Justin H. G. Williams

Characteristics of fetal anticonvulsant syndrome associated autistic disorder.

The aim of this study was to evaluate the clinical features and frequency of autistic disorder or Asperger syndrome (AS; according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM‐IV] criteria) in children exposed to anticonvulsant medication in utero. During a 20‐year study period, 626 children were born in Aberdeen to mothers taking antiepileptic drugs (AEDs). The study examined long‐term effects of prenatal exposure to AEDs in 260 children (122 males, 138 females). Of these, 26 (16 males) were reported by parents to have social or behavioural difficulties. Eleven children (6 males, 5 females) fulfilled the DSM‐IV criteria for autistic disorder and one (female) fulfilled the DSM‐IV criteria for AS. These children comprised 4.6% of the exposed children studied, and 1.9% of all exposed children born during the study period. Mean age of these children at diagnosis was 5 years 4 months (SD 2y 11mo) and 9 years 10 months (SD 3y 10mo) at the time of this study. Other children from the group of 26 had difficulties in areas of speech and language development and social communication but did not meet the criteria for an autism spectrum disorder (ASD). Sodium valproate was the drug most commonly associated with autistic disorder, five of 56 (8.9%) of the study children exposed to sodium valproate alone had either autistic disorder or AS. It was concluded that prenatal exposure to anticonvulsant medication is a risk factor for the development of an ASD. Fetal anticonvulsant syndrome associated autistic disorder is characterized by an even sex ratio, absence of regression or skill loss, and language delay in the absence of global delay.

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.

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.

Self–other relations in social development and autism: multiple roles for mirror neurons and other brain bases

Mirror neuron system dysfunction may underlie a self–other matching impairment, which has previously been suggested to account for autism. Embodied Cognition Theory, which proposes that action provides a foundation for cognition has lent further credence to these ideas. The hypotheses of a self–other matching deficit and impaired mirror neuron function in autism have now been well supported by studies employing a range of methodologies. However, underlying mechanisms require further exploration to explain how mirror neurons may be involved in attentional and mentalizing processes. Impairments in self–other matching and mirror neuron function are not necessarily inextricably linked and it seems possible that different sub‐populations of mirror neurons, located in several regions, contribute differentially to social cognitive functions. It is hypothesized that mirror neuron coding for action–direction may be required for developing attentional sensitivity to self‐directed actions, and consequently for person‐oriented, stimulus‐driven attention. Mirror neuron networks may vary for different types of social learning such as “automatic” imitation and imitation learning. Imitation learning may be more reliant on self–other comparison processes (based on mirror neurons) that identify differences as well as similarities between actions. Differential connectivity with the amygdala–orbitofrontal system may also be important. This could have implications for developing “theory of mind,” with intentional self–other comparison being relevant to meta‐representational abilities, and “automatic” imitation being more relevant to empathy. While it seems clear that autism is associated with impaired development of embodied aspects of cognition, the ways that mirror neurons contribute to these brain–behavior links are likely to be complex.

A new tool for assessing human movement: the Kinematic Assessment Tool.

The study of human behaviour ultimately requires the documentation of human movement. In some instances movements can be recorded through a simple button press on a computer input device. In other situations responses can be captured through questionnaire surveys. Nevertheless, there is a need within many neuroscience settings to capture how complex movements unfold over time (human kinematics). Current methods of measuring human kinematics range from accurate but multifarious laboratory configurations to portable but simplistic and time-consuming paper and pen methods. We describe a new system for recording the end-point of human movement that has the power of laboratory measures but the advantages of pen-and-paper tests: the Kinematic Assessment Tool. KAT provides a highly portable system capable of measuring human movement in configurable visual-spatial tasks. The usefulness of the system is shown in a study where 12 participants undertook a tracing and copying task using their preferred and non-preferred hand. The results show that it is possible to capture behaviour within complex tasks and quantify performance using objective measures automatically generated by the KAT system. The utility of these measures was indexed by our ability to distinguish the performance of the preferred and non-preferred hand using a single variable.

Do mirror neuron areas mediate mu rhythm suppression during imitation and action observation

Mu rhythm is an EEG measure of resting motor neurons, which is normally suppressed by input because of action observation or movement execution. This characteristic has caused mu suppression to be used as proxy marker for mirror neuron activation. However, there is little direct evidence that fluctuations in mu rhythm suppression reflect concurrent fluctuations in mirror neuron activity. A manual imitation paradigm was used to look at correlations between mu rhythm and BOLD response, by recording sequential EEG and fMRI measures to allow within-subject correlation analyses. Participants were instructed to imitate or observe actions involving the movement of a handle with their right hand. Mu power modulation, defined as mu power changes between conditions, correlated negatively with BOLD response in right inferior parietal lobe, premotor cortex and inferior frontal gyrus; putative mirror neuron areas. Clusters were also identified in bilateral cerebellum, left medial frontal gyrus, right temporal lobe and thalamus. This suggests that mu suppression involves a range of structures that modulate motor preparation activities and are sensitive to visual input, including but not restricted to the human analogue of the mirror neuron system.

Methodological problems undermine tests of the ideo-motor conjecture

Recent behavioural research has investigated whether viewing someone perform an action results in activation of that action by the observer. Postulated empirical support for this ‘ideo-motor (IM) conjecture’ typically rests upon two types of experimental paradigm (reaction time and movement tracking tasks). These paradigms purport to show movement facilitation when compatible movements are observed and vice versa, but only for biological stimuli. Unfortunately, these paradigms often contain confounding (and unavoidable) generic stimulus–response compatibility effects that are not restricted to observed human movement. The current study demonstrates in three experiments that equivalent compatibility effects can be produced by non-biological stimuli. These results suggest that existing empirical paradigms may not, and perhaps cannot, support the IM-conjecture.

Exercising attention within the classroom

Aim  To investigate whether increased physical exercise during the school day influenced subsequent cognitive performance in the classroom.

Cortical and subcortical mechanisms at the core of imitation

Abstract Imitation is thought to require a perception–action matching process that utilizes the “mirror neuron” system, but other cognitive functions such as error detection may also be required for even simple imitation. We sought to explore the core neural substrate of imitation by examining the imitation of simple finger actions using fMRI. Participants observed one of two actions and were instructed to imitate the action they observed, or to perform the alternative non-matching action. The contrast between imitation and non-matching actions was associated with activation in areas previously associated with imitation and “mirror neuron” functioning, including insula, intraparietal sulcus, dorsal premotor cortex, and superior temporal gyrus. Imitation was also specifically associated with activity in areas of prefrontal cortex, lateral orbitofrontal cortex (OFC), amygdala, red nucleus, thalamus, hippocampus, and substantia nigra. We suggest that lateral OFC responds to action–perception mismatch and other clusters reflect working memory, motor planning, associative learning, and visuo-motor integration of goal-directed action. Although computational models have predicted integration of these functions to enable imitation, their specific brain bases have not previously been identified. Together they offer a potentially powerful means through which matching ones actions to those of others can lead to behavioral modification and development.

How does exercise benefit performance on cognitive tests in primary‐school pupils?

Aim  We have previously demonstrated improved cognitive performance after a classroom‐based exercise regime. In this study, we examined the reproducibility of this effect in a more socio‐economically diverse sample and also investigated whether cognitive benefits of exercise were moderated by body mass index (BMI) or symptoms of attention‐deficit–hyperactivity disorder (ADHD).