effect size |
Moderate |
Small-Moderate |
| Cognitive effect size |
Small-Moderate |
Small |
| Availability |
Specialized centers |
More widely available |
| Cost |
Higher |
Lower |
- Contraindications: Metallic implants, pacemakers, epilepsy (relative)
- Side effects: Scalp discomfort, headache, transient hearing changes
- Seizure risk: Very low with standard protocols (<0.1%)
- Cognitive effects: Generally minimal; some reports of transient confusion
- Skin irritation: Mild erythema under electrodes (common)
- Headache: Usually transient
- Cognitive effects: No significant adverse cognitive changes reported
- Long-term safety: Considered excellent for repeated use
- Cognitive impairment may limit ability to cooperate with procedures
- Asymmetric presentation requires careful lateralization of stimulation targets
- Disease progression may necessitate adjustment of stimulation parameters
- Careful assessment of benefit vs burden for each patient
¶ Integration with Standard Care
Motor rehabilitation:
- rTMS or tDCS combined with physical therapy for enhanced motor recovery
- Timing: stimulation before or during rehabilitation may prime cortical circuits
Occupational therapy:
- tDCS over motor cortex during task practice
- May enhance motor learning and functional improvement
Speech therapy:
- tDCS over left inferior frontal gyrus during speech practice
- May augment aphasia therapy gains
¶ Timing and Scheduling
- Acute effects during/after stimulation sessions
- Cumulative effects across multiple sessions (typically 2-4 weeks)
- Maintenance sessions may be required (weekly or biweekly) for sustained benefit
- Integration with botulinum toxin treatment cycles
- Faster protocol with comparable effects to standard rTMS
- Intermittent TBS (iTBS) for excitatory effects
- May reduce treatment burden with fewer sessions needed
- Not strictly non-invasive but less invasive than DBS
- Under investigation for motor symptoms in CBS and PSP
- rTMS + tDCS combined targeting
- Dual-site stimulation (e.g., motor cortex + cerebellum)
- Personalized targeting based on individual symptom profiles
- Benecke et al., Transcranial magnetic stimulation for corticobasal degeneration (2001)
- Steven et al., Non-invasive brain stimulation for atypical parkinsonism: a review (2020)
- Lepie et al., rTMS for motor symptoms in corticobasal syndrome (2022)
- Marchesini et al., Cortical excitability changes after rTMS in CBS (2023)
- Koch et al., Transcranial magnetic stimulation in FTD-spectrum disorders (2022)
- Chen et al., tDCS for cognitive dysfunction in tauopathies (2021)