Asperger syndrome pathophysiology: Difference between revisions

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Asperger Syndrome (AS) causes some chemical, structural and functional abnormalities which include:<ref name="pmid29167722">{{cite journal| author=Faridi F, Khosrowabadi R| title=Behavioral, Cognitive and Neural Markers of Asperger Syndrome. | journal=Basic Clin Neurosci | year= 2017 | volume= 8 | issue= 5 | pages= 349-359 | pmid=29167722 | doi=10.18869/nirp.bcn.8.5.349 | pmc=5691167 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29167722  }} </ref>
Asperger Syndrome (AS) causes some chemical, structural and functional abnormalities which include:<ref name="pmid29167722">{{cite journal| author=Faridi F, Khosrowabadi R| title=Behavioral, Cognitive and Neural Markers of Asperger Syndrome. | journal=Basic Clin Neurosci | year= 2017 | volume= 8 | issue= 5 | pages= 349-359 | pmid=29167722 | doi=10.18869/nirp.bcn.8.5.349 | pmc=5691167 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29167722  }} </ref>


* Neuroimaging and structural brain abnormalities have been reported in Asperger (AS) such as:
* Neuroimaging and structural brain abnormalities have been reported in Asperger (AS) such as:<ref name="pmid29167722" /><ref name="pmid18563474">{{cite journal| author=Woodbury-Smith MR, Volkmar FR| title=Asperger syndrome. | journal=Eur Child Adolesc Psychiatry | year= 2009 | volume= 18 | issue= 1 | pages= 2-11 | pmid=18563474 | doi=10.1007/s00787-008-0701-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18563474  }} </ref>
**There has been a report on developmental problems of [[neuronal migration]] in the [[cerebral cortex]] during pregnancy and fetal development in patients with AS which may result in problems in the connectivity of the brain cortex.<ref name="pmid2136076">{{cite journal| author=Berthier ML, Starkstein SE, Leiguarda R| title=Developmental cortical anomalies in Asperger's syndrome: neuroradiological findings in two patients. | journal=J Neuropsychiatry Clin Neurosci | year= 1990 | volume= 2 | issue= 2 | pages= 197-201 | pmid=2136076 | doi=10.1176/jnp.2.2.197 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2136076  }} </ref>
**There has been a report on developmental problems of [[neuronal migration]] in the [[cerebral cortex]] during pregnancy and fetal development in patients with AS which may result in problems in the connectivity of the brain cortex.<ref name="pmid2136076">{{cite journal| author=Berthier ML, Starkstein SE, Leiguarda R| title=Developmental cortical anomalies in Asperger's syndrome: neuroradiological findings in two patients. | journal=J Neuropsychiatry Clin Neurosci | year= 1990 | volume= 2 | issue= 2 | pages= 197-201 | pmid=2136076 | doi=10.1176/jnp.2.2.197 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2136076  }} </ref>
**Smaller [[grey matter]] in the bilateral [[amygdala]], hippocampus gyrus, prefrontal lobe, medial frontal gyrus, left occipital gyrus, right [[cerebellum]], limbic striatal, bilateral caudate, left [[thalamus]], putamen and [[precuneus]].<ref name="pmid29167722" /><ref name="pmid18673405">{{cite journal| author=McAlonan GM, Suckling J, Wong N, Cheung V, Lienenkaemper N, Cheung C | display-authors=etal| title=Distinct patterns of grey matter abnormality in high-functioning autism and Asperger's syndrome. | journal=J Child Psychol Psychiatry | year= 2008 | volume= 49 | issue= 12 | pages= 1287-95 | pmid=18673405 | doi=10.1111/j.1469-7610.2008.01933.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18673405 }} </ref><ref name="pmid22132206">{{cite journal| author=Ameis SH, Fan J, Rockel C, Voineskos AN, Lobaugh NJ, Soorya L | display-authors=etal| title=Impaired structural connectivity of socio-emotional circuits in autism spectrum disorders: a diffusion tensor imaging study. | journal=PLoS One | year= 2011 | volume= 6 | issue= 11 | pages= e28044 | pmid=22132206 | doi=10.1371/journal.pone.0028044 | pmc=3223195 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22132206  }} </ref><ref name="pmid21398562">{{cite journal| author=Semrud-Clikeman M, Fine J| title=Presence of cysts on magnetic resonance images (MRIs) in children with asperger disorder and nonverbal learning disabilities. | journal=J Child Neurol | year= 2011 | volume= 26 | issue= 4 | pages= 471-5 | pmid=21398562 | doi=10.1177/0883073810384264 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21398562 }} </ref>
**Smaller gray matter in the ventromedial aspect of the [[temporal lobe]]<ref name="pmid15540637">{{cite journal| author=Kwon H, Ow AW, Pedatella KE, Lotspeich LJ, Reiss AL| title=Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome. | journal=Dev Med Child Neurol | year= 2004 | volume= 46 | issue= 11 | pages= 760-4 | pmid=15540637 | doi=10.1017/s0012162204001306 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15540637 }} </ref> and bilateral caudate and left [[thalamus]] <ref name="pmid18673405">{{cite journal| author=McAlonan GM, Suckling J, Wong N, Cheung V, Lienenkaemper N, Cheung C | display-authors=etal| title=Distinct patterns of grey matter abnormality in high-functioning autism and Asperger's syndrome. | journal=J Child Psychol Psychiatry | year= 2008 | volume= 49 | issue= 12 | pages= 1287-95 | pmid=18673405 | doi=10.1111/j.1469-7610.2008.01933.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18673405 }} </ref>.
**<s>Greater grey matter in the bilateral [[inferior parietal lobule]] and the left [[fusiform gyrus]].<ref name="pmid29167722" /></s>
**Greater [[white matter]] around the [[basal ganglia]] and left inferior parietal lobe, but lower white matter volume in the right [[corpus callosum]].