Intracranial recording and source localization of auditory brain responses elicited at the 50 ms latency in three children aged from 3 to 16 years.

Maturational studies of the auditory-evoked brain response at the 50 ms latency provide an insight into why this response is aberrant in a number of psychiatric disorders that have developmental origin. Here, using intracranial recordings we found that neuronal activity of the primary contributors to this response can be localised at the lateral part of Heschl's gyrus already at the age of 3.5 years. This study provides results to support the notion that deviations in cognitive function(s) attributed to the auditory P50 in adults might involve abnormalities in neuronal activity of the frontal lobe or in the interaction between the frontal and temporal lobes. Validation and localisation of progenitors of the adults' P50 in young children is a much-needed step in the understanding of the biological significance of different subcomponents that comprise the auditory P50 in the adult brain. In combination with other approaches investigating neuronal mechanisms of auditory P50, the present results contribute to the greater understanding of what and why neuronal activity underlying this response is aberrant in a number of brain dysfunctions. Moreover, the present source localisation results of auditory response at the 50 ms latency might be useful in paediatric neurosurgery practice.

Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism.

The role of serotonin in prenatal and postnatal brain development is well documented in the animal literature. In earlier studies using positron emission tomography (PET) with the tracer alpha[(11)C]methyl-l-tryptophan (AMT), we reported global and focal abnormalities of serotonin synthesis in children with autism. In the present study, we measured brain serotonin synthesis in a large group of autistic children (n = 117) with AMT PET and related these neuroimaging data to handedness and language function. Cortical AMT uptake abnormalities were objectively derived from small homotopic cortical regions using a predefined cutoff asymmetry threshold (>2 S.D. of normal asymmetry). Autistic children demonstrated several patterns of abnormal cortical involvement, including right cortical, left cortical, and absence of abnormal asymmetry. Global brain values for serotonin synthesis capacity (unidirectional uptake rate constant, K-complex) values were plotted as a function of age. K-complex values of autistic children with asymmetry or no asymmetry in cortical AMT uptake followed different developmental patterns, compared to that of a control group of non-autistic children. The autism groups, defined by presence or absence and side of cortical asymmetry, differed on a measure of language as well as handedness. Autistic children with left cortical AMT decreases showed a higher prevalence of severe language impairment, whereas those with right cortical decreases showed a higher prevalence of left and mixed handedness. Global as well as focal abnormally asymmetric development in the serotonergic system could lead to miswiring of the neural circuits specifying hemispheric specialization.

Abnormal brain tryptophan metabolism and clinical correlates in Tourette syndrome.

Symptoms in Tourette syndrome (TS) are likely related to abnormalities involving multiple neurotransmitter systems in striatal-thalamo-cortical circuitry. Although prior studies have found abnormal levels of tryptophan, serotonin, and their metabolites in blood, cerebrospinal fluid and brain tissue of TS patients, understanding of focal brain disturbances and their relationship to clinical phenotype remains poor. We used alpha-[(11)C]methyl-L-tryptophan (AMT) positron emission tomography (PET) to assess global and focal brain abnormalities of tryptophan metabolism and their relationship to behavioral phenotype in 26 children with TS and nine controls. Group comparisons on regional cortical and subcortical AMT uptake revealed decreased AMT uptake in bilateral dorsolateral prefrontal cortical and bilaterally increased uptake in the thalamus (P = 0.001) in TS children. The ratio of AMT uptake in subcortical structures to dorsolateral prefrontal cortex was significantly increased bilaterally (P < 0.01) in TS patients also. Behaviorally defined subgroups within the TS sample revealed differences in the pattern of AMT uptake in the fronto-striatal-thalamic circuit. This study demonstrates cortical and subcortical abnormalities of tryptophan metabolism in TS and provides neuroimaging evidence for a role of serotonergic mechanisms in the pathophysiology of TS.