Non-Invasive Brain Stimulation to Improve Language in Down Syndrome.

Summary

Down syndrome (DS) is associated with cognitive deficits, caused by alterations in neuroplasticity and synaptic transmission. Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), can modulate the brain's plasticity mechanisms and neurotransmitter balance.

Anodal tDCS increases cortical excitability by depolarizing neurons, while cathodal tDCS decreases it through hyperpolarization. When combined with cognitive training, tDCS may produce faster and longer-lasting therapeutic effects. Although most of the neurorehabilitation studies have applied anodal excitatory stimulation, recent evidence suggests the potential cathodal inhibitory stimulation in neurodevelopmental disorders with alteration of synaptic transmission, as people with DS. Potentially both anodal and cathodal stimulation protocols could lead to positive clinical effects in DS.

This proof-of-concept study is a double-blind, placebo-controlled, clinical trial aiming to evaluate the efficacy of two active tDCS protocols (anodal and cathodal) targeting the left inferior frontal gyrus (IFG) versus sham stimulation tDCS, combined with speech and language training, to improve language skills in adolescents and young adults with DS. The study also aims to identify the most effective parameters of tDCS treatment, for customization in adolescents and young adults with DS. Thirty-six participants, aged 12 to 21 years, will be randomly assigned to three groups receiving anodal, cathodal, or sham tDCS. Each participant will undergo 10 sessions of tDCS at 1 mA for 20 minutes, alongside speech and language training five times for two weeks.

Neuropsychological, behavioral, biomarker (including brain-derived neurotrophic factor and neurofilament light chain), and electroencephalogram assessments will be performed at baseline, post-treatment, and three months after treatment completion. The study hypothesizes that tDCS will enhance language abilities, particularly expressive vocabulary, and modulate biomarkers of brain plasticity in DS participants. The study also hypothesizes that tDCS will enhance other cognitive and behavioral functions. Since tDCS effects may last, the study will check for improvements at the three-month. If effective, this combined approach of tDCS and language training could pave the way for new rehabilitation strategies for DS.

Conditions

• Down Syndrome

Interventions

DEVICE

Active Group (Active Anodal tDCS to the left IFG or Cathodal tDCS to the left IFG)

Participants in the active tDCS group (Anodal tDCS or Cathodal tDCS) will receive stimulation set at 1 mA (milliampere), with a duration of 20 minutes per session. The stimulation will be administered in five consecutive sessions per day, five days a week, for two weeks, totaling 10 sessions, while participants will also undergo logopedic treatment for 20 minutes. The training protocol will consist of 10 minutes of training in motor planning and programming abilities and 10 minutes of training on the lexical, morphosyntactic, and functional aspects of language and communication.

DEVICE

Sham Group

For the sham condition, the same electrode placement will be used as in the anodal tDCS condition, but the current will be applied for 30 s and will be ramped down without the participant's awareness. Stimulation intensity will be set at 1 mA; the duration of stimulation will be 20 min and will be held five consecutive daily session per week for two weeks, for a total of 10 sessions. During the tDCS sessions participant will sit in a comfortable chair and a language training will be administered

Sponsors & Collaborators

• Bambino Gesù Children's Hospital IRCCS

  collaborator OTHER

• Floriana Costanzo

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

12 Years

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-27

Primary Completion

2026-03-31

Completion

2026-03-31

Countries

• Italy

Study Locations