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A study used positron emission tomography (PET) to study patterns of brain activation during auditory processing in five high-functioning adults with autism. Results found that participants showed reversed hemispheric dominance during the verbal auditory stimulation and reduced activation of the auditory cortex and cerebellum. (CR)

Children who have experienced deprivation as a result of orphanage care during early development are at increased risk for a number of cognitive, emotional, and social difficulties (MacLean, 2003). This study examined the neuropsychological and behavioral profile of internationally adopted children with language difficulties, one of the most common cognitive challenges (Behen et al., 2008). In addition to neuropsychological testing, fMRI was utilized to examine activation patterns during expressive fluency and receptive language tasks. In comparison to internationally adopted children without language difficulties and nonadopted controls, participants with language difficulty had worse performance on tasks of verbal memory and reasoning, academic skills, and working memory. Behaviorally, all internationally adopted participants, regardless of language ability, had more parent-reported hyperactivity and impulsivity compared with controls. The fMRI tasks revealed reduced activation in traditional language areas in participants with language difficulty. The impact of early adverse experience on later development is discussed. [ABSTRACT FROM PUBLISHER]

The "crowding" effect (CE), wherein verbal functions are preserved presumably at the expense of nonverbal functions, which diminish following inter-hemispheric transfer of language functions, is recognized as a specific aspect of functional reorganization, offering an insight about neural plasticity in children with neural insult to the dominant hemisphere. CE is hypothesized as a marker for language preservation or improvement after left-hemispheric injury, yet it remains challenging to fully discern it in preoperative evaluation. We present a novel DWI connectome (DWIC) approach to predict the presence of CE in 24 drug-resistant epilepsy (DRE) patients with a left-hemispheric focus and 29 young healthy controls. Psychometry-driven DWIC analysis was applied to create verbal and non-verbal modular networks. Local efficiency (LE) was assessed at individual regions of the two networks and its Z-score was compared to predict the presence of CE. Compared with a traditional organization (TO) group, wherein verbal functions are adversely affected, while non-verbal functions are preserved, the CE group showed significantly higher Z-scores in verbal network and significantly lower Z-scores in non-verbal network, corresponding to network reorganization in CE. A larger number of antiseizure drugs was significantly associated with more decreased Z-score in the right non-verbal network of the CE group and left verbal network of the TO group. These findings hold great potential to identify DRE patients whose verbal/language skills may over time be preserved due to effective inter-hemispheric reorganization and identify those whose verbal/language impairments may persist due to lack of inter-hemispheric reorganization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study investigated whether current state-of-the-art deep reasoning network analysis on psychometry-driven diffusion tractography connectome can accurately predict expressive and receptive language scores in a cohort of young children with persistent language concerns (n = 31, age: 4.25 ± 2.38 years). A dilated convolutional neural network combined with a relational network (dilated CNN + RN) was trained to reason the nonlinear relationship between "dilated CNN features of language network" and "clinically acquired language score". Three-fold cross-validation was then used to compare the Pearson correlation and mean absolute error (MAE) between dilated CNN + RN-predicted and actual language scores. The dilated CNN + RN outperformed other methods providing the most significant correlation between predicted and actual scores (i.e., Pearson's R/p-value: 1.00/<.001 and .99/<.001 for expressive and receptive language scores, respectively) and yielding MAE: 0.28 and 0.28 for the same scores. The strength of the relationship suggests elevated probability in the prediction of both expressive and receptive language scores (i.e., 1.00 and 1.00, respectively). Specifically, sparse connectivity not only within the right precentral gyrus but also involving the right caudate had the strongest relationship between deficit in both the expressive and receptive language domains. Subsequent subgroup analyses inferred that the effectiveness of the dilated CNN + RN-based prediction of language score(s) was independent of time interval (between MRI and language assessment) and age of MRI, suggesting that the dilated CNN + RN using psychometry-driven diffusion tractography connectome may be useful for prediction of the presence of language disorder, and possibly provide a better understanding of the neurological mechanisms of language deficits in young children., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background and Purpose: Pure speech delay is a common developmental disorder which, according to some estimates, affects 5%-8% of the population. Speech delay may not only be an isolated condition but also can be part of a broader condition such as global developmental delay. The present study investigated whether diffusion tensor imaging tractography-based connectome can differentiate global developmental delay from speech delay in young children., Materials and Methods: Twelve children with pure speech delay (39.1 ± 20.9 months of age, 9 boys), 14 children with global developmental delay (39.3 ± 18.2 months of age, 12 boys), and 10 children with typical development (38.5 ± 20.5 months of age, 7 boys) underwent 3T DTI. For each subject, whole-brain connectome analysis was performed by using 116 cortical ROIs. The following network metrics were measured at individual regions: strength (number of the shortest paths), efficiency (measures of global and local integration), cluster coefficient (a measure of local aggregation), and betweeness (a measure of centrality)., Results: Compared with typical development, global and local efficiency were significantly reduced in both global developmental delay and speech delay (P < .0001). The nodal strength of the cognitive network is reduced in global developmental delay, whereas the nodal strength of the language network is reduced in speech delay. This finding resulted in a high accuracy of >83% ± 4% to discriminate global developmental delay from speech delay., Conclusions: The network abnormalities identified in the present study may underlie the neurocognitive and behavioral consequences commonly identified in children with global developmental delay and speech delay. Further validation studies in larger samples are required., (© 2016 by American Journal of Neuroradiology.)

