Neuro Developmental & Pediatric Disorders

Monday 12 May 2014

Holly E Holmes¹, Frances Wiseman², James M O'Callaghan¹, Jack A Wells¹, Victor LJ Tybulewicz³, Elizabeth MC Fisher², and Mark F Lythgoe^1
1Centre for Advanced Biomedical Imaging, University College London, London, Greater London, United Kingdom, ²Department of Neurodegenerative Disease, Institute of Neurology, London, Greater London, United Kingdom, ³MRC National Institute for Medical Research, London, Greater London, United Kingdom

Down's syndrome (DS) is a genetic condition caused by the presence of a third copy of chromosome 21. Individuals with DS have a greater predisposition to Alzheimer's disease (AD). This is believed to be caused by the extra dosage of the amyloid precursor protein (APP) gene: a known AD risk factor which lies on chromosome 21. AD-like blood flow changes have previously been observed in clinical DS studies. We unveil cerebral blood flow changes in the Tc1 mouse model of DS in the absence of APP. These results suggest that other genes on chromosome 21 may be contributing to these AD-like patterns of hypoperfusion.

Thomas Mueggler¹, Dany D D'Souza¹, Barbara Biemans¹, Andreas Bruns¹, Basil Künnecke¹, Patrick Schnider², Christophe Grundschober¹, and Markus von Kienlin^1
1Pharma Research & Early Development, DTA Neuroscience, Hoffmann-La Roche, Basel, Basel-City, Switzerland, ²Pharma Research & Early Development, Small Molecule Research, Hoffmann-La Roche, Basel, Basel-City, Switzerland

The neuropeptide vasopressin is thought to play an important role in regulating social behavior. Here we investigated its role in the rat valproate (VPA) model of autism which has phenotypical changes similar to the human condition. In VPA rats we identified altered perfusion as a surrogate of disturbed neural activity in brain regions implicated in social behavior. Chronic treatment with a vasopressin V_1a receptor-specific antagonist, reversed perfusion deficits in key regions such as the striatum, ventral tegmental area and superior colliculus suggesting that V_1a antagonists have the potential to improve core symptoms of autism such as social interaction.

Chien-Hung Lu¹, Yu-Jen Chen², Yu-Chun Lo², Yung-Chin Hsu², Susan Shur-Fen Gau^3,4, and Wen-Yih Isaac Tseng^2,4
1School of Medicine, National Taiwan University, Taipei, Taipei, Taiwan, ²Center for Optoelectronic Medicine, National Taiwan University College of Medicine, Taipei, Taipei, Taiwan, ³Department of Psychiatry, National Taiwan University College of Medicine, Taipei, Taipei, Taiwan, ⁴Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei, Taipei, Taiwan

This study aimed to investigate the differences of white matter tracts across a wide range of age between autism spectrum disorder and typically developing participants using diffusion spectrum imaging. In our findings, with a large sample size (63 : 63) and a broad range of age (7-29 years). GFA presented an atypical growth pattern in ASD compared to TD in several white matter tracts. The present data suggested that the time trajectory may differentiate brain maturation in ASD.

Jeffrey I Berman^1,2, Darina Chudnovskaya¹, Wendy K Chung³, John E Spiro⁴, Timothy PL Roberts^1,2, and Simons VIP Consortium^4
1Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States, ²Radiology, University of Pennsylvania, Philadelphia, PA, United States,³Columbia University, New York, United States, ⁴Simons Foundation, New York, New York, United States

Genetic copy number variation of 16p11.2 has been associated with developmental disorders such as autism spectrum disorders (ASD). This study uses diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) to quantify microstructural alterations to the auditory radiation, Heschl’s gyrus, and arcuate fasciculus in children with 16p11.2 deletion or duplication. A significant effect of genetic copy number variation on FA, MD, and radial diffusivity was observed in each of the regions measured (p<0.05). Mean and radial diffusivities were consistently higher in the copy number variation groups indicating alterations of white matter microstructure which may impair function.

Alena Horska¹, Xin Wang¹, Matthew Ryan², Martha B Denckla², Peter B Barker¹, Harvey S Singer¹, and E Mark Mahone^2
1Johns Hopkins University, Baltimore, MD, United States, ²Kennedy Krieger Institute, Baltimore, MD, United States

Using single voxel ¹H MRS at 7T, concentrations of the neurotransmitters glutamate (Glu) and GABA were measured in prefrontal and fronto-striatal regions in pediatric patients 5-10 years old, diagnosed with ADHD and complex motor stereotypies (CMS). The control group was comprised of age-matched healthy typically developing children. Compared with controls, both patient groups had a lower overall mean GABA/Cr ratio (calculated from the 4 regions examined) and a lower striatal GABA/Cr ratio. No group differences in the GABA/Cr and NAA/Cr ratios were detected.

