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Biomedical subjects

Justin H G Williams

Publications and source records attributed to Justin H G Williams.

9 recordsLinked to original sources

Consequences of prenatal toxin exposure for mental health in children and adolescents: a systematic review.

Drug use during pregnancy is common and the developing foetus may be exposed to a range of environmental toxins that have long-term consequences for neurodevelopment. We conducted a systematic review of the literature to explore the results of longitudinal cohort studies that have examined this question. Out of 2,977 abstracts identified, 7 previous systematic reviews and 95 original articles met further selection criteria. These mostly addressed the neurodevelopmental effects of exposure to lead, polychlorinated biphenyls, mercury, cocaine, alcohol, marijuana, cigarettes and antidepressants. Radiation, opiates, steroids, amphetamines and caffeine have received much less attention. Findings are difficult to interpret because risk factors tend to cluster together and interact. However, some findings are consistent. Lead and PCB's have a general effect on brain development, whilst marijuana and alcohol appear to have long-term effects specifically on attentional skills. The effects of alcohol increase with maternal age and binge drinking is more important than average intake. The effects of cocaine diminish with age and are largely mediated through psychosocial factors, whilst the relation between smoking and later delinquency is largely mediated by genetically inherited factors. Exposure to toxins during pregnancy may constitute an important but relatively unacknowledged cause of child psychiatric morbidity.

Adolescent↗

Methodological issues in measures of imitative reaction times.

Ideomotor (IM) theory suggests that observing someone else perform an action activates an internal motor representation of that behaviour within the observer. Evidence supporting the case for an ideomotor theory of imitation has come from studies that show imitative responses to be faster than the same behavioural measures performed in response to spatial cues. In an attempt to replicate these findings, we manipulated the salience of the visual cue and found that we could reverse the advantage of the imitative cue over the spatial cue. We suggest that participants utilised a simple visuomotor mechanism to perform all aspects of this task, with performance being driven by the relative visual salience of the stimuli. Imitation is a more complex motor skill that would constitute an inefficient strategy for rapid performance.

Adult↗

The effect of orientation on prehension movement time.

We explored the relationship between hand orientation and movement time. Three groups of participants (n = 8 per group) were asked to grasp an object rotated in one of the following planes: (1) coronal; (2) sagittal; (3) horizontal. In the coronal plane, the rotational requirements directly mapped onto the neuromuscular demands associated with a single joint-level degree of freedom movement. A simple lawful relationship was found between the extent of rotation (pronation or supination) and duration. Reach-to-grasp movements to objects rotated in the sagittal and horizontal plane produced different movement patterns. These patterns increased the muscle level degrees of freedom recruited (higher neuromuscular demands) and movement duration increased correspondingly though not in a simple manner. The results of the present study show unambiguously that object orientation influences the duration of reach-to-grasp movements.

Adult↗

Neural mechanisms of imitation and 'mirror neuron' functioning in autistic spectrum disorder.

An association between autistic spectrum disorder and imitative impairment might result from dysfunction in mirror neurons (MNs) that serve to relate observed actions to motor codings. To explore this hypothesis, we employed a functional magnetic resonance imaging (fMRI) protocol previously used to identify the neural substrate of imitation, and human MN function, to compare 16 adolescent males of normal intelligence with autistic spectrum disorder (ASD) and age, sex and IQ matched controls. In the control group, in accord with previous findings, we identified activity attributable to MNs in areas of the right parietal lobe. Activity in this area was less extensive in the ASD group and was absent during non-imitative action execution. Broca's area was minimally active during imitation in controls. Differential patterns of activity during imitation and action observation in ASD and controls were most evident in an area at the right temporo-parietal junction also associated with a 'theory of mind' (ToM) function. ASD participants also failed to show modulation of left amygdala activity during imitation that was evident in the controls. This may have implications for understanding the imitation of emotional stimuli in ASD. Overall, we suggest that ASD is associated with altered patterns of brain activity during imitation, which could stem from poor integration between areas serving visual, motor, proprioceptive and emotional functions. Such poor integration is likely to adversely affect the development of ToM through imitation as well as other aspects of social cognitive function in ASD.

Adolescent↗

An fMRI study of joint attention experience.

