https://scholar.gist.ac.kr/handle/local/7979 2026-08-14T03:21:43Z https://scholar.gist.ac.kr/handle/local/19890 Title: Voice-Based Amyotrophic Lateral Sclerosis(ALS) Classification Using Deep Learning Method Author(s): MD HASIBUZZAMAN Abstract: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that severely impacts motor functions. Early identification of ALS remains a significant challenge due to the variability in its early symptoms, particularly speech and voice issues. This thesis investigates the feasibility of leveraging deep neural networks (DNNs) for automatic voice-based classification of ALS in its early stages. The study employed voice data from 20 healthy individuals, 27 ALS patients with dysarthria, and 16 ALS patients without dysarthria.Temporal features (jitter, shimmer, HNR) and time-frequency features (MFCCs) were extracted from sustained phonation of syllables and words. These features were then fed into different DNN architectures for classification. Convolutional Neural Networks (CNNs) utilizing mel-frequency cepstral coefficients (MFCCs) achieved an accuracy of 99.25% for two-class classification of ALS and healthy individuals, and 98.35% for three-class classification (ALS with dysarthria, ALS without dysarthria, and healthy individuals). This outperformed Long Short-Term Memory networks and other classical machine learning methods. This study demonstrates the potential of DNNs, particularly CNNs with MFCC features, for early and accurate ALS detection. This holds promise for improved clinical management and development of novel therapeutic interventions. 2023-12-31T15:00:00Z https://scholar.gist.ac.kr/handle/local/19854 Title: Transcriptional and translational regulation underlying LPS/IFN-γ-mediated macrophage polarization Author(s): Acquah Emmanuel Abstract: As the central component of innate immune system, macrophages’ functions include killing of invading pathogens through cytotoxic inflammatory response, phagocytosis and regulation of the immune system activities. They reflect cellular heterogeneity and are classified as M1 (classical activation) upon activation by LPS, IFN-γ or TNFα and M2 (alternative activation) when activated by IL-4/13. Several genes expressions occur during macrophage polarization that are controlled by multiple transcriptional and translational mechanisms leading to their distinct phenotypic forms and systemic innate immune responses. The present study underscores the important contributions of IFN-γ and/ or LPS in murine macrophage polarization. I stimulated BMDMs with LPS or LPS + IFN-γ and confirmed the polarized macrophage populations using flow cytometry. During LPS or LPS + IFN-γ response at early or late time point, canonical M1 genes (Nos2 and TNFα) expression were validated with RT-PCR. Here, the synergistic effect of IFN-γ with LPS to induce high expression of Nos2 and TNFα was observed while M0 genes (TBP and Adgre1) remained stable with time. Nos2, previously reported as an early expression marker showed late expression, thus, likely to be in a cell context fashion or is concentration dependent. I performed ribosome profiling coupled with RNA-seq to study global gene translation and identified LPS or IFN-γ + LPS specific genes whose expression regulations skew macrophages to M1 phenotypic state. These includes; Dusp1, Dusp2, TNF, Nos2, Socs3, Sele, NFKB, Csf2, Lyc6c2, IL6, IL10, CD83, CD86, Saa2, Egr1, Cxcl3, Cxcl10, Cxcl11 and Marco. Inducted genes were contrast in their abundance in RNA (transcriptome) compared to RPF (translatome) supporting the notion that mRNA level does not always reflect protein level. The upregulation of mitochondrial and cytosolic ribosomes coding genes identified suggested a translational level change at 1 hr and transcriptional change at 24 hrs time point. I found that IFN-γ + LPS and LPS may also modulate mRNA translation in macrophages by the enrichment of translation initiation (EIF2 signaling mTOR signaling, and regulation of eIF4 and p70S6K signaling), NF-KB pathway, Toll-like Receptor signaling and PPAR pathway which are unique pathways contributing to M1 phenotypic state and inflammatory response. Despite the difference in terms of activation and induced genes, altogether, this study provides insights into how IFN-γ and /or LPS can establish a crosstalk at the transcriptional and translational levels to achieve the differential regulation of gene sets with distinct and opposing functions. 