Transcranial Direct Current Stimulation in neurogenetic syndromes: new treatment perspectives for Down syndrome?

Abstract

This perspective review aims to explore the potential neurobiological mechanisms involved in the application of transcranial Direct Current Stimulation (tDCS) for Down syndrome (DS), the leading cause of genetically-based intellectual disability. The neural mechanisms underlying tDCS interventions in genetic disorders, typically characterized by cognitive deficits, are grounded in the concept of brain plasticity. We initially present the neurobiological and functional effects elicited by tDCS applications in enhancing neuroplasticity and in regulating the excitatory/inhibitory balance, both associated with cognitive improvement in the general population. The review begins with evidence on tDCS applications in five neurogenetic disorders, including Rett, Prader-Willi, Phelan-McDermid, and Neurofibromatosis 1 syndromes, as well as DS. Available evidence supports tDCS as a potential intervention tool and underscores the importance of advancing neurobiological research into the mechanisms of tDCS action in these conditions. We then discuss the potential of tDCS as a promising non-invasive strategy to mitigate deficits in plasticity and promote fine-tuning of the excitatory/inhibitory balance in DS, exploring implications for cognitive treatment perspectives in this population.

Keywords: GABA; excitatory/inhibitory balance; glutamate; intellectual disability; neuroplasticity; non-invasive brain stimulation; trisomy 21.

Figure 1

A multidimensional approach to treatment in Down syndrome. Pharmacological and non-pharmacological interventions serve as permissive and instructive factors of neuroplasticity. We propose that the combination of instructive and permissive factors offers the most promising approach to promote adaptive neuroplasticity in Down syndrome by enhancing BDNF levels, reducing excitation/inhibition imbalance, increasing neurotransmitter, and facilitating neuritic remodeling and synaptogenesis. Among the permissive factors, we highlight the relevance of non-invasive brain stimulation in enabling instructive cues to guide Down syndrome brain toward cognitive improvement. Created with BioRender.com.