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...2>λ3. Subjects' FA data were aligned into a common space using the nonlinear registration tool FNIRT (Andersson et al., 2007a, b), which uses a b-spline representation of the registration warp field (=-=Rueckert et al., 1999-=-). In the next step, the mean FA image was created and thinned to create a mean FA skeleton representing the centers of all tracts common to the whole study group. To exclude gray matter or CSF,Fig. 1...

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... (ASD vs. NT). To calculate brain size, total intracranial volume (TIV) was used. TIV was found after deleting non-brain tissue from T1-image of the whole head, using FSL Brain Extraction Tool (BET) (=-=Smith, 2002-=-). Given that previous studies have shown that the distribution of FA data is substantially non-Gaussian (Jones et al., 2005; Smith et al., 2006), a non-parametric two-sample permutation test was perf...

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...s were confirmed by an experienced clinician based on current presentation and developmental history of ASD participants using the Autism Diagnostic Observation Schedule using modules 3 and 4 (ADOS) (=-=Lord et al., 2000-=-) and the Autism Diagnostic InterviewRevised (ADI-R) (Lord et al., 1994). The adolescent group consisted of 16 high-functioning individuals with ASD (mean age±SD: 15.5±2.8 years; range: 10.1–19.9) and...

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...d Pierpaoli, 1996), a quantitative indexwhich is sensitive to developmental and pathological differences, such as axon myelination, diameter distribution, axon density, and architecture of WM fibers (=-=Beaulieu, 2002-=-; Pierpaoli et al., 2001). To date, three main approaches have been used to analyze DTI data (Jones, 2010). The first method, widely used in autism research, served. is voxel-based statistics of FA im...

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...twenties in the CC, the ILF, the SLF and the IFOF in typical development (Lebel et al., 2008; Snook et al., 2005). Maturation of the brain is heterogeneous and variable during post-natal development (=-=Gogtay et al., 2004-=-; Golarai et al., 2007; Luna et al., 2004; lation studied (NT and ASD, across all ages). MNI coordinates t-Peak Size x y z −23 −19 43 3.35 50 temporal part) 48 −45 −5 4.06 30 −18 −39 −5 3.02 27Scherf ...

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...Noriuchi et al., 2010; Thakkar et al., 2008). A major shortcoming of this approach, however, is the lack of a satisfactory standard registration algorithm for aligning FA images of multiple subjects (=-=Smith et al., 2006-=-). The second approach, Diffusion Tensor Tractography (DTT), compares diffusion measures along WM tracts, computed from the direction of maximal diffusion in each voxel. DTT has been used to 2. Materi...

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... Charlestown, MA, USA : Clinical l sev ie r .com/ locate /yn ic lPierpaoli, 1996; Le Bihan et al., 2001). Direction-dependent diffusivity of watermolecules is reflected in fractional anisotropy (FA) (=-=Basser and Pierpaoli, 1996-=-), a quantitative indexwhich is sensitive to developmental and pathological differences, such as axon myelination, diameter distribution, axon density, and architecture of WM fibers (Beaulieu, 2002; P...

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...tion, organization, self-monitoring, cognitive flexibility and set-shifting. The EF hypothesis is one of the proposed theories to explain the triad of impairments in autism (Hughes and Russell, 1993; =-=Ozonoff et al., 1991-=-), and EF impairments have been documented in ASD (Bennetto et al., 1996; Hughes et al., 1994; Just et al., 2007; Minshew et al., 2002; Ozonoff and Jensen, 1999; Ozonoff and McEvoy, 1994; Ozonoff et a...

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...OS social scores in both adolescents and adults. Decreased FA was also found in the IFOF, connecting the occipital cortex through the uncinate fasciculus, and terminating in the orbitofrontal cortex (=-=Catani et al., 2002-=-; Catani et al., 2003), and a negative correlation between FA in IFOF was found with ADOS and ADI-R communication scores in adolescents and in adults. These2009), and decreased FA values in the cerebe...

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...impairments in communication and reciprocal social interaction as well as by the presence of repetitive and stereotyped behaviors. birth, brain size of individuals later diagnosed with ASD is normal (=-=Courchesne et al., 2003-=-; Lainhart et al., 1997). However, in contrast to typically developing children, brain size rapidly increases during the first few years of life up to ages 2 to 4 years in children with autism, partic...

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...zlett et al., 2011; Herbert et al., 2004). WM developmental changes have been studied using Diffusion Tensor Imaging (DTI), a method based on local microstructural characteristics of water diffusion (=-=Basser and Jones, 2002-=-; Basser and Abbreviations:ADOS, AutismDiagnostic Observation Schedule; ADI-R, AutismDiagnostic Interview-Revised;AQ,AutismQuotient; ASD,AutismSpectrumDisorders; ATR, anterior thalamic radiations; CC,...

