Figure S1. The default mode network and its subcomponents across resolutions selected by MSTEPS.

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1 Supplementary material (6 Figures, 2 Tables) Supplementary results Figure S1. The default mode network and its subcomponents across resolutions selected by MSTEPS.

2 Figure S2. Functional parcellations across resolutions (or number of clusters) selected by MSTEPS.

3 Figure S3. Comparisons of effects across samples. This figure illustrates a) functional connectivity changes between MCI and Nl, b) average connectivity in Nl, and c) average connectivity in MCI in each site (ADNI2, CRIUGMa, CRIUGMb, MNI) independently of other sites and when samples are pooled together (all samples), with the ventromedial prefrontal corte as the seed.

4 Figure S4. Comparison of results across different resolutions selected by MSTEPS. a) Maps of percentage of discovery illustrating brain networks that are significantly different between MCI and Nl. b) Maps of maimum absolute effects show the magnitude of the differences between MCI and Nl of every cluster.

5 Figure S5. Comparisons of uncorrected and FDR-corrected effects related to MCI across multiple resolutions selected by MSTEPS in the ventromedial prefrontal corte as the seed.

6 Figure S6. Correspondence of effect maps across resolutions selected by MSTEPS in four selected seeds. Correlation matrices show pairwise comparisons between the eight MSTEPS resolutions of the effect maps for the a) ventromedial prefrontal corte, b) striatum, c) dorsomedial prefrontal corte, and d) middle temporal lobe.

7 Supplementary Table 1. Neuropsychological tests that were used in each study. Test ADNI2 CRIUGMa CRIUGMb MNI Mini-mental state eamination (MMSE) Montreal Cognitive Assessment (MoCA) Clinical Dementia Rating (CDR) ADAS-Cog Everyday Cognition (ECog) Trail Making (Trails A & B) (Trails A & B) (Trails A & B) (DKEFS) Boston Naming Test Digit span Colour-word interference (DKEFS) Rey Auditory Verbal Learning Test Verbal fluency (MEC) (DKEFS) Clock drawing Visual Object and Space Perception Battery Briton Spatial Anticipation Test Hooper Visual Organization Test Rey Comple Figure Aggie Figures Learning Test 16-item Free and Cued Recall (RL/RI-16) Pyramid and Palm Trees Test Weschler Memory Scale - logical memory subtest MEC - Montréal évaluation de la communication DKEFS - Delis-Kaplan Eecutive Function System

8 Supplementary Table 2. Rank of parcels based on their associated percentage of non-redundant connections that differ between MCI and Nl Rank Parcel Additional percentage of connections Cumulative percentage of connections 1 Ventromedial prefrontal corte Striatum Dorsomedial prefrontal corte Middle temporal lobe Medial frontal gyrus Hippocampus Precuneus Temporal pole Fusiform/parahippocampal gyrus Thalamus Postcentral gyrus

9 Supplementary Methods Inclusion/eclusion criteria by each individual study ADNI2 Subjects must have been either English or Spanish-speaking and between (inclusive) years of age. All subjects had a partner able to provide an independent evaluation of functioning. Criteria for Nl subjects were as follows: MMSE scores between (inclusive), a CDR of 0, non-depressed, non- MCI, and non-demented. Criteria for MCI were as follows: MMSE scores between (inclusive), a memory complaint, have objective memory loss measured by education adjusted scores on Wechsler Memory Scale Logical Memory II, a CDR of 0.5, absence of significant levels of impairment in other cognitive domains, essentially preserved activities of daily living, and an absence of dementia. CRIUGMa All subjects must have been 50 years of age or older, French-speaking or bilingual, and lived in Quebec for most of their lives. Eclusion criteria included history of psychiatric or neurological disorders, history of substance abuse, and having undergone anesthesia within the last si months of participating in the study. MCI must have subjective memory complaints, an objective memory deficit (measured as a score at least 1.5 standard deviations below the mean considering age and education), and intact functional abilities. MCI must not have met criteria for dementia. Nl subjects must not have met criteria for MCI or dementia. CRIUGMb All subjects must have been between 65 and 80 years old, had normal audition and vision at the time of study, and at least 8 years of education. Eclusion criteria included family history of early-onset AD, use of psychoactive substances within last 3 months, intellectual disabilities, signs of depression. MCI must have had memory complaints, an MMSE score equal to or greater than 24, a CDR of 0.5, and cognitive deficits equal to or higher than 1.5 standard deviations on neuropsychological tests. Nl subjects must not have met criteria for MCI or dementia. MNI Nl subjects were selected on basis of their neurological and clinical status. Initial identification of patients was based on memory complaints substantiated by an informant. A subsequent interview was conducted with a full neurological eamination including the standard Mini Mental State Eamination (MMSE). Routine blood screening was done to rule out underlying metabolic disorder. MCI diagnosis was according to the Petersen criteria which included: (i) memory complaint usually corroborated by an informant; (ii) objective memory impairment for age; (iii) essentially preserved general cognitive function; (iv) largely intact functional activities; (v) not demented. Eclusion criteria included co-morbidity with other neurological disease such as stroke, Parkinson s disease, other neurodegenerative diseases, etc; the presence of any major structural abnormalities or signs of major vascular pathology on the MRI evaluation; ais I psychiatric disorder or intellectual disability; use of psychoactive substance; previous or present use of cholinesterase inhibitor.

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