Action-related semantic content and negation polarity modulate motor areas during sentence reading: an event-related desynchronization study.

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.

Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Flash visual evoked potentials in mice can be modulated by transcranial direct current stimulation.

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.

A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis.

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 beta-endorphins (BE) and mRNA levels and allelic variants of the mu-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.

Status epilepticus.

Status epilepticus (SE) is a medical emergency. It requires prompt and adequate diagnosis and treatment, as it may induce CNS injury. It is mainly distinguished into generalised and partial SE on the basis of its major clinical features. There are very few data about SE physiopathology, but it is generally characterised by increasing unresponsiveness to treatment. SE diagnosis is based on EEG recording, associated with neuroimaging techniques and laboratory assays to detect underlying pathologies. During SE we distinguish three different conditions: initial, defined and refractory. Benzodiazepines represent first-line treatment, followed by phenytoin. Refractory SE requires ICU treatment to perform general anaesthesia.

Electroencephalographic background desynchronization during cerebral blood flow reduction.

OBJECTIVE: The aim of this study is to evaluate the usefulness of a spectral function detecting cerebral hypoperfusion. METHODS: 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. RESULTS: Group A function decreased within 20s 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. CONCLUSIONS: 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. SIGNIFICANCE: 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.

Acute effects of L-dopa on event-related desynchronization in Parkinson's disease.

We tested whether dispersible L-dopa has acute effects on event-related desynchronization (ERD) of the mu rhythm in patients with idiopathic Parkinson's disease (IPD). ERD to voluntary movement is delayed in akinetic IPD patients and improves after chronic L-dopa treatment. We evaluated ERD to self-paced finger movement in 14 IPD patients (before and 30-40 min after oral administration of dispersible L-dopa) and in 10 normal subjects. Sensorimotor ERD onset contralateral to movement was significantly delayed in IPD patients compared to normal subjects. This abnormality was no longer significant after L-dopa treatment. We conclude that a single dose of dispersible L-dopa can improve not only motor performance in IPD patients but also the timing of cortical activation of sensorimotor areas during motor programming.

Fatigue in multiple sclerosis is associated with abnormal cortical activation to voluntary movement--EEG evidence.

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.

Event-related brain potentials: laplacian transformation for multichannel time-frequency analysis.

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.

Computer-assisted EEG monitoring during carotid endarterectomy.

The purpose of this study was to develop a reliable method of EEG analysis during carotid endarterectomy. EEGs of 104 patients under general anesthesia were processed by three different methods: a) "on-line" visual analysis during surgery, b) "off-line" visual analysis in laboratory, and c) computer analysis. To identify pathological EEGs, variability and asymmetry indexes of the 0.5-3.5 Hz and 8-15 Hz bands, absolute power and variability indexes of spectral edge frequency (SEF), and main dominant frequency were evaluated. On-line visual analysis showed clamp-related modifications in 29 EEGs (27.9%). Off-line visual analysis detected 24 pathological EEGs (23.1%): 18 with major changes and 6 with moderate changes. Computer analysis showed 21 EEGs (20.19%) with at least one altered index and 7 (6.7%) with altered variability for both SEF and 8-15 Hz power. The statistical analysis was significant for SEF variability and for 8-15 Hz power variability and asymmetry (P < 0.0001, analysis of variance test). While SEF and 8-15 Hz power variability did not appear influenced by anesthesia and single electrode artifacts, 8-15 Hz power asymmetry index was confounded by the presence of contralateral internal carotid occlusion. The data show that the use of these spectral indexes adds objective information to visual analysis, supporting and making easier intraoperative strategies. Their routine clinical use does not involve additional costs remaining technical requirements unchanged compared to traditional recording.

EEG coherence in Alzheimer's disease.

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.

Event-related desynchronization to contingent negative variation and self-paced movement paradigms in Parkinson's disease.

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.

FFT approximation in Alzheimer's disease.

The electroencephalographic modifications that occur during the course of Alzheimer's disease are characterised by an increase in the potential of low frequency bands, a diminution in the potential of alpha activity, and a change in the topographical distribution of the potential of all band frequencies. In this study, the fast Fourier transform (FFT) approximation was used to characterise modifications in the electroencephalogram location or orientation of the source of the dipole equivalent of the delta, theta, alpha1, alpha2, beta1 and beta2 frequencies in 20 with patients with Alzheimer's disease and in a control group of 20 age-matched subjects. A statistical (t-test) comparison of the two groups revealed a significant change in the location of the dipolar source along the vertical axis in 18 (90%) of the patients; this change involved all the frequency bands. There was also a significant movement of the dipolar source of the alpha1 band towards the anterior regions. In addition, the control group showed that there was a significant correlation between age and a more surface expression of the source of the delta, theta, alpha1 and beta1 bands.

Total and partial coherence analysis of spontaneous and evoked EEG by means of multi-variable autoregressive processing.

The joint use of total and partial coherence between pairs of EEGs simultaneously recorded in a standard set, is shown to enhance what is caused by direct correlation between cortical subsystems and what is instead related to the spread of the electromagnetic field. A multi-variable autoregressive approach is employed in the computation, giving results even for a very short time window, thus allowing coherence to be investigated at the main cortical latencies of evoked potentials. In particular, when a combined visual and somatosensory stimulation is applied, cortical interactions are captured in the frequency domain.

Temporal segmentation and multiple-source analysis of short-latency median nerve SEPs.

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.