Restructuring the Alpha-Gamma Code in Aging Vision

Rescuing Visual Perception in Aging Adults by Restructuring the Alpha-Gamma Neural Code

Tests whether age-related visual deficits arise from disrupted alpha-gamma coupling in visual cortex (V1) and MT. Uses fMRI, source-resolved HD-EEG, and personalized complex-waveform HD-tACS to (1) quantify aging effects on phase-amplitude coupling, (2) drive PAC into a preferred "gamma-at-alpha-troughs" state, and (3) bidirectionally change perception by aligning gamma to alpha troughs vs peaks. Two five-day, double-blind, sham-controlled studies (n=120 each) target contrast sensitivity (V1) and 3D shape-from-motion (MT), aiming for mechanistic insight and remediation in older adults with implications for ADRD.

Study Overview

• Status: Not yet recruiting
• Conditions: Aging; Visual Perception; Noninvasive Brain Stimulation
• Intervention / Treatment: Device: High definition transcranial electrical current stimulation

Detailed Description

The project probes a causal account of age-related perceptual decline by focusing on alpha-gamma phase-amplitude coupling (PAC) in early visual cortex and area MT. The central hypothesis is that aging alters both the magnitude and phase structure of alpha-gamma interactions, degrading visual performance; restoring a preferred configuration-gamma power nested at alpha troughs-should improve perception.

Multimodal methods combine structural/functional MRI, high-density EEG with source reconstruction, and individualized complex-waveform HD-tACS tuned to each participant's neuroanatomy and oscillatory frequencies. Three questions drive the work: (i) Do age-related deficits track changes in alpha-gamma PAC magnitude/phase? (ii) Can frequency-coupled HD-tACS enforce the preferred PAC configuration and enhance perception, especially in more impaired older adults? (iii) Is perception bidirectionally controllable by placing gamma at alpha troughs (facilitation) versus peaks (disruption)?

Two specific aims implement matched, five-day, within-subjects, double-blind, sham-controlled experiments with 120 participants each. Aim 1 targets early visual cortex to test whether contrast sensitivity deficits scale with age, spatial frequency, and noise, and whether personalized HD-tACS can optimize PAC to improve contrast perception. Aim 2 targets MT to test whether 3D shape-from-motion (parallax) judgments decline with age as a function of surface-point lifetime and simulated depth, and whether trough- versus peak-aligned stimulation can restructure PAC to enhance motion-based shape perception. Outcomes will establish mechanistic links between PAC and visual aging and evaluate a noninvasive, personalized intervention path relevant to age-related decline and ADRD.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Robert Reinhart, PhD; Phone Number: (617) 353-9481; Email: rmgr@bu.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18+ years of age or older
• normal or corrected-to-normal visual acuity, color vision, and stereo vision

Exclusion Criteria:

• not pregnant,
• no metal implants in head,
• no implanted electronic devices,
• no history of neurological problems or head injury,
• no skin sensitivity,
• no claustrophobia,
• no dementia (normal Mini Mental State Examination between 24-30; Montreal Cognitive Assessment > 25)
• no depression (normal Beck Depression Inventory II <13; Geriatric Depression Scale < 10)
• no ophthalmological diseases (e.g., strabismus, glaucoma, cataract, macular degeneration)
• no history of psychosis
• no cognitive deficits (MMSE score>24; MoCA>25)
• cannot be taking any psychoactive medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: sham stimulation	Device: High definition transcranial electrical current stimulation; Low-intensity and safe, noninvasive application of electrical current to the human scalp with the goal of gradually modulating levels of neuronal excitability.
Experimental: active stimulation	Device: High definition transcranial electrical current stimulation; Low-intensity and safe, noninvasive application of electrical current to the human scalp with the goal of gradually modulating levels of neuronal excitability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
contrast sensitivity	Orientation identification task	Baseline (pre-stimulation) and immediately post-stimulation, collected on each of the 5 study days.
3D structural-from-motion	surface point lifetime (unlimited, 12 and 2 successive views) on 3D discrimination task	Baseline (pre-stimulation) and immediately post-stimulation, collected on each of the 5 study days.
phase-amplitude coupling	alpha phase, gamma amplitude coupling (magnitude of coherency)	Baseline (pre-stimulation) and immediately post-stimulation, collected on each of the 5 study days.

Collaborators and Investigators

• Sponsor: Boston University Charles River Campus

Study record dates

Study Major Dates

• Study Start (Estimated): January 10, 2026
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): August 31, 2030

Study Registration Dates

• First Submitted: September 15, 2025
• First Submitted That Met QC Criteria: September 27, 2025
• First Posted (Estimated): October 6, 2025

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 27, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 4230E_2

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: Yes
• product manufactured in and exported from the U.S.: Yes