Mechanism of Gamma Oscillation Synchronization in the Prefrontal-hippocampal Circuit for Memory Dysfunction in Patients With White Matter Lesions of Cerebral Small Vessel Disease

The mechanism underlying memory impairment caused by white matter lesions of cerebral small vessel disease is still unclear. The disrupted synchronization of gamma oscillations in the prefrontal-hippocampal circuit is a potential key mechanism. Our study has demonstrated that white matter lesions lead to demyelination of the connection tracts between the prefrontal lobe and hippocampus, which is closely related to memory dysfunction. However, further studies are required to explore if these microstructural changes in white matter tracts influence memory function by affecting gamma oscillations. Thus, this project will use the previously established episodic memory task and event-related potential to determine the changes in gamma oscillations in the prefrontal-hippocampal circuit and the effects on memory encoding and retrieval. Combining multimodal imaging, we will explore the mediating role of white matter microstructure damage, and establish a machine learning prediction model for memory impairment. In addition, transcranial alternation current stimulation (tACS) will be used to investigate the mechanisms of memory improvement by regulating the prefrontal-hippocampal gamma oscillations. This project will clarify the neural oscillation mechanism underlying memory impairment caused by white matter lesions of cerebral small vessel disease, with the expectation of providing new predictive indicators and interventions.

Study Overview

• Status: Recruiting
• Conditions: Vascular Cognitive Impairment; White Matter Lesions; Gamma Oscillation

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Xuanwu Hospital Capital Medical University
      • Contact: Yi Xing; Phone Number: +8613269627589; Email: xingyi_211@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Elderly population

Description

Inclusion Criteria:

• - Individuals with cerebral small vessel disease, normal cognition or mild cognitive impairment subjects;
• Participants with complete demographic data, neuropsychiatric scale assessments, imaging data, and EEG data.

Exclusion Criteria:

• Severe aphasia, physical disability, or other conditions preventing completion of neuropsychological assessments;
• History of cerebrovascular stroke with documented neurological deficits during onset and corresponding lesions on neuroimaging;
• Neurological disorders that may cause cognitive impairment, including alcohol abuse, drug addiction, traumatic brain injury, epilepsy, encephalitis, or normal-pressure hydrocephalus;
• Systemic diseases potentially contributing to mild cognitive impairment (e.g., hepatic/renal insufficiency, endocrine disorders, vitamin deficiencies);
• Current diagnosis of major depressive disorder or psychiatric disorders.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall cognitive function	Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MOCA) scale scores.	baseline and one-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Attention and executive functions	the scores are evaluated using the Clock Drawing Test (CDT), the Digit Span Test (DST), and the Trail Making Test (TMT).	Baseline and follow up
Language function	Boston Naming Test (BNT)	Baseline and one-year follow up
Memory function	Digit Span Test (DST) and the WHO-UCLA Auditory Verbal Learning Test (AVLT).	Baseline and one-year follow up
Brain imaging data	Based on DTI data, the following metrics can be extracted: Fractional Anisotropy (FA) Mean Diffusivity (MD) Axial Diffusivity (AD) Radial Diffusivity (RD)	baseline and one-year follow-up
Electroencephalogram (EEG) data.	Based on EEG data, time-frequency analysis and cross-frequency coupling analysis can be performed to extract the following metrics: Theta Band Neural Oscillation Energy Theta-Gamma Coupling Strength	baseline and one-year follow-up

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 20, 2025
• First Submitted That Met QC Criteria: June 26, 2025
• First Posted (Actual): June 29, 2025

Study Record Updates

• Last Update Posted (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cerebral Small Vessel Diseases
• Other Study ID Numbers: NO.2024092

Drug and device information, study documents

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