Elsevier

NeuroImage

Volume 60, Issue 1, March 2012, Pages 489-496
NeuroImage

EEG markers are associated to gray matter changes in thalamus and basal ganglia in subjects with mild cognitive impairment

https://doi.org/10.1016/j.neuroimage.2011.11.086Get rights and content

Abstract

Background

Gray matter (GM) changes of thalamus and basal ganglia have been demonstrated to be involved in Alzheimer's disease (AD). Moreover, the increase of two EEG markers, alpha3/alpha2 and theta/gamma ratio, have been associated with, respectively, AD converter and non-AD converter subjects with mild cognitive impairment (MCI).

Objective

To study the association of prognostic EEG markers with specific GM changes of thalamus and basal ganglia in subjects with MCI to identify different MCI populations.

Methods

74 adult subjects with mild cognitive impairment underwent EEG recording and high resolution 3D magnetic resonance imaging (MRI). The theta/gamma and alpha3/alpha2 ratio was computed for each subject. Three groups were obtained according to increasing tertile values of both alpha3/alpha2 and theta/gamma ratio. Gray matter density differences between groups were investigated using a voxel-based morphometry technique.

Results

Subjects with higher a3/a2 ratios when compared to subjects with lower and middle a3/a2 ratios showed minor atrophy in the ventral stream of basal ganglia (head of caudate nuclei and accumbens nuclei bilaterally) and of the pulvinar nuclei in the thalamus; subjects with higher t/g ratio showed minor atrophy in putamina nuclei bilaterally than subjects with middle ratio.

Conclusion

The integrated analysis of EEG and morpho-structural markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.

Highlights

► Association of EEG alpha3/alpha2 and theta/gamma ratio with changes in thalamus and basal ganglia in subjects with MCI. ► EEG markers-driven analysis. ► Increase of alpha3/alpha2 ratio ssociated with minor atrophy of caudate, accumbens and pulvinar nuclei. ► Increase of theta/gamma ratio associated with minor atrophy of putamina bilaterally.

Introduction

EEG has been demonstrated a reliable diagnostic tool in dementia research (Babiloni et al., 2006, Dauwels et al., 2010a, Dauwels et al., 2010b, Lizio et al., 2011, Rossini et al., 2008, Stam et al., 2003). The increase of high alpha relative to low alpha power has been recently demonstrated a reliable EEG marker of hippocampal atrophy as well as conversion of patients with mild cognitive impairment (MCI) in Alzheimer's disease (AD; Moretti et al., 2009c). Moreover, the increase of the theta/gamma ratio has been found associated to the atrophy of amygdala complex as well as to the conversion of MCI patient in non-AD dementias (Moretti et al., 2009a, Moretti et al., 2009b).

fMRI and PET-based studies, approaching the large scale neural connectivity issue, showed that impaired visual working memory correlated with brain activity within the posterior parietal association cortex, prefrontal cortex, as well as thalamus nuclei in AD (Bokde et al., 2009, Collette et al., 1997, Desgranges et al., 1998). A study using an associate memory task with healthy controls, mildly cognitive impaired subjects (MCI) and AD patients (Celone et al., 2006), found a pattern of activation in the hippocampus-related network in healthy controls, of hyperactivation in more mildly impaired MCI subjects, of hypoactivation in more severe MCI subjects and no activation in AD patients. The non-linear changes in activation in the network across the various groups provided further evidence of a previous study suggesting this non-linear dynamic in the hippocampus (Dickerson et al., 2005, Moretti et al., 2007a). Other studies of interest found that the activation during a task was not altered between the MCI subjects and the healthy controls (Bokde et al., 2008), suggesting that connectivity within a network is first altered due to the putative AD neuropathology and then changes in activation occur in the brain. It may be that before recruitment of compensatory regions for a cognitive task, functional connectivity would be the first step leading to increased activation in a region that would activate as a compensatory mechanism.

