A novel game-like and creativity-conducive fMRI paradigm is developed to assess the neural correlates of spontaneous improvisation and figural creativity in healthy adults. Participants were engaged in the word-guessing game of PictionaryTM, using an MR-safe drawing tablet and no explicit instructions to be “creative”. Using the primary contrast of drawing a given word versus drawing a control word (zigzag), we observed increased engagement of cerebellum, thalamus, left parietal cortex, right superior frontal, left prefrontal and paracingulate/cingulate regions, such that activation in the cingulate and left prefrontal cortices negatively influenced task performance. Further, using parametric fMRI analysis, increasing subjective difficulty ratings for drawing the word engaged higher activations in the left pre-frontal cortices, whereas higher expert-rated creative content in the drawings was associated with increased engagement of bilateral cerebellum. Altogether, our data suggest that cerebral-cerebellar interaction underlying implicit processing of mental representations has a facilitative effect on spontaneous improvisation and figural creativity.

Coordinated variations in brain morphology (e.g., cortical thickness) across individuals have been widely used to infer large-scale population brain networks. These structural correlation networks (SCNs) have been shown to reflect synchronized maturational changes in connected brain regions. Further, evidence suggests that SCNs, to some extent, reflect both anatomical and functional connectivity and hence provide a complementary measure of brain connectivity in addition to diffusion weighted networks and resting-state functional networks. Although widely used to study between-group differences in network properties, SCNs are inferred only at the group-level using brain morphology data from a set of participants, thereby not providing any knowledge regarding how the observed differences in SCNs are associated with individual behavioral, cognitive and disorder states. In the present study, we introduce two novel distance-based approaches to extract information regarding individual differences from the group-level SCNs. We applied the proposed approaches to a moderately large dataset (n=100) consisting of individuals with fragile X syndrome (FXS; n=50) and age-matched typically developing individuals (TD; n=50). Additionally, we tested the stability of proposed approaches using permutation analysis. Lastly, to test the efficacy of our method, individual contributions extracted from the group-level SCNs were examined for associations with intelligence scores and genetic data. The extracted individual contributions were stable and were significantly related to both genetic and intelligence estimates, in both typically developing individuals and participants with FXS. We anticipate that the approaches developed in this work could be used as a putative biomarker for altered connectivity in individuals with neurodevelopmental disorders.

Objective We sought to investigate neural system habituation to face and eye gaze in fragile X syndrome (FXS), a disorder characterized by eye gaze aversion, among other social and cognitive deficits. Method Participants (age 15-25 years) included 30 individuals with FXS (14 females) and a comparison group of 25 individuals without FXS (12 females) matched for general cognitive ability and autism symptoms. We used fMRI to assess brain activation during a gaze habituation task. Participants viewed repeated presentations of 4 unique faces with either direct or averted eye gaze and judged the direction of eye gaze. Results Four participants (all males, 3 FXS) were excluded due to excessive head motion during fMRI scanning. Behavioral performance did not differ between groups. Less neural habituation (and significant sensitization) for the FXS group was found for all faces (direct and averted gaze) in cingulate gyrus, fusiform gyrus, and frontal cortex. Left fusiform habituation in female participants was directly correlated with higher, more typical, levels of fragile X mental retardation protein (r(10)=0.67, p=0.02), and inversely correlated with autism symptoms (rs(12)=−0.72, p<0.004). There was no evidence for differential habituation to direct versus averted gaze within or between groups. Conclusions Impaired habituation and accentuated sensitization to face/eye gaze was distributed across multiple levels of neural processing. These results could help inform interventions such as desensitization therapy, which may help patients with FXS modulate anxiety and arousal associated with eye gaze thereby improving social functioning.

Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder, is associated with significant behavioral, social, and neurocognitive deficits. Understanding structural brain network topology in FXS provides an important link between neurobiological and behavioral/cognitive symptoms of this disorder. We investigated the connectome via whole-brain structural networks created from group-level morphological correlations. Participants included 100 individuals: 50 with FXS and 50 with typical development, age 11-23 years. Results indicated alterations in topological properties of structural brain networks in individuals with FXS. Significantly reduced small-world index indicates a shift in the balance between network segregation and integration and significantly reduced clustering coefficient suggests that reduced local segregation shifted this balance. Caudate and amygdala were less interactive in the FXS network further highlighting the importance of subcortical region alterations in the neurobiological signature of FXS. Modularity analysis indicates that FXS and typically developing groups' networks decompose into different sets of interconnected sub networks, potentially indicative of aberrant local interconnectivity in individuals with FXS. These findings advance our understanding of the effects of fragile X mental retardation protein on large-scale brain networks and could be used to develop a connectome-level biological signature for FXS.

This review presents research findings showing that music is a unique domain to assess perception, reward, emotion, and associated physiological reactions and neural circuitry of people with autism spectrum disorder (ASD). There is growing evidence, reported in several studies in this review article, indicating that music is a relative strength of people with ASD including musical pitch perception, musical memory, and identification of music-evoked emotions. Listening to music activates neural circuits of reward and emotion response, which are described. Research presented shows adults with ASD also activate these systems when listening to music, although there may be developmental differences in the physiological and neural response to music in childhood and adolescence alongside typical behavioral response. Nonetheless, studies reviewed lend support to the use of music therapy and education for people with ASD, specifically to improve social skills and communication. Neural correlates of response to music therapy and education are also discussed. Taken together, findings reviewed provide evidence for music as a strength-based approach for ASD to assess reward and emotion response and as a powerful tool for intervention.