<ref name="pmid19356262">{{cite journal| author=McAlonan GM, Cheung C, Cheung V, Wong N, Suckling J, Chua SE| title=Differential effects on white-matter systems in high-functioning autism and Asperger's syndrome. | journal=Psychol Med | year= 2009 | volume= 39 | issue= 11 | pages= 1885-93 | pmid=19356262 | doi=10.1017/S0033291709005728 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19356262  }} </ref>
**Greater [[white matter]] around the [[basal ganglia]] and left inferior parietal lobe, but lower white matter volume in the right [[corpus callosum]].<ref name="pmid19356262">{{cite journal| author=McAlonan GM, Cheung C, Cheung V, Wong N, Suckling J, Chua SE| title=Differential effects on white-matter systems in high-functioning autism and Asperger's syndrome. | journal=Psychol Med | year= 2009 | volume= 39 | issue= 11 | pages= 1885-93 | pmid=19356262 | doi=10.1017/S0033291709005728 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19356262  }} </ref>
**Larger amygdala and hippocampal in patients with AS is associated to their difficulty with emotional reactivity<ref name="pmid23672532">{{cite journal| author=Semrud-Clikeman M, Fine JG, Bledsoe J, Zhu DC| title=Magnetic resonance imaging volumetric findings in children with Asperger syndrome, nonverbal learning disability, or healthy controls. | journal=J Clin Exp Neuropsychol | year= 2013 | volume= 35 | issue= 5 | pages= 540-50 | pmid=23672532 | doi=10.1080/13803395.2013.795528 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23672532  }} </ref>
**Larger amygdala and hippocampal in patients with AS is associated to their difficulty with emotional reactivity<ref name="pmid23672532">{{cite journal| author=Semrud-Clikeman M, Fine JG, Bledsoe J, Zhu DC| title=Magnetic resonance imaging volumetric findings in children with Asperger syndrome, nonverbal learning disability, or healthy controls. | journal=J Clin Exp Neuropsychol | year= 2013 | volume= 35 | issue= 5 | pages= 540-50 | pmid=23672532 | doi=10.1080/13803395.2013.795528 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23672532  }} </ref>
**Smaller anterior cingulate cortex (ACC) in AS patients is associated with  their difficulty with self monitoring of behavior.<ref name="pmid23672532" />
**Smaller anterior cingulate cortex (ACC) in AS patients is associated with  their difficulty with self monitoring of behavior.<ref name="pmid23672532" />
**Lesion in the white matter of the right [[middle temporal gyrus]].<ref name="pmid10671397">{{cite journal| author=Volkmar FR, Klin A, Schultz RT, Rubin E, Bronen R| title=Asperger's disorder. | journal=Am J Psychiatry | year= 2000 | volume= 157 | issue= 2 | pages= 262-7 | pmid=10671397 | doi=10.1176/appi.ajp.157.2.262 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10671397  }} </ref>
**Lower fractional [[anisotropy]] (FA) is seen mostly bilaterally and in the white matter ([[internal capsule]], frontal, temporal, parietal and occipital lobe, [[Cingulum (anatomy)|cingulum]] and corpus callosum).<ref name="pmid20625995">{{cite journal| author=Bloemen OJ, Deeley Q, Sundram F, Daly EM, Barker GJ, Jones DK | display-authors=etal| title=White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults. | journal=Autism Res | year= 2010 | volume= 3 | issue= 5 | pages= 203-13 | pmid=20625995 | doi=10.1002/aur.146 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20625995  }} </ref>
**Localized disconnection in cerebellar neural pathways may lead to abnormalities in adaptive social behavior.<ref name="pmid18495494">{{cite journal| author=Catani M, Jones DK, Daly E, Embiricos N, Deeley Q, Pugliese L | display-authors=etal| title=Altered cerebellar feedback projections in Asperger syndrome. | journal=Neuroimage | year= 2008 | volume= 41 | issue= 4 | pages= 1184-91 | pmid=18495494 | doi=10.1016/j.neuroimage.2008.03.041 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18495494  }} </ref>
**Localized disconnection in cerebellar neural pathways may lead to abnormalities in adaptive social behavior.<ref name="pmid18495494">{{cite journal| author=Catani M, Jones DK, Daly E, Embiricos N, Deeley Q, Pugliese L | display-authors=etal| title=Altered cerebellar feedback projections in Asperger syndrome. | journal=Neuroimage | year= 2008 | volume= 41 | issue= 4 | pages= 1184-91 | pmid=18495494 | doi=10.1016/j.neuroimage.2008.03.041 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18495494  }} </ref>
**Lower fractional [[anisotropy]] (FA) mostly bilaterally and in the white ([[internal capsule]], frontal, temporal, parietal and occipital lobe, [[Cingulum (anatomy)|cingulum]] and corpus callosum).<ref name="pmid20625995">{{cite journal| author=Bloemen OJ, Deeley Q, Sundram F, Daly EM, Barker GJ, Jones DK | display-authors=etal| title=White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults. | journal=Autism Res | year= 2010 | volume= 3 | issue= 5 | pages= 203-13 | pmid=20625995 | doi=10.1002/aur.146 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20625995  }} </ref>
**Abnormal functional connectivity of medial temporal lobe structures (amygdala and parahippocampus gyrus) is associated with difficulty in social cognition in AS patients.<ref name="pmid15860339">{{cite journal| author=Welchew DE, Ashwin C, Berkouk K, Salvador R, Suckling J, Baron-Cohen S | display-authors=etal| title=Functional disconnectivity of the medial temporal lobe in Asperger's syndrome. | journal=Biol Psychiatry | year= 2005 | volume= 57 | issue= 9 | pages= 991-8 | pmid=15860339 | doi=10.1016/j.biopsych.2005.01.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15860339  }} </ref>
**Abnormal functional connectivity of medial temporal lobe structures (amygdala and parahippocampus gyrus) is associated with difficulty in social cognition in AS patients.<ref name="pmid15860339">{{cite journal| author=Welchew DE, Ashwin C, Berkouk K, Salvador R, Suckling J, Baron-Cohen S | display-authors=etal| title=Functional disconnectivity of the medial temporal lobe in Asperger's syndrome. | journal=Biol Psychiatry | year= 2005 | volume= 57 | issue= 9 | pages= 991-8 | pmid=15860339 | doi=10.1016/j.biopsych.2005.01.