Research Institute for Ageing

Rome, Italy

Research Institute for Ageing

Rome, Italy
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Di Lazzaro V.,Biomedical University of Rome | Di Lazzaro V.,Research Institute for Ageing | Ziemann U.,University of Tübingen
Frontiers in Neural Circuits | Year: 2013

Although transcranial magnetic stimulation (TMS) activates a number of different neuron types in the cortex, the final output elicited in corticospinal neurones is surprisingly stereotyped. A single TMS pulse evokes a series of descending corticospinal volleys that are separated from each other by about 1.5ms (i.e. ~670Hz). This evoked descending corticospinal activity can be directly recorded by an epidural electrode placed over the high cervical cord. The earliest wave is thought to originate from the direct activation of the axons of fast-conducting pyramidal tract neurones (PTN) and is therefore termed "D" wave. The later waves are thought to originate from indirect, trans-synaptic activation of PTNs and are termed "I" waves. The anatomical and computational characteristics of a canonical microcircuit model of cerebral cortex composed of layer II and III and layer V excitatory pyramidal cells, inhibitory interneurons, and cortico-cortical and thalamo-cortical inputs can account for the main characteristics of the corticospinal activity evoked by TMS including its regular and rhythmic nature, the stimulus intensity-dependence and its pharmacological modulation. In this review we summarise present knowledge of the physiological basis of the effects of transcranial magnetic stimulation of the human motor cortex describing possible interactions between TMS and simple canonical microcircuits of neocortex. According to the canonical model, a TMS pulse induces strong depolarization of the excitatory cells in the superficial layers of the circuit. This leads to highly synchronised recruitment of clusters of excitatory neurons, including layer V PTNs, and of inhibitory interneurons producing a high frequency (~670 Hz) repetitive discharge of the corticospinal axons. The role of the inhibitory circuits is crucial to entrain the firing of the excitatory networks to produce a high-frequency discharge and to control the number and magnitude of evoked excitatory discharge in layer V PTNs. In summary, simple canonical microcircuits of neocortex can explain activation of corticospinal neurons in human motor cortex by TMS. © 2013 Di_lazzaro and Ziemann.


Di Pino G.,Biomedical University of Rome | Di Pino G.,Research Institute for Ageing | Denaro L.,University of Padua | Vadala G.,Biomedical University of Rome | And 11 more authors.
Journal of Surgical Research | Year: 2014

Background By implanting electrodes inside peripheral nerves, amputee's intentions are picked up and exploited to control novel dexterous sensorized hand prostheses. Under the pretext of presenting surgical technique and clinical outcomes of the implant of invasive peripheral neural interfaces in a human amputee, this article critically comments, from the point of view of the surgeon, strengths and weaknesses of the procedure. Materials and methods Four multielectrodes were implanted in the medial and ulnar nerves of a young volunteer, which, following a car-crash, had a left transradial amputation. Both nerves were approached with a single incision in the medial aspect of the upper arm. Four weeks later, the electrodes were removed. Results Even if the trauma and the postamputation plastic processes altered the anatomy, electrodes were proficiently implanted with an overall success of 66%. Looking at the procedure from the surgeon's viewpoint unveils few still open issues. Electrodes weaknesses were related to the absence of stabilizing structures, the cable transit through the skin, the implant angle, and the unproven magnetic resonance imaging compatibility. Future investigations are needed to definitely address the better anesthesia, number and sites of incisions, the nerves to implant, and the convenience of performing epineural microdissection. Conclusions Invasive neural interfaces developmental process almost completely relies on the efforts of bioengineers and neurophysiologists; however, the surgeon is responsible for intra and perioperative factors. Therefore, he deserves to play a major role also at the stage of specifying the requirements, to satisfy the requisites of a safe, stable, and long-lasting implant. © 2014 Elsevier Inc. All rights reserved.


