Matilde Ercolani

Fronto-parietal coupling of brain rhythms in mild cognitive impairment: A multicentric EEG study

Electroencephalographic (EEG) data were recorded in 69 normal elderly (Nold), 88 mild cognitive impairment (MCI), and 109 mild Alzheimers disease (AD) subjects at rest condition, to test whether the fronto-parietal coupling of EEG rhythms is in line with the hypothesis that MCI can be considered as a pre-clinical stage of the disease at group level. Functional coupling was estimated by synchronization likelihood of Laplacian-transformed EEG data at electrode pairs, which accounts for linear and non-linear components of that coupling. Cortical rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz). Compared to the Nold subjects, the AD patients presented a marked reduction of the synchronization likelihood (delta to gamma) at both fronto-parietal and inter-hemispherical (delta to beta 2) electrodes. As a main result, alpha 1 synchronization likelihood progressively decreased across Nold, MCI, and mild AD subjects at midline (Fz-Pz) and right (F4-P4) fronto-parietal electrodes. The same was true for the delta synchronization likelihood at right fronto-parietal electrodes (F4-P4). For these EEG bands, the synchronization likelihood correlated with global cognitive status as measured by the Mini Mental State Evaluation. The present results suggest that at group level, fronto-parietal coupling of the delta and alpha rhythms progressively becomes abnormal though MCI and mild AD. Future longitudinal research should evaluate whether the present EEG approach is able to predict the cognitive decline in individual MCI subjects.

Hand cortical representation at rest and during activation: gender and age effects in the two hemispheres.

OBJECTIVE To characterize the age- and gender- dependence of sensory hand cortical representation in the two hemispheres in healthy population. METHODS In 57 adults, the cerebral activity from rolandic areas as detected by magnetoencephalography was considered both in a resting state (spectral power properties) and in response to the electrical stimulation of the contralateral median nerve (M20 and M30 cortical sources). RESULTS We found a dependence of rest and evoked activity on age (alpha rhythm slowing, high frequency power increase, M20 latency increase, M20 strength increase, no change in M30) and on gender (higher alpha frequency, higher beta power, higher spectral entropy, lower M20 amplitude in women). These changes were quite symmetrical in the two hemispheres, making the interhemispheric differences non-dependent on age and gender. Moreover, lower total power and faster alpha rhythm appeared in the dominant hemisphere. CONCLUSIONS Age and gender have a significant effect on spontaneous and evoked activity at the primary sensorimotor cortex. SIGNIFICANCE The results consolidate the reference base in healthy population, to study pathological conditions. Inter-hemispheric asymmetries are confirmed as a sensitive indicator for the early identification of possible neuronal rearrangements due to unilateral brain injuries.

Cortical Neuromodulation Modifies Cerebral Vasomotor Reactivity

Background and Purpose— Cerebral vasomotor reactivity (VMR) is a capability of cerebral vessels to dilate in response to hypercapnia. Transcranial direct current stimulation (tDCS) effects on cerebral hemodynamics have been poorly studied. Methods and Results— Ten healthy subjects underwent anodal/cathodal tDCS on the left motor cortex. Before and after tDCS, VMR assessment by transcranial Doppler and an electrocardiogram were performed. Normalized low-frequency band power of heart rate variability and its reactivity from basal to VMR condition (LFNreact) were estimated as relative markers of sympathetic activation. tDCS exerted a polarity-specific effect on both VMR (P=0.0001) and LFNreact (P=0.001). Anodal tDCS decreased VMR by 3.4%/mm Hg CO2 bilaterally and increased LFNreact, whereas cathodal tDCS increased VMR by 0.8%/mm Hg CO2 bilaterally and reduced LFNreact. Conclusions— Cerebral VMR is modified by tDCS. Based on the consensual changes with heart rate variability, we can hypothesize that the sympathetic nervous system could modulate the bihemispheric modification of VMR. Further studies are needed to confirm this hypothesis.

