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      Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism.

      Biological Psychiatry
      Autistic Disorder, pathology, physiopathology, psychology, Cerebellum, Child, Child, Preschool, Exploratory Behavior, physiology, Female, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male, Motor Activity, Stereotyped Behavior, Time Factors

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          Abstract

          Although limited environmental exploration in autism is an obvious behavioral feature and may be a manifestation of "restricted interests" as described in DSM-IV criteria, there have been no behavioral or neurobiological studies of this important aspect of the disorder. Given consistent reports of cerebellar abnormality in autism, combined with animal research showing a relationship between exploration and the cerebellum, this study aimed to test the possible link between cerebellar abnormality and exploration in autism. The relationship between visuospatial exploration, stereotyped motor movements, and magnetic resonance imaging measures of the cerebellar vermis, whole brain volume, and frontal lobes in 14 autistic and 14 normal children was investigated. Children were exposed to a large room with several exploration containers and instructed to play. Exploration behavior was videotaped and scored for percentage of time engaged in exploration, number of containers explored, as well as stereotyped movements. Children with autism spent significantly less time in active exploration and explored fewer containers overall than normal children. Measures of decreased exploration were significantly correlated with the magnitude of cerebellar hypoplasia of vermal lobules VI-VII in the autistic children, but no relationship to vermis size was found with normal control children. Further, measures of rates of stereotyped behavior were significantly negatively correlated with area measures of cerebellar vermis lobules VI-VII and positively correlated with frontal lobe volume in the autism sample. Reduced environmental exploration and repetitive behavior may have particularly important developmental consequences for children with autism because it may lead them to miss learning opportunities that fall outside their scope of interest. Our findings represent the first documented link between the restricted range of interests and stereotyped behaviors pathognomonic of autism and particular neuroanatomic sites.

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          Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers.

          To quantitate neuroanatomic parameters in healthy volunteers and to compare the values with normative values from postmortem studies. Magnetic resonance (MR) images of 116 volunteers aged 19 months to 80 years were analyzed with semiautomated procedures validated by means of comparison with manual tracings. Volumes measured included intracranial space, whole brain, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). Results were compared with values from previous postmortem studies. Whole brain and intracranial space grew by 25%-27% between early childhood (mean age, 26 months; age range, 19-33 months) and adolescence (mean age, 14 years; age range, 12-15 years); thereafter, whole-brain volume decreased such that volunteers (age range, 71-80 years) had volumes similar to those of young children. GM increased 13% from early to later (6-9 years) childhood. Thereafter, GM increased more slowly and reached a plateau in the 4th decade; it decreased by 13% in the oldest volunteers. The GM-WM ratio decreased exponentially from early childhood through the 4th decade; thereafter, it gradually declined. In vivo patterns of change in the intracranial space, whole brain, and GM-WM ratio agreed with published postmortem data. MR images accurately depict normal patterns of age-related change in intracranial space, whole brain, GM, WM, and CSF. These quantitative MR imaging data can be used in research studies and clinical settings for the detection of abnormalities in fundamental neuroanatomic parameters.
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            A clinicopathological study of autism.

            A neuropathological study of autism was established and brain tissue examined from six mentally handicapped subjects with autism. Clinical and educational records were obtained and standardized diagnostic interviews conducted with the parents of cases not seen before death. Four of the six brains were megalencephalic, and areas of cortical abnormality were identified in four cases. There were also developmental abnormalities of the brainstem, particularly of the inferior olives. Purkinje cell number was reduced in all the adult cases, and this reduction was sometimes accompanied by gliosis. The findings do not support previous claims of localized neurodevelopmental abnormalities. They do point to the likely involvement of the cerebral cortex in autism.
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              Hypoplasia of cerebellar vermal lobules VI and VII in autism.

              Autism is a neurologic disorder that severely impairs social, language, and cognitive development. Whether autism involves maldevelopment of neuroanatomical structures is not known. The size of the cerebellar vermis in patients with autism was measured on magnetic resonance scans and compared with its size in controls. The neocerebellar vermal lobules VI and VII were found to be significantly smaller in the patients. This appeared to be a result of developmental hypoplasia rather than shrinkage or deterioration after full development had been achieved. In contrast, the adjacent vermal lobules I to V, which are ontogenetically, developmentally, and anatomically distinct from lobules VI and VII, were found to be of normal size. Maldevelopment of the vermal neocerebellum had occurred in both retarded and nonretarded patients with autism. This localized maldevelopment may serve as a temporal marker to identify the events that damage the brain in autism, as well as other neural structures that may be concomitantly damaged. Our findings suggest that in patients with autism, neocerebellar abnormality may directly impair cognitive functions that some investigators have attributed to the neocerebellum; may indirectly affect, through its connections to the brain stem, hypothalamus, and thalamus, the development and functioning of one or more systems involved in cognitive, sensory, autonomic, and motor activities; or may occur concomitantly with damage to other neural sites whose dysfunction directly underlies the cognitive deficits in autism.
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