Online HD-tDCS Over the Left DLPFC During a Working Memory Task for Treating Negative Symptoms of Schizophrenia

NCT ID: NCT05582980

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-15
• Study Completion Date: 2023-03-31

Brief Summary

In this randomized double-blind trial, the investigators aim to investigate whether online high definition transcranial direct current stimulation (HD-tDCS) over the left dorsolateral prefrontal cortex (DLPFC) during a working memory task improves the severity of negative symptoms in schizophrenia patients with predominant negative symptoms.

Detailed Description

Positive (delusions and hallucinations) and negative (blunted affect, avolition-apathy, alogia and anhedonia-asociality) symptoms are recognized as core features of schizophrenia. Antipsychotic medications as the first-line treatment for schizophrenia can reduce the positive symptoms within 14-28 days but good evidence that antipsychotics have any beneficial effect on negative symptoms is scarce. Negative symptoms remain the most important unmet therapeutic needs in schizophrenia.

Accumulating functional neuroimaging research has linked the correlation between negative symptoms and reduced dorsolateral prefrontal activity. Atypical antipsychotics, the mainstream treatment for schizophrenia, are known to show little effect on patients' hypofrontality and some of them (e.g., strong dopamine receptor antagonists and clozapine) are even associated with a decrease in prefrontal activation. All these findings have driven the development of novel and effective treatments targeting the brain regions implicated in negative symptoms of schizophrenia, e.g., non-invasive brain stimulation (NIBS) of over the left DLPFC.

Transcranial direct current stimulation (tDCS) is a NIBS that has great potential to improve negative symptoms of schizophrenia. tDCS applies a weak direct current on the scalp and through the brain and rapidly leads to changes in cortical excitability by shifting membrane resting potentials, which facilitates either depolarization or hyperpolarization of the brain neurons. Repetitive stimulation during specific time intervals further enhances efficacy and prolongs the after-effects of tDCS through modifying the efficacy of N-methyl-D-aspartate receptor. An increasing number of studies attempted to reduce negative symptoms of schizophrenia by using tDCS.

Most tDCS research delivers direct current to the participants while they are at rest (offline tDCS). There has been a novel stimulation model called "online" stimulation, in which non-invasive brain stimulation is applied while the individuals are concurrently engaged in a neuropsychological task. For example, a cognitive task has been known to activate a specific brain region (e.g., working memory task and prefrontal cortex). The susceptibility of a specific brain region (i.e., prefrontal cortex) to neuro-stimulation will be enhanced if it is simultaneously activated when engaging a working memory task. Compared to the use of tDCS while the subject is at rest (offline tDCS), the application of tDCS to activate the prefrontal cortex while the subject is engaged in a working memory task (online tDCS) can potentially result in resonated effects and further enhance the neuromodulation on the target brain region, aka functional targeting.

High definition tDCS (HD-tDCS) targets cortical areas using arrays of electrodes on the scalp (i.e. a classic 4 × 1 ring configuration) and constrains the electrical current flow to a specific cortical area, allows for more accurate definition of the current field distribution than conventional tDCS and serves to optimize electrode montage to specifically target the brain areas of interest.

Our proof-of-concept study aims to investigate the efficacy of online HD-tDCS over left DLPFC as an add-on therapy to improve negative symptoms severity in schizophrenia patients with predominant negative symptoms. Moreover, it provides data on other secondary outcomes and preliminary neurophysiological data for this intervention condition.

Conditions

Schizophrenia; Schizoaffective Disorder, Mixed Type; Negative Symptoms in Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

HD-tDCS (active)

Stimulation will be applied by a battery-operated device (NeuroConn DC Stimulator Plus) via 5 carbon rubber electrodes (1 cm radius, high-definition 4 × 1 rings configuration). To target the left DLPFC, the central electrode (anode) will be placed over International 10-20 electrode position F3, with return peripheral electrodes at Fp1, Fz, C3 and F7. Stimulation will be applied at an intensity of 2 milliamp (mA), 8-sec fade in and 5-sec fade out, for 20 min, two times daily, on 5 consecutive weekdays (total 10 sessions). During each session, the subject has to perform a computerized working memory task (i.e., 2-back task). The two times daily sessions will be separated by at least 2 hours.

Group Type: EXPERIMENTAL

HD-tDCS

Intervention Type: DEVICE

See detail in arm/group descriptions regarding the intervention.

HD-tDCS (sham)

In sham stimulation, the electrode montage and protocol will be the same as the active stimulation, except the 2 mA current will be turned on for 30 sec and then ramped down to 0 mA through the remainder of the 20-min time.

Group Type: SHAM_COMPARATOR

HD-tDCS

Intervention Type: DEVICE

See detail in arm/group descriptions regarding the intervention.

Interventions

HD-tDCS

See detail in arm/group descriptions regarding the intervention.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Subjects aged 20-65 years and diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5 ) schizophrenia or schizoaffective disorder
• Duration of illness≧1 year
• With a clinical presentation of predominant negative symptoms (according to the clinical judgment of 2 experienced psychiatrists) and the Positive and Negative Syndrome Scale (PANSS) score > 70
• Receiving stable antipsychotic drug regimen >8 weeks.

Exclusion Criteria

• Subjects with current psychiatric comorbidity or active substance use disorder with the exception of caffeine and/or tobacco
• Having contraindications for tDCS, e.g., implanted brain medical devices or metal in the head
• Pregnancy at enrollment
• Having a history of seizures, intracranial neoplasms or surgery, severe head injuries, or cerebrovascular diseases

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tri-Service General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hsin-An Chang, MD

Professor, Attending Psychiatrist, Department of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hsin-An Chang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Locations

Tri-service general hospital

Taipei, , Taiwan

Countries

Taiwan

References

Ma CC, Lin YY, Chung YA, Park SY, Huang CC, Chang WC, Chang HA. The two-back task leads to activity in the left dorsolateral prefrontal cortex in schizophrenia patients with predominant negative symptoms: a fNIRS study and its implication for tDCS. Exp Brain Res. 2024 Mar;242(3):585-597. doi: 10.1007/s00221-023-06769-5. Epub 2024 Jan 16.

Reference Type: DERIVED

PMID: 38227007 (View on PubMed)

Other Identifiers

1-108-03-002

Identifier Type: -

Identifier Source: org_study_id