Marco Cursi

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder characterized by hamartomatous neurological lesions that exhibit abnormal cell proliferation and differentiation. Hyperactivation of mTOR pathway by mutations in either the Tsc1 or Tsc2 gene underlies TSC pathogenesis, but involvement of specific neural cell populations in the formation of TSC-associated neurological lesions remains unclear. We deleted Tsc1 in Emx1-expressing embryonic telencephalic neural stem cells (NSCs) and found that mutant mice faithfully recapitulated TSC neuropathological lesions, such as cortical lamination defects and subependymal nodules (SENs). These alterations were caused by enhanced generation of SVZ neural progeny, followed by their premature differentiation and impaired maturation during both embryonic and postnatal development. Notably, mTORC1-dependent Akt inhibition and STAT3 activation were involved in the reduced self-renewal and earlier neuronal and astroglial differentiation of mutant NSCs. Thus, finely tuned mTOR activation in embryonic NSCs may be critical to prevent development of TSC-associated brain lesions.

To explore cognitive, EEG, and MRI features in COVID-19 survivors up to 10 months after hospital discharge.Adult patients with a recent diagnosis of COVID-19 and reporting subsequent cognitive complaints underwent neuropsychological assessment and 19-channel-EEG within 2 months (baseline, N = 49) and 10 months (follow-up, N = 33) after hospital discharge. A brain MRI was obtained for 36 patients at baseline. Matched healthy controls were included. Using eLORETA, EEG regional current densities and linear lagged connectivity values were estimated. Total brain and white matter hyperintensities (WMH) volumes were measured. Clinical and instrumental data were evaluated between patients and controls at baseline, and within patient whole group and with/without dysgeusia/hyposmia subgroups over time. Correlations among findings at each timepoint were computed.At baseline, 53% and 28% of patients showed cognitive and psychopathological disturbances, respectively, with executive dysfunctions correlating with acute-phase respiratory distress. Compared to healthy controls, patients also showed higher regional current density and connectivity at delta band, correlating with executive performances, and greater WMH load, correlating with verbal memory deficits. A reduction of cognitive impairment and delta band EEG connectivity were observed over time, while psychopathological symptoms persisted. Patients with acute dysgeusia/hyposmia showed lower improvement at memory tests than those without. Lower EEG delta band at baseline predicted worse cognitive functioning at follow-up.COVID-19 patients showed interrelated cognitive, EEG, and MRI abnormalities 2 months after hospital discharge. Cognitive and EEG findings improved at 10 months. Dysgeusia and hyposmia during acute COVID-19 were related with increased vulnerability in memory functions over time.

EEG coherence can be used to evaluate the functionality of cortical connections and to get information about the synchronization of the regional cortical activity. We studied EEG coherence in patients affected by clinically probable Alzheimer's disease (AD) in order to quantify the modifications in the cortico-cortical or cortico-subcortical connections. The EEGs were recorded in 10 AD patients (with mild or moderate degrees of dementia) and in 10 normal age-matched subjects, at rest and eye-closed, from 16 electrodes with linked-ears reference. Spectral parameters and coherence were calculated by a multichannel autoregressive model using 50 artifact-free epochs, 1 s duration each. Alpha coherence was significantly decreased in 6 patients, the decrease being more accentuated in the area near the electrode taken into account; a significant delta coherence increase was found in a few patients between frontal and posterior regions. The AD group showed a significant decrease of alpha band coherence, in particular in temporo-parieto-occipital areas, more evident in patients with a more severe cognitive impairment. These abnormalities could reflect two different pathophysiological changes: the alpha coherence decrease could be related to alterations in cortico-cortical connections, whereas the delta coherence increase could be related to the lack of influence of subcortical cholinergic structures on cortical electrical activity.

Transcranial direct current stimulation is emerging as a promising tool for the treatment of several neurological conditions, including cerebral ischemia. The therapeutic role of this noninvasive treatment is, however, limited to chronic phases of stroke. We thus ought to investigate whether different stimulation protocols could also be beneficial in the acute phase of experimental brain ischemia.The influence of both cathodal and anodal transcranial direct current stimulation in modifying brain metabolism of healthy mice was first tested by nuclear magnetic resonance spectroscopy. Then, mice undergoing transient proximal middle cerebral artery occlusion were randomized and treated acutely with anodal, cathodal, or sham transcranial direct current stimulation. Brain metabolism, functional outcomes, and ischemic lesion volume, as well as the inflammatory reaction and blood brain barrier functionality, were analyzed.Cathodal stimulation was able, if applied in the acute phase of stroke, to preserve cortical neurons from the ischemic damage, to reduce inflammation, and to promote a better clinical recovery compared with sham and anodal treatments. This finding was attributable to the significant decrease of cortical glutamate, as indicated by nuclear magnetic resonance spectroscopy. Conversely, anodal stimulation induced an increase in the postischemic lesion volume and augmented blood brain barrier derangement.Our data indicate that transcranial direct current stimulation exerts a measurable neuroprotective effect in the acute phase of stroke. However, its timing and polarity should be carefully identified on the base of the pathophysiological context to avoid potential harmful side effects.

Converging evidence is consistent with the view that fatigue in Multiple Sclerosis is independent from pyramidal tract involvement, suggesting a possible involvement of frontal areas. During voluntary movement, changes of the EEG rhythms can be observed over sensorimotor areas. Event-related desynchronization (ERD) of the 10 and 20 Hz frequency bands occurs during motor planning and execution and is followed after movement termination by event-related synchronization (ERS), expressing cortical idling or inhibition. We evaluated the pattern of cortical activation to voluntary movement in MS patients complaining of fatigue assessed using the Fatigue Severity Scale. Fifteen MS patients complaining of fatigue, 18 MS patients without fatigue, and 14 normal controls were studied. The two patients groups were similar for age, sex, disease duration, and were not disabled (score <1.5 at the Expanded Disability Status Scale). Twenty-nine channel EEG was recorded during about 60 self-paced extensions of the right thumb. The onset latency and amount of the contralateral sensorimotor (C3 electrode) 10 and 18–22 Hz ERD were similar in the three groups. ERD was more widespread anteriorly in the fatigue group compared with normal controls (P < 0.01 over Fz electrode). Postmovement contralateral sensorimotor 18–22 Hz ERS was significantly lower in fatigue MS patients compared with normal subjects (P < 0.005) and with nonfatigue MS patients (P = 0.02). These findings are consistent with a central origin of fatigue in MS and indicate cortical dysfunction even during a simple motor task, resulting in hyperactivity during movement execution and failure of the inhibitory mechanisms intervening after movement termination.

Abstract Shortly after the application of weak transcranial direct current stimulation (tDCS) to the animal and human brain, changes in corticospinal excitability, which mainly depend on polarity, duration and current density of the stimulation protocol, have been reported. In humans, anodal tDCS has been reported to enhance motor‐evoked potentials (MEPs) elicited by transcranial brain stimulation while cathodal tDCS has been shown to decrease them. Here we investigated the effects produced by tDCS on mice motor cortex. MEPs evoked by transcranial electric stimulation were recorded from forelimbs of 12 C57BL/6 mice, under sevofluorane anaesthesia, before and after (0, 5 and 10 min) anodal and cathodal tDCS (tDCS duration 10 min). With respect to sham condition stimulation (anaesthesia), MEP size was significantly increased immediately after anodal tDCS, and was reduced after cathodal tDCS (∼20% vs. sham). Both effects declined towards basal levels in the following 10 min. Although the site and mechanisms of action of tDCS need to be more clearly identified, the directionality of effects of tDCS on mice MEPs is consistent with previous findings in humans. The feasibility of tDCS in mice suggests the potential applicability of this technique to assess the potential therapeutic options of brain polarization in animal models of neurological and neuropsychiatric diseases.

A sixth month phase II multicenter-pilot trial with a low dose of the opiate antagonist Naltrexone (LDN) has been carried out in 40 patients with primary progressive multiple sclerosis (PPMS). The primary end points were safety and tolerability. Secondary outcomes were efficacy on spasticity, pain, fatigue, depression, and quality of life. Clinical and biochemical evaluations were serially performed. Protein concentration of β-endorphins (BE) and mRNA levels and allelic variants of the μ-opiod receptor gene (OPRM1) were analyzed. Five dropouts and two major adverse events occurred. The remaining adverse events did not interfere with daily living. Neurological disability progressed in only one patient. A significant reduction of spasticity was measured at the end of the trial. BE concentration increased during the trial, but no association was found between OPRM1 variants and improvement of spasticity. Our data clearly indicate that LDN is safe and well tolerated in patients with PPMS.

