A multimodal imaging perspective on human sensorimotor behavior

Understanding motor control has been critical to motor rehabilitation after brain injuries. Neural activity can be detected non-invasively using functional magnetic resonance imaging (fMRI) that measures hemodynamic response and magnetoencephalography (MEG) that measures electrophysiological dynamics. In this dissertation, two scientific questions were investigated with two distinct functional neuroimaging techniques. First, I used fMRI to search for neural correlates of spasticity in individuals with chronic stroke. Spasticity, defined as velocity-dependent resistance to passive stretch, is common after stroke and imposes significant therapeutic challenges. It is believed that disinhibition of brainstem nuclei, possibly the lateral vestibular nuclei or pontine reticular formation, are primarily involved. As such, I aimed to localize the activity of these individual brainstem nuclei via 3T functional magnetic resonance imaging (fMRI) in a cohort of chronic stroke patients and healthy controls. Using both acoustic and visual stimuli to activate the brainstem without inducing motion in the participants. The results showed that the response of stroke patients was dominantly more correlated to age, duration of a stroke, and total brainstem volume. Another significant motor deficit that stroke patients face is the loss of individual finger control that allows fine motor control like precision pinch. In the second part of my dissertation, I investigated neural correlates of dynamic precision grip tasks, a predictor of sensorimotor impairment or decline. Visuomotor control for precision grip relies on an extensive cortical network for which research has traditionally focused on frontal and parietal regions subserving executive and visuomotor integration functions, respectively. However, the temporal dynamics of how visuomotor integration is expressed in the form of oscillatory modulation as a combination of both low and high-level functions remain unclear. Thus, I used MEG to measure dynamic oscillatory activity in the sensorimotor and visual areas to investigate their contribution to performance in a dynamic precision grip task in healthy individuals. A custom MEG-compatible sensor measured forefinger and thumb forces separately, which controlled the position of a cursor on the screen. My findings suggest that cortical oscillations in both sensorimotor and visual areas can dissociate task and movement parameters during dynamic pinch tasks and that they may share a common network for visuomotor control. My ultimate goal is to better address how the spatial and temporal profiles of neural activity connect behavior to pathologic responses.Biomedical Engineerin

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

An Instant Donning Multi-Channel EEG Headset (with Comb-Shaped Dry Electrodes) and BCI Applications

We developed a new type of electroencephalogram (EEG) headset system with comb-shaped electrodes that enables the wearer to quickly don and utilize it in daily life. Two models that can measure EEG signals using up to eight channels have been implemented. The electrodes implemented in the headsets are similar to a comb and are placed quickly by wiping the hair (as done with a comb) using the headset. To verify this headset system, donning time was measured and three brain computer interface (BCI) application experiments were conducted. Alpha rhythm-based, steady-state visual evoked potential (SSVEP)-based, and auditory steady state response (ASSR)-based BCI systems were adopted for the validation experiments. Four subjects participated and ten trials were repeated in the donning experiment. The results of the validation experiments show that reliable EEG signal measurement is possible immediately after donning the headsets without any preparation. It took approximately 10 s for healthy subjects to don the headsets, including an earclip with reference and ground electrodes. The results of alpha rhythm-based BCI showed 100% accuracy. Furthermore, the results of SSVEP-based and ASSR-based BCI experiments indicate that performance is sufficient for BCI applications; 95.7% and 76.0% accuracies were obtained, respectively. The results of BCI paradigm experiments indicate that the new headset type is feasible for various BCI applications

Physiological Signal Monitoring Bed for Infants Based on Load-Cell Sensors

Ballistocardiographs (BCGs), which record the mechanical activity of the heart, have been a subject of interest for several years because of their advantages in providing unobtrusive physiological measurements. BCGs could also be useful for monitoring the biological signals of infants without the need for physical confinement. In this study, we describe a physiological signal monitoring bed based on load cells and assess an algorithm to extract the heart rate and breathing rate from the measured load-cell signals. Four infants participated in a total of 13 experiments. As a reference signal, electrocardiogram and respiration signals were simultaneously measured using a commercial device. The proposed automatic algorithm then selected the optimal sensor from which to estimate the heartbeat and respiration information. The results from the load-cell sensor signals were compared with those of the reference signals, and the heartbeat and respiration information were found to have average performance errors of 2.55% and 2.66%, respectively. The experimental results verify the positive feasibility of BCG-based measurements in infants

Analysis of Extracellular Vesicles Using Coffee Ring

Extracellular vesicles are categorized in subsets according to their biogenesis processes. To facilitate the investigation of subsets, an effective method is needed for isolating subpopulations. The efficacy of existing density and size-based isolation methods is limited, and as a result, the correlation of properties within separated subpopulations is modest. Here, we introduced size separation with ∼48 nm resolution that exploits Marangoni flow and the coffee-ring effect in microdroplets in which extracellular vesicles are spatially deposited at different location according to size of extracellular vesicle. Interestingly, the analysis of tetraspanin proteins of the extracellular vesicles facilitated by this method reveals that the size of extracellular vesicles is correlated with expression of tetraspanin proteins (CD9, CD63, CD81) that are associated with the size of extracellular vesicles. The findings show that CD9 and CD81 are uniformly expressed regardless of size, CD63 is highly expressed only in larger extracellular vesicles. This evidence indicates that extracellular vesicles can be classified based on size and expression of CD63

Effect of Concentrated Fibroblast-Conditioned Media on In Vitro Maintenance of Rat Primary Hepatocyte.

The effects of concentrated fibroblast-conditioned media were tested to determine whether hepatocyte function can be maintained without direct contact between hepatocytes and fibroblasts. Primary rat hepatocytes cultured with a concentrated conditioned media of NIH-3T3 J2 cell line (final concentration of 55 mg/ml) showed significantly improved survival and functions (albumin and urea) compared to those of control groups. They also showed higher expression levels of mRNA, albumin and tyrosine aminotransferase compared to hepatocyte monoculture. The results suggest that culture with concentrated fibroblast-conditioned media could be an easy method for in vitro maintenance of primary hepatocytes. They also could be contribute to understand and analyze co-culture condition of hepatocyte with stroma cells