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Vincenzo Di Lazzaro

Publications and source records attributed to Vincenzo Di Lazzaro.

At least 19 recordsLinked to original sources
PubMed2026

Efficacy of citicoline as an add-on therapy in Parkinson's disease: a randomized, double-blind trial.

BACKGROUND: Citicoline is a promising therapeutic option for improving both motor and non-motor symptoms in Parkinson's disease (PD) beyond levodopa and other standard dopaminergic treatments. OBJECTIVES: The CITIPARK study evaluated the efficacy and safety of citicoline in improving clinical outcomes and quality of life (QOL) in PD patients on dopaminergic therapies. METHODS: The randomized, double-blind, multicenter trial compared citicoline (1000 mg/day intramuscular, two six-week cycles) with placebo for 24 weeks in PD under stable medications. The primary endpoint was change in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) total score; secondary endpoints included motor and non-motor subscores, QOL, clinical global impression (CGI) and safety. RESULTS: The study enrolled 485 participants, randomizing 474 (citicoline: 303; placebo: 171). Citicoline significantly increased the likelihood of achieving a minimal clinically important difference compared with placebo (OR 2.06, 95% CI 1.06-3.99; P = 0.031) on the MDS-UDPRS total score in the modified intention-to-treat population. Among secondary outcomes, the citicoline group showed greater improvement in motor function (MDS-UPDRS III -2.97 vs -0.13; p = 0.009) and a greater improvement on CGI -II and CGI-III (3.26 vs 3.59; p = 0.021 and 9.30 vs 10.38; p = 0.018, respectively). AEs occurred in 22.1% and 27.1% of the citicoline and placebo groups, respectively. CONCLUSIONS: Citicoline was well tolerated and associated with motor benefits compared with placebo in a highly compliant population. The results suggest a role of citicoline as a safe and possibly effective supportive therapy in PD treated with concomitant dopaminergic agents.

Humans↗
PubMed2006

Direct demonstration that repetitive transcranial magnetic stimulation can enhance corticospinal excitability in stroke.

BACKGROUND AND PURPOSE: Preliminary studies suggest that electrical stimulation of the damaged cortex may be able to enhance motor recovery after stroke. The hypothesis has been that this increases cortical excitability, making it easier for the system to respond to and learn from conventional physiotherapy. However, there is no direct evidence that the cortex of patients with stroke can respond in this fashion; hence, the basis of these new approaches has been questioned. METHODS: We had the opportunity to evaluate directly the effects of noninvasive cortical stimulation on the excitability of corticospinal output from the damaged hemisphere of a chronic stroke patient who had epidural electrodes implanted in the upper dorsal cord for treatment of pain. RESULTS: We found that it was possible to enhance corticospinal activity evoked by single test stimuli. CONCLUSIONS: This study confirms directly that it is possible to noninvasively manipulate cortical excitability in stroke.

Aged↗
PubMed2006

Repetitive transcranial magnetic stimulation for ALS. A preliminary controlled study.

Repetitive transcranial magnetic stimulation (rTMS) of brain can modulate cortical neurotransmission, a novel paradigm of repetitive stimulation termed continuous theta-burst stimulation (cTBS) produces a pronounced and prolonged suppression of motor cortex excitability. The aim of this preliminary study was to investigate whether cTBS of motor cortex could have any beneficial effect in patients with amyotrophic lateral sclerosis (ALS). We performed a double-blind, placebo-controlled trial. Twenty patients with definite ALS were randomly allocated to blinded active or placebo stimulation. Repetitive stimulation of the motor cortex was performed for five consecutive days every month for six consecutive months. The primary outcome was the rate of decline as evaluated with the ALS functional rating scale. The treatment was well tolerated by the patients. Fifteen patients (seven active and eight sham) completed the study and were included in the 6-months analysis. Both active and sham patients deteriorated during treatment, however, active patients showed a modest but significant slowing of the deterioration rate. Though we cannot be sure whether the effects observed can be attributed to cTBS, because of the restricted number of patients studied, further investigation on a larger group of ALS patients is warranted. The results of the pilot study might open up a new therapeutic perspective in ALS based on neuromodulation.

