LAUSR

Cognitive impairment indicates disturbed brain physiology which can be due to various mechanisms including Alzheimer's pathology. Combined functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings (EEG-fMRI) can assess the interplay between complementary measures of brain activity and EEG changes to be localized to specific brain regions. We used a two-step approach, where we first examined changes related to a syndrome of mild cognitive impairment irrespective of pathology and then studied the specific impact of amyloid pathology. After detailed clinical and neuropsychological characterization as well as a positron emission tomography (PET) scans with the tracer 11-[C]-Pittsburgh Compound B to estimate cerebral amyloid deposition, 14 subjects with mild cognitive impairment (MCI) (mean age 75.6 SD: 8.9) according to standard criteria and 21 cognitively healthy controls (HCS) (mean age 71.8 SD: 4.2) were assessed with EEG-fMRI. Thalamo-cortical alpha-fMRI signal coupling was only observed in HCS. Additional EEG-fMRI signal coupling differences between HCS and MCI were observed in parts of the default mode network, salience network, fronto-parietal network, and thalamus. Individuals with significant cerebral amyloid deposition (amyloid-positive MCI and HCS combined compared to amyloid-negative HCS) displayed abnormal EEG-fMRI signal coupling in visual, fronto-parietal regions but also in the parahippocampus, brain stem, and cerebellum. This finding was paralleled by stronger absolute fMRI signal in the parahippocampus and weaker absolute fMRI signal in the inferior frontal gyrus in amyloid-positive subjects. We conclude that the thalamocortical coupling in the alpha band in HCS more closely reflects previous findings observed in younger adults, while in MCI there is a clearly aberrant coupling in several networks dominated by an anticorrelation in the posterior cingulate cortex. While these findings may broadly indicate physiological changes in MCI, amyloid pathology was specifically associated with abnormal fMRI signal responses and disrupted coupling between brain oscillations and fMRI signal responses, which especially involve core regions of memory: the hippocampus, para-hippocampus, and lateral prefrontal cortex.