BACKGROUND: There is a lack of automated tools for the segmentation and quantification of neuromelanin (NM) and iron in the nigrosome-1 (N1). Existing tools evaluate the N1 sign, i.e., the presence or absence of the swallow-tail in iron-sensitive MRI, or globally analyze the MRI signal in an area containing the N1, without providing a volumetric delineation.PURPOSE: Present an automated method to segment the N1 and quantify differences in N1's NM and iron content between Parkinson's disease (PD) patients and healthy controls (HCs). Study whether N1 degeneration is clinically related to PD and could be used as a biomarker of the disease.STUDY TYPE: Prospective.SUBJECTS: Seventy-one PD (65.3±10.3years old, 34 female/37 male); 30 HC (62.7±7.8years old, 17 female/13 male).FIELD STRENGTH/SEQUENCE: 3T Anatomical T1-weighted MPRAGE, NM-MRI T1-weighted gradient with magnetization transfer, susceptibility-weighted imaging (SWI).ASSESSMENT: N1 was automatically segmented in SWI images using a multi-image atlas, populated with healthy N1 structures manually annotated by a neurologist. Relative NM and iron content were quantified and their diagnostic performance assessed and compared with the substantia nigra pars compacta (SNc). The association between image parameters and clinically relevant variables was studied.STATISTICAL TESTS: Nonparametric tests were used (Mann-Whitney's U, chi-square, and Friedman tests) at P=0.05.RESULTS: N1's relative NM content decreased and relative iron content increased in PD patients compared with HCs (NM-CRHC =22.55±1.49; NM-CRPD =19.79±1.92; NM-nVolHC =2.69*10-5 ±1.02*10-5 ; NM-nVolPD =1.18*10-5 ±0.96*10-5 ; Iron-CRHC =10.51±2.64; Iron-CRPD =19.35±7.88; Iron-nVolHC = 0.72*10-5 ±0.81*10-5 ; Iron-nVolPD =2.82*10-5 ±2.04*10-5 ). Binary logistic regression analyses combining N1 and SNc image parameters yielded a top AUC=0.955. Significant correlation was found between most N1 parameters and both disease duration (rhoNM-CR =-0.31; rhoiron-CR =0.43; rhoiron-nVol =0.46) and the motor status (rhoNM-nVol =-0.27; rhoiron-CR =0.33; rhoiron-nVol =0.28), suggesting NM reduction along with iron accumulation in N1 as the disease progresses.DATA CONCLUSION: This method provides a fully automatic N1 segmentation, and the analyses performed reveal that N1 relative NM and iron quantification improves diagnostic performance and suggest a relative NM reduction along with a relative iron accumulation in N1 as the disease progresses.EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Neuromelanin (NM) loss in substantia nigra pars compacta (SNc) and locus coeruleus (LC) reflects neuronal death in Parkinson's disease (PD). Since genetically-determined PD shows varied clinical expressivity, we wanted to accurately quantify and locate brainstem NM and iron, to discover whether specific MRI patterns are linked to Leucine-rich repeat kinase 2 G2019S PD (LRRK2-PD) or idiopathic Parkinson's disease (iPD). A 3D automated MRI atlas-based segmentation pipeline (3D-ABSP) for NM/iron-sensitive MRI images topographically characterized the SNc, LC, and red nucleus (RN) neuronal loss and calculated NM/iron contrast ratio (CR) and normalized volume (nVol). Left-side NM nVol was larger in all groups. PD had lower NM CR and nVol in ventral-caudal SNc, whereas iron increased in lateral, medial-rostral, and caudal SNc. The SNc NM CR reduction was associated with psychiatric symptoms. LC CR and nVol discriminated better among subgroups: LRRK2-PD had similar LC NM CR and nVol as that of controls, and larger LC NM nVol and RN iron CR than iPD. PD showed higher iron SNc nVol than controls, especially among LRRK2-PD. ROC analyses showed an AUC > 0.92 for most pairwise subgroup comparisons, with SNc NM being the best discriminator between HC and PD. NM measures maintained their discriminator power considering the subgroup of PD patients with less than 5 years of disease duration. The SNc iron CR and nVol increase was associated with longer disease duration in PD patients. The 3D-ABSP sensitively identified NM and iron MRI patterns strongly correlated with phenotypic PD features.

