No abstract

Alzheimer's Disease (AD) in elderly adds substantially to socio-economic burden necessitating early diagnosis. While recent studies in rodent models of AD have suggested diagnostic and therapeutic value for gamma rhythms in brain, the same has not been rigorously tested in humans. In this case-control study, we recruited a large population (N=244; 106 females) of elderly (>49 years) subjects from the community, who viewed large gratings that induced strong gamma oscillations in their electroencephalogram (EEG). These subjects were classified as healthy (N=227), mild-cognitively-impaired (MCI; N=12) or AD (N=5) based on clinical history and Clinical Dementia Rating scores. Surprisingly, stimulus-induced gamma rhythms, but not alpha or steady-state visually evoked responses, were significantly lower in MCI/AD subjects compared to their age and gender matched controls. This reduction was not due to differences in eye-movements or baseline power. Our results suggest that gamma could be used as potential screening tool for MCI/AD in humans.

Visual stimulus-induced gamma oscillations in electroencephalogram (EEG) recordings have been recently shown to be compromised in subjects with preclinical Alzheimer’s Disease (AD), suggesting that gamma could be an inexpensive biomarker for AD diagnosis provided its characteristics remain consistent across multiple recordings. Previous magnetoencephalography studies in young subjects have reported consistent gamma power over recordings separated by a few weeks to months. Here, we assessed the consistency of stimulus-induced slow (20–35 Hz) and fast gamma (36–66 Hz) oscillations in subjects (n = 40) (age: 50–88 years) in EEG recordings separated by a year, and tested the consistency in the magnitude of gamma power, its temporal evolution and spectral profile. Gamma had distinct spectral/temporal characteristics across subjects, which remained consistent across recordings (average intraclass correlation of ~ 0.7). Alpha (8–12 Hz) and steady-state-visually-evoked-potentials (SSVEPs) were also reliable. We further tested how EEG features can be used to identify two recordings as belonging to the same versus different subjects and found high classifier performance (AUC of ~ 0.89), with temporal evolution of slow gamma and spectral profile being most informative. These results suggest that EEG gamma oscillations are reliable across sessions separated over long durations and can also be a potential tool for subject identification.

Functional connectivity (FC) indicates the interdependencies between brain signals recorded from spatially distinct locations in different frequency bands, which is modulated by cognitive tasks and is known to change with aging and cognitive disorders. Recently, the power of narrow-band gamma oscillations induced by visual gratings has been shown to reduce with both healthy aging and in subjects with mild cognitive impairment (MCI). However, the impact of aging/MCI on stimulus-induced gamma FC has not been well studied. We recorded electroencephalogram (EEG) from a large cohort (N=229) of elderly subjects (>49 years) while they viewed large cartesian gratings to induce gamma oscillations and studied changes in alpha and gamma FC with healthy aging (N=218) and MCI (N=11). Surprisingly, we found that aging and disease changed power and FC in different ways. With healthy aging, alpha power did not change but FC decreased significantly. MCI reduced gamma but not alpha FC significantly compared with age and gender matched controls, even when power was matched between the two groups. Overall, our results show distinct effects of aging and disease on EEG power and FC, suggesting different mechanisms and the potential to use EEG stimulus-induced FC along with power for early diagnosis of Alzheimer's Disease.

Functional connectivity (FC) indicates the interdependencies between brain signals recorded from spatially distinct locations in different frequency bands, which is modulated by cognitive tasks and is known to change with ageing and cognitive disorders. Recently, the power of narrow‐band gamma oscillations induced by visual gratings have been shown to reduce with both healthy ageing and in subjects with mild cognitive impairment (MCI). However, the impact of ageing/MCI on stimulus‐induced gamma FC has not been well studied. We recorded electroencephalogram (EEG) from a large cohort (N = 229) of elderly subjects (>49 years) while they viewed large cartesian gratings to induce gamma oscillations and studied changes in alpha and gamma FC with healthy ageing (N = 218) and MCI (N = 11). Surprisingly, we found distinct differences across age and MCI groups in power and FC. With healthy ageing, alpha power did not change but FC decreased significantly. MCI reduced gamma but not alpha FC significantly compared with age and gender matched controls, even when power was matched between the two groups. Overall, our results suggest distinct effects of ageing and disease on EEG power and FC, suggesting different mechanisms underlying ageing and cognitive disorders.