2021-12-31T15:00:00Z https://scholar.gist.ac.kr/handle/local/19853 Title: Transcranial direct current stimulation (tDCS) Intervention in 5xFAD Mice: Reduction of Amyloid-Beta Levels and Restoration of Evoked Gamma-Band Oscillations Through Perineuronal Net Protection Author(s): Mahnoor Zaheer Abstract: This study investigates the potential therapeutic effects of transcranial direct current stimulation (tDCS) on various aspects of Alzheimer's disease (AD), including amyloidopathy, gliopathy, perineuronal nets (PNNs), and gamma-band oscillations (GBO). The findings suggest that tDCS may have a beneficial impact on these factors in the context of AD. First, tDCS was found to reduce the area and number of amyloid-beta (Aβ) plaques in the hippocampus and prefrontal cortex of transgenic AD mice, indicating a potential role in attenuating amyloidopathy. This reduction in Aβ plaques suggests a promising avenue for AD therapeutic interventions. Second, the study observed an enhancement of astrocyte levels in the hippocampus and prefrontal cortex of AD mice following tDCS. Astrocytes are known to play a role in amyloid plaque clearance, suggesting that tDCS may modulate gliopathy and contribute to the clearance of aberrant amyloid accumulation. Third, tDCS was associated with the restoration of perineuronal nets (PNNs), particularly in the hippocampus, which are important for stabilizing neural circuits. Preserving PNNs may reduce the loss of parvalbumin-positive (PV) interneurons and mitigate cognitive deficits in AD. Furthermore, the study found evidence of tDCS-induced restoration of gamma-band oscillations (GBO) in the frontal region of AD mice. GBO is linked to various cognitive functions, and its restoration may have a positive impact on cognitive performance in AD. Behavioral tests, including the Open Field Test (OFT), Novel Place Recognition (NPR) test, and Y-maze test, did not reveal significant differences in locomotor function or visuospatial memory between tDCS-treated and sham-treated AD mice. However, the study acknowledges limitations, including potential regional specificity of tDCS effects, uncertain functional implications of increased astrocytes, and concerns related to participant safety and data variability.Overall, this study provides compelling evidence that tDCS may hold promise as a therapeutic intervention for AD by addressing amyloidopathy, gliopathy, PNN preservation, and the restoration of GBO. Further research is needed to fully elucidate the mechanisms and clinical applicability of tDCS in the context of AD. 2023-12-31T15:00:00Z https://scholar.gist.ac.kr/handle/local/32667 Title: Therapeutic effects of acoustic stimulation at gamma band frequency in a mouse model of Alzheimer’s disease Author(s): Juho Lee Abstract: The accumulation of amyloid-beta (Aβ) is recognized as one of the neuropathologic hallmarks of Alzheimer’s disease (AD) and abnormal neurophysiologic findings have been observed such as abnormal gamma band oscillations and brain connectivity. Recently, the effects of gamma frequency entrainment on decreasing Aβ were reported using optogenetic and visual stimulations. However, the affected areas were limited to the hippocampus and visual cortex, although the therapeutic target areas should be a wider area of the brain, including the frontal cortex. Therefore, we investigated the effects of gamma entrainment using acoustic stimulation and optogenetic stimulation of the basal forebrain parvalbumin neurons that are known to regulate the cortical gamma oscillations. We used 5XFAD and 5XFAD/PV-Cre mice recapitulating major features of AD for acoustic and optogenetic stimulation, respectively. Electroencephalogram (EEG) electrodes were chronically placed on frontal and parietal sites of the skull of freely moving mice. Acoustic and optogenetic stimulation at 40 Hz were given for 2 hours per day for 2 weeks at the age of 6 months. The number of Aβ plaque and microglia was evaluated by immunohistochemistry analysis and the amount of soluble and insoluble Aβ peptides was assessed by ELISA. Evoked and spontaneous gamma power were analyzed by wavelet analysis. Coherence and phase locking value (PLV) analysis were used to assess fronto-parietal connectivity. The number of Aβ plaques decreased in the pre- and infra- limbic (PIL) and hippocampus regions (46.8% and 60.0% respectively) and soluble Aβ-40 and -42 peptides (45.5% and 67.2%, respectively) in PIL in the acoustic stimulation group compared to the untreated group. We also found that the number of activated microglia increased in PIL and hippocampus (188.3% and 98.9%, respectively). In EEG analysis, 5XFAD mice showed an increased evoked gamma power at 40 Hz, but it returned to the similar level to those of the control mice after acoustic stimulation. Conversely, spontaneous gamma power increased during the stimulation period. Connectivity analysis showed that the evoked gamma coherence did not differ between 5XFAD mice with and without acoustic stimulation, whereas PLV in spontaneous gamma oscillations showed a increasing pattern through the stimulation period in the acoustic stimulation group. Optogenetic stimulation of the basal forebrain parvalbumin neurons also resulted in a decreased level of evoked gamma power. In summary, we found that acoustic stimulation at 40 Hz for 2 weeks in 5XFAD can reduce Aβ plaque and peptides in the brain and restore abnormal neurophysiological pattern, including the gamma band oscillations and the fronto-parietal connectivity. Our data suggest that acoustic stimulation at 40 Hz might alter the natural deterioration processes of AD and have a therapeutic potential in AD. 2018-12-31T15:00:00Z