Our study evaluated motor cortex involvement during silent reading of sentences referring to hand actions. We aimed at defining whether sentential polarity (affirmative vs. negative) would modulate motor cortex activation using the event-related desynchronization (ERD) analysis of the mu rhythm. Eleven healthy volunteers performed a reading task involving 160 sentences (80 affirmative: 40 hand-related, 40 abstract; 80 negative: 40 hand-related, 40 abstract). After reading each sentence, subjects had to decide whether the verb was high or low frequency in Italian. Electroencephalographic (EEG) activity was recorded with 32 surface electrodes and mu ERD analyses were performed for each subject. Hand-action related sentences induced a greater mu ERD over the left premotor and motor hand areas compared to abstract sentences. Mu ERD was greater and temporally delayed when the hand-related verbs were presented in the negative versus affirmative form. As predicted by the “embodied semantic” theory of language understanding, motor areas were activated during sentences referring to hand actions. In addition, motor cortex activation was larger for negative than affirmative motor sentences, a finding compatible with the hypothesis that comprehension is more demanding in the specific case of motor content negation.

Motor imagery (MI) and action observation (AO) are considered effective cognitive tools for motor learning, but little work directly compared their cortical activation correlate in relation with subsequent performance. We compared AO and MI in promoting early learning of a complex four-limb, hand–foot coordination task, using electroencephalographic (EEG) and kinematic analysis. Thirty healthy subjects were randomly assigned into three groups to perform a training period in which AO watched a video of the task, MI had to imagine it, and Control (C) was involved in a distracting computation task. Subjects were then asked to actually perform the motor task with kinematic measurement of error time with respect to the correct motor performance. EEG was recorded during baseline, training and task execution, with task-related power (TRPow) calculation for sensorimotor (alpha and beta) rhythms reactive with respect to rest. During training, the AO group had a stronger alpha desynchronization than the MI and C over frontocentral and bilateral parietal areas. However, during task execution, AO group had greater beta synchronization over bilateral parietal regions than MI and C groups. This beta synchrony furthermore demonstrated the strongest association with kinematic errors, which was also significantly lower in AO than in MI. These data suggest that sensorimotor activation elicited by action observation enhanced motor learning according to motor performance, corresponding to a more efficient activation of cortical resources during task execution. Action observation may be more effective than motor imagery in promoting early learning of a new complex coordination task.

Objective. Virtual reality (VR) has been proposed as a potentially useful tool for motor assessment and rehabilitation. The objective of this study was to investigate the usefulness of VR in the assessment of short-term motor learning in multiple sclerosis (MS). Methods. Twelve right-handed MS patients and 12 control individuals performed a motor-tracking task with their right upper limb, following the trajectory of an object projected on a screen along with online visual feedback on hand position from a sensor on the index finger. A pretraining test (3 trials), a training phase (12 trials), and a posttraining test (3 trials) were administered. Distances between performed and required trajectory were computed. Results. Both groups performed worse in depth planes compared to the frontal ( x, z) plane ( P &lt; .006). MS patients performed worse than control individuals in the frontal plane at both evaluations ( P &lt; .015), whereas they had lower percent posttraining improvement in the depth planes only ( P = .03). Conclusions. The authors' VR system detected impaired motor learning in MS patients, especially for task features requiring a complex integration of sensory information (movement in the depth planes). These findings stress the need for careful customization of rehabilitation strategies, which must take into account the patients' motor, sensory, and cognitive limitations.

Drawing a clinical distinction between frontotemporal dementia (FTD) and Alzheimer's disease (AD) is tricky, particularly at the early stages of disease. This study evaluates the possibility in differentiating 39 FTD, 39 AD, and 39 controls (CTR) by means of power spectral analysis and standardized low resolution brain electromagnetic tomography (sLORETA) within delta, theta, alpha 1 and 2, beta 1, 2, and 3 frequency bands. Both analyses revealed in AD patients, relative to CTR, higher expression of diffuse delta/theta and lower central/posterior fast frequency (from alpha1 to beta2) bands. FTD patients showed diffuse increased theta power compared with CTR and lower delta relative to AD patients. Compared with FTD, AD patients showed diffuse higher theta power at spectral analysis and, at sLORETA, decreased alpha2 and beta1 values in central/temporal regions. Spectral analysis and sLORETA provided complementary information that might help characterizing different patterns of electroencephalogram (EEG) oscillatory activity in AD and FTD. Nevertheless, this differentiation was possible only at the group level because single patients could not be discerned with sufficient accuracy.

Summary Tuberous sclerosis complex (TSC) is a dominantly inherited disease with high penetrance and morbidity, and is caused by mutations in either of two genes, TSC1 or TSC2. Most affected individuals display severe neurological manifestations – such as intractable epilepsy, mental retardation and autism – that are intimately associated with peculiar CNS lesions known as cortical tubers (CTs). The existence of a significant genotype-phenotype correlation in individuals bearing mutations in either TSC1 or TSC2 is highly controversial. Similar to observations in humans, mouse modeling has suggested that a more severe phenotype is associated with mutation in Tsc2 rather than in Tsc1. However, in these mutant mice, deletion of either gene was achieved in differentiated astrocytes. Here, we report that loss of Tsc1 expression in undifferentiated radial glia cells (RGCs) early during development yields the same phenotype detected upon deletion of Tsc2 in the same cells. Indeed, the same aberrations in cortical cytoarchitecture, hippocampal disturbances and spontaneous epilepsy that have been detected in RGC-targeted Tsc2 mutants were observed in RGC-targeted Tsc1 mutant mice. Remarkably, thorough characterization of RGC-targeted Tsc1 mutants also highlighted subventricular zone (SVZ) disturbances as well as STAT3-dependent and -independent developmental-stage-specific defects in the differentiation potential of ex-vivo-derived embryonic and postnatal neural stem cells (NSCs). As such, deletion of either Tsc1 or Tsc2 induces mostly overlapping phenotypic neuropathological features when performed early during neurogenesis, thus suggesting that the timing of mTOR activation is a key event in proper neural development.

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. TSC is characterized by benign tumors arising in different organs and severe neuropsychiatric symptoms, such as epilepsy, intellectual disability, autism, anxiety and depressive behaviour. Rapamycin is a potent inhibitor of mTOR and its efficacy in treating epilepsy and neurological symptoms remains elusive. In a mouse model in which Tsc1 has been deleted in embryonic telencephalic neural stem cells, we analyzed anxiety- and depression-like behaviour by elevated-plus maze (EPM), open-field test (OFT), forced-swim test (FST) and tail-suspension test (TST), after chronic administration of rapamycin. In addition, spectral analysis of background EEG was performed. Rapamycin-treated mutant mice displayed a reduction in anxiety- and depression-like phenotype, as shown by the EPM/OFT and FST, respectively. These results were inline with EEG power spectra outcomes. The same effects of rapamycin were observed in wild-type mice. Notably, in heterozygous animals we did not observe any EEG and/or behavioural variation after rapamycin treatment. Together these results suggest that both TSC1 deletion and chronic rapamycin treatment might have a role in modulating behaviour and brain activity, and point out to the potential usefulness of background EEG analysis in tracking brain dysfunction in parallel with behavioural testing.

The event-related desynchronization (ERD) to voluntary movement is an indicator of cortical activation with a high time resolution and a specific spatial representation. We have evaluated 10 patients affected by Parkinson's disease (PD), free from L-dopa treatment for at least 12 hours, and 10 control subjects. Each subject underwent ERD examination during self-paced movement (SPM) and during contingent negative variation (CNV) paradigms. ERD was measured as the percentage decrease of alpha band power and calculated for frequency bands of 1 Hz, ranging between 8 and 12 Hz. For group comparisons, the frequency showing the highest ERD was selected for each subject and for each side. In the control group, ERD in the CNV paradigm began over the contralateral centroparietal electrodes 1475 ms before movement onset of the right hand and 1375 ms for the left. In the SPM paradigm, ERD started over the contralateral central electrodes 2150 ms and 1775 ms before movement onset of the right and left hand, respectively. In the PD group, ERD started over the contralateral central areas 800 ms and 475 ms before movement onset of the right and left hand, respectively, for CNV paradigm and 1200 ms and 750 ms for the right and left hand, respectively, for SPM paradigm. Therefore, contralateral ERD began closer to movement onset in PD compared with the control group in both paradigms. ERD over the sensorimotor areas ipsilateral to the movement was not significantly different in PD compared with the control group. The finding of delayed contralateral ERD in PD is according to the view that functional cortical activation related to movement preparation is impaired in PD. The lack of group differences in the onset of ipsilateral ERD, which appears close to movement execution than contralateral ERD both in normal subjects and in PD, suggests that different mechanisms may be involved in generating ERD over the hemispheres ipsilateral and contralateral to the movement, and that only the latter are impaired in PD.

Transcranial direct current stimulation (tDCS) in humans has been shown to affect the size of visual evoked potentials (VEPs) in a polarity-dependent way. VEPs have been widely employed in mice to study the visual system in physiological and pathological conditions and are extensively used as animal models of neurological and visual disorders. The present study was performed to evaluate whether mice VEPs could be modulated by tDCS in the same manner as in humans. We describe here the effects of 10 min tDCS (anodal, cathodal or no stimulation) on flash-VEPs in C57BL/6 mice under sevoflurane anesthesia. VEP amplitudes of the first major peak (P1) were analyzed before, at 0, 5 and 10 min after tDCS. Compared with no stimulation condition, anodal tDCS increased P1 amplitude slightly more than 25%, while cathodal stimulation had opposite effects, with a decrease of P1 amplitude by about 30%. After-effects tended to reverse toward basal levels within 10 min after tDCS. These results, suggesting polarity-dependent modulation similar to what described in humans of tDCS effects on VEPs, encourage the use of mice models to study tDCS mechanisms of action and explore therapeutic applications on neurological models of disease.

