A review of studies exploring fetal alcohol spectrum disorders through eye tracking measures

Highlights

• We review studies using eye tracking measures in fetal alcohol spectrum disorders.

• Studies mostly focused on perception, memory and executive functions.

• We identify the limits of available data and describe new research avenues.

• Guidelines are proposed, notably for diagnosis and eye tracking measures.

Abstract

The widespread cognitive and cerebral consequences of prenatal alcohol exposure have been established during the last decades, through the exploration of fetal alcohol spectrum disorders (FASD) using neuropsychological and neuroscience tools. This research field has recently benefited from the emergence of innovative measures, among which eye tracking, allowing a precise measure of the eye movements indexing a large range of cognitive functions. We propose a comprehensive review, based on PRISMA guidelines, of the eye tracking studies performed in populations with FASD. Studies were selected from the PsycINFO, PubMed and Scopus databases, and were evaluated through a standardized methodological quality assessment. Studies were classified according to the eye tracking indexes recorded (saccade characteristics, initial fixation, number of fixations, dwell time, gaze pattern) and the process measured (perception, memory, executive functions). Eye tracking data showed that FASD are mostly associated with impaired ocular perceptive/motor abilities (i.e., altered eye movements, centrally for saccade initiation), lower accuracy as well as increased error rates in saccadic eye movements involving working memory abilities, and reduced inhibitory control on saccades. After identifying the main limitations presented by the reviewed studies, we propose guidelines for future research, underlining the need to increase the standardization of diagnosis and evaluation tools, and to improve the methodological quality of eye tracking measures.

Introduction

Alcohol-related disorders encompass various conditions, all being related to physical and mental health damages (WHO, 2018). Beyond the (neuro-)psychological and brain impairments occurring during acute alcohol consumption (Bjork and Gilman, 2014;Field et al., 2010) and those related to chronic excessive alcohol consumption among individuals diagnosed with severe alcohol-use disorder (gathering former categories of alcohol abuse and alcohol dependence,Bühler and Mann, 2011;Stavro et al., 2013), the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM-5,American Psychiatric Association, 2013] includes the diagnosis of neurodevelopmental disorder associated with prenatal alcohol exposure. Such in utero exposure to alcohol has negative consequences for a large range of physiological systems, involving sensorial (Ribeiro et al., 2007), musculoskeletal (Myrie and Pinder, 2018), cardiac (Yang et al., 2015) or gastro-intestinal (Hofer and Burd, 2009) abnormalities, but is centrally harmful to the cerebral development of the fetus. This leads to the emergence of cognitive problems, as well as serious behavioral and social maladjustment (Day et al., 2013;Kodituwakku, 2009;Rasmussen, 2005). The umbrella term of “fetal alcohol spectrum disorder” (FASD) is commonly used to describe several subtypes of adverse effects caused by prenatal alcohol exposure. These subtypes include alcohol-related neurodevelopmental disorder (ARND, characterized by cognitive and neurobehavioral impairments, Chudley et al., 2005), as well as partial fetal alcohol syndrome (pFAS) and fetal alcohol syndrome (FAS), which are moreover characterized by central nervous system dysfunctions, facial dysmorphology, and growth deficits (these alterations being more intense and consistent in FAS than in pFAS). These subtypes of FASD are thus all characterized by a pervasive pattern of cognitive and/or cerebral deficits, which have been extensively documented during the last decades through the use of neuropsychological and neuroscience tools. The global description of impaired language skills (McGee et al., 2009) or reduced intellectual quotient (Vaurio et al., 2011) has been refined by more specific explorations now offering a comprehensive view of the large-scale impairments presented by this population: FASD is associated with reduced performances in motor abilities (Doney et al., 2014), attention (Bertrand et al., 2005), short-term (Aragón et al., 2008) and long-term (Crocker et al., 2011) memory, and executive functions (Khoury et al., 2015). These impairments are underpinned by structural and functional brain modifications which encompass subcortical and cortical regions (Diwadkar et al., 2013; Gautam et al., 2015; Moore et al., 2014).

