Stimulation over the cerebellum with a regular figure-of-eight coil induces reduced motor cortex inhibition in patients with progressive supranuclear palsy.

OBJECTIVE: To determine whether motor cortex inhibition by stimulation over the cerebellum with a figure-of eight coil (MISC8) may be reduced in patients with Progressive Supranuclear Palsy (PSP). METHODS: Paired pulse TMS was used to evaluate MISC8, in patients with different forms of parkinsonism and dementia. The primary outcome measures were sensitivity and specificity of motor cortex inhibition, derived from receiver operator curve analysis, in discriminating PSP from other neurodegenerative disorders. RESULTS: A total of 150 participants met inclusion criteria. According to clinical criteria, the study population included 19 PSP, 26 Parkinson's disease, 25 dementia with Lewy bodies, 15 corticobasal syndrome, 25 frontotemporal dementia and 15 Alzheimer's disease patients, and 25 healthy controls. PSP patients were characterized by a specific impairment of MISC8 (0.99 ±â€¯0.08) compared to the healthy control group and to other neurodegenerative disorders (mean range = 0.63-0.80, all p-values<0.001). Using the best cut-off index, MISC8 differentiated PSP from other diagnoses with an overall sensitivity of 100%, a specificity of 94%, and an accuracy of 97%. CONCLUSIONS: TMS is a non-invasive procedure which reliably distinguishes PSP from other neurodegenerative disorders. MISC8 could represent a useful additional diagnostic tool to be used in clinical practice.

Structural and functional imaging study in dementia with Lewy bodies and Parkinson's disease dementia.

INTRODUCTION: Dementia with Lewy Bodies (DLB) and Parkinson's disease with Dementia (PDD) are neurodegenerative disorders with complex clinical picture (parkinsonism, cognitive decline and neuropsychiatric disturbances). The conundrum of whether DLB and PDD represent the same or different entities is still under debate. Advanced neuroimaging techniques may represent a point of view to assess brain correlates in DLB and PDD. The study aimed at evaluating whether DLB and PDD may be labelled under the same disease entity or be considered distinctive pathologies. We compared DLB and PDD patients by assessing structural and functional brain imaging and including PD patients. METHODS: Patients with diagnosis of PD, PDD, DLB and a group of healthy controls for neuroimaging comparisons were recruited and changes in structural and resting-state functional MR (Regional Homogeneity, ReHo) were studied. RESULTS: No significant atrophy in VBM analysis was evident in PD. Conversely, PDD showed a significant bilateral frontal atrophy, whereas DLB was characterized by a predominant parietal, occipital atrophy; a similar involvement of subcortical regions in PDD and DLB was observed. ReHo demonstrated reduced local coherence of frontal regions in PD and in PDD, whereas DLB patients presented a reduced local connectivity in posterior regions. CONCLUSION: Different brain areas are specifically involved in PDD and DLB. In the former group, greater atrophy of frontal regions with concomitant functional connectivity impairment was evident; conversely, structural and functional damage in the posterior regions characterized DLB. Despite an overlapping clinical spectrum, DLB and PDD have different networks involved and different underlying pathogenic pathways.

Anodal transcranial direct current stimulation of parietal cortex enhances action naming in Corticobasal Syndrome.

BACKGROUND: Corticobasal Syndrome (CBS) is a neurodegenerative disorder that overlaps both clinically and neuropathologically with Frontotemporal dementia (FTD) and is characterized by apraxia, alien limb phenomena, cortical sensory loss, cognitive impairment, behavioral changes and aphasia. It has been recently demonstrated that transcranial direct current stimulation (tDCS) improves naming in healthy subjects and in subjects with language deficits. OBJECTIVE: The aim of the present study was to explore the extent to which anodal tDCS over the parietal cortex (PARC) could facilitate naming performance in CBS subjects. METHODS: Anodal tDCS was applied to the left and right PARC during object and action naming in seventeen patients with a diagnosis of possible CBS. Participants underwent two sessions of anodal tDCS (left and right) and one session of placebo tDCS. Vocal responses were recorded and analyzed for accuracy and vocal Reaction Times (vRTs). RESULTS: A shortening of naming latency for actions was observed only after active anodal stimulation over the left PARC, as compared to placebo and right stimulations. No effects have been reported for accuracy. CONCLUSIONS: Our preliminary finding demonstrated that tDCS decreased vocal reaction time during action naming in a sample of patients with CBS. A possible explanation of our results is that anodal tDCS over the left PARC effects the brain network implicated in action observation and representation. Further studies, based on larger patient samples, should be conducted to investigate the usefulness of tDCS as an additional treatment of linguistic deficits in CBS patients.

