Schizophrenia is a severe mental disorder affecting about 1% of the population worldwide.
It is characterized by hallucinations, delusions, disorganized thinking and behavior, and impaired cognitive functioning.
Current treatments with antipsychotic medications are helpful but have significant limitations, especially for cognitive deficits and negative symptoms like social withdrawal and lack of motivation.
This has driven interest in exploring novel non-drug treatments like transcranial alternating current stimulation (tACS) which may improve symptoms by altering brain oscillations.
Key Facts:
- Schizophrenia involves dysfunctional neural oscillations in alpha, theta, beta, and gamma frequency ranges associated with symptoms.
- tACS applies a weak alternating electric current to the scalp to entrain and modulate brain oscillations.
- Early research suggests tACS may improve auditory hallucinations, delusions, cognitive deficits, and negative symptoms.
- Larger sham-controlled trials are needed to replicate preliminary findings.
- tACS appears safe and well-tolerated based on current limited evidence.
The Potential for tACS in Treating Schizophrenia
Schizophrenia is considered a disorder of disrupted neural circuitry and abnormal oscillations or brain waves.
Oscillations refer to rhythmic patterns of synchronized electrical activity between networks of neurons in the brain.
These brain waves occur at different frequencies, including alpha (8-12 Hz), beta (13-30 Hz), theta (4-7 Hz), and gamma (30-200 Hz) bands.
Each frequency band is associated with various cognitive and perceptual processes.
A growing body of evidence from electroencephalography (EEG) suggests schizophrenia involves dysfunctional oscillations in selective brain regions that correlate with symptoms:
- Reduced alpha, theta and gamma correlate with cognitive deficits
- Reduced alpha correlates with hallucinations and delusions
- Reduced gamma correlates with negative symptoms
tACS may help remediate symptoms by using weak electric currents to “tune” these aberrant brain oscillations.
It involves applying sinusoidal alternating currents to the scalp to entrain endogenous oscillations to match the external stimulation frequency.
This is thought to occur through a phenomenon called frequency synchronization where interacting systems adjust their rhythms to oscillate in tandem.
tACS frequencies are matched to the bandwidth of interest.
Current is delivered through electrodes placed on targeted regions.
Session duration, number, and current intensity are adjustable stimulation parameters. Effects may persist beyond stimulation due to neuroplasticity.
tACS for Auditory Hallucinations & Delusions (Positive Symptoms)
Auditory hallucinations are a core symptom of schizophrenia, experienced as “hearing voices”.
They are associated with dysfunctional alpha oscillations in brain networks linked to speech perception and auditory processing.
Several small studies have explored using alpha tACS over the left temporoparietal junction, a key auditory area.
An initial randomized, double-blind trial in 22 schizophrenia patients found the largest reduction in auditory hallucination severity with 10 Hz alpha tACS compared to sham, though not statistically significant.
A follow-up analysis revealed enhanced alpha power and connectivity between targeted regions that correlated with hallucination improvement after alpha tACS.
Another small open-label study targeting the medial prefrontal cortex with 10 Hz tACS in 12 patients showed significant improvement in delusion severity sustained for one month.
The authors suggest tACS may have inhibited overactive self-referential thinking circuits underlying delusions.
While promising, larger controlled studies are needed to confirm benefits for hallucinations and delusions before clinical implementation.
tACS for Cognitive Deficits
Cognitive deficits in attention, memory, processing speed and executive functioning are a major source of disability in schizophrenia.
They are linked to reduced frontal theta and gamma oscillations important for cognitive control.
Several small studies have targeted the left dorsolateral prefrontal cortex with theta or gamma tACS during working memory task performance.
Two open-label reports in a total of 12 patients found enhanced accuracy and reaction times on the n-back working memory test with 6 Hz theta tACS.
However, two double-blind crossover studies comparing gamma tACS to sham stimulation in a total of 26 patients found no significant difference in working memory.
A recent randomized controlled trial using a specially configured “high definition” theta tACS montage over bilateral frontal and parietal areas did find significant cognitive improvements compared to sham.
Overall, initial results are mixed but generally supportive of cognitive benefits from tACS that warrant further controlled research.
tACS for Negative Symptoms of Schizophrenia
Negative symptoms like apathy, social withdrawal and lack of motivation account for much of the disability in schizophrenia.
They are linked to gamma oscillations important for conscious perception and motivation.
A few small open-label studies totaling 8 patients applied bilateral frontal gamma tACS and found reductions in negative symptoms and improved social and occupational functioning.
Additionally, a randomized controlled trial of 36 patients using frontal theta tACS during a working memory task found significant improvement in negative symptoms compared to sham stimulation.
These preliminary results indicate tACS may improve negative symptoms, but confirmation in larger controlled trials is needed.
Current Limitations and Future Research Directions
While early results are promising, there are several limitations:
- Most studies are small pilot trials lacking sham control groups. Larger randomized controlled trials are needed.
- Heterogeneity in protocols makes it difficult to compare findings across studies. Parameters like electrode placement, current intensity, frequency and phase need optimization.
- Long-term efficacy and safety is unknown. Studies follow patients for only up to one month post-tACS currently.
- It is unclear if tACS should be used alone or combined with medications for additive effects.
- Individual variability in skull anatomy and neural oscillations may influence effects. Individualized treatment guided by neuroimaging and EEG mapping could help.
- High definition tACS using novel multi-electrode arrays may provide greater focality and salient effects compared to conventional pads.
Future research should focus on randomized, sham-controlled trials in larger samples over extended periods to better establish efficacy.
The optimal protocols for each symptom domain need clarification.
Combining tACS concurrently with cognitive training or medications may have synergistic effects worth exploring.
Finally, tACS could be utilized to probe the causal role of oscillations in schizophrenia pathology.
Is tACS Safe? (Side Effects)
Safety data on tACS is limited but so far indicates minimal risk when appropriate protocols are followed.
Adverse effects like tingling, itching, and headache are transient, mild and resolve quickly after stimulation.
No serious events have been reported in the schizophrenia trials conducted.
Proper electrode positioning, size and current dosing are important to avoid excess charge density on the scalp.
Stimulation is well-tolerated up to 2mA with conventional large pad electrodes based on existing evidence.
Sessions should be kept under 40 minutes at frequencies below 100 Hz until more safety data emerges.
Patients on medications or with implanted devices require caution and monitoring.
TACS shows early promise in schizophrenia
In summary, tACS is an exciting noninvasive neuromodulation approach that may ameliorate symptoms in schizophrenia by correcting dysfunctional brain oscillations.
Initial pilot studies provide preliminary support for benefits in treating auditory hallucinations, delusions, cognitive deficits and negative symptoms.
However, larger sham-controlled trials are critically needed to replicate these early findings before clinical use can be recommended.
If future research continues to demonstrate efficacy, tACS could provide a novel augmentation strategy to improve functioning and quality of life in schizophrenia patients.
References
- Study: Transcranial alternating current stimulation and its role in schizophrenia: a scoping review
- Authors: Harsh Pathak et al. (2023)