Rac GTPases regulate the development of cortical/hippocampal GABAergic interneurons by affecting the early development and migration of GABAergic precursors. We have addressed the function of Rac1 and Rac3 proteins during the late maturation of hippocampal interneurons. We observed specific phenotypic differences between conditional Rac1 and full Rac3 knockout mice. Rac1 deletion caused greater generalized hyperactivity and cognitive impairment compared with Rac3 deletion. This phenotype matched with a more evident functional impairment of the inhibitory circuits in Rac1 mutants, showing higher excitability and reduced spontaneous inhibitory currents in the CA hippocampal pyramidal neurons. Morphological analysis confirmed a differential modification of the inhibitory circuits: deletion of either Rac caused a similar reduction of parvalbumin-positive inhibitory terminals in the pyramidal layer. Intriguingly, cannabinoid receptor-1-positive terminals were strongly increased only in the CA1 of Rac1-depleted mice. This increase may underlie the stronger electrophysiological defects in this mutant. Accordingly, incubation with an antagonist for cannabinoid receptors partially rescued the reduction of spontaneous inhibitory currents in the pyramidal cells of Rac1 mutants. Our results show that Rac1 and Rac3 have independent roles in the formation of GABAergic circuits, as highlighted by the differential effects of their deletion on the late maturation of specific populations of interneurons.

Abstract Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data may help to optimize anatomical and temporal resolution in the investigation of cortical function. Successful removal of fMRI scanning artifacts from continuous EEG in simultaneous recordings has been reported. We assessed the feasibility of recording reliable visual evoked potentials (VEPs) during fMRI scanning using available artifact removing procedures. EEG during administration of visual stimuli was recorded using MRI‐compatible 32‐channel equipment in nine normal subjects (mean age, 23.9 ± 2.5 years), with and without fMRI acquisition. fMRI scanning and cardioballistographic artifacts were removed after subtraction of averaged artifact waveforms. Consistency between VEPs waveforms and of P1 and N1 peak latencies and amplitudes in the two conditions was assessed. Good correlation was found between VEP waveforms (Pearson's correlation coefficient: r P between 0.76–0.94 across subjects; P &lt; 0.0001) and between latency or amplitude of P1 and N1 peaks (latencies: r = 0.7, P &lt; 0.035; amplitudes: r &gt; 0.65, P &lt; 0.05; Spearman rank correlation coefficient) in the two recording conditions. No significant differences were found between P1 and N1 parameters in the two conditions (Wilcoxon signed rank test). Consistent VEP waveforms, latencies, and amplitudes with and without fMRI scanning indicate that reliable VEPs may be obtained simultaneously with fMRI recording. This possibility might be helpful by shortening recording times and reducing variability from learning, habituation, and fatigue phenomena from separate recordings for the integration of event‐related EEG and fMRI data. Hum. Brain Mapping 24:291–298, 2005. © 2005 Wiley‐Liss, Inc.

We investigated the neural correlates underlying response inhibition and conflict detection processes using ERPs and source localization analyses simultaneously acquired during fMRI scanning. ERPs were elicited by a simple reaction time task (SRT), a Go/NoGo task, and a Stroop-like task (CST). The cognitive conflict was thus manipulated in order to probe the degree to which information processing is shared across cognitive systems. We proposed to dissociate inhibition and interference conflict effects on brain activity by using identical Stroop-like congruent/incongruent stimuli in all three task contexts and while varying the response required. NoGo-incongruent trials showed a larger N2 and enhanced activations of rostral anterior cingulate cortex (ACC) and pre-supplementary motor area, whereas Go-congruent trials showed a larger P3 and increased parietal activations. Congruent and incongruent conditions of the CST task also elicited similar N2, P3 and late negativity (LN) ERPs, though CST-incongruent trials revealed a larger LN and enhanced prefrontal and ACC activations. Considering the stimulus probability and experimental manipulation of our study, current findings suggest that NoGo N2 and frontal NoGo P3 appear to be more associated to response inhibition rather than a specific conflict monitoring, whereas occipito-parietal P3 of Go and CST conditions may be more linked to a planned response competition between the prepared and required response. LN, however, appears to be related to higher level conflict monitoring associated with response choice-discrimination but not when the presence of cognitive conflict is associated with response inhibition.

ABSTRACT Background Sensory tricks such as touching the face with fingertips often improve cervical dystonia [CD]. This study is to determine whether sensory tricks modulate motor cortex excitability, assessed by paired‐pulse transcranial magnetic stimulation [p‐pTMS]. Methods Eight patients with rotational CD underwent p‐pTMS, at rest and when the sensory trick was applied. To test intracortical inhibition [ICI] and facilitation [ICF], the amplitude ratio between conditioned and unconditioned cortical motor evoked potentials was measured at several interstimulus intervals (ISI 1, 3, 15, and 20 ms) and compared with controls mimicking patients' sensory tricks. Results At rest, a significant ICF enhancement was found at ISIs 15 through 20 in patients compared with controls, whereas no significant ICI changes were observed. Sensory tricks significantly reduced the abnormal ICF in patients and did not induce any change in controls. Conclusions In our CD patients, sensory tricks seem to improve dystonia through an inhibitory effect on motor cortex excitability. © 2014 International Parkinson and Movement Disorder Society

ObjectiveThis study assessed the long-term effect of the eversion technique for carotid endarterectomy (e-CEA) on arterial baroreflex and peripheral chemoreflex function.MethodsThe study included 13 patients who underwent, between 2001 and 2006, bilateral e-CEA and 16 who underwent bilateral standard CEA (s-CEA) to eliminate the complicating effects of intact contralateral carotid sinus function. Exclusion criteria were age >70 years, diabetes mellitus, chronic pulmonary disease, ischemic cardiac disease or medical therapy with β-blockers, cardiac arrhythmia, neurologic deficits, carotid restenosis, and previous neck or chest surgery or irradiation. Young and aged-matched healthy individuals were recruited as controls. All patients underwent standard cardiovascular reflex tests, including lying-to-standing, orthostatic hypotension, deep breathing, and Valsalva maneuver. Autonomic cardiovascular modulation was indirectly evaluated by spectral analysis of heart rate variability and systolic arterial pressure variability. The chemoreflex sensitivity to hypoxia was obtained during classic rebreathing tests from the slopes of the linear regression of minute ventilation (VE) vs arterial oxygen saturation measured by pulse oximetry (SpO2%) and partial pressure of end-tidal oxygen (PetO2).ResultsPatients (16 men; age, 62.4 ± 8.0 years) were enrolled after a mean interval of 24 ± 17 months from the last CEA. All were asymptomatic, and results of standard tests were negative. Residual baroreflex performance was documented in both patient groups, although reduced, compared with young controls. Notably, baroreflex sensitivity (msec/mm Hg) was better maintained after e-CEA than after s-CEA at rest (young controls, 19.93 ± 9.50; age-matched controls, 7.75 ± 5.68; e-CEA, 13.85 ± 14.54; and s-CEA, 3.83 ± 1.15; analysis of variance [ANOVA], P = .001); and at standing (young controls, 7.83 ± 2.55; age-matched controls, 3.71 ± 1.59; e-CEA, 7.04 ± 5.62; and s-CEA 3.57 ± 3.80; ANOVA, P = .001). Similarly, chemoreflex sensitivity to hypoxia was maintained in both patient groups, which did not differ from each other, and was reduced compared with controls (controls vs patient groups ΔVE/ΔSpO2: –1.37 ± 0.33 vs –0.33 ± 0.08 and SpO2% –0.29 ± 0.13 L/min; P = .002; ΔVE/ΔPetO2: –0.20 ± 0.1 vs –0.01 ± 0.0 and –0.07 ± 0.02 L/min/mm Hg; P = .04, ANOVA with least significant difference correction for multiple comparisons).ConclusionsOur data show that e-CEA, even when performed on both sides, preserves baroreflexes and chemoreflexes and, therefore, does not confer permanent carotid sinus denervation. Also, e-CEA does not increase long-term arterial pressure variability, and this suggests that perioperative hemodynamic derangements can be attributed to the temporary effects of surgical trauma. This study assessed the long-term effect of the eversion technique for carotid endarterectomy (e-CEA) on arterial baroreflex and peripheral chemoreflex function. The study included 13 patients who underwent, between 2001 and 2006, bilateral e-CEA and 16 who underwent bilateral standard CEA (s-CEA) to eliminate the complicating effects of intact contralateral carotid sinus function. Exclusion criteria were age >70 years, diabetes mellitus, chronic pulmonary disease, ischemic cardiac disease or medical therapy with β-blockers, cardiac arrhythmia, neurologic deficits, carotid restenosis, and previous neck or chest surgery or irradiation. Young and aged-matched healthy individuals were recruited as controls. All patients underwent standard cardiovascular reflex tests, including lying-to-standing, orthostatic hypotension, deep breathing, and Valsalva maneuver. Autonomic cardiovascular modulation was indirectly evaluated by spectral analysis of heart rate variability and systolic arterial pressure variability. The chemoreflex sensitivity to hypoxia was obtained during classic rebreathing tests from the slopes of the linear regression of minute ventilation (VE) vs arterial oxygen saturation measured by pulse oximetry (SpO2%) and partial pressure of end-tidal oxygen (PetO2). Patients (16 men; age, 62.4 ± 8.0 years) were enrolled after a mean interval of 24 ± 17 months from the last CEA. All were asymptomatic, and results of standard tests were negative. Residual baroreflex performance was documented in both patient groups, although reduced, compared with young controls. Notably, baroreflex sensitivity (msec/mm Hg) was better maintained after e-CEA than after s-CEA at rest (young controls, 19.93 ± 9.50; age-matched controls, 7.75 ± 5.68; e-CEA, 13.85 ± 14.54; and s-CEA, 3.83 ± 1.15; analysis of variance [ANOVA], P = .001); and at standing (young controls, 7.83 ± 2.55; age-matched controls, 3.71 ± 1.59; e-CEA, 7.04 ± 5.62; and s-CEA 3.57 ± 3.80; ANOVA, P = .001). Similarly, chemoreflex sensitivity to hypoxia was maintained in both patient groups, which did not differ from each other, and was reduced compared with controls (controls vs patient groups ΔVE/ΔSpO2: –1.37 ± 0.33 vs –0.33 ± 0.08 and SpO2% –0.29 ± 0.13 L/min; P = .002; ΔVE/ΔPetO2: –0.20 ± 0.1 vs –0.01 ± 0.0 and –0.07 ± 0.02 L/min/mm Hg; P = .04, ANOVA with least significant difference correction for multiple comparisons). Our data show that e-CEA, even when performed on both sides, preserves baroreflexes and chemoreflexes and, therefore, does not confer permanent carotid sinus denervation. Also, e-CEA does not increase long-term arterial pressure variability, and this suggests that perioperative hemodynamic derangements can be attributed to the temporary effects of surgical trauma.

