Elsevier

Brain Research

Volume 1417, 12 October 2011, Pages 77-86
Brain Research

Research Report
Involvement of the anterior thalamic radiation in boys with high functioning autism spectrum disorders: A Diffusion Tensor Imaging study

https://doi.org/10.1016/j.brainres.2011.08.020Get rights and content

Abstract

Background: Autism has been hypothesized to reflect neuronal disconnection. Several recent reports implicate the key thalamic relay nuclei and cortico-thalamic connectivity in the pathophysiology of autism. Accordingly, we aimed to focus on evaluating the integrity of the thalamic radiation and sought to replicate prior white matter findings in Korean boys with high-functioning autism spectrum disorders (ASD) using Diffusion Tensor Imaging (DTI). Methods: We compared fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in 17 boys with ASD and 17 typically developing controls in the anterior thalamic radiation (ATR), superior thalamic radiation (STR), posterior thalamic radiation (PTR), corpus callosum (CC), uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF). Results: The two groups were group-matched on age, IQ, handedness and head circumference. In whole-brain voxel-wise analyses, FA was significantly reduced and MD was significantly increased in the right ATR, CC, and left UF in subjects with ASD (p < 0.05, corrected). We found significantly lower FA in right and left ATR, CC, left UF and right and left ILF and significantly higher MD values of the CC in the ASD group in region of interest-based analyses. We also observed significantly higher RD values of right and left ATR, CC, left UF, left ILF in subjects with ASD compared to typically developing boys and significantly lower AD values of both ILF. Right ATR and right UF FA was significantly negatively correlated with total SRS score within the ASD group (r = −.56, p = .02). Conclusions: Our preliminary findings support evidence implicating disturbances in the thalamo-frontal connections in autism. These findings highlight the role of hypoconnectivity between the frontal cortex and thalamus in ASD.

Highlights

► We evaluate integrity of thalamic radiation and replicate prior DTI findings in ASD. ► We compare DTI parameters in ASD and controls in several ROIs. ► FA and MD in both ATR are significantly different between two groups.

Introduction

Autism spectrum disorders (ASD), which include autism, pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger's disorder, are characterized by qualitative impairments of reciprocal social interaction and deficits in communication, and stereotyped or repetitive patterns of behavior (APA, 2000). The pathophysiology of ASD remains unclear, but the hypothesis that ASD represents a disorder of neuronal connectivity (Brun et al., 2009, Gepner and Feron, 2009, Jones et al., 2010, Minshew and Williams, 2007) is supported by converging data using the Diffusion Tensor Imaging (DTI), a non-invasive MRI technique for in vivo mapping of white matter structures (Alexander et al., 2007, Barnea-Goraly et al., 2004, Ben Bashat et al., 2007, Brito et al., 2009, Keller et al., 2007, Kumar et al., 2010, Lee et al., 2007, Pugliese et al., 2009, Sundaram et al., 2008). Reductions in DTI fractional anisotropy (FA) are believed to reflect less myelinated and less mature white matter tracts (Mori et al., 2005, Vangberg et al., 2006). Most studies in ASD have confirmed decreased FA, particularly in the corpus callosum (CC) (Alexander et al., 2007, Barnea-Goraly et al., 2004, Brito et al., 2009, Keller et al., 2007, Kumar et al., 2010), although decreased FA has also been found in corticospinal tracts and cerebellar peduncles (Brito et al., 2009), the superior temporal gyrus and the temporal stem (Lee et al., 2007), the arcuate fasciculus (Kumar et al., 2010), and in frontal lobe fibers (Sundaram et al., 2008).

In ASD, preliminary lines of evidence support a role for the thalamus in the pathophysiology of autism (Hardan et al., 2006, Hardan et al., 2008a, Hardan et al., 2008b, Haznedar et al., 2006, Takarae et al., 2007, Tsatsanis et al., 2003, Waiter et al., 2005). Several groups have reported reduced or abnormal size of the thalamus in autism (Hardan et al., 2006, Hardan et al., 2008a, Tsatsanis et al., 2003, Waiter et al., 2005), and a proton magnetic resonance spectroscopy study found decreased neuronal and glial metabolites in the thalamus of patients with autism (Hardan et al., 2008b). Early functional neuroimaging studies (Buchsbaum et al., 1992, Minshew et al., 1997, Rumsey et al., 1985) observed cortical and subcortical abnormalities in the thalamus and the basal ganglia. One previous study (Chugani et al., 1997) reported that decreased serotonin synthesis was found in the dentatothalamocortical pathway including the frontal cortex and the thalamus in boys with autism. In a functional imaging study (Muller et al., 1999), decreased functional activity in the dentatothalamocortical pathway was reported in high-functioning autistic adults while performing a verbal task.

Several studies have reported abnormalities in the cortico-striato-thalamic loops, which are implicated in sensory regulation (Carlsson, 2001), in ASD. This circuit, involving the frontal lobe, the cingulate, the striatum, and the thalamus, can be distinguished between dorsal and ventral components (Alexander et al., 1986). Specifically, loops from the anterior cingulate pass via the ventral striatum to the anterior thalamus (Gemmell and O'Mara, 2002, Vertes, 2002). Using positron emission tomography, ASD patients were found to have lower glucose metabolic activity in the thalamus and ventral basal ganglia than healthy comparisons; additionally, autistic patients had lower metabolic activity in the anterior thalamus than patients with Asperger's disorder (Haznedar et al., 2006). Despite these various observations regarding thalamic circuitry, there have been only a few reports regarding the integrity of the thalamic radiation using DTI methods in ASD (Cheung et al., 2009, Tan et al., 2010). There are several thalamocortical fibers which can be visualized in the DTI study. The anterior thalamic radiation (ATR) is a major projection from the thalamus which penetrates the anterior limb of the internal capsule, carrying reciprocal connections from the hypothalamus and limbic structures to the frontal cortex (Mori et al., 2005). The superior thalamic radiation (STR) consists of fibers traveling from the ventral posterior nuclei of the thalamus to the somatosensory area in the post central gyrus of the parietal cortex. The posterior thalamic radiation (PTR) is a projection fiber from the posterior part of the thalamus to the occipital cortex, which also includes the optic radiation (Wakana et al., 2004).

