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Highlights: [•] We studied the link between seizures, inflammatory cytokines and iron metabolism. [•] Serum cytokines alterations (IL-6 increase/TNF-α decrease) in epileptic patients. [•] Changes in iron metabolism consistent with inflammation as acute phase markers. [•] Relevant relationship between epilepsy and systemic inflammation. [ABSTRACT FROM AUTHOR]

Highlights: [•] Through an ad hoc procedure (FSS), distinct sources were identified in S1 and M1. [•] No differences were found between spectral properties of patients and controls for either S1 and M1. [•] Gamma band S1–M1 coherence was bilaterally reduced in patients during movement. [•] In focal hand dystonia, uncoupling replaces the physiological sensorimotor coupling. [•] Bi-hemispheric abnormalities in unilateral dystonia suggest endophenotypic traits. [ABSTRACT FROM AUTHOR]

Abstract: Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS. [Copyright &y& Elsevier]

Abstract: The theta/gamma and alpha3/alpha2 ratio were investigated as early markers for prognosticating of progression to dementia. 76 subjects with mild cognitive impairment (MCI) underwent EEG recording, MRI scans and neuropsychological (NPS) tests. After 3 years of follow-up, three subgroups were characterized as converters to Alzheimer''s disease (AD, N =18), converters to non-AD dementia (N =14) and non-converters (N =44). The theta/gamma and alpha3/alpha2 ratio, performance on cognitive tests and hippocampal volume, as evaluated at the time of initial MCI diagnosis, were studied in the three groups. As expected, MCI to AD converters had the smallest mean hippocampal volume and poorest performance on verbal learning tests, whereas MCI to non-AD converters had poorest cognitive performance in non-verbal learning tests, abstract thinking, and letter fluency. Increased theta/gamma ratio was associated with conversion to both AD and non-AD dementia; increased alpha3/alpha2 ratio was only associated with conversion to AD. Theta/gamma and alpha3/alpha2 ratio could be promising prognostic markers in MCI patients. In particular, the increase of high alpha frequency seems to be associated with conversion in AD. EEG markers allow a mean correct percentage of correct classification up to 88.3%. Future prospective studies are needed to evaluate the sensitivity and specificity of these measures for predicting an AD outcome. [Copyright &y& Elsevier]

Abstract: Objective: Repetitive Transcranial Magnetic Stimulation (rTMS) has been recently employed as a therapeutic strategy for stroke, although its effects on cerebral hemodynamics has been poorly investigated. This study aims to examine the impact of high frequency rTMS on cerebral vasomotor reactivity (VMR). Methods: Twenty-nine healthy subjects were randomly assigned to real (19) or sham 17-Hz rTMS, applied on primary motor cortex (M1) of the dominant hemisphere. All subjects underwent Transcranial Doppler of the middle cerebral arteries to evaluate mean flow velocity and VMR before (T 0) and within 10min (T 1) following rTMS. Four subjects underwent further VMR evaluations at 2 (T 2), 5 (T 3) and 24h (T 4) after rTMS. As a control condition, 10 subjects underwent real (5) or sham rTMS on calcarine cortex. In addition, five acute stroke patients underwent five daily rTMS sessions on the affected hemisphere mimicking a therapeutic trial. Results: Following real rTMS on M1 (p =0.002) and calcarine cortex (p <0.001) VMR decreased with respect to T 0 in both hemispheres, while no change was observed after sham rTMS (p >0.6). VMR tended to remain lower than T 0 until T 3. Cerebral VMR decreased independently of the stimulated side also in the patients’ group. Conclusions: High frequency rTMS reduces cerebral VMR, possibly as a secondary effect on autonomic control of cerebral hemodynamics. Significance: The effect of rTMS on cerebral hemodynamics should be carefully considered before proceeding toward a therapeutic application in stroke patients. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Aim of the present study is to investigate the alterations of brain networks derived from EEG analysis in pre- and post-sleep onset conditions after 40 h of sleep deprivation (SD) compared to sleep onset after normal sleep in 39 healthy subjects. Functional connectivity analysis was made on electroencelographic (EEG) cortical sources of current density and small world (SW) index was evaluated in the EEG frequency bands (delta, theta, alpha, sigma and beta). Comparing pre- vs. post-sleep onset conditions after a night of SD a significant decrease of SW in delta and theta bands in post-sleep onset condition was found together with an increase of SW in sigma band. Comparing pre-sleep onset after sleep SD versus pre-sleep onset after a night of normal sleep a decreased of SW index in beta band in pre-sleep onset in SD compared to pre-sleep onset in normal sleep was evidenced. Concluding, brain functional network architecture is influenced by the SD in different ways. Brain networks topology during wake resting state needs to be further explored to reveal SD-related changes in order to prevent possible negative effects of SD on behaviour and brain function during wakefulness. The SW modulations as revealed by the current study could be used as an index of an altered balance between brain integration and segregation processes after SD. [ABSTRACT FROM AUTHOR]

Abstract: Objective: In this study the theta/gamma ratio was investigated as early marker of cognitive decline. Methods: Forty-nine subjects with mild cognitive impairment (MCI) underwent EEG recording and MRI scan. The theta/gamma ratio of the relative power at the peak frequency was computed. Based on the tertiles values of the ratio, three groups with increasing values of theta/gamma ratio were obtained. The groups were characterized by the performance on cognitive tests. Changes in functional brain connectivity, as expressed by interhemisperic and intrahemispheric EEG linear coherence in the groups were also evaluated. Results: Increase in theta/gamma ratio was associated with impairment in memory tests. This relationship was confirmed by correlation and multiple regression analysis. An independent association was found between theta/gamma ratio and alpha3/alpha2 power ratio. Coherence analysis showed modifications of interhemispheric functional coupling on temporal regions on slow frequencies. Conclusions: Theta/gamma ratio of relative power at peak frequency is significantly associated to memory decline. It could be a useful tool in detecting MCI subjects which are at major risk to develop Alzheimer’s disease (AD) or other dementias. Significance: A global modulation of brain rhythms could be driven by the pathological alterations of theta/gamma ratio. [Copyright &y& Elsevier]