Objectives: To determine safety and efficacy of the 5HT1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD)., Study Design: Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy., Results: There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P = .400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P = .006); the 2.5-mg buspirone group showed significant improvement (P = .003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P = .018) or if they showed normal levels of blood serotonin (P = .044). Adverse events did not differ significantly among treatment groups., Conclusions: Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions., Trial Registration: ClinicalTrials.gov: NCT00873509., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The objective of this study is to determine the long-term outcome of children with intractable epilepsy who have diffuse cortical hypometabolism on 2-deoxy-2-((18)F)fluoro-D-glucose positron emission tomography (FDG-PET) scans. Seventeen children with intractable epilepsy showing bilateral, diffuse cortical hypometabolism on FDG-PET were followed up through telephone interview from 1 year 4 months to 11 years 4 months (mean: 5 years 7 months ± 2 years 1 month) after their PET scans. One child succumbed to Sanfilippo disease at age 20 years. Only 2 children were seizure free. Fifty percent had walking difficulties, 56.25% were not toilet trained, all had speech difficulties, 43.75% had behavioral problems, 37.5% had poor eye contact, 75% had socialization difficulties, and 87.5% attended special schools. Three children were found to have genetic causes, including a 4-MB deletion of the mitochondrial genome, MECP2 duplication, and Lafora disease. In conclusion, the long-term outcome in this patient population is poor, and they tend to suffer from genetic/neurodegenerative diseases.

Objective: To investigate whether abnormal regional white matter architecture in the perisylvian region could be used as an easy and sensitive quantitative method to demonstrate language pathway abnormalities in children with developmental delay (DD)., Study Design: We performed diffusion tensor imaging in 15 DD subjects (age, 61.1 ± 20.9 months) and 15 age-matched typically developing (TD) children (age, 68.4 ± 19.2 months). With diffusion tensor imaging color-coded orientation maps, we quantified the fraction of fibers in the perisylvian region that are oriented in anteroposterior (AP) and mediolateral (ML) directions, and their ratio (AP/ML) was calculated., Results: The AP/ML ratio was more sensitive than tractography in characterizing perisylvian regional abnormalities in DD children. The AP/ML ratio of the left perisylvian region was significantly lower in DD children compared with TD children (P = .03). The ML component of bilateral perisylvian regions was significantly higher in DD children compared with TD children (P = .01 [left] and P = .004 [right]). No significant difference was found in the AP component in the two groups. A significant negative correlation of the left ML component with Vineland communication skills was observed (r = -0.657, P = .011)., Conclusions: The AP/ML ratio appears to be a sensitive indicator of regional white matter architectural abnormalities in the perisylvian region of DD children., (Copyright © 2012 Mosby, Inc. All rights reserved.)

