Fondazione Alberto Sordi Research Institute for Ageing

Rome, Italy

Fondazione Alberto Sordi Research Institute for Ageing

Rome, Italy
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Di Lazzaro V.,Biomedical University of Rome | Di Lazzaro V.,Fondazione Alberto Sordi Research Institute for Ageing | Rothwell J.C.,University College London | Talelli P.,University College London | And 9 more authors.
Neuroscience Letters | Year: 2013

Non-invasive brain stimulation is presently being tested as a potential therapeutic intervention for stroke rehabilitation. Following a model of competitive interactions between the hemispheres, these interventions aim to increase the plasticity of stroke hemisphere by applying either excitatory protocols to the damaged hemisphere or inhibitory protocols to the non-stroke hemisphere. Here we test the safety and feasibility of using an inhibitory protocol on the stroke hemisphere to improve the response to conventional therapy via a homeostatic increase in learning capacity. Twelve chronic stroke patients received TBS to stroke hemisphere (6 patients inhibitory TBS and 6 sham TBS) followed by physical therapy daily for 10 working days. Patients and therapists were blinded to the type of TBS. Action Research Arm Test (ARAT), Nine-Hole Pegboard Test (NHPT) and Jebsen-Taylor Test (JTT) were the primary outcome measures, grip and pinch-grip dynamometry were the secondary outcome measures. All patients improved ARAT and JTT scores for up to 3 months post-treatment. ARAT scores improved significantly in both real and sham groups, but only patients receiving real TBS significantly improved on the JTT: 3 months post-treatment mean execution time was reduced compared to baseline by 141. s for real group and by 65. s for the sham group. This small exploratory study suggests that ipsilesional inhibitory TBS is safe and that it has the potential to be used in a larger trial to enhance the gain from a late rehabilitation program in chronic stroke patients. © 2013 Elsevier Ireland Ltd.


Di Lazzaro V.,Biomedical University of Rome | Di Lazzaro V.,Fondazione Alberto Sordi Research Institute for Ageing | Pellegrino G.,Biomedical University of Rome | Pellegrino G.,Montreal Neurological Institute | And 9 more authors.
Frontiers in Neuroscience | Year: 2016

The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization. We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH) and unaffected hemisphere (UH) by measuring resting and active motor threshold (AMT) and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS) of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI), to evidence hemispheric asymmetry. AMT differed significantly between AH and UH only in the male group (p = 0.004), not in females (p > 0.200), and both LIAMT and LIRMT were significantly higher in males than in females (respectively p = 0.033 and p = 0.042). LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery. © 2016 Di Lazzaro, Pellegrino, Di Pino, Ranieri, Lotti, Florio and Capone.


Di Lazzaro V.,Biomedical University of Rome | Di Lazzaro V.,Fondazione Alberto Sordi Research Institute for Ageing | Capone F.,Biomedical University of Rome | Capone F.,Fondazione Alberto Sordi Research Institute for Ageing | And 17 more authors.
Frontiers in Neuroscience | Year: 2016

Previous studies suggested that both robot-assisted rehabilitation and non-invasive brain stimulation can produce a slight improvement in severe chronic stroke patients. It is still unknown whether their combination can produce synergistic and more consistent improvements. Safety and efficacy of this combination has been assessed within a proof-of-principle, double-blinded, semi-randomized, sham-controlled trial. Inhibitory continuous Theta Burst Stimulation (cTBS) was delivered on the affected hemisphere, in order to improve the response to the following robot-assisted therapy via a homeostatic increase of learning capacity. Twenty severe upper limb-impaired chronic stroke patients were randomized to robot-assisted therapy associated with real or sham cTBS, delivered for 10 working days. Eight real and nine sham patients completed the study. Change in Fugl-Meyer was chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes. The treatment was well-tolerated by the patients and there were no adverse events. All patients achieved a small, but significant, Fugl-Meyer improvement (about 5%). The difference between the real and the sham cTBS groups was not significant. Among several secondary end points, only the Success Rate (percentage of targets reached by the patient) improved more in the real than in the sham cTBS group. This study shows that a short intensive robot-assisted rehabilitation produces a slight improvement in severe upper-limb impaired, even years after the stroke. The association with homeostatic metaplasticity-promoting non-invasive brain stimulation does not augment the clinical gain in patients with severe stroke. © 2016 Di Lazzaro, Capone, Di Pino, Pellegrino, Florio, Zollo, Simonetti, Ranieri, Brunelli, Corbetto, Miccinilli, Bravi, Milighetti, Guglielmelli and Sterzi.