Background and ObjectivesThe 3 clinical presentations of primary progressive aphasia (PPA) reflect heterogenous neuropathology, which is difficult to be recognized in vivo. Resting-state (RS) EEG is promising for the investigation of brain electrical substrates in neurodegenerative conditions. In this study, we aim to explore EEG cortical sources in the characterization of the 3 variants of PPA.MethodsThis is a cross-sectional, single-center, memory center–based cohort study. Patients with PPA and healthy controls were consecutively recruited at the Neurology Unit, IRCCS San Raffaele Scientific Institute (Milan, Italy). Each participant underwent an RS 19-channel EEG. Using standardized low-resolution brain electromagnetic tomography, EEG current source densities were estimated at voxel level and compared among study groups. Using an RS functional MRI-driven model of source reconstruction, linear lagged connectivity (LLC) values within language and extra-language brain networks were obtained and analyzed among groups.ResultsEighteen patients with logopenic PPA variant (lvPPA; mean age = 72.7 ± 6.6; % female = 52.4), 21 patients with nonfluent/agrammatic PPA variant (nfvPPA; mean age = 71.7 ± 8.1; % female = 66.6), and 9 patients with semantic PPA variant (svPPA; mean age = 65.0 ± 6.9; % female = 44.4) were enrolled in the study, together with 21 matched healthy controls (mean age = 69.2 ± 6.5; % female = 57.1). Patients with lvPPA showed a higher delta density than healthy controls (p < 0.01) and patients with nfvPPA (p < 0.05) and svPPA (p < 0.05). Patients with lvPPA also displayed a greater theta density over the left posterior hemisphere (p < 0.01) and lower alpha2 values (p < 0.05) over the left frontotemporal regions than controls. Patients with nfvPPA showed a diffuse greater theta density than controls (p < 0.05). LLC was altered in all patients relative to controls (p < 0.05); the alteration was greater at slow frequency bands and within language networks than extra-language networks. Patients with lvPPA also showed greater LLC values at theta band than patients with nfvPPA (p < 0.05).DiscussionEEG findings in patients with PPA suggest that lvPPA-related pathology is associated with a characteristic disruption of the cortical electrical activity, which might help in the differential diagnosis from svPPA and nfvPPA. EEG connectivity was disrupted in all PPA variants, with distinct findings in disease-specific PPA groups.Classification of EvidenceThis study provides Class IV evidence that EEG analysis can distinguish PPA due to probable Alzheimer disease from PPA due to probable FTD from normal aging.

Deletion of one or more synapsin genes in mice results in a spontaneous epilepsy. In these animals, seizures can be evoked by opening or moving the cage. Aim of the present study was to characterize the evolution of the epileptic phenotype by neurophysiological examination and behavioral observation in synapsin triple knock-out (Syn-TKO) mice. Syn-TKO mice were studied from 20 postnatal days (PND) up to 6 months of age by video-EEG recording and behavioral observation. Background EEG spectral analysis was performed and data were compared to WT animals. Syn-TKO revealed rare spontaneous seizures and increased susceptibility to evoked seizures in mice from 60 to 100 PND. Spontaneous and evoked seizures presented similar duration and morphology. At times, seizures were followed by a post-ictal phase characterized by a 4 Hz rhythmic activity and immobility of the animal. Spectral analysis of background EEG evidenced a slowing of the theta-alpha peak in Syn-TKO mice compared to WT mice within the period from PND 40 to 100. These data indicate that Syn-TKO mice do not exhibit a linear progression of the epileptic phenotype, with the period corresponding to a higher susceptibility to evoked seizures characterized by background EEG slowing. This aspect might be connected to brain dysfunction often associated to epilepsy in the interictal period.

The localization of human hand primary motor area (M1) has been the object of several studies during the last decades. EEG source analysis, functional magnetic resonance imaging (fMRI) and focal transcranial magnetic stimulation (TMS) are non-invasive methods for localizing M1 with good accuracy compared to direct electrocorticography (ECoG) results. EEG sources were reconstructed with Cortical Current Density (CCD) method, allowing to evaluate simultaneous and distributed patterns of activation and to increase accuracy by constraining on information derived from fMRI (fMRI-CCD). The aim of this study was to compare the M1 contribution of movement-related cortical potentials (MRCP) with TMS and fMRI results and to test the effect of constraints strength, algorithm norm and localization methods over CCD reconstruction. Seven right-handed healthy subjects underwent 64-channel EEG recording of MRCP to right thumb movement, focal TMS mapping of the right abductor pollicis brevis muscle and fMRI during right hand movement. We found fMRI activations, EEG sources and TMS mapping corresponding to the anatomical landmark of the hand area in all subjects with fMRI and TMS center-of-gravity and in almost all subjects using fMRI-CCD with moderate constraint. A significant improvement was found using fMRI-CCD compared to CCD alone. This study confirms the usefulness of multimodal integration of fMRI, EEG and TMS in localizing M1 and the possibility to increase EEG spatial resolution using fMRI information.

Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions.Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure.The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex.Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects.

Despite the introduction of several adjuncts to improve spinal perfusion, spinal cord ischemia (SCI) remains a devastating complication of thoracoabdominal aortic aneurysm (TAAA) repair. Our aim was to assess the effects on clinical outcome of interventions triggered by motor evoked potentials (MEP) alerts. Furthermore, we want to assess whether a multimodal intraoperative neurophysiologic monitoring (IONM) protocol is helpful for stratifying patients according to the risk of SCI at the end of the vascular phase of surgery.We prospectively studied one-hundred consecutive patients who underwent TAAA repair. We applied a multimodal IONM including MEP, somatosensory evoked potentials (SEP) and peripheral nerve monitoring techniques. Signal deteriorations were classified as reversible/irreversible according to whether they recovered or not at the end of monitoring (EOM), set at the end of the vascular phase of surgery. Significant MEP changes drove a series of corrective measures aimed to improve spinal perfusion.The rate of immediate postoperative motor deficits consistent with SCI was significantly higher with irreversible MEP deteriorations compared to reversible ones. The interpretation of MEP findings at the EOM led to the development of risk categories for SCI, based on the association between MEP results and motor outcome.Our data seem to justify interventions made to reverse MEP deterioration in order to improve the clinical outcome. A multimodal IONM protocol could improve MEP interpretation at the end of the vascular phase of surgery, supporting the surgeon in their decision-making, before concluding vascular maneuvers.

