Hippocampus Modulates Vocalizations Responses at Early Auditory Centers.

Despite its prominence in learning and memory, hippocampal influence in early auditory processing centers remains unknown. Here, we examined how hippocampal activity modulates sound-evoked responses in the auditory midbrain and thalamus using optogenetics and functional MRI (fMRI) in rodents. Ventral hippocampus (vHP) excitatory neuron stimulation at 5 Hz evoked robust hippocampal activity that propagates to the primary auditory cortex. We then tested 5 Hz vHP stimulation paired with either natural vocalizations or artificial/noise acoustic stimuli. vHP stimulation enhanced auditory responses to vocalizations (with a negative or positive valence) in the inferior colliculus, medial geniculate body, and auditory cortex, but not to their temporally reversed counterparts (artificial sounds) or broadband noise. Meanwhile, pharmacological vHP inactivation diminished response selectivity to vocalizations. These results directly reveal the large-scale hippocampal participation in natural sound processing at early centers of the ascending auditory pathway. They expand our present understanding of hippocampus in global auditory networks.

Neural activity temporal pattern dictates long-range propagation targets.

Brain possesses a complex spatiotemporal architecture for efficient information processing and computing. However, it remains unknown how neural signal propagates to its intended targets brain-wide. Using optogenetics and functional MRI, we arbitrarily initiated various discrete neural activity pulse trains with different temporal patterns and revealed their distinct long-range propagation targets within the well-defined, topographically organized somatosensory thalamo-cortical circuit. We further observed that such neural activity propagation over long range could modulate brain-wide sensory functions. Electrophysiological analysis indicated that distinct propagation pathways arose from system level neural adaptation and facilitation in response to the neural activity temporal characteristics. Together, our findings provide fundamental insights into the long-range information transfer and processing. They directly support that temporal coding underpins the whole brain functional architecture in presence of the vast and relatively static anatomical architecture.

Low-frequency hippocampal-cortical activity drives brain-wide resting-state functional MRI connectivity.

The hippocampus, including the dorsal dentate gyrus (dDG), and cortex engage in bidirectional communication. We propose that low-frequency activity in hippocampal-cortical pathways contributes to brain-wide resting-state connectivity to integrate sensory information. Using optogenetic stimulation and brain-wide fMRI and resting-state fMRI (rsfMRI), we determined the large-scale effects of spatiotemporal-specific downstream propagation of hippocampal activity. Low-frequency (1 Hz), but not high-frequency (40 Hz), stimulation of dDG excitatory neurons evoked robust cortical and subcortical brain-wide fMRI responses. More importantly, it enhanced interhemispheric rsfMRI connectivity in various cortices and hippocampus. Subsequent local field potential recordings revealed an increase in slow oscillations in dorsal hippocampus and visual cortex, interhemispheric visual cortical connectivity, and hippocampal-cortical connectivity. Meanwhile, pharmacological inactivation of dDG neurons decreased interhemispheric rsfMRI connectivity. Functionally, visually evoked fMRI responses in visual regions also increased during and after low-frequency dDG stimulation. Together, our results indicate that low-frequency activity robustly propagates in the dorsal hippocampal-cortical pathway, drives interhemispheric cortical rsfMRI connectivity, and mediates visual processing.

CycleGAN with mutual information loss constraint generates structurally aligned CT images from functional EIT images.

Electrical impedance tomography (EIT) has been employed in the field of medical imaging due to its cost effectiveness, safety profile and portability, but the images generated are relatively low resolution. To address these limitations, we create a novel method using EIT images to generate high resolution structurally aligned images of lungs like those from CT scans. A way to achieve this transformation is via Cycle generative adversarial networks (CycleGAN), which have demonstrated image-to-image translation capabilities across different modalities. However, a generic implementation yields images which may not be aligned with their input image. To solve this issue, we construct and incorporate a Mutual Information (MI) constraint in CycleGAN to translate functional lung EIT images to structural high resolution CT images. The CycleGAN is first trained on unpaired EIT and CT lung images. Afterwards, we generate CT image pairs from EIT images via CycleGANs constrained with MI loss and without this loss. Finally, through generating these 1560 CT image pairs and then comparing the visual results and quantitative metrics, we show that MI constrained CycleGAN produces more structurally aligned CT images, where Normalised Mutual Information (NMI) is increased to 0.2621+/- 0.0052 versus 0.2600 +/- 0.0066, p<0.0001 for non-MI constrained images. By this process, we simultaneously provide functional and structural information, and potentially enable more detailed assessment of lungs.Clinical Relevance- By establishing a structurally aligning generative process via MI Loss in CycleGAN, this study enables EIT-CT conversion, thereby providing functional and structural images for enhanced lung assessment, from just EIT images.

Cross modality generative learning framework for anatomical transitive Magnetic Resonance Imaging (MRI) from Electrical Impedance Tomography (EIT) image.

