Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data

Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample

Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder

Background: Autism spectrum disorder (ASD) is associated with altered face processing and decreased activity in brain regions involved in face processing. The neuropeptideoxytocin has been shown to promote face processing and modulate brain activity in healthy adults. The present study examined the effects of oxytocin on the neural basis of face processing in adults with Asperger syndrome (AS). Methods: A group of 14 individuals with AS and a group of 14 neurotypical control participants performed a face-matching and a house-matching task during functional magnetic resonance imaging. The effects of a single dose of 24 IU intranasally administered oxytocin were tested in a randomized, placebo-controlled, within-subject, cross-over design. Results: Under placebo, the AS group showed decreased activity in the right amygdala, fusiform gyrus, and inferior occipital gyrus compared with the control group during face processing. After oxytocin treatment, right amygdala activity to facial stimuli increased in the AS group. Conclusions: These findings indicate that oxytocin increases the saliency of social stimuli and in ASD and suggest that oxytocin might promote face processing and eye contact in individuals with ASD as prerequisites for neurotypical social interaction

Oxytocin increases amygdala reactivity to threatening scenes in females

The neuropeptide oxytocin (OT) is well known for its profound effects on social behavior, which appear to be mediated by an OT-dependent modulation of amygdala activity in the context of social stimuli. In humans, OT decreases amygdala reactivity to threatening faces in males, but enhances amygdala reactivity to similar faces in females, suggesting sex-specific differences in OT-dependent threat-processing. To further explore whether OT generally enhances amygdala-dependent threat-processing in females, we used functional magnetic resonance imaging (fMRI) in a randomized within-subject crossover design to measure amygdala activity in response to threatening and non-threatening scenes in 14 females following intranasal administration of OT or placebo. Participants’ eye movements were recorded to investigate whether an OT-dependent modulation of amygdala activity is accompanied by enhanced exploration of salient scene features. Although OT had no effect on participants’ gazing behavior, it increased amygdala reactivity to scenes depicting social and non-social threat. In females, OT may, thus, enhance the detection of threatening stimuli in the environment, potentially by interacting with gonadal steroids, such as progesterone and estrogen

Dentate-nucleus gadolinium deposition on magnetic resonance imaging: ultrasonographic and clinical correlates in multiple sclerosis patients

Objective!#!The objective of this study is to find out whether gadolinium accumulation in the dentate nucleus (DN) after repeated gadolinium-based contrast agent (GBCA) administration in multiple sclerosis (MS) patients is related to tissue alteration detectable on transcranial ultrasound.!##!Methods!#!In this case-control study, 34 patients (17 with, and 17 age-, sex-, MS severity-, and duration-matched participants without visually rated DN T1-hyperintensity) who had received 2-28 (mean, 11 ± 7) consecutive 1.5-Tesla MRI examinations with application of linear GBCA were included. Real-time MRI-ultrasound fusion imaging was applied, exactly superimposing the DN identified on MRI to calculate its corresponding echo-intensity on digitized ultrasound image analysis. In addition, cerebellar ataxia and cognitive performance were assessed. Correlation analyses were adjusted for age, MS duration, MS severity, and time between MRI scans.!##!Results!#!DN-to-pons T1-signal intensity-ratios (DPSIR) were larger in patients with visually rated DN T1-hyperintensity compared to those without (1.16 ± 0.10 vs 1.09 ± 0.06; p = 0.01). In the combined group, DPSIR correlated with the cumulative linear-GBCA dose (r = 0.49, p = 0.003), as did the DPSIR change on last versus first MRI (r = 0.59, p = 0.003). Neither DPSIR nor globus pallidus internus-to-thalamus T1-signal intensity-ratios were related to echo-intensity of corresponding ROI's. DPSIR correlated with the dysarthria (r = 0.57, p = 0.001), but no other, subscore of the International Cooperative Ataxia Rating Scale, and no other clinical score.!##!Conclusions!#!DN gadolinium accumulation is not associated with trace metal accumulation, calcification, or other tissue alteration detectable on ultrasound. A possible mild effect of DN gadolinium accumulation on cerebellar speech function in MS patients, suggested by present data, needs to be validated in larger study samples

A peculiar case of coastal springs and geogenic saline groundwater: the Santa Cesarea Terme thermal springs (Southern Italy)