Pellegrino G.,Biomedical University of Rome | Pellegrino G.,Fondazione Alberto Sordi Research Institute for Ageing | Pellegrino G.,Montreal Neurological Institute | Tombini M.,Biomedical University of Rome | And 11 more authors.
Clinical EEG and Neuroscience | Year: 2017

Introduction. We aimed to test differences between healthy subjects and patients with respect to slow wave activity during wakefulness and sleep. Methods. Fifteen patients affected by nonlesional focal epilepsy originating within temporal areas and fourteen matched controls underwent a 24-hour EEG recording. We studied the EEG power spectral density during wakefulness and sleep in delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (12-15 Hz), and beta (16-20 Hz) bands. Results. During sleep, patients with focal epilepsy showed higher power from delta to beta frequency bands compared with controls. The effect was widespread for alpha band and above, while localized over the affected hemisphere for delta (sleep cycle 1, P =.006; sleep cycle 2, P =.008; sleep cycle 3, P =.017). The analysis of interhemispheric differences showed that the only frequency band stronger over the affected regions was the delta band during the first 2 sleep cycles (sleep cycle 1, P =.014; sleep cycle 2, P =.002). During wakefulness, patients showed higher delta/theta activity over the affected regions compared with controls. Conclusions. Patients with focal epilepsy showed a pattern of power increases characterized by a selective slow wave activity enhancement over the epileptic regions during daytime and sleep. This phenomenon was stronger and asymmetric during the first sleep cycles. © EEG and Clinical Neuroscience Society.


Suppa A.,University of Rome La Sapienza | Suppa A.,Neuromed Institute | Huang Y.Z.,Chang Gung University | Funke K.,Ruhr University Bochum | And 6 more authors.
Brain Stimulation | Year: 2016

Background/objectives: Over the last ten years, an increasing number of authors have used the theta burst stimulation (TBS) protocol to investigate long-term potentiation (LTP) and long-term depression (LTD)-like plasticity non-invasively in the primary motor cortex (M1) in healthy humans and in patients with various types of movement disorders. We here provide a comprehensive review of the LTP/LTD-like plasticity induced by TBS in the human M1. Methods: A workgroup of researchers expert in this research field review and discuss critically ten years of experimental evidence from TBS studies in humans and in animal models. The review also includes the discussion of studies assessing responses to TBS in patients with movement disorders. Main findings/discussion: We discuss experimental studies applying TBS over the M1 or in other cortical regions functionally connected to M1 in healthy subjects and in patients with various types of movement disorders. We also review experimental evidence coming from TBS studies in animals. Finally, we clarify the status of TBS as a possible new non-invasive therapy aimed at improving symptoms in various neurological disorders. © 2016 Elsevier Inc.


Di Lazzaro V.,Biomedical University of Rome | Di Lazzaro V.,Fondazione Alberto Sordi Research Institute for Ageing | Capone F.,Biomedical University of Rome | Capone F.,Fondazione Alberto Sordi Research Institute for Ageing | And 10 more authors.
Brain Stimulation | Year: 2013

Background: A large number of studies explored the biological effects of extremely low-frequency (0-300 Hz) magnetic fields (ELF-MFs) on nervous system both at cellular and at system level in the intact human brain reporting several functional changes. However, the results of different studies are quite variable and the mechanisms of action of ELF-MFs are still poorly defined. The aim of this paper is to provide a comprehensive review of the effects of ELF-MFs on nervous system. Methods: We convened a workgroup of researchers in the field to review and discuss the available data about the nervous system effects produced by the exposure to ELF-MFs. Main Findings/Discussion: We reviewed several methodological, experimental and clinical studies and discussed the findings in five sections. The first section analyses the devices used for ELF-MF exposure. The second section reviews the contribution of the computational methods and models for investigating the interaction between ELF-MFs and neuronal systems. The third section analyses the experimental data at cellular and tissue level showing the effects on cell membrane receptors and intracellular signaling and their correlation with neural stem cell proliferation and differentiation. The fourth section reviews the studies performed in the intact human brain evaluating the changes produced by ELF-MFs using neurophysiological and neuropsychological methods. The last section shows the limits and shortcomings of the available data, evidences the key challenges in the field and tracks directions for future research. © 2013 Elsevier Inc. All rights reserved.


Di Lazzaro V.,Biomedical University of Rome | Di Lazzaro V.,Fondazione Alberto Sordi Research Institute for Ageing | Dileone M.,San Bortolo Hospital | Capone F.,Biomedical University of Rome | And 11 more authors.
Brain Stimulation | Year: 2014

Background Significant changes in neurophysiological and clinical outcomes in chronic stroke had been reported after tDCS; but there is a paucity of data in acute stroke.Objective We aimed to evaluate whether a tDCS-induced modulation of primary motor cortex excitability in patients with acute stroke enhances motor recovery associated with rehabilitation and induces differential neuroplasticity.Methods We conducted two experiments in acute stroke patients. In experiment 1 (14 patients), we tested the immediate effects of bilateral tDCS alone as compared to sham tDCS on recovery. Experiment 2 (20 patients) was designed to assess effects of bilateral tDCS delivered together with constraint-induced movement therapy (CIMT). In this experiment, we included a longer follow-up (3 months) and measured, in addition to the same clinical outcomes of experiment 1, changes of motor cortex excitability and the amount of promoted LTP-like activity.Results Despite the expected improvement at 1 week, none of the clinical measures showed any different modulation in dependence of CIMT and tDCS. On the neurophysiological assessments, on the other hand, the Real-tDCS group, compared to Sham-tDCS group, showed a reduction of inter-hemispheric imbalance when considering the differences of motor evoked potential between both 3-month and 1 week follow up (P = 0.007) and three month and baseline (P = 0.015).Conclusions s Despite the lack of additional clinical changes, real bilateral tDCS, together with CIMT, significantly reduces inter-hemispheric imbalance between affected and unaffected hemispheres. These findings may shed light on plasticity changes in acute stroke and its potential impact in chronic phases. © 2014 The Authors.


