Therapeutic use of cerebellar transcranial theta burst magnetic stimulation in movement disorders. Mechanisms of action and biomarkers of efficacy

Movement disorders of different aetiology are characterized by an impairment in several interconnected areas of the motor system. Among the non-pharmacological options to improve motor symptoms, repetitive Transcranial Magnetic Stimulation (rTMS), represent a promising therapeutic tool due to its ability to induce long-term modulation of synaptic plasticity and its low incidence of side effects. Theta burst stimulation (TBS), a patterned protocol of rTMS, is able to induce long lasting excitatory (intermittent TBS) and inhibitory (continuous TBS) effects on cortical excitability and its very tolerable for patients due to its short duration. The high variability of response to TBS limits its use in clinical practice, thus research is focused on the characterization of predictors of response and biomarkers of efficacy. Among these, a common polymorphism of Brain Derived neurotrophic Factor (BDNF) gene, val66met, may influence the onset and progression of several neurodegenerative disorders and may alter the response to different TMS protocols, in particular TBS, but results are conflicting. Cerebellum is considered an interesting area of stimulation for rTMS protocols in movement disorders due to its ability to influence motor learning and control through its connections with all the areas of the motor system and its role in sensory-motor integration. Indeed, it is currently used as a target for neuromodulation in movement disorders involving different pathological mechanisms. The aim of the present study was to test the efficacy of inhibitory and excitatory cerebellar TBS in three movement disorders with different aetiology and to search possible biomarkers influencing its therapeutic effect. In the first project a single session of cerebellar continuous TBS (cTBS) was able to reduce levodopa-induced Dyskinesia in patients affected by Parkinson’s Disease (PD) and this effect was accompanied by a decrease in serum BDNF levels. Moreover, the presence of the Val66Met polymorphism of the BDNF gene was associated with a better response. In the second project 15 sessions of cerebellar intermittent TBS (iTBS) were able to improve motor symptoms in patients affected by Multiple system atrophy (MSA). No variations in serum BDNF levels after iTBS treatment were observed and apparently Val66Met polymorphism did not influence the clinical response. In the third project the excitability of primary motor cortex (M1) was increased by a single session of cerebellar iTBS in patients affected by Spino-Cerebellar ataxia 38 (SCA 38), an inherited disease characterized by mutation in the EVLOV-5 gene. iTBS was then applied for 10 sessions to the cerebellum of patients leading to an improvement of motor symptoms, especially postural stability. The Val66Met polymorphism did not influence the clinical response and the changes in motor cortex excitability. Overall, these data provide evidence for the use of cerebellar TBS in movement disorders; moreover, they suggest that BDNF Val66Met polymorphism may influence response to TBS but results vary depending on experimental model. Finally, they underline that measures of cortical excitability may provide information about the responsivity of the motor network to neuromodulation and may help to select an appropriate therapeutic protocol. Future studies will help to select other genetic, neurophysiological and imaging biomarkers leading to a better prediction and characterization of the clinical response to TBS

Quantitative Characterization of Gait Patterns in Individuals with Spinocerebellar Ataxia 38

Spinocerebellar ataxia 38 (SCA 38) is a rare autosomal neurological disease whose clinical features include, among others, severe gait disturbances that have not yet been fully characterized. In this study, we employed a computerized 3D gait analysis to obtain spatio-temporal parameters of gait and the kinematics in the sagittal plane in the hip, knee, and ankle joints of seven individuals with SCA 38, which were then compared with those of twenty unaffected individuals matched for age, sex, and anthropometric features. The results show that, in comparison with unaffected individuals, those with SCA 38 are characterized by a significantly reduced speed, stride length, and duration of the swing phase, as well as an increased step width and stance and double support phase durations. The point-by-point comparison of the angular trends at the hip, knee, and ankle joints revealed significant alterations during most part of the stance phase for hip joint and at pre-swing/swing phases for knee and ankle joints. For these latter joints, a significantly reduced dynamic range of motion was also found. Such findings provide some new insights into hip and knee kinematics for this specific form of ataxia and may be useful for monitoring the disease’s progression and designing specific, tailored rehabilitative interventions