Marano M.,Biomedical University of Rome | Quattrocchi C.,Biomedical University of Rome | Annibali O.,Biomedical University of Rome | Avvisati G.,Biomedical University of Rome | And 2 more authors.
Journal of Stroke and Cerebrovascular Diseases | Year: 2014

Cerebrovascular events are very common in sickle cell disease (SCD), and multiple mechanisms are probably involved in their pathophysiology. We report a 30-yearold woman who presented a large volume silent stroke followed 2 months later by a second large volume stroke that manifested only with transient arm weakness. In the acute phase, magnetic resonance angiography revealed a segmental stenosis of the 2 different large intracranial vessels supplying the stroke territories. Partial regression of vascular stenosis was revealed by a follow-up magnetic resonance imaging. Present case suggests that stenosis of large intracranial vessels, possibly related to vascular injury promoted by the endothelial adhesion of reticulocytes and inflammatory elements, is involved in large volume brain infarcts in SCD. © 2014 by National Stroke Association.


Capone F.,Biomedical University of Rome | Capone F.,Research Institute for Ageing | Tamburelli F.C.,Catholic University of the Sacred Heart | Pilato F.,Catholic University of the Sacred Heart | And 9 more authors.
Spine Journal | Year: 2013

Background context: Cervical spondylotic myelopathy (CSM) is a common disorder, but its management and the role of surgery are still a matter of controversy. The assessment of surgical outcome is complicated by the lack of reliable and objective methods to assess the severity of the myelopathy and its evolution. Motor-evoked potentials (MEPs) are a useful and reliable tool to measure noninvasively the involvement of the corticospinal tract in patients with CSM. Recent evidence suggests that MEPs could also have a role in monitoring the effect of surgical therapy. Purpose: The aim of the present study is to use MEPs for the functional assessment of spinal cord before and after surgery and to correlate changes in MEPs with clinical findings. Study design/setting: This is a retrospective cohort study. Patient sample: Thirty-eight patients affected by CSM who underwent surgical intervention. Outcome measures: We used the 18-point modified Japanese Orthopedic Association (mJOA) score for clinical evaluation and the central motor conduction time (CMCT) for the study of MEPs. Methods: All patients were evaluated both clinically and neurophysiologically before (7-15 days) and after (6-12 months) surgery. MEPs were recorded from the biceps, abductor digiti minimi, and tibialis anterior muscles bilaterally. Results: After surgery, the 18-point mJOA score increased significantly from 10.1 to 15.1, and the value of CMCT for tibialis anterior muscles showed a slight but significant reduction, more evident in patients with mild to moderate symptoms. Conclusions: Early surgical intervention for CSM could produce a beneficial effect on spinal cord functionality that can be detected by MEPs. © 2013 Elsevier Inc. All rights reserved.


Capone F.,Biomedical University of Rome | Capone F.,Research Institute for Ageing | Assenza G.,Biomedical University of Rome | Di Pino G.,Biomedical University of Rome | And 10 more authors.
Journal of Neural Transmission | Year: 2015

There is great interest about the therapeutic potentialities of transcutaneous vagus nerve stimulation (tVNS) applied to neuropsychiatric disorders. However, the mechanisms of action of tVNS and its impact on cortical excitability are unclear. To this regard, transcranial magnetic stimulation (TMS) can be useful because it is able of evaluating non-invasively excitatory and inhibitory circuitry of the human cortex. Aim of the present study is to investigate the effects of tVNS on cerebral cortex excitability in healthy volunteers by means of TMS. Ten healthy subjects participated in this randomized placebo-controlled double-blind study. Real tVNS was administered at left external acoustic meatus, while sham stimulation was performed at left ear lobe, both of them for 60 min. We evaluated motor thresholds, motor evoked potential amplitude, recruitment curves, and short-interval intracortical inhibition (SICI) in right and left motor cortex. Such parameters were evaluated before and 60 min after the exposure to tVNS, for both the real and the sham stimulation. Cardiovascular parameters were monitored during the stimulation. A generalized linear model for repeated measures was implemented to assess the effect of time and stimulation type on cardiovascular and neurophysiological variables. SICI, a double-pulse TMS paradigm informative of GABA-A activity, was significantly increased in right motor cortex after real tVNS. Other neurophysiological parameters, as well as cardiovascular variables, remained unchanged. Our findings confirm that tVNS is a safe and effective way to stimulate vagus nerve and provide innovative data about the possible mechanisms of action that supports the potential therapeutic application of this technique. © 2014, Springer-Verlag Wien.