Profice P.,Institute of Neurology | Renna R.,Institute of Neurology | Pilato F.,Institute of Neurology | Sestito A.,Institute of Cardiology | And 5 more authors.
Spinal Cord | Year: 2013

Study design:Case report.Objective:to report and discuss the development of sudden symptomatic sinus bradycardia in a 35-year-old woman with acute myelitis.Case report:A 35-year-old woman presented rapidly progressive weakness and hypoesthesia in the left hemibody. Five days after symptom onset, she developed symptomatic sinus bradycardia up to 30 b.p.m. Bradycardia was completely resolved ∼36 h after its onset.Results:Cervical spine magnetic resonance imaging showed a focal T2-hyperintense intramedullary lesion at C2 level, with moderate cord swelling. The lesion involved bilaterally dorsal funiculi, and left lateral and ventral funiculi. Cardiac I-123 metaiodobenzylguanidine (MIBG) scintigraphy showed a decreased cardiac MIBG uptake suggesting sympathetic denervation.Conclusion:The most likely explanation for bradycardia in our patient is the myelitis-related disruption of descending vasomotor pathways, resulting in sympathetic hypoactivity. Our case extends the spectrum of the clinical presentations of cervical myelitis and emphasizes the importance of careful cardiac monitoring in acute phase of cervical myelitis. © 2013 International Spinal Cord Society All rights reserved.


Taffoni F.,Biomedical University of Rome | Formica D.,Biomedical University of Rome | Saccomandi P.,Biomedical University of Rome | Di Pino G.,Biomedical University of Rome | And 2 more authors.
Sensors (Switzerland) | Year: 2013

During last decades, Magnetic Resonance (MR)-compatible sensors based on different techniques have been developed due to growing demand for application in medicine. There are several technological solutions to design MR-compatible sensors, among them, the one based on optical fibers presents several attractive features. The high elasticity and small size allow designing miniaturized fiber optic sensors (FOS) with metrological characteristics (e.g., accuracy, sensitivity, zero drift, and frequency response) adequate for most common medical applications; the immunity from electromagnetic interference and the absence of electrical connection to the patient make FOS suitable to be used in high electromagnetic field and intrinsically safer than conventional technologies. These two features further heightened the potential role of FOS in medicine making them especially attractive for application in MRI. This paper provides an overview of MR-compatible FOS, focusing on the sensors employed for measuring physical parameters in medicine (i.e., temperature, force, torque, strain, and position). The working principles of the most promising FOS are reviewed in terms of their relevant advantages and disadvantages, together with their applications in medicine. © 2013 by the authors; licensee MDPI, Basel, Switzerland.


Cantone M.,Biomedical University of Rome | Di Pino G.,Biomedical University of Rome | Di Pino G.,Fondazione Alberto Sordi Research Institute for Ageing | Capone F.,Biomedical University of Rome | And 9 more authors.
Clinical Neurophysiology | Year: 2014

Transcranial magnetic stimulation (TMS) is emerging as a promising tool to non-invasively assess specific cortical circuits in neurological diseases. A number of studies have reported the abnormalities in TMS assays of cortical function in dementias. A PubMed-based literature review on TMS studies targeting primary and secondary dementia has been conducted using the key words "transcranial magnetic stimulation" or "motor cortex excitability" and "dementia" or "cognitive impairment" or "memory impairment" or "memory decline". Cortical excitability is increased in Alzheimer's disease (AD) and in vascular dementia (VaD), generally reduced in secondary dementias. Short-latency afferent inhibition (SAI), a measure of central cholinergic circuitry, is normal in VaD and in frontotemporal dementia (FTD), but suppressed in AD. In mild cognitive impairment, abnormal SAI may predict the progression to AD. No change in cortical excitability has been observed in FTD, in Parkinson's dementia and in dementia with Lewy bodies. Short-interval intracortical inhibition and controlateral silent period (cSP), two measures of gabaergic cortical inhibition, are abnormal in most dementias associated with parkinsonian symptoms. Ipsilateral silent period (iSP), which is dependent on integrity of the corpus callosum is abnormal in AD. While single TMS measure owns low specificity, a panel of measures can support the clinical diagnosis, predict progression and possibly identify earlier the "brain at risk". In dementias, TMS can be also exploited to select and evaluate the responders to specific drugs and, it might become a rehabilitative tool, in the attempt to restore impaired brain plasticity. © 2014 International Federation of Clinical Neurophysiology.

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