Synchrony Between Default-Mode and Sensorimotor Networks Facilitates Motor Function in Stroke Rehabilitation: A Pilot fMRI Study

I got nothing out of this except for biomarker which means this research was totally useless for getting survivors recovered. 

Synchrony Between Default-Mode and Sensorimotor Networks Facilitates Motor Function in Stroke Rehabilitation: A Pilot fMRI Study

Changwei W. Wu^1,2*, Shang-Hua N. Lin³, Li-Ming Hsu^1,4, Shih-Ching Yeh⁵, Shiao-Fei Guu¹, Si-Huei Lee^6* and Chun-Chuan Chen^7*

• ¹Graduate Institute of Mind, Brain and Consciousness, College of Humanities and Social Sciences, Taipei Medical University, Taipei, Taiwan
• ²Brain and Consciousness Research Center, College of Humanities and Social Sciences, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan
• ³Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan
• ⁴Biomedical Research Imaging Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
• ⁵Department of Computer Science and Information Engineering, National Central University, Taoyuan, Taiwan
• ⁶Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan
• ⁷Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan

Stroke is the most common cause of complex disability in Taiwan. After stroke onset, persistent physical practice or exercise in the rehabilitation procedure reorganizes neural assembly for reducing motor deficits, known as neuroplasticity. Neuroimaging literature showed rehabilitative effects specific to the brain networks of the sensorimotor network (SMN) and default-mode network (DMN). However, whether between-network interactions facilitate the neuroplasticity after stroke rehabilitation remains a mystery. Therefore, we conducted the longitudinal assessment protocol of stroke rehabilitation, including three types of clinical evaluations and two types of functional magnetic resonance imaging (fMRI) techniques (resting state and grasp task). Twelve chronic stroke patients completed the rehabilitation protocol for at least 24 h and finished the three-time assessments: before, after rehabilitation, and 1 month after the cessation of rehabilitation. For comparison, age-matched normal controls (NC) underwent the same fMRI evaluation once without repeated measure. Increasing scores of the Fugl–Meyer assessment (FMA) and upper extremity performance test reflected the enhanced motor performances after the stroke rehabilitation process. Analysis of covariance (ANCOVA) results showed that the connections between posterior cingulate cortex (PCC) and iM1 were persistently enhanced in contrast to the pre-rehabilitation condition. The interactions between PCC and SMN were positively associated with motor performances. The enhanced cross-network connectivity facilitates the motor recovery after stroke rehabilitation, but the cross-network interaction was low before the rehabilitation process, similar to the level of NCs. Our findings suggested that cross-network connectivity plays a facilitatory role following the stroke rehabilitation, which can serve as a neurorehabilitative biomarker for future intervention evaluations.

Introduction

Stroke is the most common cause of complex disability in Taiwan (Hsieh and Chiou, 2014). Most stroke patients survive the initial insult but are left with cognitive impairments, such as movement, sensation, language, memory, and emotion (Carey, 2012). Therefore, rehabilitation protocols (Where the fuck are they?)play essential roles in post-stroke intervention to lessen the disabilities and regain their quality of life. However, rehabilitative neuroplasticity is a time-dependent process, and the efficacy is unique to each patient (Kolb et al., 2010). Therefore, successful rehabilitative training and an effective evaluation approach are of great importance for post-stroke healthcare, assisting patients returning to meaningful daily activities. Currently, clinical guidelines for stroke rehabilitation are available (Carey, 2012), but the typical evaluation of stroke rehabilitation relies on the patients’ and physicians’ subjective opinions on patients’ motor improvements. Subjective evaluations on behavioral performances may not reflect the ongoing neurophysiological progress following neurorehabilitation. Henceforth, current neuroimaging methodologies, such as functional magnetic resonance imaging (fMRI), offer the possibility to frame post-stroke neuroplasticity objectively (Carey and Seitz, 2007; Liu et al., 2017). These approaches are especially useful when the neural mechanisms of post-stroke recovery over time reflect different pathophysiological phases after ischemic stroke (Carey and Seitz, 2007).

Pathophysiological abnormalities in brain functions can be evaluated by fMRI through two different strategies: brain activity on task engagement and brain connectivity in a resting state. Compared with the limb movement performance in healthy participants, higher contra-lesional motor activity was observed in stroke patients (Enzinger et al., 2008; Carey L. et al., 2011), suggesting the reduced inhibition to the contra-lesional motor cortex during task engagements (Nowak et al., 2009). The task-evoked brain activity was proved to be associated with behavioral performances (Carey L. M. et al., 2011). In contrast, the resting state functional connectivity (RSFC) provides another viewpoint of the brain integrity during a spontaneous state without task engagements (Biswal et al., 1995). The inter-hemispheric RSFC may act as the cognitive reserve in support of task events, and the ipsilesional RSFC usually associates with unilateral neuropathologies in recent studies (Fan et al., 2015). Literature also showed that inter-hemispheric RSFC of sensorimotor network (SMN) was disrupted after stroke onset (Carter et al., 2010; van Meer et al., 2010; Zhang et al., 2016), associated with the reduction of limb movements and gait (Enzinger et al., 2008; van Meer et al., 2012).

Beyond the SMN, the post-stroke connectivity loss in the default-mode network (DMN) and frontoparietal network (FPN) were also found to be associated with cognitive impairments in literature (Tuladhar et al., 2013; Li et al., 2014; Liu et al., 2017). A previous study showed that decreased RSFC of DMN was associated with cognitive decline in stroke patients (Liu et al., 2014), and the attention deficits following stroke onset were associated with FPN (Lincoln et al., 2000; Bajaj et al., 2015). Furthermore, longitudinal RSFC studies disclosed plausible neural reorganizations after stroke onset. For example, Miao et al. observed the progressive inter-hemispheric RSFC normalization in the SMN (van Meer et al., 2012), and the DMN connectivity was restored 3 months after stroke (Park et al., 2014). However, although the brain functionality is accomplished by internetwork integrity as a whole unit, a majority of literature focused on connectivity disruptions of one specific network after stroke (Zhang et al., 2016; Veldsman et al., 2018). Most recent studies demonstrated that inter-network connections serve important roles in cognitive functions. For example, Wang et al. (2014) stated that subcortical stroke affects not only the intra-network connectivity but also the internetwork RSFC. Lam et al. (2018) described the coupling between contra-lesional motor and FPNs correlated with the post-stroke motor outcome. To date, these studies reported the internetwork interactions between stroke patients and controls, yet evaluate the cross-network interactions along the neurorehabilitation process. Therefore, it remains elusive whether the cross-network interactions interfere or facilitate brain reorganizations along the stroke rehabilitation process.

Targeting this issue, we hypothesized that the internetwork connectivity between SMN, DMN, and FPN contributes to regaining of motor functions along the stroke rehabilitation process. To attain this goal, we recruited 15 subcortical stroke patients for longitudinal fMRI assessments. We performed longitudinal assessments three times along the rehabilitative intervention (pre-rehab, post-rehab, 1 month follow up). For each assessment, the patients performed a grasp task and resting state fMRI to evaluate both brain activity and functional connectivity.