Di Lazzaro V.,Biomedical University of Rome | Di Lazzaro V.,Research Institute for Ageing | Pellegrino G.,Biomedical University of Rome | Pellegrino G.,Research Institute for Ageing | And 15 more authors.
Brain Stimulation | Year: 2015

Background BDNF gene polymorphism impacts human motor cortex function and plasticity.Objective/hypothesis Using transcranial magnetic stimulation (TMS), we investigated whether BDNF polymorphism influences cortical plastic changes in acute stroke.Methods Twenty patients were recruited within 10 days of their first-ever ischemic stroke and genotyped for BDNF polymorphism. Blinded to the latter, we evaluated the excitability of the affected and unaffected hemisphere by measuring resting and active motor threshold and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation, a protocol of repetitive TMS inducing LTP-like activity. We also computed laterality indexes to assess inter-hemispheric excitability imbalance.Results Demographics, threshold and amplitude of motor-evoked potentials did not differ between those with (8 patients) and without polymorphism. Excitability of the unaffected hemisphere was significantly higher than the excitability of the affected hemisphere as probed by each measure. This imbalance was exaggerated in those without polymorphism; laterality indexes of rest motor thresholds were 0.016 ± 0.050 and 0.139 ± 0.028 for patients with and without polymorphism [t = 2.270, P = 0.036]. Exaggerated hemispheric imbalance also persisted after intermittent theta burst stimulation, which failed to induce any difference between groups.Conclusions Our results suggest that inter-hemispheric imbalance with greater excitability over unaffected hemisphere, is several times stronger in stroke patients without, as opposed to with, polymorphism. © 2015 Elsevier Inc. All rights reserved.


Renna R.,Catholic University | Pilato F.,Catholic University | Profice P.,Catholic University | Della Marca G.,Catholic University | And 7 more authors.
Journal of Stroke and Cerebrovascular Diseases | Year: 2014

Background Approximately 10%-14% of ischemic strokes occur in young adults. Aims To investigate risk factors and etiologies of strokes of young adults admitted to the "stroke unit" of Policlinico "Gemelli" of Rome from December 2005 to January 2013. Methods In all, 150 consecutive patients younger than 50 years diagnosed with ischemic stroke were enrolled. Clinical evaluation consisted of a complete neurologic examination and the National Institutes of Health Stroke Scale. Diagnostic workup consisted of anamnesis, extensive laboratory, radiologic, and cardiologic examination. Stroke etiologies were classified according to the Trial of Org 10172 in Acute Stroke Treatment. Results Patients' mean age was 41 ± 8.0 years. The most common risk factors were dyslipidemia (52.7%), smoking (47.3%), hypertension (39.3%), and patent foramen ovale (PFO, 32.8%). Large-artery atherosclerosis was diagnosed as the cause of stroke in 17 patients (11.3%). Cardioembolism was presumed in 36 patients (24%), most of them presented a PFO at transesophageal echocardiography. Small-vessel occlusion was diagnosed in 12 patients (8%); all of them were hypertensive and most of them presented additional risk factors. Forty-one patients (27.3%) presented a stroke of other determined etiology and 44 (29.3%) presented a stroke of undetermined etiology. The 3-year survival was 96.8% and recurrent strokes occurred in only 3 cases. Conclusions Traditional vascular risk factors are also very common in young adults with ischemic stroke, but such factors increase the susceptibility to stroke dependent to other causes as atherosclerosis and small-artery occlusion represent less than 20% of cases. Prognosis quoadvitam is good, being characterized by low mortality and recurrence rate. © 2014 by National Stroke Association.


