Faculty Bibliography

Neuropsychological studies suggest that good long-term language outcome is possible following extensive early left-hemisphere damage. We explored the brain organization for language in children with early unilateral lesion, using [15O]-water PET. In 12 patients with left lesion (LL) and 9 patients with right lesion (RL), cerebral blood flow changes during listening to sentences and repetition were studied. A rightward shift of language activations in the LL group was found in perisylvian areas and multiple other, mostly temporo-parietal, regions. The hypothesis of intrahemispheric reorganization in the LL group found only limited support. The number of activated regions was overall greater in the RL group. Unexpected findings included a stronger subcortical and cerebellar language involvement in the RL group. We suggest that (a) early left lesion is associated with enhanced language participation of the right hemisphere in and beyond the classical language areas, and (b) postlesional effects are in part additive (recruitment of noncanonical areas), in part subtractive (functional depression in areas normally involved in language).

In order to study differences in response to neocortical injury sustained at different ages at the neurotransmitter level, we examined the density in D2 dopamine receptors in the neostriatum of cats hemidecorticated neonatally (N = 4) or in adulthood (N = 4), as well as in intact brains (N = 6). Receptor densities were measured using quantitative autoradiography and [3H]-spiperone binding in 12 regions of the neostriatum and nucleus accumbens septi. We found that the anterior lateral caudate nucleus on both sides of the brain contained a higher D2 receptor density in neonatal-lesioned as compared to adult-lesioned brains. Ipsilateral to the lesion, the increase was 101% (P < 0.05) and contralaterally it amounted to 77% (P < 0.05). Moreover, this region of the ipsilateral caudate nucleus of neonatal-lesioned cats tended to be more densely labeled than that of intact brain by 58% (P < 0.1). D2 receptor densities in adult-lesioned cats did not differ from that of intact controls. Comparison of these data with those of a former morphological study using the same animals suggested that this bilateral elevation of D2 receptor density in neonatally lesioned brains represents a higher mean density of binding sites per neuron. The elevation in the neonatal-lesioned cats might be a response of the striatum to neuroplastic changes in the striatal neuropil, including the corticostriatal afferents, since such changes are different in neonatal- as compared to adult-lesioned cats.

Recent evidence suggests disturbances of serotonin synthesis affecting the dentato-thalamo-cortical pathway in autistic boys. We studied possible effects of such disturbances on brain activations for language in autistic adults. Four autistic and five normal men were studied while listening to, repeating, and generating sentences, using [15(O)]-water positron emission tomography (PET). Activation in the right dentate nucleus and in the left frontal area 46 was reduced during verbal auditory and expressive language and enhanced during motor speech functions in the autism as compared to the control group. The thalamus showed group differences concordant with area 46 for expressive language. The results may indicate atypical functional specialization of the dentato-thalamo-cortical pathway and are compatible with a model of region-specific biochemical disturbances in the developing autistic brain.

Studies with positron emission tomography indicate that the human brain undergoes a period of postnatal maturation that is much more protracted than previously suspected. In the newborn, the highest degree of glucose metabolism (representative of functional activity) is in primary sensory and motor cortex, cingulate cortex, thalamus, brain stem, cerebellar vermis, and hippocampal region. At 2 to 3 months of age, glucose utilization increases in the parietal, temporal, and primary visual cortex; basal ganglia; and cerebellar hemispheres. Between 6 and 12 months, glucose utilization increases in frontal cortex. These metabolic changes correspond to the emergence of various behaviors during the first year of life. The measurement of absolute rates of glucose utilization during development indicates that the cerebral cortex undergoes a dynamic course of metabolic maturation that persists until ages 16-18 years. Initially, there is a rise in the rates of glucose utilization from birth until about age 4 years, at which time the child's cerebral cortex uses over twice as much glucose as that of adults. From age 4 to 10 years, these very high rates of glucose consumption are maintained, and only after then is there a gradual decline of glucose metabolic rates to reach adult values by age 16-18 years. Correlations between glucose utilization rates and synaptogenesis are discussed, and the argument is made that these findings have important implications with respect to human brain plasticity following injury as well as to "critical periods" of maximal learning capacity.

Local cerebral serotonin synthesis capacity was measured with alpha-[C-11]methyl-L-tryptophan ([C-11]AMT) in normal adult human brain (n = 10; five males, five females; age range, 18-38 years, mean 28.3 years) by using positron emission tomography (PET). [C-11]AMT is an analog of tryptophan, the precursor for serotonin synthesis, and is converted to alpha-[C-11]methyl-serotonin ([C-11]AM-5HT), which is trapped in serotonergic neurons because [C-11]AM-5HT is not degraded by monoamine oxidase. Kinetic analysis of [C-11] activity in brain after injection of [C-11]AMT confirmed the presence of a compartment with unidirectional uptake that represented approximately 40% of the activity in the brain at 50 min after tracer administration. The undirectional rate constant K, which represents the uptake of [C-11]AMT from the plasma to brain tissue followed by the synthesis and physiologic trapping of [C-11]AM-5HT, was calculated using the Patlak graphic approach on a pixel-by-pixel basis, thus creating parametric images. The rank order of K values for different brain regions corresponded well to the regional concentrations of serotonin in human brain (P < .0001). High serotonin synthesis capacity values were measured in putamen, caudate, thalamus, and hippocampus. Among cortical regions, the highest values were measured in the rectal gyrus of the inferior frontal lobe, followed by transverse temporal gyrus; anterior and posterior cingulate gyrus; middle, superior, and inferior temporal gyri; parietal cortex; occipital cortex, in descending order. Values in women were 10-20% higher (P < .05, MANOVA) throughout the brain than those measured in men. Differences in the serotonin synthesis capacity between men and women measured in this study may reflect gender differences of importance to both normal and pathologic behavior. This study demonstrates the suitability of [C-11]AMT as a tracer for PET scanning of serotonin synthesis capacity in human brain and provides normal adult values for future comparison with patient groups.

The capacity of the developing brain for compensatory reorganization after early hemispherectomy has been previously shown in neurobehavioral studies, above all with regard to language recovery. The present study examines the organization of motor and language areas by means of [(15)O]-water positron emission tomography (PET) in a 6-year-old boy who underwent right functional hemispherectomy at age 3 years. The results suggest that compensatory allocation for movement of the weak hand primarily involves the premotor, inferior frontal, and insular cortices, and the supplementary motor area in the retained hemisphere, as well as the bilateral cerebellum. Receptive language and prosodic functions primarily activated the left perisylvian cortices. However, language and motor activations were also seen in cortical and subcortical remains on the hemispherectomized side suggesting incomplete disconnection by functional hemispherectomy.