The large neural network altered in AD encompasses also thalamic structure (Frisoni et al., 2006, Frisoni et al., 2007, Frisoni et al., 2008, Frisoni et al., 2009, van Strien et al., 2009). In particular, atrophy of the thalamus and basal ganglia has been demonstrated to be involved in AD and in the symptomatic development (Canu et al., 2010, Cherubini et al., 2010). Alzheimer's disease (AD) is associated with neuronal loss not only in the hippocampus and amygdala but also in the thalamus and basal ganglia. Anterodorsal, centromedial, and pulvinar nuclei are the main sites of degeneration in AD (Zarei et al., 2010). Moreover, volumes of putamen and thalamus were found significantly reduced in patients diagnosed with probable Alzheimer's disease and the decrease in volume correlated linearly with impaired global cognitive performance (de Jong et al., 2008) . These findings strongly suggest that, beside neo-cortical atrophy, deep gray matter structures in Alzheimer's disease suffer structural changes and that degenerative processes in the basal ganglia and thalamus may contribute to cognitive decline in Alzheimer's disease.

The relationship between the sources of different EEG rhythms and thalamus–basal ganglia structure has been widely studied and accepted. For instance, findings in human and animal studies suggest that coordinated simultaneous theta activity is observed in two networks linked, respectively to striatal nucleus (Llinas et al., 1999) and to the frontal-anterior thalamic system (Gevins and Smith, 2000, Kirk and Mackay, 2003, Schmiedt et al., 2005). The alpha rhythm generation is quite more complex. The alpha dominant rhythm arises from the continuous interplay between posterior thalamus, posterior cingulated and parieto-occipital cortical areas (Cantero et al., 2009, Steriade, 2006). As a consequence, the alpha rhythm is more linked to the thalamus so the a3/a2 ratio is expected to be more associated with the thalamic or thalamus-related structure modifications. On the contrary the theta/gamma ratio is more associated with fronto-basal ganglia networks and it could more associated with modifications in these structures. Accordingly, different EEG oscillations based on different anatomical networks have been suggested to have different functions. Specifically, synchrony of theta oscillations, impinging on fronto-striatal circuits plays a crucial role in top-down modulated higher order visual processing. On the other hand, changes in alpha and gamma oscillatory activity, impinging on thalamo-cortical posterior networks, have been shown to play a relevant functional role during perceptual, executive and mnemonic processes (Klimesch, 1997; Gevins et al., 2000). As a consequence, modifications in theta/gamma and alpha3/alpha2 ratio would like to reflect anatomopathological changes in those deep brain structures.

In the present study the association of EEG indexes with gray matter (GM) changes in thalamus and basal ganglia has been studied in subjects with MCI. The working hypothesis was that modifications of both EEG markers could be underpinned by different deep brain structures, unveiling the possibility to identify different MCI populations. Results show that subjects with higher a3/a2 ratios when compared to subjects with lower and middle a3/a2 ratios showed minor atrophy in the ventral stream of basal ganglia (head of caudate nuclei and accumbens nuclei bilaterally) and of the pulvinar nuclei in the thalamus; subjects with higher t/g ratio showed minor atrophy in putamina nuclei bilaterally than subjects with middle ratio.

Section snippets

Subjects

For the present study, 74 subjects with MCI were recruited from the memory Clinic of the Scientific Institute for Research and Care (IRCCS) of Alzheimer's and psychiatric diseases ‘Fatebenefratelli’ in Brescia. The data of the same subjects were used in previously published works of our group (Moretti et al., 2009c).

Diagnostic criteria

Patients were taken from a prospective project on the natural history of MCI. The project was aimed to study the natural history of non-demented persons with apparently primary

Low-a3/a2 group

Subjects with low a3/a2 ratio exhibited a region of GM more atrophic than subjects with high a3/a2 ratios located in the head of caudate, specifically in the ventral part and accumbens nuclei bilaterally, slightly wider on the left side (see Fig. 1).