Sponges architecture by colour: new insights into the fibres morphogenesis, skeletal spatial layout and morpho-anatomical traits of a marine horny sponge species (Porifera)

This paper focuses on the skeletal architecture and morphotraits of the Mediterranean horny sponge Sarcotragus spinosulus (Demospongiae, Keratosa, Dictyoceratida, Irciniidae). This special endoskeletal system consists of a dense, variably complex connective architecture, which extends throughout the entire sponge body and is embedded in an abundant jelly-like extracellular matrix (ECM). To investigate the topographic arrangement and micro-morphotraits of these connective structures in detail and by colour, also during morphogenetic processes, histology techniques using light microscopy are essential. New information is provided on the coordinated morphogenetic processes that characterize the growth and assembly of collagenic prototype structures in the matrix of fibrous skeletal elements and drive skeleton remodelling. Our results also highlight some novelties and some remarkable peculiarities of fibrous, filamentous and fibrillar components at the levels of both composition and structure. The morphofunctional significance of skeletal architecture is suggested in the background of the anatomical complexity of S. spinosulus

Recent Changes in Peatland Testate Amoeba Functional Traits and Hydrology Within a Replicated Site Network in Northwestern Quebec, Canada

Northern peatlands, which are highly heterogeneous ecosystems, are a globally important carbon (C) store. Understanding the drivers and predicting the future trajectory of the peatland C store requires upscaling from cores and sites to regions and continents, alongside a detailed understanding of the mechanisms governing their C sequestration. Studies incorporating replication are therefore important to quantify how peatland heterogeneity may affect upscaling from local-scale dynamics to models. In addition, we need to better understand the processes driving observed variability, but the interplay between plants, microbes and C cycling in peatlands remains poorly understood. One approach to address both issues is to examine replicated microbiological functional traits within a multi-proxy framework to provide an ecosystem-level perspective on ecological and biogeochemical processes. Peatland testate amoebae are a functionally important group of protists that are well suited to such an approach. Analysing testate amoeba functional traits provides an opportunity to examine processes that may affect key peatland ecosystem services, such as C sequestration. Here, we compared four key testate amoeba functional traits (mixotrophy, biovolume, aperture size and aperture position) to C accumulation, hydrological and vegetation changes in 12 post-Little Ice Age peat records. Samples were collected from high-boreal and low-subarctic regions in northwestern Quebec, Canada in an experimental design that includes internal and external replication at both site and regional scales. Our results showed that correspondence between C accumulation, hydrology and testate amoeba functional traits varied, but recent changes in mixotrophy and aperture size, which may affect peatland C sequestration potential and microbial food web structure, respectively, showed tentative links to recent C accumulation increases. Vegetation, especiallySphagnumabundance was important in promoting mixotrophy and small aperture size in testate amoeba communities. Future impacts of climate change on peatland vegetation will further influence the functional role of testate amoebae on C sequestration through changing mixotrophic testate amoeba abundance.Peer reviewe

Newly initiated carbon stock, organic soil accumulation patterns and main driving factors in the High Arctic Svalbard, Norway

High latitude organic soils form a significant carbon storage and deposition of these soils is largely driven by climate. Svalbard, Norway, has experienced millennial-scale climate variations and in general organic soil processes have benefitted from warm and humid climate phases while cool late Holocene has been unfavourable. In addition to direct effect of cool climate, the advancing glaciers have restricted the vegetation growth, thus soil accumulation. Since the early 1900’s climate has been warming at unprecedented rate, assumingly promoting organic soil establishment. Here we present results of multiple organic soil profiles collected from Svalbard. The profiles have robust chronologies accompanied by soil property analyses, carbon stock estimations and testate amoeba data as a proxy for soil moisture. Our results reveal relatively recent initiation of organic soils across the Isfjorden area. The initiation processes could be linked to glacier retreat, and improvement of growing conditions and soil stabilization. Carbon stock analyses suggested that our sites are hot spots for organic matter accumulation. Testate amoebae data suggested drying of soil surfaces, but the reason remained unresolved. If continued, such a process may lead to carbon release. Our data suggest that detailed palaeoecological data from the Arctic is needed to depict the on-going processes and to estimate future trajectories.Peer reviewe