Abstract: The International Federation of Clinical Neurophysiology (IFCN) is in the process of updating its Recommendations for clinical practice published in 1999. These new recommendations dedicated to somatosensory-evoked potentials (SEPs) update the methodological aspects and general clinical applications of standard SEPs, and introduce new sections dedicated to the anatomical–functional organization of the somatosensory system and to special clinical applications, such as intraoperative monitoring, recordings in the intensive care unit, pain-related evoked potentials, and trigeminal and pudendal SEPs. Standard SEPs have gained an established role in the health system, and the special clinical applications we describe here are drawing increasing interest. However, to prove clinically useful each of them requires a dedicated knowledge, both technical and pathophysiological. In this article we give technical advice, report normative values, and discuss clinical applications. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Objective: The present study evaluates the potential relationship between hippocampal atrophy and EEG brain rhythmicity, as assessed by relative band power and alpha frequency indices in a cohort of subjects with mild cognitive impairment (MCI). Methods: Eighty-eight subjects falling within the definition of MCI patients were enrolled. All subjects underwent EEG recording and magnetic resonance imaging (MRI). Volumetric morphometry estimates of the hippocampal region were computed. Individual EEG frequencies were indexed by the theta/alpha transition frequency (TF) and the individual alpha frequency (IAF). The relative power was separately computed for delta, theta, alpha1, alpha2 and alpha3 frequency bands. The MCI cohort was classified into four subgroups, based on the mean and standard deviations of the hippocampal volume of a normal elderly control sample. Results: The group with moderate hippocampal atrophy showed the highest increase in the theta power on frontal regions, and of the alpha2 and alpha3 powers on frontal and temporo-parietal areas. The analysis of the individual alpha frequency markers showed that the values for the alpha markers were highest in the group with the smallest hippocampal volume, whereas in the group with moderate hippocampal atrophy, these values were lower than in the group with severe atrophy. Conclusions: The relationship between hippocampal atrophy and EEG activity changes in MCI subjects is not proportional to the hippocampal atrophy. Therefore, EEG markers could represent a new tool for differential diagnosis. Significance: The hippocampal atrophy induces different brain synchronization/desynchronization patterns. EEG changes model the brain activity induced by a discrete change of the hippocampal volume. The changes in the EEG rhythmicity differ greatly from those in MCI patients with subcortical vascular damage. [Copyright &y& Elsevier]

Abstract: Objective: We evaluated the changes induced by cerebrovascular (CV) damage on brain rhythmicity recorded by electroencephalography (EEG) in a cohort of subjects with mild cognitive impairment (MCI). Methods: We enrolled 99 MCI subjects (Mini-Mental State Examination [MMSE] mean score 26.6). All subjects underwent EEG recording and magnetic resonance imaging (MRI). EEGs were recorded at rest. Individual EEG frequencies were indexed by the θ/α transition frequency (TF) and by the individual α frequency (IAF) with power peak in the extended α range (5–14Hz). Relative power was separately computed for δ, θ, α1, α2, and α3 frequency bands on the basis of the TF and IAF values. Subsequently, we divided the cohort in four sub-groups based on subcortical CV damage as scored by the age-related white matter changes scale (ARWMC). Results: CV damage was associated with ‘slowing’ of TF proportional to its severity. In the spectral bandpower the severity of vascular damage was associated with increased δ power and decreased α2 power. No association of vascular damage was observed with IAF and α3 power. Moreover, the θ/α1 ratio could be a reliable index for the estimation of the individual extent of CV damage. Conclusions: EEG analysis may show physiological markers sensitive to CV damage. The appropriate use of this EEG index may help the differential diagnosis of different forms of cognitive decline, namely primary degenerative and secondary to CV damage. Significance: The EEG neurophysiological approach, together with anatomical features from imaging, could be helpful in the understanding of the functional substrate of dementing disorders. [Copyright &y& Elsevier]

Abstract: In patients affected by monohemispheric stroke in the middle cerebral artery territory, who do not regain a normal neurological function, a positive contribution to the clinical recovery seems to be made by the involvement of primary hand representation areas in the affected hemisphere (AH), excessively asymmetric to its homologous in the unaffected hemisphere (UH). We investigated primary sensory hand areas in 41 chronic patients who had improved their clinical status without reaching complete recovery. The location and strength of the first cerebral sources activated by a contralateral galvanic median nerve stimulation (M20 and M30) were evaluated in both hemispheres, together with their interhemispheric differences. The source displacement in the AH with respect to the UH was positively correlated with clinical recovery (Spearman’s ρ =0.584, p =0.003). The excessive interhemispheric asymmetry – as defined on the basis of reference ranges in the healthy population – could be interpreted as the involvement of neuronal pools in the AH outside the hand ‘omega zone’ of the Rolandic sulcus, revealing the presence of plasticity phenomena. The present data provide support to a positive role of cerebral plasticity phenomena, partially contributing to post-stroke recovery in patients unable to achieve normal neurological function. [Copyright &y& Elsevier]

