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

Couldn't make heads or tails of what use this could be in stroke recovery.

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

Christian La^1,2*, Pouria Mossahebi², Veena A. Nair², Brittany M. Young^1,2, Julie Stamm², Rasmus Birn^3,4, Mary E. Meyerand^1,2,3,5 and Vivek Prabhakaran^1,2,3,4

• ¹Neuroscience Training Program, University of Wisconsin–Madison, Madison, WI, USA
• ²Department of Radiology, University of Wisconsin–Madison, Madison, WI, USA
• ³Department of Medical Physics, University of Wisconsin–Madison, Madison, WI, USA
• ⁴Department of Psychiatry, University of Wisconsin–Madison, Madison, WI, USA
• ⁵Department of Bio-Medical Engineering, University of Wisconsin–Madison, Madison, WI, USA

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.

Introduction

The default-mode network (DMN) is considered a central network of the cortical system. Primarily comprised of the precuneus/posterior cingulate cortex (pC/PCC), the medial prefrontal cortex (mPFC), and bilateral inferior parietal lobules (IPLs), this network consists of regions actively recruited during a state of rest, where no goal-directed behavior is required (Fransson, 2005; Fox and Raichle, 2007; Raichle, 2010). In healthy individuals, in addition to being highly active during the passive condition of rest, activity within the DMN is actively suppressed during goal-directed task performance facilitating the various goal-directed processes (Raichle et al., 2001; Fransson, 2005; Fox and Raichle, 2007). Disruption of DMN network activity/de-activity pattern contributes to the impairment of functional networks associated with a variety of behaviors observed in cognitively impaired populations (Grady et al., 2006, 2010; Persson et al., 2007; Lustig and Jantz, 2014), such as a decline in speed of processing, executive and/or memory functions. Investigation of this network has gained popularity in recent years, in particular for its utility in describing aging and a variety of neurological (e.g., Alzheimer’s and Parkinson’s disease) and psychiatric (such as Schizophrenia, Autism, and ADHD) disease states, where abnormal DMN activity has been consistently found (Greicius et al., 2004; Persson et al., 2007; Damoiseaux et al., 2008; Greicius, 2008; Broyd et al., 2009).

Resting-state fMRI or rs-fMRI is a rapidly evolving method allowing one to explore the intrinsic low-frequency fluctuations (LFOs) and the intrinsic connectivity networks (ICNs) of the brain (Beckmann et al., 2005; Damoiseaux et al., 2006; Fox and Raichle, 2007; Cole et al., 2010; Schölvinck et al., 2010; Patriat et al., 2013). Analysis of functional connectivity (Friston et al., 1993), a method to assess the temporal correlation of distant brain regions, can be used to investigate the functional organization of the brain without an overt task or external input (Biswal et al., 1995; Van Den Heuvel and Pol, 2010). In addition, spatial patterns of resting functional activity can be extracted by computing the amplitude of the low-frequency fluctuation (ALFF; Yu-Feng et al., 2007). Because of the passive nature of the resting-state condition, a rs-fMRI scan is highly advantageous as it allows the investigation of patients that would otherwise have difficulty with task performance. This approach is less susceptible to variability in task-related behavior such as motivation and attention.

Recent studies using rs-fMRI have also demonstrated significant differences in the DMN in patients following the onset of a stroke, with lesion in regions not belonging to the DMN (Tuladhar et al., 2013; Park et al., 2014). Specifically, stroke patients exhibited decreased network co-activation within the regions of the DMN, primarily over the regions of the PCC. However, ischemic stroke is dissimilar to the aforementioned disease states (e.g., Alzheimer’s disease, Parkinson’s disease) in the acute nature of the injury, imposing rapid network changes and network re-organization, and thus may have a different mechanism of network disruption in comparison to more progressive disorders. Despite the disruption in vasculature, the investigations of stroke patients can bring new insight into the source and underlying mechanism of cortical network disruption. The investigation of stroke population also allows for an assessment of time-dependent, stroke-related cortical changes and cortical re-organization following initial onset, and permits the eventual longitudinal assessment of network recovery in the later stages of stroke.

Here, we aimed to investigate the disruption of the DMN—a network shown to be subjected to the diaschisis effect of the stroke lesion—and two selected task-positive networks occurring in patients following the event an ischemic stroke in a cross-sectional study using rs-fMRI. Specifically, we assessed these changes via an investigation of the distribution of LFOs in the frequency domain. The DMN is not regularly investigated in stroke population because of its low susceptibility to direct stroke-related lesion injury. However, the DMN has been demonstrated to be susceptible to changes through indirect mechanism such as diaschisis effects (Tuladhar et al., 2013; Park et al., 2014). Detailed investigations of amplitude information of those LFOs power spectra have been implemented by subdividing the frequency distribution of these spontaneous oscillations into distinct infra-slow frequency ranges (i.e., slow-5: 0.01–0.027 Hz, slow-4: 0.027–0.073 Hz, slow-3: 0.073–0.198 Hz, slow-2: 0.198–0.25 Hz; Penttonen and Buzsáki, 2003; Buzsáki and Draguhn, 2004; Zuo et al., 2010), with significant slow-4 and slow-5 oscillations demonstrated to be primarily restricted to gray matter; while slow-2 and slow-3 oscillations restricted to white matter (Zuo et al., 2010). Many areas exhibiting maximal low-frequency oscillation amplitudes were also found in regions of the DMN.

Using an approach of component fractional ALFF (fALFF), where estimates of relative spectral power are computed for network component oscillation (Calhoun et al., 2011; Gohel and Biswal, 2014), our group has previously provided evidence that implicated specific fluctuation within the slow-5 oscillations range (0.01–0.027 Hz) in the disruption of the DMN of stroke population in their later stage, unsettling the balance between slow-4 and slow-5 oscillation within the resting state, potentially disrupting the communication between distal nodes within a system [La et al., 2014; La et al., submitted]. This finding was in accord with the results from Zhu et al. (2015), where they found that regions with altered activity after stroke were more extensive within the slow-5 band. However, whether this reduction of oscillation power is unique to the DMN, or whether those changes extends beyond the DMN following the event of an ischemic stroke had yet to be explored and was investigated here. In this study, we examined the amplitudes of the slow-5 oscillations in three independent subcomponents of the DMN, as well as two components of ‘task-positive’ systems (primary visual and sensorimotor) for the investigation of stroke-related diaschisis effect on various network of the cortical system.

More at link.