The authors evaluated postsurgical reorganization of the arcuate fasciculus longitudinally using diffusion tensor imaging in 10 children with intractable epilepsy, whose resections included the left arcuate fasciculus. Evaluation of fractional anisotropy before and after surgery (mean follow-up: 7.5 months) showed a significant increase (P = .002) in the right arcuate fasciculus during follow-up. There was marked enlargement of the right arcuate fasciculus postsurgically in 8 patients. The change in right arcuate fasciculus fractional anisotropy values showed a positive correlation with interval between resection and postsurgical magnetic resonance imaging (MRI) (P = .044). Comparison of 10 age-matched controls to patients pre- and postsurgery showed significantly reduced presurgery fractional anisotropy in the left (P = .018) and right (P = .036) arcuate fasciculus and no difference in postsurgery fractional anisotropy in the right arcuate fasciculus (P = .399) in patients. These findings suggest a compensatory reorganization in the right arcuate fasciculus in children with intractable epilepsy following left arcuate fasciculus resection.

Purpose: To determine the relationship between calcified cortex and perfusion status of white matter and seizure severity in patients with Sturge-Weber Syndrome (SWS), a sporadic neurocutaneous disorder characterized by a leptomeningeal angioma, progressive brain ischemia, and a high incidence of seizures using susceptibility weighted imaging (SWI) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI)., Materials and Methods: Fifteen children (ages: 0.9-10 years) with unilateral SWS prospectively underwent magnetic resonance imaging (MRI). The degree of cortical calcification was assessed using SWI while perfusion status was quantified using DSC-PWI images (asymmetries of various perfusion parameters). Comparisons between calcification, perfusion status, and seizure variables were performed., Results: Patients with severely calcified cortex demonstrated significantly lower perfusion in the ipsilateral white matter (mean asymmetry: -0.52 ± 0.22) as compared to patients with only mildly calcified cortex or no calcification (mean asymmetry: 0.08 ± 0.25). Patients with severely calcified cortex also suffered from a higher seizure burden (a composite measure of seizure frequency and epilepsy duration; P = 0.01) and a trend for earlier seizure onset and longer epilepsy duration., Conclusion: Severe calcification in the affected hemisphere is related to severely decreased perfusion in underlying white matter and is associated with more severe epilepsy in SWS patients., (Copyright © 2011 Wiley-Liss, Inc.)

Background and Purpose: Low brain tissue perfusion due to abnormal venous drainage is thought to be a central mechanism of brain damage in SWS. Here, HR-PWI was used to quantify WM perfusion abnormalities and to correlate these with brain atrophy and clinical variables., Materials and Methods: Fourteen children (age range, 0.8-10.0 years) with unilateral SWS underwent MR imaging examinations, including HR-PWI. rCBV, rCBF, and MTT in the affected WM and in contralateral homotopic WM were measured. AI for each perfusion parameter was correlated with age, brain atrophy, and motor and seizure variables as well as IQ., Results: Increased perfusion was seen in the affected hemisphere in 5 children and decreased perfusion in 9 children. Brain atrophy was more severe in the low-perfusion group (P = .01) and was related to both CBF-AI and CBV-AI (r = -0.69, P = .007; r = -0.64, P = .014, respectively). Older children had lower CBV values on the affected side (r = -0.62, P = .02). Longer duration of epilepsy was related to lower CBF (more negative CBF-AI, r = -0.58, P = .03) and low CBV (r = -0.55, P = .04) on the affected side. Lower perfusion was associated with more frequent seizures (rCBF-AI: r = -0.56, P = .04; rCBV-AI: r = -0.63, P = .02)., Conclusions: Increased perfusion in the affected cerebral WM may indicate an early stage of SWS without severe brain atrophy. Decreased perfusion is associated with frequent seizures, long duration of epilepsy, and brain atrophy.