Abstract: The present study was undertaken to investigate after-effects of 7 Hz non-painful prolonged stimulation of the median nerve on somatosensory-evoked fields (SEFs). The working hypothesis that conditioning peripheral stimulations might produce delayed interfering (“gating”) effects on the response of somatosensory cortex to test stimuli was evaluated. In the control condition, electrical thumb stimulation induced SEFs in ten subjects. In the experimental protocol, a conditioning median nerve stimulation at wrist preceded 6 electrical thumb stimulations. Equivalent current dipoles fitting SEFs modeled responses of contralateral primary area (SI) and bilateral secondary somatosensory areas (SII) following control and experimental conditions. Compared to the control condition, conditioning stimulation induced no amplitude modulation of SI response at the initial stimulus-related peak (20 ms). In contrast, later response from SI (35 ms) and response from SII were significantly weakened in amplitude. Gradual but fast recovery towards control amplitude levels was observed for the response from SI-P35, while a slightly slower cycle was featured from SII. These findings point to a delayed “gating” effect on the synchronization of somatosensory cortex after peripheral conditioning stimulations. This effect was found to be more lasting in SII area, as a possible reflection of its integrative role in sensory processing. [Copyright &y& Elsevier]

Abstract: High plasma concentration of homocysteine is an independent risk factor for Alzheimer’s disease (AD), due to microvascular impairment and consequent neural loss [ Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 346(7):476–483]. Is high plasma homocysteine level related to slow electroencephalographic (EEG) rhythms in awake resting AD subjects, as a reflection of known relationships between cortical neural loss and these rhythms? To test this hypothesis, we enrolled 34 mild AD patients and 34 subjects with mild cognitive impairment (MCI). Enrolled people were then subdivided into four sub-groups of 17 persons: MCI and AD subjects with low homocysteine level (MCI− and AD−, homocysteine level <11 μmol/l); MCI and AD subjects with high homocysteine level (MCI+ and AD+, homocysteine level ≥11 μmol/l). Resting eyes-closed EEG data were recorded. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Results showed that delta (frontal and temporal), theta (central, frontal, parietal, occipital, and temporal), alpha 1 (parietal, occipital, and temporal), and alpha 2 (parietal and occipital) sources were stronger in magnitude in AD+ than AD− group. Instead, no difference was found between MCI− and MCI+ groups. In conclusion, high plasma homocysteine level is related to unselective increment of cortical delta, theta, and alpha rhythms in mild AD, thus unveiling possible relationships among that level, microvascular concomitants of advanced neurodegenerative processes, and synchronization mechanisms generating EEG rhythms. [Copyright &y& Elsevier]

Abstract: In this study, we tested whether there is a somatotopic sensory organization in human anterior cingulate cortex (ACC) and supplementary motor area (SMA), as a reflection of central feed-back sensory processing for motor control. To this aim, fMRI recordings were performed in 15 normal young adults during nonpainful and painful electric stimulation of median nerve at the wrist and tibial nerve at the medial malleolus. Results showed that the representation of median nerve area was more anterior in the ACC and more inferior in the SMA than the one of tibial nerve area. This was true for both nonpainful and painful stimulation intensities. These results point to a somatotopic sensory organization of human ACC and SMA. [Copyright &y& Elsevier]

Abstract: Movement control requires continuous and reciprocal exchange of information between activities of motor areas involved in the task program execution and those elaborating proprioceptive sensory information. Our aim was to investigate the sensorimotor interactions in the region dedicated to hand control in healthy humans, focusing onto primary sensory and motor cortices, by selecting the time window at very early latencies. Through magnetoencephalographic recordings, we obtained a simultaneous assessment of sensory cortex activity modulation due to movement and of motor cortex activity modulation due to sensory stimulation, by eliciting a galvanic stimulation to the nerve (the median nerve) innervating a muscle (the opponens pollicis), at rest or during voluntary contraction. The primary sensory and motor cortices activities were investigated respectively through excitability in response to sensory stimulation and the cortico-muscular coherence. The task was performed bilaterally. A clear reduction of the cortico-muscular coherence was found in the short time window following stimuli (between around 150–450 ms). In the same time period, the motor control of isometric contraction was preserved. This could suggest that cortical component of voluntary movement control was transiently mediated by neuronal firing rate tuning more than by cortico-muscular synchronization. In addition to the known primary sensory cortex inhibition due to movement, a more evident reduction was found for the component known to include a contribution from primary motor areas. Gating effects were lower in the dominant left hemisphere, suggesting that sensorimotor areas dominant for hand control benefit of narrowing down gating effects. [Copyright &y& Elsevier]

Abstract: The present study focused on functional coupling between human bilateral auditory cortices and on possible influence of right over left auditory cortex during dichotic listening of complex non-verbal tones having near (competing) compared with distant non-competing fundamental frequencies. It was hypothesized that dichotic stimulation with competing tones would induce a decline of functional coupling between the two auditory cortices, as revealed by a decrease of electroencephalography coherence and an increase of directed transfer function from right (specialized for the present stimulus material) to left auditory cortex. Electroencephalograph was recorded from T3 and T4 scalp sites, overlying respectively left and right auditory cortices, and from Cz scalp site (vertex) for control purposes. Event-related coherence between T3 and T4 scalp sites was significantly lower for all electroencephalography bands of interest during dichotic listening of competing than non-competing tone pairs. This was a specific effect, since event-related coherence did not differ in a monotic control condition. Furthermore, event-related coherence between T3 and Cz and between T4 and Cz scalp sites showed no significant effects. Conversely, the directed transfer function results showed negligible influence at group level of right over left auditory cortex during dichotic listening. These results suggest a decrease of functional coupling between bilateral auditory cortices during competing dichotic stimuli as a possible neural substrate for the lateralization of auditory stimuli during dichotic listening. [Copyright &y& Elsevier]

