Plasticity and dystonia: a hypothesis shrouded in variability.

Studying plasticity mechanisms with Professor John Rothwell was a shared highlight of our careers. In this article, we discuss non-invasive brain stimulation techniques which aim to induce and quantify plasticity, the mechanisms and nature of their inherent variability and use such observations to review the idea that excessive and abnormal plasticity is a pathophysiological substrate of dystonia. We have tried to define the tone of our review by a couple of Professor John Rothwell's many inspiring characteristics; his endless curiosity to refine knowledge and disease models by scientific exploration and his wise yet humble readiness to revise scientific doctrines when the evidence is supportive. We conclude that high variability of response to non-invasive brain stimulation plasticity protocols significantly clouds the interpretation of historical findings in dystonia research. There is an opportunity to wipe the slate clean of assumptions and armed with an informative literature in health, re-evaluate whether excessive plasticity has a causal role in the pathophysiology of dystonia

Optical properties of Ge-oxygen defect center embedded in silica films

The photo-luminescence features of Ge-oxygen defect centers in a 100nm thick Ge-doped silica film on a pure silica substrate were investigated by looking at the emission spectra and time decay detected under synchrotron radiation excitation in the 10-300 K temperature range. This center exhibits two luminescence bands centered at 4.3eV and 3.2eV associated with its de-excitation from singlet (S1) and triplet (T1) states, respectively, that are linked by an intersystem crossing process. The comparison with results obtained from a bulk Ge-doped silica sample evidences that the efficiency of the intersystem crossing rate depends on the properties of the matrix embedding the Ge-oxygen defect centers, being more effective in the film than in the bulk counterpart.Comment: 10 pages, 3 figures, in press on J. Non cryst. solids (2007

Search for noncompetitive 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid receptor (AMPAR) antagonists: Synthesis, pharmacological properties, and computational studies

Abstract The development of new 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor (AMPAR) negative modulators has received considerable interest due to their crucial role in specific neurological diseases. In recent years, our research group has been engaged in the development of new AMPAR ligands and chemical and biological studies of various 2,3-benzodiazepin-4-(thi)ones (CFMs) and their analogous cyclofunctionalized have been reported. Electrophysiological experiments confirmed that their effects are mediated through the AMPAR complex in a selective and noncompetitive fashion. Moreover, we carried out computational studies which suggested the possible binding site for noncompetitive antagonists; we also developed a 3D ligand-based pharmacophore model in order to map common structural features of highly potent compounds. Our hypothesis was successfully used as a frame work for the design of a new class of allosteric modulators containing a tetrahydroisoquinoline skeleton and led to the discovery of a very potent AMPAR antagonist with marked antiepileptic effects

Abnormal plasticity of sensorimotor circuits extends beyond the affected body part in focal dystonia

Objective: To test whether abnormal sensorimotor plasticity in focal hand dystonia is a primary abnormality or is merely a consequence of the dystonic posture. Methods: This study used the paired associative stimulation (PAS) paradigm, an experimental intervention, capable of producing long term potentiation (LTP) like changes in the sensorimotor system in humans. PAS involves transcranial magnetic stimulation combined with median nerve stimulation. 10 patients with cranial and cervical dystonia, who showed no dystonic symptoms in the hand, and nine patients with hemifacial spasm (HFS), a non-dystonic condition, were compared with 10 healthy age matched controls. Motor evoked potential amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in the abductor pollicis brevis and the first dorsal interosseus muscles. Results: Patients with dystonia showed a stronger increase in corticospinal excitability than healthy controls and patients with HFS. In addition, patients with dystonia showed a loss of topographical specificity of PAS induced effects, with a facilitation in both the median and ulnar innervated muscles. While PAS conditioning led to a prolonged CSP in healthy controls and patients with HFS, it had no effect on the duration of the CSP in patients with cranial and cervical dystonia. Conclusion: The data suggests that excessive motor cortex plasticity is not restricted to the circuits clinically affected by dystonia but generalises across the entire sensorimotor system, possibly representing an endophenotypic trait of the disease

Designing a double-coated cathode with high entropy oxides by microwave-assisted hydrothermal synthesis for highly stable Li–S batteries

Nowadays, Li-S batteries are considered as one of the most promising alternatives to Li-ion technology in the near future, thanks to their high specific capacity and their significantly lower environmental impact and production costs. Consequently, many efforts have been directed to tackle with the inherent issues that affect Li-S batteries. One of the main problems is the so-called shuttle effect, which basically entails the unwanted migration of lithium polysulfides (LiPSs) from the cathode to the anode side, causing the degradation of the cell. Here, we report an effective strategy to restrain the shuttle effect and increase the kinetics at the cathode of the lithium-sulfur (Li-S) battery. A functional layer including high entropy oxides (HEO) coated onto the sulfur cathode allows to exploit the HEOs capability as promoter catalysts for the conversion of LiPSs. Pure HEO powders are synthesized by fast, highly efficient microwave irradiation, followed by heat treatment at 930 degrees C. The formation of highly crystalline HEO is confirmed by X-ray diffraction analysis. The LiPSs adsorption capability of HEO is evaluated by UV-vis and X-ray photoelectron spectroscopy analyses. The effect of the HEO-coated sulfur cathode on the electrochemical performance of the Li-S battery is studied by cyclic voltammetry and galvanostatic charge/discharge. The cell with double-coated cathode delivers an initial discharge capacity of 1173 mAh/g at C/10 with 45% capacity retention over 500 cycles at C/5, approaching similar to 99% coulombic efficiency.[GRAPHICS]

Altered dynamics of visual contextual interactions in Parkinson\u27s disease.

