Joseph Piven

Visual scanning of faces in autism.

The visual scanpaths of five high-functioning adult autistic males and five adult male controls were recorded using an infrared corneal reflection technique as they viewed photographs of human faces. Analyses of the scanpath data revealed marked differences in the scanpaths of the two groups. The autistic participants viewed nonfeature areas of the faces significantly more often and core feature areas of the faces (i.e., eyes, nose, and mouth) significantly less often than did control participants. Across both groups of participants, scanpaths generally did not differ as a function of the instructions given to the participants (i.e., “Please look at the faces in any manner you wish.” vs. “Please identify the emotions portrayed in these faces.”). Autistic participants showed a deficit in emotion recognition, but this effect was driven primarily by deficits in the recognition of fear. Collectively, these results indicate disorganized processing of face stimuli in autistic individuals and suggest a mechanism that may subserve the social information processing deficits that characterize autism spectrum disorders.

Abnormal Processing of Social Information from Faces in Autism

Autism has been thought to be characterized, in part, by dysfunction in emotional and social cognition, but the pathology of the underlying processes and their neural substrates remain poorly understood. Several studies have hypothesized that abnormal amygdala function may account for some of the impairments seen in autism, specifically, impaired recognition of socially relevant information from faces. We explored this issue in eight high-functioning subjects with autism in four experiments that assessed recognition of emotional and social information, primarily from faces. All tasks used were identical to those previously used in studies of subjects with bilateral amygdala damage, permitting direct comparisons. All subjects with autism made abnormal social judgments regarding the trustworthiness of faces; however, all were able to make normal social judgments from lexical stimuli, and all had a normal ability to perceptually discriminate the stimuli. Overall, these data from subjects with autism show some parallels to those from neurological subjects with focal amygdala damage. We suggest that amygdala dysfunction in autism might contribute to an impaired ability to link visual perception of socially relevant stimuli with retrieval of social knowledge and with elicitation of social behavior.

Macrocephaly in children and adults with autism

OBJECTIVE To explore the frequency and onset of macrocephaly in autism and its relationship to clinical features. METHOD Head circumferences at birth, during early childhood, and at the time of examination were studied in a community-based sample of autistic children and adults. The authors investigated whether head circumference at the time of examination was associated with clinical features. RESULTS Fourteen percent of the autistic subjects had macrocephaly: 11% of males and 24% of females. In most, the macrocephaly was not present at birth; in some it became apparent in early and middle childhood as a result of increased rate of head growth. A small relationship was noted between head circumference percentile and less severe core features of autism. Neither macrocephaly nor head circumference percentile was associated with nonverbal IQ, verbal status, seizure disorder, neurological soft signs or minor physical anomalies in the autistic subjects. CONCLUSION Macrocephaly is common in autism and usually is not present at birth. Rates of head growth may be abnormal in early and middle childhood in some (37%) children with autism. Macrocephaly does not define a homogeneous subgroup of autistic individuals according to clinical features.

Differences in White Matter Fiber Tract Development Present From 6 to 24 Months in Infants With Autism

OBJECTIVE Evidence from prospective studies of high-risk infants suggests that early symptoms of autism usually emerge late in the first or early in the second year of life after a period of relatively typical development. The authors prospectively examined white matter fiber tract organization from 6 to 24 months in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months. METHOD The participants were 92 high-risk infant siblings from an ongoing imaging study of autism. All participants had diffusion tensor imaging at 6 months and behavioral assessments at 24 months; a majority contributed additional imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for ASDs and 64 infants did not. Microstructural properties of white matter fiber tracts reported to be associated with ASDs or related behaviors were characterized by fractional anisotropy and radial and axial diffusivity. RESULTS The fractional anisotropy trajectories for 12 of 15 fiber tracts differed significantly between the infants who developed ASDs and those who did not. Development for most fiber tracts in the infants with ASDs was characterized by higher fractional anisotropy values at 6 months followed by slower change over time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs had lower values. CONCLUSIONS These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life. Longitudinal data are critical to characterizing the dynamic age-related brain and behavior changes underlying this neurodevelopmental disorder.

An MRI study of the basal ganglia in autism.