Abstract: Previous evidence from functional magnetic resonance imaging (fMRI) has shown that a painful galvanic stimulation mainly activates a posterior sub-region in the secondary somatosensory cortex (SII), whereas a non-painful sensory stimulation mainly activates an anterior sub-region of SII [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for non-painful and painful stimuli: an fMRI study. Neuroimage 20 (3), 1625–1638.]. The present study, combining fMRI with magnetoencephalographic (MEG) findings, assessed the working hypothesis that the activity of such a posterior SII sub-region is characterized by an amplitude and temporal evolution in line with the bilateral functional organization of nociceptive systems. Somatosensory evoked magnetic fields (SEFs) recordings after alvanic median nerve stimulation were obtained from the same sample of subjects previously examined with fMRI [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for non-painful and painful stimuli: an fMRI study. Neuroimage 20 (3), 1625–1638.]. Constraints for dipole source localizations obtained from MEG recordings were applied according to fMRI activations, namely, at the posterior and the anterior SII sub-regions. It was shown that, after painful stimulation, the two posterior SII sub-regions of the contralateral and ipsilateral hemispheres were characterized by dipole sources with similar amplitudes and latencies. In contrast, the activity of anterior SII sub-regions showed statistically significant differences in amplitude and latency during both non-painful and painful stimulation conditions. In the contralateral hemisphere, the source activity was greater in amplitude and shorter in latency with respect to the ipsilateral. Finally, painful stimuli evoked a response from the posterior sub-regions peaking significantly earlier than from the anterior sub-regions. These results suggested that both ipsi and contra posterior SII sub-regions process painful stimuli in parallel, while the anterior SII sub-regions might play an integrative role in the processing of somatosensory stimuli. [Copyright &y& Elsevier]

Abstract: Objective: Repetitive transcranial magnetic stimulation (rTMS) is proposed for the treatment of drug-resistant depression. Studies performed in accordance with evidence-based medicine (EBM) are scarce, particularly in seeking optimal treatment and evaluation parameters. We aimed to test various types of rTMS in a large sample of depressed patients following EBM rules and to investigate treatment-related changes in plasma levels of neurotransmitters involved in depression. Methods: Seventy-one drug-resistant depressed patients were randomly assigned to low (1Hz) or high (17Hz) rate TMS, applied for 5 days over the left dorsolateral prefrontal cortex (L-DLPFC). Patients were separated into two study designs. One group (20 patients) received only active treatment, while the other entered a double-blind, placebo-controlled, crossover design. Pre- and post-treatment blood samples were taken for evaluation of plasma levels of dopamine and serotonin. Results: After a week of treatment patients had a measurable benefit. However, overall the placebo stimulation did not differ significantly from real stimulation, nor were differences observed between the two rates of rTMS. The only difference emerged when the real stimulation was applied at 17Hz following placebo treatment. Plasma levels of neurotransmitters between active and placebo rTMS were similar. Conclusions: Using the treatment schedule of 1 week, although a clinical improvement after active treatment was indeed observed, this was both clinically and biochemically indistinguishable from that seen in the placebo arm. Significance: This suggests that most of the previous emphasis, for short period of treatment, should be tempered down and that further work is required in order to verify whether optimal stimulation and evaluation parameters for TMS-treatment of depression beyond the placebo effect may be found following EBM rules. [Copyright &y& Elsevier]

Abstract: Objective: To test a technique called Directed Transfer Function (DTF) for the estimation of human cortical connectivity, by means of simulation study and human study, using high resolution EEG recordings related to finger movements. Methods: The method of the Directed Transfer Function (DTF) is a frequency-domain approach, based on a multivariate autoregressive modeling of time series and on the concept of Granger causality. Since the spreading of the potential from the cortex to the sensors makes it difficult to infer the relation between the spatial patterns on the sensor space and those on the cortical sites, we propose the use of the DTF method on cortical signals estimated from high resolution EEG recordings, which exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. The simulation study was followed by an analysis of variance (ANOVA) of the results obtained for different levels of Signal to Noise Ratio (SNR) and temporal length, as they have been systematically imposed on simulated signals. The whole methodology was then applied to high resolution EEG data recorded during a visually paced finger movement. Results: The statistical analysis performed returns that during simulations, DTF is able to estimate correctly the imposed connectivity patterns under reasonable operative conditions, i.e. when data exhibit a SNR of at least 3 and a length of at least 75s of non-consecutive recordings at 64Hz of sampling rate, equivalent, more generally, to 4800 data samples. Conclusions: Functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in any practical EEG recordings, by combining high resolution EEG techniques, linear inverse estimation and the DTF method. Significance: The estimation of cortical connectivity can be performed not only with hemodynamic measurements, by using functional MRI recordings, but also with modern EEG recordings treated with advanced computational techniques. [Copyright &y& Elsevier]

Abstract: Nowadays, several types of brain imaging device are available to provide images of the functional activity of the cerebral cortex based on hemodynamic, metabolic, or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions communicate with each other. In this study, advanced methods for the estimation of cortical connectivity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are presented. These methods include a subject''s multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual magnetic resonance images, multidipole source model, and regularized linear inverse source estimates of cortical current density. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI. We estimate functional cortical connectivity by computing the directed transfer function (DTF) on the estimated cortical current density waveforms in regions of interest (ROIs) on the modeled cortical mantle. The proposed method was able to unveil the direction of the information flow between the cortical regions of interest, as it is directional in nature. Furthermore, this method allows to detect changes in the time course of information flow between cortical regions in different frequency bands. The reliability of these techniques was further demonstrated by elaboration of high-resolution EEG and fMRI signals collected during visually triggered finger movements in four healthy subjects. Connectivity patterns estimated for this task reveal an involvement of right parietal and bilateral premotor and prefrontal cortical areas. This cortical region involvement resembles that revealed in previous studies where visually triggered finger movements were analyzed with the use of separate EEG or fMRI measurements. [Copyright &y& Elsevier]

