Altered visual entrainment in patients with Alzheimer’s disease: magnetoencephalography evidence

Abstract

Recent research has indicated that rhythmic visual entrainment may be useful in clearing pathological protein deposits in the central nervous system of mouse models of Alzheimer’s disease. However, visual entrainment studies in human patients with Alzheimer’s disease are rare, and as such the degree to which these patients exhibit aberrations in the neural tracking of rhythmic visual stimuli is unknown. To fill this gap, we recorded magnetoencephalography during a 15 Hz visual entrainment paradigm in amyloid-positive patients on the Alzheimer’s disease spectrum and compared their neural responses to a demographically-matched group of biomarker-negative healthy controls. Magnetoencephalography data were imaged using a beamformer and virtual sensor data were extracted from the peak visual entrainment responses. Our results indicated that, relative to healthy controls, participants on the Alzheimer’s disease spectrum exhibited significantly stronger 15 Hz entrainment in primary visual cortices relative to a pre-stimulus baseline period. However, the two groups exhibited comparable absolute levels of neural entrainment, and higher absolute levels of entertainment predicted greater Mini-mental Status Examination scores, such that those patients whose absolute entrainment amplitude was closer to the level seen in controls had better cognitive function. In addition, 15 Hz periodic activity, but not aperiodic activity, during the pre-stimulus baseline period was significantly decreased in patients on the Alzheimer’s disease spectrum. This pattern of results indicates that patients on the Alzheimer’s disease spectrum exhibited increased visual entrainment to rhythmic stimuli, and that this increase is likely compensatory in nature. More broadly, these results show that visual entrainment is altered in patients with Alzheimer’s disease and should be further examined in future studies, as changes in the capacity to entrain visual stimuli may prove useful as a marker of Alzheimer’s disease progression.

Slope of the power spectral density flattens at low frequencies (<150 Hz) with healthy aging but also steepens at higher frequency (>200 Hz) in human electroencephalogram

“…However, there was no significant change in slopes between controls and cases in either LFR or HFR in either eyes open and eyes closed conditions (eyes closed: Fig. 5B-D), consistent with previous studies which also did not find any changes in PSD slope with MCI/AD (Benwell et al, 2020; Springer et al, 2022).…”

“…It could be due to a small sample size, although we found significant differences in power at both low-frequencies (Figure 5) and in the gamma band (Murty et al, 2021) with the same sample size. Further, this null result is consistent with previously documented MEG observations (Benwell et al, 2020; Springer et al, 2022). This suggests that the relationship between PSD slope and E/I balance could be complicated and dependent on other factors, as discussed above.…”

“…Change in aperiodic activity is suggested to be a plausible biomarker for some neurological and psychiatric diseases like schizophrenia (Molina et al, 2020), attention deficit hyperactivity disorder (ADHD; (Robertson et al, 2019;Ostlund et al, 2021)) and Fragile X Syndrome (Wilkinson and Nelson, 2021), although the aperiodic activity was unchanged in other diseases such as Alzheimer's Disease (AD) (Benwell et al, 2020;Springer et al, 2022).…”

“…Change in aperiodic activity is suggested to be a plausible biomarker for some neurological and psychiatric diseases like schizophrenia (Molina et al, 2020), attention deficit hyperactivity disorder (ADHD; (Robertson et al, 2019; Ostlund et al, 2021)) and Fragile X Syndrome (Wilkinson and Nelson, 2021), although the aperiodic activity was unchanged in other diseases such as Alzheimer’s Disease (AD) (Benwell et al, 2020; Springer et al, 2022). Recently, reduction in the slope with increasing age has been observed across several studies under different task paradigms (Voytek et al, 2015; Dave et al, 2018; Tran et al, 2020) or even in resting state conditions (Thuwal et al, 2021; Hill et al, 2022; Merkin et al, 2023).…”

“…However, the slope is unchanged in subjects with early Alzheimer's Disease (AD) and their controls. Our results shed new light on the properties of neural noise and the neurophysiological processes affecting AD and the aperiodic activity.Change in aperiodic activity is suggested to be a plausible biomarker for some neurological and psychiatric diseases like schizophrenia (Molina et al, 2020), attention deficit hyperactivity disorder (ADHD; (Robertson et al, 2019;Ostlund et al, 2021)) and Fragile X Syndrome (Wilkinson and Nelson, 2021), although the aperiodic activity was unchanged in other diseases such as Alzheimer's Disease (AD) (Benwell et al, 2020;Springer et al, 2022).Recently, reduction in the slope with increasing age has been observed across several studies under different task paradigms (…”