Background and Purpose: Thalamocortical connections play a crucial role in complex cognitive functioning, and several neuropsychiatric disorders may involve aberrant thalamocortical circuitry. Here, we quantified the cortical pattern and age-related changes of thalamocortical connections by using probabilistic tractography in children and adolescents. We hypothesized that detectable asymmetry (left>right) exists in thalamocortical fiber connections and the connectivity increases with age during maturation., Materials and Methods: Diffusion tensor imaging was acquired in 15 normally developing children (age range, 8.3-17.3 years; 11 males), and fiber tracking was initiated from the thalami. The cortical distribution of ipsilateral thalamocortical fibers was quantified by using a landmark-constrained conformal mapping technique. Furthermore, hemispheric asymmetries and potential age-related changes in regional thalamocortical connections were assessed., Results: The left thalamus had significantly higher overall cortical connectivity than the right thalamus (P < .001). Left prefrontal cortical areas showed significantly higher thalamic connectivity compared with homotopic regions of the right hemisphere (P < .001), regardless of the applied parameters. There was an increase of overall thalamocortical connectivity with age, with the most pronounced age-related increases in bilateral prefrontal areas (P < .002). However, thalamic connectivity of some other cortical regions (right sensorimotor, left inferior temporal) showed a decrease with age., Conclusions: Our results indicate a region-specific left>right asymmetry and robust developmental changes in thalamocortical (particularly thalamo-prefrontal) connectivity during late childhood and adolescence. These data further add to our knowledge about structural lateralizations and their development in the maturing brain.

Children with autistic spectrum disorder are known to have histopathological abnormalities in the cerebellum. Diffusion tensor imaging has been utilized to study abnormalities in connectivity and microintegrity in brains of such children. A region of interest approach was adopted to study cerebellar outflow and inflow pathways in 27 children (24 males; mean age, 5.0 years) with autism, and comparison was made with 16 normally developing controls. An increase in the mean diffusivity of bilateral superior cerebellar peduncles in those with autistic spectrum disorder was noted, as was a reversal of the asymmetry pattern in fractional anisotropy of the middle cerebellar peduncle and the inferior cerebellar peduncle in the autistic spectrum disorder group, compared with controls. This study reiterates the underconnectivity between the cerebellum and neocortex, using diffusion tensor imaging.

Background: Sturge-Weber syndrome (SWS) with unilateral hemispheric involvement is a clinical model of early onset, chronic, often progressive hemispheric injury, resulting in variable neuro-cognitive impairment., Aims: To evaluate if abnormal diffusion and metabolism of the thalamus, a central relay station with extensive cortical connections, may serve as a simple imaging marker of neuro-cognitive dysfunction in SWS., Methods: We obtained both diffusion tensor imaging and FDG PET in 20 children (11 girls; age range: 3-12.4 years) with unilateral SWS. Diffusion parameters as well as FDG uptake were measured in thalami, compared to normal control values, and correlated with the extent of cortical hypometabolism, deep venous abnormalities and cognitive (IQ) as well as fine motor functions., Results: Children with SWS had significantly higher thalamic glucose metabolic asymmetry than controls (p=0.001). Thalamic metabolic asymmetries correlated positively with the asymmetry of thalamic diffusivity (p=0.001) and also with the extent of cortical hypometabolism (p<0.001). Severe thalamic asymmetries of glucose metabolism and diffusion were strong predictors of low IQ (metabolism: p=0.002; diffusivity: p=0.01), even after controlling for age and extent of cortical glucose hypometabolism in children with left hemispheric involvement. Ipsilateral thalamic glucose hypometabolism was also associated with impairment of fine motor functions (p=0.002)., Conclusions: Both diffusion and glucose metabolic abnormalities of the thalamus are closely related to cognitive functions, independent of age and cortical metabolic abnormalities, in children with unilateral SWS. Thalamic metabolic asymmetry is a robust but simple imaging marker of neuro-cognitive outcome in children with early unilateral hemispheric injury caused by Sturge-Weber syndrome., (Copyright (c) 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

We applied diffusion-tensor MRI (DT-MRI) to investigate directly the water diffusivity within subcortical gray matter structures comprising the fronto-striato-thalamic (FST) circuit, which is implicated in the pathophysiology of Tourette syndrome (TS). We investigated the structural integrity of basal ganglia and thalamus in 23 children with TS and 35 age-matched healthy controls (NC), and examined the association of DT-MRI measures to tic severity and comorbid symptoms. We measured parallel (lambda(1)) and perpendicular (lambda(23)) diffusivity, mean diffusivity (MD), and fractional anisotropy (FA) in both hemispheres. Compared with NC, the TS group showed a significant increase in lambda(1) (P = 0.003) and MD (P = 0.027) in the bilateral putamen, an increase in lambda(23) in right thalamus (P = 0.008), and a reversed asymmetry of FA (P = 0.03) in the thalamus. There was a significant positive correlation between lambda(23) in right thalamus and tic severity. TS patients showed significantly lower left caudate volume (P = 0.011) and bilateral thalamic volumes (left, P = 0.035, right P = 0.006) compared with NC. These findings support the notion that microstructural dysfunction measured by DT-MRI in component regions of the FST circuit contribute to the pathophysiology in TS., ((c) 2008 Movement Disorder Society.)

