Jean-Marc Melgari

Muscles in "concert": study of primary motor cortex upper limb functional topography.

Background Previous studies with Transcranial Magnetic Stimulation (TMS) have focused on the cortical representation of limited group of muscles. No attempts have been carried out so far to get simultaneous recordings from hand, forearm and arm with TMS in order to disentangle a ‘functional’ map providing information on the rules orchestrating muscle coupling and overlap. The aim of the present study is to disentangle functional associations between 12 upper limb muscles using two measures: cortical overlapping and cortical covariation of each pair of muscles. Interhemispheric differences and the influence of posture were evaluated as well. Methodology/Principal Findings TMS mapping studies of 12 muscles belonging to hand, forearm and arm were performed. Findings demonstrate significant differences between the 66 pairs of muscles in terms of cortical overlapping: extremely high for hand-forearm muscles and very low for arm vs hand/forearm muscles. When right and left hemispheres were compared, overlapping between all possible pairs of muscles in the left hemisphere (62.5%) was significantly higher than in the right one (53.5% ). The arm/hand posture influenced both measures of cortical association, the effect of Position being significant [p = .021] on overlapping, resulting in 59.5% with prone vs 53.2% with supine hand, but only for pairs of muscles belonging to hand and forearm, while no changes occurred in the overlapping of proximal muscles with those of more distal districts. Conclusions/Significance Larger overlapping in the left hemisphere could be related to its lifetime higher training of all twelve muscles studied with respect to the right hemisphere, resulting in larger intra-cortical connectivity within primary motor cortex. Altogether, findings with prone hand might be ascribed to mechanisms facilitating coupling of muscles for object grasping and lifting -with more proximal involvement for joint stabilization- compared to supine hand facilitating actions like catching. TMS multiple-muscle mapping studies permit a better understanding of motor control and ‘plastic’ reorganization of motor system.

Sensorimotor integration in focal task-specific hand dystonia: A magnetoencephalographic assessment

To obtain a direct sensorimotor integration assessment in primary hand cortical areas (M1) of patients suffering from focal task-specific hand dystonia, magnetoencephalographic (MEG) and opponens pollicis electromyographic (EMG) activities were acquired during a motor task expressly chosen not to induce dystonic movements in our patients, to disentangle abnormalities indicating a possible substrate on which dystonia develops. A simple isometric contraction was performed either alone or in combination with median nerve stimulation, i.e. when a non-physiological sensory inflow was overlapping with the physiological feedback. As control condition, median nerve stimulation was also performed at rest. The task was performed bilaterally both in eight patients and in 16 healthy volunteers. In comparison with results in controls we found that in dystonic patients: i) MEG-EMG coherence was higher; ii) it reduced much less during galvanic stimulation in the hemisphere contralateral to the dystonic arm, simultaneously with iii) stronger inhibition of the sensory areas responsiveness due to movement; iv) the cortical component including contributions from sensory inhibitory and motor structures was reduced and v) much more inhibited during movement. It is documented that a simultaneous cortico-muscular coherence increase occurs in presence of a reduced M1 responsiveness to the inflow from the sensory regions. This could indicate an unbalance of the fronto-parietal functional impact on M1, with a weakening of the parietal components. Concurrently, signs of a less differentiated sensory hand representation--possibly due to impaired inhibitory mechanisms efficiency--and signs of a reduced repertoire of voluntary motor control strategies were found.

Alpha and beta EEG power reflects L-dopa acute administration in parkinsonian patients

Aim: To evaluate the effect of an acute L-dopa administration on eye-closed resting state electroencephalographic (EEG) activity of cognitively preserved Parkinsonian patients. Methods: We examined 24 right-handed patients diagnosed as uncomplicated probable Parkinson’s disease (PD). Each patient underwent Unified Parkinson’s Disease Rating Scale (UPDRS)-part-III evaluation before and 60 min after an oral load of L-dopa-methyl-ester/carbidopa 250/25 mg. Resting condition eyes-closed EEG data were recorded both pre- and post L-dopa load. Absolute EEG power values were calculated at each scalp derivation for Delta, Theta, Alpha and Beta frequency bands. UPDRS scores (both global and subscale scores) and EEG data (power values of different frequency bands for each scalp derivation) were submitted to a statistical analysis to compare Pre and Post L-Dopa conditions. Finally, a correlation analysis was carried out between EEG spectral content and UPDRS scores. Results: Considering EEG power spectral analysis, no statistically significant differences arose on Delta and Theta bands after L-dopa intake. Conversely, Alpha and Beta rhythms significantly increased on centro-parietal scalp derivations, as a function of L-dopa administration. Correlation analysis indicated a significant negative correlation between Beta power increase on centro-parietal areas and UPDRS subscores (Rigidity of arms and Bradykinesia). A minor significant negative correlation was also found between Alpha band increase and resting tremor. Conclusions: Assuming that a significant change in EEG power spectrum after L-dopa intake may be related to dopaminergic mechanisms, our findings are consistent with the hypothesis that dopaminergic defective networks are implicated in cortical oscillatory abnormalities at rest in non-demented PD patients.

