Papers by Sergio Barbieri
Deep Brain Stimulation (DBS), besides an effective therapeutic tool, is a fascinating physiologic... more Deep Brain Stimulation (DBS), besides an effective therapeutic tool, is a fascinating physiological "window" on human subcortical structures. In fact, local field potential (LFPs) recordings in patients provide an amount of physiological data on basal ganglia, especially in relation to their motor, cognitive and affective functions. In this study we aimed to assess a novel methodological approach for estimating the
Journal of Neurology Neurosurgery and Psychiatry, 1997
Objectives—To report the long term effect of the combined treatment with high dose intravenous im... more Objectives—To report the long term effect of the combined treatment with high dose intravenous immunoglobulins (IVIg) and oral cyclophosphamide (CTX) in patients with multifocal motor neuropathy, and to determine whether the association of oral CTX in these patients may help to delay and, possibly, suspend IVIg infusions.METHODSSix patients with multifocal motor neuropathy responding to an initial course of IVIg (0.4

Parkinsonism & Related Disorders, 2015
Introduction: The possibility that deep brain stimulation (DBS) in Parkinson's disease (PD) alter... more Introduction: The possibility that deep brain stimulation (DBS) in Parkinson's disease (PD) alters patients' decisions and actions, even temporarily, raises important clinical, ethical and legal questions. Abnormal moral decision-making can lead to ethical rules violations. Previous experiments demonstrated the subthalamic (STN) activation during moral decision-making. Here we aim to study whether STN DBS can affect moral decision-making in PD patients. Methods: Eleven patients with PD and bilateral STN DBS implant performed a computerized moral task in ON and OFF stimulation conditions. A control group of PD patients without DBS implant performed the same experimental protocol. All patients underwent motor, cognitive and psychological assessments. Results: STN stimulation was not able to modify neither reaction times nor responses to moral task both when we compared the ON and the OFF state in the same patient (reaction times, p ¼ .416) and when we compared DBS patients with those treated only with the best medical treatment (reaction times: p ¼ .408, responses: p ¼ .776). Conclusions: Moral judgment is the result of a complex process, requiring cognitive executive functions, problem-solving, anticipations of consequences of an action, conflict processing, emotional evaluation of context and of possible outcomes, and involving different brain areas and neural circuits. Our data show that STN DBS leaves unaffected moral decisions thus implying relevant clinical and ethical implications for DBS consequences on patients' behavior, on decision-making and on judgment ability. In conclusion, the technique can be considered safe on moral behavior.

Acta neurochirurgica. Supplement, 2005
Deep brain stimulation electrodes implanted in the subthalamic nucleus of patients with Parkinson... more Deep brain stimulation electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease allow electrophysiological recordings from the human basal ganglia. Subthalamic local field potential recordings revealed the presence of multiple rhythms, from the classical EEG frequency range (<50 Hz), to surprisingly high frequencies (70 Hz and 300 Hz). Fast rhythms are particularly attractive because of their likely interaction with the excitatory mechanisms of action of deep brain stimulation. Here we investigated whether the two rhythms at 70 Hz and at 300 Hz represent distinct modes of operation, and therefore different targets, within the subthalamic nucleus. We retrospectively analyzed the dataset we used to describe the 300 Hz rhythm (Foffani, Priori et al., Brain 126: 2153-2163, 2003) searching for significant 70 Hz oscillations after levodopa administration. Whereas (as previously reported) 300 Hz activity was a consistent feature in the dataset, significan...

Muscle fatigue induced by a previous sustained contraction temporarily decreases the motor output... more Muscle fatigue induced by a previous sustained contraction temporarily decreases the motor output, transiently worsening motor performance. Whether muscle fatigue alters motor performance also in dystonia-a disorder whose main pathophysiological abnormality is motor overflow-remains unknown. To assess the effects of muscle fatigue in patients with focal occupational upper limb dystonia, we studied the effect of a previous maximum fatiguing voluntary contraction on motor performance in 10 musicians with focal occupational dystonia, in 3 musicians with hand motor impairment due to non-dystonic disorders, and in 5 normal musicians. The fatigu-ing task consisted of grasping a spring handgrip as long as possible until the task failed. In dystonic musicians, a fatiguing contraction significantly improved motor performance. The improvement lasted less than 5 minutes and appeared only after fatigue of the affected upper limb. In contrast, in musicians with non-dystonic motor impairment, motor performance remained unchanged or worsened, and normal musician performance consistently worsened. © 2001 Movement Disorder Society.

