Filippo Zappasodi

Mapping distributed sources of cortical rhythms in mild Alzheimer's disease. A multicentric EEG study

The study aimed at mapping (i) the distributed electroencephalographic (EEG) sources specific for mild Alzheimers disease (AD) compared to vascular dementia (VaD) or normal elderly people (Nold) and (ii) the distributed EEG sources sensitive to the mild AD at different stages of severity. Resting EEG (10-20 electrode montage) was recorded from 48 mild AD, 20 VaD, and 38 Nold subjects. Both AD and VaD patients had 24-17 of mini mental state examination (MMSE). EEG rhythms 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). Cortical EEG sources were modeled by low resolution brain electromagnetic tomography (LORETA). Regarding issue i, there was a decline of central, parietal, temporal, and limbic alpha 1 (low alpha) sources specific for mild AD group with respect to Nold and VaD groups. Furthermore, occipital alpha 1 sources showed a strong decline in mild AD compared to VaD group. Finally, distributed theta sources were largely abnormal in VaD but not in mild AD group. Regarding issue ii, there was a lower power of occipital alpha 1 sources in mild AD subgroup having more severe disease. Compared to previous field studies, this was the first investigation that illustrated the power spectrum profiles at the level of cortical (macroregions) EEG sources in mild AD patients having different severity of the disease with respect to VaD and normal subjects. Future studies should evaluate the clinical usefulness of this approach in early differential diagnosis, disease staging, and therapy monitoring.

Auditory sensory processing in autism: a magnetoencephalographic study

BACKGROUND Patients with autism show clinical features suggestive of abnormal processing of auditory and other sensory information. We hypothesized that low-functioning autistic subjects present abnormalities in discriminating simple auditory stimuli at sensory system preconscious stages of cortical processing. METHODS To verify our hypothesis, we used magnetoencephalographic measurements of mismatch field (MMF), which reflects the detection of a change in the physical characteristics of a repetitive sound. Fourteen patients (aged 8-32 years) who met DSM-IV diagnostic criteria for autistic disorder participated in an auditory oddball experiment. Ten healthy participants matched for age and gender acted as control subjects. RESULTS Significant differences in cerebral responses between patients and control subjects were recorded. Whereas control subjects showed a clearly identifiable MMF, with distinct generators in the M100 brain wave with regard to latency, position, and strength, no identifiable MMF was present in the autistic group. CONCLUSIONS Our findings suggest that low-functioning autistic subjects present a dysfunction at preconscious stages of cortical auditory discrimination, playing a role in the abnormal processing of auditory sensory afferences. The attention independence of the MMF allows for exclusion of an effect related to impaired attention or task-related responses.

Inhibition of auditory cortical responses to ipsilateral stimuli during dichotic listening: evidence from magnetoencephalography

The present magnetoencephalography (MEG) study on auditory evoked magnetic fields (AEFs) was aimed at verifying whether during dichotic listening the contralateral auditory pathway inhibits the ipsilateral one, as suggested by behavioural and patient studies. Ten healthy subjects were given a randomized series of three complex tones (261, 293 and 391 Hz, 500 ms duration), which were delivered monotically and dichotically with different intensities [60, 70 or 80 dBA (audio decibels)]. MEG data were recorded from the right auditory cortex. Results showed that the M100 amplitude over the right auditory cortex increased progressively when tones of increasing intensity were provided at the ipsilateral (right) ear. This effect on M100 was abolished when a concurrent tone of constant intensity was delivered dichotically at the contralateral (left) ear, suggesting that the contralateral pathway inhibited the ipsilateral one. The ipsilateral inhibition was present only when the contralateral tone fundamental frequency was similar to the ipsilateral tone. It was proposed that the occlusion mechanism would be exerted in cortical auditory areas as the dichotic effects were observed at M100 but not M50 component. This is the first evidence showing a neurophysiological inhibition driven by the contralateral auditory pathway over the ipsilateral one during dichotic listening.