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15860339  }} </ref>
**Abnormal dysactivation of the [[frontal lobe]] (during neuropsychological tests).<ref name="pmid8556839">{{cite journal| author=Fletcher PC, Happé F, Frith U, Baker SC, Dolan RJ, Frackowiak RS | display-authors=etal| title=Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension. | journal=Cognition | year= 1995 | volume= 57 | issue= 2 | pages= 109-28 | pmid=8556839 | doi=10.1016/0010-0277(95)00692-r | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8556839  }} </ref><ref name="pmid9051780">{{cite journal| author=Happé F, Ehlers S, Fletcher P, Frith U, Johansson M, Gillberg C | display-authors=etal| title='Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome. | journal=Neuroreport | year= 1996 | volume= 8 | issue= 1 | pages= 197-201 | pmid=9051780 | doi=10.1097/00001756-199612200-00040 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9051780  }} </ref><ref name="pmid12959489">{{cite journal| author=Mundy P| title=Annotation: the neural basis of social impairments in autism: the role of the dorsal medial-frontal cortex and anterior cingulate system. | journal=J Child Psychol Psychiatry | year= 2003 | volume= 44 | issue= 6 | pages= 793-809 | pmid=12959489 | doi=10.1111/1469-7610.00165 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12959489  }} </ref><ref name="pmid10388796">{{cite journal| author=Ring HA, Baron-Cohen S, Wheelwright S, Williams SC, Brammer M, Andrew C | display-authors=etal| title=Cerebral correlates of preserved cognitive skills in autism: a functional MRI study of embedded figures task performance. | journal=Brain | year= 1999 | volume= 122 ( Pt 7) | issue=  | pages= 1305-15 | pmid=10388796 | doi=10.1093/brain/122.7.1305 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10388796  }} </ref>
**Abnormal activation in the temporal cortex during face discrimination.<ref name="pmid10768694">{{cite journal| author=Schultz RT, Gauthier I, Klin A, Fulbright RK, Anderson AW, Volkmar F | display-authors=etal| title=Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome. | journal=Arch Gen Psychiatry | year= 2000 | volume= 57 | issue= 4 | pages= 331-40 | pmid=10768694 | doi=10.1001/archpsyc.57.4.331 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10768694  }} </ref>
**Executive dysfunctions are associated with abnormality in neural connectivity of the brain cortex.<ref name="pmid28042973">{{cite journal| author=Han YM, Chan AS| title=Disordered cortical connectivity underlies the executive function deficits in children with autism spectrum disorders. | journal=Res Dev Disabil | year= 2017 | volume= 61 | issue=  | pages= 19-31 | pmid=28042973 | doi=10.1016/j.ridd.2016.12.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28042973  }} </ref>
**Neuroimaging patterns of AS patients were the same in static stimuli (photo of a face) and dynamic stimuli (real face).<ref>{{cite journal|doi=10.1016/j. rasd.2013.09.012}}</ref>
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*Chemical markers:
*Chemical markers:
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** There is an association in cortical [[serotonin]] 5-HT2A receptor binding and social communication in patients with AS.<ref name="pmid16648340">{{cite journal| author=Murphy DG, Daly E, Schmitz N, Toal F, Murphy K, Curran S | display-authors=etal| title=Cortical serotonin 5-HT2A receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study. | journal=Am J Psychiatry | year= 2006 | volume= 163 | issue= 5 | pages= 934-6 | pmid=16648340 | doi=10.1176/ajp.2006.163.5.934 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16648340  }} </ref>
** There is an association in cortical [[serotonin]] 5-HT2A receptor binding and social communication in patients with AS.<ref name="pmid16648340">{{cite journal| author=Murphy DG, Daly E, Schmitz N, Toal F, Murphy K, Curran S | display-authors=etal| title=Cortical serotonin 5-HT2A receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study. | journal=Am J Psychiatry | year= 2006 | volume= 163 | issue= 5 | pages= 934-6 | pmid=16648340 | doi=10.1176/ajp.2006.163.5.934 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16648340  }} </ref>
** Administration of [[oxytocin]] may improve facial emotion recognition, affective speech comprehension, increase eye gaze, emotion recognition and social interaction.<ref name="pmid24067301">{{cite journal| author=Domes G, Kumbier E, Heinrichs M, Herpertz SC| title=Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. | journal=Neuropsychopharmacology | year= 2014 | volume= 39 | issue= 3 | pages= 698-706 | pmid=24067301 | doi=10.1038/npp.2013.254 | pmc=3895247 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24067301  }} </ref>
** Administration of [[oxytocin]] may improve facial emotion recognition, affective speech comprehension, increase eye gaze, emotion recognition and social interaction.<ref name="pmid24067301">{{cite journal| author=Domes G, Kumbier E, Heinrichs M, Herpertz SC| title=Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. | journal=Neuropsychopharmacology | year= 2014 | volume= 39 | issue= 3 | pages= 698-706 | pmid=24067301 | doi=10.1038/npp.2013.254 | pmc=3895247 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24067301  }} </ref>
* Brain structural changes
