Response inhibition and serotonin in autism:a functional MRI study using acute tryptophan depletion

It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target

White Light Interferometric Surface Profiler

We describe an optical system for 3-D profilometry based on the white light interferometer. We detail a simple way to construct a profiler that uses two simple algorithms which deal efficiently and quickly with the data. The system has a theoretically unlimited range and can deal with rough and smooth surface

Modernization of the Hilger and Watts Guage-block Interferometer

The Hilger & Watts gauge-block interferometer was designed and manufactured commercially in the 1950s. The instrument uses isotope lamps as wavelength standards to perform absolute length calibration of gauge blocks (slip gauges) up to 100 mm in length, to an accuracy of approximately 1 ppm. It is entirely manually operated. In order to make the instrument more suitable for the modern laboratory, new hardware has been added, and a customized software package developed to automate the measurement process. This paper shows how interferograms may be imaged successfully at each of the eight available wavelengths, and the critical fringe fraction measurement automated, ensuring an accuracy better than ±0.05 fringe. To demonstrate the validity of the new system, representative data are presented alongside data obtained using the traditional method and from an external accredited laboratory

Effects of acute tryptophan depletion on neural processing of facial expressions of emotion in humans

Introduction Acute tryptophan depletion (ATD) temporarily lowers brain serotonin (5-HT) synthesis, and behavioral studies have shown that this alters the processing of facial expressions of emotion. Materials and methods The neural basis for these alterations is not known. Therefore, we employed ATD and event-related functional magnetic resonance imaging (fMRI) to examine neural responses during incidental processing of fearful, happy, sad, and disgusted facial expressions. Fourteen healthy male controls (age, 28 ± 10) were scanned under both placebo (SHAM) and depletion (ATD) conditions. Results and discussion We predicted that ATD would be associated with changes in neural activity within facial emotion-processing networks. We found that serotonergic modulation did not affect performance on the fMRI tasks, but was associated with widespread effects on neural response to components of face processing networks for fearful, disgusted, and happy but not sad expressions across differing intensities. Conclusion Hence, the 5-HT system affects brain function (in ‘limbic’ and ‘face processing’ regions) during incidental processing of emotional facial expressions; but this varies with emotion type and intensities

Serotonin and the neural processing of facial emotions in adults with autism

Context: People with autism spectrum disorders (ASDs) have lifelong deficits in social behavior and differences in behavioral as well as neural responses to facial expressions of emotion. The biological basis to this is incompletely understood, but it may include differences in the role of neurotransmitters such as serotonin, which modulate facial emotion processing in health. While some individuals with ASD have significant differences in the serotonin system, to our knowledge, no one has investigated its role during facial emotion processing in adults with ASD and control subjects using acute tryptophan depletion (ATD) and functional magnetic resonance imaging. Objective: To compare the effects of ATD on brain responses to primary facial expressions of emotion in men with ASD and healthy control subjects. Design: Double-blind, placebo-controlled, crossover trial of ATD and functional magnetic resonance imaging to measure brain activity during incidental processing of disgust, fearful, happy, and sad facial expressions. Setting: Institute of Psychiatry, King\u27s College London, and South London and Maudsley National Health Service Foundation Trust, England. Participants: Fourteen men of normal intelligence with autism and 14 control subjects who did not significantly differ in sex, age, or overall intelligence. Main Outcome Measures: Blood oxygenation level-dependent response to facial expressions of emotion. Results: Brain activation was differentially modulated by ATD depending on diagnostic group and emotion type within regions of the social brain network. For example, processing of disgust faces was associated with interactions in medial frontal and lingual gyri, whereas processing of happy faces was associated with interactions in middle frontal gyrus and putamen. Conclusions: Modulation of the processing of facial expressions of emotion by serotonin significantly differs in people with ASD compared with control subjects. The differences vary with emotion type and occur in social brain regions that have been shown to be associated with group differences in serotonin synthesis/receptor or transporter density. Arch Gen Psychiatry. 2012; 69(10): 1003-1013. Published online June 4, 2012. doi: 10.1001/archgenpsychiatry.2012.51

Serotonin and the Neural Processing of Facial Emotions in Adults With Autism:An fMRI Study Using Acute Tryptophan Depletion

Context: People with autism spectrum disorders (ASDs) have lifelong deficits in social behavior and differences in behavioral as well as neural responses to facial expressions of emotion. The biological basis to this is incompletely understood, but it may include differences in the role of neurotransmitters such as serotonin, which modulate facial emotion processing in health. While some individuals with ASD have significant differences in the serotonin system, to our knowledge, no one has investigated its role during facial emotion processing in adults with ASD and control subjects using acute tryptophan depletion (ATD) and functional magnetic resonance imaging. Objective: To compare the effects of ATD on brain responses to primary facial expressions of emotion in men with ASD and healthy control subjects. Design: Double-blind, placebo-controlled, crossover trial of ATD and functional magnetic resonance imaging to measure brain activity during incidental processing of disgust, fearful, happy, and sad facial expressions. Setting: Institute of Psychiatry, King's College London, and South London and Maudsley National Health Service Foundation Trust, England. Participants: Fourteen men of normal intelligence with autism and 14 control subjects who did not significantly differ in sex, age, or overall intelligence. Main Outcome Measures: Blood oxygenation level-dependent response to facial expressions of emotion. Results: Brain activation was differentially modulated by ATD depending on diagnostic group and emotion type within regions of the social brain network. For example, processing of disgust faces was associated with interactions in medial frontal and lingual gyri, whereas processing of happy faces was associated with interactions in middle frontal gyrus and putamen. Conclusions: Modulation of the processing of facial expressions of emotion by serotonin significantly differs in people with ASD compared with control subjects. The differences vary with emotion type and occur in social brain regions that have been shown to be associated with group differences in serotonin synthesis/receptor or transporter density. Arch Gen Psychiatry. 2012; 69(10): 1003-1013. Published online June 4, 2012. doi: 10.1001/archgenpsychiatry.2012.51