Aged↗
PubMed2006

Phasic increases in cortical beta activity are associated with alterations in sensory processing in the human.

Oscillatory activity in the beta (beta)-frequency band (13-35 Hz) can be recorded over the sensorimotor cortex in humans. It is coherent with electromyographic activity (EMG) during tonic contraction, but whether the cortical beta-oscillations are primarily motor or sensorimotor in function remains unclear. We tested the hypothesis that cortical beta-activity is associated with an up-regulation of sensory inputs that may be relevant to the organization of the motor response. We recorded cortical somatosensory potentials (SEPs) elicited by electrical stimuli to the median nerve at the wrist triggered by increases of electroencephalographic (EEG) beta-activity in the contralateral fronto-central EEG and compared these to SEPs presented at random intervals. The involvement of motor cortex in the triggering EEG activity was confirmed by a simultaneous elevation of cortico-spinal synchrony in the beta-band. The negative cortical evoked potential peaking at 20 ms and the positive evoked potential peaking at 30 ms after median nerve shocks were increased in size when elicited after phasic increases in beta-activity. The functional coupling of sensory and motor cortices in the beta-band was confirmed in recordings of electrocorticographic activity in two patients with chronic pain syndromes, suggesting a means by which beta-activity may simultaneously influence cortical sensory processing, motor output and promote sensory-motor interaction.

Adult↗
PubMed2006

GABAA receptor subtype specific enhancement of inhibition in human motor cortex.

Inhibition is of fundamental importance to regulate activity in cortical circuits. Inhibition is mediated through a diversity of different interneurones and gamma-aminobutyric acid A receptor (GABA(A)R) subtypes. Here we employed paired-pulse transcranial magnetic stimulation (TMS) to measure short interval intracortical inhibition (SICI), a GABA(A)R-mediated inhibition in human motor cortex, to address the question of which GABA(A)R subtype is responsible for this form of inhibition. It has been shown that classical benzodiazepines (diazepam and lorazepam) have a non-selective affinity profile at different alpha-subunit-bearing subtypes of the GABA(A)R while zolpidem has a 10-fold greater affinity to the alpha1-subunit-bearing GABA(A)R compared with those bearing the alpha2- or alpha3-subunit. We found that, in seven healthy subjects, a single oral dose of 20 mg of diazepam or 2.5 mg of lorazepam significantly increased SICI, whereas 10 mg of zolpidem did not change SICI. This dissociation occurred despite equal sedation by all three drugs, an alpha1-subunit GABA(A)R-mediated effect. The findings strongly suggest that SICI is not mediated by the alpha1-subunit-bearing subtype of the GABA(A)R but by those bearing either the alpha2- or alpha3-subunit. This study represents an attempt by means of TMS to identify GABA(A)R subtype-specific action at the systems level of human cortex, a highly relevant issue because the different alpha-subunit-bearing subtypes of the GABA(A)R are differently involved in benzodiazepine-mediated effects such as sedation, amnesia or anxiolysis, in developmental cortical plasticity, and in neurological disorders such as epilepsy.

Adult↗
PubMed2005

Dissociated effects of diazepam and lorazepam on short-latency afferent inhibition.

Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short-latency afferent inhibition, SAI). This can be tested by coupling electrical stimulation of peripheral nerve with transcranial magnetic stimulation (TMS) of the motor cortex. SAI is reduced by the anticholinergic drug scopolamine, and in patients with Alzheimer's disease. Therefore, it is possible that SAI is a marker of central cholinergic activity important for memory function. The benzodiazepine lorazepam also reduces SAI. Since benzodiazepines impair memory formation, but do not do so uniformly, with a maximum amnesic effect after lorazepam but less or no effect after diazepam, we were interested in testing in this non-behavioural study to what extent the effects of lorazepam and diazepam on circuits involved in SAI could be dissociated. In addition, and for control, we tested the effects of lorazepam and diazepam on short-interval intracortical inhibition (SICI), a motor cortical inhibition mediated through the GABA(A) receptor. Lorazepam markedly reduced SAI, whereas diazepam slightly increased it. In contrast, both benzodiazepines uniformly increased SICI. Our findings demonstrate opposite effects of lorazepam and diazepam on SAI, an inhibition modulated by central cholinergic activity, but the same effects on SICI, a marker of neurotransmission through the GABA(A) receptor. This dissociation suggests, for the first time, that TMS measures of cortical inhibition provide the opportunity to segregate differences of benzodiazepine action in human central nervous system circuits.

Adult↗
PubMed2005

Existing motor state is favored at the expense of new movement during 13-35 Hz oscillatory synchrony in the human corticospinal system.

Oscillations in local field potentials in the beta-frequency band (13-35 Hz) are a pervasive feature of human and nonhuman primate motor cortical areas. However, the function of such synchronous activity across populations of neurons remains unknown. Here, we test the hypothesis that beta activity may promote existing motor set and posture while compromising processing related to new movements. Three experiments were performed. First, healthy subjects were instructed to make reaction time movements of the outstretched index finger in response to imperative cues triggered by transient increases in corticospinal synchrony, as evidenced by phasic elevations of beta-frequency band microtremor and intermuscular synchrony. Second, healthy subjects were instructed to resist a stretch to the index finger triggered in the same way. Finger acceleration in the reaction time task and transcortical components of the stretch reflex were measured and compared with those elicited by random cue or stretch presentation. Finally, we sought a correlation between finger acceleration in the reaction time task and cortical synchrony directly measured from the electrocorticogram in two patients undergoing functional neurosurgery. We demonstrate that movements are slowed and transcortical responses to stretch are potentiated during periods of elevated beta-band cortical synchrony. The results suggest that physiological periods of beta synchrony are associated with a cortical state in which postural set is reinforced, but the speed of new movements impaired. The findings are of relevance to Parkinson's disease, in which subcortical and cortical beta-band synchronization is exaggerated in the setting of increased tone and slowed movements.

Adult↗
PubMed2005

Oscillatory pallidal local field potential activity inversely correlates with limb dyskinesias in Parkinson's disease.

Levodopa induced dyskinesias (LIDs) are poorly understood and yet are a major cause of disability in Parkinson's disease (PD). The activity of neurons in the basal ganglia of patients with PD tends to be strongly synchronized at frequencies under 30 Hz, leading to oscillatory local field potentials (LFPs). As dopaminergic therapy acutely suppresses this synchronization, we investigated whether this suppression may contribute to LIDs. Accordingly, we sought an inverse correlation between oscillatory synchronization and dyskinesia activity across time. To this end, we recorded pallidal LFPs in two Parkinsonian subjects exhibiting LIDs following surgery for deep brain stimulation. We correlated LFP power with simultaneously recorded EMG from the dyskinetic contralateral upper limb. We found highly significant inverse correlations between the oscillatory LFP activity under 30 Hz and dyskinetic EMG (maximum r = -0.65, P < 0.001 and r = -0.33, P < 0.001 for activities over 13-30 Hz in each subject). The inverse relationship between oscillatory pallidal LFP activity and dyskinetic EMG was maintained over time periods of a few seconds and was focal. This observation links the suppression of oscillatory synchronization in the pallidum with dyskinetic muscle activity in PD.

Action Potentials↗
PubMed2005

Reciprocal interactions between oscillatory activities of different frequencies in the subthalamic region of patients with Parkinson's disease.

