Centro Clinico Per la Neurostimolazione

Milano, Italy

Centro Clinico Per la Neurostimolazione

Milano, Italy
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Ferrucci R.,Centro Clinico per la Neurostimolazione | Brunoni A.R.,University of Sao Paulo | Parazzini M.,CNR Institute of Biomedical Engineering | Vergari M.,U.O. Neurofisiopatologia | And 8 more authors.
Cerebellum | Year: 2013

Neuroimaging studies suggest that the cerebellum contributes to human cognitive processing, particularly procedural learning. This type of learning is often described as implicit learning and involves automatic, associative, and unintentional learning processes. Our aim was to investigate whether cerebellar transcranial direct current stimulation (tDCS) influences procedural learning as measured by the serial reaction time task (SRTT), in which subjects make speeded key press responses to visual cues. A preliminary modeling study demonstrated that our electrode montage (active electrode over the cerebellum with an extra-cephalic reference) generated the maximum electric field amplitude in the cerebellum. We enrolled 21 healthy subjects (aged 20-49 years). Participants did the SRTT, a visual analogue scale and a visual attention task, before and 35 min after receiving 20-min anodal and sham cerebellar tDCS in a randomized order. To avoid carry-over effects, experimental sessions were held at least 1 week apart. For our primary outcome measure (difference in RTs for random and repeated blocks) anodal versus sham tDCS, RTs were significantly slower for sham tDCS than for anodal cerebellar tDCS (p=0.04), demonstrating that anodal tDCS influenced implicit learning processes. When we assessed RTs for procedural learning across the one to eight blocks, we found that RTs changed significantly after anodal stimulation (interaction time×blocks 1/8: anodal, p=0.006), but after sham tDCS, they remained unchanged (p=0.094). No significant changes were found in the other variables assessed. Our finding that anodal cerebellar tDCS improves an implicit learning type essential to the development of several motor skills or cognitive activity suggests that the cerebellum has a critical role in procedural learning. tDCS could be a new tool for improving procedural learning in daily life in healthy subjects and for correcting abnormal learning in neuropsychiatric disorders.


Parazzini M.,CNR Institute of Electronics, Computer and Telecommunication Engineering | Rossi E.,CNR Institute of Electronics, Computer and Telecommunication Engineering | Rossi E.,Polytechnic of Milan | Ferrucci R.,University of Milan | And 6 more authors.
Clinical Neurophysiology | Year: 2014

Objective: Transcranial Direct Current Stimulation (tDCS) over the cerebellum (or cerebellar tDCS) modulates working memory, changes cerebello-brain interaction, and affects locomotion in humans. Also, the use of tDCS has been proposed for the treatment of disorders characterized by cerebellar dysfunction. Nonetheless, the electric field (E) and current density (J) spatial distributions generated by cerebellar tDCS are unknown. This work aimed to estimate E and J distributions during cerebellar tDCS. Methods: Computational electromagnetics techniques were applied in three human realistic models of different ages and gender. Results: The stronger E and J occurred mainly in the cerebellar cortex, with some spread (up to 4%) toward the occipital cortex. Also, changes by ±1. cm in the position of the active electrode resulted in a small effect (up to 4%) in the E and J spatial distribution in the cerebellum. Finally, the E and J spreads to the brainstem and the heart were negligible, thus further supporting the safety of this technique. Conclusions: Despite inter-individual differences, our modeling study confirms that the cerebellum is the structure mainly involved by cerebellar tDCS. Significance: Modeling approach reveals that during cerebellar tDCS the current spread to other structures outside the cerebellum is unlike to produce functional effects. © 2013 International Federation of Clinical Neurophysiology.


Priori A.,Centro Clinico per la Neurostimolazione | Priori A.,University of Milan | Ciocca M.,Centro Clinico per la Neurostimolazione | Ciocca M.,University of Milan | And 4 more authors.
Journal of Physiology | Year: 2014

Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists. © 2014 The Authors.


Priori A.,Centro Clinico per la Neurostimolazione | Priori A.,University of Milan | Giannicola G.,Centro Clinico per la Neurostimolazione | Giannicola G.,University of Milan | And 6 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2013

