A Multivariate Surface-Based Analysis of the Putamen in Premature Newborns: Regional Differences within the Ventral Striatum

Many children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamo-cortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus) between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiato-thalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity disorder and attention-related learning disabilities in preterm neonates. © 2013 Shi et al

Censoring Distances Based on Labeled Cortical Distance Maps in Cortical Morphometry

Shape differences are manifested in cortical structures due to neuropsychiatric disorders. Such differences can be measured by labeled cortical distance mapping (LCDM) which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed distances of gray matter (GM) voxels with respect to GM/white matter (WM) surface. Volumes and descriptive measures (such as means and variances) for each subject and the pooled distances provide the morphometric differences between diagnostic groups, but they do not reveal all the morphometric information contained in LCDM distances. To extract more information from LCDM data, censoring of the distances is introduced. For censoring of LCDM distances, the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, and distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances. Furthermore, the analysis of censored distances provides information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs) of subjects with major depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy control (Ctrl) subjects are used. A significant reduction in laminar thickness of the VMPFC and perhaps shrinkage in MDD and HR subjects is observed when compared to Ctrl subjects. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.Comment: 25 pages, 10 figure

Thermal response of Sanabria lake to global change (NW Spain)

Are large water bodies able to act as sensors of global change? As accumulators of water and heat, some of their thermal characteristics might be altered by long term (decadal) hydrometeorological changes and thus may be used as indicators of the effects of global change on fluvial ecosystems. This work focuses on the effect of global change (climate change plus water quantity and land use changes) in the internal organization of Sanabria Lake, specifically in its thermal annual cycle. The existence of temporal trends in the thermal behaviour of the lake was investigated based on the water temperature profiles are available since 1986. Data analyses include the non-parametric Mann-Kendall trend test and the Sen slope estimate to evaluate long term and seasonal patterns of hydrometeorological and in-lake thermal variables. The main results surprisingly point to a net lake cooling that could be explained by a stronger thermocline and a weaker vertical transfer of heat to the hypolimnion during the stratification period. These results contribute to understand and quantify the effects of global change on Iberian freshwater bodies.Peer ReviewedPostprint (published version

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Reward circuitry is perturbed in the absence of the serotonin transporter

The serotonin transporter (SERT) modulates the entire serotonergic system in the brain and influences both the dopaminergic and norepinephrinergic systems. These three systems are intimately involved in normal physiological functioning of the brain and implicated in numerous pathological conditions. Here we use high-resolution magnetic resonance imaging (MRI) and spectroscopy to elucidate the effects of disruption of the serotonin transporter in an animal model system: the SERT knock-out mouse. Employing manganese-enhanced MRI, we injected Mn^(2+) into the prefrontal cortex and obtained 3D MR images at specific time points in cohorts of SERT and normal mice. Statistical analysis of co-registered datasets demonstrated that active circuitry originating in the prefrontal cortex in the SERT knock-out is dramatically altered, with a bias towards more posterior areas (substantia nigra, ventral tegmental area, and Raphé nuclei) directly involved in the reward circuit. Injection site and tracing were confirmed with traditional track tracers by optical microscopy. In contrast, metabolite levels were essentially normal in the SERT knock-out by in vivo magnetic resonance spectroscopy and little or no anatomical differences between SERT knock-out and normal mice were detected by MRI. These findings point to modulation of the limbic cortical–ventral striatopallidal by disruption of SERT function. Thus, molecular disruptions of SERT that produce behavioral changes also alter the functional anatomy of the reward circuitry in which all the monoamine systems are involved

Cortical thickness and sulcal depth: insights on development and psychopathology in paediatric epilepsy.

BackgroundThe relationship between cortical thickness (CThick) and sulcal depth (SDepth) changes across brain regions during development. Epilepsy youth have CThick and SDepth abnormalities and prevalent psychiatric disorders.AimsThis study compared the CThick-SDepth relationship in children with focal epilepsy with typically developing children (TDC) and the role played by seizure and psychopathology variables.MethodA surface-based, computational high-resolution three-dimesional (3D) magnetic resonance image analytic technique compared regional CThick-SDepth relationships in 42 participants with focal epilepsy and 46 TDC (6-16 years) imaged in a 1.5 Tesla scanner. Psychiatric interviews administered to each participant yielded psychiatric diagnoses. Parents provided seizure-related information.ResultsThe TDC group alone demonstrated a significant negative medial fronto-orbital CThick-SDepth correlation. Focal epilepsy participants with but not without psychiatric diagnoses showed significant positive pre-central and post-central CThick-SDepth associations not found in TDC. Although the history of prolonged seizures was significantly associated with the post-central CThick-SDepth correlation, it was unrelated to the presence/absence of psychiatric diagnoses.ConclusionsAbnormal CThick-SDepth pre-central and post-central associations might be a psychopathology biomarker in paediatric focal epilepsy.Declaration interestNone.Copyright and usage© 2015 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence

Persistent Homology in Sparse Regression and its Application to Brain Morphometry

Sparse systems are usually parameterized by a tuning parameter that determines the sparsity of the system. How to choose the right tuning parameter is a fundamental and difficult problem in learning the sparse system. In this paper, by treating the the tuning parameter as an additional dimension, persistent homological structures over the parameter space is introduced and explored. The structures are then further exploited in speeding up the computation using the proposed soft-thresholding technique. The topological structures are further used as multivariate features in the tensor-based morphometry (TBM) in characterizing white matter alterations in children who have experienced severe early life stress and maltreatment. These analyses reveal that stress-exposed children exhibit more diffuse anatomical organization across the whole white matter region.Comment: submitted to IEEE Transactions on Medical Imagin