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...owever, in contrast to typically developing children, brain size rapidly increases during the first few years of life up to ages 2 to 4 years in children with autism, particularly in frontal regions (=-=Courchesne et al., 2001-=-; Hazlett et al., 2011; Sparks et al., 2002). The observed increase tends to stabilize during adolescence, resulting in a normal brain size in adulthood (Redcay and Courchesne, 2005), but see Piven et...

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...in ASD. Differences of WM were however absent in adults. Several studies report a decrease of the behavioral difficulties experienced by high-functioning individuals with ASD as they enter adulthood (=-=Howlin et al., 2004-=-; Seltzer et al., 2003; Shattuck et al., 2007). The present results, showing a normalization of diffusion indices over time, may represent one of the mechanisms underlying this behavioral amelioration...

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...×128, scan time 11:57. 2.3. Tract-based Spatial Statistics DTI data processing was carried out using FMRIB's Diffusion Toolkit (FDT), part of FSL v.4.1.6 (FMRIB software Library) (Smith et al., 2004; =-=Woolrich et al., 2009-=-). Motion and eddy current correction was performed and diffusion tensors were fitted onto corrected data. The six independent elements of the diffusion tensor were calculated from each diffusion-weig...

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...0 permutations. Thresholdfree Cluster Enhancement (TFCE) was performed in order to enhance cluster-like structures without prior definition of a cluster-forming threshold or extensive data smoothing (=-=Smith and Nichols, 2009-=-). In order to control for multiple voxel-wise comparisons, family-wise error correctionwas performed and the resulting significance threshold was pb0.05, corrected for multiple comparisons. In order ...

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...al and social functioning (Paul et al., 2007). Developmental studies report a gradual increase of the FA from childhood until twenties in the CC, the ILF, the SLF and the IFOF in typical development (=-=Lebel et al., 2008-=-; Snook et al., 2005). Maturation of the brain is heterogeneous and variable during post-natal development (Gogtay et al., 2004; Golarai et al., 2007; Luna et al., 2004; lation studied (NT and ASD, ac...

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...rments in autism (Hughes and Russell, 1993; Ozonoff et al., 1991), and EF impairments have been documented in ASD (Bennetto et al., 1996; Hughes et al., 1994; Just et al., 2007; Minshew et al., 2002; =-=Ozonoff and Jensen, 1999-=-; Ozonoff and McEvoy, 1994; Ozonoff et al., 1991). A few studies have investigated the nature and extent of developmental changes in EF. In a 3-year follow-up study, no significant improvements were o...

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...as assessed using the Wechsler non-verbal scale (Wechsler, 1997; Wechsler and Naglieri, 2006). All participants completed the Autism Quotient (AQ) self-report questionnaire (Baron-Cohen et al., 2006; =-=Woodbury-Smith et al., 2005-=-). Both adolescent and adult groups were matched for age and IQ (see Table 1 for participants' characteristics). 2.2. Data acquisition Data were acquired using a 3 T high-speed echoplanar-imaging devi...

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...ecially during the first 12 months (Gao et al., 2009; Hermoye et al., 2006). FA values continue to increase, albeit at a slower rate during late childhood and adolescence (Barnea-Goraly et al., 2005; =-=Schmithorst et al., 2002-=-; Schmithorst and Yuan, 2010), and, in adulthood, tend to decrease with age (Abe et al., 2008; Barrick et al., 2010; Madden et al., 2004; Pfefferbaum and Sullivan, 2003; Sullivan et al., 2001; Sulliva...

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...e IFOF in typical development (Lebel et al., 2008; Snook et al., 2005). Maturation of the brain is heterogeneous and variable during post-natal development (Gogtay et al., 2004; Golarai et al., 2007; =-=Luna et al., 2004-=-; lation studied (NT and ASD, across all ages). MNI coordinates t-Peak Size x y z −23 −19 43 3.35 50 temporal part) 48 −45 −5 4.06 30 −18 −39 −5 3.02 27Scherf et al., 2007) and may be especially sensi...

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...with autism (mean age 12.4 years) (Ozonoff and McEvoy, 1994). Griffith et al., reported the same finding regarding perseverative errors in autistic children (mean age 4.3 years) over a 1-year period (=-=Griffith et al., 1999-=-). In a recent study examining a 3-year period, Pellicano showed that children (mean age 5.6 years) with ASD obtained significantly lower planning scores than typical controls. Over time, although EF ...

