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

Surfactant Aided Reductive Carbonylation of Nitrobenzene inWater Catalyzed by Pd Complexes

The catalytic carbonylation of nitroarenes is a field of high interest from a technological point of view, since provides an environmentally benign route to a number of important industrial products, such as isocyanates, carbamates, ureas, azoarenes and azoxyarenes, amines, amides, oximes and several types of heterocyclic compounds. The reductive carbonylation of nitrobenzene in water carried out by using Pd(II)-solvable catalyst precursors, leads to aniline, as major product. In the present paper we propose the micellar catalytic reductive carbonylation of nitrobenzene in water. The Pd(II) catalyst precursors tested are synthesized by using cheaper commercial insolvable ligands, such as triphenylphosphine (PPh3), 1,3- bis(diphenylphosphino)propane (dppp) and 1, 10-phenantroline (phen). The influence on the conversion and on the selectivity of such precursors has been evaluated in combination with commercial anionic (SDS), cationic (TBAB) and non ionic (Triton X 100) surfactants. We have found that all the Pd(II) complexes tested are efficiently dissolved in each O/W emulsions but the conversion is strongly influenced by the nature of ligand. By using Pd(OAc)2(PPh3)2, high selectivity towards azo- and azo-oxybenzene has been obtained. The influence of some reaction parameters has been further evaluated and optimized

New insights into cortico-basal-cerebellar connectome: clinical and physiological considerations

The current model of the basal ganglia system based on the 'direct', 'indirect' and 'hyperdirect' pathways provides striking predictions about basal ganglia function that have been used to develop deep brain stimulation approaches for Parkinson's disease and dystonia. The aim of this review is to challenge this scheme in light of new tract tracing information that has recently become available from the human brain using MRI-based tractography, thus providing a novel perspective on the basal ganglia system. We also explore the implications of additional direct pathways running from cortex to basal ganglia and between basal ganglia and cerebellum in the pathophysiology of movement disorders

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

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

Cognitive processess and cognitive reserve in multiple sclerosis

Multiple Sclerosis (MS) is characterized by motor, cognitive, and neuropsychiatric symptoms, which can occur independently. While MS is traditionally considered an inflammatory disease of the white matter, degeneration of gray matter is increasingly recognized as an important contributor to the progressive cognitive decline. A protective factor against the progression of cognitive dysfunction in MS could be the cognitive reserve, defined as resistance to brain dysfunction. Aim of the present study is to evaluate the role of cognitive reserve for different aspects of cognitive dysfunction of patients with MS. We found that patients with MS and lower cognitive reserve have poorer neuropsychological performance and slower information speed processing. These findings support the notion that intellectual reserve may protect some aspects of cognitive function in patients with MS

Hydrogenation of nitrobenzene to 4-aminophenol in a fully reusable solvent system, by using Pt, Rh, Pd supported on carbon-CF3COOH catalytic system

4-Aminophenol is an important raw material for several products in the field of dyes, photographs and pharmaceutics. For instance, paracetamol (N-acetyl-4-aminophenol) a widely employed analgesic and antipyretic whose production is in continuous growth specially in the far east region. Industrial synthesis of paracetamol is based mainly on 4-aminophenol, which is obtained by three different routes: i) nucleophilic substitution of the Cl of the 4-chloronitrobenzene, ii) reduction of 4-nitro-phenol, iii) selective hydrogenation of nitrobenzene [1]. The selective hydrogenation of nitrobenzene is however, the most convenient from both economical and environmental point of view [1, 2]. The major concern of this process is, however, the presence of H2SO4, which is origin of corrosion, safety, environmental and separation problems. The reaction is typically carried out in CSTR in which the biphasic reaction medium is used to accomplish simultaneously the Pt catalyzed hydrogenation of nitrobenzene and the acid catalyzed Bamberger rearrangement of the intermediate N-phenylhydroxylamine. From environmental point of view, the major drawback of the process is the neutralization of the acidic phase, with the consequent by-production of sulfate salts, which are undesired wastes. Starting from recent results obtained in the Beckmann rearrangement of the cyclohexanone oxime in CH3CN-CF3COOH system [3], here we show some findings on the hydrogenation of nitrobenzene to 4-aminophenol in a single liquid phase CH3CN-H2O-CF3COOH and in the presence a hydrogenation catalyst. The easy of recovery of solvent and catalysts allows to develop a greener process than that based on the biphasic H2SO4-nitrobenzene syste

Pd(II)-catalyzed emulsion copolymerization of carbon monoxide with ethene in CH2Cl2/water as a solvent

Chemical, physical and mechanical characteristics of alt poly(1-oxo-trimethylene) [1] well fit with a wide range of industrial applications and recently several researchers have shown a renovated keen interest for the application of such a polymer in the field of fibers [2]. In order to obtain fibers, however, high molecular weight polymers are required. In some papers we have reported that high molecular weight polymers require high pressure and low temperature but the nature of the solvent must be considered too [2-4]. The choose of the solvent influences both the activity of the catalyst and the average molecular weight of the polymer. Usually the catalysis is efficiently carried out in methanol by using the [Pd(OAc)2(DPPP)] complex in the presence of an acid (p-toluenesulfonic, TsOH) [5] which leads to polymers with not so high average molecular weight. By replacing methanol with CH3COOH-water also [PdCl2(DPPP)] complex efficiently catalyzes the reaction leading also to an increase of the polymer molecular weight [3]. By continuing the research on the influence of the solvent on the molecular weight, here we report our preliminary results on the preparation of alt- poly(1-oxo-trimethylene) by emulsion catalytic polymerization. The [PdCl2(DPPP)] complex has been dissolved in a CH2Cl2-H2O emulsion and the productivity has been optimized

The catalytic copolymerization of ethene with carbon monoxide efficiently carried out in water/dichloromethane/sodium dodecylsulfate emulsion

The CO-ethene copolymerization has been efficiently carried out in the water/CH2Cl2 emulsion by using water insolvable Pd(II) complexes. By using the surfactant SDS very high molecular weight copolymers have been obtained with high productivity (ca. 13,000 g/(gPd.h))

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