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Erratum: No difference in hippocampus volume detected on magnetic resonance imaging in autistic individuals (Journal of Autism and Developmental Disorders 28:2 (105-110))
... An increase in hippocampal volume, persisting to adolescence, has also been reported in the literature [16]. However, other studies involving autistic adolescents and young adults showed no significant difference [17], or even a decrease in hippocampal volume [18]. Likewise, the orbitofrontal cortical thickness of ASD subjects was found to be enlarged in Ecker et al. [10], while decreased in other studies [11,19]. ...
... GLCMs are second-order statistics which estimate the properties of two or more pixel values occurring at specific locations relative to each other. Specifically, GLCM entries correspond to the co-occurrence probability P d,θ (i, j) of having intensities i and j in two pixels separated by a translation vector defined using direction θ and offset d (also known as distance) [11,[16][17][18][19]. Given a 2D image I of size N × N, the co-occurrence matrix P d,θ (i, j) can be defined element-wise as ...
... Our proposed approach differs from traditional techniques, which mostly rely on morphological and volumetric characteristics [16][17][18]. Research suggests that the white matter in young children with ASD may be abnormally homogeneous, and this may reflect poor organization or differentiation of pathways in the temporal lobe [58]. Another study using multimodality neuroimaging (e.g. ...
Abstract Background Emerging evidence suggests the presence of neuroanatomical abnormalities in subjects with autism spectrum disorder (ASD). Identifying anatomical correlates could thus prove useful for the automated diagnosis of ASD. Radiomic analyses based on MRI texture features have shown a great potential for characterizing differences occurring from tissue heterogeneity, and for identifying abnormalities related to these differences. However, only a limited number of studies have investigated the link between image texture and ASD. This paper proposes the study of texture features based on grey level co-occurrence matrix (GLCM) as a means for characterizing differences between ASD and development control (DC) subjects. Our study uses 64 T1-weighted MRI scans acquired from two groups of subjects: 28 typical age range subjects 4–15 years old (14 ASD and 14 DC, age-matched), and 36 non-typical age range subjects 10–24 years old (20 ASD and 16 DC). GLCM matrices are computed from manually labeled hippocampus and amygdala regions, and then encoded as texture features by applying 11 standard Haralick quantifier functions. Significance tests are performed to identify texture differences between ASD and DC subjects. An analysis using SVM and random forest classifiers is then carried out to find the most discriminative features, and use these features for classifying ASD from DC subjects. Results Preliminary results show that all 11 features derived from the hippocampus (typical and non-typical age) and 4 features extracted from the amygdala (non-typical age) have significantly different distributions in ASD subjects compared to DC subjects, with a significance of p
... In vivo brain imaging studies of brain anatomy in autism have also reported megencephaly (Piven et al., 1995), as well as abnormal gyrification of cortical regions (including the parietal lobe) (Piven et al., 1990;Courchesne et al., 1993), hypoplasia of the cerebellar vermal lobules (Courchesne et al., 1988;Hashimoto et al., 1995) and decreased volume of the corpus callosum (Piven et al., 1997), the anterior cingulate (Hazneder et al., 1997;Abell et al., 1999) and the left inferior frontal gyrus and occipitotemporal junction (Abell et al., 1999). Contrary to animal models (Bachevalier, 1994), in human autism the hippocampal complex is reported to be of normal size (Piven et al., 1998), and one study reported an increase in volume of the (left) amygdala, bilateral anterior cerebellar lobes and vermis, and the lateral temporal lobe visual cortex (Abell et al., 1999). Thus, imaging studies of autism suggest regionally distributed differences in brain anatomy. ...
... We hypothesize that the functional abnormalities we observed, and the social deficits of autism, may arise from impaired learning and representation of the motivational meaning of social stimuli during a critical period of early brain development. Moreover, if such mechanisms contribute fundamentally to autism, it is probable that, in the majority of people with autism, this would result from abnormal connectivity due to widespread anomalies in regional brain maturation rather than simply focal lesions of medial temporal lobe structures (Piven et al., 1998;Abell et al., 1999). However, more detailed studies of the neural mechanisms contributing to the development of emotional skills in children are needed to enhance understanding of the patho-aetiology of autism and to aid the interpretation of studies of adults with autism. ...
... The results for both structures are equivocal. Several studies of hippocampal volume have failed to find differences in children and adults with autism (7)(8)(9)(10). There have been reports of smaller hippocampal volume (11,12) as well as larger hippocampal volume (13) in autism, although the latter finding was true only before statistical correction for total brain volume. ...
... To our knowledge, there is only one previous study suggesting larger hippocampal volume in autism (13) (however, see Table 1, footnote "b"). As previously discussed, there are also negative findings with respect to hippocampal volumes in autism (7,8), one report of smaller hippo-campal volume (11), and one report of smaller subregional volume within the hippocampus proper (12). In our view, the hippocampal segmentation criteria used in the current study are most similar to those used in the studies by Aylward et al. (11) and Sparks et al. (13). ...
Structural and functional abnormalities in the medial temporal lobe, particularly the hippocampus and amygdala, have been described in people with autism. The authors hypothesized that parents of children with a diagnosis of autistic disorder would show similar changes in these structures.
Magnetic resonance imaging scans were performed in 17 biological parents of children with a diagnosis of DSM-IV autistic disorder. The scans were compared with scans from 15 adults with autistic disorder and 17 age-matched comparison subjects with no personal or familial history of autism. The volumes of the hippocampus, amygdala, and total brain were measured in all participants.
The volume of the left hippocampus was larger in both the parents of children with autistic disorder and the adults with autistic disorder, relative to the comparison subjects. The hippocampus was significantly larger in the adults with autistic disorder than in the parents of children with autistic disorder. The left amygdala was smaller in the adults with autistic disorder, relative to the other two groups. No differences in total brain volume were observed between the three groups.
The finding of larger hippocampal volume in autism is suggestive of abnormal early neurodevelopmental processes but is partly consistent with only one prior study and contradicts the findings of several others. The finding of larger hippocampal volume for the parental group suggests a potential genetic basis for hippocampal abnormalities in autism.
... In vivo brain imaging studies of brain anatomy in autism have also reported megencephaly (Piven et al., 1995), as well as abnormal gyrification of cortical regions (including the parietal lobe) (Piven et al., 1990;Courchesne et al., 1993), hypoplasia of the cerebellar vermal lobules (Courchesne et al., 1988;Hashimoto et al., 1995) and decreased volume of the corpus callosum (Piven et al., 1997), the anterior cingulate (Hazneder et al., 1997;Abell et al., 1999) and the left inferior frontal gyrus and occipitotemporal junction (Abell et al., 1999). Contrary to animal models (Bachevalier, 1994), in human autism the hippocampal complex is reported to be of normal size (Piven et al., 1998), and one study reported an increase in volume of the (left) amygdala, bilateral anterior cerebellar lobes and vermis, and the lateral temporal lobe visual cortex (Abell et al., 1999). Thus, imaging studies of autism suggest regionally distributed differences in brain anatomy. ...
... We hypothesize that the functional abnormalities we observed, and the social deficits of autism, may arise from impaired learning and representation of the motivational meaning of social stimuli during a critical period of early brain development. Moreover, if such mechanisms contribute fundamentally to autism, it is probable that, in the majority of people with autism, this would result from abnormal connectivity due to widespread anomalies in regional brain maturation rather than simply focal lesions of medial temporal lobe structures (Piven et al., 1998;Abell et al., 1999). However, more detailed studies of the neural mechanisms contributing to the development of emotional skills in children are needed to enhance understanding of the patho-aetiology of autism and to aid the interpretation of studies of adults with autism. ...
Although high-functioning individuals with autistic disorder (i.e. autism and Asperger syndrome) are of normal intelligence, they have life-long abnormalities in social communication and emotional behaviour. However, the biological basis of social difficulties in autism is poorly understood. Facial expressions help shape behaviour, and we investigated if high-functioning people with autistic disorder show neurobiological differences from controls when processing emotional facial expressions. We used functional MRI to investigate brain activity in nine adults with autistic disorder (mean age +/- standard deviation 37 +/- 7 years; IQ 102 +/- 15) and nine controls (27 +/- 7 years; IQ 116 +/- 10) when explicitly (consciously) and implicitly (unconsciously) processing emotional facial expressions. Subjects with autistic disorder differed significantly from controls in the activity of cerebellar, mesolimbic and temporal lobe cortical regions of the brain when processing facial expressions. Notably, they did not activate a cortical 'face area' when explicitly appraising expressions, or the left amygdala region and left cerebellum when implicitly processing emotional facial expressions. High-functioning people with autistic disorder have biological differences from controls when consciously and unconsciously processing facial emotions, and these differences are most likely to be neurodevelopmental in origin. This may account for some of the abnormalities in social behaviour associated with autism.
... Despite the evidence from postmortem research that implicates the limbic cortex in autism, neither structural imaging studies nor functional imaging studies have sys-tematically evaluated the structures of the limbic circuit in patients with autism. One recent magnetic resonance imaging (MRI) study reported no difference in the hippocampal volume between autistic individuals and normal volunteers (3), and another study that examined only the posterior hippocampus had equivocal findings (4). ...