Interestingly, various neuroscience techniques [e.g., magnetoencephalography (MEG)Bolaños et al., 2017; electrophysiology,Gerhold et al., 2017] have been recently used to increase the theoretical and experimental knowledge regarding the behavioral and brain correlates of FASD. Among these innovative tools, eye tracking measures appear as a very promising technique, notably to offer a better understanding of the links between cognitive and cerebral impairments. Indeed, by allowing the precise detection of eye position and gaze direction with a high temporal resolution, eye tracking indexes bring new insights regarding the underlying brain mechanisms involved in a large variety of cognitive tasks (Luna et al., 2008). The blooming research field of eye tracking in healthy and pathological populations has developed a large range of experimental paradigms linking eye-related measures (including ocular pursuit, saccadic movements, gaze scanpaths or pupillary diameter,Leigh and Kennard, 2004;Lisberger, 2010) with cognitive or brain functions (Eckstein et al., 2017;Popa et al., 2015). Beyond their general usefulness to renew the understanding of neurocognitive abilities in healthy and pathological samples, eye tracking measures appear particularly adapted to deepen the results obtained in FASD through behavioral and neuroscience techniques. Indeed, on the one hand, the various physiological eye movements measured by means of eye tracking are under the control of specific neural networks responsible of programming motor schemes to orient (i.e., saccades) or to maintain (e.g., fixation, smooth pursuit) the gaze towards a certain portion of space (seeBaird-Gunning and Lueck, 2018;Shaikh and Zee, 2018for recent reviews). For instance, it is known that frontal and parietal regions are part of a network controlling saccades (e.g.,Coe and Munoz, 2017;Wardak et al., 2011), and that the control of saccade accuracy is undertaken by the cerebellum (e.g.,Beh et al., 2017;Kunimatsu et al., 2016). On the other hand, recent studies have identified the main brain areas impacted in FASD. Most of them highlighted that the volume and structure of the brain, especially in the corpus callosum, cerebellum, and parietal regions, are altered. They also acknowledged some functional and neurochemical differences in various brain regions (seeDonald et al., 2015;Lebel et al., 2011;Norman et al., 2009for reviews). Because of the striking overlap between the regions damaged in FASD and the ones involved in eye movements, analyzing gaze patterns appears as an optimal method for understanding how these structural damages cause functional impairments in FASD. Using eye tracking measures to observe abnormal gaze patterns in FASD participants could thus inform on the integrity of the underlying brain structures.

Several studies have already applied eye tracking measures to populations presenting FASD, but no review has been proposed on this topic, which hampers to obtain a comprehensive overview of this emerging research field. Therefore, our objective is to propose a review of all the studies which used valid eye tracking measures among populations presenting FASD. This global research question was specified through the PICOS procedure (Population, Intervention, Comparator, Outcome, Setting;Liberati et al., 2009). Regarding Population, we considered studies that included human participants presenting prenatal alcohol exposure. We considered the whole spectrum of fetal alcohol disorders, including FAS, pFAS, or ARND. Concerning Intervention, we included studies proposing a reliable clinical diagnosis or valid measure of prenatal alcohol exposure. Regarding Comparator, studies were considered if they offered a reliable comparison between the experimental group (confronted with prenatal alcohol exposure) and a matched control group. The Outcome was focused on studies that proposed at least one reliable eye tracking measure (i.e., initial fixation, number/time of saccades, eye movements, gaze direction, dwell time, pupillary measure) as a main dependent variable. Finally, regarding the Setting, we included studies related to any type of design based on comparisons between groups or experimental conditions (i.e., interventional, observational, cross-sectional). Single-case or case series studies were excluded, as well as papers not reporting experimental data (i.e., reviews, meta-analyses, replies, commentaries, errata).