Although ample evidence suggests that high-frequency deep brain stimulation (DBS) is an effective therapy in patients with Tourette syndrome (TS), its pathophysiology and the neurophysiological mechanisms underlying these benefits remain unclear. The DBS targets mainly used to date in TS are located within the basal ganglia-thalamo-cortical circuit compromised in this syndrome: the medial and ventral thalamic nuclei, which are way stations within the circuit, the globus pallidus and the nucleus accumbens. Neuronal activity can be electrophysiologically recorded from deep brain structures during DBS surgery (intraoperative microrecordings) or within few days after DBS electrode implantation (local field potentials, LFPs). Recordings from the thalamus in patients with TS showed that the power in low-frequency oscillations (2-15. Hz) was higher than power in high frequency oscillations (<45. Hz) and that activity in gamma band (25-45. Hz) increases when patients' clinical status improved. Effective thalamic DBS for tic reduction seems to increase high frequency band oscillations (25-45. Hz). The same oscillatory pattern persists after DBS for 1. year, therefore showing that in TS DBS does not induce persistent neuroplastic changes in the neural activity in the stimulated structures. Neurophysiological recordings from deep brain structures suggest that tics originate not from the cortex but from neuronal dysfunction in deep brain structures such as the thalamus and globus pallidus. In conclusion, DBS can induce its beneficial effects in TS by modulating specific neural rhythms in the cortico-basal ganglia thalamic network. DBS could reduce tics related increased low-frequency activity by shifting the basal ganglia-thalamic oscillation power to higher frequencies. © 2013 Elsevier Ltd.


Rossi E.,Polytechnic of Milan | Rosa M.,Centro Clinico per la Neurostimolazione | Rossi L.,Centro Clinico per la Neurostimolazione | Priori A.,Centro Clinico per la Neurostimolazione | Marceglia S.,Polytechnic of Milan
Journal of Biomedical Informatics | Year: 2014

Background: The web-based systems available for multi-centre clinical trials do not combine clinical data collection (Electronic Health Records, EHRs) with signal processing storage and analysis tools. However, in pathophysiological research, the correlation between clinical data and signals is crucial for uncovering the underlying neurophysiological mechanisms. A specific example is the investigation of the mechanisms of action for Deep Brain Stimulation (DBS) used for Parkinson's Disease (PD); the neurosignals recorded from the DBS target structure and clinical data must be investigated. Objective: The aim of this study is the development and testing of a new system dedicated to a multi-centre study of Parkinson's Disease that integrates biosignal analysis tools and data collection in a shared and secure environment. Methods: We designed a web-based platform (WebBioBank) for managing the clinical data and biosignals of PD patients treated with DBS in different clinical research centres. Homogeneous data collection was ensured in the different centres (Operative Units, OUs). The anonymity of the data was preserved using unique identifiers associated with patients (ID BAC). The patients' personal details and their equivalent ID BACs were archived inside the corresponding OU and were not uploaded on the web-based platform; data sharing occurred using the ID BACs. The system allowed researchers to upload different signal processing functions (in a .dll extension) onto the web-based platform and to combine them to define dedicated algorithms. Results: Four clinical research centres used WebBioBank for 1. year. The clinical data from 58 patients treated using DBS were managed, and 186 biosignals were uploaded and classified into 4 categories based on the treatment (pharmacological and/or electrical). The user's satisfaction mean score exceeded the satisfaction threshold. Conclusions: WebBioBank enabled anonymous data sharing for a clinical study conducted at multiple centres and demonstrated the capabilities of the signal processing chain configuration as well as its effectiveness and efficiency for integrating the neurophysiological results with clinical data in multi-centre studies, which will allow the future collection of homogeneous data in large cohorts of patients. © 2014 Elsevier Inc.


Rosa M.,Centro Clinico per la Neurostimolazione | Giannicola G.,Centro Clinico per la Neurostimolazione | Marceglia S.,Centro Clinico per la Neurostimolazione | Marceglia S.,Polytechnic of Milan | And 4 more authors.
International Review of Neurobiology | Year: 2012

We review the data concerning the neurophysiology of deep brain stimulation (DBS) in humans, especially in reference to Parkinson's disease. The electric field generated by DBS interacts with the brain in complex ways, and several variables could influence the DBS-induced biophysical and clinical effects. The neurophysiology of DBS comprises the DBS-induced effects per se as well as neurophysiological studies designed to record electrical activity directly from the basal ganglia (single-unit or local field potential) through the electrodes implanted for DBS. In the subthalamic nucleus, DBS locally excites and concurrently inhibits at single-unit level, synchronizes low-frequency activity, and desynchronizes beta activity and also induces neurochemical changes in cyclic guanosine monophosphate (cGMP) and GABA concentrations. DBS-induced effects at system level can be studied through evoked potentials, autonomic tests, spinal cord segmental system, motor cortical and brainstem excitability, gait, and decision-making tasks. All these variables are influenced by DBS, suggesting also distant effects on nonmotor structures of the brain. Last, advances in understanding the neurophysiological mechanisms underlying DBS led researchers to develop a new adaptive DBS technology designed to adapt stimulation settings to the individual patient's clinical condition through a closed-loop system controlled by signals from the basal ganglia. © 2012 Elsevier Inc.


