Restructuring the Alpha-Gamma Code in Aging Vision

Purpose

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.

Conditions

  • Aging
  • Visual Perception
  • Noninvasive Brain Stimulation

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

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 Design

Phase
Early Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Basic Science
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
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.
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.

Recruiting Locations

111 Cummington Mall, Boston University
Boston, Massachusetts 02215
Contact:
Robert Reinhart, PhD
617-353-9481
rmgr@bu.edu

More Details

Status
Recruiting
Sponsor
Boston University Charles River Campus

Study Contact

Robert Reinhart, PhD
(617) 353-9481
rmgr@bu.edu

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.