Movement-induced uncoupling of primary sensory and motor areas in focal task-specific hand dystonia

INTRODUCTION Due to growing evidence of sensorimotor integration impairment in focal task-specific hand dystonia, we aimed at describing primary sensory (S1) and primary motor (M1) cortex source activities and their functional cross-talk during a non-dystonia-inducing sensorimotor task free of biases generated by the interfering with the occurrence of dystonic movements. METHOD Magnetoencephalographic brain signals and opponens pollicis (OP) electromyographic activities were acquired at rest and during a simple isometric contraction performed either alone or in combination with median nerve stimulation. The task was performed separately with the right and left hand by eight patients suffering from focal task-specific hand dystonia and by eight healthy volunteers. Through an ad hoc procedure Functional Source Separation (FSS), distinct sources were identified in S1 (FSS1) and M1 (FSM1) devoted to hand control. Spectral properties and functional coupling (coherence) between the two sources were assessed in alpha [8,13]Hz, beta [14,32]Hz and gamma [33,45]Hz frequency bands. RESULTS No differences were found between spectral properties of patients and controls for either FSM1 or FSS1 cerebral sources. Functional coupling between FSM1 and FSS1 (gamma band coherence), while comparable between dystonic patients and healthy controls at rest, was selectively reduced in patients during movement. All findings were present in both hemispheres. DISCUSSION Because previous literature has shown that gamma-band sensory-motor synchronization reflects an efficiency index of sensory-motor integration, our data demonstrate that, in dystonic patients, uncoupling replaces the functional coupling required for efficient sensory-motor control during motor exertion. The presence of bi-hemispheric abnormalities in unilateral hand dystonia supports the presence of an endophenotypic trait.

Relationship among Diffusion Tensor Imaging, EEG Activity, and Cognitive Status in Mild Cognitive Impairment and Alzheimer's Disease Patients

Magnetic resonance (MR) diffusion tensor imaging (DTI) can detect microstructural alterations by means of fractional anisotropy (FA) in patients with dementia, also in relation to cognitive status. The present study aimed at investigating the possible relation among white matter damage in DTI, quantitative electroencephalography (EEG) spectral power, and cognitive status in Alzheimers disease (AD) and mild cognitive impairment (MCI) patients. Forty-seven subjects (8 moderate AD, 18 mild AD, 12 MCI, and 9 healthy controls) underwent brain MR, neuropsychological evaluation, and resting EEG recording. A progressive increase of EEG delta and theta spectral power was observed from controls to patients, mainly in more anterior areas, with a parallel widespread decrease of beta power. Moreover, a progressive decrease of FA from controls to patients in frontal areas and in the corpus callosum (genu) was observed. Correlation analyses indicated convergence among EEG rhythms changes, DTI values, and cognitive status mainly over anterior areas. The decrease of FA values and EEG spectral power changes might represent markers of neurodegenerative dysfunction, possibly preceding macrostructural atrophy.

An Unusual Cause of Dementia: Essential Diagnostic Elements of Corticobasal Degeneration—A Case Report and Review of the Literature

Corticobasal degeneration (CBD) is an uncommon, sporadic, neurodegenerative disorder of mid- to late-adult life. We describe a further example of the pathologic heterogeneity of this condition. A 71-year-old woman initially presented dysarthria, clumsiness, progressive asymmetric bradykinesia, and rigidity in left arm. Rigidity gradually involved ipsilateral leg; postural instability with falls, blepharospasm, and dysphagia subsequently developed. She has been previously diagnosed as unresponsive Parkinsons Disease. At our clinical examination, she presented left upper-arm-fixed-dystonia, spasticity in left lower limb and pyramidal signs (Babinski and Hoffmann). Brain MRI showed asymmetric cortical atrophy in the right frontotemporal cortex. Neuropsychological examination showed an impairment in visuospatial functioning, frontal-executive dysfunction, and hemineglect. This case demonstrates that association of asymmetrical focal cortical and subcortical features remains the clinical hallmark of this condition. There are no absolute markers for the clinical diagnosis that is complicated by the variability of presentation involving also cognitive symptoms that are reviewed in the paper. Despite the difficulty of diagnosing CBD, somatosensory evoked potentials, motor evoked potentials, long latency reflexes, and correlations between results on electroencephalography (EEG) and electromyography (EMG) provide further support for a CBD diagnosis. These techniques are also used to identify neurophysiological correlates of the neurological signs of the disease.