In this study, we aimed to examine the white matter integrity of the thalamic radiations using the DTI in a sample of Korean boys with high functioning ASD and age and sex matched healthy controls and to add an evidence of involvement of ATR, which has been much less interesting for DTI researchers in ASD, because disturbances in the thalamo-frontal connections in ASD have rarely been focused so far. We hypothesized that the integrity of the ATR, which refers to the thalamo-frontal connections, would be particularly abnormal in ASD subjects compared to the healthy control subjects. We also examined several white matter structures that underlie social processing and the principal cerebral commissure, the CC, to confirm previous reports of abnormality in these tracts (Alexander et al., 2007, Barnea-Goraly et al., 2004, Brito et al., 2009, Keller et al., 2007, Kumar et al., 2010, Sundaram et al., 2008).

Section snippets

Results

As shown in Table 1, the groups did not differ significantly on age, IQ, handedness, or head circumference. The CPT RT SD was significantly higher in the ASD group than in the control group (t = 2.05, df = 32, p = .049). The nine clinically referred boys with ASD did not differ significantly from the eight boys ascertained from the epidemiological study on any of the demographic, clinical, or IQ measures (data not shown). Accordingly, all subsequent analyses combined all boys with ASD, regardless of

Discussion

In the present study, we found that FA in the right anterior thalamic radiation (ATR) was significantly lower and MD in the right ATR was significantly higher in subjects with ASD than healthy control subjects in both whole-brain voxel-wise analyses and ROI-based analyses. In addition, RD in both ATR was significantly higher in subjects with ASD than in healthy control subjects in ROI-based analyses. In contrast to the findings regarding the ATR, we did not find a significant difference in any

Conclusion

In conclusion, our observation of abnormal values in the ATR in ASD and our confirmation of abnormalities in white matter tracts that subserve social processing provide additional support for the centrality of dysconnection in the pathophysiology of autism. Furthermore, our results highlight the importance of thalamo-cortical circuitry in ASD which should be confirmed independently.

Subjects

ASD and healthy normal subjects were recruited from a child and adolescent psychiatric clinical group and from an ongoing community epidemiological study in the city of Koyang in South Korea. We initially enrolled and scanned 51 children (39 boys, 12 girls), but 5 boys and 2 girls met at least one exclusion criterion. Because only two girls with ASD remained, we limited analyses to male subjects. Accordingly, we analyzed the data of 34 boys (17 ASD patients and 17 typically developing controls

Acknowledgments

This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (KRF-2008-314-E00134).

References (55)

  • T.B. Jones et al.

    Sources of group differences in functional connectivity: an investigation applied to autism spectrum disorder

    Neuroimage.

    (2010)
  • K.H. Karlsgodt et al.

    White matter integrity and prediction of social and role functioning in subjects at ultra-high risk for psychosis

    Biol. Psychiatry

    (2009)
  • J.E. Lee et al.

    Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism

    Neurosci. Lett.

    (2007)
  • L. Pugliese et al.

    The anatomy of extended limbic pathways in Asperger syndrome: a preliminary diffusion tensor imaging tractography study

    Neuroimage

    (2009)
  • E.D. Ross

    Sensory-specific amnesia and hypoemotionality in humans and monkeys: gateway for developing a hodology of memory

    Cortex

    (2008)
  • S.M. Smith et al.

    Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference

    Neuroimage

    (2009)
  • S.M. Smith et al.

    Advances in functional and structural MR image analysis and implementation as FSL

    Neuroimage

    (2004)
  • S.M. Smith et al.

    Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data

    Neuroimage

    (2006)
  • Y. Takarae et al.

    Atypical involvement of frontostriatal systems during sensorimotor control in autism

    Psychiatry Res.

    (2007)
  • G.C. Tan et al.

    Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2

    Neuroimage

    (2010)
  • K.D. Tsatsanis et al.

    Reduced thalamic volume in high-functioning individuals with autism

    Biol. Psychiatry

    (2003)
  • T.R. Vangberg et al.

    Changes in white matter diffusion anisotropy in adolescents born prematurely

    Neuroimage

    (2006)
  • G.D. Waiter et al.

    Structural white matter deficits in high-functioning individuals with autistic spectrum disorder: a voxel-based investigation

    Neuroimage

    (2005)
  • G.E. Alexander et al.

    Parallel organization of functionally segregated circuits linking basal ganglia and cortex

    Annu. Rev. Neurosci.

    (1986)
  • APA

    American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders

    (2000)
  • A.R. Brito et al.

    Diffusion tensor imaging findings in school-aged autistic children

    J. Neuroimaging

    (2009)
  • C.C. Brun et al.

    Mapping brain abnormalities in boys with autism

    Hum. Brain Mapp.

    (2009)
  • Cited by (0)

    This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (KRF-2008-314-E00134).

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