Biomedical subjects

Ralph-Axel Müller

Publications and source records attributed to Ralph-Axel Müller.

9 recordsLinked to original sources

PubMed2006

Eye movement and visual search: are there elementary abnormalities in autism?

Although atypical eye gaze is commonly observed in autism, little is known about underlying oculomotor abnormalities. Our review of visual search and oculomotor systems in the healthy brain suggests that relevant networks may be partially impaired in autism, given regional abnormalities known from neuroimaging. However, direct oculomotor evidence for autism remains limited. This gap is critical since oculomotor abnormalities might play a causal role in functions known to be impaired in autism, such as imitation and joint attention. We integrate our oculomotor review into a developmental approach to language impairment related to nonverbal prerequisites. Oculomotor abnormalities may play a role as a sensorimotor defect at the root of impairments in later developing functional systems, ultimately resulting in sociocommunicative deficits.

Attention↗

PubMed2006

Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism.

BACKGROUND: Autism is a neurodevelopmental disorder affecting sociocommunicative behavior, but also sensorimotor skill learning, oculomotor control, and executive functioning. Some of these impairments may be related to abnormalities of the caudate nuclei, which have been reported for autism. METHODS: Our sample was comprised of 8 high-functioning males with autism and 8 handedness, sex, and age-matched controls. Subjects underwent functional MRI scanning during performance on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI) effects were identified as interregional blood oxygenation level dependent (BOLD) signal cross-correlation, using the caudate nuclei as seed volumes. RESULTS: In the control group, fcMRI effects were found in circuits with known participation of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits). Although in the autism group fcMRI effects within these circuits were less pronounced or absent, autistic subjects showed diffusely increased connectivity mostly in pericentral regions, but also in brain areas outside expected anatomical circuits (such as visual cortex). CONCLUSION: These atypical connectivity patterns may be linked to developmental brain growth disturbances recently reported in autism and suggest inefficiently organized functional connectivity between caudate nuclei and cerebral cortex, potentially accounting for stereotypic behaviors and executive impairments.

Journal Article↗

PubMed2006

Partially enhanced thalamocortical functional connectivity in autism.

Based on evidence for thalamic abnormalities in autism, impairments of thalamocortical pathways have been suspected. We examined the functional connectivity between thalamus and cerebral cortex in terms of blood oxygen level dependent (BOLD) signal cross-correlation in 8 male participants with high-functioning autism and matched normal controls, using functional MRI during simple visuomotor coordination. Both groups exhibited widespread connectivity, consistent with known extensive thalamocortical connectivity. In a direct group comparison, overall more extensive connectivity was observed in the autism group, especially in the left insula and in right postcentral and middle frontal regions. Our findings are inconsistent with the hypothesis of general underconnectivity in autism and instead suggest that subcortico-cortical connectivity may be hyperfunctional, potentially compensating for reduced cortico-cortical connectivity.

Adolescent↗

PubMed2005

Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism.

Some recent evidence has suggested abnormalities of the dorsal stream and possibly the mirror neuron system in autism, which may be responsible for impairments of joint attention, imitation, and secondarily for language delays. The current study investigates functional connectivity along the dorsal stream in autism, examining interregional blood oxygenation level dependent (BOLD) signal cross-correlation during visuomotor coordination. Eight high-functioning autistic men and eight handedness and age-matched controls were included. Visually prompted button presses were performed with the preferred hand. For each subject, functional connectivity was computed in terms of BOLD signal correlation with the mean time series in bilateral visual area 17. Our hypothesis of reduced dorsal stream connectivity in autism was only in part confirmed. Functional connectivity with superior parietal areas was not significantly reduced. However, the autism group showed significantly reduced connectivity with bilateral inferior frontal area 44, which is compatible with the hypothesis of mirror neuron defects in autism. More generally, our findings suggest that dorsal stream connectivity in autism may not be fully functional.

Adolescent↗

PubMed2005

Activity and functional connectivity of inferior frontal cortex associated with response conflict.

The traditional Stroop test of cognitive interference requires overt speech responses. One alternative, the counting Stroop, generates cognitive interference similar to the traditional Stroop test but allows button press responses. Previous counting Stroop studies have used concrete words in the control condition, which may have masked inferior frontal activation. We studied 7 healthy young adults using fMRI on a counting Stroop condition, with a nonlinguistic control condition (geometric shapes). As expected, we found activation in bilateral inferior frontal gyri, as well as in lateral and medial prefrontal, inferior parietal, and extrastriate cortices. Additional functional connectivity analyses using inferior frontal activation clusters (right area 44, left area 47) as seed volumes showed connectivity with superior frontal area 8 and anterior cingulate gyrus, suggesting that the role of inferior frontal cortex was related to response conflict and inhibition. Connectivity with left perisylvian language areas was not observed, which further underscores the nonlinguistic nature of inferior frontal activity. We conclude that bilateral inferior frontal cortex is involved in response suppression associated with interference in the counting Stroop task.

