Functional Integrity of Thalamocortical Circuits Differentiates Normal Aging from Mild Cognitive Impairment

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 (similar to 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 30:3944-3957, 2009. (C) 2009 Wiley-Liss, Inc.