In this MEG study, we investigated cortical alpha/sigma and beta ERD/ERS induced by median nerve stimulation to extend previous evidence on different resonant and oscillatory behavior of SI and SII (NeuroImage 13 [2001] 662). Here, we tested whether simple somatosensory stimulation could induce a distinctive sequence of alpha/sigma and beta ERD/ERS over SII compared to SI. We found that for both alpha/sigma (around 10 Hz) and beta (around 20 Hz) rhythms, the latencies of ERD and ERS were larger in bilateral SII than in contralateral SI. In addition, the peak amplitude of alpha/sigma and beta ERS was smaller in bilateral SII than in contralateral SI. These results indicate a delayed and prolonged activation of SII responses, reflecting a protracted information elaboration possibly related to SII higher order role in the processing of somatosensory information. This temporal dynamics of alpha/sigma and beta rhythms may be related to a sequential activation scheme of SI and SII during the somatosensory information processes. Future studies should evaluate in SII the possible different functional significance of alpha/sigma with respect to beta rhythms during somatosensory processing. [Copyright &y& Elsevier]

The secondary somatosensory cortex (SII) is strongly involved in the processing of somatosensory tactile and nociceptive sensations. We investigated the effect on SII responses of simultaneous painful and nonpainful electrical stimulations delivered to the thumb and little finger. According to the “bimodal” (i.e., nociceptive, tactile) organization of SII, it was expected that simultaneous painful and nonpainful stimulations would lead to modality interference with a marked reduction (“gating”) of somatosensory evoked fields (SEFs) generated in SII. Eight different stimulus conditions were studied. Two conditions were simultaneous “unimodal” (thumb and little finger nonpainful; thumb and little finger painful) and two conditions were simultaneous “bimodal” (thumb nonpainful and little finger painful; thumb painful and little finger nonpainful). As a reference, four conditions included stimulations at single sites (thumb nonpainful, little finger nonpainful, thumb painful, little finger painful). The gating phenomenon was defined as the percentage of difference between the intensities of SII activation after simultaneous compared to the sum of the separate stimulations. Results showed that simultaneous stimulations induced gating effects on SEFs generated by SII. No significant gating differences were observed after the two unimodal stimulations, suggesting a negligible effect of global energy on gating. Instead, the gating effects on bilateral SII activity were stronger after simultaneous bimodal when compared to unimodal stimulations. Our findings hint that there could be a greater level of integration/convergence of painful and nonpainful stimuli in SII with respect to SI. Future studies should explore if it could have an important role in exploring pain relief. [Copyright &y& Elsevier]

Previous simulation studies have stressed the importance of the use of fMRI priors in the estimation of cortical current density. However, no systematic variations of signal-to-noise ratio (SNR) and number of electrodes were explicitly taken into account in the estimation process. In this simulation study we considered the utility of including information as estimated from fMRI. This was done by using as the dependent variable both the correlation coefficient and the relative error between the imposed and the estimated waveforms at the level of cortical region of interests (ROI). A realistic head and cortical surface model was used. Factors used in the simulations were the different values of SNR of the scalp-generated data, the different inverse operators used to estimated the cortical source activity, the strengths of the fMRI priors in the fMRI-based inverse operators, and the number of scalp electrodes used in the analysis. Analysis of variance results suggested that all the considered factors significantly afflict the correlation and the relative error between the estimated and the simulated cortical activity. For the ROIs analyzed with simulated fMRI hot spots, it was observed that the best estimation of cortical source currents was performed with the inverse operators that used fMRI information. When the ROIs analyzed do not present fMRI hot spots, both standard (i.e., minimum norm) and fMRI-based inverse operators returned statistically equivalent correlation and relative error values. [Copyright &y& Elsevier]

The aim of this study is to present a package including standard software for the electroencephalographic (EEG), electro-oculographic (EOG) and electromyographic (EMG) preliminary data analysis, which may be suitable to standardize the results of many EEG research centers studies (i.e. multi-centric studies) especially focused on event-related potentials. In particular, our software package includes (semi)automatic procedures for (i) EOG artifact detection and correction, (ii) EMG analysis, (iii) EEG artifact analysis, (iv) optimization of the ratio between artifact-free EEG channels and trials to be rejected. The performances of the software package on EOG–EEG–EMG data related to cognitive–motor tasks were evaluated with respect to the preliminary data analysis performed by two expert electroencephalographists (gold standard). Due to its extreme importance for multi-centric EEG studies, we compared the performances of two representative ‘regression’ methods for the EOG correction in time and frequency domains. The aim was the selection of the most suitable method in the perspective of a multi-centric EEG study. The results showed an acceptable agreement of approximately 95% between the human and software behaviors, for the detection of vertical and horizontal EOG artifacts, the measurement of hand EMG responses for a cognitive–motor paradigm, the detection of involuntary mirror movements, and the detection of EEG artifacts. Furthermore, our results indicated a particular reliability of a ‘regression’ EOG correction method operating in time domain (i.e. ordinary least squares). These results suggest that such a software package could be used for multi-centric EEG studies. [Copyright &y& Elsevier]