Anodal Transcranial Direct Current Stimulation Enhances Procedural Consolidation

The primary motor cortex (M1) area recruitment enlarges while learning a finger tapping sequence. Also M1 excitability increases during procedural consolidation. Our aim was to investigate whether increasing M1 excitability by anodal transcranial DC stimulation (AtDCS) when procedural consolidation occurs was able to induce an early consolidation improvement. Forty-seven right-handed healthy participants were trained in a nine-element serial finger tapping task (SFTT) executed with the left hand. Random series blocks were interspersed with training series blocks. Anodal or sham tDCS was administered over the right M1 after the end of the training session. After stimulation, the motor skills of both trained and a new untrained sequential series blocks were tested again. For each block, performance was estimated as the median execution time of correct series. Early consolidation of the trained series, assessed by the performance difference between the first block after and the last block before stimulation normalized by the random, was enhanced by anodal and not by sham tDCS. Stimulation did not affect random series execution. No stimulation effect was found on the on-line learning of the trained and new untrained series. Our results suggest that AtDCS applied on M1 soon after training improves early consolidation of procedural learning. Our data highlight the importance of neuromodulation procedures for understanding learning processes and support their use in the motor rehabilitation setting, focusing on the timing of the application.

‘Free’ copper in serum of Alzheimer’s disease patients correlates with markers of liver function

SummaryNon-ceruloplasmin bound copper (‘free’) seems slightly elevated in Alzheimer’s disease (AD) patients. To test the hypothesis of a correlation between ‘free’ copper and liver function in AD. We evaluated 51 AD patients and 53 controls through typical tests for chronic liver disease (AST, ALT, γ-GT, Albumin, prothrombin time – PT-, bilirubins), along with copper, ceruloplasmin, iron, cholesterol in the serum and apolipoprotein E epsilon4 (APOE4) genotype. Absolute serum copper and ‘free’ copper were higher, albumin was lower and PT longer in AD patients than in controls. ‘Free’ copper correlated negatively with markers of liver function, in that albumin and albumin/PT ratio (r = −0.43, p = 0.004), and positively with direct bilirubin. Copper and ‘free’ copper were higher in the APOE4 carriers. These results suggest that abnormalities in copper metabolism might have an effect on liver function in AD.

Estimating true brain connectivity from EEG/MEG data invariant to linear and static transformations in sensor space

The imaginary part of coherency is a measure to investigate the synchronization of brain sources on the EEG/MEG sensor level, robust to artifacts of volume conduction meaning that independent sources cannot generate a significant result. It does not mean, however, that volume conduction is irrelevant when true interactions are present. Here, we analyze in detail the possibilities to construct measures of true brain interactions which are strictly invariant to linear spatial transformations of the sensor data. Specifically, such measures can be constructed from maximization of imaginary coherency in virtual channels, bivariate measures as a corrected variate of imaginary coherence, and global measures indicating the total interaction contained within a space or between two spaces. A complete theoretic framework on this question is provided for second order statistical moments. Relations to existing linear and nonlinear approaches are presented. We applied the methods to resting state EEG data, showing clear interactions at all bands, and to a combined measurement of EEG and MEG during rest condition and a finger tapping task. We found that MEG was capable of observing brain interactions which were not observable in the EEG data.

Brain activity preceding a 2D manual catching task.

We investigated the event-related desynchronization (ERD) and synchronization (ERS) properties of cortical EEG rhythms in regions of interest (ROI) during the preparation of a 2D task for manual catching of a moving object. EEG signals were recorded through a 32-channel system in eleven healthy subjects during the interception task consisting of 2D catching with the right hand of a handle moving at constant velocity (1.5 m/s) on a predefined straight trajectory. The first session of catching movements (CATCHING_PRE) was compared with a second session after 1 h with identical characteristics (CATCHING_POST) and with other two conditions, where the subjects had to reach and grasp the handle fixed in the medium of platform (REACHING) and they looked at the object moving without catching it (GAZE TRACKING). Changes of cortical rhythms were correlated with dynamic and kinematic indexes of motor performance in both catching sessions. Movements requiring different strategies (predictive versus prospective) are supported by specific changes of cortical EEG rhythms: in the CATCHING condition a more evident power decrease (ERD) in alpha 2 and beta band in the sensorimotor region contralateral to the catching hand was observed, while in the REACHING one a bilateral ERD in beta band was found. Motor learning and movement automatization were characterized by a significant reduction of theta ERS in the anterior cingulate cortex (ACC), a ROI linked to focused attention, and with a shift of neuronal activation in alpha 2 band from the bilateral superior parietal areas to the homologous area of the left hemisphere. Finally, our EEG findings are consistent with the role of supplementary motor (SMA), premotor and prefrontal areas in motor planning and preparation. In particular, theta ERS in left SMA significantly correlated with an improvement of motor performance, as evidenced by its correlation with the training-related reduction of interception time (IT).