Bronchopulmonary dysplasia (BPD) is the most frequent chronic lung disease in preterm newborn infants. It is a multifactorial disease caused by the interaction between environmental and genetic factors. The aim of this study is to identify genetic variants contributing to BPD development using next-generation sequencing (NGS) technology. We prospectively evaluated 378 premature newborn infants with a gestational age <32 weeks in a multicentre study from 12 Italian neonatal intensive care unit from 2009 to 2012. Infants were divided into two groups: normal controls (225) and BPD-affected infants (141) with mild (65, 46.1%), moderate (40, 28.4%) and severe (36, 25.5%) BPD. BPD was more frequent in infants with lower weight and gestational age. Antenatal steroid administration was more frequent in the control group. Postnatal infection, respiratory distress syndrome, patent ductus arterious, cerebral haemorrhage, surfactant administration, ventilatory support, diuretics and postnatal steroid administration correlated with severity of BPD. Among BPD, moderate and severe cases will be selected as BPD "extreme phenotypes", and in fact variations in 28-day oxygen need-based BPD were previously shown to be fully attributable to environmental effects whereas dependence on supplemental oxygen at 36 weeks seems to better reflect underlying genetic susceptibility. Exome analysis by NGS is in progress. Identifications of genetic markers predisposing to BPD may allow development of personalized and preventive treatments.

PurposeThe development of new drugs for the treatment of epilepsy is a major challenge for modern neurology and its first steps demand basic research. Preclinical studies on animal models of epilepsy are mainly based on the analysis of brain electrical activity to detect seizures, when they are not just limited to behavioral tests like the Racine scale.MethodsIn the present review, we discuss the importance of using time-locked video and EEG recordings (Video-EEG) coupled with behavioral tests as tools to monitor and analyze the effects of anti-epileptic drugs in pre-clinical research. Particularly, we focus on the utility of a multimodal approach based on EEG/behavioral analysis to study the beneficial effects of chronic rapamycin treatment as a potential anti-epileptogenic therapy for a broad spectrum of epilepsy, including both genetic (as in tuberous sclerosis complex) and acquired diseases.ResultsChanges and synchronization of neuronal activity of different areas have been correlated with specific behavior in both physiological and pathological conditions. In the epileptic brain, during a seizure there is an abnormal activation of many cells all at once, altering different networks.ConclusionA multimodal approach based on video, EEG analysis and behavioral tests would be the best option in preclinical studies of epilepsy.

The neuronal mechanisms involved in brain plasticity after skilled motor learning are not completely understood. We aimed to study the short-term effects of keyboard training in music-naive subjects on the motor/premotor cortex activity and interhemispheric interactions, using electroencephalography and transcranial magnetic stimulation (TMS). Twelve subjects (experimental group) underwent, before and after a two week-piano training: (1) hand-motor function tests: Jamar, grip and nine-hole peg tests; (2) electroencephalography, evaluating the mu rhythm task-related desynchronization (TRD) during keyboard performance; and (3) TMS, targeting bilateral abductor pollicis brevis (APB) and abductor digiti minimi (ADM), to obtain duration and area of ipsilateral silent period (ISP) during simultaneous tonic contraction of APB and ADM. Data were compared with 13 controls who underwent twice these measurements, in a two-week interval, without undergoing piano training. Every subject in the experimental group improved keyboard performance and left-hand nine-hole peg test scores. Pre-training, ISP durations were asymmetrical, left being longer than right. Post-training, right ISPAPB increased, leading to symmetrical ISPAPB. Mu TRD during motor performance became more focal and had a lesser amplitude than in pre-training, due to decreased activity over ventral premotor cortices. No such changes were evidenced in controls. We demonstrated that a 10-day piano-training was associated with balanced interhemispheric interactions both at rest and during motor activation. Piano training, in a short timeframe, may reshape local and inter-hemispheric motor cortical circuits.

The purpose of this study was to determine whether LDL oxidation could play an important pathogenic role in early restenosis after carotid endarterectomy. An immunologic and biochemical study was performed on a group of patients who underwent carotid endarterectomy, and the degree of intima-media thickness was measured 6 months after surgery.Fifty-two consecutive patients were included in the study. The presence of antibodies against oxidized LDL in the serum at the time of surgery was evaluated and compared with echo Doppler flow imaging 6 months after the operation. A statistically significant correlation was found between the arterial wall thickness at the site of surgery and the absolute value of IgG antibodies against oxidized LDL (P<0.012) and IgM immunocomplexes (P<0.043).The presence of antibodies against oxidized LDL at the time of surgery seems to predict a greater intima-media wall hyperplasia at 6 months after surgery, usually recognized as early restenosis.

The aim of this study is to evaluate the usefulness of a spectral function detecting cerebral hypoperfusion. Continuous electroencephalographic monitoring was employed during 47 consecutive carotid endarterectomies. Patients were assigned to 3 different groups according to the entity of electroencephalographic changes during carotid clamping (major changes: group A; moderate changes: group B; no change: group C). The desynchronization function, indicating the reduction of the 8–15 Hz band power, and the desynchronization index were calculated. Group A function decreased within 20 s from clamping, with a constant slope (7.14). Desynchronization indexes were: 76.85% (group A), 40.23% (group B) and 15.29% (group C). Difference among groups was statistically significant (P<0.0001). A case of syncope due to asystole is also reported, showing the same pattern in the descending phase of the function. The stereotyped time course of the desynchronization function describes the cerebral reaction to significant blood flow reduction. Values of desynchronization index exceeding 65% seem to correctly detect patients with cerebral hypoxic risk. The analysis of the 8–15 Hz band desynchronization is helpful in the evaluation of cerebral hypoperfusion during carotid endarterectomy. This method could be employed in monitoring different clinical situations of ischemia.

BACKGROUND: A growing body of evidence suggests a link between cognitive and pathological changes in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobar dementia (FTLD). Cognitive deficits have been investigated much less extensively in primary lateral sclerosis (PLS) than in ALS. OBJECTIVE: to investigate bioelectrical activity to Stroop test, assessing frontal function, in ALS, PLS and control groups. METHODS: 32 non-demented ALS patients, 10 non-demented PLS patients and 27 healthy subjects were included. Twenty-nine electroencephalography (EEG) channels with binaural reference were recorded during covert Stroop task performance, involving mental discrimination of the stimuli and not vocal or motor response. Group effects on event related potentials (ERPs) latency were analyzed using statistical multivariate analysis. Topographic analysis was performed using low resolution brain electromagnetic tomography (LORETA). RESULTS: ALS patients committed more errors in the execution of the task but they were not slower, whereas PLS patients did not show reduced accuracy, despite a slowing of reaction times (RTs). The main ERP components were delayed in ALS, but not in PLS, compared with controls. Moreover, RTs speed but not ERP latency correlated with clinical scores. ALS had decreased frontotemporal activity in the P2, P3 and N4 time windows compared to controls. CONCLUSION: These findings suggest a different pattern of psychophysiological involvement in ALS compared with PLS. The former is increasingly recognized to be a multisystems disorder, with a spectrum of executive and behavioural impairments reflecting frontotemporal dysfunction. The latter seems to mainly involve the motor system, with largely spared cognitive functions. Moreover, our results suggest that the covert version of the Stroop task used in the present study, may be useful to assess cognitive state in the very advanced stage of the disease, when other cognitive tasks are not applicable.

ABSTRACT Introduction There are no data on quantitative electromyography (EMG) of the external urethral sphincter (EUS) in men. The aim of this study was to obtain reference data from a group of neurologically healthy continent men with prostate pathology using a standardized technique. Methods : Sixty‐six subjects without neurological disorders were included. Motor unit potential (MUP) and interference pattern (IP) analysis were performed using multi‐MUP and turns/amplitude techniques, respectively. Results : Of 66 patients, 51 (mean age, 65.17; SD, 6.70) had localized prostate cancer (PCa), and 15 (mean age 61.67, SD 6.25) had benign prostate hyperplasia (BPH). Descriptive MUP parameters and IP‐clouds were obtained, respectively in the BPH and PCa groups. No group differences were found. Conclusions : This study provides quantitative EMG measures of EUS functionality in continent men with prostate pathology. The data could be used as reference values for patients undergoing prostate surgery to identify postoperative changes in EUS function possibly influencing continence. Muscle Nerve 50: 571–576, 2014

Conflicting reports on the usefulness of intraoperative monitoring of visual function by means of visual evoked potentials (VEPs) are reported. In order to verify the real usefulness of this method in supporting pituitary surgery, we studied 10 patients with pituitary microadenoma without any visual problems to collect normative data. 10 patients (mean age 50 yrs), undergoing trans-sphenoidal surgery for pituitary microadenomas, were studied with intraoperative VEP monitoring. All patients had a normal pre- and postoperative visual function. ERG responses were recorded in 5 patients, mean latency = 54,11 ms (±3.98 DS). Intraoperative VEPs were recorded in 18 of 20 sides (90%). The variability of N2 latency did not exceed 10% of the baseline value (before surgical manoeuvres, mean = 140.95 ms ± 18.88 SD) and the P2–N2 amplitude variability was less than 50% in all but one patient. Our study confirms that generally VEPs remain stable during microsurgical procedures. Intraoperative VEP recording might be a potentially useful tool in the monitoring of the functional integrity of the posterior visual pathway.