Po-Hsiang Chan¹, Yu-Sheng Tseng¹, Chun-jung Chen¹, Teng-Yi Huang¹, and Tzu-Chao Chuang^2
1Department of Electrical Engineering, National Taiwan University of Science and Technology, Taipe, Taipei, Taiwan, ²Department of Electrical Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan, R.O.C, Taipei, Taiwan

This study aims to develop a classification method based on support vector machine (SVM) for attention deficit hyperactivity disorder (ADHD) patients. We proposed to use SVM to classify subject groups based on the brain functional connectivity obtained from resting-state fMRI datasets and brain cortical thickness obtained from 3D T1 MPRAGE datasets. We identified that SVM classifier did not perform well (accuracy of ~ 57%) if all the available features were selected into SVM training. Using the proposed feature selection approach, the maximum accuracies increased to 68 ¡V 99 %. The results support that feature selection according to absolute weightings of a pre-trained SVM hyperplane is an efficient method to increase the classification accuracies.

Rodrigo de Luis-Garcia¹, Gemma Cabus-Pinol², Carlos Imaz-Roncero², Daniel Argibay-Quinones¹, Gonzalo Barrio-Arranz¹, Santiago Aja-Fernandez¹, and Carlos Alberola-Lopez^1
1Laboratorio de Procesado de Imagen, Universidad de Valladolid, Valladolid, Valladolid, Spain, ²Hospital Clinico Universitario, Valladolid, Valladolid, Spain

The impact of ADHD on white matter connectivity has not been well stablished yet, and the effects of treatment on the brain structure have not been sufficiently explored. We investigated the effects of ADHD and treatment with methylphenidate in the white matter of children using a tractography selection method that allows the robust extraction of several fiber bundles of interest. Differences in the Mean Diffusivity were found between ADHD patients under treatment and normal controls and between ADHD patients under treatment and drug-naive ADHD patients, indicating that the use of psychostimulants may modify the brain connectivity.

Arjun Sethi¹, Quinton Deeley¹, Sagari Sarkar¹, Marco Catani¹, Flavio Dell'Acqua¹, Declan DGM Murphy¹, and Michael C Craig^1
1Institute of Psychiatry, King's College London, London, England, United Kingdom

This work supports the importance of the white matter underpinning a mediodorsal component of the default-mode network (the dorsal cingulum) in conduct disorder and callous unemotional traits. Diffusion MRI tractography shows that decreased radial diffusivity in this tract portion is reduced in adolescents with conduct disorder, and that radial diffusivity is negatively correlated with callous-unemotional traits in the whole sample.

Mark Drakesmith¹, Anirban Dutt², Glyn Lewis³, Anthony S David², and Derek K Jones^1
1CUBRIC, Cardiff University, Cardiff, Wales, United Kingdom, ²Institute of Psychiatry, Kings College London, London, United Kingdom, ³Academic Unit of Psychiatry, University of Bristol, Bristol, United Kingdom

Few studies have examined white-matter correlates of psychotic experiences in an at-risk population. We show using DTI and quantitative T1 white-matter differences associated with sub-clinical psychotic experiences. Individuals with psychotic experiences show reduced FA, AD and increased RD in left medial frontal white matter. No differences in T1 were identified. A number of variables, especially auditory hallucinations, negatively correlate with FA, globally. Some variables also negatively correlate with T1, suggesting a positive correlation with myelination. Future identification of subjects who transition to full psychosis will enable isolation of more specific white-matter predictors of psychosis.

Zhihao Li¹, Priya Santhanam¹, Claire Coles², Mary Ellen Lynch², Stephan Hamann³, and Xiaoping Hu^1
1Biomedical Engineering, Emory University & Georgia Institute of Technology, Atlanta, Georgia, United States, ²Psychiatry and Behavioral Science, Emory University, Atlanta, Georgia, United States, ³Psychology, Emory University, Atlanta, Georgia, United States

The present fMRI study examined the developmental effect of prenatal cocaine exposure (PCE) on default mode network (DMN) deactivations in longitudinally followed adolescents. Comparing age 17 to 15 while performing the same memory task, DMN deactivation was reduced in the control group but increased in the adolescents with PCE. The present results provide direct evidence supporting the view of a long-term effect of PCE on arousal regulation.