Adult↗

PubMed2004

Abnormal activity patterns in premotor cortex during sequence learning in autistic patients.

BACKGROUND: Evidence for frontal abnormality in autism has accumulated in recent years. Our own studies have shown abnormal activation in prefrontal cortex during finger tapping and visuomotor coordination. Studies in healthy adults suggest reduced premotor and increased prefrontal activity during advanced learning stages. We examined hemodynamic changes during visuomotor learning in autistic patients. METHODS: We studied eight high-functioning autistic patients and eight control subjects during learning of an 8-digit sequence over a period of 8 min, using functional magnetic resonance imaging. RESULTS: Autistic patients showed overall less prefrontal activation during late visuomotor learning; however, the main finding was a complementary one of enhanced activation in right pericentral and premotor cortex. In the autism group, Brodmann areas 3, 4, and 6 of the right hemisphere became more involved during late learning stages (trials 25-48), compared with early stages (trials 1-24). This effect was not seen in the control group. CONCLUSIONS: Our findings suggests that in autistic patients 1) primary sensorimotor and premotor cortex, which is normally predominant in early stages of visuomotor learning, plays an atypical role in later stages, even when learning is evident; and 2) handedness and side of execution interact with asymmetry of visuomotor learning activations, contrary to what is seen in normal adults.

Adult↗

PubMed2004

Cerebellar function in autism: functional magnetic resonance image activation during a simple motor task.

BACKGROUND: The cerebellum is one of the most consistent sites of neuroanatomic abnormality in autism, yet it is still unclear how such pathology impacts cerebellar function. In normal subjects, we previously demonstrated with functional magnetic resonance imaging (fMRI) a dissociation between cerebellar regions involved in attention and those involved in a simple motor task, with motor activation localized to the anterior cerebellum ipsilateral to the moving hand. The purpose of the present investigation was to examine activation in the cerebella of autistic patients and normal control subjects performing this motor task. METHODS: We studied eight autistic patients and eight matched normal subjects, using fMRI. An anatomic region-of-interest approach was used, allowing a detailed examination of cerebellar function. RESULTS: Autistic individuals showed significantly increased motor activation in the ipsilateral anterior cerebellar hemisphere relative to normal subjects, in addition to atypical activation in contralateral and posterior cerebellar regions. Moreover, increased activation was correlated with the degree of cerebellar structural abnormality. CONCLUSIONS: These findings strongly suggest dysfunction of the autistic cerebellum that is a reflection of cerebellar anatomic abnormality. This neurofunctional deficit might be a key contributor to the development of certain diagnostic features of autism (e.g., impaired communication and social interaction, restricted interests, and stereotyped behaviors).

Adolescent↗

PubMed2004

Are nonlinguistic functions in "Broca's area" prerequisites for language acquisition? FMRI findings from an ontogenetic viewpoint.

There is incomplete consensus on the anatomical demarcation of Broca's area in the left inferior frontal gyrus and its functional characterization remains a matter of debate. Exclusive syntactic specialization has been proposed, but is overall inconsistent with the neuroimaging literature. We examined three functional MRI (fMRI) datasets on lexicosemantic decision, tone discrimination, and visuomotor coordination for potential overlap of activation. A single site of convergent activation across all three paradigms was found in the left inferior frontal lobe (area 44/45). This result is discussed in the context of animal and human studies showing inferior frontal participation in visuomotor and audiomotor functions as well as working memory. We propose that Broca's area involvement in lexical semantics and syntax emerges from these nonlinguistic functions, which are prerequisites for language acquisition.

Adult↗

PubMed2003

Abnormal variability and distribution of functional maps in autism: an FMRI study of visuomotor learning.

OBJECTIVE: Autism is a neurally based psychiatric disorder, but there is no consensus regarding the underlying neurofunctional abnormalities. Previous functional magnetic resonance imaging (fMRI) studies of simple movement suggested individually variable and scattered functional brain organization in autism. The authors examined whether such abnormalities generalize to multimodal processing (visually driven motor sequence learning). METHOD: Eight male autistic patients and eight comparison subjects matched with the patients on age, gender, and handedness were examined by using fMRI while they performed finger press movements prompted by visually presented repeating six-digit sequences. Hemodynamic responses to the six-digit sequences were statistically compared to responses to single-digit stimuli in one experiment and to regular six-digit sequences in another experiment. RESULTS: Both groups showed activations in bilateral premotor, superior parietal, and occipital cortices in both experiments. Task-by-group interactions showed that superior parietal activations were less pronounced in the autism group, whereas prefrontal cortex and more posterior parietal loci showed greater activation in the autism group than in the comparison group. The distances between Individual subjects' activation peaks and the groupwise peak were greater in the autism group than in the comparison group. CONCLUSIONS: The results support earlier findings of abnormal variability and scatter of functional maps in autism. They are consistent with evidence from other studies suggesting early-onset disturbances in the development of cerebello-thalamo-cortical pathways in autism.

Adolescent↗