<h3>Objective:</h3> The aim of this study is to explore the value of EEG analysis in the characterization of the three clinical presentations of primary progressive aphasia (PPA). <h3>Background:</h3> The analysis of EEG cortical sources is promising for the investigation of neurodegenerative disorders. <h3>Design/Methods:</h3> A resting-state 19-channel EEG was obtained in 48 patients diagnosed with PPA (21 nonfluent/agrammatic variant PPA [nfv-PPA], 18 logopenic variant PPA [lv-PPA], 9 semantic variant PPA [sv-PPA]) and in 21 matched healthy controls. Applying seed-based analysis on 3T fMRI data of an independent group of young healthy controls (n.40), we built the maps of three networks belonging to the left perisylvian language network (nodes: middle temporal gyrus–MTG, inferior frontal gyrus–IFG, anterior temporal lobe–ATL) and the maps of default-mode network (DMN) and salience network (SN). Using eLORETA, EEG current source density (CSD) and linear-lagged connectivity (LLC) values were estimated and compared. CSD and LLC analysis were performed at whole-brain level and at network level, respectively. <h3>Results:</h3> Patients showed a low-to-moderate cognitive impairment. At CSD analysis lv-PPA patients showed a higher delta density than nfvPPA, svPPA and healthy subjects. They also showed a higher theta density relative to controls. Level of statistical significance showed a pronounced descending posterior-to-anterior and left-to-right gradient over the brain cortex at theta band. Also nfvPPA patients deviated from healthy subjects in terms of widespread higher theta density. LLC analysis pointed out a significantly higher connectivity at delta and theta frequency bands characterizing all three groups of patients relative to controls in language networks. Connectivity disruption was also evident in non-language networks. <h3>Conclusions:</h3> Findings in PPA patients suggest that Alzheimer’s disease (AD), but not fronto-temporal degeneration (FTD), might induce a characteristic disruption of the cortical electrical activity in lvPPA patients, detectable by EEG. EEG might thus help in the differential diagnosis between AD-related and FTD-related PPA variants. <b>Disclosure:</b> Giordano Cecchetti has nothing to disclose. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Philips. Federica Agosta has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier INC. Silvia Basaia has nothing to disclose. Dr. Spinelli has nothing to disclose. Ms. Cividini has nothing to disclose. Marco Cursi has nothing to disclose. The institution of Elisa Canu has received research support from Italian Ministry of Health . Dr. Leocadi has nothing to disclose. Roberto Santangelo, 4503 has nothing to disclose. Dr. Caso has nothing to disclose. Dr. Fanelli has nothing to disclose. Dr. Minicucci has nothing to disclose. Giuseppe Magnani has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

La narrazione di Pomponio circa l’origine e lo svolgimento del diritto è una delletestimonianze principali sul problema della certezza del diritto a Roma. Il confrontocon le riflessioni di Cicerone e Tacito sulla legge, da una parte, e con la classificazionedelle fonti del diritto di Gaio, dall’altra, lascia emergere la peculiare prospettiva diPomponio che configura lo ius certum come una categoria storica che nella fase piùantica del diritto romano si identificherebbe nelle leges, da quelle regie a quelle delleXII tavole, sulla base del voto popolare e della pubblicità.

Abstract Background The analysis of EEG cortical sources is promising for the investigation of neurodegenerative disorders. The aim of this study is to explore its value in the characterization of the three clinical presentations of primary progressive aphasia (PPA). Method A resting‐state 19‐channel EEG was obtained in 48 patients diagnosed with PPA (21 nonfluent/agrammatic variant PPA [nfv‐PPA], 18 logopenic variant PPA [lv‐PPA], 9 semantic variant PPA [sv‐PPA]) and in 21 matched healthy controls. Using eLORETA, EEG current source density (CSD) values were estimated at voxel‐level and compared among groups of patients and controls. Result Patients showed a low‐to‐moderate cognitive impairment. Lv‐PPA cases showed a higher delta density over the left frontal and temporal regions when compared to sv‐PPA subjects, and in left precuneus and posterior cingulate when compared to nfv‐PPA patients. They also displayed a higher delta density in left frontal, parietal and temporal regions than healthy subjects, and lower alpha1 density in left occipital regions compared with other patient groups. Lv‐PPA patients also showed reduced alpha2, beta1 and beta2 density over the left occipital regions when compared to healthy subjects. No significant differences were found in terms of CSD among sv‐PPA, nfv‐PPA and healthy subjects. Conclusion Consistently with our previous studies, findings in PPA patients suggest that Alzheimer’s disease (AD), but not fronto‐temporal degeneration (FTD), might induce a characteristic disruption of the cortical electrical activity, detectable by EEG. EEG might thus help in the differential diagnosis between AD‐related and FTD‐related PPA variants.

We aimed to study short-term effects of keyboard training in music-naive subjects on motor cortex activity and interhemispheric interactions, using electroencephalography and transcranial magnetic stimulation (TMS). Twelve subjects underwent, before and after a two week-piano training: (1) hand-motor function tests: Jamar, grip and nine-hole peg tests (NHPT); (2) electroencephalography, evaluating the mu rhythm task-related desynchronization (TRD) during keyboard performance, and (3) TMS, targeting bilateral abductor pollicis brevis (APB) and abductor digiti minimi (ADM), to obtain duration and area of ipsilateral silent periods (ISP). We included ten controls who also underwent these measurements twice, without training. Trained subjects improved keyboard performance and left-hand NHPT scores. Pre-training, ISP durations were asymmetrical (left ISP > right ISP). Post-training, right ISPAPB increased, leading to symmetrical ISPAPB. Mu TRD during bimanual performance also became symmetric, more focal and with a lower amplitude than in pre-training, owing to decreased activity over the ventral premotor cortices. These bilateral modifications correlated with keyboard performance and NHPT scores. No performance or neurohysiological changes were evidenced in controls. A 10-day piano-training was associated with rebalanced interhemispheric interactions both at rest and during motor activation. Piano training, in a short timeframe, may reshape local and inter-hemispheric motor cortical circuits.

During a visual-motor task the movement strategies and the learning processes are investigated. A group of 10 normal young volunteers underwent the experiment. The EEG signal was recorded through the 10-20 acquisition system during the execution of a task after a visual input. Each subject repeated the movement several times in three different conditions: i) without knowledge of the performance; ii) with visual feedback; iii) with knowledge of the result. The signal was transformed through Laplacian operator in order to eliminate the spurious coherence and then time-variant coherence was calculated. Different trends of the coherence function have been evidenced in subjects learning and not learning the better movement strategy. In particular, relations have been found between frontal, central and occipital electrodes in medium and high frequency ranges.

Short-latency (10-50 ms) median nerve somatosensory evoked potentials (SEPs) from four normal subjects were analysed by means of temporal segmentation techniques and source derivation methods. In each case the responses were recorded using 32 electrodes. Dipolar optimization was carried out with a time-varying technique, using three different approaches: regional source estimation, spherical source estimation (one radial and one tangential component), and multiple dipolar approach. This was to assess the relative influence on the dipolar solution of the different optimization techniques. The effect of the different number of channels in the estimation procedures has been also investigated. The methods of optimization are crucial, particularly for the orientation of P22. In all cases the source location estimated with the 32-electrode montage was shifted towards the centre of the spheres.

As long as the Romans had contact with the people of Italy only, their treaties embodied the concept of societas. The new formula and societas and the expression amicitia seem to have arisen only when Rome came into contact with other peoples in the Mediterranean area. The article aims to demonstrate that the roots of these new relationships are in international relations in the ancient Near East, and that the Romans adopted them from the Greeks. Later, they adapted the formula to their policy of expansion by using it to impose the maiestas populi Romani.

To assess the efficacy of botulinum toxin (BT-A) and additional physiotherapy in subjects affected by progressive multiple sclerosis (MS) with chronic lower limb spasticity. 15 patients able to walk with assistance were consecutively recruited in a open-label study. All patients received a set of intramuscular injections of BT-A performed with EMG-guidance, according to each patient’s individual pattern of spasticity, followed by additional physiotherapy. Each patient was assessed at baseline, 6 and 12 weeks for muscle tone, spasms frequency, leg pain, gait velocity, self-analysis of gait function. 7 patients received a further treatment session after 4 months and were retested after 4 and 8 months. We observed a significant (P < 0.05) reduction of muscle tone, spasm frequency and pain and a partial improvement of gait velocity and function after 6 weeks. The results did not change at 12 week follow-up. The seven patients who received a second set of injections maintained their scores after 4 months e three of them after 8 months. Injections of BT-A, followed by additional physiotherapy, are effective on spasms and pain in patients affected with multiple sclerosis. BT-A injections can otherwise improve gait function for several months in patients able to walk with assistance.

