Cortical rhythms reactivity in AD, LBD and normal subjects: A quantitative MEG study
Introduction
Alzheimer's disease (AD) and Lewy body dementia (LBD) are, respectively, the first and the second cause of dementia in the elderly population [24]. AD and LBD are due to dementing processes expressing partly different clinical phenotypes and different neuropathological characteristics [13], [18], [40]. The clinical diagnosis of these two types of dementia is actually based on criteria classifying possible and probable types. The NINCDS-ADRDA criteria [25], focused on multiple cognitive impairments and their temporal progression, are used for AD diagnosis; while LBD diagnosis is based on the consensus criteria established in [23] and focused on the presence of hallucinations, parkinsonism and fluctuating cognition.
Studies based on quantitative electroencephalography (QEEG) have been carried out to possibly disclose AD by comparing spectral power results in AD patients and age-matched control subjects during spontaneous activity with closed eyes. These studies showed that: the relative powers in theta and alpha bands might be considered as predictors of dementia [16]; the power ratios between fast and slow EEG activities might be useful to discriminate between different stages of Alzheimer's disease [4]; the spectral profile in theta and in alpha bands revealed the highest statistical significance in differentiating AD patient group from controls [34]. Additionally when compared to age-matched controls, AD patients showed in the resting condition a significantly lower EEG alpha power [38] as well as a significant reduction of the number of alpha sources in all cortical regions [1]. EEG changes focusing on brain activity in closed eyes and open eyes conditions were studied by means of spectral analysis and non-linear dynamical methods [37], [19]. EEG spectral changes from rest to photic stimulation [38] or from rest to mental calculation [41] were also investigated. All these studies showed a reduced cortical reactivity in AD patients with respect to controls.
In addition, EEG spectral coherence was used to examine the effects of dementia on the functional connections between brain areas [6], [20], [17], and to evaluate if the loss of alpha coherence was related to the severity of cognitive impairment in AD patients [8], [21]. However, the majority of QEEG studies deal with patients affected by probable AD, as LBD has only recently been identified as a distinct clinical and neuropathological entity. A greater slowing of the EEG in LBD than in Alzheimer's disease was reported [7], whereas the low EEG frequencies amplitude and the P3 latency were significantly different within patients affected or unaffected by fluctuating cognition [30]. These EEG findings suggested that studies of cortical activity and reactivity in different types of dementia could provide useful information on the progression of these dementing processes. However, a reference electrode is always needed when recording an EEG signal and the choice of the reference location is a crucial matter. Some montages (bipolar or Laplacian) are best suited for close-up viewing of highly localized activity, whereas common electrode reference is better for distance viewing potentials that are widespread over the scalp. Moreover, in EEG studies the relative power density for each frequency band is computed in order to reduce the great intra-subject variability. Indeed, repeated EEG measurements showed greater variability in absolute power density than in relative power density [16]. This limitation can be overcome by magnetoencephalographic recordings (MEG). MEG is a non-invasive method able to investigate neuronal functioning by measuring the associated magnetic field. The amplitude of the magnetic field recorded by the sensor is inversely related to the squared distance between the source and the measurement site; consequently, the recorded signal originates predominantly from cortical generators. Furthermore, MEG signal is a reference-free signal, therefore becoming an ideal tool to compute absolute power of cortical rhythms. Specifically the use of the absolute power, compared to the use of the relative spectral power [16], overcomes the masking of a generalized power decrease spreading all over the frequency bands which may occur during a task performance.
Both MEG and EEG measure the same sources, and both exhibit excellent temporal resolution. However, the revealed magnetic fields are mainly produced by intracellular currents, whereas extracellular volume currents are mostly responsible for the electric potentials. This explains why the MEG spatial pattern is more focal than the corresponding EEG potential distribution. On the other hand, if the head is modelled by a sphere, only the tangential intracellular currents would produce magnetic fields measurable outside the sphere. By contrast, EEG potentials are sensitive to both radial and tangential sources. Finally, the EEG signal recorded from the scalp is distorted by the different conductivity of cranial structures and by the inevitable use of reference channels that might turn out in a wrong interpretation of spectral coherence results.
Despite these advantages, few MEG studies deal with spontaneous cortical activity and cortical reactivity in AD patients [11], [5]. The first study showed that the current dipole density in the delta and theta bands could be useful to assess functional modifications of AD patients’ brain, the second study showed that, compared to healthy controls, AD patients featured a reduced cortical reactivity to eyes opening and task performance, as well as a decrease in coherences values.
The present study aims at further characterizing a population of probable AD and probable LBD together with a group of age-matched normal subjects by investigating by means of MEG measurements their cortical reactivity and spectral coherence of brain activity. To pursue this goal, we compared the power changes of slow and fast cortical rhythms in different brain areas during closed eyes and open eyes conditions as well as during simple mental task and rest conditions. Additionally spectral coherence values were used to investigate whether different degrees of cognitive impairment and different types of dementing processes might differently affect long and short cortical connections.
Section snippets
Subjects
Fifteen patients with probable AD and 7 patients with diagnosis of probable LBD were selected according to NINCDS-ADRDA and LBD consensus criteria. We also analysed 9 control subjects with age, sex, educational and occupational level (actual or past) matching the patients to minimise possible differences in cognitive performances. Demographic, clinical and neuropsychological data on AD and LBD patients and control subjects are reported in Table 1. Each patient underwent Mini Mental State
Neuropsychological data
All 15 AD patients, 7 LBD patients and 9 control subjects completed the neuropsychological tests. Table 1 summarises the demographic and neuropsychological data for each group of subjects. All the neuropsychological tests distinguished controls from patients (Student's t-test revealed p < 0.0001). UPDRS part III motor-subscale, Y/H Scale, CAF and ODFAS test differentiated LBD from AD patients (p < 0.0001). None of the probable AD patients had CAF values greater than 0, while all probable LBD
Discussion and conclusions
In this study MEG recordings were used to evaluate the cortical rhythms reactivity in moderate and severe AD, LBD and healthy age-matched control subjects. Additionally, our study analysed a wide range of frequency bands in different recording conditions: open eyes (OE), closed eyes (CE), and a simple mental task (TASK). Our analysis was based on the computation of the percentage variation of the absolute mean spectral power in selected frequency bands. The absolute spectral power can be
Acknowledgement
This work was partially supported by a grant from the Italian Ministry of Research to the Center of Excellence on Aging of the University of Chieti.
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