Objectives: A neural system matching action observation and execution seems to operate in the human brain, but its possible role in processing sensory inputs reaching the cortex during movement observation is unknown.Methods: We investigated somatosensory evoked potentials (SEPs), somatosensory evoked fields (SEFs) and the temporal spectral evolution of the brain rhythms (&ap;10 and &ap;20 Hz) following electrical stimulation of the right median nerve in 15 healthy subjects, during the following randomly intermingled conditions: a pure cognitive/attentive task (mental calculation); the observation of a motoric act (repetitive grasping) with low cognitive content (‘Obs-grasp’); and the observation of a complex motoric act (finger movement sequence), that the subject had to recognize later on, therefore reflecting an adjunctive cognitive task (‘Obs-seq’). These conditions were compared with an absence of tasks (‘Relax’) and actual motor performance.Results: The post-stimulus rebound of the &ap;20 Hz beta magnetoencephalographic rhythm was reduced during movement observation, in spite of little changes in the &ap;10 Hz rhythm. Novel findings were: selective amplitude increase of the pre-central N30 SEP component during both ‘Obs-grasp’ and ‘Obs-seq’, as opposed to the ‘gating effect’ (i.e. amplitude decrease of the N30) occurring during movement execution. The strength increase of the 30 ms SEF cortical source significantly correlated with the decrease of the &ap;20 Hz post-stimulus rebound, suggesting a similar pre-central origin.Conclusions: Changes took place regardless of either the complexity or the cognitive content of the observed movement, being related exclusively with the motoric content of the action. It is hypothesized that the frontal ‘mirror neurons’ system, known to directly facilitate motor output during observation of actions, may also modulate those somatosensory inputs which are directed to pre-central areas. These changes are evident even in the very first phases (i.e. few tens of milliseconds) of the sensory processing. [ABSTRACT FROM AUTHOR]

Objective: We investigated the effect of bilateral subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) on intracortical inhibition (ICI) in patients with advanced Parkinson''s disease (PD).Methods: The activity of intracortical inhibitory circuits was studied in 4 PD patients implanted with stimulating electrodes both in STN and GPi by means of paired-pulse transcranial magnetic stimulation, delivered in a conditioning-test design at short (1–6 ms) interstimulus intervals (ISI). The effect of apomorphine on the same PD patients was also investigated.Results: We observed that implanted PD patients showed a significant increase in ICI during either bilateral STN or GPi DBS at 3 ms ISI, and during bilateral STN DBS at 2 ms ISI in comparison to their off DBS condition. The same statistical improvement was observed during apomorphine infusion at 3 and 2 ms ISI. In each condition, the electrophysiological changes were associated with a significant clinical improvement as measured by the Unified Parkinson''s Disease Rating Scale motor examination.Conclusions: These results are consistent with the hypothesis that basal ganglia DBS can mimic the effects of pharmacological dopaminergic therapy on PD patients cortical activity. We propose that in PD patients, the basal ganglia DBS-induced improvement of ICI may be related to a recovery in modulation of thalamo-cortical motor pathway. [ABSTRACT FROM AUTHOR]

Introduction Motor evoked potentials (MEPs) elicited by a train of consecutive, individual transcranial magnetic stimuli demonstrate fluctuations in amplitude with respect to time when recorded from a relaxed muscle. The influence of time-varying, instantaneous modifications of the electroencephalography (EEG) properties immediately preceding the transcranial magnetic stimulation (TMS) has rarely been explored. Objective The aim of this study was to investigate the influence of the pre-TMS motor cortex and related areas EEG profile on time variants of the MEPs amplitude. Materials & methods MRI-navigated TMS and multichannel TMS-compatible EEG devices were used. For each experimental subject, posthoc analysis of the MEPs amplitude that was based on the 50th percentile of the MEPs amplitude distribution provided two subgroups corresponding to “high” (large amplitude) and “low” (small amplitude). The pre-stimulus EEG characteristics (coherence and spectral profile) from the motor cortex and related areas were analyzed separately for the “high” and “low” MEPs and were then compared. Results On the stimulated hemisphere, EEG coupling was observed more often in the high compared to the low MEP trials. Moreover, a paradigmatic pattern in which TMS was able to lead to significantly larger MEPs was found when the EEG of the stimulated motor cortex was coupled in the beta 2 band with the ipsilateral prefrontal cortex and in the delta band with the bilateral centro-parietal-occipital cortices. Conclusions This data provide evidence for a statistically significant influence of time-varying and spatially patterned synchronization of EEG rhythms in determining cortical excitability, namely motor cortex excitability in response to TMS. [ABSTRACT FROM AUTHOR]

Introduction The cortical representation of a muscle can be significantly modified by plastic reorganization following a limb amputation. These plastic changes are not immutable and can be further modified restoring by the use of prosthesis like new bionic anthropomorphic prosthesis connected to the peripheral nervous system via bidirectional neural interfaces. Transcranial magnetic stimulation (TMS) is a non-invasive technique commonly used to assess topographical reorganization of motor brain areas. Objective The aim of this study is to evaluate the motor cortical reorganization of primary motor cortex with the TMS mapping technique in a left trans-radial amputee patient following the use of a novel prosthetic system able to provide somatosensory feed-back from the lost hand of the user. Materials and methods Cortical motor output was mapped via TMS (intensity 10% above standardized excitability motor Threshold) for each hemisphere at the beginning, after 1 month and 2 month of training with the new prosthetic system. Peripheral responses were recorded from forearm flexor and extensor carpi ulnaris muscles of both limbs. Resting and Active motor threshold were also collected during separate mapping of right and left hemispheres. Results No significant differences were found in the motor thresholds between the two hemispheres before and after implantation. Pre-surgical TMS motor maps showed a slight abnormal interhemispheric asymmetry of motor cortex topography, resulted in a smaller area of representation of muscles governing the stump compared to the area for the intact limb. Following training, post-surgical maps, showed a reduction and a partial reversal of this asymmetry because of an enlargement of the excitable area on the right hemisphere contralateral to the stump, leading towards a more symmetrical muscle representation in the two hemispheres, as in control subjects. Conclusions Our experiment provides a direct and unique evidence of brain plasticity changes occurring in the motor cortex following the use of a prosthetic system able to restore a somatosensory feedback from the missing limb after amputation. [ABSTRACT FROM AUTHOR]