No regions of GM tissue loss were found when patients with low a3/a2 ratio were compared to those with middle a3/a2 ratio.

Middle a3/a2 group

Subjects with middle a3/a2 ratio, contrasted to individuals with high a3/a2 ratios, showed the same cerebral atrophic areas

Preliminary remarks

In this study we have considered the GM changes of deep brain structures, basal ganglia and thalamus, based on brain electrical activity markers. As a consequence, the analysis of anatomical structural changes in MCI patients was EEG marker-driven. This is a crucial point for considering the results of the present study. Indeed, it is not a simple detection of atrophy pattern between two clinically different populations of subjects, but it would investigate the association of EEG markers with

Conclusion

The integrated analysis of EEG and morpho-structural markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.

Conflict of interest statement

Moretti D V: I state that I have no actual or potential conflicts of interest.

Paternicò D: I state that I have no actual or potential conflicts of interest.

Binetti G: I state that I have no actual or potential conflicts of interest.

Zanetti O: I state that I have no actual or potential conflicts of interest.

Frisoni G B: I state that I have no actual or potential conflicts of interest.

Acknowledgments

The work is funded by Fatebenefratelli Association for Research.

References (67)

  • W. Klimesch

    EEG-alpha rhythms and memory processes

    Int. J. Psychophysiol.

    (1997)
  • W. Klimesch

    EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis

    Brain Res. Rev.

    (1999)
  • W. Klimesch et al.

    EEG alpha oscillations: the inhibition timing hypothesis

    Brain Res. Rev.

    (2007)
  • B.H. Kopell et al.

    Anatomy and physiology of the basal ganglia: implications for DBS in psychiatry

    Neurosci. Biobehav. Rev.

    (2008)
  • J.M. Logan et al.

    Underrecruitment and non-selective recruitment: dissociable neural mechanisms associated with aging

    Neuron

    (2002)
  • D.V. Moretti et al.

    Computerized processing of EEG-EOG-EMG artifacts for multi-centric studies in EEG oscillations and event-related potentials

    Int. J. Psychophysiol.

    (2003)
  • D.V. Moretti et al.

    Individual analysis of EEG frequency and band power in mild Alzheimer's disease

    Clin. Neurophysiol.

    (2004)
  • D.V. Moretti et al.

    Vascular damage and EEG markers in subjects with mild cognitive impairment

    Clin. Neurophysiol.

    (2007)
  • D.V. Moretti et al.

    Hippocampal atrophy and EEG markers in subjects with mild cognitive impairment

    Clin. Neurophysiol.

    (2007)
  • D.V. Moretti et al.

    Increase of theta/gamma ratio is associated with memory impairment

    Clin. Neurophysiol.

    (2009)
  • D.V. Moretti et al.

    Increase of theta/gamma and alpha3/alpha2 ratio is associated with amygdalo-hippocampal complex atrophy

    J. Alzheimer Dis.

    (2009)
  • P.M. Rossini et al.

    Is it possible to automatically distinguish resting EEG data of normal elderly vs. mild cognitive impairment subjects with high degree of accuracy?

    Clin. Neurophysiol.

    (2008)
  • C. Schmiedt et al.

    Event-related theta oscillations during working memory tasks in patients with schizophrenia and healthy controls

    Brain Res. Cogn. Brain Res.

    (2005)
  • G. Spalletta et al.

    Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease

    Am. J. Geriatr. Psychiatry

    (2010)
  • M. Steriade

    Grouping of brain rhythms in corticothalamic systems

    Neuroscience

    (2006)
  • M. Zarei et al.

    Combining shape and connectivity analysis: an MRI study of thalamic degeneration in Alzheimer's disease

    Neuroimage

    (2010)
  • K. Basar et al.

    Nucleus accumbens and impulsivity

    Prog. Neurobiol.

    (2010)
  • R.A. Berman et al.

    Functional identification of a pulvinar path from superior colliculus to cortical area MT

    J. Neurosci.

    (2010)
  • R. Cabeza et al.

