Maite Aznárez-Sanado

Cortical hypoperfusion in Parkinson's disease assessed using arterial spin labeled perfusion MRI.

Alterations in cerebral perfusion and metabolism in Parkinsons disease have been assessed in several studies, using nuclear imaging techniques and more recently magnetic resonance imaging. However, to date there is no consensus in the literature regarding the extent and the magnitude of these alterations. In this work, arterial spin labeled perfusion MRI was employed to quantify absolute cerebral blood flow in a group of early-to-moderate Parkinsons disease patients and age-matched healthy controls. Perfusion comparisons between the two groups showed that Parkinsons disease is characterized by wide-spread cortical hypoperfusion. Subcortically, hypoperfusion was also found in the caudate nucleus. This pattern of hypoperfusion could be related to cognitive dysfunctions that have been previously observed even at the disease early stages. The present results were obtained by means of whole brain voxel-wise comparisons of absolute perfusion values, using statistical parametric mapping, thus avoiding the potentially biased global mean normalization procedure. In addition, this work demonstrates that between-group comparison of relative perfusion values after global mean normalization, introduced artifactual relative perfusion increases, where absolute perfusion was in fact preserved. This has implications for perfusion studies of other brain disorders.

Continuous performance of a novel motor sequence leads to highly correlated striatal and hippocampal perfusion increases.

The time course of changes in regional cerebral perfusion during a continuous motor learning task performed with the right hand was monitored using the arterial spin labeling (ASL) technique at high field (3 T). ASL allowed measuring explicit learning related effects in neural activity elicited throughout a 6 minute task period. During this time learning took place as demonstrated by performance improvement. Comparing the initial and final learning phases, perfusion decreases were detected in most of the cortical regions recruited during early learning. More interestingly however perfusion increases were observed in a few cortical and subcortical regions of the contralateral hemisphere: the supplementary motor area, the primary somatosensory area, the posterior insula and posterior putamen, the hippocampus and bilaterally the retrosplenial cortex. Moreover, perfusion increases in the posterior putamen and hippocampus were highly correlated during the learning period. These results support the hypothesis that the striatum and hippocampus form interactive memory systems with parallel processing.

Effects on resting cerebral blood flow and functional connectivity induced by metoclopramide: a perfusion MRI study in healthy volunteers

BACKGROUND AND PURPOSE The substituted benzamide, metoclopramide, is a dopamine receptor antagonist and is widely prescribed in the symptomatic treatment of nausea and vomiting, although it can cause adverse motor and non‐motor side effects. The effects of metoclopramide on brain metabolism have not been investigated to date.

The neural substrate and functional integration of uncertainty in decision making: an information theory approach.

Decision making can be regarded as the outcome of cognitive processes leading to the selection of a course of action among several alternatives. Borrowing a central measurement from information theory, Shannon entropy, we quantified the uncertainties produced by decisions of participants within an economic decision task under different configurations of reward probability and time. These descriptors were used to obtain blood oxygen level-dependent (BOLD) signal correlates of uncertainty and two clusters codifying the Shannon entropy of task configurations were identified: a large cluster including parts of the right middle cingulate cortex (MCC) and left and right pre-supplementary motor areas (pre-SMA) and a small cluster at the left anterior thalamus. Subsequent functional connectivity analyses using the psycho-physiological interactions model identified areas involved in the functional integration of uncertainty. Results indicate that clusters mostly located at frontal and temporal cortices experienced an increased connectivity with the right MCC and left and right pre-SMA as the uncertainty was higher. Furthermore, pre-SMA was also functionally connected to a rich set of areas, most of them associative areas located at occipital and parietal lobes. This study provides a map of the human brain segregation and integration (i.e., neural substrate and functional connectivity respectively) of the uncertainty associated to an economic decision making paradigm.

Right parietal dominance in spatial egocentric discrimination

Egocentric tactile perception is crucial for skilled hand motor control. In order to better understand the brain functional underpinnings related to this basic sensorial perception, we performed a tactile perception functional magnetic resonance imaging (fMRI) experiment with two aims. The first aim consisted of characterizing the neural substrate of two types of egocentric tactile discrimination: the spatial localization (SLD) and simultaneity succession discrimination (SSD) in both hands to define hemispheric dominance for these tasks. The second goal consisted of characterizing the brain activation related to the spatial attentional load, the functional changes and their connectivity patterns induced by the psychometric performance (PP) during SLD. We used fMRI in 25 right-handed volunteers, applying pairs of sinusoidal vibratory stimuli on eight different positions in the palmar surface of both hands. Subjects were required either to identify the stimulus location with respect to an imaginary midline (SLD), to discriminate the simultaneity or succession of a stimuli pair (SSD) or to simply respond to stimulus detection. We found a fronto-parietal network for SLD and frontal network for SSD. During SLD we identified right hemispheric dominance with increased BOLD activation and functional interaction of the right supramarginal gyrus with contralateral intra-parietal sulcus for right and left hand independently. Brain activity correlated to spatial attentional load was found in bilateral structures of intra-parietal sulcus, precuneus extended to superior parietal lobule, pre-supplementary motor area, frontal eye fields and anterior insulae for both hands. We suggest that the right supramarginal gyrus and its interaction with intra-parietal lobule may play a pivotal role in the phenomenon of tactile neglect in right fronto-parietal lesions.