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...ning and execution, inhibition, organization, self-monitoring, cognitive flexibility and set-shifting. The EF hypothesis is one of the proposed theories to explain the triad of impairments in autism (=-=Hughes and Russell, 1993-=-; Ozonoff et al., 1991), and EF impairments have been documented in ASD (Bennetto et al., 1996; Hughes et al., 1994; Just et al., 2007; Minshew et al., 2002; Ozonoff and Jensen, 1999; Ozonoff and McEv...

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... is one of the proposed theories to explain the triad of impairments in autism (Hughes and Russell, 1993; Ozonoff et al., 1991), and EF impairments have been documented in ASD (Bennetto et al., 1996; =-=Hughes et al., 1994-=-; Just et al., 2007; Minshew et al., 2002; Ozonoff and Jensen, 1999; Ozonoff and McEvoy, 1994; Ozonoff et al., 1991). A few studies have investigated the nature and extent of developmental changes in ...

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...., 2004; Golarai et al., 2007; Luna et al., 2004; lation studied (NT and ASD, across all ages). MNI coordinates t-Peak Size x y z −23 −19 43 3.35 50 temporal part) 48 −45 −5 4.06 30 −18 −39 −5 3.02 27=-=Scherf et al., 2007-=-) and may be especially sensitive to factors affecting the speed of neuronal maturation as well as myelin development, which may play a major role in autism etiology (Chomiak et al., 2010; Rodier, 200...

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... during early childhood, especially during the first 12 months (Gao et al., 2009; Hermoye et al., 2006). FA values continue to increase, albeit at a slower rate during late childhood and adolescence (=-=Barnea-Goraly et al., 2005-=-; Schmithorst et al., 2002; Schmithorst and Yuan, 2010), and, in adulthood, tend to decrease with age (Abe et al., 2008; Barrick et al., 2010; Madden et al., 2004; Pfefferbaum and Sullivan, 2003; Sull...

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...orly to emotion-related regions, including the amygdala and the orbitofrontal cortex (Philippi et al., 2009). The right ILF plays an important role in the recognition of emotional facial expressions (=-=Kleinhans et al., 2008-=-; Pugliese et al., 2009) and damages to the right ILF after a stroke have been associated with emotion recognition impairments (Philippi et al., 2009). Damage to the right IFOF results in overall faci...

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...he ILF, the SLF and the IFOF in typical development (Lebel et al., 2008; Snook et al., 2005). Maturation of the brain is heterogeneous and variable during post-natal development (Gogtay et al., 2004; =-=Golarai et al., 2007-=-; Luna et al., 2004; lation studied (NT and ASD, across all ages). MNI coordinates t-Peak Size x y z −23 −19 43 3.35 50 temporal part) 48 −45 −5 4.06 30 −18 −39 −5 3.02 27Scherf et al., 2007) and may ...

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...ain tissue from T1-image of the whole head, using FSL Brain Extraction Tool (BET) (Smith, 2002). Given that previous studies have shown that the distribution of FA data is substantially non-Gaussian (=-=Jones et al., 2005-=-; Smith et al., 2006), a non-parametric two-sample permutation test was performed to study between-group (ASD vs. NT) differences using the randomise tool available in FSL (http://www.fmrib.ox. ac.uk/...

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...ldren, brain size rapidly increases during the first few years of life up to ages 2 to 4 years in children with autism, particularly in frontal regions (Courchesne et al., 2001; Hazlett et al., 2011; =-=Sparks et al., 2002-=-). The observed increase tends to stabilize during adolescence, resulting in a normal brain size in adulthood (Redcay and Courchesne, 2005), but see Piven et al. (1996). Brain enlargement has been ass...

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...elligence Quotient (PIQ) was assessed using the Wechsler non-verbal scale (Wechsler, 1997; Wechsler and Naglieri, 2006). All participants completed the Autism Quotient (AQ) self-report questionnaire (=-=Baron-Cohen et al., 2006-=-; Woodbury-Smith et al., 2005). Both adolescent and adult groups were matched for age and IQ (see Table 1 for participants' characteristics). 2.2. Data acquisition Data were acquired using a 3 T high-...

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...oning (Paul et al., 2007). Developmental studies report a gradual increase of the FA from childhood until twenties in the CC, the ILF, the SLF and the IFOF in typical development (Lebel et al., 2008; =-=Snook et al., 2005-=-). Maturation of the brain is heterogeneous and variable during post-natal development (Gogtay et al., 2004; Golarai et al., 2007; Luna et al., 2004; lation studied (NT and ASD, across all ages). MNI ...

