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      Regional Cerebral Glucose Metabolism and its Association with Phenotype and Cognitive Functioning in Patients with Autism

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          Abstract

          Introduction:

          In spite of three decades of neuroimaging, we are unable to find consistent and coherent anatomical or pathophysiological basis for autism as changes are subtle and there are no studies from India.

          Aim:

          To study the regional cerebral glucose metabolism in children with autism using positron emission tomography (PET) scan and to study the behavior and cognitive functioning among them.

          Materials and Methods:

          Ten subjects (8–19 years) meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for autism were evaluated on Childhood Autism Rating Scale (CARS), trail making test (TMT) A and B, Wisconsin card sorting test, Raven's progressive matrices, and PET scan. A control group of 15 matched subjects without any brain pathology or neurological disorder was similarly studied.

          Results:

          Four out of the ten patients with autism had abnormal PET scan findings, and in contrast, none of the patients in the control group had abnormal PET scan. Of the four patients with abnormality in the PET scan, two patients had findings suggestive of hypometabolism in cerebellum bilaterally; one patient showed bilateral hypometabolism in anterior temporal cortices and cerebellum, and the fourth patient had hypermetabolism in the bilateral frontal cortices and medial occipital cortices. Subjects with autism performed poorly on neuropsychological testing. Patients with abnormal PET scan findings had significantly higher scores on the “body use” domain of CARS indicating more stereotypy.

          Conclusion:

          Findings of this study support the view of altered brain functioning in subjects with autism.

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          Most cited references39

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          Social intelligence in the normal and autistic brain: an fMRI study.

          There is increasing support for the existence of 'social intelligence' [Humphrey (1984) Consciousness Regained], independent of general intelligence. Brothers et al. 1990) J. Cog. Neurosci., 4, 107-118] proposed a network of neural regions that comprise the 'social brain': the orbito-frontal cortex (OFC), superior temporal gyrus (STG) and amygdala. We tested Brothers' theory by examining both normal subjects as well as patients with high-functioning autism or Asperger syndrome (AS), who are well known to have deficits in social intelligence, and perhaps deficits in amygdala function [Bauman & Kemper (1988) J. Neuropath. Exp. Neurol., 47, 369]. We used a test of judging from the expressions of another person's eyes what that other person might be thinking or feeling. Using functional magnetic resonance imaging (fMRI) we confirmed Brothers' prediction that the STG and amygdala show increased activation when using social intelligence. Some areas of the prefrontal cortex also showed activation. In contrast, patients with autism or AS activated the fronto-temporal regions but not the amygdala when making mentalistic inferences from the eyes. These results provide support for the social brain theory of normal function, and the amygdala theory of 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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              Localized enlargement of the frontal cortex in early autism.

              Evidence from behavioral, imaging, and postmortem studies indicates that the frontal lobe, as well as other brain regions such as the cerebellum and limbic system, develops abnormally in children with autism. It is not yet clear to what extent the frontal lobe is affected; that is, whether all regions of frontal cortex show the same signs of structural maldevelopment. In the present study, we measured cortical volume in four subregions of the frontal cortex in 2-year-old to 9-year-old boys with autism and normal control boys. The dorsolateral region showed a reduced age effect in patients when compared with control subjects, with a predicted 10% increase in volume from 2 years of age to 9 years of age compared with a predicted 48% increase for control subjects. In a separate analysis, dorsolateral and medial frontal regions were significantly enlarged in patients aged 2 to 5 years compared with control subjects of the same age, but the precentral gyrus and orbital cortex were not. These data indicate regional variation in the degree of frontocortical overgrowth with a possible bias toward later developing or association areas. Possible mechanisms for these regional differences are discussed.
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                Author and article information

                Journal
                Indian J Psychol Med
                Indian J Psychol Med
                IJPsyM
                Indian Journal of Psychological Medicine
                Medknow Publications & Media Pvt Ltd (India )
                0253-7176
                0975-1564
                May-Jun 2017
                : 39
                : 3
                : 262-270
                Affiliations
                [1]Department of Psychiatry, Shridevi Institute of Medical Sciences and Research Hospital, Tumkur, Karnataka, India
                [1 ]Department of Psychiatry, M. M. Institute of Medical Sciences and Research, Ambala, Haryana, India
                [2 ]Department of Nuclear Medicine, PGIMER, Chandigarh, India
                [3 ]Department of Psychiatry, PGIMER, Chandigarh, India
                [4 ]Department of Anaesthesia and Pain Management, Max Super Speciality Hospital, Mohali, Punjab, India
                Author notes
                Address for correspondence: Dr. Sandeep Grover Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012, India. E-mail: drsandeepg2002@ 123456yahoo.com
                Article
                IJPsyM-39-262
                10.4103/0253-7176.207344
                5461834
                28615758
                17574d00-4080-4af7-b337-b3886f4393a2
                Copyright: © 2017 Indian Psychiatric Society

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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                Categories
                Original Article

                Clinical Psychology & Psychiatry
                autism,autism spectrum disorder,neuropsychological functioning,positron emission tomography scan

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