Differing Patterns of Altered Slow-5 Oscillations in Healthy Aging and Ischemic Stroke

Abstract

The 'default-mode' network (DMN) has been investigated in the presence of various disorders, such as Alzheimer's disease and Autism spectrum disorders. More recently, this investigation has expanded to include patients with ischemic injury. Here, we characterized the effects of ischemic injury in terms of its spectral distribution of resting-state low-frequency oscillations and further investigated whether those specific disruptions were unique to the DMN, or rather more general, affecting the global cortical system. With 43 young healthy adults, 42 older healthy adults, 14 stroke patients in their early stage (<7 days after stroke onset), and 16 stroke patients in their later stage (between 1 to 6 months after stroke onset), this study showed that patterns of cortical system disruption may differ between healthy aging and following the event of an ischemic stroke. The stroke group in the later stage demonstrated a global reduction in the amplitude of the slow-5 oscillations (0.01-0.027 Hz) in the DMN as well as in the primary visual and sensorimotor networks, two 'task-positive' networks. In comparison to the young healthy group, the older healthy subjects presented a decrease in the amplitude of the slow-5 oscillations specific to the components of the DMN, while exhibiting an increase in oscillation power in the task-positive networks. These two processes of a decrease DMN and an increase in 'task-positive' slow-5 oscillations may potentially be related, with a deficit in DMN inhibition, leading to an elevation of oscillations in non-DMN systems. These findings also suggest that disruptions of the slow-5 oscillations in healthy aging may be more specific to the DMN while the disruptions of those oscillations following a stroke through remote (diaschisis) effects may be more widespread, highlighting a non-specificity of disruption on the DMN in stroke population. The mechanisms underlying those differing modes of network disruption need to be further explored to better inform our understanding of brain function in healthy individuals and following injury.

Keywords: aging; fALFF; low-frequency oscillations; rs-fMRI; slow-5 oscillations; stroke.

FIGURE 1

Lesion Density Map for 30 ischemic stroke patients (early and late combined), with most lesions not overlapping.

FIGURE 2

Consistent group ICA derived components. Top to bottom: posterior DMN (pDMN), anterior DMN (aDMN), ventral DMN (vDMN), primary visual, and primary sensorimotor, with slices chosen to allow a comprehensive depiction of the functional networks.

FIGURE 3

Component spectral distribution organized by population group: (A) young healthy adult (YHA), (B) old healthy adult (OHA), (C) stroke-early, and (D) stroke-late. Colored plots in each panel representing the mean of a distinct component, the shaded area portraying the standard error of the mean. Color coding is as follow: pDMN (magenta), aDMN (cyan), vDMN (yellow), visual (black), and motor (white). Population spectral distribution appeared highly disrupted in the stroke-late population with non-unique distribution peak, and wider spectral distribution with lower overall amplitude.

FIGURE 4

Spectra difference plot for: Top row: each of the three components of the DMN: (A) pDMN, (B) aDMN, (C) vDMN, Bottom row: two non-DMN components of (D) primary visual, and (E) primary sensorimotor. For each panel, top graph is a representation of the smoothed mean spectra with young (green), old (blue), and stroke-late (red). The bottom panels represent the difference between the mean spectra, with purple plot characterizing the difference between YHA and OHA, and the orange plot indicating the difference between stroke-late and OHA. Solid vertical lines demark limits of the slow-5 oscillation range (0.01–0.027 Hz) and dotted vertical lines mark the upper limit of the slow-4 frequency range (0.027–0.073 Hz). The boxes below the plots indicate the statistical significance for the discrete bin analysis of amplitude. Within the DMN, differences in stroke-late vs. OHA were noted to have large negative deflection in the slow-5 range, indicating a further reduction of the slow-5 oscillations on top of the observed reduction from aging (OHA – YHA). In the two assessed ‘task-positive’ networks, stroke-late groups exhibited a similar decrease in the oscillations. However, the aging process demonstrated a different pattern with a surge of slow-5 oscillations amplitude in those components (black arrows), coupled with a reduction of slow-4 oscillations.

FIGURE 5

Component fALFF for each investigated component in terms of slow-5 oscillations (0.01–0.027 Hz) and slow-4 oscillations (0.027–0.073 Hz). In all five of the components assessed, the stroke-early group did not exhibit difference in its component fALFF measure compared to the OHA. In contrast, the stroke-late group presented a significant decrease in component fALFF in the slow-5 oscillations that was observed in pDMN, aDMN, and vDMN, while the difference observed in the visual and sensorimotor component were not significant. Aging, in the other hand, was associated with an increase in slow-5 component fALFF in those two task-positive networks (not attaining statistical significance [ANOVA], but trending in significance with two-sample t-test, p ≤ 0.1). Additionally, ratio of slow-5 to [slow-5 and slow4] combined demonstrated significance in post hoc two-sample t-tests (illustrated here by the *p < 0.05).

FIGURE 6

Resting state relative oscillation power as recorded by fALFF (0.01–0.073 Hz). Difference in resting-state fALFF between the aging-effect and the stroke-related effect. The resting-state fALFF in the OHA exhibited lower values in comparison to their younger counterpart (YHA), while levels of resting-state fALFF in the ischemic stroke-late group remained the same as the OHA, suggesting that disruption following the event of a stroke may be more due to a reallocation of the oscillation power from the slow-5 frequency range to the slow-4 frequency range, rather than a decrease of power of the total resting-state oscillations. *p < 0.05.

FIGURE 7

Confidence Intervals for DMN and ‘visual–sensorimotor’ combined components single-factor ANOVA. With the combined components, clear reduction of slow-5 fALFF in the stroke-late (SUBA) population can be observed in comparison to the acute stroke group and healthy old individuals within the DMN. Reductions in the stroke-early (ACU) group were very similar to the healthy older adults (OHA), and did not reach statistical significance. In contrast, behavior of the ‘visual–sensorimotor’ component differed between the healthy aging effect and the effect observed in the stroke-late patient population. In this ‘task-positive’ composite component, the stroke-late population exhibited a trend toward significance in a reduction of slow-5 oscillations (negative in SUBA-Old contrast), while the old presented an increase in those slow-5 oscillations compared to the young (negative in YNG-OLD contrast). **p < 0.001, *p < 0.05, ^#p < 0.1.