Mild Trigonocephaly - Autism - Ken

Our subjects consisted of 14 autistic individuals and 14 controls ranging in age from 3 to 37 years. A (99m)Tc HMPAO single photon emission computed tomogram (SPECT) was used to examine blood flow variations between autistic subjects, compared to an age- and gender-matched control group. We found significant hypoperfusion in the prefrontal areas of autistic individuals as compared to normals in every case (p < 0.01). As the age of the autistic individuals increased the hypoperfusion of verbal-associated areas in the left temporal lobe and frontal areas became more evident. The findings were significant at the p < 0.001 level. The changes in perfusion over time correlated with language development and acquisition as individuals matured. We conclude that autistic individuals have a deficiency in prefrontal areas associated with word identification and language formation skills. This subsequently prevents development of true verbal fluency and development in the temporal and frontal areas associated with speech and communication.

Increased central-parietal EEG theta-2 activity (about 6.5 per sec) was found in children with cognitive disorders (in Rett's syndrome, fragile X-syndrome, infantile autism) and in elderly patients with Alzheimer-type dementia (with prevalence of neuropsychological "frontal" disorders) in the presence of suppressed alpha rhythm. This theta-activity was closely associated with cognitive deficits and possessed a specific functional topography, namely it focused in the parietal region and suppressed by both visual stimulation and motor tests. The similar EEG pattern was observed in some patients treated with neuroleptics and/or during hyperventilation. By taking into account the data available in the literature on motor, oculomotor, regional cerebral blood flow and the probability prediction in frontal lobar dysfunction, it is suggested that the theta-activity described appears in the visuomanual coordination system and is a physiological correlate of decreased functional status of frontal lobes.

Brain single-photon emission computed tomography was performed in 22 autistic and 10 nonautistic disabled patients. The regional cerebral blood flow in both laterotemporal and dorso-medio-lateral frontal areas decreased significantly in the autistic group compared with in nonautistic group. In the autistic group, the regional cerebral blood flow was significantly higher in the right temporal and right parietal lobes than that in the left ones. Inversely, the regional cerebral blood flow in the frontal and occipital lobes was significantly higher on the left side than on the right side. In the nonautistic group, except for in the dorso-medio-lateral frontal lobes (left > right), there was no difference in the regional cerebral blood flow in either cerebrum or cerebellum. A positive correlationship between regional cerebral flow and development quotient (intelligence quotient) was observed in the left laterotemporal and both dorso-medio-lateral frontal areas, and a negative one was observed in the cerebellar vermis area. These results suggest that the regional cerebral blood flow decrease in the temporal and frontal areas relates to not only the brain mechanism of autism reported previously but also intelligence levels.

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.

The ability to attribute mental states to others ('theory of mind') pervades normal social interaction and is impaired in autistic individuals. In a previous positron emission tomography scan study of normal volunteers, performing a 'theory of mind' task was associated with activity in left medial prefrontal cortex. We used the same paradigm in five patients with Asperger syndrome, a mild variant of autism with normal intellectual functioning. No task-related activity was found in this region, but normal activity was observed in immediately adjacent areas. This result suggests that a highly circumscribed region of left medial prefrontal cortex is a crucial component of the brain system that underlies the normal understanding of other minds.

OBJECTIVE: The authors investigated the metabolic maturation of the frontal cortex in pre-school autistic children. METHOD: Regional cerebral blood flow (CBF) in five children with primary autism diagnosed according to the DSM-III-R criteria was studied longitudinally. Regional CBF in each of the autistic children was measured with single photon emission computed tomography twice during their development: at the age of 3-4 years and 3 years later. At each stage, the autistic children were compared to an age-matched comparison group of five nonautistic children with normal development. RESULTS: A transient frontal hypoperfusion was found in the autistic children at ages 3-4 years; this corresponded to the pattern of perfusion observed in much younger normal children. By the ages of 6-7, the autistic children's frontal perfusion had attained normal values. CONCLUSIONS: Since CBF patterns in children are related to maturational changes in brain function, these results indicate a delayed frontal maturation in childhood autism. Such a delayed brain maturational process is consistent with the clinical data and cognitive performance of autistic children.

BACKGROUND. The mind's ability to think about the mind has attracted substantial research interest in cognitive science in recent decades, as 'theory of mind'. No research has attempted to identify the brain basis of this ability, probably because it involves several separate processes. As a first step, we investigated one component process-the ability to recognise mental state terms. METHOD. In Experiment 1, we tested a group of children with autism (known to have theory of mind deficits) and a control group of children with mental handicap, for their ability to recognise mental state terms in a word list. This was to test if the mental state recognition task was related to traditional theory of mind tests. In Experiment 2, we investigated if in the normal brain, recognition of mental state terms might be localised. The procedure employed single photon emission computerised tomography (SPECT) in normal adult volunteers. We tested the prediction (based on available neurological and animal lesion studies) that there would be increased activation in the orbito-frontal cortex during this task, relative to a control condition, and relative to an adjacent frontal area (frontal-polar cortex). RESULTS. In Experiment 1, the group with autism performed significantly worse than the group without autism. In Experiment 2, there was increased cerebral blood flow during the mental state recognition task in the right orbito-frontal cortex relative to the left frontal-polar region. CONCLUSIONS. This simple mental state recognition task appears to relate to theory of mind, in that both are impaired in autism. The SPECT results implicate the orbito-frontal cortex as the basis of this ability.