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...a normal brain size in adulthood (Redcay and Courchesne, 2005), but see Piven et al. (1996). Brain enlargement has been associated with increases in WM volume (Ben Bashat, 2011; Hazlett et al., 2011; =-=Herbert et al., 2004-=-). WM developmental changes have been studied using Diffusion Tensor Imaging (DTI), a method based on local microstructural characteristics of water diffusion (Basser and Jones, 2002; Basser and Abbre...

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...nd Russell, 1993; Ozonoff et al., 1991), and EF impairments have been documented in ASD (Bennetto et al., 1996; Hughes et al., 1994; Just et al., 2007; Minshew et al., 2002; Ozonoff and Jensen, 1999; =-=Ozonoff and McEvoy, 1994-=-; Ozonoff et al., 1991). A few studies have investigated the nature and extent of developmental changes in EF. In a 3-year follow-up study, no significant improvements were observed in planning effici...

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...ain the triad of impairments in autism (Hughes and Russell, 1993; Ozonoff et al., 1991), and EF impairments have been documented in ASD (Bennetto et al., 1996; Hughes et al., 1994; Just et al., 2007; =-=Minshew et al., 2002-=-; Ozonoff and Jensen, 1999; Ozonoff and McEvoy, 1994; Ozonoff et al., 1991). A few studies have investigated the nature and extent of developmental changes in EF. In a 3-year follow-up study, no signi...

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...6), a quantitative indexwhich is sensitive to developmental and pathological differences, such as axon myelination, diameter distribution, axon density, and architecture of WM fibers (Beaulieu, 2002; =-=Pierpaoli et al., 2001-=-). To date, three main approaches have been used to analyze DTI data (Jones, 2010). The first method, widely used in autism research, served. is voxel-based statistics of FA images (VBM-like), in whic...

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...lescence (Barnea-Goraly et al., 2005; Schmithorst et al., 2002; Schmithorst and Yuan, 2010), and, in adulthood, tend to decrease with age (Abe et al., 2008; Barrick et al., 2010; Madden et al., 2004; =-=Pfefferbaum and Sullivan, 2003-=-; Sullivan et al., 2001; Sullivan and Pfefferbaum, 2006). In this study we assessed WM integrity in younger (from 10 to 20 years old) and older (from 21 to 43 years old) participants with ASD compared...

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...f WM were however absent in adults. Several studies report a decrease of the behavioral difficulties experienced by high-functioning individuals with ASD as they enter adulthood (Howlin et al., 2004; =-=Seltzer et al., 2003-=-; Shattuck et al., 2007). The present results, showing a normalization of diffusion indices over time, may represent one of the mechanisms underlying this behavioral amelioration. Moreover, the presen...

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...l abnormalities. A reduced FA in the CT, also reported in Brito et al. (2009) and Shukla et al. (2011a) may be related to the clumsiness often reported in ASD. In accordance with several DTI studies (=-=Alexander et al., 2007-=-; Brito et al., 2009; Keller et al., 2007; Kumar et al., 2010; Noriuchi et al., 2010; Shukla et al., 2011a), we observed a reduced FA in adolescents with ASD in the genu, body and splenium of the CC. ...

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...oxel group-wise comparison of anisotropy is performed on a common space (Ben Bashat et al., 2007; Bloemen et al., 2010; Cheung et al., 2009; Conturo et al., 2008; Groen et al., 2010; Ke et al., 2009; =-=Keller et al., 2007-=-; Lee et al., 2007; Noriuchi et al., 2010; Thakkar et al., 2008). A major shortcoming of this approach, however, is the lack of a satisfactory standard registration algorithm for aligning FA images of...

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...., 2002; Schmithorst and Yuan, 2010), and, in adulthood, tend to decrease with age (Abe et al., 2008; Barrick et al., 2010; Madden et al., 2004; Pfefferbaum and Sullivan, 2003; Sullivan et al., 2001; =-=Sullivan and Pfefferbaum, 2006-=-). In this study we assessed WM integrity in younger (from 10 to 20 years old) and older (from 21 to 43 years old) participants with ASD compared to NT. Developmental changes were then investigated by...

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... order to assess FA values in long-range connections. TBSS has been applied to autism research in recent studies performed in children and adolescents (Ameis et al., 2011; Barnea-Goraly et al., 2010; =-=Cheng et al., 2010-=-; Kumar et al., 2010; Sahyoun et al., 2010a; Shukla et al., 2011a; Weinstein et al., 2011). Previous DTI studies have shown that WM development is not a linear process. Moreover, the rate of change in...

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...ate childhood and adolescence (Barnea-Goraly et al., 2005; Schmithorst et al., 2002; Schmithorst and Yuan, 2010), and, in adulthood, tend to decrease with age (Abe et al., 2008; Barrick et al., 2010; =-=Madden et al., 2004-=-; Pfefferbaum and Sullivan, 2003; Sullivan et al., 2001; Sullivan and Pfefferbaum, 2006). In this study we assessed WM integrity in younger (from 10 to 20 years old) and older (from 21 to 43 years old...

