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 (approximately 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.

Increased synchronization and decreased neural complexity underlie thalamocortical oscillatory dynamics in mild cognitive impairment.

Abnormal patterns of electroencephalographic (EEG) alpha oscillations in preclinical stages of dementia reveal a selective vulnerability of thalamocortical circuits to the cascade of neurodegenerative events heralding Alzheimer's disease (AD). EEG-alpha slowing characterizes both mild cognitive impairment (MCI) and healthy aging, but it remains ambiguous whether different neural mechanisms underlie this oscillatory behavior in normal and pathological senescence. In this study, we show that the strength of phase coupling and the level of phase predictability between thalamocortical and cortico-cortical EEG sources of low alpha frequency are abnormally facilitated in MCI patients when compared to healthy elderly subjects. Additionally, we found a loss of neural complexity intrinsic to both thalamic and cortical generators of lower alpha in MCI patients, which likely influenced the aberrant phase synchronization behavior between EEG-alpha sources in this high risk group of AD. Taken together, these results suggest that different neural mechanisms account for the well known slowing of alpha rhythm present in normal aging and MCI patients. Whether these anomalous neural coding mechanisms of lower alpha generation in MCI patients represent a potential electrophysiological marker of mild AD is a topic for future research.