Background
The
Fragile X Mental Retardation-1 (
FMR1) premutation is a prevalent genetic alteration affecting 1 in 291 women [
1]. The premutation occurs when the CGG element on the 5′ untranslated region of the
FMR1 expands within the range of 55–200 repeats [
2]. The expanded CGG sequence shows generational instability and women “carriers” of the
FMR1 premutation are at risk of passing the mutation to their offspring, which causes fragile X syndrome when the expansion exceeds 200 repeats [
3].
Besides conferring familial risk, the
FMR1 premutation is associated with its own clinical consequences, which include increased risk for mental health disorders [
4], mild cognitive deficits [
5], and physical health complications such as fragile X-associated premature ovarian insufficiency and fragile X-associated tremor ataxia syndrome (FXTAS; [
6,
7]). Much existing research on the
FMR1 premutation has focused on men, who show social-cognitive difficulties such as decreased ability to “read” mental and emotional states from the eyes [
8]. Atypical brain and autonomic responses to social stimuli, such as reduced conductance response when greeting an unfamiliar person and diminished amygdala activation when viewing fearful faces, are also seen in males with the premutation [
9,
10]. Less research has focused on females, but emerging work suggests a similar profile of social-cognitive weaknesses. For instance, risk for autism is increased among females with the premutation, with about 5% meeting criteria for autism spectrum disorder [
11]. Women with the
FMR1 premutation also exhibit increased personality features consistent with the broad autism phenotype [
12] and decreased sensitivity to biological motion [
13]. Yet, the phenotypic signature of the
FMR1 premutation is not fully understood, and few investigations have focused on language features in this group.
Difficulty with pragmatic language (i.e., social language) is a recently documented feature of the
FMR1 premutation that is prime for further study, given its clinical relevance. As a group, women with the
FMR1 premutation commit more pragmatic language violations during conversation than do control women, which includes features such as over-talkativeness and introducing inappropriate topics [
12]. At the family level, these features are clinically significant; pragmatic language difficulties among mothers with the
FMR1 premutation are associated with poor language outcomes for their children with fragile X syndrome [
14]. Additionally, these pragmatic language features may have negative consequences at the individual level. Pragmatic impairments are associated with lower quality friendships [
15], social rejection [
16], emotional difficulties [
17], and feelings of loneliness [
18] in other clinical groups, although individual effects have not yet been studied in the premutation.
While impaired use of eye gaze to infer mental/emotional states has been documented among men with the premutation (i.e., [
8]), social-cognitive abilities involving the eye gaze have not been investigated among women with the
FMR1 premutation. The present study sought to address this gap in the literature, with a focus on differential sensitivity to direct and averted gaze. The eyes represent a powerful modality for gleaning information about the social world, lending clues into the thoughts, beliefs, desires, and emotional state of others [
19]. Sensitivity to the direction of eye gaze is hypothesized to represent a biologically prepared skill, as very young infants exhibit enhanced neural processing in response to direct gaze and are able to distinguish direct from averted gaze [
20,
21]. This innate sensitivity to eye gaze is crucial to the development of theory of mind, or the ability to attribute mental states to others, and is thought to provide the foundation for the later development of social and communication skills [
20,
22]. Human preference for direct gaze over averted gaze is well documented, with more efficient detection of direct gaze during visual search tasks [
23,
24] and longer disengagement latencies in response to direct gaze [
25]. The increased saliency of direct gaze has evolutionary significance, as direct gaze represents a primary communicative channel by which humans exchange social-cognitive information, facilitating adaptive social engagement [
26]. Consistent with this notion, research shows that direct gaze facilitates the retrieval of social-cognitive knowledge, with enhanced recognition of emotions, faces, speech, and gender observed under direct gaze conditions relative to averted gaze [
27‐
33]. In sum, the eyes, and the direction of eye gaze in particular, represent a valuable source of information needed for social approach and engagement.
A number of empirical studies support a role of social gaze in language acquisition [
34‐
37]. According to the social-pragmatic theory, social-cognitive skills, such as the ability to “read the mind from the eyes,” are fundamental to language development because they allow communicative partners to establish a shared context that can be used to infer the meaning behind words and utterances [
38,
39]. Eye gaze in particular represents a medium through which communication partners exchange critical information about intentions, moods, and emotions [
40,
41]. During conversation, conversational partners spend a great deal of time attending closely to others’ eye gaze patterns [
42‐
44]. Eye gaze provides information on speaker intent and can be useful in resolving conversational ambiguities [
45] and in detecting deception [
46]. Information on the conversational partner’s interest and understanding is also conveyed through gaze, allowing the speaker to adopt their message to enhance the listener’s engagement and comprehension [
43,
47]. Eye gaze is also used to establish listener/speaker roles so that disruptive turn-taking, such as interruptions and overlapping speech, are kept at a minimum [
48,
49]. Thus, suboptimal use of gaze signals can lead to a number of maladaptive conversational strategies. This study tested the hypothesis that aberrant attention to social gaze contributes to pragmatic deficits in the
FMR1 premutation.
The present study
This study employed an eye-tracking paradigm to record the time spent dwelling on the eyes in response to an animated face displaying either direct or averted gaze. The study’s first objective was to determine whether attention to the eyes in response to direct gaze and averted gaze, reflecting perceived salience, differed across women with the
FMR1 premutation and control women. The second aim was to determine whether attention to the eyes under direct and averted gaze conditions was associated with pragmatic language variation in these groups. The
FMR1 premutation is a highly prevalent genetic condition, making efforts to define its phenotype and associated mechanisms a public health imperative. This work is also important because of its implications for understanding the underpinnings of language behaviors relevant to both atypical and typical populations as they present during adulthood—an understudied and underserved developmental period. The following research questions were tested:
1.
Does attention to the eyes in response to direct and averted gaze differ in women with the FMR1 premutation contrasted to control women? It was hypothesized that women with the FMR1 premutation would spend less time dwelling on the eyes than control women, reflecting social-cognitive weaknesses in this group. It was hypothesized that both groups would dwell on the eyes longer in the direct gaze condition than in the averted gaze condition, consistent with evidence supporting preferential attention to direct gaze.
2.
Is attention to the eyes in response to direct and averted gaze associated with pragmatic language variation in women with the FMR1 premutation contrasted to control women? Consistent with the notion that eye gaze is a necessary source of information for social engagement, it was hypothesized that dwelling on the eyes in response to direct and averted gaze would be associated with increased pragmatic language competence in both groups.