Spontaneous oscillatory markers of cognitive status in two forms of dementia

Abstract

Abnormal oscillatory brain activity in dementia may indicate incipient neuronal/synaptic dysfunction, rather than frank structural atrophy. Leveraging a potential link between the degree of abnormal oscillatory activity and cognitive symptom severity, one could localize brain regions in a diseased but pre-atrophic state, which may be more amenable to interventions. In the current study, we evaluated the relationships among cognitive deficits, regional volumetric changes, and resting-state magnetoencephalography abnormalities in patients with mild cognitive impairment (MCI; N = 10; age: 75.9 ± 7.3) or primary progressive aphasia (PPA; N = 12; 69.7 ± 8.0), and compared them to normal aging [young (N = 18; 24.6 ± 3.5), older controls (N = 24; 67.2 ± 9.7]. Whole-brain source-level resting-state estimates of relative oscillatory power in the delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), and beta (15-30 Hz) bands were combined with gray matter volumes and cognitive scores to examine between-group differences and brain-behavior correlations. Language and executive function (EF) abilities were impaired in patients with PPA, while episodic memory was impaired in MCI. Widespread oscillatory speeding and volumetric shrinkage was associated with normal aging, whereas the trajectory in PPA indicated widespread oscillatory slowing with additional volumetric reductions. Increases in delta and decreases in alpha power uniquely predicted group membership to PPA. Beyond volumetric reductions, more delta predicted poorer memory. In patients with MCI, no consistent group difference among oscillatory measures was found. The contributions of delta/alpha power on memory abilities were larger than volumetric differences. Spontaneous oscillatory abnormalities in association with cognitive symptom severity can serve as a marker of neuronal dysfunction in dementia, providing targets for promising treatments.

Keywords: dementia; magnetoencephalography; mild cognitive impairment; normal aging; primary progressive aphasia; resting-state.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1

Results from the rotated principal component analysis (rPCA) on cognitive test scores. (a) Factor loadings representing the positive (in red) and the negative (in blue) correlations between cognitive test scores and four factors or rotated components (RC1‐4) derived from rPCA. Factor loadings with bootstrap ratios greater than 2.0 are highlighted by thick black lines. The first three RCs loaded highly onto test scores of language (RC1), memory (RC2) and executive function (RC3) abilities, respectively. RC1‐language (b) and RC3‐executive function (d) scores significantly differed between older controls and PPA but not MCI, whereas MCI differed from older controls on RC2‐memory (c) scores; horizontal lines within the boxplots in b–d represent the median, the bars represent the interquartile range, and the superimposed dots represent individual data points. a.u. = arbitrary units; *significance at p < .05; **significance at p < .001 [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

(a) Design saliences from a significant latent variable 1 (LV1; p < .001) obtained from the partial least squares (PLS) analysis comparing young and older controls. Bootstrap ratio (BSR) maps thresholded at ±4.0 are shown for the differences in gray matter (GM) volumes (b) and the relative MEG power estimates of delta (c), theta (d), alpha (e), and beta (e); the overlay maps were smoothed using the linear resampling mode in AFNI and the 3D cortical surface render with BSR were generated using the AFNI‐SUMA suite. Positive values of BSR (red‐yellow) demonstrate a positive association with the design saliences, that is, older > younger, and negative values of BSR (blue) demonstrate a negative association, that is, older < younger. L = left; R = right; P = posterior; PreCG = precentral gyrus; IFG = inferior frontal gyrus; CG = cingulate gyrus; INS = insula; TPJ = temporoparietal junction; MeFG = medial frontal gyrus; Thal = thalamus; PHG = parahippocampal gyrus; IPL = inferior parietal lobe; PoCG = postcentral gyrus; MTG = middle temporal gyrus; STG = superior temporal gyrus; SFG = superior frontal gyrus [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

(a) Design saliences from a significant latent variable 1 (LV1; p < .001) obtained from the PLS analysis comparing PPA and age‐matched controls. Bootstrap ratio (BSR) maps thresholded at ±4.0 are shown for the differences in GM volumes (b) and the relative MEG power estimates of delta (c), theta (d), alpha (e), and beta (e); positive values of BSR (red/yellow) demonstrate a positive association with the design saliences, that is, PPA > controls, and negative values of BSR (blue) demonstrate a negative association, that is, PPA < controls. PLS = partial least squares; L = left; R = right; P = posterior; IFG = inferior frontal gyrus; MTG = middle temporal gyrus; FFG = fusiform gyrus; PHG = parahippocampal gyrus; ACC = anterior cingulate cortex; SFG = superior frontal gyrus [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

(a) Scatter plot between design (RC2‐memory factor scores) and brain scores from a significant latent variable 1 (LV1; p = .011) obtained from the behavioral PLS analysis in PPA with RC2 scores are displayed. Bootstrap ratio (BSR) maps thresholded at ±4.0 are shown for the correlation with GM volumes (b) and the relative MEG power estimates of delta (c), theta (d), alpha (e), and beta (e); positive BSR values (red/yellow) demonstrate a positive correlation, and negative BSR values (blue) demonstrate a negative correlation. PLS = partial least squares; L = left; R = right; P = posterior; corr = correlation; PoCG = postcentral gyrus; AG = angular gyrus; MTG = middle temporal gyrus; PreCun = precuneus; FFG = fusiform gyrus; MOG = middle occipital gyrus; MeFG = medial frontal gyrus; ACC = anterior cingulate cortex; TPJ = temporoparietal junction; SPL = superior parietal lobe; PCC = posterior cingulate cortex [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

(a) Scatter plot between design (RC3‐executive function factor scores) and brain scores from a significant latent variable 1 (LV1; p = .027) obtained from the behavioral PLS analysis in PPA with RC3 scores are displayed. Bootstrap ratio (BSR) maps thresholded at ±4.0 are shown for the correlation with GM volumes (b) and the relative MEG power estimates of delta (c), theta (d), alpha (e), and beta (e); positive BSR values (red/yellow) demonstrate a positive correlation, and negative BSR values (blue) demonstrate a negative correlation. PLS = partial least squares; L = left; R = right; P = posterior; corr = correlation; PCC = posterior cingulate cortex; CG = cingulate gyrus; PreCun = precuneus; SPL = superior parietal lobe; MTG = middle temporal gyrus; PoCG = postcentral gyrus; SFG = superior frontal gyrus; INS = insula; IFG = inferior frontal gyrus [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 6

(a) Scatter plot between design (RC2‐memory factor scores) and brain scores from a significant latent variable 1 (LV1; p = .014) obtained from the behavioral PLS analysis in MCI with RC2 scores are displayed. Bootstrap ratio (BSR) maps thresholded at ±4.0 are shown for the correlation with GM volumes (b) and the relative MEG power estimates of delta (c), theta (d), alpha (e), and beta (e); positive BSR values (red/yellow) demonstrate a positive correlation, and negative BSR values (blue) demonstrate a negative correlation. PLS = partial least squares; L = left; R = right; P = posterior; corr = correlation; SFG = superior frontal gyrus; IFG = inferior frontal gyrus; PHG = parahippocampal gyrus; IPL = inferior parietal lobe; PoCG = postcentral gyrus; FFG = fusiform gyrus; ITG = inferior temporal gyrus; SPL = superior parietal lobe; MOG = middle occipital gyrus; PreCG = precentral gyrus; INS = insula; STG = superior temporal gyrus [Color figure can be viewed at http://wileyonlinelibrary.com]