Synchronization of neuronal activity evident in the local field potential (LFP) recorded in the subthalamic region of patients with Parkinson's disease occurs at low frequencies (< 30 Hz) and, in some patients following treatment with levodopa, at high frequencies between 65 and 85 Hz. Here we investigate the functional relationship between these different activities by determining whether spontaneous fluctuations in their strength are correlated across time. To this end, we analysed recordings of LFPs from macroelectrodes inserted in the subthalamic area of 16 patients with Parkinson's disease, after treatment with anti-parkinsonian medication. Time-evolving autospectra of LFPs with significant 65-85 Hz peaks (from 21 sides) were computed and correlations between frequency components determined over time. LFP activity in the 5-32 Hz band was significantly negatively correlated with that in the 65-85 Hz band in data averaged across all 21 sides, as well as in 15 (71%) of the individual records. Negative correlations were relatively selective for interactions between these frequency bands and occurred over time epochs of as little as 40 s. They occurred about 50 min after levodopa and were recorded concurrently with contralateral levodopa-induced dyskinesias in all but four cases. Positive correlations were not seen between activities in the 5-32 Hz and 65-85 Hz bands. The spontaneous negative correlations suggest a reciprocal relationship between population synchrony in the high- and low-frequency ranges, and raise the possibility that spontaneous fluctuations in the balance between these activities may contribute to levodopa-induced dyskinesias.

Action Potentials↗
PubMed2004

Transcranial magnetic stimulation and BDNF plasma levels in amyotrophic lateral sclerosis.

Low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex results in lasting changes of excitatory neurotransmission. We investigated the effects of suprathreshold 1 Hz rTMS on brain derived neurotrophic factor (BDNF) plasma levels in 10 healthy subjects and effects of either 1 Hz or 20 Hz rTMS in four amyotrophic lateral sclerosis (ALS) patients. BDNF levels were progressively decreased by 1 Hz rTMS in healthy subjects; there was no effect of 1 Hz rTMS on BDNF plasma levels in ALS patients, an effect probably due to the loss of motor cortex pyramidal cells. High frequency rTMS determined a transitory decrease in BDNF plasma levels. Cumulatively these findings suggest that rTMS might influence the BDNF production by interfering with neuronal activity.

Adult↗
PubMed2004

Motor cortex stimulation for amyotrophic lateral sclerosis. Time for a therapeutic trial?

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) of the brain can modulate neurotransmission. The aim of this preliminary study was to investigate whether rTMS of the motor cortex at low (1 Hz) or high (20 Hz) frequencies can have any beneficial effect in a transgenic rat model of amyotrophic lateral sclerosis (ALS) and in a few patients with ALS. METHODS: The effects of chronic rTMS were evaluated in 20 transgenic rats overexpressing the human G93A mutant superoxide dismutase 1 gene. Several cycles of rTMS were also performed in 4 ALS patients and the rate of progression of the disease before and during rTMS treatment was compared. RESULTS: No effects of rTMS was observed in transgenic rats. The rTMS treatment was well tolerated by the patients. All ALS patients continued to deteriorate. However, in the patients exposed to low-frequency rTMS the rate of progression during treatment was slightly slower than that evaluated before treatment; an opposite tendency was observed in patients exposed to high frequencies. CONCLUSIONS: Though we cannot be sure whether the effects observed in the patients can be attributed to rTMS, further investigation using low-frequency motor cortex stimulation on a larger group of ALS patients is warranted. SIGNIFICANCE: The results of the pilot study in humans might open up a new therapeutic perspective in ALS based on neuromodulation.

Amyotrophic Lateral Sclerosis↗
PubMed2004

Effects of stimulation of the subthalamic area on oscillatory pallidal activity in Parkinson's disease.