... Although we hypothesized both volumetric and metabolic changes in the amygdala and hippocampus in our group of highfunctioning patients with autism spectrum disorders, we did not find any significant differences for these structures compared with findings in healthy volunteers. The absence of significant group differences in hippocampal volume is in accord with some earlier studies (3,4). Our findings may also reflect the characteristics of our patient population: none had seizure disorder, which is known to affect hippocampal size (23). ...
Cytoarchitectonic changes in the anterior cingulate cortex, hippocampus, subiculum, entorhinal cortex, amygdala, mammillary bodies, and septum were reported in a postmortem study of autism. Previously, the authors found smaller cingulate volume and decreased metabolism of the cingulate in seven autistic patients. In this study, they measured the volume and glucose metabolism of the amygdala, hippocampus, and cingulate gyrus in an expanded group of 17 patients with autism spectrum disorders (autism [N=10] or Asperger's disorder [N=7]) and 17 age- and sex-matched healthy volunteers.
Subjects performed a serial verbal learning test during (18)F-deoxyglucose uptake. The amygdala, hippocampus, and cingulate gyrus were outlined on magnetic resonance imaging scans, volumes of the structures were applied to matching coregistered positron emission tomography scans, and three-dimensional significance probability mapping was performed.
Significant metabolic reductions in both the anterior and posterior cingulate gyri were visualized in the patients with autism spectrum disorders. Both Asperger's and autism patients had relative glucose hypometabolism in the anterior and posterior cingulate as confirmed by analysis of variance; regional differences were also found with three-dimensional significance probability mapping. No group differences were found in either the metabolism or the volume of the amygdala or the hippocampus. However, patients with autism spectrum disorders showed reduced volume of the right anterior cingulate gyrus, specifically in Brodmann's area 24'.
Compared with age- and sex-matched healthy volunteers, patients with autism spectrum disorders showed significantly decreased metabolism in both the anterior and posterior cingulate gyri.
... Structural MRI studies of the hippocampus have also provided inconsistent results (for review, see Cody et al., 2002). Some studies have reported decreased volumes of the hippocampus (Aylward et al., 1999), whereas others have reported increased volumes (Sparks et al., 2002), and still others have found no significant differences (Piven et al., 1998;Haznedar et al., 2000;Howard et al., 2000). A number of factors may contribute to the inconsistent findings, including subject diagnostic criteria (e.g., whether study participants with autism or Asperger syndrome were included), exclusionary criteria (e.g., whether study participants with a seizure disorder were included), the age group measured, and the neuroanatomical definition of the amygdala and hippocampus. ...
... There have been relatively few studies of autism to date that have published volumetric analyses of the hippocampal formation. In general, studies focusing primarily on adults have found no difference in hippocampal volume between autism and control subjects (Piven et al., 1998;Haznedar et al., 2000;Howard et al., 2000). One exception is Aylward et al. (1999), who reported a decrease in hippocampal volume in adolescents and adults with autism after controlling for total cerebral volume. ...
Autism is a neurodevelopmental disorder characterized by impairments in reciprocal social interaction, deficits in verbal and nonverbal communication, and a restricted repertoire of activities or interests. We performed a magnetic resonance imaging study to better define the neuropathology of autistic spectrum disorders. Here we report findings on the amygdala and the hippocampal formation. Borders of the amygdala, hippocampus, and cerebrum were defined, and their volumes were measured in male children (7.5-18.5 years of age) in four diagnostic groups: autism with mental retardation, autism without mental retardation, Asperger syndrome, and age-matched typically developing controls. Although there were no differences between groups in terms of total cerebral volume, children with autism (7.5-12.5 years of age) had larger right and left amygdala volumes than control children. There were no differences in amygdala volume between the adolescent groups (12.75-18.5 years of age). Interestingly, the amygdala in typically developing children increases substantially in volume from 7.5 to 18.5 years of age. Thus, the amygdala in children with autism is initially larger, but does not undergo the age-related increase observed in typically developing children. Children with autism, with and without mental retardation, also had a larger right hippocampal volume than typically developing controls, even after controlling for total cerebral volume. Children with autism but without mental retardation also had a larger left hippocampal volume relative to controls. These cross-sectional findings indicate an abnormal program of early amygdala development in autism and an abnormal pattern of hippocampal development that persists through adolescence. The cause of amygdala and hippocampal abnormalities in autism is currently unknown.
... Indeed, recent association studies for schizotypy have failed to identify correlations with total hippocampal volume per se [92], while subfield analyses do report effects on particular subregions related to subclinical psychotic-like features [20]. Moreover, studies have found increased [83,84], decreased [93] and no association [94,95] of hippocampal volumes with ASD. One potential source for this inconsistency in results is variation of unmeasured cooccurring subclinical expressions. ...
Psychiatric disorders show high co-morbidity, including co-morbid expressions of subclinical psychopathology across multiple disease spectra. Given the limitations of classical case-control designs in elucidating this overlap, new approaches are needed to identify biological underpinnings of spectra and their interaction. We assessed autistic-like traits (using the Autism Quotient, AQ) and schizotypy - as models of subclinical expressions of disease phenotypes and examined their association with volumes and regional cerebral blood flow (rCBF) of anterior, mid- and posterior hippocampus segments from structural MRI scans in 318 and arterial spin labelling (ASL) in 346 nonclinical subjects, which overlapped with the structural imaging sample (N = 298). We demonstrate significant interactive effects of positive schizotypy and AQ social skills as well as of positive schizotypy and AQ imagination on hippocampal subfield volume variation. Moreover, we show that AQ attention switching modulated hippocampal head rCBF, while positive schizotypy by AQ attention to detail interactions modulated hippocampal tail rCBF. In addition, we show significant correlation of hippocampal volume and rCBF in both region-of-interest and voxel-wise analyses, which were robust after removal of variance related to schizotypy and autistic traits. These findings provide empirical evidence for both the modulation of hippocampal subfield structure and function through subclinical traits, and in particular how only the interaction of phenotype facets leads to significant reductions or variations in these parameters. This makes a case for considering the synergistic impact of different (subclinical) disease spectra on transdiagnostic biological parameters in psychiatry.
... Furthermore, postmortem neuropathology of the limbic system, including the amygdala, hippocampus, and surrounding cortical areas, was found in all six autistic cases investigated by Bauman and Kemper (1985, 1994. Magnetic resonance imaging studies of the medial temporal region in autistic individuals have revealed disproportionately large hemispheric white-matter volumes in the temporal region (Filipek, 1996), increased amygdala-hippocampal boundary tissue (Abell et al., 1999;Reiss, Lee, & Freund, 1994), and decreased amygdala volumes (Aylward et al., 1999), although normal hippocampal volumes were found in several autistic cases (Piven, Bailey, Ranson, & Arndt, 1998;Saitoh, Courchesne, Egaas, Lincoln, & Schreibman, 1995). Finally, a recent functional neuroimaging study (Baron-Cohen et al., 2000) reported dysfunction of the amygdala in people with autism and Asperger's syndrome. ...
Normal infant monkeys and infant monkeys with neonatal damage to either the medial temporal lobe or the inferior temporal visual area were assessed in dyadic social interactions at 2 and 6 months of age. Unlike the normal infant monkeys, which developed strong affiliative bonds and little or no behavioral disturbances, the lesioned monkeys (each of which was observed with an unoperated control) exhibited socioemotional abnormalities and aberrant behaviors. The socioemotional changes predominated at 6 months of age and were particularly severe in monkeys with medial temporal lesions. In both the pattern and time course, the socioemotional deficits produced by the neonatal medial temporal lesions bear a striking resemblance to the behavioral syndrome in children with autism. Further analysis of these lesion-induced abnormalities in nonhuman primates may therefore provide insight into this debilitating human developmental disorder.
... Studies in typically developed individuals highlight hippocampal and amygdalar activation in response to emotional music (Gosselin et al., 2007;Koelsch, 2014;Koelsch et al., 2013), which has also been reported in autistic individuals (Caria et al., 2011). Studies are inconsistent with regard to volume and activity in limbic system areas (e.g., amygdala, hippocampus) in autistic individuals compared to neurotypical controls (Aylward et al., 1999;Eilam-Stock et al., 2016;Groen et al., 2010;Haar et al., 2016;Kim et al., 2010;Munson et al., 2006;Murphy et al., 2012;Nicolson et al., 2006;Nordahl et al., 2012;Piven et al., 1998;Schumann & Amaral, 2006;Sparks et al., 2002). ...
The interest in music and musical abilities of autistic children have been observed since the earliest descriptions of the condition. Music is a universal language known for millennia and music-based interventions including music therapy have found several applications in the fields of developmental psychology and mental health over the last decades. This group of complementary therapies aims to help the clients to optimize their health, using various facets of musical experience and the relationships formed through them. Several psychological theories and neurobiological models may explain the specific mechanisms through which music-based interventions work for autistic individuals. The present chapter aims to describe the sensorimotor, attentional, emotional, and social processes underpinning the potential effectiveness of music therapy in this population and to provide an overview of the most recent literature findings. At the end of the chapter, an account of the autistic giftedness and talent for music is presented.
... In ASD controls right and left hippocampus increased by 8.54% and 9.16% respectively. In contrast, few researchers have found no significant differences in hippocampus structure 33,34 . ...
