Effects of tDCS for Enhancing Cognitive Function in Individuals With Persistent Post-Concussion Syndrome

Transcranial Direct Current Stimulation Clinical Trial

Official title:

Effects of Transcranial Direct Current Stimulation for Enhancing Cognitive Function in Individuals With Persistent Post-Concussion Syndrome: A Pilot fMRI/1H-MRS Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06376500
• Other study ID #: HSEARS20240223001
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: February 2028

Study information

• Verified date: April 2024
• Source: The Hong Kong Polytechnic University
• Contact: Yvonne Han, PhD
• Phone: +852 2766 7578
• Email: yvonne.han[@]polyu.edu.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Globally, 10 million new traumatic brain injury (TBI) cases are estimated annually, with mild traumatic brain injury (mTBI) accounting for 75-90% of all TBI cases. It is estimated that 40-80% of individuals with mTBI may experience the post-concussion syndrome (PCS), which is characterized by a range of physical, cognitive, and emotional symptoms. Although the underlying basis of cognitive dysfunction of patients with persistent PCS remains to be clarified, converging evidence shows that the clinical symptoms is underpinned by abnormal neural information processing as a result of axonal injury due to mTBI. Recent studies have demonstrated abnormalities in both structural and functional cortical connectivity, and a loss of cortical excitability-inhibitory (E/I) balance after TBI. Yet, there is no consensus for treating chronic symptoms of concussion, and PCS remains a chronic and highly disabling condition. One potential treatment option is transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that has been shown to modify behavior by enhancing connectivity between targeted brain areas. However, research on the therapeutic effect of tDCS on PCS symptoms is limited, and the neurologic mechanisms underlying its effects are not well understood. The proposed study aims to address these knowledge gaps by examining the effects of tDCS on the central nervous system function in patients with PCS, with a specific focus on functional cortical connectivity and cognitive functions such as processing speed and executive function. The study also aims to add value to existing evidence by potentially opening new directions for designing intervention programs for the treatment of PCS after mTBI.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: February 2028
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• being 18 years old or older;
• having a history of a mild TBI (less than 30 minutes loss of consciousness) 1-6 years prior to the study;
• able to communicate in Chinese.

Exclusion Criteria:

• being without a confirmed diagnosis from the medical practitioner;
• having a history of other neurological and psychiatric disorders, skull defect, recent medical instability (within 3 weeks);
• being pregnant;
• being medication for a psychiatric condition (e.g., major depression, anxiety, schizophrenia);
• with any implanted devices or suffering from real claustrophobia or feel uncomfortable in small, enclosed spaces, like MRI tunnel

Related Conditions & MeSH terms

• Functional Magnetic Resonance Imaging
• Magnetic Resonance Spectroscopy
• Post-Concussion Syndrome
• Syndrome
• Transcranial Direct Current Stimulation

Intervention

Device:
• tDCS with cognitive training programme
Participants will complete tDCS over 10 sessions in 2 weeks (once per day, for 10 consecutive working days), while performing the executive function training tasks. The training session will last for 20 minutes and it is comprised of 5 exercises targeting at information processing speed and executive function capacities. Each exercise lasts for approximately 4 minutes, totaling approximately 20 minutes.

Locations

Country	Name	City	State
Hong Kong	The Hong Kong Polytechnic University	Hung Hom	Kowloon

Sponsors (1)

Lead Sponsor	Collaborator
The Hong Kong Polytechnic University

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory mediator - default mode network (DMN) activation	The DMN activation, indexed by fMRI resting state data will be assessed. Neuroimaging data will be acquired from the whole brain using a 64-channel head coil on a 3T Siemens MRI scanner. Resting-state data will be registered to each participant's high-resolution structural image and then normalized into the standard Montreal Neurological Institute (MNI) space. Mediation analyses will be performed to determine if the enhanced network organization in PCS patients, as indexed by DMN activation, will mediate the beneficial effect of tDCS	First day of intervention,1 day after the last day of intervention (2 time points, up to 2 weeks)
Other	Exploratory mediator - excitability-inhibitory (E/I) ratio	The E/I ratio, indexed by MRS data will be assessed. The MRS acquisition protocol is adopted from Sapey-Triomphe and the colleagues. Magnetic resonance spectra will be acquired using the Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) sequence, allowing for simultaneous quantification of GABA + and Glx (glutamine and glutamate). The MRS acquisition parameters will be set as follows: 320 averages, TR = 2000 ms, TE = 80 ms, 2048 data points, 2000 Hz spectral width, MOIST water suppression, 90°excitation/180°refocusing pulses, 20 ms editing pulses at frequencies 1.9 ppm for GABA. Interleaved Water Reference correction will be used to limit the effect of scanner drift. Twenty unsuppressed water reference scans (at TE = 80 ms) will also be acquired. Mediation analyses will be performed to determine if the enhanced network organization in PCS patients, as indexed by E/I balance, will mediate the beneficial effect of tDCS	First day of intervention,1 day after the last day of intervention (2 time points, up to 2 weeks)
Primary	Executive function	The executive function of the PCS subjects will be assessed using the Executive Composite score, which combines scores from various executive function tests.Simple-task processing speed will be evaluated using the CANTAB® 5-choice Reaction Time (RTI) task, which measures the ability to focus on relevant information while ignoring distractions. It requires participants to react as soon as a yellow dot appears on screen. Complex-task processing speed will be assessed using the computerized version of the Wisconsin Card Sorting Test (WCST), which assesses cognitive flexibility. The test requires subjects to correctly match the response cards with several stimulus cards according to feedback provided based on a rule. The mean reaction time is calculated for the trials giving a correct answer during WCST. The reaction time measured from both tasks will be converted to standard scores and averaged to yield an executive composite score. Lower scores indicate poorer executive functioning.	First day of intervention, 1 day after the last day of intervention (2 time points, up to 2 weeks)
Secondary	Change in CANTAB® cognitive test - Reaction Time (RTI)	RTI assesses motor and mental response speeds, reaction time, response accuracy and impulsivity. It consists of 30 trials with five potential targets and requires participants to make flexible responses as fast as possible to the target stimulus (shown in yellow). Specifically, movement and reaction time will be measured, where shorter duration reflects faster processing speed.	First day of intervention,1 day after the last day of intervention (2 time points, up to 2 weeks)
Secondary	Change in CANTAB® cognitive test - Multitasking Test (MTT)	MTT assesses the ability to resolve the interference of task-irrelevant information (stroop-like effect). The test displays an arrow which can appear on either the left or right side of the screen and can point to either the left or right side. In each trial, participants are presented with a cue that indicates which button to press according to two different rules. And the rules that participants have to follow may change from trial to trial in a randomized order. Participant's response latencies and error scores will be measured.	First day of intervention,1 day after the last day of intervention (2 time points, up to 2 weeks)
Secondary	Change in CANTAB® cognitive test - Spatial Working Memory (SWM)	SWM assess the memory ability of visuospatial information. Participants are required to search the tokens from a number of boxes but not pressing the boxes which tokens have been found. Errors (lower scores indicate lower repetition on pressing the same boxes that token has been found) and strategy (lower scores suggest higher strategy use in begin of choosing the same boxes) will be measured.	First day of intervention,1 day after the last day of intervention (2 time points, up to 2 weeks)