Data from large multicenter clinical trials (PREEMPT) demonstrated efficacy and safety of onabotulinumtoxin A for prophylactic treatment of chronic migraine (CM), prophylactic drug-free patients. This study aimed to confirm the efficacy of onabotulinumtoxin A in CM patients with unsatisfactory chronic polytherapy. 26 CM patients (18 females) taking multiple prophylactic/symptomatic medications entered the study. The overall dose ranged between 155 and 170 U administered in 31–34 sites following PREEMPT protocol, repeated at 12 weeks intervals. Main efficacy variables included number of headache/migraine days and episodes, total cumulative headache hours, MIDAS and HIT-6 scores; all items were assessed at baseline and at the 12th-week and 24th-week follow-up. The following variables showed statistically significant changes at 12th-week time-point: headache/migraine days, moderate/severe headache days, migraine episodes, total cumulative hours of headache; slight, not significant MIDAS and HIT-6 scores’ improvement was observed. All the efficacy indicators further improved at the 24-week follow-up, even though only headache days and >4 h episodes number were significant. Adverse event were uncommon and did not require treatment discontinuation. Treatment with onabotulinumtoxin A reduced frequency and duration of headache, as well as need for drug consumption and was well tolerated in most cases.

Sensory trick (ST), i.e. the improvement of dystonic posture by application of a sensory stimulus, is a typical Cervical Dystonia (CD) feature. Though its exact mechanism is still unknown, cortical sensorimotor integration processes are likely to be involved. Short latency afferent inhibition (SAI), the physiological inhibition of motor evoked potentials (MEP) mediated by somatosensory stimulation, could potentially help to understand this phenomenon. We evaluated by means of SAI whether the inhibitory effect of somatosensory afferent volley is preserved in CD patients; Moreover, we assessed if sensory trick may change SAI profile in patients with CD. We performed SAI at rest and during ST performance in 2 groups of CD patients: group 1 (n = 13), patients high-responsive to ST and group 2 (n = 8), patients no- or slightly responsive to ST. Results: We found an overall SAI impairment in both CD groups at rest; rather unexpectedly, SAI was less effective and MEP amplitude increased with ST in group 1, while just slight or no effect was observed in group 2. The physiological inhibition of sensory stimuli over motor cortex, measured with SAI, is decreased in our CD patients. The trick-related dystonia relief seems to occur through a paradoxical enhancement of the sensorimotor circuitry, at least in high-responsive ST patients.

Abstract Forms of strict liability in the law of delicts: The heavy legacy of Roman law. In Roman law there are two forms of delictual strict liability - i.e. liability for damages, regardless of the participation of the liable person to the harmful act. According to the first model, the pater familias / dominus is liable, because he is the only one in the family who can pay compensation. The second model is instead based on a reference to culpa in eligendo or in vigilando, and the strict liability is justified by the need to ensure an absolute protection of the injured person. The civilian tradition has built its theory of strict liability on this second model, speaking of culpa in vigilando or in eligendo even when - after the distinction between iniuria and culpa was introduced by Chr. Thomasius - strict liability was conceived as liability without fault. This has led to a gap, in the European civil codes, between the dogmatic construction of vicarious liability as subjective, because based on culpa, and its actual nature of objective liability, regardless of fault.

A large multicentre clinical trial (PREEMPT) demonstrated the efficacy and safety of onabotulinumtoxin A for prophylactic treatment of chronic migraine (CM) in prophylactic drug-free patients. This study aimed to verify the efficacy of repetitive injections of onabotulinumtoxin A in CM patients with ineffective chronic poly-therapy. Patients and methods: we studied 45 CM patients (36 females and 9 males) taking multiple prophylactic/symptomatic medications who were treated with onabotulinumtoxin-A for a follow up period of 9 months. The overall dose ranged between 155 and 180 U administered in 31–36 sites following PREEMPT protocol, repeated at 12 weeks intervals. The main evaluated variables to establish drug efficacy included number of headache/migraine days and episodes, total cumulative headache hours, MIDAS and HIT-6 scores; all items were assessed at baseline and after 12–24–36 weeks during follow-up. Results: all variables showed statistically significant changes after 36-weeks time-point. We observed a responder rate (partially responder plus completely responder patients) of about 40% after the first treatment; the rate reached 90% after the third treatment. Adverse events were uncommon and did not require treatment discontinuation. Conclusions: repeated treatments with onabotulinumtoxin A in CM patients with unsatisfactory prophylactic drug treatments, was very effective in improving all variables examined, determining a measurable positive impact on quality of life.

A classic hallmark of cervical dystonia (CD) is the improvement of dystonic symptoms during a specific maneuver, defined ‘sensory trick’ (ST). Even if the mechanism by which ST improves dystonia is not well understood, it is likely that cortical sensorimotor integration processes are involved. In a previous preliminary study, we evaluated the short latency afferent inhibition (SAI) in a group of CD patients and the effects of ST on the SAI profile. To date, we have increased our sample including 28 patients with primary CD (18 with ST, CD+, and 10 without ST, CD-) and 11 controls. The analysis of variance showed no significant differences between CD- patients and controls. On the contrary, a remarkable trend toward a reduced SAI was observed in CD+ patients when they did not perform ST. Interestingly, SAI was further reduced in CD+ patients when they performed ST, reaching a strong statistical relevance. Our results show the presence of an abnormal sensorimotor integration in CD+ patients. Furthermore, they prove that ST acts by modulating the abnormal link between sensory input and motor output.

No AccessLa mancipatio decemvirale e il nuovo diritto dei plebeiMaria Floriana CursiMaria Floriana CursiSearch for more papers by this authorhttps://doi.org/10.14220/9783737003025.145SectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail About Previous chapter Next chapter FiguresReferencesRelatedDetails Download book cover 1ISBN: 978-3-8471-0302-8 eISBN: 978-3-7370-0302-5HistoryPublished online:January 2015 PDF download

The mancipatio familiae was a new form of succession, based on the will of the de cuius, but lacking of the heredis institutio. This novelty is due to the needs of the plebeian economy, which was interested more in the material trasmission of property than in the creation of a ‘political’ heir.

To study short-term effects of keyboard training in music-naive subjects on motor cortex activity and interhemispheric interactions, using electroencephalography and transcranial magnetic stimulation (TMS). Twelve subjects underwent, before and after a two week-piano training: (1) hand-motor function tests: Jamar, grip and nine-hole peg tests (NHPT); (2) electroencephalography, evaluating the mu rhythm task-related desynchronization (TRD) during keyboard performance, and (3) TMS, targeting bilateral abductor pollicis brevis (APB) and abductor digiti minimi (ADM), to obtain duration and area of ipsilateral silent periods (ISP). We included ten controls who also underwent these measurements twice, without training. Trained subjects improved keyboard performance and left-hand NHPT scores. Pre-training, ISP durations were asymmetrical (left ISP > right ISP). Post-training, right ISPAPB increased, leading to symmetric ISPAPB. Mu TRD during bimanual performance also became symmetric, more focal and of lower amplitude than in pre-training, owing to decreased activity over ventral premotor cortices. These bilateral modifications correlated with keyboard performance and NHPT scores. No performance or neurohysiological changes were evidenced in controls. A 10-day piano-training was associated with rebalanced interhemispheric interactions both at rest and during motor activation. Piano training, in a short timeframe, may reshape local and inter-hemispheric motor cortical circuits.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive degeneration of the corticospinal tract motor neurons. Growing evidence, especially derived from studies in murine models, could suggest that ALS is a distal axonopathy in which axonal degeneration occurs early during the disease, preceding the degeneration of motoneuron soma in the ventral horn of the spinal cord and the onset of symptoms (Fischer et al., 2004; Dadon-Nachum et al., 2011). A combination of molecular and subcellular events, such as protein misfolding, oxidative damage, mitochondrial alterations, impairment of glutamate transmission leading to excitotoxicity, and axonal transport impairment has been implicated in motoneuron vulnerability in ALS (Ferraiuolo et al., 2011). These observations led to consider the neuromuscular junction (NMJ) as a major player in the initiation and progression of ALS. Aim of this study was to investigate the functionality of the NMJ through all the course of the disease in the hSOD1G93A ALS mouse model, by means of single-fiber electromyography (SFEMG) technique. A comprehensive neurophysiological investigation (including sciatic nerve conduction, MEPs by transcranial electrical stimulation and sSFEMG) was carried out on 5 WT and 5 hSOD1G93A mice, at different time-points (50-70-90-110 ± 3 PND). In the early pre-symptomatic phase (50 PND), hSOD1G93A mice presented a significant jitter elongation [MCD (mean ± SE): 18.36 ± 3.21 in hSOD1G93A, 8.23 ± 0.84 in WT; p 0.021] together with increased fiber density [FD (mean ± SE): 1.62 ± 0.17 in hSOD1G93A, 1.27 ± 0.10 in WT; p 0.117] when compared with controls, suggestive of recent reinnervation process. No difference were found in peripheral conduction and MEPs parameters at the same time-point. Our results show that the neuromuscular transmission of hSOD1G93A mice is altered since the early presymptomatic phase of the disease. This probably derive from an early denervation-reinnervation process resulting in immature collateral nerve terminals and instability of neuromuscular transmission. SFEMG seems to be more sensitive in detecting the early signs of the disease compared to the other neurophysiological techniques, and could be a valuable tool for monitoring the effectiveness of new experimental therapeutic approach.

The paper aims to demostrate a change in the jurisprudential interpretation of the rules of the XII tables about the killing of the thief. In archaic law, the self-defense was allowed on the objective basis of a theft committed during the night, or during the day by an armed thief. The influence of the lex Aquilia, and particularly of the subjective idea of iniuria - identified with dolus or culpa - led the jurists to admit the self-defense only when the victim subjectively felt an imminent danger.

