Comparing serially acquired fMRI scans is a typical way to detect functional brain changes in different conditions. However, this approach introduces additional variation on physical and ...physiological conditions, which results in substantial noise. To improve sensitivity and accuracy of signal detection in such highly noisy fMRI data, potentially important information should be incorporated. Here we propose a new significance indicator, the critical regularization value (CR-value), which detects significantly changed voxels by taking both the magnitude of the voxel-wise signal variation and spatial smoothness into account. The CR-value allows voxels that survive in a stronger sparse constraint to be considered as more significant. We demonstrate our method using a simulation dataset and a real fMRI dataset collected from the previous study. The results show that CR-value more accurately detects the true activation than GLM P-value, Posterior Probability Maps (PPM) and the Threshold Free Cluster Enhancement (TFCE) in noisy datasets.
This chapter focuses on the use of diffusion MRI to study individual differences in white matter microstructure in the healthy human brain. White matter pathways play an important role in the human ...brain by connecting spatially separated areas of the central nervous system and enabling rapid and efficient information exchange. Recent developments in magnetic resonance imaging, such as diffusion imaging, have allowed their structural properties to be probed in vivo. With the help of refined imaging and analysis techniques, it has become apparent that these differences are meaningful and can be related to behavioral and functional differences. Even in the brains of non-expert healthy adults, inter-individual variation in gross brain structure is shown to correlate with normal variation in specific behavioral abilities. The complex non-linear dynamics in such a highly connected system as the brain make it difficult to predict the effect of subtle changes in conduction speed, signal attenuation, and frequency spread on its functioning. The current research supports the hypothesis that individual differences in white matter structure are behaviorally relevant and that they can be studied in vivo with diffusion MRI. A better understanding of the behavioral relevance of white matter structure will not only contribute to a better understanding of the healthy brain but also promises to benefit patients recovering from brain injury or illness. In vivo markers of white matter integrity could be used as measures of recovery and responsiveness to treatment. It might also be possible to predict responsiveness to treatment and thereby allow better decisions to be made regarding the most effective treatment strategy.
Among non-motor manifestations of Parkinson's Disease (PD), peripheral, sensory symptoms are particularly relevant. Smell dysfunction starts very early and frequently precedes the PD motor symptoms ...by years (being often a cue to the diagnosis). Moreover, olfactory system could be, together with gut, one of those peripheral sites where PD pathology first develops. Unlike smell loss, the relationship between PD and taste impairment is far less established. It can start early in the course of the disease but more frequently appears in advanced stages, in parallel with the advent of MCI, likely reflecting cortical involvement. Among PD patients has been demonstrated an increase in the frequency of the non-tasters for PROP (prototypical gustatory stimulus, 6- n-propylthiouracil), a genetically determined bitter taste which is mediated by TAS2RS38 receptor, and a significant increase of the recessive non-testing variant of this receptor. TAS2R38 receptors are expressed also in other tissues, such as in the epithelia of the gut and nasal cavities, where they can influence epithelial immunity ad its interaction with microbiota. Those pieces of evidence suggest that not only systematic assessment of taste and smell can be of a remarkable help for clinicians in the early diagnosis, but also that understanding the mechanisms of sensory involvement in PD could increase the knowledge of the pathophysiology of the disease.
Deficits in olfaction are among the most frequent non-motor symptoms in Parkinson's disease (PD) and can be detected early compared with motor symptoms. The reason for the early onset, as well as the ...mechanism involved remains unknown. We aimed to characterize the olfactory performance of patients with PD and age-matched healthy control (HC) participants in association with gender and a specific polymorphism in the odorant-binding protein IIa (OBPIIa) gene, which plays a crucial role in the perception of odors. The olfactory performance was assessed using the odor identification part of the Sniffin' Sticks test in 249 participants (patients with PD: n = 131 and HC participants: n = 118). All participants were genotyped for the rs2590498 polymorphism of the OBPIIa gene, whose major allele A is associated with a higher retronasal perception than the minor allele G. A higher number of men with PD than women with PD exhibited hyposmia. Importantly, OBPIIa gene polymorphism showed an effect on PD-related olfactory deficits only in women. Women with PD carrying two sensitive alleles (AA) showed a better olfactory performance than women with PD with at least one insensitive allele (G); the olfactory scores of the AA genotype women with PD were not different from those of HC participants. In conclusion, our results confirmed a sex effect on the reduced olfactory performance of patients with PD and identified the OBPIIa locus, which may provide a mechanism to determine the risk factor for olfactory deficits in women with PD at the molecular level.
The non-tasting form of the bitter taste receptor, TAS2R38, has been shown as a genetic risk factor associated with the development of Parkinson's disease (PD). Specific taste receptors that are ...expressed in the lower gastrointestinal tract may respond to alteration in gut microbiota composition, detecting bacterial molecules, and regulate immune responses. Given the importance of brain-gut-microbiota axis and gene-environment interactions in PD, we investigate the associations between the genetic variants of TAS2R38 and gut microbiota composition in 39 PD patients. The results confirm that the majority of PD patients have reduced sensitivity to 6-n-propylthiouracil (PROP) and are carriers of at least one non-functional TAS2R38 AVI haplotype. Moreover, we found this correlation to be associated with a reduction in bacteria alpha-diversity with a predominant reduction of Clostridium genus. We hypothesised that the high frequency of the non-taster form of TAS2R38 associated with a diminuition of Clostridium bacteria in PD might determine a reduction in the activation of protective signalling-molecules useful in preserving gut homeostasis. This pilot study, by identifying a decrease in specific bacteria associated with a reduced sensitivity to PROP, adds essential information that opens new avenues of research into the association of PD microbiota composition and sensory modification.
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