Carbonate aquifers, located in foreland tectonic settings, could represent important thermal water resources outside the volcanic areas, supplying spas or geothermal installations. Thermal springs constitute the discharge areas of deep marine and continental groundwaters flowing within these carbonate aquifers whose hydraulic conductivity and the relevant geothermal fluid migration are strictly controlled by both the discontinuity network and the karst processes involving the foreland environment. An example of these springs occurs along the south-easternmost portion of the Apulia region (Southern Italy) where some sulphurous and warm waters (22-33 °C) flow out in partially submerged caves located along the coast, thus supplying the spas of Santa Cesarea Terme. These springs are known from ancient times (Aristotele in III century BC) and the physical-chemical features of their thermal waters resulted to be partly influenced by the sea level variations. Some hypotheses about the origin of these warm waters were proposed up to now by previous researches but some uncertainties still exist. For this reason, the area has been selected in order to define the conceptual model of the geothermal resources related to the thermal springs and, as a consequence, the origin of the thermal springs. It is one of the pilot site of the Vigor Project (Evaluation of the geothermal potential of Regions of Convergence), promoted by the Italian Ministry of Economic Development and National Research Council. Santa Cesarea Terme zone is located within the Apulia carbonate platform, the foreland of the southern Apennines, which consists of Jurassic-Cretaceous limestones, thick more than 5 km in the study area and affected by intense karst processes, resting above the Late Triassic evaporite (Burano Fm) and, unconformably, overlaid by Cenozoic calcareous successions. Belonging to a coastal area, the studied groundwater, whose top is located almost to the sea level, is involved in saltwater intrusion and therefore the salt-fresh water interface occurs at some meters below the sea level moving inland. Geological and hydrogeological surveys, including geo-electrical prospecting, and chemical and isotopic analyses of both groundwater and seawater have been carried out. Stable isotopes (δ18O, δD) were used to define the origin of the thermal waters and the recharge mechanism of the geothermal systems while the unstable isotope (3H) was determined for estimating the age of the thermal waters and to define the conceptual model of this low temperature geothermal resource. All the data have been analysed to improve the knowledge of the groundwater flow system, thus assessing the possibility of using low-temperature geothermal fluids to fulfil the thermal needs of the town of Santa Cesarea Terme. In this narrow area, the source of geogenic salinization of spring groundwater was referred to ascending very deep groundwater, more saline than current sea water.The geochemical composition and the physical features of the sampled waters suggest that thermal waters should be moving from ancient seawaters subjected to intense evaporation processes, infiltrated at great depth within the seabed substratum. Afterwards, these thermal fluids should flow up through the almost vertical structures, related to the transtensional structures, identified within a narrow sector of the studied territory

Neural correlates of risk taking in violent criminal offenders characterized by emotional hypo- and hyper-reactivity

Recent approaches suggest that emotional reactivity can be used to differentiate between subgroups of individuals who are at risk for showing elevated levels of aggression and violence. In this study, we examined how emotion governs decision making within two subgroups of antisocial criminal offenders with either emotional hypo- or hyper-reactivity compared with healthy, noncriminal controls. Offenders were recruited from high-security forensic treatment facilities and penal institutions and underwent functional magnetic resonance imaging during a financial decision-making task. In this task, participants were required to choose between low-risk (bonds) and high-risk alternatives (stocks). Bonds were always the safe choice; stocks could win or lose, with a varying degree of uncertainty. We found that emotionally hypo-reactive offenders differed most from healthy controls by showing diminished neural activation in the rostral anterior cingulate cortex in response to uncertainty as well as decreased activity in the prefrontal cortex when trying to regulate their behavior accordingly (i.e., when consistently choosing “safe alternatives”). Hence, the data indicate that emotionally hypo-reactive offenders (with psychopathic traits) constitute a special subgroup within antisocial offenders characterized in particular by a limited capacity to emotionally represent uncertainty and to anticipate punishment

Basal forebrain and hippocampus as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment-a multicenter DTI and volumetry study

Background: Hippocampal grey matter (GM) atrophy predicts conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Pilot data suggests that mean diffusivity (MD) in the hippocampus, as measured with diffusion tensor imaging (DTI), may be a more accurate predictor of conversion than hippocampus volume. In addition, previous studies suggest that volume of the cholinergic basal forebrain may reach a diagnostic accuracy superior to hippocampal volume in MCI. Objective: The present study investigated whether increased MD and decreased volume of the hippocampus, the basal forebrain and other AD-typical regions predicted time to conversion from MCI to AD dementia. Methods: 79 MCI patients with DTI and T1-weighted magnetic resonance imaging (MRI) were retrospectively included from the European DTI Study in Dementia (EDSD) dataset. Of these participants, 35 converted to AD dementia after 6-46 months (mean: 21 months). We used Cox regression to estimate the relative conversion risk predicted by MD values and GM volumes, controlling for age, gender, education and center. Results: Decreased GM volume in all investigated regions predicted an increased risk for conversion. Additionally, increased MD in the right basal forebrain predicted increased conversion risk. Reduced volume of the right hippocampus was the only significant predictor in a stepwise model combining all predictor variables. Conclusion: Volume reduction of the hippocampus, the basal forebrain and other AD-related regions was predictive of increased risk for conversion from MCI to AD. In this study, volume was superior to MD in predicting conversion