Autism Spectrum Disorder (ASD) is widely developing neurodevelopmental disorder. The ASD is a lifelong neurodevelopmental disorder that effects the social interaction and behavior of human beings. In this review, we presented structural magnetic resonance imaging (sMRI) studies that were examined in structural brain abnormalities of ASD patients. To date sMRI results were distinct, due to the diversity of the ASD itself. The accelerated brain volume is the uniform finding of ASD. However, the recent investigation reports have started to interpret the structural abnormalities of ASD patient’s brain. The most common abnormalities found in total brain volume, cerebellum, amygdala, hippocampal, basal ganglia, insula, gray and white matter. Limited sMRI research has been done on less than 2 years ASD children. Future research should include autistic children less than 2 years along with functional MRI and diffusion tensor imaging.
... While many researchers have found increased volume in the amygdala (Groen et al., 2010;Howard et al., 2000;Kim et al., 2010;Munson et al., 2006;Murphy et al., 2012;Nordahl et al., 2012;Sparks et al., 2002;Schumann et al., 2004) others have found no evidence for this increase (Haar et al., 2014) and one study even found significantly decreased volume within the amygdala (Aylward et al., 1999). Similarly, while some studies have found increased volume in the hippocampus (Groen et al., 2010;Murphy et al., 2012, Rojas et al., 2006, others have found no significant differences in hippocampal volume (Aylward et al., 1999;Piven et al., 1998) and some have found significantly decreased volume within the hippocampus (Eilam-Stock et al., 2016;Nicolson et al., 2006;Schumann et al., 2004;Sparks et al., 2002). ...
Autism spectrum disorder (ASD) is a prevalent and fast-growing pervasive neurodevelopmental disorder worldwide. Despite the increasing prevalence of ASD and the breadth of research conducted on the disorder, a conclusive etiology has yet to be established and controversy still exists surrounding the anatomical abnormalities in ASD. In particular, structural asymmetries have seldom been investigated in ASD, especially in subcortical regions. Additionally, the majority of studies for identifying structural biomarkers associated with ASD have focused on small sample sizes. Therefore, the present study utilizes a large-scale, multi-site database to investigate asymmetries in the amygdala, hippocampus, and lateral ventricles, given the potential involvement of these regions in ASD. Contrary to prior work, we are not only computing volumetric asymmetries, but also shape asymmetries, using a new measure of asymmetry based on spectral shape descriptors. This measure represents the magnitude of the asymmetry and therefore captures both directional and undirectional asymmetry. The asymmetry analysis is conducted on 437 individuals with ASD and 511 healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE) database. Results reveal significant asymmetries in the hippocampus and the ventricles, but not in the amygdala, in individuals with ASD. We observe a significant increase in shape asymmetry in the hippocampus, as well as increased volumetric asymmetry in the lateral ventricles in individuals with ASD. Asymmetries in these regions have not previously been reported, likely due to the different characterization of neuroanatomical asymmetry and smaller sample sizes used in previous studies. Given that these results were demonstrated in a large cohort, such asymmetries may be worthy of consideration in the development of neurodiagnostic classification tools for ASD. Keywords: Autism, Asymmetry, MRI, Amygdala, Hippocampus, Ventricles
... Les études concernant l'hippocampe dans les TSA mettent en évidence des résultats divergents : certaines études n'ont montré aucune anomalie chez les sujets autistes (Piven et al., 1998), tandis que d'autres ont décrit une réduction significative du volume de l'hippocampe chez les personnes avec TSA par rapport aux témoins (Aylward et al., 1999). ...
Les troubles du spectre autistique (TSA) sont des troubles neuro-développementaux caractérisés notamment par des anomalies des interactions sociales. Des études en eye-tracking ont permis de mettre en évidence de façon objective des anomalies de la perception sociale dans les TSA, caractérisées par une diminution du regard vers des stimuli sociaux. Des études sur le fonctionnement cérébral, par des méthodes TEP et SPECT, ont mis en évidence une diminution du débit sanguin cérébral (DSC) au repos au niveau des régions temporales, notamment au niveau du sillon temporal supérieur (STS), chez des enfants avec TSA. Nous avons aujourd’hui la possibilité de mesurer le DSC au repos en IRM avec la séquence arterial spin labelling (ASL). Dans cette thèse nous avons confirmé la diminution du DSC au repos au niveau du STS chez des enfants avec TSA par la méthode IRM-ASL, ce qui pourraient permettre son utilisation en tant que biomarqueur dans les TSA. Nous suggérons également que le DSC au repos pourrait être un indice plus pertinent pour l’étude du fonctionnement cérébral de base dans les TSA. De plus, par une étude transversale en eye-tracking utilisant les mêmes stimuli sur une large tranche d’âge, nous avons montré l’impact de l’âge sur la perception sociale chez des participants avec TSA et des témoins. Enfin, nous avons mis en évidence des anomalies de perception sociale par l’eye-tracking et de fonctionnement cortical au niveau du STS par l’IRM-ASL, chez des enfants ayant un kyste arachnoïdien de la fosse postérieure. Une meilleure connaissance des difficultés sociales subjacentes à ce trouble peut avoir un impact majeur sur la prise en charge de ces enfants.
... Nevertheless, the HPC abnormalities, either structural or functional are somewhat heterogeneous. Some studies suggest that there are differences in HPC volume and shape 84 , as well as HPC connectivity 85 between patients with ASD and controls, whereas other studies have not found the same differences 86 . ...
Several mouse models of autism spectrum disorder (ASD), including the BTBR T + tf/J (BTBR) inbred strain, display a diverse array of behavioral deficits with particular face validity. Here we propose that phenotyping these preclinical models of ASD should avoid excessive reliance on appearance validity of the behavioral observations. BTBR mice were examined in three non-diagnostic symptoms modalities, beside an anatomical investigation for construct validity. The BTBR strain displayed poor sensorimotor integration as reflected by shorter stride length and greater latency on the balance beam task (BBT) when compared with C57BL/6 (B6) controls. Also, locomotor indices in the open-field task (OFT) revealed that BTBR mice traveled longer distances with a remarkably faster exploration than the B6 group in favor of hyperactivity and impulsiveness. Furthermore, analysis of spatial performance including search strategies in the Morris water task (MWT) indicated spatial impairment in the BTBR strain due to failure to employ spatial strategies during navigation. Quantitative cytoarchitectonics and volumetric examinations also indicated abnormal cortical and subcortical morphology in the BTBR mice. The results are discussed in relation to the neuroanatomical correlates of motor and cognitive impairments in the BTBR strain. We conclude that non-diagnostic autistic-like symptoms in the BTBR mouse strain can be impacted by autism risk factors in a similar way than the traditional diagnostic signs.
... Despite disparate attention performance between the ASD and TDC groups, there were no gross volumetric differences in structures typically thought to be involved in attention processes. The finding of "normal" ROI structural volumes in ASD in the current study are consistent with several volumetric studies (Bigler et al., 2003;Piven, Bailey, Ranson, & Arndt, 1998, Trontel, et al., 2013 that have not found unique differences in gross brain morphology in ASD and suggest that the neuropathology of ASD is not consistently expressed at the level of gross morphology. Further, contrary to our hypotheses, none of the classic attention-related ROI volumes such as the superior frontal gyrus, anterior cingulate cortex, precuneus, or cerebellum were significantly related to attention performance for any of the groups. ...
Studies have shown that individuals with autism spectrum disorder (ASD) tend to perform significantly below typically developing individuals on standardized measures of attention, even when controlling for IQ. The current study sought to examine within ASD whether anatomical correlates of attention performance differed between those with average to above-average IQ (AIQ group) and those with low-average to borderline ability (LIQ group) as well as in comparison to typically developing controls (TDC). Using automated volumetric analyses, we examined regional volume of classic attention areas including the superior frontal gyrus, anterior cingulate cortex, and precuneus in ASD AIQ (n = 38) and LIQ (n = 18) individuals along with 30 TDC. Auditory attention performance was assessed using subtests of the Test of Memory and Learning (TOMAL) compared among the groups and then correlated with regional brain volumes. Analyses revealed group differences in attention. The three groups did not differ significantly on any auditory attention-related brain volumes; however, trends toward significant size–attention function interactions were observed. Negative correlations were found between the volume of the precuneus and auditory attention performance for the AIQ ASD group, indicating larger volume related to poorer performance. Implications for general attention functioning and dysfunctional neural connectivity in ASD are discussed.
... Other investigations, such as ref. 37, have shown no significant differences in hippocampal volume between ASD and control subjects. Recent studies on autism have focused on finding abnormalities related to brain development. ...
We propose using multi-scale image textures to investigate links between neuroanatomical regions and clinical variables in MRI. Texture features are derived at multiple scales of resolution based on the Laplacian-of-Gaussian (LoG) filter. Three quantifier functions (Average, Standard Deviation and Entropy) are used to summarize texture statistics within standard, automatically segmented neuroanatomical regions. Significance tests are performed to identify regional texture differences between ASD vs. TDC and male vs. female groups, as well as correlations with age (corrected p < 0.05). The open-access brain imaging data exchange (ABIDE) brain MRI dataset is used to evaluate texture features derived from 31 brain regions from 1112 subjects including 573 typically developing control (TDC, 99 females, 474 males) and 539 Autism spectrum disorder (ASD, 65 female and 474 male) subjects. Statistically significant texture differences between ASD vs. TDC groups are identified asymmetrically in the right hippocampus, left choroid-plexus and corpus callosum (CC), and symmetrically in the cerebellar white matter. Sex-related texture differences in TDC subjects are found in primarily in the left amygdala, left cerebellar white matter, and brain stem. Correlations between age and texture in TDC subjects are found in the thalamus-proper, caudate and pallidum, most exhibiting bilateral symmetry.