The human brain undergoes structural and functional changes across the lifespan. The study of motor sequence learning in elderly subjects is of particularly interest since previous findings in young adults might not replicate during later stages of adulthood. The present functional magnetic resonance imaging (fMRI) study assessed the performance, brain activity and functional connectivity patterns associated with motor sequence learning in late middle adulthood. For this purpose, a total of 25 subjects were evaluated during early stages of learning [i.e., fast learning (FL)]. A subset of these subjects (n = 11) was evaluated after extensive practice of a motor sequence [i.e., slow learning (SL) phase]. As expected, late middle adults improved motor performance from FL to SL. Learning-related brain activity patterns replicated most of the findings reported previously in young subjects except for the lack of hippocampal activity during FL and the involvement of cerebellum during SL. Regarding functional connectivity, precuneus and sensorimotor lobule VI of the cerebellum showed a central role during improvement of novel motor performance. In the sample of subjects evaluated, connectivity between the posterior putamen and parietal and frontal regions was significantly decreased with aging during SL. This age-related connectivity pattern may reflect losses in network efficiency when approaching late adulthood. Altogether, these results may have important applications, for instance, in motor rehabilitation programs.

The ability to appropriately perceive distances in activities of daily living, such as driving, is necessary when performing complex maneuvers. With aging, certain driving behaviors and cognitive functions change; however, it remains unknown if egocentric distance perception (EDP) performance is altered and whether its neural activity also changes as we grow older. To that end, 19 young and 17 older healthy adults drove in a driving simulator and performed an functional magnetic resonance imaging (fMRI) experiment where we presented adults with an EDP task. We discovered that (a) EDP task performance was similar between groups, with higher response times in older adults; (b) older adults showed higher prefrontal and parietal activation; and (c) higher functional connectivity within frontal and parietal-occipital-cerebellar networks; and (d) an association between EDP performance and hard braking behaviors in the driving simulator was found. In conclusion, EDP functioning remains largely intact with aging, possibly due to an extended and effective rearrangement in functional brain resources, and may play a role in braking behaviors while driving.

Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the pre-supplementary motor area and the inferior frontal gyrus are key components of the right hemisphere ¿inhibitory network¿. Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson¿s disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, PD patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally and the insula. Using the stop-signal delay as regressor, contralateral underactivation in the right dorsolateral prefrontal cortex, inferior frontal and anterior putamen were found in patients. This finding indicates dysfunction of the right inhibitory network in left-sided PD. Functional connectivity analysis of the left subthalamic nucleus showed a significant increase of connectivity with bilateral insula. In contrast, the right subthalamic nucleus showed increased connectivity with visuomotor and sensorimotor regions of the cerebellum. We conclude that altered inhibitory control in left-sided Parkinson's disease is associated with reduced activation in regions dedicated to inhibition in healthy controls, which then requires engagement of additional regions not observed in controls to successfully stop ongoing actions.

This study presents a short and valid questionnaire for evaluating Facebook usage by the Spanish-speaking population. In order to achieve this aim, the Facebook scales developed by Ellison and collaborators (i.e., Facebook Intensity, Actual Friends, Connection Strategies, and Relationship Maintenance Behavior) were translated into Spanish and then grouped into a 31-item questionnaire: the Spanish Facebook Battery (SFB). Subsequently, the reliability and construct validity of the SFB was tested once administered to a sample of Spanish speakers (N=433) by means of an exploratory factor analysis (EFA) with iterated principal axis factoring and Promax rotation methods. The SFB showed high internal (¿=.89) and acceptable retest (¿=.65) reliability whereas the EFA indicated the retention of five dimensions that explained 89% of the total variance in this sample data. A main dimension related to Facebook Intensity was found to account for almost half of the total variance, whereas the other four dimensions were found to be associated with Online Connection Strategies, Relationship Maintenance Behaviors, Maintaining Connection Strategies, and Offline Connection Strategies. Therefore, the factor analysis returned a dimensional structure of the SFB that differed slightly from the original scales composition, stressing the difference between online and offline connection strategies in this population sample. In summary, this article proposes a short and valid tool which could be useful for assessing Facebook usage among Spanish-speakers. https://rdcu.be/bnCtQ

