Apraxia and motor dysfunction in corticobasal syndrome

Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS.   Methods: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM.   Results: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/2 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices.   Conclusions: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine

The association of hydration status with physical signs, symptoms and survival in advanced cancer-The use of Bioelectrical Impedance Vector Analysis (BIVA) technology to evaluate fluid volume in palliative care: An observational study

Background Hydration in advanced cancer is a controversial area; however, current hydration assessments methods are poorly developed. Bioelectrical impedance vector analysis (BIVA) is an accurate hydration tool; however its application in advanced cancer has not been explored. This study used BIVA to evaluate hydration status in advanced cancer to examine the association of fluid status with symptoms, physical signs, renal biochemical measures and survival. Materials and methods An observational study of 90 adults with advanced cancer receiving care in a UK specialist palliative care inpatient unit was conducted. Hydration status was assessed using BIVA in addition to assessments of symptoms, physical signs, performance status, renal biochemical measures, oral fluid intake and medications. The association of clinical variables with hydration was evaluated using regression analysis. A survival analysis was conducted to examine the influence of hydration status and renal failure. Results The hydration status of participants was normal in 43 (47.8%), 'more hydrated' in 37 (41.1%) and 'less hydrated' in 10 (11.1%). Lower hydration was associated with increased symptom intensity (Beta = -0.29, p = 0.04) and higher scores for physical signs associated with dehydration (Beta = 10.94, p = 0.02). Higher hydration was associated with oedema (Beta = 2.55, p<0.001). Median survival was statistically significantly shorter in 'less hydrated' patients (44 vs. 68 days; p = 0.049) and in pre-renal failure (44 vs. 100 days; p = 0.003). Conclusions In advanced cancer, hydration status was associated with clinical signs and symptoms. Hydration status and pre-renal failure were independent predictors of survival. Further studies can establish the utility of BIVA as a standardised hydration assessment tool and explore its potential research application, in order to inform the clinical management of fluid balance in patients with advanced cancer

School Effects on the Wellbeing of Children and Adolescents

Well-being is a multidimensional construct, with psychological, physical and social components. As theoretical basis to help understand this concept and how it relates to school, we propose the Self-Determination Theory, which contends that self-determined motivation and personality integration, growth and well-being are dependent on a healthy balance of three innate psychological needs of autonomy, relatedness and competence. Thus, current indicators involve school effects on children’s well-being, in many diverse modalities which have been explored. Some are described in this chapter, mainly: the importance of peer relationships; the benefits of friendship; the effects of schools in conjunction with some forms of family influence; the school climate in terms of safety and physical ecology; the relevance of the teacher input; the school goal structure and the implementation of cooperative learning. All these parameters have an influence in promoting optimal functioning among children and increasing their well-being by meeting the above mentioned needs. The empirical support for the importance of schools indicates significant small effects, which often translate into important real-life effects as it is admitted at present. The conclusion is that schools do make a difference in children’s peer relationships and well-being

Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue. METHODS: Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects. RESULTS: We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects. CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue

Pulse Profile Variability of PSR J1022+1001 in NANOGrav Data

\ua9 2025. The Author(s). Published by the American Astronomical Society.Pulse profile stability is a central assumption of standard pulsar timing methods. Thus, it is important for pulsar timing array experiments such as the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) to account for any pulse profile variability present in their data sets. We show that in the NANOGrav 15 yr data set, the integrated pulse profile of PSR J1022+1001 as seen by the Arecibo radio telescope at 430, 1380, and 2030 MHz varies considerably in its shape from observation to observation. We investigate the possibility that this is due to the “ideal feed assumption” (IFA), on which NANOGrav’s routine polarization calibration procedure relies. PSR J1022+1001 is ∼90% polarized in one pulse profile component, and also has significant levels of circular polarization. Time-dependent deviations in the feed’s polarimetric response (PR) could cause mixing between the intensity I and the other Stokes parameters, leading to the observed variability. We calibrate the PR using a mixture of measurement equation modeling and measurement equation template matching techniques. The resulting profiles are no less variable than those calibrated using the IFA method, nor do they provide an improvement in the timing quality of this pulsar. We observe the pulse shape in 25 MHz bandwidths to vary consistently across the band, which cannot be explained by interstellar scintillation in combination with profile evolution with frequency. Instead, we favor phenomena intrinsic to the pulsar as the cause

Of Asian Forests and European Fields: Eastern U.S. Plant Invasions in a Global Floristic Context