... Hashimoto et al. (1995) found decreased brainstem volume, while Herbert et al. (2003) and Piven et al., (1992) reported no volumetric differences and Jou, Minshew, Melhem, Keshavan and Hardan (2009) found decreased GMV in the brainstem. Inconsistent findings of volumetric studies of the hippocampus have ranged from no differences between ASD subjects and controls (Bigler et al., 2003;Piven, Bailey, Ranson, & Arndt, 1998) to increased or decreased volumes (Schumann et al., 2004;Sparks et al., 2002). That volumetric differences might lie along a spectrum is suggested by the finding that increased amygdala volumes were associated with social and communication deficits by some studies (Schumann, Barnes, Bloss, Lord, & Courchesne, 2009;Sparks et al., 2002) pointing to a neurological ASD subtype. ...
... The earlier findings of the 1980s–1990s Damasio andMaurer (1978);Bauman and Kemper (1985);Gaffney et al. (1987a,b);Courchesne et al. (1988);Gaffney et al. (1988);Horwitz et al. (1988);Minshew and Payton (1988);Ritvo and Garber (1988);Gaffney et al. (1989);Garber et al. (1989);Murakami et al. (1989);Nowell et al. (1990);Hsu et al. (1991); ZolaMorgan et al. (1991);Garber and Ritvo (1992);George et al. (1992);Hashimoto et al. (1992Hashimoto et al. ( , 1993);Holttum et al. (1992);Kleiman et al. (1992);Piven et al. (1992);Bailey et al. (1993);Courchesne et al. (1993Courchesne et al. ( , 1994a,b);Adolphs et al. (1994);Bachevalier (1994);Bauman and Kemper (1994);Minshew and Dombrowski (1994);Egaas et al. (1995);Hashimoto et al. (1995);Piven et al. (1995);Saitoh et al. (1995);Zilbovicius et al. (1995);Schaefer et al. (1996);Giedd et al. (1996);Piven et al. (1996);Siegel et al. (1996);Ciesielski et al. (1997);Elia et al. (1997);Lainhart et al. (1997);Piven et al. (1997);Bailey et al. (1998);Dawson et al. (1998);Piven et al. (1998);Abell et al. (1999);Aylward et al. (1999);Courchesne et al. (1999);Fombonne et al. (1999);Gillberg (1999);Levitt et al. (1999);Manes et al. (1999);Sears et al. (1999);Townsend et al. (1999)have many contradictions. However, the much better spatial resolution and contrast of the recent advanced MRI technology made the recent findings of the 2000s–2010s more consistentBrambilla et al. (2003);Stanfield et al. (2008);Chen et al. (2011). ...
Magnetic resonance imaging (MRI) modalities have emerged as powerful means that facilitate non-invasive clinical diagnostics of various diseases and abnormalities since their inception in the 1980s. Multiple MRI modalities, such as different types of the sMRI and DTI, have been employed to investigate facets of ASD in order to better understand this complex syndrome. This paper reviews recent applications of structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI), to study autism spectrum disorder (ASD). Main reported findings are sometimes contradictory due to different age ranges, hardware protocols, population types, numbers of participants, and image analysis parameters. The primary anatomical structures, such as amygdalae, cerebrum, and cerebellum, associated with clinical-pathological correlates of ASD are highlighted through successive life stages, from infancy to adulthood. This survey demonstrates the absence of consistent pathology in the brains of autistic children and lack of research investigations in patients under 2 years of age in the literature. The known publications also emphasize advances in data acquisition and analysis, as well as significance of multimodal approaches that combine resting-state, task-evoked, and sMRI measures. Initial results obtained with the sMRI and DTI show good promise toward the early and non-invasive ASD diagnostics.
... Temporal lobe abnormality in autism is a likely candidate because core symptoms of the disorder center on deficits in language and social behavior, which are frequently accompanied by intellectual impairment-all functions thought to be subserved, at least in part, by the temporal lobes (2,3). Several neuroimaging studies demonstrated temporal lobe abnormalities in autism, including volume differences in the hippocampus and amygdala when compared with age-and sex-matched control subjects (4 -6), although not all found differences (7). Other studies demonstrated an association between autism and lesions of the temporal lobe in individuals with tuberous sclerosis (8,9). ...
BACKGROUND AND PURPOSE: Because of increased prevalence of macrocephaly in autism, head size must be controlled for in studies that examine volumetric findings of the temporal lobe in autistic subjects. We prospectively examined temporal lobe structures in individuals with autism who were normocephalic or macrocephalic (head circumference > 97th percentile) and in control subjects who were normocephalic or macrocephalic or who had a reading disorder (unselected for head size). The rationale for the reading disorder group was to have control subjects with potential temporal lobe anomalies, but who were not autistic. METHODS: In individuals aged 7-31 years, autism was diagnosed on the basis of standardized interview and diagnostic criteria. Control subjects ranged in age from 7 to 22 years. All subjects were male. MR morphometrics of the major temporal lobe structures were based on ANALYZE segmentation routines, in which total brain volume and total intracranial volume (TICV) were calculated. Both group comparisons and developmental analyses were performed. RESULTS: No distinct temporal lobe abnormalities of volume were observed once head size (TICV) was controlled for. In autistic and control subjects, robust growth patterns were observed in white and gray matter that differed little between the groups. Although subtle differences were observed in some structures (ie, less white matter volume in the region of the temporal stem and overall temporal lobe), none was statistically significant. CONCLUSION. No major volumetric anomalies of the temporal lobe were found in cases of autism when IQ, TICV, and age were controlled. Temporal lobe abnormalities that may be associated with autism are likely to be more related to functional organization within the temporal lobe than to any gross volumetric difference.
... A study that included autistic adolescents and young adults reported a decrease in hippocampal volume [51]. Where autism is concerned, various studies have shown no significant differences in hippocampal volume [53,54]. ...
... Unfortunately, volumeten been plagued by small group sizes and variability in diagnostic , there is considerable inconsistency in the findings across studies. differences in amygdala (Munson et al., 2006;Schumann et al., Aylward et al., 1999;Piven et al., 1998) have been inconsistent, with acreased volume while others report small decreases or no differ-5; Zeegers et al., 2009). This disagreement may in part relate to nparing results across studies, it appears that there may be some ;data in early childhood but not in adolescence or adulthood 95 monstrate a head circ rcer aile) (Courchesne r ain size in children (Ba nod may potentially re: This working hypoth volumetric analysis of hig In these investigations, su mize gray/white brain ncombined into three-din marked on these reconstr Several studies using this AD is larger than age-mat The effect is most robustl A question prompted volume reflect differences , or E observed both in cortical 2005). ...
Written for the wide range of physicians and professionals who treat children and adults with autism spectrum disorders (ASDs), this book reviews the scientific research on the nature and causes of autism, outlines best treatment practices with children and describes a comprehensive assessment and treatment approach for adults. Topics covered include: • Classification, epidemiology and diagnosis • Neurodevelopmental abnormalities • Recommendations for early screening and evaluating at-risk children • Early interventions based on applied behavioral analysis • The critical role of special education, speech-language therapy, occupational therapy and assistive technology in treating children • Pharmacotherapy • Complementary and alternative treatments • Development of individualized and person-centered treatments for adults The Autism Spectrum is an invaluable resource for all those working with ASDs including pediatricians, psychiatrists, behavioral psychologists, special educators, nurses and therapists.
... Comme pour l'amygdale, les études concernant l'hippocampe aboutissent à des résultats divergents. Certaines études n'ont montré aucune anomalie chez des sujets enfants et adultes autistes avec ou sans déficience intellectuelle (Piven et al., 1998;Howard et al., 2000), tandis que d'autres ont montré une diminution ou une augmentation du volume de l'hippocampe dans l'autisme (Aylward et al., 1999;Sparks et al., 2002;Schumann et al., 2004;Nicolson et al., 2006). Encore une fois, les résultats contradictoires peuvent être attribués à l'hétérogénéité des participants, ainsi qu'aux différentes méthodes de neuroimagerie utilisées (Stigler et al., 2011) (Figure 5). ...
Autism is a pervasive developmental disorder associated with alterations of neural circuits. Neuroimaging studies in autism have revealed anatomo-fonctional abnormalities, particularly located within the superior temporal sulcus (STS). In normal subjects, STS is largely implicated in social perception and social cognition. Deficits in social cognition and particularly in social perception are the core symptoms of autism. Indeed, abnormalities of social perception have been described in adults and children with autism. These abnormalities are characterized by a lack of preference for the eyes. In this thesis, we have shown that it is possible to modulate neural activity within the right STS using a transcranial magnetic stimulation (TMS) protocol, with significant effects on social perception parameters, measured by eye-tracking during passive visualization of social scenes. Furthermore, social perception parameters were correlated with rest cerebral blood flow (CBF), measured with arterial spin labelling (ASL) MRI. We have shown that the healthy young volunteers who looked more to the eyes during passive visualization of social scenes were those who had higher rest CBF values within right temporal regions. In addition, this correlation was also observed in children with autism: children who looked more to the eyes during passive visualization of social scenes were those who had higher rest CBF values within right temporal regions. Finally, preliminary results concerning application of the TMS protocol in adults with autism open up new perspectives on innovate therapeutically strategies.