Clozapine-induced alteration of glucose homeostasis in the rat: the contribution of hypothalamic-pituitary-adrenal axis activation.

BACKGROUND/AIMS: To our knowledge, a suitable animal model to investigate how atypical antipsychotics may induce diabetes in patients has not received much attention. METHODS: We investigated the effects of acute as well as subchronic administration of clozapine on food intake, body weight gain, glucose tolerance and insulin secretion in response to glucose in Sprague-Dawley rats. We then evaluated the effects of clozapine on corticosterone secretion and 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) and phosphoenolpyruvate carboxykinase (PEPCK) expression in the liver. We investigated the in vitro effects of clozapine on glucose uptake and development of differentiated myotubes in skeletal muscle cell (C2C12) cultures. RESULTS: Clozapine administration caused hyperglycemia (p < 0.05) in female rats. In male rats, the increase of plasma glucose levels after clozapine injection was not statistically significant. The increase of plasma insulin concentrations and the intraperitoneal glucose tolerance test results proved that clozapine reduced insulin sensitivity in female rats. These endocrine and metabolic effects of clozapine were not related to changes in feeding behavior of fat accumulation. We observed a stimulatory effect of clozapine on corticosterone (p < 0.01) secretion in both female and male rats. Chronic clozapine administration upregulated PEPCK and 11beta-HSD-1 expression in rat liver. Clozapine did not inhibit basal and insulin-induced glucose transport in murine myotubes but it was able to antagonize the stimulatory effect of alpha-methyl-5-hydroxytryptamine on glucose uptake. CONCLUSION: Clozapine induces sex-related alterations of glucose homeostasis and insulin sensitivity in rodents. We discussed the possible contribution of clozapine-induced activation of HPA and clozapine antagonistic activity at peripheral 5-HT(2A) receptors to the observed metabolic alterations.

Cannabinoid receptor antagonists counteract sensorimotor gating deficits in the phencyclidine model of psychosis.

Clinical and laboratory findings suggest that cannabinoids and their receptors are implicated in schizophrenia. The role of cannabinoids in schizophrenia remains however poorly understood, as data are often contradictory. The primary aim of this study was to investigate whether the cannabinoid CB1 receptor antagonists rimonabant and AM251 are able to reverse deficits of sensorimotor gating induced by phencyclidine and to mimic the 'atypical' antipsychotic profile of clozapine. The prepulse inhibition (PPI) of the startle reflex was used to measure deficits of sensorimotor gating. PPI-disruptive effects of phencyclidine and their antagonism by rimonabant, AM251, and clozapine were studied in rats. The effects of rimonabant were carefully examined taking into account dose ranges, vehicle, and route of administration. We also examined the ability of rimonabant to reduce the PPI-disruptive effects of dizocilpine and apomorphine. Rimonabant as well as AM251 significantly counteracted the phencyclidine-disruptive model of PPI, comparable to the restoring effect of clozapine; no augmentation effect was observed with rimonabant and clozapine as cotreatment. Rimonabant also significantly attenuated the PPI disruptive effects of dizocilpine and apomorphine. Taken together, our results indicate that CB1 receptor antagonists do produce 'atypical' antipsychotic profile mimicking that of clozapine in the phencyclidine disruption of sensorimotor gating. Our findings further suggest that CB1 receptor antagonism may be involved in restoring disturbed interactions between the activity of the endocannabinoid system and glutamate neurotransmitter system implied in schizophrenia.