Introduction Transcranial direct current stimulation (tDCS) is well establishedamong the non-invasive brain stimulation techniques as a method to modulate brain excitability. Polarity-dependent modulations of membrane potentials are detected after the application of anodal and cathodal stimulation, leading to changes in the electrical activity of the neurons. Objective The main aim of the present study was to test the hypothesis that tDCS can affect in a polarityspecific manner the functional coupling of the sensorimotor areas during the eyes-open resting condition as revealed by total EEG coherence (i.e., coherence across the average of all combinations of the electrode pairs placed around the stimulation electrode). Material & methods The changes in the total EEG coherence were evaluated pre-, during, and post-anodal and cathodal tDCS. Results While no differences were observed in the connectivity characteristics of the two pre-stimulation periods, a connectivity increase was observed in the alpha 2 band in the post-anodal tDCS with respect to pre-anodal and post-cathodal tDCS. Conclusions The present study suggests that a specific approach based on the analyses of the functional coupling of EEG rhythms might enhance understanding of tDCS-induced effects on cortical connectivity. Moreover, this result suggests that anodal tDCS could possibly modify cortical connectivity more effectively with respect to cathodal tDCS. [ABSTRACT FROM AUTHOR]

Introduction Transcranial direct current stimulation (tDCS) is a non-invasive technique that is increasingly used in neuroscience, as it has the potential to induce cortical excitability changes (Nitsche et al., 2008; Woods et al., 2016). Specifically, tDCS has been widely applied to study cognition. Nevertheless, differently from motor system, applying tDCS in cognitive domains does not allow to have a direct physiological measure able to monitor polarity-dependent effects on cortical excitability. Event related potentials (ERPs) and TMS-evoked potentials (TEPs) could represent valuable surrogate markers of cortical excitability changes (Kesser et al., 2011; Miniussi and Thut, 2010). Objective The purpose of the present study was verifying the capability of tDCS to modulate cortical reactivity (using TEPs) of prefrontal cortex and characterizing the electrophysiological correlates (using ERPs) of cognitive processes underlying a working memory task. Materials & methods A sample of healthy young participants performed a 3-back task while EEG was recording before and after applying 13 min of tDCS (anodal, cathodal and sham sessions) over the left dorsolateral prefrontal cortex (DLPFC). TEPs were also collected before and after the tDCS. Results Results showed no tDCS polarity-dependent differences in task performance. However, increased prefrontal activity was observed at 150–200 ms over the stimulated region after cathodal tDCS. Furthermore, parietal activity underlying P3 component, which was typically related to working memory processes (Kesser et al., 2011), was larger after cathodal tDCS. Surprisingly, differences were found only after cathodal tDCS. These results were consistent with TEPs, which were modulated by tDCS in a polarity-dependent manner. Conclusion Our findings demonstrate that tDCS is able to induce prefrontal cortical activity and reactivity changes, which can be assessed by EEG and TMS-EEG measures, even when behavioral data are not sensitive enough to reveal functional modifications. Overall, these results suggest potential clinical application of tDCS and utility of ERPs and TEPs to monitor cortical excitability modifications induced by the stimulation protocols. [ABSTRACT FROM AUTHOR]

Introduction Transcranial direct current stimulation (tDCS) is a non-invasive method modulating cortical excitability in a polarity-dependent way. At present, only few studies investigated the effects of tDCS on the modulation of functional connectivity between remote cortical areas. Objective In the present study we aimed to investigate the impact of bipolar tDCS on cortical networks connectivity through graph theoretical analysis. Materials & methods High-density EEG recordings were acquired before and after bipolar anodal, cathodal and sham tDCS applied over the primary motor cortex of the dominant hemisphere in 14 healthy subjects. Results Results showed that, after bipolar anodal tDCS stimulation over the dominant primary motor cortex the related brain network presented a more small-worldnessy, meaning a global tendency to be more random in its functional connections respect to prestimulus condition in both hemispheres. Conclusions Our results suggest that tDCS is able to modulate globally the cortical connectivity of the brain, modifying the underlying functional organization via complex pattern of direct and indirect cortical activations or inhibitions of the stimulated networks, which might be related to changes in synaptic efficiency of the motor network and related brain areas. [ABSTRACT FROM AUTHOR]

Introduction The capacity of repetitive TMS to transiently interfere with cognitive processes in humans may offer an experimental platform for pharmacological studies. Developing compounds could then be tested to reverse artificially generated cognitive dysfunction, providing first hints of efficacy. In the FP7-IMI European ’Pharmacog’ Project, an rTMS protocol previously published in the literature, was adapted and validated as a ’cognitive challenge model’ to mimic episodic memory dysfunction occurring in early Alzheimer’s disease. However, it would be desirable to test whether the effects of TMS are comparable and reproducible across different centres and time-point assessments. Objectives Our main aims were, (1) to find out if visual memory interference through rTMS administration could be replicated using our specific experimental settings and task adaptations (Fig. 1), (2) to test if results are comparable in two centres and (3) to investigate if the effects obtained are reproducible when subjects are re-tested 15 days later. Methods 68 healthy young male subjects were included. Neuronavigated (Fig. 1) repetitive TMS was applied over the left dorsolateral prefrontal cortex (LDLPFC) or the Vertex area (control condition) during encoding of pictures, for latter memory recognition. Subjects attended one of two research centres in three main occasions: On visit 1, rTMS was applied using a sham coil and served as a baseline measure. On visit 2, real rTMS was administered. On visit 3, 15 days later, a subsample ( N = 21) performed the same protocol to test for reproducibility of effects. Results A time (visit 1 vs visit 2) × TMS type (LDLPFC vs Vertex) ANOVA and posterior pairwise comparisons revealed that only rTMS delivered over the LDLPFC and during visit 2 day resulted in a significant decrease in subsequent memory recognition ( F = 8.95, p = 0.004; Fig. 2a). No centre effect observed ( F = 0.03, p = 0.96). Initial rTMS effects could not be replicated in the subsample (Fig. 2b). Conclusions Our findings offers positive evidence regarding the feasibility of adapting a rTMS cognitive interference protocol, to conduct new experimental research in separate independent institutions. The factors underlying the lack of test–retest reproducibility of the interference should be further investigated. [ABSTRACT FROM AUTHOR]

