The Effect of Combined Brain Stimulation and Exercise for Improving Cognitive Function in Schizophrenia

Feasibility of an Integrative Treatment of Brain Stimulation and Exercise on Cognitive Function in Schizophrenia: A Pilot Randomized Controlled Trial

The study will investigate the (1) additive and synergistic effects of tDCS and aerobic exercise on cognitive function and clinical symptoms in schizophrenia, and (2) neurophysiological mechanisms (mediators) underlying these effects.

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia; Cognitive Functions
• Intervention / Treatment: Behavioral: Aerobic exercise; Device: Active tDCS; Device: Sham tDCS

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Prof. Jessie LIN; Phone Number: +852 2766 6718; Email: jx-jessie.lin@polyu.edu.hk

Study Locations

• Hong Kong
  • Kowloon
    • Hung Hom, Kowloon, Hong Kong
      • The Hong Kong Polytechnic University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Schizophrenia spectrum disorders;
• Aged from 18 to 65.
• Chinese-speaking (to enable cognitive testing).
• Ability to understand the nature of the study and to give informed consent.
• Fewer than 10 hours of physical exercise in the previous 3 months.

Exclusion Criteria:

• Severe physical illness (Myocardial Infarction, Hypertension, Fracture, Spinal problems in which exercise with mild-to-moderate intensity may be contraindicated).
• Comorbid diagnoses of organic brain syndrome, substance misuse, history of epilepsy or seizure, intellectual disability, significant head trauma, active suicidal ideation or self-harm behaviors.
• Known pregnancy, or other contraindication to tDCS or MRI (e.g., have a cardiac/heart pacemaker, brain aneurysm clips, any implanted metallic or electrical device, or any internal metal foreign objects).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Waitlist control group
Active Comparator: Active tDCS and aerobic exercise	Behavioral: Aerobic exercise; Aerobic exercise training will be conducted twice per week, over a period of 6 weeks, supervised by a well-trained facilitator. Each 45-minute session consists of a warm-up (10 minutes), treadmill walking (15 minutes), stationary bike cycling (15 minutes), and cool-down stretching (5 minutes). Heart rate will be monitored throughout training by a wearable device, and 60% of the maximum heart rate (roughly calculated by 220-age) should be maintained for at least 20 minutes during each session. Participants may stop exercising at any time if they feel uncomfortable.; Device: Active tDCS; Active tDCS will be applied using a wearable stimulator (Liftid) at a constant stimulation intensity of 1.2 mA for 20 minutes. The device has been designed for anodal stimulation targeting the dorsolateral prefrontal cortex (DLPFC) using the F3 (anode) to F4 (cathode) montages.
Sham Comparator: Sham tDCS and aerobic exercise	Behavioral: Aerobic exercise; Aerobic exercise training will be conducted twice per week, over a period of 6 weeks, supervised by a well-trained facilitator. Each 45-minute session consists of a warm-up (10 minutes), treadmill walking (15 minutes), stationary bike cycling (15 minutes), and cool-down stretching (5 minutes). Heart rate will be monitored throughout training by a wearable device, and 60% of the maximum heart rate (roughly calculated by 220-age) should be maintained for at least 20 minutes during each session. Participants may stop exercising at any time if they feel uncomfortable.; Device: Sham tDCS; Sham tDCS will be performed using the same device but without stimulation. During the aerobic exercise training, all participants will wear the device, and a facilitator will turn on the stimulation for participants receiving a-tDCS+AE intervention, and pretend to turn on the stimulation for participants receiving s-tDCS+AE intervention after the first 10-minute warm-up section.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hong Kong List Learning Test (HKLLT)	A Chinese verbal memory test designed to assess the processes and organizational strategies involved in learning verbal information. The test consists of two different 16-item two-character Chinese word lists, namely the random and blocked conditions. Total learning score, short-term, and long-term memory will be recorded in both conditions.	Baseline and after the 6-week interventions

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rapid Visual Information Processing (RVP)	A measure of sustained attention. A white box is shown in the center of the screen, inside which digits from 2 to 9 appear in a pseudo-random order, at the rate of 100 digits per minute. Participants are requested to detect target sequences of digits (for example, 2-4-6, 3-5-7, 4-6-8). When the participant sees the target sequence, they must respond by selecting the button in the center of the screen as quickly as possible. The level of difficulty varies depending on whether the participant must watch for one- or three-target sequences at the same time.	Baseline and after the 6-week interventions
Digit Span (DGS)	A measure of verbal short-term and working memory. The participant will hear a sequence of digits and will immediately be prompted to verbally repeat it. If the participant responds correctly, the next trial presents a longer sequence. The task terminates when participants respond incorrectly on three occasions at a span length.	Baseline and after the 6-week interventions
The Verbal Fluency Test (VFT)	A measure of executive function. Participants have to name as many animals as possible in 60 seconds.	Baseline and after the 6-week interventions
6-Minute Walking Test	A sub-maximal exercise test to assess the aerobic capacity and endurance. The subject has to walk as far as possible along a track for 6 minutes.	Baseline and after the 6-week interventions
The Fatigue Assessment Scale (FAS)	A 10-item self-report instrument that evaluates fatigue symptoms.	Baseline and after the 6-week interventions
The sit-and-reach test	A common measure of flexibility, specifically assessing the lower back and hamstring muscles. The subject is seated against the wall, arms outstretched towards the box. A sliding ruler is used to measure the position of the fingertips.	Baseline and after the 6-week interventions
Standing Balance Test	Give the subject a minute to practice their balancing before starting the test. Then ask the person to stand on one foot for as long as possible. The total length of time a person can stay in the balance position will be recorded. The timing stops when the elevated foot touches the ground or the person hops or otherwise loses their balance position. The test will be conducted with the person having their arms on their waist. Repeat the test on the other leg.	Baseline and after the 6-week interventions
Positive and Negative Syndrome Scale (PANSS)	Measuring symptom severity of patients with schizophrenia. It contains 33 items across three subscales (Positive, Negative, and General), rated from 1-7 on each item based on clinical interviews as well as reports from family members or primary care hospital workers.	Baseline and after the 6-week interventions
Calgary Depression Scale (CDS)	A 9-item scale to evaluate depression, rated from 0 to 3.	Baseline and after the 6-week interventions
Magnetic Resonance Imaging (MRI)	Both structural and resting-state functional MRI will be acquired on a 3 Tesla MRI scanner (Prisma, Siemens, Germany). For registration purposes, high-resolution T1-weighted anatomical images will be acquired during 3-D MP-RAGE (parameters: slice thickness=1mm, echo time=3.26ms, repetition time=2250ms, inversion time=900ms, flip angle=9°, in-plane voxel size 1×1 mm2, acquisition time=5 minutes). Functional scans (resting state) will use a gradient-echo echo-planar imaging (parameters: repetition/echo time=800/37ms; flip angle=52°; field of view=208mm; 2mm isotropic [no gap]; no. of dynamics=380, acquisition time=5 minutes). The resting fMRI scan will be repeated for 5 times with a total acquisition time of 25 minutes.	Baseline and after the 6-week interventions

Collaborators and Investigators

• Sponsor: The Hong Kong Polytechnic University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 30, 2026
• First Submitted That Met QC Criteria: July 30, 2026
• First Posted (Actual): August 4, 2026

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: July 30, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: P0048824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No