Transcranial magnetic stimulation and epilepsy.

Epileptic conditions are characterized by an altered balance between excitatory and inhibitory influences at the cortical level. Transcranial magnetic stimulation (TMS) provides a noninvasive evaluation of separate excitatory and inhibitory functions of the cerebral cortex. In addition, repetitive TMS (rTMS) can modulate the excitability of cortical networks. We review the different ways that TMS has been used to investigate pathophysiological mechanisms and effects of antiepileptic drugs in patients with epilepsy and epileptic myoclonus. The safety of different TMS techniques is discussed too. Finally, we discuss the therapeutic prospects of rTMS in this field.     

Involvement of the parietal cortex in perceptual learning (Eureka effect): An interference approach using rTMS

The neural mechanisms underlying perceptual learning are still under investigation. Eureka effect is a form of rapid, long-lasting perceptual learning by which a degraded image, which appears meaningless when first seen, becomes recognizable after a single exposure to its undegraded version. We used online interference by focal 10-Hz repetitive transcranial magnetic stimulation (rTMS) to evaluate whether the parietal cortex (PC) is involved in Eureka effect, as suggested by neuroimaging data. RTMS of the PC did not affect recognition of degraded pictures when displayed 2 s after the presentation of their undegraded version (learning phase). However, rTMS delivered over either right or left intraparietal sulcus simultaneously to the undegraded image presentation, disrupted identification of the degraded version of the same pictures when displayed 30 min after the learning phase. In contrast, recognition of degraded images was unaffected by rTMS over the vertex or by sham rTMS, or when rTMS of either PC was delivered 2 s after the presentation of the undegraded image. Findings strongly support the hypothesis that both PC at the level of the intraparietal sulcus play a pivotal role in the Eureka effect particularly in consolidation processes, and contribute to elucidate the neural network underlying rapid perceptual learning.     

Properly timed injections of cortisol and prolactin produce long-term reductions in obesity, hyperinsulinaemia and insulin resistance in the Syrian hamster (Mesocricetus auratus)

Naturally obese female Syrian hamsters were injected daily with prolactin at 0 or 12 h after cortisol injections for 10 days while held in constant light. Controls were similarly injected with saline. Animals were then held on short daylengths (10 h light:14 h darkness) for 10 weeks. They were allowed free access to food and water from birth to time of death. Ten weeks after treatment, retroperitoneal fat stores, plasma concentrations of insulin and glucose, and hypoglycaemic responsiveness to exogenous insulin were determined. The control groups as well as the 12-h hormone treatment group were obese, hyperinsulinaemic and insulin resistant. However, the 0-h treatment dramatically reduced retroperitoneal fat stores (41-55%), plasma insulin concentration (60-70%) and the insulin to glucose ratio (63-68%) compared with controls. Values for these parameters in the 0-h treatment groups were similar to those of their lean litter-mates. Furthermore, the 0-h group but not the 12-h group was more sensitive than control animals to the hypoglycaemic effects of exogenous insulin at doses 0.2 and 2.0 U/kg body weight. These results demonstrate that timed daily injections of cortisol and prolactin in specific temporal relationships can produce marked reductions in obesity, hyperinsulinaemia and insulin resistance in the Syrian hamster that persist long after the termination of treatment. This study also suggests an important role for the interactions of circadian neuroendocrine systems in the regulation of these metabolic states.     

FTIR Microanalysis and Phase Behaviour of Ethylene/1‐Hexene Random Copolymers

Ethylene/1‐hexene random copolymers with 1‐hexene content in the range of 1–5 mol‐%, synthesised in the presence of new heterogeneous catalyst systems based on bis‐carboxylato and ‐bis‐chloro‐carboxylato titanium chelate complexes, have been characterised by FTIR microspectroscopy (FTIR‐M), DSC calorimetry and X‐ray scattering. The co‐monomer content and sequence distribution in the various samples were determined by means of both FTIR‐M and ¹³C NMR spectroscopy. The deformation bands of methyl groups in the region of 1 400–1 330 cm^?1 were used for the structural analysis of these copolymers. The effect of composition on the crystallinity and phase transitions of copolymers was analysed both in 1 500–1 300 and 760–690 cm^?1 frequency ranges as a function of the annealing temperature. A neat variation of the absorbance ratio of methyl band at 1 378 cm^?1 was recorded between 110 and 130 °C corresponding to the melting range of the copolymer crystals. The crystallisation behaviour of the copolymers was examined by DSC in dynamic and isothermal conditions; the isothermal kinetics were analysed according to the Avrami model. A marked decrease in the bulk crystallisation rate, accompanied by changes in the nucleation and growth of crystals, was found with an increase in the co‐monomer content. The melting behaviour of isothermally crystallised samples was also investigated and the melting temperatures of the copolymers at equilibrium conditions were related to the composition; the experimental data were consistent with the Flory exclusion model of side branches from the crystalline phase. The lowering of crystal growth rate in the copolymers has been accounted for by an increase in the free energy of formation of critical size nuclei due to the effect of the side branches.