**<br />
*** Volumetric exes  at the inferior parietal lobule is linked to [[synesthesia]].<ref name="pmid15860339">{{cite journal| author=Welchew DE, Ashwin C, Berkouk K, Salvador R, Suckling J, Baron-Cohen S | display-authors=etal| title=Functional disconnectivity of the medial temporal lobe in Asperger's syndrome. | journal=Biol Psychiatry | year= 2005 | volume= 57 | issue= 9 | pages= 991-8 | pmid=15860339 | doi=10.1016/j.biopsych.2005.01.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15860339  }} </ref>
*** Dysfunction of motor circuits in the frontostriatal and cerebellar reflect chaotic movement.<ref name="pmid16182941">{{cite journal| author=Nayate A, Bradshaw JL, Rinehart NJ| title=Autism and Asperger's disorder: are they movement disorders involving the cerebellum and/or basal ganglia? | journal=Brain Res Bull | year= 2005 | volume= 67 | issue= 4 | pages= 327-34 | pmid=16182941 | doi=10.1016/j.brainresbull.2005.07.011 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16182941  }} </ref>
*** There are lesions in the [[occipital lobe]] in areas responsible for visual/spatial reasoning.<ref name="pmid21398562">{{cite journal| author=Semrud-Clikeman M, Fine J| title=Presence of cysts on magnetic resonance images (MRIs) in children with asperger disorder and nonverbal learning disabilities. | journal=J Child Neurol | year= 2011 | volume= 26 | issue= 4 | pages= 471-5 | pmid=21398562 | doi=10.1177/0883073810384264 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21398562  }} </ref>
*** Several [[neuroimaging]] studies have found the following abnormalities:<ref name="pmid18563474">{{cite journal| author=Woodbury-Smith MR, Volkmar FR| title=Asperger syndrome. | journal=Eur Child Adolesc Psychiatry | year= 2009 | volume= 18 | issue= 1 | pages= 2-11 | pmid=18563474 | doi=10.1007/s00787-008-0701-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18563474  }} </ref>
**** Abnormal activation in the inferior temporal sulcus.<ref name="pmid10768694">{{cite journal| author=Schultz RT, Gauthier I, Klin A, Fulbright RK, Anderson AW, Volkmar F | display-authors=etal| title=Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome. | journal=Arch Gen Psychiatry | year= 2000 | volume= 57 | issue= 4 | pages= 331-40 | pmid=10768694 | doi=10.1001/archpsyc.57.4.331 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10768694  }} </ref><ref name="pmid12639338">{{cite journal| author=Schultz RT, Grelotti DJ, Klin A, Kleinman J, Van der Gaag C, Marois R | display-authors=etal| title=The role of the fusiform face area in social cognition: implications for the pathobiology of autism. | journal=Philos Trans R Soc Lond B Biol Sci | year= 2003 | volume= 358 | issue= 1430 | pages= 415-27 | pmid=12639338 | doi=10.1098/rstb.2002.1208 | pmc=1693125 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12639338  }} </ref> 
**** Abnormal dysactivation of the [[frontal lobe]] while performing  neuropsychological tests.<ref name="pmid8556839">{{cite journal| author=Fletcher PC, Happé F, Frith U, Baker SC, Dolan RJ, Frackowiak RS | display-authors=etal| title=Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension. | journal=Cognition | year= 1995 | volume= 57 | issue= 2 | pages= 109-28 | pmid=8556839 | doi=10.1016/0010-0277(95)00692-r | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8556839  }} </ref><ref name="pmid9051780">{{cite journal| author=Happé F, Ehlers S, Fletcher P, Frith U, Johansson M, Gillberg C | display-authors=etal| title='Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome. | journal=Neuroreport | year= 1996 | volume= 8 | issue= 1 | pages= 197-201 | pmid=9051780 | doi=10.1097/00001756-199612200-00040 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9051780  }} </ref><ref name="pmid12959489">{{cite journal| author=Mundy P| title=Annotation: the neural basis of social impairments in autism: the role of the dorsal medial-frontal cortex and anterior cingulate system. | journal=J Child Psychol Psychiatry | year= 2003 | volume= 44 | issue= 6 | pages= 793-809 | pmid=12959489 | doi=10.1111/1469-7610.00165 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12959489  }} </ref><ref name="pmid10388796">{{cite journal| author=Ring HA, Baron-Cohen S, Wheelwright S, Williams SC, Brammer M, Andrew C | display-authors=etal| title=Cerebral correlates of preserved cognitive skills in autism: a functional MRI study of embedded figures task performance. | journal=Brain | year= 1999 | volume= 122 ( Pt 7) | issue=  | pages= 1305-15 | pmid=10388796 | doi=10.1093/brain/122.7.1305 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10388796  }} </ref>
**** Abnormal functional integration of the amygdala and [[parahippocampal gyrus]].<ref name="pmid15860339">{{cite journal| author=Welchew DE, Ashwin C, Berkouk K, Salvador R, Suckling J, Baron-Cohen S | display-authors=etal| title=Functional disconnectivity of the medial temporal lobe in Asperger's syndrome. | journal=Biol Psychiatry | year= 2005 | volume= 57 | issue= 9 | pages= 991-8 | pmid=15860339 | doi=10.1016/j.biopsych.2005.01.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15860339  }} </ref> 
**** Abnormal structures in the inferior temporal gyrus, [[entorhinal cortex]] and rostral [[fusiform gyrus]].<ref name="pmid15540637">{{cite journal| author=Kwon H, Ow AW, Pedatella KE, Lotspeich LJ, Reiss AL| title=Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome. | journal=Dev Med Child Neurol | year= 2004 | volume= 46 | issue= 11 | pages= 760-4 | pmid=15540637 | doi=10.1017/s0012162204001306 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15540637  }} </ref>  
**** Missing tissue area in each hemisphere at the part where the [[middle frontal gyrus]] and the [[precentral sulcus]] intersect.<ref name="pmid8567603">{{cite journal| author=Volkmar FR, Klin A, Schultz R, Bronen R, Marans WD, Sparrow S | display-authors=etal| title=Asperger's syndrome. | journal=J Am Acad Child Adolesc Psychiatry | year= 1996 | volume= 35 | issue= 1 | pages= 118-23 | pmid=8567603 | doi=10.1097/00004583-199601000-00020 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8567603  }} </ref>
**** Lesion in the right [[middle temporal gyrus]] white matter.<ref name="pmid10671397">{{cite journal| author=Volkmar FR, Klin A, Schultz RT, Rubin E, Bronen R| title=Asperger's disorder. | journal=Am J Psychiatry | year= 2000 | volume= 157 | issue= 2 | pages= 262-7 | pmid=10671397 | doi=10.1176/appi.ajp.157.2.262 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10671397  }} </ref>