Transplantation Proceedings, 2007
Bacterial contamination is one of the potential risks of blood salvage and reinfusion during orth... more Bacterial contamination is one of the potential risks of blood salvage and reinfusion during orthotopic liver transplantation (OLT) because cell-saver machines lack antibacterial protection devices. This study was designed to analyze the potential bacterial contamination of blood salvaged during OLT; a secondary end point was to evaluate whether reinfusion of potentially contaminated blood may have been responsible for clinically manifested infective complications in the same patient. After induction of anesthesia, a blood sample was drawn from the central venous catheter (CVC) immediately after its positioning, to exclude potential coexisting hematic contamination of the recipient. During the procedure, 2 other samples of salvaged blood were collected for bacteriological analysis. Twenty-six of 38 samples of salvaged blood were positive for microorganisms, whereas 12 did not reveal the presence of infectious agents.

Social Neuroscience, 2011
Although lesional, neuroimaging, and brain stimulation studies have provided an insight into the ... more Although lesional, neuroimaging, and brain stimulation studies have provided an insight into the neural mechanisms of judgement and decision-making, all these works focused on the cerebral cortex, without investigating the role of subcortical structures such as the basal ganglia. Besides being an effective therapeutic tool, deep brain stimulation (DBS) allows local field potential (LFP) recordings through the stimulation electrodes thus providing a physiological &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;window&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; on human subcortical structures. In this study we assessed whether subthalamic nucleus LFP oscillations are modulated by processing of moral conflictual, moral nonconflictual, and neutral statements. To do so, in 16 patients with Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (8 men) bilaterally implanted with subthalamic nucleus (STN) electrodes for DBS, we recorded STN LFPs 4 days after surgery during a moral decision task. During the task, recordings from the STN showed changes in LFP oscillations. Whereas the 14--30 Hz band (beta) changed during the movement executed to perform the task, the 5--13 Hz band (low-frequency) changed when subjects evaluated the content of statements. Low-frequency band power increased significantly more during conflictual than during nonconflictual or neutral sentences. We conclude that STN responds specifically to conflictual moral stimuli, and could be involved in conflictual decisions of all kinds, not only those for moral judgment. LFP oscillations provide novel direct evidence that the neural processing of conflictual decision-making spreads beyond the cortex to the basal ganglia and encompasses a specific subcortical conflict-dependent component.

PLoS ONE, 2010
Decision often implies a utilitarian choice based on personal gain, even at the expense of damagi... more Decision often implies a utilitarian choice based on personal gain, even at the expense of damaging others. Despite the social implications of utilitarian behavior, its neurophysiological bases remain largely unknown. To assess how the human brain controls utilitarian behavior, we delivered transcranial direct current stimulation (tDCS) over the ventral prefrontal cortex (VPC) and over the occipital cortex (OC) in 78 healthy subjects. Utilitarian judgment was assessed with the moral judgment task before and after tDCS. At baseline, females provided fewer utilitarian answers than males for personal moral dilemmas (p = .007). In males, VPC-tDCS failed to induce changes and in both genders OC-tDCS left utilitarian judgments unchanged. In females, cathodal VPC-tDCS tended to decrease whereas anodal VPC-tDCS significantly increased utilitarian responses (p = .005). In males and females, reaction times for utilitarian responses significantly decreased after cathodal (p,.001) but not after anodal (p = .735) VPC-tDCS. We conclude that ventral prefrontal tDCS interferes with utilitarian decisions, influencing the evaluation of the advantages and disadvantages of each option in both sexes, but does so more strongly in females. Whereas cathodal tDCS alters the time for utilitarian reasoning in both sexes, anodal stimulation interferes more incisively in women, modifying utilitarian reasoning and the possible consequent actions. The genderrelated tDCS-induced changes suggest that the VPC differentially controls utilitarian reasoning in females and in males. The gender-specific functional organization of the brain areas involved in utilitarian behavior could be a correlate of the moral and social behavioral differences between the two sexes.

Neurosignals, 2011
In the past years, local field potential (LFP) signals recorded from the subthalamic nucleus (STN... more In the past years, local field potential (LFP) signals recorded from the subthalamic nucleus (STN) in patients undergoing deep brain stimulation (DBS) for Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) disclosed that DBS has a controversial effect on STN beta oscillations recorded 2-7 days after surgery for macroelectrode implantation. Nothing is known about these DBS-induced oscillatory changes 30 days after surgery. We recorded STN LFPs during ongoing DBS in 7 patients with PD, immediately (hyperacute phase) and 30 days (chronic phase) after surgery. STN LFP recordings showed stationary intranuclear STN beta LFP activity in hyperacute and chronic phases, confirming that beta peaks were also present in chronic recordings. Power spectra of nuclei with significant beta activity (54% of the sample) showed that it decreased significantly during DBS (p=0.021) under both recording conditions. The time course of beta activity showed more evident DBS-induced changes in the chronic than in the hyperacute phase (p=0.014). DBS-induced changes in STN beta LFPs in patients undergoing DBS in chronic phase provide useful information for developing a new neurosignal-controlled adaptive DBS system.