     

Atrio-ventricular block during left atrial flutter ablation

We present a case of a patient treated with catheter ablation for atrial fibrillation aiming to pulmonary veins isolation. During ablation, atrial fibrillation organized into a left atrial flutter. Electroanatomic and electrophysiologic mapping revealed the anterior left atrium area between the mitral annulus and left atrium septum as a critical region for flutter ablation. After a few pulses of radiofrequency, complete atrio-ventricular block appeared. Finally, we propose pace mapping of the mitral annulus to detect left dislodgment of the compact atrio-ventricular node.     

Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor

GPR37 is an orphan G protein-coupled receptor expressed in mammalian brain, and its insoluble aggregates are found in the brain samples of juvenile Parkinson's disease patients. We have produced a Gpr37 knock-out mouse strain and identified several phenotypic features that are similar to those reported for mutants of genes encoding components of synaptic dopamine vesicles. Our results reveal an unanticipated role of GPR37 in regulating substantia nigra-striatum dopaminergic signaling. Gpr37(-/-) mice are viable, with normal brain development and anatomy, but they exhibit reduced striatal dopamine content, enhanced amphetamine sensitivity, and specific deficits in motor behavior paradigms sensitive to nigrostriatal dysfunction. These functional alterations are not associated with any substantial loss of substantia nigra neurons or degeneration of striatal dopaminergic afferences, the main histological marks of Parkinson's disease. The inactivation of GPR37, in fact, has protective effects on substantia nigra neurons, causing resistance to treatment with the Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.     

Abnormal motor cortex excitability during linguistic tasks in adductor‐type spasmodic dysphonia

In healthy subjects (HS), transcranial magnetic stimulation (TMS) applied during ‘linguistic’ tasks discloses excitability changes in the dominant hemisphere primary motor cortex (M1). We investigated ‘linguistic’ task‐related cortical excitability modulation in patients with adductor‐type spasmodic dysphonia (ASD), a speech‐related focal dystonia. We studied 10 ASD patients and 10 HS. Speech examination included voice cepstral analysis. We investigated the dominant/non‐dominant M1 excitability at baseline, during ‘linguistic’ (reading aloud/silent reading/producing simple phonation) and ‘non‐linguistic’ tasks (looking at non‐letter strings/producing oral movements). Motor evoked potentials (MEPs) were recorded from the contralateral hand muscles. We measured the cortical silent period (CSP) length and tested MEPs in HS and patients performing the ‘linguistic’ tasks with different voice intensities. We also examined MEPs in HS and ASD during hand‐related ‘action‐verb’ observation. Patients were studied under and not‐under botulinum neurotoxin‐type A (BoNT‐A). In HS, TMS over the dominant M1 elicited larger MEPs during ‘reading aloud’ than during the other ‘linguistic’/‘non‐linguistic’ tasks. Conversely, in ASD, TMS over the dominant M1 elicited increased‐amplitude MEPs during ‘reading aloud’ and ‘syllabic phonation’ tasks. CSP length was shorter in ASD than in HS and remained unchanged in both groups performing ‘linguistic’/‘non‐linguistic’ tasks. In HS and ASD, ‘linguistic’ task‐related excitability changes were present regardless of the different voice intensities. During hand‐related ‘action‐verb’ observation, MEPs decreased in HS, whereas in ASD they increased. In ASD, BoNT‐A improved speech, as demonstrated by cepstral analysis and restored the TMS abnormalities. ASD reflects dominant hemisphere excitability changes related to ‘linguistic’ tasks; BoNT‐A returns these excitability changes to normal.