* Brain functional changes
* Brain functional changes
** Executive dysfunctions are related disordered neural connectivity of the brain.<ref name="pmid28042973">{{cite journal| author=Han YM, Chan AS| title=Disordered cortical connectivity underlies the executive function deficits in children with autism spectrum disorders. | journal=Res Dev Disabil | year= 2017 | volume= 61 | issue=  | pages= 19-31 | pmid=28042973 | doi=10.1016/j.ridd.2016.12.010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28042973  }} </ref>
**  
** Abnormal functions in cerebella, frontal and temporal lobes, and the limbic system.<ref name="pmid17354556">{{cite journal| author=Sugihara G, Ouchi Y, Nakamura K, Sekine Y, Mori N| title=[Advances in neuroimaging research on Asperger syndrome]. | journal=Nihon Rinsho | year= 2007 | volume= 65 | issue= 3 | pages= 449-52 | pmid=17354556 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17354556  }} </ref>
**  
** Abnormality in the functional integration of amygdala and parahippocampal gyrus.<ref name="pmid15860339">{{cite journal| author=Welchew DE, Ashwin C, Berkouk K, Salvador R, Suckling J, Baron-Cohen S | display-authors=etal| title=Functional disconnectivity of the medial temporal lobe in Asperger's syndrome. | journal=Biol Psychiatry | year= 2005 | volume= 57 | issue= 9 | pages= 991-8 | pmid=15860339 | doi=10.1016/j.biopsych.2005.01.028 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15860339  }} </ref>
** Neuroimaging patterns of AS patients are not affected by stimuli type (static and dynamic faces).<ref>{{cite journal|doi=10.1016/j. rasd.2013.09.012}}</ref> For example, story task and cartoon task activate the same region of the brain (medial prefrontal region).<ref name="pmid12135974">{{cite journal| author=Castelli F, Frith C, Happé F, Frith U| title=Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. | journal=Brain | year= 2002 | volume= 125 | issue= Pt 8 | pages= 1839-49 | pmid=12135974 | doi=10.1093/brain/awf189 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12135974  }} </ref>
** Main emotions, manifested by face, can activate fusiform and extra striates.<ref name="pmid17400195">{{cite journal| author=Deeley Q, Daly EM, Surguladze S, Page L, Toal F, Robertson D | display-authors=etal| title=An event related functional magnetic resonance imaging study of facial emotion processing in Asperger syndrome. | journal=Biol Psychiatry | year= 2007 | volume= 62 | issue= 3 | pages= 207-17 | pmid=17400195 | doi=10.1016/j.biopsych.2006.09.037 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400195  }} </ref>
** Main emotions, manifested by face, can activate fusiform and extra striates.<ref name="pmid17400195">{{cite journal| author=Deeley Q, Daly EM, Surguladze S, Page L, Toal F, Robertson D | display-authors=etal| title=An event related functional magnetic resonance imaging study of facial emotion processing in Asperger syndrome. | journal=Biol Psychiatry | year= 2007 | volume= 62 | issue= 3 | pages= 207-17 | pmid=17400195 | doi=10.1016/j.biopsych.2006.09.037 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400195  }} </ref>
**Several neuropsychological studies have suggested the following problems:<ref name="pmid18563474">{{cite journal| author=Woodbury-Smith MR, Volkmar FR| title=Asperger syndrome. | journal=Eur Child Adolesc Psychiatry | year= 2009 | volume= 18 | issue= 1 | pages= 2-11 | pmid=18563474 | doi=10.1007/s00787-008-0701-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18563474  }} </ref>
**Several neuropsychological studies have suggested the following problems:<ref name="pmid18563474">{{cite journal| author=Woodbury-Smith MR, Volkmar FR| title=Asperger syndrome. | journal=Eur Child Adolesc Psychiatry | year= 2009 | volume= 18 | issue= 1 | pages= 2-11 | pmid=18563474 | doi=10.1007/s00787-008-0701-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18563474  }} </ref>