Developmental Tuning and Decay in Senescence of Oscillations Linking the Corticospinal System

There is increasing evidence of the importance of synchronous activity within the corticospinal system for motor control. We compared oscillatory activity in the primary sensorimotor cortex [EEG of sensorimotor cortex (SMC-EEG)] and a motor neuronal pool [surface electromyogram of opponens pollicis (OP-EMG)], and their coherence in children (4–12 years of age), young adults (20–35 years of age), and elderly adults (>55 years of age). The ratio between lower (2–13 Hz) and higher (14–32 Hz) frequencies in both SMC-EEG and OP-EMG decreased with age, correlating inversely with motor performance. There was evidence for larger, more distributed cortical networks in the children and elderly compared with young adults. Corticomuscular coherence (CMC) was present in all age groups and shifted between frontal and parietal cortical areas. In children, CMC was smaller and less stationary in amplitude and frequency than in adults. Young adults had single peaks of CMC clustered near the modal frequency (23 Hz); multiple peaks with a broad spread of frequencies occurred in children and the elderly; the further the frequency of the maximum peak CMC was from 23 Hz, the poorer the performance. CMC amplitude was inversely related to performance in young adults but was not modulated in relation to performance in children and the elderly. We propose that progressive fine-tuning of the frequency coding and stabilization of the dynamic properties within and between corticospinal networks occurs during adolescence, refining the capacity for efficient dynamic communication in adulthood. In old age, blurring of the tuning between networks and breakdown in their integration occurs and is likely to contribute to a decrement in motor control.

Local and remote effects of transcranial direct current stimulation on the electrical activity of the motor cortical network

We systematically investigated the effects of cathodal and anodal Transcranial Direct Current Stimulation (CtDCS, AtDCS) on the electric activity of primary motor cortex during a motor task. High‐density electroencephalography was used to define the spatial diffusion of tDCS after effects. Ten healthy subjects performed a finger tapping task with the right hand before and after three separate sessions of 20 minutes of Sham, AtDCS or CtDCS over left primary motor cortex (M1). During movement, we found an increment of low alpha band Event‐Related Desynchronization (ERD) in bilateral central, frontal areas and in the left inferior parietal region, as well as an increment of beta ERD in fronto‐central and parieto‐occipital regions, after AtDCs compared to Sham and CtDCS. In the rest pre‐movement period, after Sham as well as AtDCS, we documented an increment of low alpha band power over the course of pre‐ and post‐stimulation recording sessions, localized in the sensorimotor and parieto‐occipital regions. On the contrary, after CtDCS no increment of low alpha power was found. Finally beta band coherence among signals from left sensorimotor cortex and activity of bilateral parietal, occipital and right frontal regions was higher after AtDCS compared with Sham condition. Similarly, theta coherence with parietal and frontal regions was enhanced after AtDCS. We hypothesize that the local modulation of membrane polarization, as well as long‐lasting synaptic modification induced by tDCS over M1, could result in changes of both local band power and functional architecture of the motor network. Hum Brain Mapp 35:2220–2232, 2014.

Free copper and resting temporal EEG rhythms correlate across healthy, mild cognitive impairment, and Alzheimer's disease subjects.

OBJECTIVE The present study tested the hypothesis that the serum copper abnormalities were correlated with alterations of resting electroencephalographic (EEG) rhythms across the continuum of healthy elderly (Hold), mild cognitive impairment (MCI), and AD subjects. METHODS Resting eyes-closed EEG rhythms 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), estimated by LORETA, were recorded in 17 Hold, 19 MCI, 27 AD- (MMSE< or =20), and 27 AD+ (MMSE20) individuals and correlated with copper biological variables. RESULTS Across the continuum of Hold, MCI and AD subjects, alpha sources in parietal, occipital, and temporal areas were decreased, while the magnitude of the delta and theta EEG sources in parietal, occipital, and temporal areas was increased. The fraction of serum copper unbound to ceruloplasmin positively correlated with temporal and frontal delta sources, regardless of the effects of age, gender, and education. CONCLUSIONS These results sustain the hypothesis of a toxic component of serum copper that is correlated with functional loss of AD, as revealed by EEG indexes. SIGNIFICANCE The present study represents the first demonstration that the fraction of serum copper unbound to ceruloplasmin is correlated with cortical delta rhythms across Hold, MCI, and AD subjects, thus unveiling possible relationships among the biological parameter, advanced neurodegenerative processes, and synchronization mechanisms regulating the relative amplitude of selective EEG rhythms.