    Task-independent and task specific age effects on brain activity during working memory, visual attention and episodic retrieval

    Cereb Cortex

    (2004)
  • E. Canu et al.

    Microstructural diffusion changes are independent of macrostructural volume loss in moderate to severe Alzheimer's disease

    J. Alzheimers Dis.

    (2010)
  • K.A. Celone et al.

    Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis

    J. Neurosci.

    (2006)
  • A. Cherubini et al.

    Combined volumetry and DTI in subcortical structures of mild cognitive impairment and Alzheimer's disease patients

    J. Alzheimers Dis.

    (2010)
  • F. Collette et al.

    Functional anatomy of verbal and visuo-spatial span tasks in Alzheimer's disease

    Hum. Brain Mapp.

    (1997)
  • Cited by (44)

    • BOLD and EEG signal variability at rest differently relate to aging in the human brain

      2020, NeuroImage
      Citation Excerpt :

      Therefore, greater SDBETA in sensorimotor brain regions could be interpreted as a compensatory mechanism to account for a decline of motor performance during aging (Quandt et al., 2016). It should be noted that the present findings of age-related alterations of brain signal variability at different frequencies might be influenced by several anatomical factors which might influence EEG-generators such as reduced cortical grey matter (Babiloni et al., 2013; Moretti et al., 2012), white-matter (Nunez et al., 2015; Valdés-Hernández et al., 2010), and increased amount of cerebrospinal fluid (CSF; Hartikainen et al., 1992; Stomrud et al., 2010), but also alterations of cerebral glucose metabolism (Dierks et al., 2000). Localized or global disturbances of brain anatomy and function might lead to deviations in the EEG sources, resulting in EEG amplitude changes.

    • Alignment of alpha-band desynchronization with syntactic structure predicts successful sentence comprehension

      2018, NeuroImage
      Citation Excerpt :

      Electrophysiological data were analyzed using the Fieldtrip toolbox (Oostenveld et al., 2011). For time–frequency decomposition, we used individually adjusted frequency bands based on each participant's individual alpha frequency (IAF; Grandy et al., 2013; Klimesch, 1999; Klimesch et al., 1996a; Moretti et al., 2012; Smit et al., 2006). To this end, we first segmented the EC and EO resting-state EEG into 150 continuous 2-s epochs each.

    • The electrophysiology of neuroHIV: A systematic review of EEG and MEG studies in people with HIV infection since the advent of highly-active antiretroviral therapy

      2017, Clinical Neurophysiology
      Citation Excerpt :

      A recent study reported that, considered together, participants with either mild cognitive impairment or Alzheimer’s disease had lower cortical gray matter volumes that correlated with the amount of decreased alpha and increased delta sources (Babiloni et al., 2013). Mild cognitive impairment-related changes in sub-cortical grey matter volumes have also been associated with EEG indices (such as alpha 3/alpha 2 and theta/gamma ratios) (Moretti et al., 2012). Both cortical and subcortical volumes have been shown to be reduced in HIV+ compared to HIV− groups, even in the HAART era (Sanford et al., 2017).

    • Involvement of mirror neuron system in prodromal Alzheimer's disease

      2016, BBA Clinical
      Citation Excerpt :

      The three groups of MCI has been demonstrated in previous studies to be different in nature. In particular, the higher alpha3/alpha 2 EEG frequency power ratio MCI group is at major risk to convert to Alzheimer's disease, as well as to have different patterns of hippocampal atrophy as compared to the other alpha3/alpha2 frequency power ratio MCI groups [23,32]. Although these previous results have been obtained at a group level, given the extensive initial assessment and the prolonged follow-up, we are quite confident that the MCI patients individuated with higher alpha3/alpha 2 EEG frequency power ratio belong to prodoromal AD group.

    View all citing articles on Scopus
    1

    On the behalf of all coauthors I declare that appropriate approval and procedures were used concerning human subjects.

    View full text