Anxiety symptoms are elevated among people with joint hypermobility. The underlying neural mechanisms are attributed theoretically to effects of variant connective tissue on the precision of interoceptive representations contributing to emotions.

To investigate the neural correlates of anxiety and hypermobility using functional neuroimaging.

We used functional magnetic resonance neuroimaging to quantify regional brain responses to emotional stimuli (facial expressions) in people with generalised anxiety disorder (GAD) (N = 30) and a non-anxious comparison group (N = 33). All participants were assessed for joint laxity and were classified (using Brighton Criteria) for the presence and absence of hypermobility syndrome (HMS: now considered hypermobility spectrum disorder).

Participants with HMS showed attenuated neural reactivity to emotional faces in specific frontal (inferior frontal gyrus, pre-supplementary motor area), midline (anterior mid and posterior cingulate cortices) and parietal (precuneus and supramarginal gyrus) regions. Notably, interaction between HMS and anxiety was expressed in reactivity of the left amygdala (a region implicated in threat processing) and mid insula (primary interoceptive cortex) where activity was amplified in people with HMS with GAD. Severity of hypermobility in anxious, compared with non-anxious, individuals correlated with activity within the anterior insula (implicated as the neural substrate linking anxious feelings to physiological state). Amygdala-precuneus functional connectivity was stronger in participants with HMS, compared with non-HMS participants.

The predisposition to anxiety in people with variant connective tissue reflects dynamic interactions between neural centres processing threat (amygdala) and representing bodily state (insular and parietal cortices). Correspondingly, interventions to regulate amygdala reactivity while enhancing interoceptive precision may have therapeutic benefit for symptomatic hypermobile individuals.

Every day, we may choose something new randomly (random exploration) or select something new with no prior information (de-novo exploration). The link between exploration and anxiety has only been studied using trait-like anxiety questionnaires, but an experimental manipulation of anxiety could have different results. Individual differences (e.g., sex or novelty-seeking (NS) trait) also impact specific exploration strategies. Thus, we examined if anxiety manipulation in a task would influence different exploration strategies while also looking at sex, NS bias and trait anxiety.

117 healthy subjects (58 female) completed online questionnaires (novelty-seeking dimension of the Cloninger's Tridimentional Personality Questionnaire (TPQ-NS), trait anxiety questionnaire (STAI)) and performed the Maggie's farm task. This task allows to review different exploration strategies, promoting exploration via the number of available choices (horizon). The threat of aversive stimuli (loud noises appearing at random times) was used to emulate anxiety, in a between-subject design. Comparing computational models of exploration, the best-fitting model (evaluated by Bayesian Information Criterion) in our data was a Thompson model with an ε-greedy element (random exploration) and a novelty bonus η (de-novo exploration). We used repeated-measures ANOVA, comparing the effect of horizon on the ε and η parameters with the anxiety category as a between-subject factor. We used partial Pearson's correlations of ε and η derivatives (mean and standardised-difference (SD) across horizon) with STAI and TPQ-NS measures correcting for participant's reported stress levels and anxiety category. Partial correlations analyses were repeated after splitting the data by sex.

There was no between-subject effect of anxiety category on the horizon of either ε (F(1,1) = 0.253, p = 0.6) or η (F(1,1) = 0.305, p = 0.58). SD of ε was negatively correlated with TPQ-NS (r = −0.184, p = 0.050) but no other partial correlation was significant. When splitting by sex, SD of ε was negatively correlated with the STAI score (r = −0.341, p = 0.01) in females and the TPQ-NS score in males (r = −0.275, p = 0.038). The mean η positively correlated with the STAI score (r = 0.318, p = 0.016) in males.

While the experimentally modulated anxiety did not affect the exploration parameters, individual differences in NS and trait anxiety are suggested to affect random and de-novo exploration in a sex-dependent manner. Imaging research, or research into anxiety population could help further solidify these results in the future.