Introduction: Essential tremor (ET) is one of the most common movement disorders. Despite its high prevalence and heritability, its genetic etiology remains elusive with only a few susceptibility genes identified and poorly replicated. Our aim was to find novel candidate genes involved in ET predisposition through whole exome sequencing. Methods: We studied eight multigenerational families (N = 40 individuals) with an autosomal-dominant inheritance using a comprehensive strategy combining whole exome sequencing followed by case-control association testing of prioritized variants in a separate cohort comprising 521 ET cases and 596 controls. We further performed gene-based burden analyses in an additional dataset comprising 789 ET patients and 770 healthy individuals to investigate whether there was an enrichment of rare deleterious variants within our candidate genes. Results: Fifteen variants co-segregated with disease status in at least one of the families, among which rs749875462 in CCDC183, rs535864157 in MMP10 and rs114285050 in GPR151 showed a nominal association with ET. However, we found no significant enrichment of rare variants within these genes in cases compared with controls. Interestingly, MMP10 protein is involved in the inflammatory response to neuronal damage and has been previously associated with other neurological disorders. Conclusions: We prioritized a set of promising genes, especially MMP10, for further genetic and functional studies in ET. Our study suggests that rare deleterious coding variants that markedly increase susceptibility to ET are likely to be found in many genes. Future studies are needed to replicate and further infer biological mechanisms and potential disease causality for our identified genes.

Background: Increasing clinical and scientific attention is given to the transition of neurological stages from child to adult. Data on brain plasticity during adolescence is interesting for providing adequate evidence-based medical attention to neurological conditions in this population. Acquired aphasia is well described in adults and children, but not in adolescence. Objective: We describe a 5-year follow-up of language in three adolescent subjects with post-brain injury aphasia. Methods: We analysed and scored formal aspects of language three times, language hemispheric dominance twice with dichotic listening test and functional magnetic resonance imaging (fMRI) brain activation patterns that supported expressive and comprehensive language during the recovery period. Results: We found similarities to both paediatric and adult aphasia in these three adolescents. While the level of recovery resembled that of children with aphasia, a more efficient language rehabilitation occurred in those who remained with left hemispheric dominance in the chronic stage, as it is reported in adults. Conclusions: Our analysis and long-term follow-up provide data for a better understanding on how the injured brain matures during adolescence. More studies with larger samples will help to understand the function of the remaining networks and the recovery from injury in this particular age group.

One key aspect of motivation is the ability of agents to overcome excessive weighting of intrinsic subjective costs. This contribution aims to analyze the subjective cost of effort and assess its neural correlates in sedentary volunteers. We recruited a sample of 57 subjects who underwent a decision-making task using a prospective, moderate, and sustained physical effort as devaluating factor. Effort discounting followed a hyperbolic function, and individual discounting constants correlated with an indicator of sedentary lifestyle (global physical activity questionnaire; R = -0.302, P = 0.033). A subsample of 24 sedentary volunteers received a functional magnetic resonance imaging scan while performing a similar effort-discounting task. BOLD signal of a cluster located in the dorsomedial prefrontal cortex correlated with the subjective value of the pair of options under consideration (Z > 2.3, P < 0.05; cluster corrected for multiple comparisons for the whole brain). Furthermore, effort-related discounting of reward correlated with the signal of a cluster in the ventrolateral prefrontal cortex (Z > 2.3, P < 0.05; small volume cluster corrected for a region of interest including the ventral prefrontal cortex and striatum). This study offers empirical data about the intrinsic subjective cost of effort and its neural correlates in sedentary individuals.