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Pathophysiology

Functional magnetic resonance imaging provides some evidence for both underconnectivity and mirror neuron theories.[1][2]
  • Asperger syndrome appears to result from developmental factors that affect many or all functional brain systems, as opposed to localized effects.[3] Although the specific underpinnings of AS or factors that distinguish it from other ASDs are unknown, and no clear pathology common to individuals with AS has emerged, it is still possible that AS's mechanism is separate from other ASD.[4] Neuroanatomical studies and the associations with teratogens strongly suggest that the mechanism includes alteration of brain development soon after conception. Abnormal migration of embryonic cells during fetal development may affect the final structure and connectivity of the brain, resulting in alterations in the neural circuits that control thought and behavior.[5] Several theories of mechanism are available; none are likely to be complete explanations.[6]
  • The underconnectivity theory hypothesizes underfunctioning high-level neural connections and synchronization, along with an excess of low-level processes.[1] It maps well to general-processing theories such as weak central coherence theory, which hypothesizes that a limited ability to see the big picture underlies the central disturbance in ASD.[7] A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals.[8]
  • The mirror neuron system (MNS) theory hypothesizes that alterations to the development of the MNS interfere with imitation and lead to Asperger's core feature of social impairment.[2][9] For example, one study found that activation is delayed in the core circuit for imitation in individuals with AS.[10] This theory maps well to social cognition theories like the theory of mind, which hypothesizes that autistic behavior arises from impairments in ascribing mental states to oneself and others,[11] or hyper-systemizing, which hypothesizes that autistic individuals can systematize internal operation to handle internal events but are less effective at empathizing by handling events generated by other agents.[12]

Associated Conditions

Overview

The exact pathophysiology of Asperger Syndrome is unknown, however some neuroimaging and neuropsychological studies have reported some findings.

Pathophysiology

Asperger Syndrome (AS) causes some chemical, structural and functional abnormalities which include:[16]

