Case report

We report functional brain mapping of a right-handed male who was 22 years old at the time of study. Signs of autism, such as social withdrawal, echolalia, stereotypic and repetitive motor mannerisms, persistent preoccupation with parts of objects, and self-harm were detected during the second year of life. Normal schooling was unsuccessful. At the age of 4 years he was admitted to a day-care psychiatric unit. He was also examined by a neuropaediatrician. The diagnosis of autism was made by a psychiatrist and a psychologist according to DSM-IV criteria (American Psychiatric Association, 1994). Diagnosis was confirmed by the Autism Diagnostic Interview - Revised (ADI-R) (Reference Lord, Ruttei and Le CouteurLord et al, 1994) (social interaction scores: 29; verbal communication scores: 24; non-verbal communication scores: 12; stereotypy scores: 9; age-onset criteria: 3). At the age of 20 years his global IQ was 66 (Wechsler Adult Intelligence Scale - Revised; Reference WechslerWechsler, 1981), with a score of 45 for performance and 83 for verbal abilities. He had typical autistic speech abnormalities (verbal perseveration, stereotypy, echolalia, abnormal prosody, neologism). Meticulous clinical evaluation was also performed. He had no infectious, metabolic, neurological or genetic diseases. He is not dysmorphic. Electroencephalography and magnetic resonance imaging (MRI) were normal.

An ethics committee approved this study and examination was performed with the informed written consent of the parents.

Brain imaging protocol

Positron emission tomography (PET) uses positron-emitting labelled carriers to produce an image of brain activity. One of the applications of PET is the study of functional brain activity by measuring regional cerebral blood flow during the performance of cognitive tasks. Regional changes in cerebral blood flow between two tasks reflect the mobilisation of functional units specific to the new task. Hence it is possible to identify the brain regions activated by the stimulus. The purpose of this study was to identify the regions activated by performance of the calendar task. To do this, blood flow images were obtained at base-line and during performance of the task and the two images were subtracted. Those regions that had been activated showed a change in blood flow.

Task

In the calendar task dates were chosen randomly over a period of 16 years (1982-1998). During the scan, dates were given orally by the investigator and the young man was asked to answer orally the day of the week that corresponded to the date (e.g. 26 February 1982 Friday). Fifteen dates were given during 100 s of PET acquisition (1 question/answer every 6 s).

In the word repetition control task a list of French objects was selected (e.g. car, house, toys). The investigator gave orally the name of an object and the young man was asked to repeat it orally (50 words during the 100 s of PET acquisition) in order to control for auditory perception and word production.

Image acquisition

Scanning was performed using an ECAT Exact HR+962 PET camera (Siemens, Knoxville, Tennessee, USA). Attenuation-corrected data were reconstructed into 63 slices, with a resulting resolution of 5 mm full width at half maximum. Relative cerebral blood flow was determined from the distribution of radioactivity after bolus intravenous injections of H ¹⁵ ₂O (Reference Fox, Mintun and RaichleFox et al, 1984). Twenty seconds before each scan, 10 mCi of H ¹⁵ ₂O was administered by an intravenous bolus injection. Data were collected over 80 s. The young man was lying in the scanner in a quiet darkened room. Three measurements of relative cerebral blood flow were performed: (1) at rest; (2) during the auditory calendar task; and (3) during a control repetition of words. Tasks started 20 s before image acquisition. Three-dimensional Three-dimensional T1 high-resolution MRI of the brain (General Electric 1.5-T Signa system, GE Medical Systems, Milwaukee, Wisconsin, USA) was also performed on the same day.

Image analysis

Statistical parametric mapping software (SPM96, Wellcome Department of Cognitive Neurology, London) was used for image realignment, transformation into standard stereotactic space (Reference Talairach and TournouxTalairach & Tournoux, 1988), smoothing (15 mm Gaussian kernel) and statistical analysis (Reference Friston, Holmes and WorsleyFriston et al, 1995). State-dependent differences in global flow were corrected using proportional scaling. To assess the individual pattern of activation we designed a multistudy model matrix. Images of five normal controls during rest were included in the model, allowing an estimation of inter-participant variability.

The three conditions (rest, calendar task and word repetition) were compared using the t-statistic subsequently transformed into a normally distributed Zstatistic. Z-maps were thresholded at 3.09 (P<0.001).

CLINICAL IMPLICATIONS

1. ▪ The capacity to associate a day of the week with a corresponding date is associated in this individual with significant activation of a fronto-temporal network including the hippocampus, which is highly implicated in memory processing.

2. ▪ Functional brain imaging opens a new perspective for investigating the cerebral networks involving exceptional capacities in autism.

3. ▪ The present results may lead to the speculation that during development people with autism can 'overdevelop' a normal brain circuit, giving rise to prodigious capacity, despite their severe cognitive and behavioural handicaps.

LIMITATIONS

1. ▪ A single case study is inadequate for establishing a general mechanism for this capacity in autism.

2. ▪ We cannot generalise the findings from a single individual to savant abilities in populations with autism.

3. ▪ Owing to the unusual nature of the calendar task, we did not ask our control group to participate in it, and so we could not compare the pattern of brain activation that it produced in a savant and in controls.