Background
Methods
Animals
LFP
Electrode arrays and surgery
LFP recording
Preprocessing
Channel selection
Behavioral states
Human participants
MEG
Recording
Preprocessing
LFP and MEG analysis
Time–frequency analysis
Peak frequency
Weighted phase lag index
Amplitude envelope correlation
Statistics
Results
Subjects
Mice
Human participants
Mutation carriers | Healthy controls | P value | |
---|---|---|---|
N | 11 | 33 | - |
Age (years) | 49 [20–61] | 49 [20–62] | 0.957 |
Female/male (n) | 8/3 | 24/9 | > 0.999 |
PSEN1/APP (n) | 9/2 | - | - |
Education (Verhage) | 6 [5–7] | 6 [1–7] | 0.742 |
Global cognition (MMSE) | 29 [27–30] (n = 11) | 27 [27–30] (n = 7) | 0.375 |
Estimated years before symptom onset | 1 [− 16–22] | - | - |
Absolute power
APP/PS1 mice show an age-dependent increase in absolute power
Human APP and PSEN1 mutation carriers have similar absolute power as age-matched controls
Relative power
Relative power shifts from low to high frequencies in APP/PS1 mice
Hippocampal relative theta power is increased in human APP and PSEN1 mutation carriers
Peak frequency
Theta peak frequency is largely unaltered in APP/PS1 mice
Alpha peak frequency is reduced in human APP and PSEN1 mutation carriers
Functional connectivity
APP/PS1 mice show an age-dependent decrease in phase- but not amplitude-based theta/alpha connectivity
Human APP/PSEN1 mutation carriers show increased phase-based gamma connectivity and decreased amplitude-based beta connectivity
Discussion
LFP/MEG parameter | APP/PS1 mice | Mutation carriers | Symptomatic ADa |
---|---|---|---|
Total power | |||
(Pre)frontal cortex | Unchanged | Unchanged | Unknown |
Parietal cortex | Increased (3–6 moa) | Unchanged | Unknown |
Hippocampus | Increased (3–6 moa) | Unchanged | Increased |
Absolute power | |||
(Pre)frontal cortex | Unchanged | Unchanged | Increased δ, θ |
Parietal cortex | Increased θ, α, β, γ1, γ2 (3–6 moa) | Unchanged | Increased δ, θ, in-/decreased α, decreased β |
Hippocampus | Increased δ, θ, α, β, γ1, γ2 (3–6 moa) | unchanged | Increased θ, in-/decreased α, decreased β |
Relative power | |||
(Pre)frontal cortex | Decreased θ, increased β, γ1 (3–12 moa) | Unchanged | Increased θ, increased α, decreased β |
Parietal cortex | Decreased θ, increased β, γ1 (3–12 moa) | Unchanged | Increased δ, θ, in-/decreased α, decreased β |
Hippocampus | Increased β (3–12 moa) | Increased θ | Increased θ, decreased α, β |
Peak frequency | |||
Parietal cortex | Unchanged | Decreased α peak frequency | Decreased α peak frequency |
Hippocampus | Unchanged | Decreased α peak frequency | Decreased α peak frequency |
Phase-based connectivity | |||
(Pre)frontal-parietal | Decreased θ, α wPLI (6–12 moa) | Unchanged | Unchanged (suggested increased θ, in-/decreased α) |
(Pre)frontal-hippocampal | Decreased θ, α wPLI (6–12 moa) | Increased γ wPLI | Unchanged (suggested increased θ) |
Amplitude-based connectivity | |||
(Pre)frontal-parietal | Unchanged | Decreased β AECc | Decreased α, β |
(Pre)frontal-hippocampal | Increased β AECc (9–12 moa) | Decreased β AECc | Decreased α, β |