... Individuals with autism have poorer adaptive function than would be predicted by IQ alone (Volkmar et al., 1993 Cognitive defi cits might be related in part to the memory system and limbic region abnormalities. Reduced volume of both the hippocampal formation and amygdala were noticed in subjects examined by Aylward et al. (1999), but not in populations examined by other researchers (Piven et al., 1998). Neurons in the hippocampus have reduced complexity of dendritic arbors. ...
... Yet, this reduction only existed in the right hippocampus, while no significant differences were noted in the left hippocampus. Additional divergent findings are in the literature, with some reporting an increase in hippocampal volume (Barnea-Goraly et al., 2014;Schumann et al., 2004;Groen et al., 2010), while others reporting no difference compared with controls (Piven et al., 1998;Haznedar et al., 2000;Palmen et al., 2006). The lack of consistent results could be due to heterogeneous diagnosis criteria, inclusion and exclusion criteria, age distribution of the tested cohort, and imaging techniques in various studies. ...
Autism Spectrum Disorder (ASD) is a clinically diagnosed, heterogeneous, neurodevelopmental condition, whose underlying causes have yet to be fully determined. A variety of studies have investigated either cortical, subcortical, or cerebellar anatomy in ASD, but none have conducted a complete examination of all neuroanatomical parameters on a single, large cohort. The current study provides a comprehensive examination of brain development of children with ASD between the ages of 4 and 18 years who are carefully matched for age and sex with typically developing controls at a ratio of one-to-two. Two hundred and ten magnetic resonance images were examined from 138 Control (116 males and 22 females) and 72 participants with ASD (61 males and 11 females). Cortical segmentation into 78 brain-regions and 81,924 vertices was conducted with CIVET which facilitated a region-of-interest- (ROI-) and vertex-based analysis, respectively. Volumes for the cerebellum, hippocampus, striatum, pallidum, and thalamus and many associated sub regions were derived using the MAGeT Brain algorithm. The study reveals cortical, sub-cortical and cerebellar differences between ASD and Control group participants. Diagnosis, diagnosis-by-age, and diagnosis-by-sex interaction effects were found to significantly impact total brain volume but not total surface area or mean cortical thickness of the ASD participants. Localized (vertex-based) analysis of cortical thickness revealed no significant group differences, even when age, age-range, and sex were used as covariates. Nonetheless, the region-based cortical thickness analysis did reveal regional changes in the left orbitofrontal cortex and left posterior cingulate gyrus, both of which showed reduced age-related cortical thinning in ASD. Our finding of region-based differences without significant vertex-based results likely indicates non-focal effects spanning the entirety of these regions. The hippocampi, thalamus, and globus pallidus, were smaller in volume relative to total cerebrum in the ASD participants. Various sub-structures showed an interaction of diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-age-range, in the case where age was divided into childhood (age < 12) and adolescence (12 < age < 18). This is the most comprehensive imaging-based neuro-anatomical paediatric and adolescent ASD study to date. These data highlight the neurodevelopmental differences between typically developing children and those with ASD, and support aspects of the hypothesis of abnormal neuro-developmental trajectory of the brain in ASD.
... There were no gross volumetric differences between the ASD and TDC groups in mesial temporal lobe structures typically thought to be involved in memory processes. The finding of "normal" ROI structural volumes in ASD in the current study is consistent with several volumetric studies (Bigler et al., 2003;Piven, Bailey, Ranson, & Arndt, 1998;Saitoh, Courchesne, Egaas, Lincoln, & Shreibman, 1995) that have not found unique differences in gross temporal lobe morphology in ASD. Since memory differences in both AIQ and LIQ ASD were shown compared to TDC individuals, the absence of gross morphological differences implies that memory function in ASD is likely due to disrupted neural connectivity within memory networks rather than the absolute size of mesial temporal lobe structures. ...
Studies have shown that individuals with autism spectrum disorder (ASD) tend to perform significantly below typical developing individuals on standardized measures of memory, even when not significantly different on measures of IQ. The current study sought to examine within ASD whether anatomical correlates of memory performance differed between those with average-to-above-average IQ (AIQ group) and those with low-average to borderline ability (LIQ group) as well as in relations to typically developing comparisons (TDC). Using automated volumetric analyses, we examined regional volume of classic memory areas including the hippocampus, parahippocampal gyrus, entorhinal cortex, and amygdala in an all-male sample AIQ (n = 38) and LIQ (n = 18) individuals with ASD along with 30 typically developing comparisons (TDC). Memory performance was assessed using the Test of Memory and Learning (TOMAL) compared among the groups and then correlated with regional brain volumes. Analyses revealed group differences on almost all facets of memory and learning as assessed by the various subtests of the TOMAL. The three groups did not differ on any region of interest (ROI) memory-related brain volumes. However, significant size-memory function interactions were observed. Negative correlations were found between the volume of the amygdala and composite, verbal, and delayed memory indices for the LIQ ASD group, indicating larger volume related to poorer performance. Implications for general memory functioning and dysfunctional neural connectivity in ASD are discussed.
... Structural MRI studies of the hippocampus have also provided inconsistent results (Cody et al., 2002). Some studies have reported decreased volumes of the hippocampus (Aylward et al., 1999), whereas others have reported increased volumes (Rodier et al., 1996a(Rodier et al., , 1996b, and still others have found no significant differences (Haznedar et al., 2000;Howard et al., 2000;Piven et al., 1998). ...
... Individuals with autism have poorer adaptive function than would be predicted by IQ alone (Volkmar et al., 1993 Cognitive defi cits might be related in part to the memory system and limbic region abnormalities. Reduced volume of both the hippocampal formation and amygdala were noticed in subjects examined by Aylward et al. (1999), but not in populations examined by other researchers (Piven et al., 1998). Neurons in the hippocampus have reduced complexity of dendritic arbors. ...
Multi-regional qualitative and quantitative study of autistic subjects brains revealed a broad spectrum of developmental alterations suggesting that there is no one brain structure, neuronal population, neurotransmitter or neuropeptide defect which might be considered as the single cause of the autistic phenotype. Delay of neuronal growth, appears as a common developmental alteration detected in many brain regions. However, the study of major regulatory systems of the brain: nucleus basalis of Meynert (cholinergic system), the substantia nigra (dopaminergic system), hypothalamic NPV and NSO (oxytocin and vasopressin) suggest that the neuronal populations playing a key role in production of neurotransmitters or neuropeptides are not affected (substantia nigra) or show rather limited distortion of developmental trajectories (NBMC, NSO, NPV). However, brain structures that are regulated by these centers reveal much broader and more significant developmental delays of neuronal growth. Global pattern of developmental alterations reflects the complexity of desynchronized development of neurons, neuronal networks, and brain structures most likely contributing to the complex clinical manifestations of autism. Significant interindividual differences in pattern of qualitative developmental abnormalities, topography, and severity of delayed neuronal growth appear to be the major factors determining broad spectrum of interindividual differences observed in clinical studies.
... 14,15,19 Paradoxical and conflicting structural and functional brain neuroimaging findings in autism spectrum disorder have been summarized in several extensive reviews. 2,14,15,19,20 In particular, gray matter structures such as the hippocampus [21][22][23] have been reported to be enlarged in autistic children 24,25 and adults. [26][27][28] The relaxation time and diffusion tensor imaging microstructural correlates of such paradoxical macrostructural findings have not been reported in the same study. ...
Quantitative magnetic resonance imaging (MRI) studies of the microstructure and macrostructure in children with autism report contradictory results due, in part, to the autistic population heterogeneity from factors such as variation in intellect and inadequately accounting for age-related changes in brain development. In this report, the authors compared global and regional volumetry, relaxometry, anisotropy, and diffusometry of gray and white matter in 10 autism spectrum disorder children relative to the age-related trajectories obtained from 38 typically developing controls while controlling for nonverbal intellect using a validated quantitative MRI method. The normalized hippocampus volume increased with age in both autistic and typically developing individuals with limbic structures larger in autistic patients. Hippocampus volume, but not diffusivity or relaxation time, was larger in autistic children. Hippocampus volume was inversely correlated with nonverbal intellect across control individuals. The pattern of hippocampal abnormalities suggests a disturbance in early brain development in autistic children independent of intellect.
... However, the results from prior studies have been inconsistent. For example, the amygdala and cerebellum have been reported to be normal ( Piven et al. 1998 ;Allen et al. 2004), smaller ( Courchesne et al. 1988 ;Aylward et al. 1999), and increased in size (Howard et al. 2000 ;Sparks et al. 2002). This variability may have arisen because most studies used relatively small heterogeneous samples consisting of mixed populations of people from different parts of the diagnostic spectrum. ...