Although much is now known about eye movement detection, little is known about the higher cognitive processes involved in joint attention. We developed video stimuli which when watched, engender an experience of joint attention in the observer. This allowed us to compare an experience of joint attention to nonjoint attention within an fMRI scanning environment. Joint attention was associated with activity in the ventromedial frontal cortex, the left superior frontal gyrus (BA10), cingulate cortex, and caudate nuclei. The ventromedial frontal cortex has been consistently shown to be activated during mental state attribution tasks. BA10 may serve a cognitive integration function, which in this case seems to utilize a perception-action matching process. The activation we identified in BA10 overlaps with a location of increased grey matter density that we recently found to be associated with autistic spectrum disorder. This study therefore constitutes evidence that the neural substrate of joint attention also serves a mentalizing function. The developmental failure of this substrate in the left anterior frontal lobe may be important in the etiology of autistic spectrum disorder.

Adolescent↗

Structural white matter deficits in high-functioning individuals with autistic spectrum disorder: a voxel-based investigation.

A number of imaging and neuropathological studies have reported structural abnormalities in white matter areas such as the corpus callosum in autism spectrum disorder (ASD). Differences in both global brain volume and the size of specific neural structures have been reported. In order to expand these previously reported findings and to describe more precisely the nature of such structural changes, we performed a voxel-based morphometric whole brain analysis, using a group-specific template, in male adolescents with ASD. Fifteen individuals with normal intelligence and ASD, and a group of 16 controls, matched for age, sex, and IQ, were investigated. High-resolution T1-weighted 3D data sets were acquired and analysed. Local white matter volume deficits were found in the corpus callosum, particularly in the anterior splenium and isthmus, and right hemisphere. White matter volume deficits were also found in the left middle temporal, right middle frontal, and left superior frontal gyri. No significant areas of increased white matter volume were found. Our findings support the hypothesis that reduced white matter volume in the corpus callosum and right hemisphere may play a role in the pathophysiology of ASD.

Adolescent↗

A voxel-based investigation of brain structure in male adolescents with autistic spectrum disorder.

Autistic spectrum disorder (ASD) has been associated with abnormal neuroanatomy in many imaging and neuropathological studies. Both global brain volume differences and differences in the size of specific neural structures have been reported. Here, we report a voxel-based morphometric whole brain analysis, using a group specific template, on 16 individuals of normal intelligence with autistic spectrum disorder (ASD), and a group of 16 age-, sex- and IQ-matched controls. Total grey matter volume was increased in the ASD group relative to the control group, with local volume increases in the right fusiform gyrus, the right temporo-occipital region and the left frontal pole extending to the medial frontal cortex. A local decrease in grey matter volume was found in the right thalamus. A decrease in global white matter volume in the ASD group did not reach significance. We found the increase in grey matter volume in ASD subjects was greatest in those areas recognised for their role in social cognition, particularly face recognition (right fusiform gyrus), mental state attribution: 'theory of mind' (anterior cingulate and superior temporal sulcus) and perception of eye gaze (superior temporal gyrus). The picture as a whole may reflect an abnormally functioning social cognitive neural network. We suggest that increased grey matter volume may play a pivotal role in the aetiology of the autistic syndrome.

Adolescent↗

A systematic review of action imitation in autistic spectrum disorder.

Imitative deficits have been associated with autistic spectrum disorder (ASD) for many years, most recently through more robust methodologies. A fresh, systematic review of the significance, characteristics, and underlying mechanism of the association is therefore warranted. From 121 candidates, we focused on 21 well-controlled studies involving 281 cases of ASD. Overall, children with ASD performed worse on imitative tasks (Combined Logit p value < .00005). The emerging picture is of delayed development in imitation, implicating a deficit in mapping neural codings for actions between sensory and motor modalities, rather than in motivation or executive function. We hypothesise that ASD is characterised by abnormal development of these mappings. such that they are biased towards object-oriented tasks at the expense of those required for action imitation per se.

Adolescent↗

Visual-auditory integration during speech imitation in autism.

Children with autistic spectrum disorder (ASD) may have poor audio-visual integration, possibly reflecting dysfunctional 'mirror neuron' systems which have been hypothesised to be at the core of the condition. In the present study, a computer program, utilizing speech synthesizer software and a 'virtual' head (Baldi), delivered speech stimuli for identification in auditory, visual or bimodal conditions. Children with ASD were poorer than controls at recognizing stimuli in the unimodal conditions, but once performance on this measure was controlled for, no group difference was found in the bimodal condition. A group of participants with ASD were also trained to develop their speech-reading ability. Training improved visual accuracy and this also improved the children's ability to utilize visual information in their processing of speech. Overall results were compared to predictions from mathematical models based on integration and non-integration, and were most consistent with the integration model. We conclude that, whilst they are less accurate in recognizing stimuli in the unimodal condition, children with ASD show normal integration of visual and auditory speech stimuli. Given that training in recognition of visual speech was effective, children with ASD may benefit from multi-modal approaches in imitative therapy and language training.

Adolescent↗