An Exploratory Evaluation of Game Experience in a Gamified Online Telehealth Learning Module.

The human visual cortex (V1) differs from other cortical regions both at phenotypic (i.e., spatial pattern of inter-individual variation) and genetic (i.e., molecular architecture) levels (; ). Before birth, retinal activity plays a critical role in the normal development of the V1 (; ; ). Spontaneous waves of neuronal activity are generated by the retinal ganglion cells (RGCs) and transmitted, via the lateral geniculate nucleus, to the subventricular zone of the developing V1 (; ; ). These thalamocortical afferents are known to play an essential role in the expansion of the progenitor pool in the outer subventricular zone, in particular in the nascent V1 (). The absence of retinal waves, caused by bilateral enucleation in nonhuman primates before birth, is associated with lower (vs. controls) cortical surface area (; ; ). The generation of retinal waves by RGCs requires cholinergic signaling from amacrine cells. The knockout (KO) of the β2 subunit of the nicotinic receptor in the mouse impairs this signaling and reduces retinal waves (; ; ). Prenatal exposure to maternal cigarette smoking (PEMCS) is a common adverse exposure (; ). Cigarette smoke contains thousands of chemicals, with nicotine being the main pharmacologically active molecule acting via nicotinic acetylcholine receptors (; ). Although previous studies have pointed to the association between PEMCS and cortical growth (; ; ; ), little is known about the underlying mechanisms. Here, we explore a possible mechanistic pathway involving the known relationship between cholinergic retinal waves and the development of the V1. We included participants from two community-based cohorts: the UK Biobank (UKB) and the Saguenay Youth Study (SYS) cohorts. These cohorts were approved by the Institutional Ethics Committees (UKB: 2022-3689, SYS: 2004-215), and consent was obtained from participants and/or their guardians in case of minors (see below).