... Inconsistencies exist in the literature regarding changes in the morphology of the hippocampi of children when compared to adults with ASD. Some groups have noted no changes in the hippocampi in children and adults with autism [Haznedar et al., 2000;Howard et al., 2000;Piven, Bailey, Ranson, & Arndt, 1998;Saitoh, Courchesne, Egaas, Lincoln, & Schreibman, 1995], while other researchers have reported decreased hippocampal volume in adolescents and adults with ASD [Aylward et al., 1999], or increased volume of hippocampi in children with autism [Sparks et al., 2002]. ...
Structural alterations in brain morphology have been inconsistently reported in children compared to adults with autism spectrum disorder (ASD). We assessed these differences by performing meta-analysis on the data from 19 voxel-based morphometry studies. Common findings across the age groups were grey matter reduction in left putamen and medial prefrontal cortex (mPFC) and grey matter increases in the lateral PFC, while white matter decreases were seen mainly in the children in frontostriatal pathways. In the ASD sample, children/adolescents were more likely than adults to have increased grey matter in bilateral fusiform gyrus, right cingulate and insula. Results show that clear maturational differences exist in social cognition and limbic processing regions only in children/adolescents and not in adults with ASD, and may underlie the emotional regulation that improves with age in this population.
... Unfortunately, structural neuroimaging studies have produced somewhat conflicting results so far. Aside from a convergent finding of increased brain volume in individuals with autism (Piven et al. 1995(Piven et al. , 1996Hardan et al. 2001b), neuroanatomic findings have been difficult to replicate for regions such as the corpus callosum (Belmonte et al. 1995, Piven et al. 1997, Manes et al. 1999, Hardan et al. 2000, the amygdala and hippocampus (Piven et al. 1998, Aylward et al. 1999, Howard et al. 2000, Saitoh et al. 2001, and the cerebellar vermis (Courchesne et al. 1988(Courchesne et al. , 1994Piven et al. 1992;Hardan et al. 2001a). Possible sources of non-convergent results might include variation in diagnostic criteria used in recruitment, IQ differences in individuals, differences across studies in mean age of individuals, and differences in MRI acquisition, processing, and analysis. ...
Efforts to examine the structural neuroanatomy of autism by using traditional methods of imaging analysis have led to variable findings, often based on methodological differences in image acquisition and analysis. A voxel-based computational method of whole-brain anatomy allows examination of small patterns of tissue differences between groups. High-resolution structural magnetic resonance images were acquired for nine males with high-functioning autism (HFA; mean age 14y [SD3y 4mo]), 11 with Asperger syndrome (ASP; mean age 13y 6mo [SD2y 5mo]), and 13 comparison (COM) participants (mean age 13y 7mo [SD 3y 1mo]). Using statistical parametric mapping, we examined contrasts of gray matter differences between the groups. Males with HFA and ASP had a pattern of decreased gray matter density in the ventromedial regions of the temporal cortex in comparison with males from an age-matched comparison group. Examining contrasts revealed that the COM group had increased gray matter density compared with the ASP or combined HFA and ASP group in the right inferior temporal gyrus, entorhinal cortex, and rostral fusiform gyrus. The ASP group had less gray matter density in the body of the cingulate gyrus in comparison with either the COM or HFA group. The findings of decreased gray matter density in ventromedial aspects of the temporal cortex in individuals with HFA and ASP lends support to theories suggesting an involvement of these areas in the pathophysiology of autism, particularly in the integration of visual stimuli and affective information.
... Volumetric studies of the hippocampus in autism versus healthy controls have revealed divergent findings. Several studies have noted no difference in hippocampal volume (Bigler et al., 2003;Haznedar et al., 2000;Howard et al., 2000;Piven et al., 1998;Saitoh et al., 1995). However, other researchers have reported decreased or increased hippocampal volume (Aylward et al., 1999;Nicolson et al., 2006;Schumann et al., 2004;Sparks et al., 2002). ...
The neurobiology of autism spectrum disorders (ASDs) has become increasingly understood since the advent of magnetic resonance imaging (MRI). Initial observations of an above-average head circumference were supported by structural MRI studies that found evidence of increased total brain volume and early rapid brain overgrowth in affected individuals. Subsequent research revealed consistent abnormalities in cortical gray and white matter volume in ASDs. The structural integrity and orientation of white matter have been further elucidated via diffusion tensor imaging methods. The emergence of functional MRI techniques led to an enhanced understanding of the neural circuitry of ASDs, demonstrating areas of dysfunctional cortical activation and atypical cortical specialization. These studies have provided evidence of underconnectivity in distributed cortical networks integral to the core impairments associated with ASDs. Abnormalities in the default-mode network during the resting state have also been identified. Overall, structural and functional MRI research has generated important insights into the neurobiology of ASDs. Additional research is needed to further delineate the underlying brain basis of this constellation of disorders.
... Similarly, in vivo volumetric studies have yielded conflicting results. Hippocampal volume has been reported to be either decreased (Aylward et al., 1999;Saitoh et al., 2001) or not different (Saitoh et al., 1995;Piven et al., 1998;Haznedar et al., 2000;Howard et al., 2000); and amygdala volume has been reported as decreased (Pierce et al., 2001;Schultz, 2005), increased (Abell et al., 1999;Howard et al., 2000;Sparks et al., 2002) and not different (Haznedar et al., 2000). Also, functional magnetic resonance imaging (fMRI) studies found that the amygdaloid region (and particularly the right side) is hypoactive when individuals with ASD process emotional faces, suggesting that neuro-circuitry in this region may develop abnormally (Pierce et al., 2001). ...
People with autistic spectrum disorders (ASD, including Asperger syndrome) may have developmental abnormalities in the amygdala-hippocampal complex (AHC). However, in vivo, age-related comparisons of both volume and neuronal integrity of the AHC have not yet been carried out in people with Asperger syndrome (AS) versus controls. We compared structure and metabolic activity of the right AHC of 22 individuals with AS and 22 healthy controls aged 10-50 years and examined the effects of age between groups. We used structural magnetic resonance imaging (sMRI) to measure the volume of the AHC, and magnetic resonance spectroscopy ((1)H-MRS) to measure concentrations of N-acetyl aspartate (NAA), creatine+phosphocreatine (Cr+PCr), myo-inositol (mI) and choline (Cho). The bulk volume of the amygdala and the hippocampus did not differ significantly between groups, but there was a significant difference in the effect of age on the hippocampus in controls. Compared with controls, young (but not older) people with AS had a significantly higher AHC concentration of NAA and a significantly higher NAA/Cr ratio. People with AS, but not controls, had a significant age-related reduction in NAA and the NAA/Cr ratio. Also, in people with AS, but not controls, there was a significant relationship between concentrations of choline and age so that choline concentrations reduced with age. We therefore suggest that people with AS have significant differences in neuronal and lipid membrane integrity and maturation of the AHC.
... Likewise, to date no consistent hippocampal findings in individuals with autism have been reported. Some studies revealed no hippocampus size anomalies in autism (Haznedar et al. 2000, Howard et al. 2000, Piven et al. 1998, others reported both decreased volume (Aylward et al. 1999) or increased volume of the hippocampus (Sparks et al. 2002). Concerning the cingulate, Haznedar et al. have reported that individuals with autism displayed a decreased volume (Haznedar et al. 2000). ...
Neuroimaging studies done by means of magnetic resonance imaging (MRI) have provided important insights into the neurobiological basis for autism. The aim of this article is to review the current state of knowledge regarding brain abnormalities in autism. Results of structural MRI studies dealing with total brain volume, the volume of the cerebellum, caudate nucleus, thalamus, amygdala and the area of the corpus callosum are summarised. In the past 5 years also new MRI applications as functional MRI and diffusion tensor imaging brought considerable new insights in the pathophysiological mechanisms of autism. Dysfunctional activation in key areas of verbal and non-verbal communication, social interaction, and executive functions are revised. Finally, we also discuss white matter alterations in important communication pathways in the brain of autistic patients.
... However, the results from prior studies have been inconsistent. For example, the amygdala and cerebellum have been reported to be normal (Piven et al. 1998 ;Allen et al. 2004), smaller (Courchesne et al. 1988 ;Aylward et al. 1999), and increased in size (Howard et al. 2000 ;Sparks et al. 2002). This variability may have arisen because most studies used relatively small heterogeneous samples consisting of mixed populations of people from different parts of the diagnostic spectrum. ...
Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype.
We used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender.
VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome.
Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.
... There is also evidence of abnormalities in amygdala volume in autism ( Abell et al., 1999;Schumann & Amaral, 2006;Sparks et al., 2002); this has resulted in theories emphasizing abnormalities in amygdala as central to autism spectrum disorder, especially to social symptoms (Nacewicz et al., 2006). However, studies of the hippocampus and limbic systems have been limited by small sample sizes, varied age ranges of the subjects, and varied severity of autistic symptoms ( Aylward et al., 1999;Piven, Bailey, Ranson, & Arndt, 1998;Saitoh, Courchesne, Egaas, Lincoln, & Schreibman, 1995). ...
Autism is a neurodevelopmental disorder characterized by social and communication deficits, and repetitive behavior. Studies investigating the integrity of brain systems in autism suggest a wide range of gray and white matter abnormalities that are present early in life and change with development. These abnormalities predominantly affect association areas and undermine functional integration. Executive function, which has a protracted development into adolescence and reflects the integration of complex widely distributed brain function, is also affected in autism. Evidence from studies probing response inhibition and working memory indicate impairments in these core components of executive function, as well as compensatory mechanisms that permit normative function in autism. Studies also demonstrate age-related improvements in executive function from childhood to adolescence in autism, indicating the presence of plasticity and suggesting a prolonged window for effective treatment. Despite developmental gains, mature executive functioning is limited in autism, reflecting abnormalities in wide-spread brain networks that may lead to impaired processing of complex information across all domains.