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...2005; Schmithorst et al., 2002; Schmithorst and Yuan, 2010), and, in adulthood, tend to decrease with age (Abe et al., 2008; Barrick et al., 2010; Madden et al., 2004; Pfefferbaum and Sullivan, 2003; =-=Sullivan et al., 2001-=-; Sullivan and Pfefferbaum, 2006). In this study we assessed WM integrity in younger (from 10 to 20 years old) and older (from 21 to 43 years old) participants with ASD compared to NT. Developmental c...

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...been applied to autism research in recent studies performed in children and adolescents (Ameis et al., 2011; Barnea-Goraly et al., 2010; Cheng et al., 2010; Kumar et al., 2010; Sahyoun et al., 2010a; =-=Shukla et al., 2011a-=-; Weinstein et al., 2011). Previous DTI studies have shown that WM development is not a linear process. Moreover, the rate of change in FA values and other WM indices varies across the brain. Neverthe...

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...ion and reciprocal social interaction as well as by the presence of repetitive and stereotyped behaviors. birth, brain size of individuals later diagnosed with ASD is normal (Courchesne et al., 2003; =-=Lainhart et al., 1997-=-). However, in contrast to typically developing children, brain size rapidly increases during the first few years of life up to ages 2 to 4 years in children with autism, particularly in frontal regio...

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... and the processing and regulation of emotions) may be particularly altered during development. A recent comprehensive review reporting the results of all DTI studies in autism between 2004 and 2012 (=-=Travers et al., 2012-=-) underlines the atypical developmental trajectory of white matter in autism. 54 R. Bakhtiari et al. / NeuroImage: Clinical 1 (2012) 48–565. Conclusion During typical development, maturation of WM tra...

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...2 NT were included in the final analysis. (M/ 49R. Bakhtiari et al. / NeuroImage: Clinical 1 (2012) 48–56investigate the integrity of specific WM tracts in individuals with autism in several studies (=-=Catani et al., 2008-=-; Knaus et al., 2009; Kumar et al., 2010; Pugliese et al., 2009; Sahyoun et al., 2010b; Sundaram et al., 2008; Thomas et al., 2011; Weinstein et al., 2011). This approach has however been criticized f...

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...t al., 2009; Shukla et al., 2011a; Sundaram et al., 2008). The left ILF is involved in language (Mandonnet et al., 2007). Decreased ILF volume has been reported in high-functioning children with ASD (=-=Waiter et al., 2005-=-), and a decreased FA in this region was reported by Jou et al. in children with ASD (Jou et al., 2010; Jou et al., 2011). In adolescents with ASD, alterations in myelin structure were also observed b...

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...ice for the current study in order to assess FA values in long-range connections. TBSS has been applied to autism research in recent studies performed in children and adolescents (Ameis et al., 2011; =-=Barnea-Goraly et al., 2010-=-; Cheng et al., 2010; Kumar et al., 2010; Sahyoun et al., 2010a; Shukla et al., 2011a; Weinstein et al., 2011). Previous DTI studies have shown that WM development is not a linear process. Moreover, t...

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...rst method, widely used in autism research, served. is voxel-based statistics of FA images (VBM-like), in which a voxelby-voxel group-wise comparison of anisotropy is performed on a common space (Ben =-=Bashat et al., 2007-=-; Bloemen et al., 2010; Cheung et al., 2009; Conturo et al., 2008; Groen et al., 2010; Ke et al., 2009; Keller et al., 2007; Lee et al., 2007; Noriuchi et al., 2010; Thakkar et al., 2008). A major sho...

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...ch as axon myelination, diameter distribution, axon density, and architecture of WM fibers (Beaulieu, 2002; Pierpaoli et al., 2001). To date, three main approaches have been used to analyze DTI data (=-=Jones, 2010-=-). The first method, widely used in autism research, served. is voxel-based statistics of FA images (VBM-like), in which a voxelby-voxel group-wise comparison of anisotropy is performed on a common sp...

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...rison of anisotropy is performed on a common space (Ben Bashat et al., 2007; Bloemen et al., 2010; Cheung et al., 2009; Conturo et al., 2008; Groen et al., 2010; Ke et al., 2009; Keller et al., 2007; =-=Lee et al., 2007-=-; Noriuchi et al., 2010; Thakkar et al., 2008). A major shortcoming of this approach, however, is the lack of a satisfactory standard registration algorithm for aligning FA images of multiple subjects...