Giannicola G.,Centro Clinico per la Neurostimolazione | Marceglia S.,Centro Clinico per la Neurostimolazione | Rossi L.,Centro Clinico per la Neurostimolazione | Mrakic-Sposta S.,Centro Clinico per la Neurostimolazione | And 6 more authors.
Experimental Neurology | Year: 2010

Local field potentials (LFPs) recorded through electrodes implanted in the subthalamic nucleus (STN) for deep brain stimulation (DBS) in patients with Parkinson's disease (PD) show that oscillations in the beta frequency range (8-20. Hz) decrease after levodopa intake. Whether and how DBS influences the beta oscillations and whether levodopa- and DBS-induced changes interact remains unclear. We examined the combined effect of levodopa and DBS on subthalamic beta LFP oscillations, recorded in nine patients with PD under four experimental conditions: without levodopa with DBS turned off; without levodopa with DBS turned on; with levodopa with DBS turned on; and with levodopa with DBS turned off. The analysis of STN-LFP oscillations showed that whereas levodopa abolished beta STN oscillations in all the patients (p= 0.026), DBS significantly decreased the beta oscillation only in five of the nine patients studied (p= 0.043). Another difference was that whereas levodopa completely suppressed beta oscillations, DBS merely decreased them. When we combined levodopa and DBS, the levodopa-induced beta disruption prevailed and combining levodopa and DBS induced no significant additive effect (p=0.500). Our observations suggest that levodopa and DBS both modulate LFP beta oscillations. © 2010 Elsevier Inc.


Monti A.,University of Trento | Ferrucci R.,Centro Clinico Per la Neurostimolazione | Ferrucci R.,University of Milan | Fumagalli M.,Centro Clinico Per la Neurostimolazione | And 6 more authors.
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2013

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia.


Boggio P.S.,Mackenzie Presbyterian University | Ferrucci R.,Centro Clinico per la Neurostimolazione | Ferrucci R.,University of Milan | Mameli F.,Centro Clinico per la Neurostimolazione | And 8 more authors.
Brain Stimulation | Year: 2012

Background: Immediately after patients with Alzheimer's disease (AD) receive a single anodal transcranial direct current stimulation (tDCS) session their memory performance improves. Whether multiple tDCS sessions improve memory performance in the longer term remains unclear. Objective: In this study we aimed to assess memory changes after five consecutive sessions of anodal tDCS applied over the temporal cortex in patients with AD. Methods: A total of 15 patients were enrolled in two centers. Cognitive functions were evaluated before and after therapeutic tDCS. tDCS was delivered bilaterally through two scalp anodal electrodes placed over the temporal regions and a reference electrode over the right deltoid muscle. The stimulating current was set at 2 mA intensity and was delivered for 30 minutes per day for 5 consecutive days. Results: After patients received tDCS, their performance in a visual recognition memory test significantly improved. We found a main effect of tDCS on memory performance, i.e., anodal stimulation improved it by 8.99% from baseline, whereas sham stimulation decreased it by 2.62%. tDCS failed to influence differentially general cognitive performance measures or a visual attention measure. Conclusions: Our findings show that after patients with AD receive anodal tDCS over the temporal cerebral cortex in five consecutive daily sessions their visual recognition memory improves and the improvement persists for at least 4 weeks after therapy. These encouraging results provide additional support for continuing to investigate anodal tDCS as an adjuvant treatment for patients with AD. © 2012 Elsevier Inc. All rights reserved.


Ferrucci R.,Centro Clinico per la Neurostimolazione | Ferrucci R.,University of Milan | Cortese F.,Centro Clinico per la Neurostimolazione | Priori A.,Centro Clinico per la Neurostimolazione | Priori A.,University of Milan
Cerebellum | Year: 2015

Cerebellar transcranial direct current stimulation (cerebellar tDCS) is a non-invasive technique for inducing prolonged functional changes in the human cerebellum. Available data show that this simple and safe technique can modulate several motor and non-motor cerebellar functions in healthy humans. Also, preliminary data suggest that cerebellar tDCS is a possible therapeutic option in patients with cerebellar disorders. To provide a reference for those approaching this technique for the first time in healthy humans and patients, we here briefly and practically review the methodology for cerebellar tDCS, discussing electrode types, positions, DC duration and intensity. Recent modelling studies confirm that the electric field generated with the methodology reviewed here reaches the cerebellum at a strength within the range of values for modulating activity in the cerebellar neurons experimentally assessed. © 2014, The Author(s).

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