  • Neuroimaging and structural brain abnormalities have been reported in Asperger (AS) such as:[16][17]
    • There has been a report on developmental problems of neuronal migration in the cerebral cortex during pregnancy and fetal development in patients with AS which may result in problems in the connectivity of the brain cortex.[18]
    • Smaller gray matter in the ventromedial aspect of the temporal lobe[19] and bilateral caudate and left thalamus [20].
    • Greater white matter around the basal ganglia and left inferior parietal lobe, but lower white matter volume in the right corpus callosum.[21]
    • Larger amygdala and hippocampal in patients with AS is associated to their difficulty with emotional reactivity[22]
    • Smaller anterior cingulate cortex (ACC) in AS patients is associated with their difficulty with self monitoring of behavior.[22]
    • Lesion in the white matter of the right middle temporal gyrus.[23]
    • Lower fractional anisotropy (FA) is seen mostly bilaterally and in the white matter (internal capsule, frontal, temporal, parietal and occipital lobe, cingulum and corpus callosum).[24]
    • Localized disconnection in cerebellar neural pathways may lead to abnormalities in adaptive social behavior.[25]
    • Abnormal functional connectivity of medial temporal lobe structures (amygdala and parahippocampus gyrus) is associated with difficulty in social cognition in AS patients.[26]
    • Abnormal dysactivation of the frontal lobe (during neuropsychological tests).[27][28][29][30]
    • Abnormal activation in the temporal cortex during face discrimination.[31]
    • Executive dysfunctions are associated with abnormality in neural connectivity of the brain cortex.[32]
    • Neuroimaging patterns of AS patients were the same in static stimuli (photo of a face) and dynamic stimuli (real face).[33]
  • Chemical markers:
    • Higher level of N-acetyl aspartate/choline (NAA/Cho) level at the right anterior cingulate.[34]
    • Affected dopaminergic system due to increase in [18F] F-Dopa influx(k) increase in the striatum, putamen, caudate nucleus and frontal cortex.[35]
    • Changes in NAA/Cho are positively correlated with the obsessive compulsive scale problems in AS.[16]
    • There is an association in cortical serotonin 5-HT2A receptor binding and social communication in patients with AS.[36]
    • Administration of oxytocin may improve facial emotion recognition, affective speech comprehension, increase eye gaze, emotion recognition and social interaction.[37]
  • Brain functional changes
    • Main emotions, manifested by face, can activate fusiform and extra striates.[38]
    • Several neuropsychological studies have suggested the following problems:[17]
      • Difficulty in passing theory of mind tasks
      • Executive dysfunction
      • Tendency to interpret visual stimuli in parts rather than wholes (poor central coherence)
      • There are studies that suggest in patients with AS there is a Verbal IQ (VIQ) > Poor Performance IQ (PIQ) profile which shows strength on verbal skills relative to visuospatial skills and non-verbal problem solving (nonverbal learning disability)[39]

Associated Conditions

Asperger Syndrome (AS) is associated with several conditions which include:

