Ralph Axel Müller

Brain Mapping of Language and Auditory Perception in High-Functioning Autistic Adults: A PET Study

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.

Functional brain reorganization in children

Developmental brain plasticity in association with focal brain injury is dependent on a number of factors, including age of the individual at the time of injury, size and topography of the brain lesion, maturational state of the brain system injured, integrity of brain areas surrounding and contralateral to the lesion, presence and duration of epilepsy, and medication effects. Recently developed functional neuroimaging tools now make it possible to study non-invasively several aspects of human brain functional reorganization in response to injury. Clinical models which are suitable for the study of developmental brain plasticity include patients who have undergone cortical resections for the alleviation of intractable epilepsy, patients who have sustained unilateral cerebrovascular insults at various periods of development, patients with chronic progressive unilateral brain injury such as in the Sturge-Weber syndrome, and patients with early sensory deprivation such as blind or deaf subjects. Although evidence of functional brain reorganization can be demonstrated in these models, it is emphasized that the neurobiological rules that govern intrahemispheric versus interhemispheric reorganization of function in the brain are, at present, poorly understood.

Receptive and expressive language activations for sentences: a Pet study

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.

Impairment of dentato-thalamo-cortical pathway in autistic men: language activation data from positron emission tomography

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.

Brain Organization of Language after Early Unilateral Lesion: A PET Study☆☆☆

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).

Plasticity of motor organization in children and adults

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 > 10years) 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.

Brain organization for language in children, adolescents, and adults with left hemisphere lesion: a PET study.

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.

Brain Organization of Motor and Language Functions Following Hemispherectomy: A [15O]-Water Positron Emission Tomography Study

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 [15O]-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 (J Child Neurol 1998; 13:16-22).

Brain Activation During Intermittent Photic Stimulation: A [15O]‐Water PET Study on Photosensitive Epilepsy

Purpose: 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.

Developmental changes of cortical and cerebellar motor control: a clinical positron emission tomography study with children and adults.

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. (J Child Neurol 1998; 13:550-556).