Neurological Sciences, 2004
To test a new tool for the neurophysiological identification of the human subthalamic nucleus (ST... more To test a new tool for the neurophysiological identification of the human subthalamic nucleus (STN) during stereotactic surgery for the implantation of deep-brain-stimulation (DBS) electrodes, we analysed off-line the intraoperative signals recorded from patients with Parkinson&amp;amp;#39;s disease. We estimated the power spectral density (PSD) along each penetration track (8 patients, 13 sides) and determined the spatial correlation of the PSD with the target location estimated from neuroimaging procedures (&amp;amp;quot;anatomical target&amp;amp;quot;), and with the final target location derived from standard intraoperative neurophysiological procedures for STN localization (&amp;amp;quot;clinical target&amp;amp;quot;). At each step we recorded the &amp;amp;#39;on-line&amp;amp;#39; signal for 120 seconds; because the PSD was estimated by calculating the periodogram for 6-second epochs of neural signal, we had 20 epochs at each step. When the electrode track crossed the STN, the PSD in the 0.25-2.5 kHz band increased, peaking on average &amp;amp;lt;0.5 mm cranial to the clinical target and 1.00+/-1.51 mm caudal to the anatomical target. When the track was outside the nucleus, the PSD remained unchanged. Even on recordings with low signal-to-noise ratio, off-line PSD analysis of neural signals showed a good correspondence with the target indicated by the surgical team. On-line intraoperative estimation of the PSD may be a simple, reliable, rapid and complementary approach to electrophysiological monitoring during STN surgery for Parkinson&amp;amp;#39;s disease.

Neurological Sciences, 2001
Although deep brain stimulation (DBS) is a clinically effective therapy for patients with advance... more Although deep brain stimulation (DBS) is a clinically effective therapy for patients with advanced Parkinson's disease (PD), its physiological effects on the brain and possible actions on non-motor functional systems remain largely unknown. This study evaluated the effects of DBS of the subthalamic nucleus (STN) on neurophysiological variables and on cardiovascular physiology. Nine patients affected by PD undergoing chronic DBS of the STN have been studied. We performed electroencephalography (EEG), somatosensory (SEPs) and visual evoked potentials (VEPs), exteroceptive masseteric silent period and sympathetic skin response (SSR) studies with DBS ON and OFF. To assess the effects of stimulation on the cardiovascular system the tilt test and plasma renin activity were studied. When we turned the DBS OFF, both SEP N20 and the VEP P100 component increased significantly in amplitude whereas the SSR decreased in amplitude and increased in latency. Although plasma renin activity tended to increase with DBS OFF, its modification induced by postural changes and blood pressure values did not significantly differ with DBS ON and OFF. We conclude that DBS of the STN in PD, besides inducing a clinical improvement, induces several non-motor effects.

Movement Disorders, 2010
Deep brain stimulation (DBS) of the ventralis oralis (VO) complex of the thalamus improves tics i... more Deep brain stimulation (DBS) of the ventralis oralis (VO) complex of the thalamus improves tics in patients with Tourette syndrome (TS). To neurophysiologically describe the VO complex we recorded, in seven patients with TS undergoing DBS electrode implantation, single-unit activity during surgery and local field potentials (LFPs) a few days after surgery. Single unit recordings showed that the VO complex is characterized by a localized pattern of bursting neuronal activity. LFP spectra demonstrated that VO of TS patients has a prominent oscillatory activity at low frequencies (2-7 Hz) and in the a-band (8-13 Hz), and a virtually absent beta activity. In each patient, the main LFP frequency significantly correlated with single-unit interburst frequency. In conclusion, we observed an oscillatory bursting activity in the VO as target region in patients with severe TS undergoing DBS surgery.

Movement Disorders, 2001
Muscle fatigue induced by a previous sustained contraction temporarily decreases the motor output... more Muscle fatigue induced by a previous sustained contraction temporarily decreases the motor output, transiently worsening motor performance. Whether muscle fatigue alters motor performance also in dystonia-a disorder whose main pathophysiological abnormality is motor overflow-remains unknown. To assess the effects of muscle fatigue in patients with focal occupational upper limb dystonia, we studied the effect of a previous maximum fatiguing voluntary contraction on motor performance in 10 musicians with focal occupational dystonia, in 3 musicians with hand motor impairment due to non-dystonic disorders, and in 5 normal musicians. The fatigu-ing task consisted of grasping a spring handgrip as long as possible until the task failed. In dystonic musicians, a fatiguing contraction significantly improved motor performance. The improvement lasted less than 5 minutes and appeared only after fatigue of the affected upper limb. In contrast, in musicians with non-dystonic motor impairment, motor performance remained unchanged or worsened, and normal musician performance consistently worsened. © 2001 Movement Disorder Society.
Journal of the Peripheral Nervous System, 2000