The pattern of neuronal discharge within the basal ganglia is disturbed in Parkinson's disease (PD). In particular, there is a tendency for neuronal elements to synchronise at around 20 Hz in the absence of dopaminergic treatment, whereas this activity can be replaced by spontaneous synchronisation at much higher frequencies (>70 Hz) following dopaminergic treatment [J. Neurosci. 21 (2001) 1033; Brain 126 (2003) 2153]. In two PD patients (3 sides), we show that stimulating the subthalamic area at around 20 Hz exacerbates synchronisation at similar frequencies in the globus pallidus interna, the major output structure of the human basal ganglia. In contrast, stimulating the subthalamic area at >70 Hz suppresses pallidal activity at about 20 Hz. Clinically, stimulation of the subthalamic area at similar high frequencies reverses parkinsonism and forms the basis of therapeutic deep brain stimulation in PD. The results point to a possible common mechanism by which both dopaminergic treatment associated synchronisation of subthalamic activity at very high frequency and synchronisation imposed by therapeutic stimulation of the subthalamic area inhibit an abnormal and potentially deleterious synchronisation of basal ganglia output at around 20 Hz. If this activity is unchecked by synchronisation at higher frequency, then pathological 20-Hz oscillations may cascade through the basal ganglia, increasing at subsequent levels of processing.

Aged↗
PubMed2003

Patterning of globus pallidus local field potentials differs between Parkinson's disease and dystonia.

Here we test the hypothesis that there are distinct temporal patterns of synchronized neuronal activity in the pallidum that characterize untreated and treated parkinsonism and dystonia. To this end we recorded local field potentials (LFPs) from the caudal and rostral contact pairs of macroelectrodes implanted into the pallidum of patients for the treatment of Parkinson's disease (12 cases recorded on and off medication, 17 macroelectrodes) and dystonia (10 cases, 19 macroelectrodes). Percentage LFP power in the 11-30 Hz band was decreased and that in the 4-10 Hz band increased across both contact pairs in treated Parkinson's disease compared with untreated Parkinson's disease. Dystonic patients had even less 11-30 Hz power and greater 4-10 Hz power compared with untreated or treated Parkinson's disease patients. The change in the 4-10 Hz band in patients with dystonia was particularly manifest in the more rostral contact pair, presumed to be within or bridging the globus pallidus externus. We conclude that untreated and treated Parkinson's disease and dystonia are characterized by different spatiotemporal patterns of activity in the human pallidum.

Adult↗
PubMed2003

Corticospinal volleys evoked by transcranial stimulation of the brain in conscious humans.

The direct recording in conscious humans of corticospinal volleys evoked by different magnetic and electric techniques of transcranial stimulation demonstrates that it is possible to activate neurones of the motor cortex in several different ways. Lateral electrical stimulation of the motor cortex preferentially activates the axons of corticospinal neurones in the subcortical white matter, and evokes a D-wave in pyramidal tract. The way of activation of corticospinal neurones using magnetic stimulation depends on the direction of the electrical current induced in the brain and on the shape of the coil. Monophasic magnetic stimulation with a focal figure-of-eight coil inducing posterior-anterior current in the brain activates corticospinal neurones trans-synaptically recruiting an 11-wave, with later I-waves appearing in sequence at higher intensities and a D-wave at very high intensities. If the induced current is rotated to the anterior-posterior direction late I-waves are preferentially recruited and when a D-wave is recruited, it has a later onset than the electrical D-wave, suggesting an activation nearer the cell body of the pyramidal neurones. A latero-medial induced current activates both corticospinal axons at the same point as electrical stimulation evoking a D wave and cortico-cortical axons evoking I-waves. A nonfocal large circular coil centered at the vertex is capable of activating pyramidal neurones both at the initial segment and trans-synaptically evoking a D wave with a longer latency than the electrical D-wave and I-waves. Using a biphasic magnetic stimulation, both phases of the biphasic pulse are capable of activating descending motor output and the pattern of recruitment of descending activity depends on the intensity of the stimulus and the relative threshold of each volley to each direction of current flow.

Consciousness↗