Functional integrity of thalamocortical circuits differentiates normal aging from mild cognitive impairment

Abstract

Resonance in thalamocortical networks is critically involved in sculpting oscillatory behavior in large ensembles of neocortical cells. Neocortical oscillations provide critical information about the integrity of thalamocortical circuits and functional connectivity of cortical networks, which seem to be significantly disrupted by the neuronal death and synapse loss characterizing Alzheimer's disease (AD). By applying a novel analysis methodology to overcome volume conduction effects between scalp electroencephalographic (EEG) measurements, we were able to estimate the temporal activation of EEG‐alpha sources in the thalamus and parieto‐occipital regions of the cortex. We found that synaptic flow underlying the lower alpha band (7.5–10 Hz) was abnormally facilitated in patients with mild cognitive impairment (MCI) as compared to healthy elderly individuals, particularly from thalamus to cortex (∼38% higher). In addition, the thalamic generator of lower alpha oscillations was also abnormally activated in patients with MCI. Regarding the upper alpha subdivision (10.1–12.5 Hz), both controls and patients with MCI showed a bidirectional decrease of thalamocortical synaptic transmission, which was age‐dependent only in the control group. Altogether, our results suggest that functional dynamics of thalamocortical networks differentiate individuals at high risk of developing AD from healthy elderly subjects, supporting the hypothesis that neurodegeneration mechanisms are active years before the patient is clinically diagnosed with dementia. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.

Extensive White Matter Dysfunction in Cognitively Impaired Patients with Secondary-Progressive Multiple Sclerosis

“…30 Thalamocortical circuit integrity has additionally been found to differentiate normal aging from mild cognitive impairment. 31 This suggests that thalamic radiations are implicated in a wide range of cognitive tasks. Furthermore, significantly reduced FA was recently reported in the inferior longitudinal fasciculus, a component of the sagittal stratum, of patients with mild cognitive impairment.…”

Cerebral and blood correlates of reduced functional connectivity in mild cognitive impairment

“…Therefore, bilateral GM loss of thalamus characterizing our aMCI sample might account for impaired alpha connectivity between anterior and posterior regions of the brain, likely due to synaptic dysfunction or synaptic loss of thalamocortical neurons. This hypothesis is supported by studies showing amyloid deposits and neurofibrillary tangles in the thalamus of AD patients (Rudelli et al 1984;Masliah et al 1989;Braak and Braak 1991) together with significant GM loss (Karas et al 2004) that further correlated with impaired cognitive functioning (de Jong et al 2008), and by studies showing altered patterns of functional connectivity between thalamus and precuneus in aMCI subjects (Cantero et al 2009a;Wang et al 2012;Zhou et al 2013).…”

“…Consequently, and given that oscillatory EEG activity results from summated excitatory and inhibitory postsynaptic potentials primarily generated by synaptic activity of large pyramidal neurons in the cerebral cortex (Lopes da Silva and Van Rotterdam 1993), synaptic dysfunction occurring in aMCI subjects may be reflected in abnormal patterns of EEG coupling. Accordingly, restingstate EEG alpha rhythms not only are significantly different in aMCI when compared with HO subjects (Babiloni et al 2006a;Cantero et al 2009a), but they are also able to predict progressive cognitive deterioration (Babiloni et al 2014) and stability of MCI status over time (Babiloni et al 2011). However, up to now only a few studies have established a link between abnormalities of EEG rhythms and cortical atrophy in aMCI subjects (Babiloni et al 2006b(Babiloni et al , 2013.…”

“…The precuneus is a region of the superior parietal lobe also involved in EEG-alpha generation (Toth et al 2007;Michels et al 2008;Cantero et al 2009a). An emerging Fig.…”

Estudo da análise da razão alfa/teta em pacientes com doença de Alzheimer provável

“…Nós sabemos que o tálamo conjuntamente com o cuneos e pré-cuneos são os principais geradores da atividade alfa do paciente em repouso (Cantero et al, 2009). …”