P10.13 Changing effective connectivity in course of limbic encephalitis: a TMS+EEG study

Results: Background activity in both control and mutant mice was composed by phases of 1 4 Hz or 6 9 Hz. In mutants, concomitantly with a rising number of seizures, normal background activity progressively got worse by decrease in amplitude, slowing of activity and manifestation of epileptiform abnormalities. Treatment of mutant mice with rapamycin fully reverted the mutant phenotype. Conclusions: Spontaneous epileptic seizures were observed in 100% of mutant mice, that died within day 18 if not treated with rapamycin. Video-EEG proved to be essential to study this model of epilepsy and effects of rapamycin treatment. Moreover, we showed that is possible to perform it also in very young mice.

W9.2 De-coupling of primary sensory and primary motor areas in focal task-specific hand dystonia: a magnetoencephalographic study

J.M. Melgari1, F. Zappasodi2, C. Porcaro3, L. Tomasevic4, E. Cassetta5, F. Tecchio4, P.M. Rossini1 1Neurology, University Campus Bio-Medico, Rome, Italy, 2Dept. of Clinical Sciences and Bioimaging, ‘G. D’Annunzio’ University, Chieti, Italy, Chieti, Italy, 3School of Psychology and Birmingham University Imaging Centre, University of Birmingham, Birmingham, UK, 4ISTC-CNR, Rome, Italy, 5AFaR, Fatebenefratelli hospital, Isola Tiberina, Rome, Italy

P21.10 M1 excitability and cerebral connectivity: a TMS+EEG study

Introduction and Objective: Previous studies in relapsing remitting Multiple Sclerosis patients found evoked potentials to be reliable predictors of long term disability. Induction strategy is becoming increasingly used in MS and it is particularly valid as therapeutic strategy if applied in the early phases of the disease. The aim of this study was to assess the role of EPs in predicting future disability and the risk of conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndromes (CIS). Methods: We retrospectively analyzed 91 patients with CIS. Medical files were reviewed for clinical presentation. All patients underwent multimodal EPs after a mean time of 2±1.9 months from onset: visual (VEP), somatosensory (SEP) and motor (MEP) evoked potentials were obtained in all patients, brainstem auditory evoked potentials (BAEP) in 86. Each EP received an abnormality score from 0 to 3 (normal to absent; maximum possible multimodal total sum score = 36). Results: Average global score of abnormal EPs was 5±4. Basal global EPs score significantly correlated with EDSS5 (ø = 0.27 p = 0.008) and disability progression (EDSS5 EDSS2; ø = 0.30 p = 0.004). EP global score >5 predicted a higher risk of disability at 5 years, defined as an EDSS 3 (PPV = 24% p = 0.001). Lower limb SEP and MEP sum score were better able to predict the development of disability at 5 years (46% p = 0.0001). Subclinical EP abnormalities predicted the development of involvement of the corresponding FS at 5 years. This predictive value was found for VEP (PPV = 15.8% p = 0.04) BAEP (PPV = 55.6% p = 0.04), SEP (PPV = 30.6% p = 0.03), MEP (PPV = 90% p = 0.03). When excluding, in monofocal patients, EPs related to the symptomatic pathway, patients with 2 or 3 abnormal EPs at onset had a higher risk of conversion to CDMS (PPV = 40.4% p = 0.05). Conclusions: The present findings suggest that multimodal EPs at onset in patients with CIS have a predictive value regarding the evolution of disability. Moreover, a subclinical wide involvement of multiple sensorimotor pathways, detected as abnormalities in at least 2 EPs, increases the risk of conversion to CDMS.

P23-15 De-coupling of primary sensory from primary motor areas in focal task-specific hand dystonia: A MEG study

clinical diagnosis of this condition (7 men and 9 women, mean age of 51±18 years). For normal control, 19 aged-matched healthy subjects (11 men and 8 women, mean age of 49±18 years) were studied. Results: Fourteen out of 16 patients showed giant SEPs. P25 and N35 amplitudes in the patient group were 11.5±6.4mV and 18.9±11.6mV, respectively, and both were significantly larger compared with normal controls (P< 0.05). There was a significant positive correlation between age at SEP examination and N20, P25 and N35 amplitudes both in the patient and normal groups (P< 0.05). The linear regression gradient of N35 amplitude with respect to the age was significantly larger in the patient group than in the normal control groups (P< 0.05). Furthermore, older patients showed significantly severer myoclonus than younger patients (P< 0.05). Conclusions: Therefore, SEP amplitude increases with age in patients with BAFME to a greater extent than in normal controls, and it may suggest a progressive increase in cortical excitability based on progressive pathophysiology in BAFME.