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., ((c) 2007 Movement Disorder Society.)

Background and Purpose: Impaired cortical venous outflow and abnormal deep venous collaterals are common in Sturge-Weber syndrome (SWS), but their relation to brain metabolism and function is poorly understood. In this study, advanced MR imaging techniques, such as susceptibility-weighted imaging (SWI) and diffusion tensor imaging (DTI), were applied in conjunction with positron-emission tomography (PET), to assess cortical and white matter structural abnormalities and their relation to cortical glucose metabolism and cognitive functions in children with unilateral SWS., Materials and Methods: Thirteen children (age, 1.5-10.3 years) with unilateral SWS underwent MR imaging with SWI and DTI, glucose metabolism PET, and comprehensive neuropsychologic assessment prospectively. The MR imaging and PET images were coregistered and cortical regions showing decreased glucose metabolism were compared with locations of SWI signal intensity abnormalities, changes in white matter water diffusion, and cognitive functions., Results: SWI detected both cortical abnormalities (n=8) and deep transmedullary veins (n=9), including those in young children with no cortical SWI signal intensity changes. These veins were often located under cortex adjacent to hypometabolic regions. DTI showed abnormal water diffusion both under hypometabolic cortex and in adjacent white matter with collateral veins. Cognitive dysfunction was associated with abnormal water diffusion in the posterior white matter., Conclusions: Transmedullary venous collaterals can be detected early by SWI and persist in white matter adjacent to damaged cortex in children with SWS. Microstructural white matter damage extends beyond cortical abnormalities and may contribute to cognitive impairment. SWI and DTI can be incorporated into clinical MR imaging acquisitions to objectively assess microstructural abnormalities at different stages of SWS.

Early global deprivation of institutionalized children may result in persistent specific cognitive and behavioral deficits. In order to examine brain dysfunction underlying these deficits, we have applied positron emission tomography using 2-deoxy-2-[(18)F]fluoro-D-glucose in 10 children (6 males, 4 females, mean age 8.8 years) adopted from Romanian orphanages. Using statistical parametric mapping (SPM), the pattern of brain glucose metabolism in the orphans was compared to the patterns obtained from two control groups: (i) a group of 17 normal adults (9 males, 8 females, mean age 27.6 years) and (ii) a group of 7 children (5 males and 2 females, mean age 10.7 years) with medically refractory focal epilepsy, but normal glucose metabolism pattern in the contralateral hemisphere. Consistent with previous studies of children adopted from Romanian orphanages, neuropsychological assessment of Romanian orphans in the present study showed mild neurocognitive impairment, impulsivity, and attention and social deficits. Comparing the normalized glucose metabolic rates to those of normal adults, the Romanian orphans showed significantly decreased metabolism bilaterally in the orbital frontal gyrus, the infralimbic prefrontal cortex, the medial temporal structures (amygdala and head of hippocampus), the lateral temporal cortex, and the brain stem. These findings were confirmed using a region-of-interest approach. SPM analysis showed significantly decreased glucose metabolism in the same brain regions comparing the orphans to the nonepileptic hemisphere of the childhood epilepsy controls. Dysfunction of these brain regions may result from the stress of early global deprivation and may be involved in the long-term cognitive and behavioral deficits displayed by some Romanian orphans., (Copyright 2001 Academic Press.)