Over the last decades, psychophysical and electrophysiological studies in patients and animal models of Parkinson\u27s disease (PD), have consistently revealed a number of visual abnormalities. In particular, specific alterations of contrast sensitivity curves, electroretinogram (ERG), and visual-evoked potentials (VEP), have been attributed to dopaminergic retinal depletion. However, fundamental mechanisms of cortical visual processing, such as normalization or gain control computations, have not yet been examined in PD patients. Here, we measured electrophysiological indices of gain control in both space (surround suppression) and time (sensory adaptation) in PD patients based on steady-state VEP (ssVEP). Compared with controls, patients exhibited a significantly higher initial ssVEP amplitude that quickly decayed over time, and greater relative suppression of ssVEP amplitude as a function of surrounding stimulus contrast. Meanwhile, EEG frequency spectra were broadly elevated in patients relative to controls. Thus, contrary to what might be expected given the reduced contrast sensitivity often reported in PD, visual neural responses are not weaker; rather, they are initially larger but undergo an exaggerated degree of spatial and temporal gain control and are embedded within a greater background noise level. These differences may reflect cortical mechanisms that compensate for dysfunctional center-surround interactions at the retinal level

Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation

AbstractHomeostatic plasticity is thought to stabilize neural activity around a set point within a physiologically reasonable dynamic range. Over the last ten years, a wide range of non-invasive transcranial brain stimulation (NTBS) techniques have been used to probe homeostatic control of cortical plasticity in the intact human brain. Here, we review different NTBS approaches to study homeostatic plasticity on a systems level and relate the findings to both, physiological evidence from in vitro studies and to a theoretical framework of homeostatic function. We highlight differences between homeostatic and other non-homeostatic forms of plasticity and we examine the contribution of sleep in restoring synaptic homeostasis. Finally, we discuss the growing number of studies showing that abnormal homeostatic plasticity may be associated to a range of neuropsychiatric diseases

Visuospatial exploration and art therapy intervention in patients with Parkinson's disease: an exploratory therapeutic protocol

Abstract Though abnormalities of visuospatial function occur in Parkinson's disease, the impact of such deficits on functional independence and psychological wellbeing has been historically under- recognized, and effective treatments for this impairment are unknown. These symptoms can be encountered at any stage of the disease, affecting many activities of daily living, and negatively influencing mood, self-efficacy, independence, and overall quality of life. Furthermore, visuospatial dysfunction has been recently linked to gait impairment and falls, symptoms that are known to be poor prognostic factors. Here, we aim to present an original modality of neurorehabilitation designed to address visuospatial dysfunction and related symptoms in Parkinson's disease, known as "Art Therapy". Art creation relies on sophisticated neurologic mechanisms including shape recognition, motion perception, sensory-motor integration, abstraction, and eye-hand coordination. Furthermore, art therapy may enable subjects with disability to understand their emotions and express them through artistic creation and creative thinking, thus promoting self-awareness, relaxation, confidence and self-efficacy. The potential impact of this intervention on visuospatial dysfunction will be assessed by means of combined clinical, behavioral, gait kinematic, neuroimaging and eye tracking analyses. Potential favorable outcomes may drive further trials validating this novel paradigm of neurorehabilitation

From real to virtual prism adaptation therapy: a systematic review on benefits and challenges of a new potential rehabilitation approach

Prism adaptation (PA) is a sensorimotor technique that has been shown to alleviate neglect symptoms. Due to its demonstrated functional effectiveness, PA has recently been implemented in virtual reality environments. However, research on virtual prism adaptation (VPA) is limited and it lacks a standardized methodological approach. It is crucial to investigate whether VPA can be effective in inducing traditional effect of PA and to have potential utility in a rehabilitation context. Clarifying this aspect would allow the use of VPA in a wider range of contexts and neurological disorders, with the additional opportunity to overcome PA traditional limits. The aim of the present study is to revise current literature on VPA in both healthy individuals and patients highlighting also its advantages and limitations. Studies performed between 2013 and 2023 and fulfilling the inclusion criteria were searched on three electronic databases, by combining the terms “Virtual prism adaptation” and “Virtual prism adaptation therapy. Out of 123 articles, only 16 met the inclusion criteria. The current literature review suggests that VPA may serve as a potentially useful tool for inducing visuomotor adaptation, with most studies conducted in healthy individuals. The high variability in the methodologies observed among studies suggests that more standardized approaches are needed to gain a deeper understanding of the mechanisms underlying adaptation and aftereffects when PA is administered in a virtual environment. Future studies should also address practical applications and clinical efficacy of VPA, particularly in patients with spatial neglect

Protonation-Induced Microphase Separation in Thin Films of a Polyelectrolyte-Hydrophilic Diblock Copolymer

Block copolymers composed of poly(oligo ethylene glycol methyl ether methacrylate) and poly(2-vinylpyridine) are disordered in the neat state but can be induced to order by protonation of the P2VP block, demonstrating a tunable and responsive method for triggering assembly in thin films. Comparison of protonation with the addition of salts shows that microphase separation is due to selective protonation of the P2VP block. Increasing acid incorporation and increasing 2-vinylpyridine content for P2VP minority copolymers both promote increasingly phase-separated morphologies, consistent with protonation increasing the effective strength of segregation between the two blocks. The self-assembled nanostructures formed after casting from acidic solutions may be tuned based on the amount and type of acid incorporation as well as the annealing treatment applied after casting, where both aqueous and polar organic solvents are shown to be effective. Therefore, POEGMA-b-P2VP is a novel ion-containing block copolymer whose morphologies can be facilely tuned during casting and processing by controlling its exposure to acid.United States. Dept. of Energy. Office of Basic Energy Sciences (Award DE-SC0001088)National Science Foundation (U.S.) (Award CMMI-1246740