... Decreased hippocampal measures have been found in juvenile and adult male patients with autism, mostly highfunctioning [5,65] when compared to age-and gendermatched healthy controls, even after total brain adjustment. However, several controlled MRI studies have reported no abnormalities in this region in mentally and non-mentally retarded male individuals with autism [39,43,57,64,68] ( Table 2). Enlarged amygdala volumes have been described in adolescent and adult patients with autism, mostly highfunctioning males [1,43,68], but not in all studies [5,39] ( Table 2). ...
Autism is a neurodevelopmental disorder that severely disrupts social and cognitive functions. MRI is the method of choice for in vivo and non-invasively investigating human brain morphology in children and adolescents. The authors reviewed structural MRI studies that investigated structural brain anatomy and development in autistic patients. All original MRI research papers involving autistic patients, published from 1966 to May 2003, were reviewed in order to elucidate brain anatomy and development of autism and rated for completeness using a 12-item check-list. Increased total brain, parieto-temporal lobe, and cerebellar hemisphere volumes were the most replicated abnormalities in autism. Interestingly, recent findings suggested that the size of amygdala, hippocampus, and corpus callosum may also be abnormal. It is conceivable that abnormalities in neural network involving fronto-temporo-parietal cortex, limbic system, and cerebellum may underlie the pathophysiology of autism, and that such changes could result from abnormal brain development during early life. Nonetheless, available MRI studies were often conflicting and could have been limited by methodological issues. Future MRI investigations should include well-characterized groups of autistic and matched healthy individuals, while taking into consideration confounding factors such as IQ, and socioeconomic status.
In the present paper the use of CeO2-based materials in the automotive three-way catalysts (TWCs) is considered. The multiple roles of CeO2 as a TWC promoter and in particular the oxygen storage/release capacity (OSC) are critically discussed. Attention is focused on the advanced OSC materials containing ZrO2, which are employed in the last generation of catalytic automotive converters.
Neurodevelopmental disorders are a diverse group of behaviourally-relevant multifactorial disorders related to an impairment of growth, maturation, or development of the central nervous system. The role of the hippocampus, however, has only recently been acknowledged. These disorders affect memory, emotion, cognitive abilities, and behaviour. Individuals with neurodevelopmental disorders might have comorbid disorders including intellectual impairment, seizures, and anxiety. The hippocampus is known to be vulnerable to hypoxia, stress, and malnutrition, and thus plays a clinically relevant role in children born preterm, after having experienced febrile seizures, fetal alcohol, or cocaine. Hippocampal dysfunctions are also known to be inherent as seen in Angelman syndrome, fragile-X syndrome, or Down syndrome. Complex interactions between environmental conditions and genetically predispositions are discussed in relation to neurodevelopmental disorders such as autism spectrum disorder, attention-deficit hyperactivity disorder, or Gilles de la Tourette syndrome in which hippocampal alterations are reported as well. However, even in normal brain development, there is a relationship between hippocampal structure and cognitive function as pointed out at the beginning of this chapter. Here, the structure-function relationship of the hippocampus within these complex syndromes and findings of developmental impairments are reviewed. The introduction of magnetic resonance imaging (MRI), particularly with volumetric analysis, but also of functional imaging methods such as functional MRI (fMRI), positron emission tomography (PET), or single-photon emission computed tomography (SPECT) facilitated the study of hippocampal changes associated with deficits in children in recent years.
This chapter provides a snapshot of results of studies that provide information about the maturation of brain anatomy. It is divided into four sections: methodological issues, typical pediatric brain development, examples of atypical brain development, and a discussion of the present and future role of structural neuroimaging in the study of neurodevelopment. The chapter first presents a brief history of neuroimaging techniques as a background to major structural imaging modalities currently in use, and discusses issues related to image analysis methods and study design. It the reviews major steps of brain development, followed by a summary of findings from neuroimaging studies. The most consistent structural abnormality in MRI studies of Autism is enlarged total brain size. The realization of how much plasticity can be exhibited in even the adult brain has also begun to hint at how complex the relationship is between brain structure and development.
Hippocampal atrophy is found in many psychiatric disorders that are more prevalent in women. Sex differences in memory and spatial skills further suggest that males and females differ in hippocampal structure and function. We conducted the first meta-analysis of male-female difference in hippocampal volume (HCV) based on published MRI studies of healthy participants of all ages, to test whether the structure is reliably sexually dimorphic. Using four search strategies, we collected 68 matched samples of males' and females' uncorrected HCVs (in 4418 total participants), and 36 samples of male and female HCVs (2183 participants) that were corrected for individual differences in total brain volume (TBV) or intracranial volume (ICV). Pooled effect sizes were calculated using a random-effects model for left, right, and bilateral uncorrected HCVs and for left and right HCVs corrected for TBV or ICV. We found that uncorrected HCV was reliably larger in males, with Hedges' g values of 0.545 for left hippocampus, 0.526 for right hippocampus, and 0.557 for bilateral hippocampus. Meta-regression revealed no effect of age on the sex difference in left, right, or bilateral HCV. In the subset of studies that reported it, both TBV (g=1.085) and ICV (g= 1.272) were considerably larger in males. Accordingly, studies reporting HCVs corrected for individual differences in TBV or ICV revealed no significant sex differences in left and right HCVs (Hedges' g ranging from +0.011 to -0.206). In summary, we found that human males of all ages exhibit a larger HCV than females, but adjusting for individual differences in TBV or ICV results in no reliable sex difference. The frequent claim that women have a disproportionately larger hippocampus than men was not supported.
Copyright © 2015. Published by Elsevier Inc.
Autism is a neurodevelopmental disorder with a range of clinical presentations. These presentations vary from mild to severe and are referred to as autism spectrum disorders. The most common clinical sign of autism spectrum disorders is social interaction impairment, which is associated with verbal and non-verbal communication deficits and stereotyped and repetitive behaviors. Thanks to recent brain imaging studies, scientists are getting a better idea of the neural circuits involved in autism spectrum disorders. Indeed, functional brain imaging, such as positron emission tomography, single foton emission tomographyand functional MRI have opened a new perspective to study normal and pathological brain functioning. Three independent studies have found anatomical and rest functional temporal lobe abnormalities in autistic patients. These alterations are localized in the superior temporal sulcus bilaterally, an area which is critical for perception of key social stimuli. In addition, functional studies have shown hypoactivation of most areas implicated in social perception (face and voice perception) and social cognition (theory of mind). These data suggest an abnormal functioning of the social brain network in autism. The understanding of the functional alterations of this important mechanism may drive the elaboration of new and more adequate social re-educative strategies for autistic patients.
Objective: To find out whether the neurodevelopmental disorders autism and childhood-onset schizophrenia have a common developmental pathway and whether the abnormalities detected are ‘disorder-specific’, by reviewing magnetic resonance imaging (MRI) studies.
Methods: As a result of a Medline search, we were able to access 28 studies on autism and 12 studies on childhood-onset schizophrenia, which focused on children and adolescents.
Results: Larger lateral ventricles were found to be a common abnormality in both disorders. ‘Disorder-specific’ abnormalities in patients with autism were larger brains, a larger thalamic area, and a smaller right cingulate gyrus. Subjects with childhood-onset schizophrenia were found to have smaller brains, a smaller amygdalum and thalamus, and a larger nucleus caudatus. In subjects with childhood-onset schizophrenia, abnormalities appeared to progress over a limited period of time.
Conclusions: Because the study designs varied so much, the results should be interpreted cautiously. Before abnormalities found in the disorders can be designated as equal or ‘disorder-specific’, it will be essential to perform large longitudinal and cross-sectional follow-up studies.