Purpose: To identify brain regions with abnormal function in children with intractable partial epilepsy and aggressive behavior by using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)., Methods: Six children (mean age, 9.9 years) with intractable partial epilepsy and aggressive behavior underwent detailed psychodevelopmental assessment and FDG-PET scanning. The objective technique of statistical parametric mapping (SPM) was applied to define focal abnormalities of glucose metabolism, and compared those with those of a group of normal adult subjects (n = 17) as well as age-matched children with epilepsy with similar seizure characteristics but without aggression (n = 7). The findings were analyzed further by using a region-of-interest (ROI) approach., Results: The aggressive children all showed developmental delay, and four of them also manifested autistic symptoms. SPM analysis demonstrated extensive glucose hypometabolism in the aggressive group bilaterally in the temporal and prefrontal cortex compared with that in normal adult controls. A focal area of medial prefrontal glucose hypometabolism was defined in the aggressive children as compared with the nonaggressive pediatric group with SPM, whereas ROI comparison of these groups confirmed prefrontal hypometabolism and also showed glucose hypometabolism of the temporal neocortex in the aggressive children. Severity of aggression correlated inversely with glucose metabolism of the left temporal as well as bilateral medial prefrontal cortex., Conclusions: Bilateral prefrontal and temporal neocortical brain glucose hypometabolism in children with epilepsy and aggressive behavior may indicate a widespread dysfunction of cortical regions, which normally exert an inhibitory effect on subcortical aggressive impulses. PET studies may be used to elucidate the neurobiologic basis of aggressive behavior in children.

We investigated the vasoactive intestinal peptide receptor type 2 (VIPR2) gene as a candidate gene for autism. We searched for mutations in the VIPR2 gene in autistic individuals, and 10 novel polymorphisms were identified. Three polymorphisms in the upstream region were studied in detail, and there was no significant difference in the frequencies between the autistic group (n = 14) and unrelated controls (n = 52). The distribution of the genotypes in two of the three polymorphisms differed somewhat between autistic subjects with gastrointestinal problems and those without. Moreover, there was a trend showing a correlation between the genotypes for the third polymorphism and the severity of stereotypical behavior as ranked by the Gilliam Autism Rating Scale. These preliminary results suggest that VIPR2 may have a role in gastrointestinal symptoms and stereotypical behaviors in autism, although a larger collection of samples suitable for transmission disequilibrium tests is necessary to validate the results.

1. There is evidence for pronounced brain plasticity during postnatal maturation. The authors hypothesized that left-hemisphere lesion would be associated with greater than normal language participation of the right hemisphere and that atypical asymmetry of perisylvian language activations would be enhanced after lesion occurring in early childhood as compared to lesion occurring later in life. 2. Eleven patients with left-hemisphere lesion (aged 8-33 yrs.) and 9 normal adult comparison subjects were studied, using [15O]-water positron emission tomography. One patient group (N = 6) had early lesion onset (< or = 6 years of age), a second group (N = 5) had lesion onset later in life (> or = 10 years of age). Regional cerebral blood flow (rCBF) changes during listening to sentences (minus rest) and sentence generation (minus repetition) were compared between groups in predefined regions of interest. 3. Variance of regional activations within early and late lesion onset groups was considerable and qualitative inspection revealed only few robust group differences. However, when 4 patient pairs were approximately matched for chronological age, lesion site and VIQ, significantly reduced leftward asymmetry of activations in early lesion patients was found in the prefrontal, inferior frontal, and inferior parietal regions for expressive language, with concordant and marginally significant trends in the inferior frontal and superior temporal regions for receptive language. 4. The results suggest enhanced postlesional plasticity in childhood, while also reflecting strong individual variability probably due to clinical and demographic factors beside lesion onset.

Functional neuroimaging studies have shown enhanced right-hemisphere language activations in adults with left-hemisphere damage. We hypothesized that this effect would be stronger in patients with lesion occurring early in development. Using [15O]-water PET, we studied eight normal adults and 23 patients with unilateral left lesion during rest, listening to sentences, and sentence repetition. Thirteen patients had lesions with early onset (< 5 years) and ten had lesions with late onset (> 20 years). For listening to sentences, frontotemporal blood flow increases were significantly stronger in the left than in the right hemisphere in normal adults. This normal asymmetry was reduced in patients with late lesion and reversed in those with early lesion. For sentence repetition, analogous group differences were significant for the basal ganglia, but failed to reach significance for the (pre)motor and insular regions. We conclude that left lesion leads to alterations in the asymmetry of language activations (in and beyond the perisylvian areas). In addition, rightward shifts of language activation tend to be stronger as a consequence of early (as compared to late) lesion. Finally, postlesional reorganization appears to reflect a coexistence of 'additive' and 'subtractive' effects, i.e., activation in some regions that are not normally involved in language processing and lack of activation in other (undamaged) regions that are normally activated by language tasks.