Structural brain abnormalities have recently been discovered using magnetic resonance imaging in infantile autism, a neurodevelopmental disorder of unknown etiology. However, functional neuroimaging studies in autism using positron emission tomography have had conflicting results and have not explained how the known structural brain abnormalities in autism act in a functioning brain to produce autistic behavior. Using a new technology, high-resolution brain single photon emission tomography, we studied and scanned four young adults with infantile autism and four age-matched controls using the labeled ligand 99mTc-D,L-hexamethyl-propylene amine oxime (99mTc-HMPAO). Total brain perfusion was significantly decreased in autism subjects (range, 58% to 72% of controls, p less than or equal to .02). In addition to the globally decreased perfusion, the autism group also had regionally decreased flow in the right lateral temporal and right, left, and midfrontal lobes compared with controls (p less than or equal to .02, Mann-Whitney t-test).

OBJECTIVE: Bilateral temporal hypoperfusion at rest was recently described in autism. In normal adults, these regions are activated by listening to speech-like sounds. To investigate auditory cortical processing in autism, the authors performed a positron emission tomography activation study. METHOD: Regional cerebral blood flow was measured in five autistic adults and eight comparison subjects during rest and while listening to speech-like sounds. RESULTS: Similar to the comparison subjects, autistic patients showed a bilateral activation of the superior temporal gyrus. However, an abnormal pattern of hemispheric activation was observed in the autistic group. The volume of activation was larger on the right side in the autistic patients, whereas the reverse pattern was found in the comparison group. The direct comparison between the two groups showed that the right middle frontal gyrus exhibited significantly greater activation in the autistic group. Conversely, the left temporal areas exhibited less activation in autistic patients. CONCLUSIONS: These findings suggest that abnormal auditory cortical processing is implicated in the language impairments and the inadequate response to sounds typically seen in autism.

There is no clear evidence from imaging studies for specific structural abnormalities in the brains of people with autism. The most robust observation is of greater total brain volume. There is evidence that this greater volume is not present at birth, but appears during the first few years. This brain enlargement might be a marker of abnormal connectivity due to lack of pruning. While abnormalities have often been reported in the cerebellum and the amygdala, these are difficult to interpret since both increases and decreases in the size of these structures have been observed. Another way of identifying the neural basis of autism is to investigate brain systems underlying cognitive functions compromised in this disorder such as face perception and 'theory of mind'. Autistic people fail to activate the 'fusiform face area' during face perception tasks and show weak activation of medial frontal cortex and superior temporal gyrus when performing theory of mind tasks. These problems stem from a lack of integration of sensory processing with cognitive evaluation. I speculate that this problem reflects a failure of top-down modulation of early sensory processing. The problem could result from abnormal connectivity and lack of pruning.

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

The neuro-anatomical substrate of autism has been the subject of detailed investigation. Because previous studies have not demonstrated consistent and specific neuro-imaging findings in autism and most such studies have been performed in adults and school-aged children, we performed a retrospective review in young children in search of common functional and anatomical abnormalities with brain single-photon emission tomography (SPET) using technetium-99m ethyl cysteinate dimer (ECD) and correlative magnetic resonance imaging (MRI). The patient population was composed of 23 children aged 28-92 months (mean: 54 months) who met the diagnostic criteria of autism as defined in the DSM-IV and CARS. Brain SPET was performed after intravenous injection of 185-370 MBq of 99mTc-ECD using a brain-dedicated annular crystal gamma camera. MRI was performed in all patients, including T1, T2 axial and T1 sagittal sequences. SPET data were assessed visually. Twenty patients had abnormal SPET scans revealing focal areas of decreased perfusion. Decreased perfusion of the cerebellar hemisphere (20/23), thalami (19/23), basal ganglia (5/23) and posterior parietal (10/23) and temporal (7/23) areas were noted on brain SPET. By contrast all patients had normal MRI findings without evidence of abnormalities of the cerebellar vermis, cerebellar hemisphere, thalami, basal ganglia or parietotemporal cortex. In conclusion, extensive perfusion impairments involving the cerebellum, thalami and parietal cortex were found in this study. SPET may be more sensitive in reflecting the pathophysiology of autism than MRI. However, further studies are necessary to determine the significance of thalamic and parietal perfusion impairment in autism.

Autistic disorder is an early and severe developmental disorder characterized by deficits in verbal and nonverbal language, social skills, cognitive functioning and an abnormal repertoire of behaviors. Current research, however, has failed to identify the neurobiological mechanisms that underlie autism or those cortical brain regions, if any, that are abnormal. METHODS: We examined regional cerebral blood flow (rCBF) in six young, severely autistic patients. High-resolution brain SPECT with 99mTc-HMPAO was performed while five of the six patients were under general anesthesia. The scans reflected the subjects' rCBF in their usual alert behavioral state, since the tracer was injected at least 15 min prior to anesthesia and is rapidly extracted and fixed in the brain. A computer-automated cortical region of interest (ROI) generator was used to define 12 annular cortical regions (region 1 = left frontal, clockwise to region 12 = right frontal) for count data acquisition. The ratio of average counts in each ROI to whole-slice counts for the autistic patients was compared to age-matched controls using repeated measures (splt-plot) ANOVA statistical analysis for three representative brain levels. RESULTS: In the autistic patients, cortical regions 3, 4, and 10 were abnormally low at the cortical level canthomeatal (CM) + 3.5 cm. At level CM + 5.5 cm, regions 3, 4, 5 and 10 were abnormally low, and at level CM + 7.5 cm, regions 7 and 9 were also abnormally low. These regions correspond to abnormally low rCBF values located predominately in the temporal and parietal lobes, with the left cerebral hemisphere showing greater rCBF abnormalities than the right. CONCLUSION: Our findings suggest that the temporal and parietal lobes have abnormal rCBF in autism. HMPAO brain SPECT in combination with general anesthesia is particularly useful for imaging severely noncompliant patients.