Fiber tract associated with autistic traits in healthy adults
Introduction
Autism Spectrum Disorder (ASD) was proposed as a developmental disorder with a triad of impairments in social interaction, communication, and imagination (Wing, 1988, Wing, 1997), and it was defined in the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) as neurodevelopmental disorder with impairment of social communication and restricted and repetitive behaviors (American Psychiatric Association, 2013). ASD was previously considered to have aberrant brain function in specific regions such as the cerebral cortex, cerebellum, amygdala, basal ganglia, and mesolimbic system (Allely et al., 2014, Cauda et al., 2011, Courchesne, 1997, Stanfield et al., 2008, Via et al., 2011). Recently, ASD has been increasingly considered a disorder of impaired brain networks (Just et al., 2012, Kana et al., 2011, Vissers et al., 2012), in which white matter abnormalities can be the neural underpinnings. Previous diffusion tensor imaging (DTI) studies in people with ASD repeatedly reported the reduction of fractional anisotropy (FA), which indicates impaired white matter integrity (Walker et al., 2012). A recent study has examined the developmental trajectory of white matter in 6- to 24-month infants with high risk of ASD, showing rapid increase and subsequent stoppage of FA of several fiber tracts in very young infants with ASD and supporting the consistent findings of reduced FA in individuals with ASD (Wolff et al., 2012). Brain alterations in individuals in ASD are also evident in high autistic traits in healthy people (Nummenmaa and Engell, 2012, Wallace et al., 2012), which is in line with the notion that ASD forms a continuum from autism to healthy population (Baron-Cohen et al., 2001a, Constantino and Todd, 2003, Robinson et al., 2011). These findings suggest that there is reduced white matter integrity in the brain of people with ASD and that such alterations can be related to autistic traits in healthy people.
The posterior superior temporal sulcus (pSTS), which has many inputs and outputs of white matter fibers (Lahnakoski et al., 2012), has been repeatedly reported to play a key role in the pathophysiology of ASD (Pelphrey et al., 2011, Zilbovicius et al., 2006). In addition, growing evidence has indicated that there is reduced FA of white matter around pSTS of people with ASD. Reduced FA in the white matter region adjacent to pSTS has been reported by several DTI studies using voxel-based morphometry (VBM) (Barnea-Goraly et al., 2004, Bloemen et al., 2010, Groen et al., 2011), a widely used automated imaging-analysis method for exploring regional brain alterations. Recently, some studies used tract-based spatial statistics (TBSS), which is a voxelwise analysis method for DTI and is robust for registration errors inherent in VBM (Smith et al., 2006), to show a reduction of FA in the pSTS region in children and adolescent with ASD (Barnea-Goraly et al., 2010, Jou et al., 2011b, Shukla et al., 2011a). However, it is difficult from these voxelwise techniques to know on which fiber tracts these FA changes are located, because several white matter tracts run adjacent to pSTS, including the arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF) and inferior fronto-occipital fasciculus (IFOF) (Catani and de Schotten, 2012).
How can we investigate the detailed location of FA change? Diffusion tractography reconstructs each individual white matter fiber trajectory using directional information in DTI data. Integrating tractography technique with voxelwise method is helpful for investigating on which fiber tracts FA is reduced in the pSTS-adjacent white matter region. So far, two studies have employed this strategy. Kumar et al. found reduced FA around the STS region in TBSS in young children with ASD and confirmed the reduction of FA for several fibers using tractography, although their findings were not significant after correcting for IQ (Kumar et al., 2010). Using VBM, Jou et al. showed clusters of FA reduction in the pSTS region in children with ASD, and then revealed by tractography that clusters can be either on IFOF or ILF (Jou et al., 2011a). However, it still remains unclear which fibers in pSTS (e.g., ILF and IFOF) have FA alterations in people with ASD.
In the current study, we aimed to identify the anatomy of autistic trait-related FA alterations in the pSTS region with a method using TBSS and subsequent tractography. We used the autism spectrum quotient (AQ), a well-validated self-report questionnaire of autistic tendency (Baron-Cohen et al., 2001b, Wakabayashi et al., 2006), for a large sample of healthy adults and investigated regions where FA values would be associated with autistic traits using TBSS. We then performed tractography and examined in which fiber tract in pSTS such autistic-trait-related FA alterations were located.
Section snippets
Participants
Ninety-seven healthy adults participated in this study (mean age 28 years; age range, 19–55 years; 47 females; 5 left-handed subjects). Autism spectrum traits were measured with AQ for all participants. To assess the intelligence quotient (IQ), vocabulary task and block design of the Wechsler adult intelligence scale revised (WAIS-R) were carried out. The structured clinical interview for DSM-IV axis I disorders (SCID) was performed by trained psychiatrists to check for current or past history
Results
The demographic data and AQ score are shown in Table 1. There was no gender difference in age and AQ score. AQ was correlated with age. Although two participants had higher AQ score than the cut-off level, we confirmed that they revealed no impairments in social interaction and communication in a detailed interview by experienced psychiatrists.
TBSS revealed 5 clusters with a significantly negative correlation between FA and AQ (Table 2). No clusters showed a significantly positive correlation.
Discussion
We found that autistic traits in healthy adults were significantly correlated with the FA values of white matter in several regions such as IFOF/ILF, PLIC/corona radiata, fornix, corpus callosum (CC), AF and anterior thalamic radiation (ATR). In the region of pSTS, a key brain area in the pathophysiology of ASD, we found altered white matter integrity in IFOF.
The fibers in which the current TBSS revealed FA negatively correlated with AQ were similar to those where previous TBSS was found with
The role of funding source
This work was supported by grants-in-aid for scientific research A (24243061), B (23390290), S (22220003), and on Innovative Areas (23118004, 23120009), from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Young Scientists A (23680045), B (23791329) from the Japan Society for the Promotion of Science, and a Health and Labour Science Research Grant for Research on Applying Health Technology (H25-seishin-jitsuyouka-ippan-001) from the Ministry of
Contributors
Hidehiko Takahashi and Toshiya Murai designed the study. Genichi Sugihara wrote the protocol. Manabu Kubota and Akihiko Sasamoto operated the magnetic resonance imaging (MRI) machine. Toshihiko Aso and Hidenao Fukuyama supervised the operation of MRI and analysis of the data. Jun Miyata managed the analyses. Kimito Hirose wrote the draft of the manuscript. All authors contributed and have approved the final manuscript.
Conflict of interest
All authors declare that they have no conflicts of interest.
Acknowledgments
The authors wish to extend their gratitude to Ryosaku Kawada, Yusuke Tanaka, Shinsuke Fujimoto, Shiho Ubukata, Yukiko Matsumoto, Masanori Isobe, Yasuo Mori, Shuraku Son, Kousuke Tsurumi, Naoto Yokoyama and all other staffs for their assistance in data acquisition and processing, and most of all, to the volunteers for participating in the study.
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