Robust estimation of fractal measures for characterizing the structural complexity of the human brain: Optimization and reproducibility

High-resolution isotropic three-dimensional reconstructions of human brain gray and white matter structures can be characterized to quantify aspects of their shape, volume and topological complexity. In particular, methods based on fractal analysis have been applied in neuroimaging studies to quantify the structural complexity of the brain in both healthy and impaired conditions. The usefulness of such measures for characterizing individual differences in brain structure critically depends on their within-subject reproducibility in order to allow the robust detection of between-subject differences. This study analyzes key analytic parameters of three fractal-based methods that rely on the box-counting algorithm with the aim to maximize within-subject reproducibility of the fractal characterizations of different brain objects, including the pial surface, the cortical ribbon volume, the white matter volume and the gray matter/white matter boundary. Two separate datasets originating from different imaging centers were analyzed, comprising 50 subjects with three and 24 subjects with four successive scanning sessions per subject, respectively. The reproducibility of fractal measures was statistically assessed by computing their intra-class correlations. Results reveal differences between different fractal estimators and allow the identification of several parameters that are critical for high reproducibility. Highest reproducibility with intra-class correlations in the range of 0.9-0.95 is achieved with the correlation dimension. Further analyses of the fractal dimensions of parcellated cortical and subcortical gray matter regions suggest robustly estimated and region-specific patterns of individual variability. These results are valuable for defining appropriate parameter configurations when studying changes in fractal descriptors of human brain structure, for instance in studies of neurological diseases that do not allow repeated measurements or for disease-course longitudinal studies.

Functional asymmetries in early learning during right, left, and bimanual performance in right-handed subjects.

To elucidate differences in activity and connectivity during early learning due to the performing hand.

Dopaminergic modulation of the trade-off between probability and time in economic decision-making

Studies on animals and humans have demonstrated the importance of dopamine in modulating decision-making processes. In this work, we have tested dopaminergic modulation of economic decision-making and its neural correlates by administering either placebo or metoclopramide, a dopamine D2-receptor antagonist, to healthy subjects, during a functional MRI study. The decision-making task combined probability and time delay with a fixed monetary reward. For individual behavioral characterization, we used the Probability Time Trade-off (PTT) economic model, which integrates the traditional trade-offs of reward magnitude-time and reward magnitude-probability into a single measurement, thereby quantifying the subjective value of a delayed and probabilistic outcome. A regression analysis between BOLD signal and the PTT model index permitted to identify the neural substrate encoding the subjective reward-value. Behaviorally, medication reduced the rate of temporal discounting over probability, reflected in medicated subjects being more prone to postpone the reward in order to increase the outcome probability. In addition, medicated subjects showed less activity during the task in the postcentral gyrus as well as frontomedian areas, whereas there were no differences in the ventromedial orbitofrontal cortex (VMOFC) between groups when coding the subjective value. The present study demonstrates by means of behavior and imaging that dopamine modulation alters the probability-time trade-off in human economic decision-making.

Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: A systematic review and meta-analysis

HighlightsRisk of injury in children and adolescents with ADHD is increased.ADHD medications reduce this risk.Results were robust to sensitivity analyses.Study was pre‐registered in PROSPERO and reporting guidelines were followed. ABSTRACT A systematic review with meta‐analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents (“risk analysis”); 2) assess the effect of ADHD medications on this risk (“medication analysis”). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex‐controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1.53 (95% CI = 1.40,1.67) and 1.39 (95% CI = 1.06,1.83), respectively. For the medication analysis, we meta‐analysed studies that avoided the confounding‐by‐indication bias [four studies with a self‐controlled methodology and another comparing risk over time and groups (a “difference in differences” methodology)]. The pooled effect size was 0.879 (95% CI = 0.838,0.922) (13,254 individuals with ADHD). ADHD is significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self‐controlled studies.

Risk of poisoning in children and adolescents with ADHD: a systematic review and meta-analysis

Poisoning, a subtype of physical injury, is an important hazard in children and youth. Individuals with ADHD may be at higher risk of poisoning. Here, we conducted a systematic review and meta-analysis to quantify this risk. Furthermore, since physical injuries, likely share causal mechanisms with those of poisoning, we compared the relative risk of poisoning and injuries pooling studies reporting both. As per our pre-registered protocol (PROSPERO ID CRD42017079911), we searched 114 databases through November 2017. From a pool of 826 potentially relevant references, screened independently by two researchers, nine studies (84,756 individuals with and 1,398,946 without the disorder) were retained. We pooled hazard and odds ratios using Robust Variance Estimation, a meta-analytic method aimed to deal with non-independence of outcomes. We found that ADHD is associated with a significantly higher risk of poisoning (Relative Risk = 3.14, 95% Confidence Interval = 2.23 to 4.42). Results also indicated that the relative risk of poisoning is significantly higher than that of physical injuries when comparing individuals with and without ADHD (Beta coefficient = 0.686, 95% Confidence Interval = 0.166 to 1.206). These findings should inform clinical guidelines and public health programs aimed to reduce physical risks in children/adolescents with ADHD.