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Carrillo F.,Hospital Universitario Virgen Del Rocio | Palomar F.J.,Hospital Universitario Virgen Del Rocio | Palomar F.J.,Research Center Biomedica en Red sobre Enfermedades Neurodegenerativas | Conde V.,Hospital Universitario Virgen Del Rocio | And 7 more authors.
Brain Stimulation | Year: 2013

Background: Although functional changes in the activation of the cerebellum in Parkinson's disease (PD) patients have been consistently described, it is still debated whether such altered cerebellar activation is a natural consequence of PD pathophysiology or rather it involves compensatory mechanisms. Objective/Hypothesis: We used different forms of cerebellar transcranial magnetic stimulation to evaluate the hypothesis that altered cerebello-cortical interactions can be observed in PD patients and to evaluate the role of dopaminergic treatment. Methods: We studied the effects of a single cerebellar magnetic pulse over the excitability of the contralateral primary motor cortex tested with motor-evoked potentials (MEPs) (cerebellar-brain inhibition - CBI) in a group of 16 PD patients with (ON) and without dopaminergic treatment (OFF), and in 16 age-matched healthy controls. Moreover, we also tested the effects of cerebellar continuous theta-burst stimulation (cTBS) on MEP amplitude, short intracortical inhibition (SICI) and short intracortical facilitation (SICF) tested in the contralateral M1 in 13 PD patients in ON and OFF and in 16 age-matched healthy controls. Results: CBI was evident in controls but not in PD patients, even when tested in both ON and OFF conditions. Similarly, cerebellar cTBS reduced MEP amplitude and SICI in controls but not in PD patients under any condition. Conclusion(s): These results demonstrate that PD patients have deficient short-latency and long-lasting cerebellar-thalamocortical inhibitory interactions that cannot be promptly restored by standard dopaminergic medication. © 2013 Elsevier Inc. All rights reserved.

Koch G.,Laboratorio Of Neurologia Clinica E Comportamentale | Koch G.,University of Rome Tor Vergata
Restorative Neurology and Neuroscience | Year: 2010

Long-term therapy with levodopa and dopamine agonists in Parkinson's disease (PD) patients is complicated by the development of fluctuations in motor response, such as levo-dopa induced dyskinesia (LID). Repetitive Transcranial Magnetic Stimulation (rTMS) has been recently put forward as a possible therapeutic tool able to LID in PD. Trains of 1 Hz rTMS applied either over the supplementary motor area (SMA) or the primary motor cortex (M1) were able to induce a transient reduction in the severity of LID, confirming that an over-activity of these areas plays a crucial role in the pathophysiology of LID. However, repeated sessions of rTMS were not effective in inducing persistent beneficial clinical effects. Functional or metabolic changes have been reported in the cerebellum in studies in PD patients treated with procedures known to alleviate LID, such as deep brain stimulation. Therefore, the effects of rTMS applied over the lateral cerebellum has been recently tested in patients with LID. A two-week course of bilateral cerebellar rTMS induced persistent clinical beneficial effects, reducing peak-dose LID for up to four weeks after the end of the daily stimulation period. These findings demonstrate that rTMS is a potential tool in individuating the best cortical targets and the optimal parameters of stimulation able to improve LID in dyskinetic PD patients. © 2010 IOS Press and the authors. All rights reserved.

Koch G.,Laboratorio Of Neurologia Clinica E Comportamentale | Koch G.,University of Rome Tor Vergata
Functional Neurology | Year: 2010

Non-invasive brain stimulation methods, such as repetitive transcranial magnetic stimulation (rTMS), are currently used to modulate the excitability of the cerebral cortex, providing important insights into mechanisms of cortical plasticity. Used to create long-lasting changes in the excitability of synapses, rTMS has been intensively investigated as a therapeutic tool in several neurological and psychiatric conditions and given some promising results. Recent studies have shown that rTMS of cerebellar structures is capable of inducing long-lasting changes in the excitability of cerebellothalamo-cortical pathways. Thus, this novel approach may be important for investigating the functions of cerebellar plasticity. Indeed, cerebellar rTMS has been shown to modulate motor control, cognitive functions, emotion and mood. Moreover, recent studies seem to indicate that long-lasting modifications of cerebellar pathways could be usefully exploited in the treatment of several pathological conditions characterized by altered cortical excitability, such as Parkinson's disease, stroke, depression and schizophrenia. The high potential of cerebellar rTMS as a therapeutic tool in neurology could depend on the possibility of modulating several interconnected remote areas, through the activation of different systems, such as the cerebello-thalamo-cortical and limbic-thalamo-cortical networks. © CIC Edizioni Internazionali.

Cerasa A.,National Research Council Italy | Fasano A.,University of Toronto | Morgante F.,Messina University | Koch G.,Laboratorio Of Neurologia Clinica E Comportamentale | And 2 more authors.
Frontiers in Neurology | Year: 2014

Maladaptive plasticity can be defined as behavioral loss or even development of disease symptoms resulting from aberrant plasticity changes in the human brain. Hyperkinetic movement disorders, in the neurological or psychiatric realms, have been associated with maladaptive neural plasticity that can be expressed by functional changes such as an increase in transmitter release, receptor regulation, and synaptic plasticity or anatomical modifications such as axonal regeneration, sprouting, synaptogenesis, and neurogenesis. Recent evidence from human and animal models provided support to the hypothesis that these phenomena likely depend on altered dopamine turnover induced by long-term drug treatment. However, it is still unclear how and where these altered mechanisms of cortical plasticity may be localized. This study provides an up-to-date overview of these issues together with some reflections on future studies in the field, particularly focusing on two specific disorders (levodopa-induced dyskinesias in Parkinson's disease patients and tardive dyskinesias in schizophrenic patients) where the modern neuroimaging approaches have recently provided new fundamental insights. © 2014 Cerasa, Fasano, Morgante, Koch and Quattrone.

Fogelson N.,University of La Coruna | Ribolsi M.,University of Rome Tor Vergata | Fernandez-Del-Olmo M.,University of La Coruna | Rubino I.A.,University of Rome Tor Vergata | And 4 more authors.
Psychophysiology | Year: 2011

Deficits in processing contextual information are one of the main features of cognitive dysfunction in schizophrenia, but the neurophysiologic substrate underlying this dysfunction is poorly understood. We used ERPs to investigate local contextual processing in schizophrenic patients. Local context was defined as the occurrence of a short predictive series of stimuli occurring before delivery of a target event. Response times of predicted targets were faster in controls compared to patients. Schizophrenia patients failed to generate the P3b latency shift between predicted and random targets that was observed in controls and demonstrated a prominent reduction of the peak of an early latency context dependent positivity. The current study provides evidence of contextual processing deficits in schizophrenia patients by demonstrating alteration in the behavioral and neural correlates of local contextual processing.© 2011 Society for Psychophysiological Research.

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