It has been demonstrated that in young volunteers the characteristics of the ongoing EEG activity immediately preceding a TMS of M1 influence the following MEP amplitude. In this study we explored whether there is an effect of ageing on this EEG-MEP interactions. Then by means of a TMS-EEG experiment, the pre-stimulus EEG characteristics (coherence and spectral profile) of the stimulated M1 were analysed for “high” and “low” MEPs, classified according to the 50th percentile of their amplitude distribution and thus compared in the two groups. On the stimulated hemisphere the EEG coupling was observed more often in the high compared to the low MEP trials in both groups. The coupling in the beta2 band of the stimulated M1 with the ipsilateral prefrontal cortex was able to led to significantly larger MEPs both in young and old subjects. In contrast, the coupling in the delta band of M1 with the ipsilateral parieto-occipital cortices had an effect on the MEP’s size only in young subjects. Moreover, this coupling was significantly higher in elderly brain than in young brain both for high and low MEPs. These data provide evidence for an age-related influence of time-varying synchronization of EEG rhythms in determining M1 excitability. [ABSTRACT FROM AUTHOR]

Several experimental studies have shown that, nevertheless motor symptoms are late events in the natural history of Alzheimer’s disease (AD), neuropathological progression in the motor cortex parallels that in other brain cortices generally considered more specific targets of the aggression. In the last years we have clearly demonstrated that motor cortex excitability is enhanced in AD since the early stages of the disease and this is probably related to its severity and progression. To further investigate, for the first time without peripheral or attentional confounding effects, the neurophysiological hallmarks of motor cortex functionality in AD we used here transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG). We then demonstrated that in mild AD, despite the lack of clinical manifestations, the sensorimotor system is strongly hyper-excitable and its connectivity is deeply rearranged with the recruitment of additional neural sources, the activation of reverberant circuits and their integration in the distributed excitatory network subtending sensorimotor functions. [ABSTRACT FROM AUTHOR]

Ulnar neuropathy at elbow (UNE) is often related to postures and work-hobby activities. The use of mobile-phones has drastically increased in the last decades leading to prolonged phone posture (PPP) with flexed elbow. We aimed to assess the effect of PPP in patients with symptoms of UNE and in symptom-free subjects. Patients with pure sensory symptoms of UNE and negative neurophysiological tests (min-UNE) and symptoms-free subjects were enrolled. We evaluated ulnar motor nerve conduction velocity across elbow at baseline and after 6, 9, 12, 15, 18 min of PPP. Thirty-eight symptom-free subjects and thirty-eight patients were enrolled and 121 ulnar nerves were studied. Conduction velocity of ulnar nerve across the elbow significantly changed over PPP time both in control group and, at a greater extent, in patients with min-UNE. Conduction velocity during PPP showed different evolution between the two groups. The changes became significantly different after 6 min of PPP and progressively increased, with the greatest difference at 15 min. In conclusion, PPP causes a modification of nerve function, expressed by slowing of motor nerve conduction velocity, which is greater in patients with min-UNE although it also occurs in symptom-free subjects. Excessive PPP should be avoided in patients with UNE-symptoms. [ABSTRACT FROM AUTHOR]

The large majority (80%) of people with multiple sclerosis (MS) complain of fatigue, which is the most disabling symptom in half of them. While the few drugs used to treat MS fatigue are limitedly useful, it was recently observed the efficacy of a personalized neuromodulation treatment, supporting the concept that interventions modifying the sensorimotor network activity balances could be suitable non-pharmacological treatments for MS fatigue. Aim of the present study is to strengthen knowledge of the brain unbalances, which proper neuromodulations should target to compensate. We collected electroencephalographic (EEG) data in 18 people with mild MS, while they were in resting state with open eyes. To ensure a wide range of fatigue, we enrolled patients to have Higher- or Lower-Fatigue based on scores of the modified Fatigue Impact Scale (mFIS). We selected the graph theory small-world index, calculated on networks of cortical nodes estimated by eLORETA, to evaluate the characteristics of left and right frontal (Motor) and parieto-occipital-temporal (Sensory) brain networks separately. Fatigue symptoms increased together with the small-world index in the Sensory network of the left dominant hemisphere. This finding hones understanding of the targets of neuromodulation interventions, indicating the sensory network of the dominant left hemisphere as a specific target. [ABSTRACT FROM AUTHOR]

Functional connectivity, revealed by EEG, evaluates time synchronization in anatomically distinct but functionally collaborating brain regions. Structural connection, revealed by diffusion tensor imaging (DTI), detects fractional anisotropy (FA). FA decreases in pathological aging corpus callosum (CC) and could reflect functional disconnections. We investigated correlations between structural damage of CC (MRI-DTI) and functional abnormalities of brain integration (cortical Characteristic Path Length of EEG). Resting state EEG and MRI were evaluated in 9 healthy controls-Nold, 10 Mild Cognitive Impairment – MCI, 10 mild Alzheimer Disease – AD, 11 moderate AD. Undirected and weighted brain network was built to evaluate graph Path Length weighting network edges by eLORETA lagged connectivity. Callosal FA reduction was associated to a loss of brain interhemispheric functional connectivity characterized by increased delta and decreased alpha Path Length. Global (path length as index of how efficient is the information transfer inside network) functional measure can reflect the reduction of fibers connecting the hemispheres as revealed by DTI. Functional and structural disconnections do not share the same timing (functional coming first) in the prodromal stage of disease, but in disease evolution (from healthy to dementia) it is possible to obtain statistical correlations between connectivity’s indexes. [ABSTRACT FROM AUTHOR]