Background: Biogeographic patterns of species invasions hold important clues to solving the recalcitrant ‘who’, ‘where’, and ‘why ’ questions of invasion biology, but the few existing studies make no attempt to distinguish alien floras (all non-native occurrences) from invasive floras (rapidly spreading species of significant management concern), nor have invasion biologists asked whether particular habitats are consistently invaded by species from particular regions. Methodology/Principal Findings: Here I describe the native floristic provenances of the 2629 alien plant taxa of the Eastern Deciduous Forest of the Eastern U.S. (EUS), and contrast these to the subset of 449 taxa that EUS management agencies have labeled ‘invasive’. Although EUS alien plants come from all global floristic regions, nearly half (45%) have native ranges that include central and northern Europe or the Mediterranean (39%). In contrast, EUS invasive species are most likely to come from East Asia (29%), a pattern that is magnified when the invasive pool is restricted to species that are native to a single floristic region (25 % from East Asia, compared to only 11 % from northern/central Europe and 2 % from the Mediterranean). Moreover, East Asian invaders are mostly woody (56%, compared to just 23 % of the total alien flora) and are significantly more likely to invade intact forests and riparian areas than European species, which dominate managed or disturbed ecosystems. Conclusions/Significance: These patterns suggest that the often-invoked ‘imperialist dogma ’ view of global invasion

The Anomalous Acceleration of PSR J2043+1711: Long-period Orbital Companion or Stellar Flyby?

\ua9 2025. The Author(s). Published by the American Astronomical Society.Based on the rate of change of its orbital period, PSR J2043+1711 has a substantial peculiar acceleration of 3.5 \ub1 0.8 mm s-1 yr-1, which deviates from the acceleration predicted by equilibrium Milky Way (MW) models at a 4σ level. The magnitude of the peculiar acceleration is too large to be explained by disequilibrium effects of the MW interacting with orbiting dwarf galaxies (∼1 mm s-1 yr-1), and too small to be caused by period variations due to the pulsar being a redback. We identify and examine two plausible causes for the anomalous acceleration: a stellar flyby, and a long-period orbital companion. We identify a main-sequence star in Gaia DR3 and Pan-STARRS DR2 with the correct mass, distance, and on-sky position to potentially explain the observed peculiar acceleration. However, the star and the pulsar system have substantially different proper motions, indicating that they are not gravitationally bound. However, it is possible that this is an unrelated star that just happens to be located near J2043+1711 along our line of sight (chance probability of 1.6%). Therefore, we also constrain possible orbital parameters for a circumbinary companion in a hierarchical triple system with J2043+1711; the changes in the spindown rate of the pulsar are consistent with an outer object that has an orbital period of 60 kyr, a companion mass of 0.3 M⊙ (indicative of a white dwarf or low-mass star), and a semimajor axis of 1900 au. Continued timing and/or future faint optical observations of J2043+1711 may eventually allow us to differentiate between these scenarios

Estrus cyclicity of spinogenesis: underlying mechanisms

Hippocampal spine density varies with the estrus cycle. The cyclic change in estradiol levels in serum was hypothesized to underlie this phenomenon, since treatment of ovariectomized animals with estradiol induced an increase in spine density in hippocampal dendrites of rats, as compared to ovariectomized controls. In contrast, application of estradiol to hippocampal slice cultures did not promote spinogenesis. In addressing this discrepancy, we found that hippocampal neurons themselves are capable of synthesizing estradiol de novo. Estradiol synthesis can be suppressed by aromatase inhibitors and by knock-down of Steroid Acute Regulatory Protein (StAR) and enhanced by substrates of steroidogenesis. Expression of estrogen receptors (ERs) and synaptic proteins, synaptogenesis, and long-term potentiation (LTP) correlated positively with aromatase activity in hippocampal cultures without any difference between genders. All effects due to inhibition of aromatase activity were rescued by application of estradiol to the cultures. Most importantly, gonadotropin-releasing hormone (GnRH) increased estradiol synthesis dose-dependently via an aromatase-mediated mechanism and consistently increased spine synapse density and spinophilin expression. As a consequence, our data suggest that cyclic fluctuations in spine synapse density result from pulsative release of GnRH from the hypothalamus and its effect on hippocampal estradiol synthesis, rather than from varying levels of serum estradiol. This hypothesis is further supported by higher GnRH receptor (GnRH-R) density in the hippocampus than in the cortex and hypothalamus and the specificity of estrus cyclicity of spinogenesis in the hippocampus, as compared to the cortex