Functional neuroimaging data regarding the development of motor organization in normal children and adolescents are virtually unavailable because of ethical concerns. As an alternative approach, we studied child and adult lesion patients, focusing on movement of the hand ipsilateral to the lesion and on brain activations in the contralesional hemisphere. [15O]-water positron emission tomography was performed during rest and sequential finger-thumb tapping in 10 children (aged 6 to 14 years) and 15 adults (aged 18 to 74 years) with unilateral lesion. We expected more distinct activation/deactivation patterns during movement in adults than in children. While there were no group differences in activation of primary and secondary motor cortices, deactivations in nonmotor cortex were significantly more pronounced in adults than in children. This indirectly supports our hypothesis of developmental focalization of cerebral motor control. Activations in the cerebellum and vermis were significantly stronger in the adults than in the children, possibly reflecting normal developmental patterns.

Positron emission tomography (PET) studies have shown normal or elevated levels of glucose metabolism in neuronal heterotopia, raising the issue of potential participation of heterotopic neurons in cognitive processing. We studied three patients with heterotopic malformations, using [(15)O]water PET and experimental conditions selected according to the location of the malformations. Task performance was associated with blood flow increases of > 17% within the heterotopia in each patient. In two, these occurred in left frontal heterotopia during sentence generation. In the third patient, activations for facial and visuospatial discrimination and picture naming were found in a right posterior heterotopion. Our findings may reflect participation of heterotopia in cognitive function and suggest that heterotopic neurons synapse with neurons in other brain regions.

Objective: There is extensive evidence for post-lesional plasticity in the language and motor domains. We examined possible domain-specific differences in reorganizational patterns, hypothesizing that interhemispheric reorganization would be predominantly homotopic for language, but predominantly nonhomotopic for motor control., Design: Using oxygen 15-water positron emission tomography, regional cerebral blood flow was studied during rest, listening to sentences, repetition of sentences, and finger tapping of the right hand. Task-specific primary, secondary, and tertiary regions of interest were defined according to the degree of regional involvement in language/motor functions as documented in previous studies. Regional activations were compared within and across functional domains., Patients: Nine patients (aged 4-20 years) with unilateral left hemisphere lesion involving both the primary motor and perisylvian language cortices were studied. Two samples of healthy adults were included for additional comparisons., Main Outcome Measure: Hemispheric asymmetry of blood flow changes within regions of interest., Results: As predicted, rightward asymmetry of activations in primary and secondary regions was stronger for language than for movement, but the expected inverse difference for tertiary regions (greater rightward asymmetry of motor activations) was not found. Within-domain comparisons showed that for listening to sentences, rightward asymmetry was strongest in primary and weakest in tertiary regions, whereas the inverse differences were found for movement., Conclusion: The findings suggest a greater potential for homotopic interhemispheric reorganization in the language than in the motor domain. Interhemispheric motor reorganization was generally limited.

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)., (Copyright 1998 Academic Press.)

Most language mapping studies have focussed on activations for single-word tasks. We examined activations for verbal auditory and generation tasks using sentence stimuli. [15O]-water PET was performed in 4 female and 5 male normal adults. Listening to sentences (minus rest) activated the superior and middle temporal gyri bilaterally, but mean activation was significantly stronger on the left. The strongest activation for sentence generation (minus repetition) was seen in the left middle and inferior frontal gyri (area 46). This focus appears to be anterior to activations reported for single-word generation, possibly due to greater verbal working memory demands of the sentential task. Additional activation of the left inferior temporal lobe can be attributed to lexicosemantic processing.

We explored the effects of maturational plasticity on motor activations for the affected hand in patients with unilateral lesion involving the rolandic cortex. Ten patients with early lesion (onset < 4 years), seven patients with late lesion (onset > or = 10 years) and eight normal adults underwent [15O]-water positron emission tomography (PET). Rolandic activations in the contralesional hemisphere were enhanced in both patient groups when compared to normal adults. Secondary motor and frontoparietal nonmotor cortices were more activated in the early than in the late lesion group, suggesting a greater potential for reorganization during early development than later in life. Cerebellar activations were similar in late lesion patients and normal adults, but significantly weaker in early lesion patients.