Faculty Bibliography

OBJECTIVE:The authors investigated chronic cerebellar reorganization following unilateral cortical lesions in children and adults using PET to measure benzodiazepine receptor (BZR) binding with [11C]flumazenil (FMZ) and glucose metabolism with 2-deoxy-2[18F]fluoro-D-glucose (FDG). BACKGROUND:Crossed cerebellar diaschisis (CCD) is defined as decreased metabolism or blood flow in the cerebellum contralateral to a cortical insult measured by functional neuroimaging, and is typically seen in adults with large frontal or parietal lesions. The authors previously reported that CCD of glucose metabolism was not as prominent in children as in adults, and that some children showed a paradoxical pattern of increased glucose utilization in cerebellar cortex contralateral to the cortical lesion. The current study investigated whether CCD is associated with alterations in the gamma-aminobutyric acid (GABA(A))/BZR complex. METHODS:Patients with frontal lesions alone or with parietal lesions were compared with patients with temporal lesions, which are typically not associated with CCD. RESULTS:Children with lesion onset before 1 year of age showed significantly higher glucose utilization in contralateral posterior quadrangular and superior semilunar lobules of cerebellar cortex than did adults. Two patterns of change in cerebellar BZR binding were seen in children: 1) Five of 10 children showed increased BZR binding in the dentate nucleus contralateral to the lesion, and 2) the remaining five children showed no increase in dentate nucleus BZR binding but showed increased binding in the lateral lobules of the cerebellar cortex contralateral to the lesion. Adults showed increased binding only in contralateral dentate nucleus and not in cerebellar cortex. The size and severity of the supratentorial lesion, as well as age at the time of injury, were important factors in these findings. CONCLUSIONS:Reorganization of GABA-mediated mechanisms and glucose metabolism in cerebellum following cortical injury differs with size of lesion and age at the time of injury.

Serotonin content, serotonin uptake sites, and serotonin receptor binding measured in animal studies are all higher in the developing brain, compared with adult values, and decline before puberty. Furthermore, a disruption of synaptic connectivity in sensory cortical regions can result from experimental increase or decrease of brain serotonin before puberty. The purpose of the present study was to determine whether brain serotonin synthesis capacity is higher in children than in adults and whether there are differences in serotonin synthesis capacity between autistic and nonautistic children. Serotonin synthesis capacity was measured in autistic and nonautistic children at different ages, using alpha[11C]methyl-L-tryptophan and positron emission tomography. Global brain values for serotonin synthesis capacity (K complex) were obtained for autistic children (n = 30), their nonautistic siblings (n = 8), and epileptic children without autism (n = 16). K-complex values were plotted according to age and fitted to linear and five-parameter functions, to determine developmental changes and differences in serotonin synthesis between groups. For nonautistic children, serotonin synthesis capacity was more than 200% of adult values until the age of 5 years and then declined toward adult values. Serotonin synthesis capacity values declined at an earlier age in girls than in boys. In autistic children, serotonin synthesis capacity increased gradually between the ages of 2 years and 15 years to values 1.5 times adult normal values and showed no sex difference. Significant differences were detected between the autistic and epileptic groups and between the autistic and sibling groups for the change with age in the serotonin synthesis capacity. These data suggest that humans undergo a period of high brain serotonin synthesis capacity during childhood, and that this developmental process is disrupted in autistic children.

We examined the brain organization for language and auditory functions in five high-functioning autistic and five normal adults, using [15O]-water positron emission tomography (PET). Cerebral blood flow was studied for rest, listening to tones, and listening to, repeating, and generating sentences. The autism group (compared to the control group) showed (a) reversed hemispheric dominance during verbal auditory stimulation; (b) a trend towards reduced activation of auditory cortex during acoustic stimulation; and (c) reduced cerebellar activation during nonverbal auditory perception and possibly expressive language. These results are compatible with findings of cerebellar anomalies and may suggest a tendency towards atypical dominance for language in autism.

PURPOSE/OBJECTIVE:Intermittent photic stimulation (IPS) is an activation procedure used during electroencephalogram (EEG) recording to elicit paroxysmal discharges in individuals with photosensitivity. Specific responses on EEG recording may be provoked by IPS at different frequencies of flickering in normal individuals and in patients with photosensitive epilepsy. METHODS:Changes in regional cerebral blood flow (rCBF) were studied during IPS in two groups of subjects by using [15O]-water positron emission tomography (PET): a control group consisting of eight healthy adults with photic driving response during IPS on EEG recording (mean age, 25 +/- 10.5 years) without history of neurologic or psychiatric abnormalities and a patient group consisting of four adults (mean age, 33 +/- 7.5 years) with history of photosensitive epilepsy. [15O]-water PET scanning with concomitant EEG monitoring was performed during baseline and IPS at 4-, 14-, and 30-Hz frequencies. RESULTS:The control group showed photic driving response at 14-Hz IPS frequency. The patient group showed photoparoxysmal response at 14 and 30 Hz, but not at 4 Hz. Changes in rCBF were determined by means of statistical parametric mapping. Increases in rCBF in occipital cortex (Brodmann's areas 17, 18, and 19) were observed in both groups. In addition, during photic driving responses, the control group showed rCBF increases in the insula and in the thalamus, on the right side. The patient group showed a significant rCBF increase in the hypothalamic region inferior to the left caudate nucleus during photoparoxysmal response. This activation was not found in the control group. Increased rCBF also was observed in the patient group in the head of the left caudate nucleus, in the left hippocampus, and in left insula during IPS without photoparoxysmal response. No activations in these regions were observed during photoparoxysmal response. CONCLUSIONS:These data may indicate involvement of the hypothalamus in photosensitive epilepsy and may suggest a modulatory function of the caudate nucleus, which might be associated with an inhibition of epileptic discharges during IPS in patients with photosensitive epilepsy.