The expression quasi delict cannot be found in Roman legal sources. It has been created on the basis of a title of the JustinianInstitutes (I. 4.5), dealing with “the obligations which arise as though from delict” (quasi ex delicto); in the text of the Institutes, we find a closely related expression, quasi ex maleficio teneri, probably derived from Gaius’sRes cottidianae (or Aurea) in D. 44.7.5.4–6.

This article presents the results of an in-depth case study of the World Anti-Doping Agency (WADA), a global cross-sector social partnership (CSSP) through which governments and sport collaborate to address the social issue of doping in sport. The authors specifically explore how WADA has managed two key issues (securing financial contributions and the 2007 presidential election) using institutional and resource-dependence theories to better understand the question of why and how a sport CSSP responds strategically to its environmental and resource constraints in its precursory, establishment, and continuance phases. In doing so, the authors contribute to the sport management literature by providing new theoretical insights in the context of an international CSSP whose governance model challenges traditional management theories (Selsky & Parker, 2005) and is increasingly relevant in the current era of global management of social issues (Scherer & Palazzo, 2010). Findings suggest that for global CSSPs internal and external legitimacy is imperative through securing moral and geopolitical legitimacy, and there is value in considering resource-dependence and institutional theories as complementary rather than competing frameworks.

OBJECTIVE: To investigate the effects of skill training on interhemispheric interactions and brain activity using electroencephalography (EEG) and transcranial magnetic stimulation (TMS).BACKGROUND: Cortical plasticity induced by skill training has been shown to be beneficial to several common movement disorders such as stroke or Parkinson disease. However, the neuronal mechanisms responsible for such cortical changes are still not understood.DESIGN/METHODS: 12 right-handed, music-naïve subjects underwent a motor training consisting in ten 35-minute sessions, playing an electronic keyboard. Before and after training, subjects underwent hand motor function and neurophysiological assessments using EEG and TMS. The EEG recording aimed at evaluating the mu task-related desynchronization (TRD) during motor performance. TMS, targeting the bilateral abductor pollicis brevis (APB) and abductor digiti minimi (ADM), was performed to obtain resting motor threshold (RMT), amplitude of motor evoked potentials at 120 % RMT, and ipsilateral silent period (ISP) duration during voluntary tonic co-contraction of APB and ADM.RESULTS: All subjects dramatically improved their motor performance. Left hand 9HPT scores improved in every subject. Pre-training, ISP durations were asymmetrical, left ISPs being longer than right ISPs. Post-training, right ISPAPB increased, leading to symmetrical durations. Sensorimotor rhythms activation during bimanual performance became also symmetric, more focal and had a lesser amplitude than in pre-training. These modifications of bilateral motor cortex function were correlated with motor performance.CONCLUSIONS: This shows how skill training, even in a short timeframe, can modulate local and inter-hemispheric cortical functioning, sharing similarities with data reported on musicians. The reduced and more symmetrical cortical activation during motor performance was accompanied by a rebalance of interhemispheric inhibition, previously in favor of the dominant hemisphere. These findings bring additional evidence that skilled training has a beneficial effect on motor cortex function and should be considered as a potential preventive strategy to limit the impact of neurological insults.Disclosure: Dr. Houdayer has nothing to disclose. Dr. Cursi has nothing to disclose. Dr. Nuara has nothing to disclose. Dr. Zanini has nothing to disclose. Dr. Gatti has nothing to disclose. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, and Bayer Schering. Dr. Leocani has nothing to disclose.

Our aim was to evaluate the functional integrity of external urethral sphincter (EUS) in men undergoing prostate biopsy (PBx) and the presence of predictive factors for post-surgery urinary incontinence. 53 continent men without pelvic or neurological disorders were included. Before the PBx an EMG analysis of EUS was performed. Motor Unit Potentials (MUPs) and Interference Pattern (IP) analysis were obtained from each muscle using multi-MUP and turn/amplitude automatic analysis. A mean of 30 MUPs from each muscle were sampled. Mean values (± SD) of MUP parameters were: amplitude 493,48 μV (± 372,18), duration 7,11 ms (± 2,27), area 423,05 μVms (± 364,22), phases 3,76 (± 1,83), turns 2,33 (± 1,71). From 49 muscle 1799 IP samples were obtain. Mean (± SD) values were: turn/s were 274,87 (± 218,82), amplitude/turn 327,35 (± 127,47), turns/amplitude ratio 3,25 (± 4,37). The turn/amplitude “cloud” was determined. Our results represent a control data to assess any neurophysiological changes in patients who develop urinary incontinence after surgery.

OBJECTIVE: To investigate the effects of skill training on interhemispheric interactions and brain activity using electroencephalography (EEG) and transcranial magnetic stimulation (TMS).BACKGROUND: Cortical plasticity induced by skill training has been shown to be beneficial to several common movement disorders such as stroke or Parkinson disease. However, the neuronal mechanisms responsible for such cortical changes are still not understood.DESIGN/METHODS: 12 right-handed, music-naïve subjects underwent a motor training consisting in ten 35-minute sessions, playing an electronic keyboard. Before and after training, subjects underwent hand motor function and neurophysiological assessments using EEG and TMS. The EEG recording aimed at evaluating the mu task-related desynchronization (TRD) during motor performance. TMS, targeting the bilateral abductor pollicis brevis (APB) and abductor digiti minimi (ADM), was performed to obtain resting motor threshold (RMT), amplitude of motor evoked potentials at 120 % RMT, and ipsilateral silent period (ISP) duration during voluntary tonic co-contraction of APB and ADM.RESULTS: All subjects dramatically improved their motor performance. Left hand 9HPT scores improved in every subject. Pre-training, ISP durations were asymmetrical, left ISPs being longer than right ISPs. Post-training, right ISPAPB increased, leading to symmetrical durations. Sensorimotor rhythms activation during bimanual performance became also symmetric, more focal and had a lesser amplitude than in pre-training. These modifications of bilateral motor cortex function were correlated with motor performance.CONCLUSIONS: This shows how skill training, even in a short timeframe, can modulate local and inter-hemispheric cortical functioning, sharing similarities with data reported on musicians. The reduced and more symmetrical cortical activation during motor performance was accompanied by a rebalance of interhemispheric inhibition, previously in favor of the dominant hemisphere. These findings bring additional evidence that skilled training has a beneficial effect on motor cortex function and should be considered as a potential preventive strategy to limit the impact of neurological insults.Disclosure: Dr. Houdayer has nothing to disclose. Dr. Cursi has nothing to disclose. Dr. Nuara has nothing to disclose. Dr. Zanini has nothing to disclose. Dr. Gatti has nothing to disclose. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, and Bayer Schering. Dr. Leocani has nothing to disclose.

This study describes our experience with neuromonitoring in thoracoabdominal aortic aneurysms (TAAA) repair, focusing on the set up of a monitoring protocol, aimed to optimize the detection of spinal cord ischemia. A retrospective observational study was carried out on 62 consecutive patients (37 men; mean age 63.8 years) undergoing TAAA repair between February 2016 and March 2017. All patients underwent Motor Evoked Potentials (MEPs), Somatosensory Evoked Potentials (SSEPs), neurophysiological monitoring of peripheral ischemia, and continuous control of other intraoperative variables. The mortality rate was 9.6%, and the incidence of immediate and delayed neurological deficits was 6.4% and 3.2% respectively. Significant MEP changes occurred in 41.6% of patients, recovering in 85% of cases. Permanent MEPs changes occurred in 3 patients (15%), 2 of them developed immediate paraplegia. Significant SSEPs changes occurred in 6 patients (12.2%) and recovered in all but one, awaking with paraplegia. False negative and positive rate were both 1.6%. Our data are consistent with the literature. However, a consensus is still lacking with regard to an intraoperative protocol for monitoring, which limits the comparison of different studies. Our method demonstrated a good reliability and could contribute to the setup of a consensus protocol.

Onabotulinumtoxin-A (BT-A) is an authorised prophylactic therapy in chronic migraine (CM). Its efficacy has been proved by both clinical trials and observational studies. Few data are still available on the efficacy of BT-A injection and the most adequate treatment interval after the first year of follow-up. This study aimed to verifyefficacy, safety and the most adequate timing of BT-A injections in CM patients during the second year of treatment. we evaluated 20 CM patients with medication overuse MO (17 females and 3 males) treated with BT-A for 24 months. After the fourth treatment, we decided to retreat responder patients based on their clinical result. Main efficacy variables were registered at each visit, including days of headache/migraine, total cumulative headache hours, MIDAS and HIT-6 scores, together with symptomatic drugs intake. All variables at week 24 maintained the improvement evidenced at week 12. Adverse events were rare and did not require treatment discontinuation. Most of the patients (n = 13) continued to perform trimestral injections, 5 patients every 4 months and 2 patients every 6 months. BT-A in CM patients is effective even after two years of treatment when administered with an individualised interval according to the clinical outcome.