Neuronal functionality assessed by magnetoencephalography is related to oxidative stress system in acute ischemic stroke

The hypoxic brain damage induced by stroke is followed by an ischemia-reperfusion injury modulated by oxidative stress. Magnetoencephalographic (MEG) recording of rest and evoked cortical activities is a sensitive method to analyse functional changes following the acute ischemic damage. We aimed at investigating whether MEG signals are related to oxidative stress compounds in acute stroke. Eighteen stroke patients and 20 controls were enrolled. All subjects underwent MEG assessment to record background activity and somatosensory evoked responses (M20 and M30) of rolandic regions, neurological examination assessed by National Institute of Health Stroke Scale (NIHSS) and plasmatic measurement of copper, iron, zinc, ceruloplasmin, transferrin, total peroxides and Total Anti-Oxidant Status. Magnetic Resonance was performed to estimate the lesion site and volume. Delta power and M20 equivalent current dipole (ECD) strength in the affected hemisphere (AH) correlated with NIHSS scores (respectively, rho=.692, p=.006 and rho=-.627, p=.012) and taken together explained 67% of NIHSS variability (p=.004). Higher transferrin and lower peroxides levels correlated with better clinical status (respectively, rho=-.600, p=.014 and rho=.599, p=.011). Transferrin also correlated with AH M20 ECD strength (rho=.638 p=.014) and inversely with AH delta power (rho=-.646 p=.023) and the lesion volume, especially in cortico-subcortical stroke (p=.037). Our findings strengthen MEG reliability in honing the evaluation of neuronal damage in acute ischemic stroke also demonstrating an association between the MEG parameters most representing the clinical status and the oxidative stress compounds. Our results meet at a possible protective role of transferrin in limiting the oxidative damage in acute stroke.

Regional personalized electrodes to select transcranial current stimulation target

Rationale: Personalizing transcranial stimulations promises to enhance beneficial effects for individual patients. Objective: To stimulate specific cortical regions by developing a procedure to bend and position custom shaped electrodes; to probe the effects on cortical excitability produced when the properly customized electrode is targeting different cortical areas. Method: An ad hoc neuronavigation procedure was developed to accurately shape and place the personalized electrodes on the basis of individual brain magnetic resonance images (MRI) on bilateral primary motor (M1) and somatosensory (S1) cortices. The transcranial alternating current stimulation (tACS) protocol published by Feurra et al. (2011b) was used to test the effects on cortical excitability of the personalized electrode when targeting S1 or M1. Results: Neuronal excitability as evaluated by tACS was different when targeting M1 or S1, with the General Estimating Equation model indicating a clear tCS Effect (p < 0.001), and post hoc comparisons showing solely M1 20 Hz tACS to reduce M1 excitability with respect to baseline and other tACS conditions. Conclusions: The present work indicates that specific cortical regions can be targeted by tCS properly shaping and positioning the stimulating electrode. Significance: Through multimodal brain investigations continuous efforts in understanding the neuronal changes related to specific neurological or psychiatric diseases become more relevant as our ability to build the compensating interventions improves. An important step forward on this path is the ability to target the specific cortical area of interest, as shown in the present pilot work.

Extrauterine maturation of somatosensory pathways in preterm infants: A somatosensory evoked potential study

OBJECTIVE To evaluate the reliability of somatosensory evoked potential (SEP) recordings in preterm infants to monitor the intra-uterine and extrauterine maturation of somatosensory pathways. METHODS We performed SEPs in 35 neurologically normal preterm babies (range 23-35 weeks gestational age--GA). Twenty-four of all infants were evaluated after the first 2 weeks of life, at a minimum post-menstrual age (PMA) of 31 weeks, and 31 at term corrected age. In 15 infants we obtained longitudinal recordings at both epochs. Cross-sectional and longitudinal values of first cortical potential (N1) were analyzed in relation of PMA and matched with those measured in a group of 11 fullterm babies. RESULTS Reproducible cortical SEPs were found in 92% of preterm babies at first recording, and in all 31 neonates at follow-up. A significant inverse correlation between the latency values of N1 and PMA at the time of first recording was observed, showing that latencies of these components rapidly decrease with increasing PMA. Regression analysis showed no significant effect on N1 latency at term correct age in dependence of GA, suggesting that extrauterine life does not affect maturation of somatosensory pathways. Interestingly, the occurrence of idiopathic respiratory distress (RDS) during clinical course after birth correlated with a delayed N1 latency at term corrected age. CONCLUSIONS Extrauterine life does not affect maturation of somatosensory pathways in preterms without neurological deficit. Finally, the mild negative influence of RDS on maturational changes was evident. SIGNIFICANCE SEPs could be considered a useful tool for a non-invasive assessment of somatosensory pathways integrity in preterm infants.