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... other WM indices varies across the brain. Nevertheless in typical development, there is a general trend toward an increase in FA values during early childhood, especially during the first 12 months (=-=Gao et al., 2009-=-; Hermoye et al., 2006). FA values continue to increase, albeit at a slower rate during late childhood and adolescence (Barnea-Goraly et al., 2005; Schmithorst et al., 2002; Schmithorst and Yuan, 2010...

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... served. is voxel-based statistics of FA images (VBM-like), in which a voxelby-voxel group-wise comparison of anisotropy is performed on a common space (Ben Bashat et al., 2007; Bloemen et al., 2010; =-=Cheung et al., 2009-=-; Conturo et al., 2008; Groen et al., 2010; Ke et al., 2009; Keller et al., 2007; Lee et al., 2007; Noriuchi et al., 2010; Thakkar et al., 2008). A major shortcoming of this approach, however, is the ...

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...which a voxelby-voxel group-wise comparison of anisotropy is performed on a common space (Ben Bashat et al., 2007; Bloemen et al., 2010; Cheung et al., 2009; Conturo et al., 2008; Groen et al., 2010; =-=Ke et al., 2009-=-; Keller et al., 2007; Lee et al., 2007; Noriuchi et al., 2010; Thakkar et al., 2008). A major shortcoming of this approach, however, is the lack of a satisfactory standard registration algorithm for ...

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... (M/ 49R. Bakhtiari et al. / NeuroImage: Clinical 1 (2012) 48–56investigate the integrity of specific WM tracts in individuals with autism in several studies (Catani et al., 2008; Knaus et al., 2009; =-=Kumar et al., 2010-=-; Pugliese et al., 2009; Sahyoun et al., 2010b; Sundaram et al., 2008; Thomas et al., 2011; Weinstein et al., 2011). This approach has however been criticized for potentially resulting in erroneous an...

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...2 months (Gao et al., 2009; Hermoye et al., 2006). FA values continue to increase, albeit at a slower rate during late childhood and adolescence (Barnea-Goraly et al., 2005; Schmithorst et al., 2002; =-=Schmithorst and Yuan, 2010-=-), and, in adulthood, tend to decrease with age (Abe et al., 2008; Barrick et al., 2010; Madden et al., 2004; Pfefferbaum and Sullivan, 2003; Sullivan et al., 2001; Sullivan and Pfefferbaum, 2006). In...

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...crease, albeit at a slower rate during late childhood and adolescence (Barnea-Goraly et al., 2005; Schmithorst et al., 2002; Schmithorst and Yuan, 2010), and, in adulthood, tend to decrease with age (=-=Abe et al., 2008-=-; Barrick et al., 2010; Madden et al., 2004; Pfefferbaum and Sullivan, 2003; Sullivan et al., 2001; Sullivan and Pfefferbaum, 2006). In this study we assessed WM integrity in younger (from 10 to 20 ye...

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...tiari et al. / NeuroImage: Clinical 1 (2012) 48–56was calculated using eigenvalues of tensor: λ1>λ2>λ3. Subjects' FA data were aligned into a common space using the nonlinear registration tool FNIRT (=-=Andersson et al., 2007a-=-, b), which uses a b-spline representation of the registration warp field (Rueckert et al., 1999). In the next step, the mean FA image was created and thinned to create a mean FA skeleton representing...

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...us callosum is involved in the interhemispheric connection of multiple brain areas and is important for motor coordination, as well as for higher-order cognition and emotional and social functioning (=-=Paul et al., 2007-=-). Developmental studies report a gradual increase of the FA from childhood until twenties in the CC, the ILF, the SLF and the IFOF in typical development (Lebel et al., 2008; Snook et al., 2005). Mat...

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...mon space (Ben Bashat et al., 2007; Bloemen et al., 2010; Cheung et al., 2009; Conturo et al., 2008; Groen et al., 2010; Ke et al., 2009; Keller et al., 2007; Lee et al., 2007; Noriuchi et al., 2010; =-=Thakkar et al., 2008-=-). A major shortcoming of this approach, however, is the lack of a satisfactory standard registration algorithm for aligning FA images of multiple subjects (Smith et al., 2006). The second approach, D...

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... of specific WM tracts in individuals with autism in several studies (Catani et al., 2008; Knaus et al., 2009; Kumar et al., 2010; Pugliese et al., 2009; Sahyoun et al., 2010b; Sundaram et al., 2008; =-=Thomas et al., 2011-=-; Weinstein et al., 2011). This approach has however been criticized for potentially resulting in erroneous and completely artifactual pathways bearing no correspondence with the underlying neuroanato...