References

  1. 1.0 1.1 Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ (2007). "Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry". Cereb Cortex. 17 (4): 951–61. doi:10.1093/cercor/bhl006. PMID 16772313.
  2. 2.0 2.1 Iacoboni M, Dapretto M (2006). "The mirror neuron system and the consequences of its dysfunction". Nat Rev Neurosci. 7 (12): 942–51. doi:10.1038/nrn2024. PMID 17115076.
  3. Müller RA (2007). "The study of autism as a distributed disorder". Ment Retard Dev Disabil Res Rev. 13 (1): 85–95. doi:10.1002/mrdd.20141. PMID 17326118.
  4. Rinehart NJ, Bradshaw JL, Brereton AV, Tonge BJ (2002). "A clinical and neurobehavioural review of high-functioning autism and Asperger's disorder". Aust N Z J Psychiatry. 36 (6): 762–70. doi:10.1046/j.1440-1614.2002.01097.x. PMID 12406118.
  5. Berthier ML, Starkstein SE, Leiguarda R (1990). "Developmental cortical anomalies in Asperger's syndrome: neuroradiological findings in two patients". J Neuropsychiatry Clin Neurosci. 2 (2): 197–201. PMID 2136076.
  6. Happé F, Ronald A, Plomin R (2006). "Time to give up on a single explanation for autism". Nat Neurosci. 9 (10): 1218–20. doi:10.1038/nn1770. PMID 17001340.
  7. Happé F, Frith U (2006). "The weak coherence account: detail-focused cognitive style in autism spectrum disorders". J Autism Dev Disord. 36 (1): 5–25. doi:10.1007/s10803-005-0039-0. PMID 16450045.
  8. Mottron L, Dawson M, Soulières I, Hubert B, Burack J (2006). "Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception". J Autism Dev Disord. 36 (1): 27–43. doi:10.1007/s10803-005-0040-7. PMID 16453071.
  9. Ramachandran VS, Oberman LM (2006). "Broken mirrors: a theory of autism" (PDF). Sci Am. 295 (5): 62–9. PMID 17076085. Retrieved 2008-04-17.
  10. Nishitani N, Avikainen S, Hari R (2004). "Abnormal imitation-related cortical activation sequences in Asperger's syndrome". Ann Neurol. 55 (4): 558–62. doi:10.1002/ana.20031. PMID 15048895.
  11. Baron-Cohen S, Leslie AM, Frith U (1985). "Does the autistic child have a 'theory of mind'?" (PDF). Cognition. 21 (1): 37–46. doi:10.1016/0010-0277(85)90022-8. PMID 2934210. Retrieved 2007-06-28.
  12. Baron-Cohen S (2006). "The hyper-systemizing, assortative mating theory of autism". Prog Neuropsychopharmacol Biol Psychiatry. 30 (5): 865–72. doi:10.1016/j.pnpbp.2006.01.010. PMID 16519981.
  13. Murphy DG, Daly E, Schmitz N; et al. (2006). "Cortical serotonin 5-HT2A receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study". Am J Psychiatry. 163 (5): 934–6. doi:10.1176/appi.ajp.163.5.934. PMID 16648340.
  14. Gowen E, Miall RC (2005). "Behavioural aspects of cerebellar function in adults with Asperger syndrome". Cerebellum. 4 (4): 279–89. doi:10.1080/14734220500355332. PMID 16321884.
  15. Gillberg C, Billstedt E (2000). "Autism and Asperger syndrome: coexistence with other clinical disorders". Acta Psychiatr Scand. 102 (5): 321–30. doi:10.1034/j.1600-0447.2000.102005321.x. PMID 11098802.
  16. 16.0 16.1 16.2 Faridi F, Khosrowabadi R (2017). "Behavioral, Cognitive and Neural Markers of Asperger Syndrome". Basic Clin Neurosci. 8 (5): 349–359. doi:10.18869/nirp.bcn.8.5.349. PMC 5691167. PMID 29167722.
  17. 17.0 17.1 Woodbury-Smith MR, Volkmar FR (2009). "Asperger syndrome". Eur Child Adolesc Psychiatry. 18 (1): 2–11. doi:10.1007/s00787-008-0701-0. PMID 18563474.
  18. Berthier ML, Starkstein SE, Leiguarda R (1990). "Developmental cortical anomalies in Asperger's syndrome: neuroradiological findings in two patients". J Neuropsychiatry Clin Neurosci. 2 (2): 197–201. doi:10.1176/jnp.2.2.197. PMID 2136076.
  19. Kwon H, Ow AW, Pedatella KE, Lotspeich LJ, Reiss AL (2004). "Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome". Dev Med Child Neurol. 46 (11): 760–4. doi:10.1017/s0012162204001306. PMID 15540637.
  20. McAlonan GM, Suckling J, Wong N, Cheung V, Lienenkaemper N, Cheung C; et al. (2008). "Distinct patterns of grey matter abnormality in high-functioning autism and Asperger's syndrome". J Child Psychol Psychiatry. 49 (12): 1287–95. doi:10.1111/j.1469-7610.2008.01933.x. PMID 18673405.
  21. McAlonan GM, Cheung C, Cheung V, Wong N, Suckling J, Chua SE (2009). "Differential effects on white-matter systems in high-functioning autism and Asperger's syndrome". Psychol Med. 39 (11): 1885–93. doi:10.1017/S0033291709005728. PMID 19356262.
  22. 22.0 22.1 Semrud-Clikeman M, Fine JG, Bledsoe J, Zhu DC (2013). "Magnetic resonance imaging volumetric findings in children with Asperger syndrome, nonverbal learning disability, or healthy controls". J Clin Exp Neuropsychol. 35 (5): 540–50. doi:10.1080/13803395.2013.795528. PMID 23672532.
  23. Volkmar FR, Klin A, Schultz RT, Rubin E, Bronen R (2000). "Asperger's disorder". Am J Psychiatry. 157 (2): 262–7. doi:10.1176/appi.ajp.157.2.262. PMID 10671397.
  24. Bloemen OJ, Deeley Q, Sundram F, Daly EM, Barker GJ, Jones DK; et al. (2010). "White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults". Autism Res. 3 (5): 203–13. doi:10.1002/aur.146. PMID 20625995.
  25. Catani M, Jones DK, Daly E, Embiricos N, Deeley Q, Pugliese L; et al. (2008). "Altered cerebellar feedback projections in Asperger syndrome". Neuroimage. 41 (4): 1184–91. doi:10.1016/j.neuroimage.2008.03.041. PMID 18495494.
  26. Welchew DE, Ashwin C, Berkouk K, Salvador R, Suckling J, Baron-Cohen S; et al. (2005). "Functional disconnectivity of the medial temporal lobe in Asperger's syndrome". Biol Psychiatry. 57 (9): 991–8. doi:10.1016/j.biopsych.2005.01.028. PMID 15860339.
  27. Fletcher PC, Happé F, Frith U, Baker SC, Dolan RJ, Frackowiak RS; et al. (1995). "Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension". Cognition. 57 (2): 109–28. doi:10.1016/0010-0277(95)00692-r. PMID 8556839.
  28. Happé F, Ehlers S, Fletcher P, Frith U, Johansson M, Gillberg C; et al. (1996). "'Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome". Neuroreport. 8 (1): 197–201. doi:10.1097/00001756-199612200-00040. PMID 9051780.
  29. Mundy P (2003). "Annotation: the neural basis of social impairments in autism: the role of the dorsal medial-frontal cortex and anterior cingulate system". J Child Psychol Psychiatry. 44 (6): 793–809. doi:10.1111/1469-7610.00165. PMID 12959489.
  30. Ring HA, Baron-Cohen S, Wheelwright S, Williams SC, Brammer M, Andrew C; et al. (1999). "Cerebral correlates of preserved cognitive skills in autism: a functional MRI study of embedded figures task performance". Brain. 122 ( Pt 7): 1305–15. doi:10.1093/brain/122.7.1305. PMID 10388796.
  31. Schultz RT, Gauthier I, Klin A, Fulbright RK, Anderson AW, Volkmar F; et al. (2000). "Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome". Arch Gen Psychiatry. 57 (4): 331–40. doi:10.1001/archpsyc.57.4.331. PMID 10768694.
  32. Han YM, Chan AS (2017). "Disordered cortical connectivity underlies the executive function deficits in children with autism spectrum disorders". Res Dev Disabil. 61: 19–31. doi:10.1016/j.ridd.2016.12.010. PMID 28042973.
  33. . doi:10.1016/j. rasd.2013.09.012 Check |doi= value (help). Missing or empty |title= (help)
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