Journal of Neurology, Neurosurgery & Psychiatry, 1997
Objectives-To report the long term eVect of the combined treatment with high dose intravenous imm... more Objectives-To report the long term eVect of the combined treatment with high dose intravenous immunoglobulins (IVIg) and oral cyclophosphamide (CTX) in patients with multifocal motor neuropathy, and to determine whether the association of oral CTX in these patients may help to delay and, possibly, suspend IVIg infusions. Methods-Six patients with multifocal motor neuropathy responding to an initial course of IVIg (0.4 g/kg/day for five consecutive days) were followed up for 37 to 61 (mean 47) months. All patients were subsequently treated with periodic IVIg infusions (0.4 g/kg/day for two days at clinical worsening) and oral CTX (1-3 mg/kg/day). Improvement was assessed using the Rankin disability scale, a functional impairment scale for upper and lower limbs, and the MRC rating scale on the 20 most aVected muscles. Electrophysiological and antiglycolipid antibody studies were performed before treatment, then yearly during follow up. Results-All patients improved during treatment and, by the end of follow up or before worsening after therapy suspension, the median Rankin (P=0.0335) and upper (P=0.0015) and lower limb (P=0.0301) impairment scores and the mean MRC (P=0.0561) score were improved. By that time the number of nerves with partial motor conduction block was reduced (P=0.0197) and antiglycolipid antibody titres had decreased in all but one patient. All patients required periodic IVIg infusions to maintain improvement but, after three to seven months of oral CTX, the interval between IVIg infusions could be progressively prolonged until, in three patients, both treatments could be stopped for up to two years before clinical worsening. The main complications, both related to oral CTX, were haemorrhagic cystitis in two patients and persistent amenorrhea in one patient. Conclusions-IVIg can induce and maintain improvement in multifocal motor neuropathy but does not eradicate the disease. Oral CTX may help to induce a sustained remission but it is not devoid of side eVects and might therefore be reserved for patients with multifocal motor neuropathy who require frequent IVIg infusions to maintain improvement.
Journal of Neurology, 1997
Multifocal motor neuropathy (MMN) is characterized by a progressive, asymmetric lower motor neuro... more Multifocal motor neuropathy (MMN) is characterized by a progressive, asymmetric lower motor neuron weakness with or without mild sensory involvement . Early diagnosis of MMN is important because it often responds to treatment . Although the presence of motor conduction block (MCB) is considered an essential feature of MMN, no agreed definition of MCB currently exists . Detailed electrophysiological findings before and after intravenous immunoglobulin (IVIg) treatment have been reported [4], but there have been no studies to date on the spontaneous or treatment-induced variations of the neurophysiological parameters over time in this condition.

Journal of Neurology, 1991
In recent years, new neuroimaging techniques have revived interest in syringomyelia with respect ... more In recent years, new neuroimaging techniques have revived interest in syringomyelia with respect to indications and results of surgery. Fifty patients, 36 of whom underwent surgery, have been reviewed. All patients but 3 underwent a new clinical assessment and 33 of them were also neurophysiologically investigated. In approximately one-third of the non-surgically treated patients the clinical course was benign. In 26 of the surgically treated patients an improvement was noted at the short-term assessment both for spasticity and pain, but in most of them it was not maintained in the medium term. Therefore, an accurate selection of the patients to be treated surgically is strongly recommended, particularly when the natural history of the disease is considered. Decompression of the posterior fossa seems to give the best results, yet no curative surgical treatment has been devised to date.

Journal of Neural Engineering, 2007
The clinical efficacy of high-frequency deep brain stimulation (DBS) for Parkinson's disease and ... more The clinical efficacy of high-frequency deep brain stimulation (DBS) for Parkinson's disease and other neuropsychiatric disorders likely depends on the modulation of neuronal rhythms in the target nuclei. This modulation could be effectively measured with local field potential (LFP) recordings during DBS. However, a technical drawback that prevents LFPs from being recorded from the DBS target nuclei during stimulation is the stimulus artefact. To solve this problem, we designed and developed 'FilterDBS', an electronic amplification system for artefact-free LFP recordings (in the frequency range 2-40 Hz) during DBS. After defining the estimated system requirements for LFP amplification and DBS artefact suppression, we tested the FilterDBS system by conducting experiments in vitro and in vivo in patients with advanced Parkinson's disease undergoing DBS of the subthalamic nucleus (STN). Under both experimental conditions, in vitro and in vivo, the FilterDBS system completely suppressed the DBS artefact without inducing significant spectral distortion. The FilterDBS device pioneers the development of an adaptive DBS system retroacted by LFPs and can be used in novel closed-loop brain-machine interface applications in patients with neurological disorders. 6
Journal of Cognitive Neuroscience, 2011
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Papers by Sergio Barbieri