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...inical 1 (2012) 48–56investigate the integrity of specific WM tracts in individuals with autism in several studies (Catani et al., 2008; Knaus et al., 2009; Kumar et al., 2010; Pugliese et al., 2009; =-=Sahyoun et al., 2010b-=-; Sundaram et al., 2008; Thomas et al., 2011; Weinstein et al., 2011). This approach has however been criticized for potentially resulting in erroneous and completely artifactual pathways bearing no c...

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...ystem and in emotion regulation. 4.2. Language processing A decreased FA was found in adolescents with ASD bilaterally in the ILF. Abnormalities in the ILF in ASD have been observed in other studies (=-=Brito et al., 2009-=-; Jou et al., 2011; Pugliese et al., 2009; Shukla et al., 2011a; Sundaram et al., 2008). The left ILF is involved in language (Mandonnet et al., 2007). Decreased ILF volume has been reported in high-f...

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...in the ILF in ASD have been observed in other studies (Brito et al., 2009; Jou et al., 2011; Pugliese et al., 2009; Shukla et al., 2011a; Sundaram et al., 2008). The left ILF is involved in language (=-=Mandonnet et al., 2007-=-). Decreased ILF volume has been reported in high-functioning children with ASD (Waiter et al., 2005), and a decreased FA in this region was reported by Jou et al. in children with ASD (Jou et al., 20...

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...y is performed on a common space (Ben Bashat et al., 2007; Bloemen et al., 2010; Cheung et al., 2009; Conturo et al., 2008; Groen et al., 2010; Ke et al., 2009; Keller et al., 2007; Lee et al., 2007; =-=Noriuchi et al., 2010-=-; Thakkar et al., 2008). A major shortcoming of this approach, however, is the lack of a satisfactory standard registration algorithm for aligning FA images of multiple subjects (Smith et al., 2006). ...

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...pically developing children, brain size rapidly increases during the first few years of life up to ages 2 to 4 years in children with autism, particularly in frontal regions (Courchesne et al., 2001; =-=Hazlett et al., 2011-=-; Sparks et al., 2002). The observed increase tends to stabilize during adolescence, resulting in a normal brain size in adulthood (Redcay and Courchesne, 2005), but see Piven et al. (1996). Brain enl...

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... planning scores than typical controls. Over time, although EF abilities improved significantly in both groups, children with ASDmade significantly more gains in planning tasks than typical children (=-=Pellicano, 2010-=-). In line with the behavioral developmental results described above, we observed WM differences in the SLF in the younger group. Those differences were absent in the adult group, pointing to amaturat...

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...ed statistics of FA images (VBM-like), in which a voxelby-voxel group-wise comparison of anisotropy is performed on a common space (Ben Bashat et al., 2007; Bloemen et al., 2010; Cheung et al., 2009; =-=Conturo et al., 2008-=-; Groen et al., 2010; Ke et al., 2009; Keller et al., 2007; Lee et al., 2007; Noriuchi et al., 2010; Thakkar et al., 2008). A major shortcoming of this approach, however, is the lack of a satisfactory...

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... the final analysis. (M/ 49R. Bakhtiari et al. / NeuroImage: Clinical 1 (2012) 48–56investigate the integrity of specific WM tracts in individuals with autism in several studies (Catani et al., 2008; =-=Knaus et al., 2009-=-; Kumar et al., 2010; Pugliese et al., 2009; Sahyoun et al., 2010b; Sundaram et al., 2008; Thomas et al., 2011; Weinstein et al., 2011). This approach has however been criticized for potentially resul...

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...t al., 2007) and may be especially sensitive to factors affecting the speed of neuronal maturation as well as myelin development, which may play a major role in autism etiology (Chomiak et al., 2010; =-=Rodier, 2004-=-). Our data indicate that in adolescents with ASD, the substrate of higher integrative functions (including areas involved in speech processing, executive functions, and the processing and regulation ...

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... connections. TBSS has been applied to autism research in recent studies performed in children and adolescents (Ameis et al., 2011; Barnea-Goraly et al., 2010; Cheng et al., 2010; Kumar et al., 2010; =-=Sahyoun et al., 2010a-=-; Shukla et al., 2011a; Weinstein et al., 2011). Previous DTI studies have shown that WM development is not a linear process. Moreover, the rate of change in FA values and other WM indices varies acro...

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...a slower rate during late childhood and adolescence (Barnea-Goraly et al., 2005; Schmithorst et al., 2002; Schmithorst and Yuan, 2010), and, in adulthood, tend to decrease with age (Abe et al., 2008; =-=Barrick et al., 2010-=-; Madden et al., 2004; Pfefferbaum and Sullivan, 2003; Sullivan et al., 2001; Sullivan and Pfefferbaum, 2006). In this study we assessed WM integrity in younger (from 10 to 20 years old) and older (fr...