Auslöser zur Durchführung der vorliegenden Arbeit war eine amerikanische Studie, in welcher bei autistischen Kindern fünf Wochen nach einmaliger intravenöser Sekretinapplikation eine deutliche Symptomverbesserung beobachtet werden konnte (Horvath et al., 1998). Ziel der vorliegenden Arbeit war die Untersuchung der Wirkung von peripher, d.h. intraperitoneal appliziertem Sekretin auf den Stoffwechsel von Neurotransmittern im Gehirn der Ratte, um damit einen Beitrag zur Klärung der bislang wenig erforschten Funktion von Sekretin im zentralen Nervensystem zu leisten. Anhand von Literaturangaben, die einen Zusammenhang mit Autismus belegten, wurden der Hippokampus als zu untersuchendes Areal und Aminosäuren, Katecholamine sowie Indolamine als zu untersuchende Substanzen ausgewählt. Grundlage der Arbeit bildeten tierexperimentelle Untersuchungen an frei beweglichen Ratten. Dabei wurden Mikrodialysesonden in den Hippokampus eingeführt und Fraktionen im Abstand von 20min. über einen Zeitraum von 4h mit einer Vorlaufzeit von 2h gesammelt. Verglichen wurden jeweils die Konzentrationen der gemessenen Substanzen vor und nach Sekretingabe (30 klinische Einheiten/ kg Körpergewicht intraperitoneal) im Vergleich zur Kochsalz-Kontrolle. Die Bestimmung von Aminosäuren und parallel dazu auch von Acylcarnitinen erfolgte mittels Tandem-Massenspektrometrie. Glutamat, gamma-Aminobuttersäure (GABA)und Aspartat wurden mittels Hochdruck-Flüssigkeitschromatographie (HPLC)und Fluoreszenzdetektion bestimmt. Zur Analyse der Katecholamine und Indolamine fand die HPLC mit elektrochemischer Detektion Anwendung. Zur Analyse von Katecholaminen und Indolaminen wurde zunächst eine neue Methode als Weiterentwicklung einer bestehenden Methode entwickelt. Die Gabe von Sekretin führte im Hippokampus zu einem gegenüber den mit Kochsalzlösung behandelten Tieren statistisch signifikanten Anstieg von Glutamat und gamma-Aminobuttersäure, während bei den Katecholaminen und Indolaminen nur ein leichter, jedoch nicht signifikanter Anstieg von Noradrenalin und 5-Hydroxyindol-3-Essigsäure beobachtet werden konnte. Interessanterweise zeigte sich bei einigen Acylcarnitinen, darunter Benzoylcarnitin und Isovalerylcarnitin, ebenfalls ein signifikanter Anstieg der gemessenen Konzentrationen nach Sekretingabe. Erstmals wurden in dieser Arbeit nach Erstbeschreibung der Bestimmung von Carnitin und Acetylcarnitin (Zhu et al., 2000) auch längerkettige Acylcarnitine mittels Mikrodialyse und Tandem-MS bestimmt. In der Gesamtschau der Ergebnisse konnte ein Effekt der intraperitonealen Injektion von Sekretin vor allem auf die hippokampalen Konzentrationen von GABA und Glutamat gezeigt werden. Damit ist unter Berücksichtigung der bisherigen Literaturangaben davon auszugehen, dass auch Sekretin ähnlich wie die anderen Mitglieder der Sekretinfamilie sowohl periphere als auch zentrale Wirkungen ausübt. Zukünftige Studien sollten die Frage nach einer zentralnervösen Wirkung von Sekretin auf andere Hirnareale ausweiten und auch den Einfluss unterschiedlicher Verabreichungsformen (intravenös, intracerebroventrikulär) auf die zentralen Wirkungen von Sekretin untersuchen. 1998, Horvath et al. (1998) observed a marked improvement in speech, eye contact, and attention in autistic children five weeks after treatment with intravenous secretin, which occurred in the course of an endoscopic investigation. Since the discovery of secretin in 1902 by Bayliss and Starling only little has been published on the cerebral functions of this primarily gastrointestinal hormone. Aim of this study was the investigation of the effect of peripherally applied secretin on the metabolism of neurotransmitters in the rat brain in order to make a contribution to the current debate on the still widely unknown role of secretin in the central nervous system. The microdialysis-experiments were performed in the hippocampus of freely moving rats. We chose the hippocampus as an area of interest and gamma-amino-butyric acid, glutamate, catecholamines (norepinephrine, epinephrine, dopamine and metabolites) and indolamines as substances to measure due to previous studies showing a link to childhood autism. Microdialysis probes were inserted under isoflurane anesthesia. Secretin was injected intraperitoneally (8.7 microg/kg i.p.), microdialysate was collected for 4h (once every 20 min). For the analysis of amino acids and acylcarnitines we used tandem-mass spectrometry. Glutamate, gamma-amino butyric acid and aspartate were measured by liquid chromatography and fluorescence detection. The analysis of catecholamines and indolamines was performed by high pressure liquid chromatography and electrochemical detection. After application of secretin a slight, though statistically not significant increase in extracellular concentrations of norepinephrine and the serotonin metabolite 5-hydroxyindole acetic acid could be observed, while the remaining substances remained unaffected. Glutamate and gamma-amino butyric acid increased significantly after the application of secretin. Interestingly also some acylcarnitines, for example isovalerylcarnitine and benzoylcarnitine, showed a statistically significant increase of their extracellular levels after application of secretin. After the first description of analysis of carnitine und acetylcarnitine with microdialysis in 1999, this study measured for the first time longchain acylcarnitines by the application of microdialysis. This study showed for the first time an effect of peripherally applied secretin on the metabolism of gamma-amino butyric acid and glutamate in the rat hippocampus. Reviewing the current literature we can conclude that these results strengthen the role of secretin as a neuroactive peptide, as it has been shown for other members of the secretin family of peptides. Future studies should emphasize the role of secretin as a neuropeptide in other relevant brain areas, such as the amygdala. Furthermore other forms of application (intravenous, intracerebroventricular application) should be of interest in future studies.
With increased recognition in the media, heightened prevalence, and advances in research technologies, investigation into the causes of autism has broadened in recent years. Studies at the molecular, structural, and behavioral levels have resulted in significant findings, linking autism to qualitative differences in neurological function and an alteration of early development. Familial aggregation of autism demonstrate a strong genetic factor, although genetics can not completely account for its pathogenesis. Studies show autism having one of the most complex pathologies among neurodevelopmental disorders. Future studies applying sophisticated methodologies in new areas may shed light on current mysteries surrounding the disorder.
We addressed the controversies surrounding the size of the neocerebellar vermis in autism and examined cerebellar size in light of recent reports of enlarged brain size in this disorder. In this study we use detailed MRI (1.5 mm) to examine the area of cerebellar lobules I through V and VI and VII and the volume of the total cerebellum in 35 autistic subjects and 36 controls. No abnormalities in the size of cerebellar lobules VI and VII in autistic individuals were detected, but the volume of the total cerebellum was significantly increased. We conclude that selective neocerebellar size abnormalities are not present in autistic individuals. Enlarged total cerebellar volume detected in this study is consistent with previous reports of regional brain enlargement in autism and also consistent with theories hypothesizing that the primary defect in autism is the result of abnormal development of a distributed neural network involving a number of regions of the brain.
To determine whether volumes of hippocampus and amygdala are abnormal in people with autism.
Neuropathologic studies of the limbic system in autism have found decreased neuronal size, increased neuronal packing density, and decreased complexity of dendritic arbors in hippocampus, amygdala, and other limbic structures. These findings are suggestive of a developmental curtailment in the maturation of the neurons and neuropil.
Measurement of hippocampus, amygdala, and total brain volumes from 1.5-mm coronal, spoiled gradient-recalled echo MRI scans in 14 non-mentally retarded autistic male adolescents and young adults and 14 individually matched, healthy community volunteers.
Amygdala volume was significantly smaller in the autistic subjects, both with (p = 0.006) and without (p = 0.01) correcting for total brain volume. Total brain volume and absolute hippocampal volume did not differ significantly between groups, but hippocampal volume, when corrected for total brain volume, was significantly reduced (p = 0.04) in the autistic subjects.
There is a reduction in the volume of amygdala and hippocampus in people with autism, particularly in relation to total brain volume. The histopathology of autism suggests that these volume reductions are related to a reduction in dendritic tree and neuropil development, and likely reflect the underdevelopment of the neural connections of limbic structures with other parts of the brain, particularly cerebral cortex.
As structural brain abnormalities have been reported in infantile autism, the aim of this study was to determine whether such findings also exist in Asperger Syndrome (AS).
The diagnosis of Asperger Syndrome was based on the criteria in ICD-10 and DSM-IV. Brain magnetic resonance imaging (MRI) was performed with a 1.5 T imager. T2-weighted axial and coronal slices and T1-weighted three dimensional sagittal slices were obtained and visual and quantitative analysis were performed.
There were 28 Asperger individuals, 17 children and adolescents (age 6-19 years, mean 12.4 years), 11 adults (age 20-60 years, mean 37. 9 years) and 28 healthy age and gender matched controls.
Mild inconsistent alterations were detected in 13/28 of the individuals with Asperger Syndrome compared to 6/23 in the comparable controls. There were no differences between the right and left hemispheres, nor was there any abnormality in terms of myelination or migration. The anterior-posterior diameters of the mesencephalon were statistically significantly shorter in the Asperger syndrome individuals than in the controls.
No consistent focal brain abnormalities for Asperger Syndrome were detected. The reduced diameters of the mesencephalon in the Asperger group support the hypothesis that the mesencephalon may be involved in the pathogenesis of Asperger Syndrome.
Social and emotional processing uses neural systems involving structures ranging from the brain stem to the associational cortex. Neuroimaging research has attempted to identify abnormalities in components of these systems that would underlie the behavioral abnormalities seen in disorders of social and emotional processing, notably autism spectrum disorders, the focus of this review. However, the findings have been variable. The most replicated anatomic finding (a tendency toward large brains) is not modular, and metabolic imaging and functional imaging (although showing substantial atypicality in activation) are not consistent regarding specific anatomic sites. Moreover, autism spectrum disorder demonstrates substantial heterogeneity on multiple levels. Here evidence is marshaled from a review of neuroimaging data to support the claim that abnormalities in social and emotional processing on the autism spectrum are a consequence of systems disruptions in which the behaviors are a final common pathway and the focal findings can be variable, downstream of other pathogenetic mechanisms, and downstream of more pervasive abnormalities.
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