CoNDA Research Project Leaders

Kuan-Hua Chen, PhD

Interpersonal MEG/EEG Correlations & Physiobehavioral Synchrony in Dementia Patients and Caregivers

Dementia is associated with profound neurodegeneration in large-scale brain networks and increased cognitive, emotional, and social impairments that are difficult not only for the person with dementia (PWD) but also for the caregiver (CG). Caring for a loved one with dementia can be a meaningful part of family life; however, disruptive symptoms can produce deleterious effects and undermine CGs’ mental and physical health. Interpersonal connectedness is typically studied using self-report, which can be limited in dementia research due to PWDs’ functional declines and CGs’ increased stress and burden. Interpersonal physiobehavioral synchrony refers to the degrees to which people’s peripheral physiological responses and behaviors are interpersonally synchronized during dyadic interactions, which provides an alternative, more objective, less cognitively demanding measure to study PWD-CG connectedness. Past research has found diminished physiobehavioral synchrony between PWDs and CGs, and this effect was linked to PWD behavioral symptoms and associated with adverse CG health outcomes. Yet, the neural mechanisms for reduced PWD-CG physiobehavioral synchrony; and its pathways to longitudinal CG health changes remain unclear. To address these knowledge gaps, we focus on interpersonal neural response correlations between PWDs and CGs—the degree to which their brain responses are interpersonally correlated (showing similar patterns of changes) during watching a video replay of their own dyadic interactions. We apply magnetoencephalography (MEG) combined with electroencephalogram (EEG). This MEG/EEG approach offers superior temporal and spatial resolutions, allowing us to study physiobehavioral synchrony (which is highly temporal dynamic and can change in sub-second time scale) and the precise related neural regions and networks associated with its changes in dementia. We use a transdiagnostic approach by including multiple types of dementia while focusing on common PWD behavioral symptoms. In 90 PWD-spousal CG dyads, we determine how lower PWD-CG neural response correlations contribute to diminished PWD-CG physiobehavioral synchrony (Aim 1), how social contexts play a role (by moderating the association between PWD-CG neural response correlations and physiobehavioral synchrony; Aim 2), and the pathway through which reduced PWD-CG neural response correlations contribute to longitudinal CG health declines (Aim 3). The project will be utilizing resources and support from the UNMC CoNDA, including its MEG and MRI cores, mentorships from internal and external experts, and the collaborative environment. Research activities of this project will lead to a successful R01 application to advance the understanding of how dementia affects PWDs, CGs, their dyadic processes, and health. Research findings will advance the identification of the neurobiological markers/mechanisms for reduced physiobehavioral synchrony (and more broadly reduced interpersonal connectedness) in dementia and the brain-behavior-social pathways for adverse CG health outcomes.

Dr. Chen is an Assistant Professor in the Department of Neurological Sciences at the University of Nebraska Medical Center. His research examines changes in the brain and socioemotional functioning in persons with dementia, and how these changes affect health and well-being in their family/caregivers. His research also develops innovative technologies to conduct assessments and interventions in the real world and address health disparity issues. 

Christopher Kovach, PhD

Investigating the Role of Attention in Perceptual and Cognitive Consequences of Parkinson’s Disease

Cognitive and emotional impairments are a significant source of morbidity in Parkinson’s disease (PD), beyond the hallmark motor symptoms; yet they remain a poorly understood aspect of the disorder. Among the significant and debilitating non-motor symptoms of PD are deficits in the perception of social cues, such as facial expressions of emotion. Perceptual deficits in PD might arise through several mechanisms, and as yet, no unified model of motor and perceptual symptoms has been convincingly demonstrated. Attention is crucial for the perception of complex stimuli; hence one possibility is that impaired perception in PD is a consequence of abnormal control of attention. Because eye movement is altered in PD in a manner consistent with other motoric changes, and because normal eye movement is closely linked to visuospatial attention, this possibility points to a common origin for attentional, perceptual, and oculomotor symptoms of the disorder. Attentional control is, moreover, an essential element of a wide range of cognitive processes, including working memory and executive function, raising the prospect of a more broadly unified model of cognitive and motor symptoms in PD, stemming from networks common to attentional and motor control. We propose a focused test of this theoretical perspective by examining whether and how abnormal eye movements in PD associate with impaired perceptual judgment of facial emotion, under the working hypothesis that impaired perception of facial expression will correlate tightly with abnormal patterns of gaze to faces. The opportunity to record from and stimulate structures targeted by therapeutic deep brain stimulation (DBS) will allow a detailed interrogation of the hypothesis and inform models of neural pathways governing attentional control. This combination of methods will allow the hypothesis to be tested across three levels of analysis: (1) through between-group comparisons of PD patients, matched comparison healthy subjects, and DBS patients treated for essential tremor (ET); (2) through within-group correlational analyses, afforded by the wide variability of non-motor deficits in PD; and (3) through within-subject comparisons across manipulations of DBS. Results of the study will inform future therapeutic strategies for cognitive symptoms of PD.

Christopher K. Kovach, PhD,  is a systems and computational neuroscientist who joined the UNMC Department of Neurosurgery as a research faculty member in September 2023.  Dr. Kovach decided to pursue a career in neuroscience research after completing undergraduate degrees in biology and physics at the University of Kansas and two years of medical school at the University of Iowa Carver College of Medicine. After finishing his PhD at the University of Iowa in 2008 and postdoctoral fellowships at Iowa and Caltech, he spent nine years as a research scientist in the Department of Neurosurgery at the University of Iowa Hospitals and Clinics, where he developed new methods of spectral analysis for brain signals, implementing them in publicly shared software packages.

Haiying Shen, MD, PhD

Modulating PNNs to Mitigate Epileptogenesis and Neurobehavioral Deficits in Mouse Models

Epilepsy is a brain disorder where seizures become frequent and long-lasting over time. While current medications can help control seizures, they do not stop epilepsy from developing, and their effectiveness often decreases with use. A key factor in this process is the breakdown of protective structures around brain cells called perineuronal nets (PNNs). These nets support specific brain cells that help keep brain activity balanced. However, during seizures, harmful enzymes break down PNNs, leading to increased seizure risk and cognitive problems. The Shen Lab's research aims to understand how PNNs influence epilepsy development and whether preserving them can prevent seizures from worsening. In his CoNDA Research Project, Dr. Shen will study (i) how PNNs change in different stages of epilepsy, (ii) how a key protein, OTX2, helps maintain PNN strength, and (iii) whether a safe, FDA-approved drug, dolutegravir, can protect PNNs and reduce seizures. By learning how to keep PNNs intact, we hope to develop new treatments that not only control seizures but also prevent epilepsy from progressing, improving the quality of life for people with epilepsy.

Dr. Haiying Shen, MD, PhD is an Assistant Professor in the Division of Pediatric Neurology at UNMC. He attended medical school and completed his residency at the Third Medical University in Chongqing, China, before completing a Fellowship at Boston University School of Medicine in Boston. Dr. Shen's research interests include exploring adenosine-based mechanisms in enurobehavioral disorders, studying treatment and prevention against epilepsy and its comorbidities, translational neuroscience, and adenosine manipulation in malignant tumors.