1. High-resolution MRI scans were obtained from 35 relatively high-functioning persons with autism and 36 healthy controls, comparable in age, gender, and IQ. 2. Volumetric measurements were obtained from manual tracing of the bilateral caudate, putamen, and globus pallidus. 3. An increased volume of the caudate nuclei was found in subjects with autism. Caudate enlargement was proportional to increased total brain volume in subjects with autism. 4. Caudate volume was associated with compulsions and rituals, difficulties with minor change, and complex motor mannerisms in autism. 5. Based on evidence of caudate abnormalities, a second MRI study was completed which replicated the finding of caudate enlargement in autism using an independent sample. 6. The caudate may be part of an abnormal distributed neural network in autism and involved in the ritualistic--repetitive behaviors of the disorder.

Regional Brain Enlargement in Autism: A Magnetic Resonance Imaging Study

OBJECTIVE To determine whether increased brain volume in autism, suggested in previous studies, is the result of general or regional brain size differences and to study the effect of gender on brain size and pattern of enlargement. METHOD Total brain volume and cerebral cortical lobe volumes were examined in 35 autistic and 36 comparison subjects using magnetic resonance imaging and an automated method of brain volume measurement. RESULTS After controlling for height and nonverbal IQ, the authors detected a significant diagnosis x gender effect (F = 7.4; p = .009) for total brain volume. A repeated-measures analysis of variance indicated that the pattern of enlargement (brain region x diagnosis) in autistic subjects differed from that in controls (F = 4.88; p = .0004). Subsequent sex-specific analysis revealed significantly increased total brain volume in autistic males but not females. Analysis of lobe sizes showed significant enlargement in autistic subjects in temporal, parietal, and occipital, but not frontal lobes. CONCLUSIONS These results suggest that brain size is increased in autism and that differences are not generalized but appear to be the result of a pattern of enlargement with increases in the size of specific cortical lobes.

Personality and Language Characteristics in Parents From Multiple-Incidence Autism Families

Several studies have suggested that the genetic liability for autism may be expressed in non-autistic relatives of autistic probands, in behavioral characteristics that are milder but qualitatively similar to the defining features of autism. We employ a variety of direct assessment approaches to examine both personality and language in parents ascertained through having two autistic children (multiple-incidence autism parents) and parents of Down syndrome probands. Multiple-incidence autism parents had higher rates of particular personality characteristics (rigidity, aloofness, hypersensitivity to criticism, and anxiousness), speech and pragmatic language deficits, and more limited friendships than parents in the comparison group. The implications of these findings for future genetic studies of autism are discussed.

An MRI study of autism: The cerebellum revisited

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.

Examination of AVPR1a as an autism susceptibility gene.

Impaired reciprocal social interaction is one of the core features of autism. While its determinants are complex, one biomolecular pathway that clearly influences social behavior is the arginine–vasopressin (AVP) system. The behavioral effects of AVP are mediated through the AVP receptor 1a (AVPR1a), making the AVPR1a gene a reasonable candidate for autism susceptibility. We tested the genes contribution to autism by screening its exons in 125 independent autistic probands and genotyping two promoter polymorphisms in 65 autism affected sibling pair (ASP) families. While we found no nonconservative coding sequence changes, we did identify evidence of linkage and of linkage disequilibrium. These results were most pronounced in a subset of the ASP families with relatively less severe impairment of language. Thus, though we did not demonstrate a disease-causing variant in the coding sequence, numerous nontraditional disease-causing genetic abnormalities are known to exist that would escape detection by traditional gene screening methods. Given the emerging biological, animal model, and now genetic data, AVPR1a and genes in the AVP system remain strong candidates for involvement in autism susceptibility and deserve continued scrutiny.

Personality characteristics of the parents of autistic individuals

Personality characteristics of 87 parents of autistic probands and 38 parents of Downs syndrome probands were examined using a standardized personality interview. Using best-estimate ratings derived from subject and informant interviews, parents of autistic individuals were rated significantly higher than controls on three characteristics: aloof, untactful and undemonstrative. When ratings were based on interviews with subjects only, parents of autistic probands were rated as significantly more aloof, untactful and unresponsive. There were no significant differences between parent groups on ratings based on informant interviews only. The implications of these findings for future family studies of autism are discussed.