Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity Marcel Adam Just, Vladimir L. Cherkassky, Timothy A. Keller ans Nancy J. Minshew Brain, 127: , 2004

Introduction of autism Named by Dr. Leo Kanner in 1943 –A population of individuals who were very isolated and aloof. Autism means “self” Autism is a syndrome disorder. It has four diagnostic criteria which must be present: –Impairment in social interaction –Impairment in communication –Restricted, repetitive stereotyped patterns of behavior –Onset prior to age three

Introduction of autism (con’t) The symptoms of autism occur on a continuum from mild to severe –Diagnostic subgroups of autism high-functioningII IIIIV High IQ Low IQ 60 Fluent/Verbal speechNonverbal

Dr. Temple Grandin –B.A. (Psychology), Franklin Pierce College, –M.S. (Animal Science), Arizona State University (part time), –Ph.D. (Animal Science), University of Illinois (part time), 1989.

Language processing areas Left inferior frontal gyrusLeft superior and middle temporal gyrus

Broca’s aphasia (agrammatic aphasia) –"Yes... ah... Monday... er... Dad and Peter H... (his own name), and Dad.... er... hospital... and ah... Wednesday... Wednesday, nine o'clock... and oh... Thursday... ten o'clock, ah doctors... two... an' doctors... and er... teeth... yah." Wernicke’s aphasia (fluent aphasia) –"I called my mother on the television and did not understand the door. It was too breakfast, but they came from far to near. My mother is not too old for me to be young.

Language processing areas Syntactic processing Semantic processing Working memory functions Lexical processing Left inferior frontal gyrus Left superior and middle temporal gyrus

Previous study of high-functioning autism A preserved or even enhanced ability in the narrower- scope task of reading individual words. A deficit in the broader-scope task of processing grammatically (Goldstein et al, 1994) Brain activation in Broca’s area and Wernicke’s area may play a central role in accounting for the language comprehension abnormalities in autism –PET study: less lateralization in the perisylvian and temporal areas in autism (Muller el al, 1999) –Morphometric study: Broca’s and Wernicke’s areas of left hemisphere are smaller than the homologue of right hemisphere in autism (Herbert et al, 2002)

Methods Group matching: –17 high-functioning autistic participants –17 healthy normal participants (verbal IQ- matched) Sentence comprehension task Active sentence The cook thanked the father. (main sentence) Who was thanked? (probe) cook-father Passive sentence The editor was saved by the secretary. Who was saving? editor-secretary

Active sentences Passive sentences Filled with fixation epochs (24s)

Behavioural performance Reaction time: Error rates: autisticcontrol active2456 ms3061 ms passive2803 ms3447 ms autisticcontrol active8%5% passive13%7% Autistic group took reliably shorter than control group F(1,32)=4.36, p<0.05 Autistic group is slightly but not reliably higher than control group

Hypothesis (part I) Autistic participants may rely more on an enhanced word-processing ability and rely less on integrating processes that bring the words of a sentences together into an integrated syntactic and semantic structure Wernicke’s area Broca’s area Using fMRI to examine the brain activation

Results Broca’s area And adjacent areas Wernicke’s area Secondary visual area

Hypothesis (part II) Complex cognitive processing (eq. language processing) needs large-scale cortical networks to collaborate. The activation in a set of cortical areas should be synchronized, indicating collaboration among areas Synchronization: compute the correlation or covariance between activation levels in two activated areas Synchronization is taken as evidence of “functional connectivity” Underconnectivity: lower level of functional connectivity among autism

Results

Result

Conclusions The autism group perform the task faster and less accurately The autism group produced reliably more activation than the control group in Wernicke’s area The autism group produce reliably less activation than the control group in Broca’s area The functional connectivity was consistently lower for the autistic than the control participants

Discussion The higher brain activation in Wernicke’s area is consistent with their hyperlexicality or unusual strength in processing single words The lower brain activation in Broca’s area is consistent with the finding that high-functioning autism are impaired in their ability to process the meaning of complex sentences –The lower activation of secondary visual cortex may also be consistent with this account. The use of mental imagery might be another way to form an integration of the meaning of a sentence Underconnectivity is unlikely to be specific to language. It is also shown in non-language task. Any facet that is dependent on the coordination or integration of brain regions is susceptible to disruption in autism, particularly when the computational demand of the coordination is large. Underconnectivity vs weak central coherence theory (Frith, 1989)