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... anger and fear, and it has been suggested that impairment in fear recognition can result from a damage to the IFOF (Philippi et al., 2009). In line with previous studies (Barnea-Goraly et al., 2010; =-=Jou et al., 2011-=-; Noriuchi et al., 2010; Shukla et al., 2011a, but see Weinstein et al., 2011), we found a reduced FA in the cingulum in adolescents with ASD. The cingulum is medial to the cingulate gyrus and connect...

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...ade of face information conveyed from the occipito-temporal regions, including the Fusiform Face Area (FFA) anteriorly to emotion-related regions, including the amygdala and the orbitofrontal cortex (=-=Philippi et al., 2009-=-). The right ILF plays an important role in the recognition of emotional facial expressions (Kleinhans et al., 2008; Pugliese et al., 2009) and damages to the right ILF after a stroke have been associ...

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...ly in frontal regions (Courchesne et al., 2001; Hazlett et al., 2011; Sparks et al., 2002). The observed increase tends to stabilize during adolescence, resulting in a normal brain size in adulthood (=-=Redcay and Courchesne, 2005-=-), but see Piven et al. (1996). Brain enlargement has been associated with increases in WM volume (Ben Bashat, 2011; Hazlett et al., 2011; Herbert et al., 2004). WM developmental changes have been stu...

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...h autistic traits. 4.3. Executive functioning A positive correlation between FA in the SLF and executive function (EF) performance has been shown in typically developing children, independent of age (=-=Vestergaard et al., 2011-=-). Executivefunctions (EF) include skills required for action planning and execution, inhibition, organization, self-monitoring, cognitive flexibility and set-shifting. The EF hypothesis is one of the...

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...as the method of choice for the current study in order to assess FA values in long-range connections. TBSS has been applied to autism research in recent studies performed in children and adolescents (=-=Ameis et al., 2011-=-; Barnea-Goraly et al., 2010; Cheng et al., 2010; Kumar et al., 2010; Sahyoun et al., 2010a; Shukla et al., 2011a; Weinstein et al., 2011). Previous DTI studies have shown that WM development is not a...

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...−39 −5 3.02 27Scherf et al., 2007) and may be especially sensitive to factors affecting the speed of neuronal maturation as well as myelin development, which may play a major role in autism etiology (=-=Chomiak et al., 2010-=-; Rodier, 2004). Our data indicate that in adolescents with ASD, the substrate of higher integrative functions (including areas involved in speech processing, executive functions, and the processing a...

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...t et al., 2007). Decreased ILF volume has been reported in high-functioning children with ASD (Waiter et al., 2005), and a decreased FA in this region was reported by Jou et al. in children with ASD (=-=Jou et al., 2010-=-; Jou et al., 2011). In adolescents with ASD, alterations in myelin structure were also observed bilaterally in the SLF, a pathway connecting the frontal lobes to temporal and parietal lobes (Wakana e...

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...nt in adults. Several studies report a decrease of the behavioral difficulties experienced by high-functioning individuals with ASD as they enter adulthood (Howlin et al., 2004; Seltzer et al., 2003; =-=Shattuck et al., 2007-=-). The present results, showing a normalization of diffusion indices over time, may represent one of the mechanisms underlying this behavioral amelioration. Moreover, the present data suggest that it ...

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...n adolescents with ASD in the genu, body and splenium of the CC. Differences in callosal size has been reported in children with autism, with the rostral body tending to normalize by mid-adolescence (=-=Frazier et al., 2012-=-). Here we also found a negative correlation between the splenium of the CC and the ADI-R communication scores in adults. Correlation with age in the CC was significantly different between groups when...

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... transmission in this region, due to altered myelin structure, has been reported in recent studies (Shukla et al., 2011b; Weinstein et al., 2011), and may be at the basis of language deficits in ASD (=-=Levy et al., 2010-=-). In adolescents, FA values in the left SLF were positively correlated with ADI-R communication scores. Abnormalities in the right SLF have also been associated with attention deficits (Konrad et al....

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...sorder not otherwise specified (2 participants) and 19 NT (28.6±5.6 years; range: 22.2–42.9). Performance Intelligence Quotient (PIQ) was assessed using the Wechsler non-verbal scale (Wechsler, 1997; =-=Wechsler and Naglieri, 2006-=-). All participants completed the Autism Quotient (AQ) self-report questionnaire (Baron-Cohen et al., 2006; Woodbury-Smith et al., 2005). Both adolescent and adult groups were matched for age and IQ (...