Primary sensory and motor cortex activities during voluntary and passive ankle mobilization by the SHADE orthosis

This study investigates cortical involvement during ankle passive mobilization in healthy subjects, and is part of a pilot study on stroke patient rehabilitation. Magnetoencephalographic signals from the primary sensorimotor areas devoted to the lower limb were collected together with simultaneous electromyographic activities from tibialis anterior (TA). This was done bilaterally, on seven healthy subjects (aged 29 ± 7), during rest, left and right passive ankle dorsiflexion (imparted through the SHADE orthosis, O‐PM, or neuromuscular electrical stimulation, NMES‐PM), and during active isometric contraction (IC‐AM). The effects of focussing attention on ankle passive movements were considered. Primary sensory (FSS1) and motor (FSM1) area activities were discriminated by the Functional Source Separation algorithm. Only contralateral FSS1 was recruited by common peroneal nerve stimulation and only contralateral FSM1 displayed coherence with TA muscular activity. FSM1 showed higher power of gamma rhythms (33–90 Hz) than FSS1. Both sources displayed higher beta (14–32 Hz) and gamma powers in the left than in the right hemisphere. Both sources displayed a bilateral reduction of beta power during IC‐AM with respect to rest. Only FSS1 beta band power reduced during O‐PM. No beta band modulation was observed of either source during NMES‐PM. Mutual FSS1‐FSM1 coherence in gamma2 band (61–90 Hz) showed a slight trend towards an increase when focussing attention during O‐PM. Somatosensory and motor counterparts of lower limb cortical representations were discriminated in both hemispheres. SHADE was effective in generating repeatable dorsiflexion and inducing primary sensory involvement similarly to voluntary movement. Hum Brain Mapp, 2010.

Cerebral Hemodynamics and Systemic Endothelial Function Are Already Impaired in Well-Controlled Type 2 Diabetic Patients, with Short-Term Disease

Objective Impaired cerebral vasomotor reactivity (VMR) and flow-mediated dilation (FMD) were found in selected subgroups of type 2 diabetes mellitus (T2DM) patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN). Research Design and Methods Twenty-six T2DM patients with short-term (4.40±4.80 years) and well-controlled (HbA1C = 6.71±1.29%) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also. Results FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively) compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p<.001 and p<.05). T2DM patients also displayed reduced VMR values than controls (39.4% SD 12.4 vs 51.7%, SD 15.5; p<.05). Sympatho-vagal balance was not different in T2DM patients compared to healthy subjects. FMD and shear rate FMD did not correlate with VMR in T2DM patients or in controls (p>.05). Conclusions In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved.

WO02 Cortical correlate of passive mobilisation of the ankle joint by means of the SHADE orthosis

WO02 Cortical correlate of passive mobilisation of the ankle joint by means of the SHADE orthosis Simone Pittaccio 1, Filippo Zappasodi 2, Stefano Viscuso 1, Francesca Mastrolilli 3 , Matilde Ercolani 3, Francesco Passarelli 3 , Franco Molteni 4, Paolo Maria Rossini 5, Franca Tecchio 6 1CNR-IENI, Unità di Lecco, Italy; 2CNR-ISTC, Unità MEG, Ospedale Fatebenefratelli, Isola Tiberina, Rome, Italy; 3AFaR, Ospedale Fatebenefratelli, Isola Tiberina, Rome, Italy; 4Ospedale Valduce, Clinica Villa Beretta, Costamasnaga, Italy; 5Dept. of Neurology, ‘Campus Bio-Medico’ University, Rome, Italy; 6IRCCS San Raffaele, Tosinvest Sanità, Cassino, Italy

S5.3 Prognostic value of contralesional delta band EEG activity in acute stroke

S5.3 Prognostic value of contralesional delta band EEG activity in acute stroke G. Assenza1, F. Zappasodi2, P. Pasqualetti3, S. Assenza4, M. Ercolani5, L. Fraioli6, C. Gaudino7, F. Passarelli8, F. Tibuzzi9, F. Vernieri1, P.M. Rossini1, F. Tecchio10 1Neurologia Clinica, Universita Campus Biomedico, Rome, Italy, 2Department of Clinical Sciences and Bioimaging, G. D’Annunzio University, Chieti-Pescara, Italy, 3Medical Statistics & Information Technology, Fatebenefratelli Association for Research, Rome, Italy, 4Casa di Cura San Raffaele Cassino, Cassino, Italy, 5AFaR, Department of Neuroscience, Hosp. Fatebenefratelli, Isola Tiberina, Rome, Italy, 6Casa di Cura San Raffaele Cassino, Rome, Italy, 7Radiologia e Diagnostica per immagini, Universita Campus Biomedico, Rome, Italy, 8Dipartimento di Neuroscienze Ospedale Fatefenefratelli, Isola Tiberina, Rome, Italy, 9Dipartimento di Neuroscienze Ospedale Fatebenefratelli Isola Tiberina, Rome, Italy, 10LET’S Laboratory of Electrophysiology for Translational neuroScience Unita MEG Osp. FBF Isola tiberina, Rome, Italy