Capone F.,Biomedical University of Rome | Capone F.,Research Institute for Ageing | Profice P.,University Cattolica | Pilato F.,University Cattolica | And 4 more authors.
Spine Journal | Year: 2013

Background context Low back pain (LBP) is a very common complaint in pregnancy. For this reason, it is often considered directly attributable to the pregnancy rather than a medical problem requiring diagnostic workup. Pregnancy-related LBP should be differentiated from the rare cases of LBP associated with serious spinal diseases. Hemangioblastoma is a vascular tumor of the central nervous system that very rarely can involve the spinal cord. Pregnancy can increase the growth of hemangioblastomas, leading to the appearance of neurologic symptoms. Purpose To describe an unusual cause of LBP in pregnancy. Study design A case report. Methods A 38-year-old woman, with a history of surgical resection of a cerebellar hemangioblastoma at the age of 15 years, presented at 38 weeks of gestation with worsening LBP and numbness of the lower limbs. Diagnostic workup led to a diagnosis of spinal hemangioblastoma. The tumor was removed after cesarean section in the 39th week of gestation. Results The detection of spinal hemangioblastoma resulted in a good outcome for both mother and infant. Conclusions This case emphasizes the main role of clinical evaluation in establishing the diagnostic workup, especially in pregnancy. Although LBP is commonly reported, this patient's medical history and the presence of clinical signs on neurologic examination suggested the need for further investigation.


Capone F.,Biomedical University of Rome | Capone F.,Research Institute for Ageing | Capone G.,University Utrecht | Ranieri F.,Biomedical University of Rome | And 6 more authors.
Neurobiology of Learning and Memory | Year: 2014

Random number generation (RNG) is a procedurally-simple task related to specific executive functions, such as updating and monitoring of information and inhibition of automatic responses.The effect of practice on executive functions has been widely investigated, however little is known on the impact of practice on RNG. Transcranial direct current stimulation (tDCS) allows to modulate, non-invasively, brain activity and to enhance the effects of training on executive functions.Hence, this study aims to investigate the effect of practice on RNG and to explore the possibility to influence it by tDCS applied over dorsolateral prefrontal cortex. Twenty-six healthy volunteers have been evaluated within single session and between different sessions of RNG using several measures of randomness, which are informative of separable cognitive components servicing random behavior.We found that repetition measures significantly change within single session, seriation measures significantly change both within and between sessions, while cycling measures are not affected by practice. tDCS does not produce any additional effect, however a sub-analysis limited to the first session revealed an increasing trend in seriation measure after anodal compared to cathodal stimulation.Our findings support the hypothesis that practice selectively and consistently influences specific cognitive components related to random behavior, while tDCS transiently affects RNG performance. © 2014 Elsevier Inc.


Di Lazzaro V.,Biomedical University of Rome | Di Lazzaro V.,Research Institute for Ageing | Rothwell J.C.,University College London
Journal of Physiology | Year: 2014

A number of methods have been developed recently that stimulate the human brain non-invasively through the intact scalp. The most common are transcranial magnetic stimulation (TMS), transcranial electric stimulation (TES) and transcranial direct current stimulation (TDCS). They are widely used to probe function and connectivity of brain areas as well as therapeutically in a variety of conditions such as depression or stroke. They are much less focal than conventional invasive methods which use small electrodes placed on or in the brain and are often thought to activate all classes of neurones in the stimulated area. However, this is not true. A large body of evidence from experiments on the motor cortex shows that non-invasive methods of brain stimulation can be surprisingly selective and that adjusting the intensity and direction of stimulation can activate different classes of inhibitory and excitatory inputs to the corticospinal output cells. Here we review data that have elucidated the action of TMS and TES, concentrating mainly on the most direct evidence available from spinal epidural recordings of the descending corticospinal volleys. The results show that it is potentially possible to test and condition specific neural circuits in motor cortex that could be affected differentially by disease, or be used in different forms of natural behaviour. However, there is substantial interindividual variability in the specificity of these protocols. Perhaps in the future it will be possible, with the advances currently being made to model the electrical fields induced in individual brains, to develop forms of stimulation that can reliably target more specific populations of neurones, and open up the internal circuitry of the motor cortex for study in behaving humans. © 2014 The Authors.

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