This paper presents a cross-modality generative learning framework for transitive magnetic resonance imaging (MRI) from electrical impedance tomography (EIT). The proposed framework is aimed at converting low-resolution EIT images to high-resolution wrist MRI images using a cascaded cycle generative adversarial network (CycleGAN) model. This model comprises three main components: the collection of initial EIT from the medical device, the generation of a high-resolution transitive EIT image from the corresponding MRI image for domain adaptation, and the coalescence of two CycleGAN models for cross-modality generation. The initial EIT image was generated at three different frequencies (70 kHz, 140 kHz, and 200 kHz) using a 16-electrode belt. Wrist T1-weighted images were acquired on a 1.5T MRI. A total of 19 normal volunteers were imaged using both EIT and MRI, which resulted in 713 paired EIT and MRI images. The cascaded CycleGAN, end-to-end CycleGAN, and Pix2Pix models were trained and tested on the same cohort. The proposed method achieved the highest accuracy in bone detection, with 0.97 for the proposed cascaded CycleGAN, 0.68 for end-to-end CycleGAN, and 0.70 for the Pix2Pix model. Visual inspection showed that the proposed method reduced bone-related errors in the MRI-style anatomical reference compared with end-to-end CycleGAN and Pix2Pix. Multifrequency EIT inputs reduced the testing normalized root mean squared error of MRI-style anatomical reference from 67.9% ± 12.7% to 61.4% ± 8.8% compared with that of single-frequency EIT. The mean conductivity values of fat and bone from regularized EIT were 0.0435 ± 0.0379 S/m and 0.0183 ± 0.0154 S/m, respectively, when the anatomical prior was employed. These results demonstrate that the proposed framework is able to generate MRI-style anatomical references from EIT images with a good degree of accuracy.

Functional MRI reveals brain-wide actions of thalamically-initiated oscillatory activities on associative memory consolidation.

As a key oscillatory activity in the brain, thalamic spindle activities are long believed to support memory consolidation. However, their propagation characteristics and causal actions at systems level remain unclear. Using functional MRI (fMRI) and electrophysiology recordings in male rats, we found that optogenetically-evoked somatosensory thalamic spindle-like activities targeted numerous sensorimotor (cortex, thalamus, brainstem and basal ganglia) and non-sensorimotor limbic regions (cortex, amygdala, and hippocampus) in a stimulation frequency- and length-dependent manner. Thalamic stimulation at slow spindle frequency (8 Hz) and long spindle length (3 s) evoked the most robust brain-wide cross-modal activities. Behaviorally, evoking these global cross-modal activities during memory consolidation improved visual-somatosensory associative memory performance. More importantly, parallel visual fMRI experiments uncovered response potentiation in brain-wide sensorimotor and limbic integrative regions, especially superior colliculus, periaqueductal gray, and insular, retrosplenial and frontal cortices. Our study directly reveals that thalamic spindle activities propagate in a spatiotemporally specific manner and that they consolidate associative memory by strengthening multi-target memory representation.

Global and regional lung function assessment using portable electrical impedance tomography (EIT) system: clinical study.

Recent development of affordable, portable and self-administrable electrical impedance tomography (EIT) system demonstrated the feasibility of using standalone EIT and subject's anthropometrics to predict the gold standard spirometry indicators for lung-function assessment. Compared to spirometry, the system showed the advantage of providing spatial mapping of the spirometry indicators. Nevertheless, the previous study was limited to healthy subjects. Here, we recruited (N=88): 47 lung disease patients and 41 healthy controls to perform simultaneous EIT and spirometry measurements to validate the capabilities of the system. Lung disease patients include 13 interstitial lung disease (ILD), 10 asthma, 8 chronic obstructive pulmonary disease (COPD), 8 bronchiectasis, and 8 with other diseases including left pneumonectomy, lung cancer, lung tumor, lymphangioleiomyomatosis, motor neuron disease, heart failure and bronchiolitis obliterans syndrome. The results showed significant correlation of the predicted global spirometry indicators (p<0.0001) and significant distinguishability between most disease groups and healthy subjects demonstrating the capability of the EIT system in diagnostic screening. Furthermore, the regional mapping of the spirometry indicators is evaluated and shown to be distinct for each disease group, providing an additional dimension for medical professionals to diagnose and monitor lung disease patients.Clinical Relevance- This establishes the significance of EIT-based global and regional indicators for assessing lung function on lung disease patients.

Portable electrical impedance tomography (EIT) system stages non-alcoholic fatty liver disease for potential screening and monitoring at home.

This study demonstrates the feasibility of predicting NAFLD using multi-spectral electrical impedance tomography (EIT), group source separation, constant reference EIT and anthropometric measures. Vibration-controlled Transient Elastography (VCTE) Controlled Attenuated Parameter (CAP; n = 121) and magnetic resonance imaging-proton density fat fraction (MRI-PDFF; n = 34) achieved a sensitivity of 70.9% and specificity of 73.8% with our CAP predicting model and sensitivity of 77.8% and specificity of 80.0% with our MRI-PDFF predicting model. In summary, a portable EIT can be a cost-effective and self-administrable alternative for widespread home-based and community-based diagnostic screening and treatment monitoring of NAFLD.Clinical Relevance- Portable multi-spectral EIT system has the sensitivity and specificity to potentially unlock biomedical imaging in telemedicine for home-based and community-based screening, staging and monitoring for NAFLD.

Electric impedance tomography enables portable and non-invasive approach to screen and monitor chronic kidney disease.

Chronic kidney disease (CKD) is an escalating global health concern, and non-invasive means for early CKD detection is eagerly awaited. Here, we explore the potential of using home-based frequency-difference electrical impedance tomography (fdEIT) to evaluate CKD based on bio-conductivity characteristics. We performed bio-conductivity measurement in vivo paired with standard estimated glomerular filtration rate (eGFR) measurements on a N=126 CKD patients by EIT and traditional blood and urine tests, respectively. We developed an EIT processing pipeline that extracts the kidney regions from EIT images. We further developed a regression model and a CKD classification scheme. Our results showed a significant correlation between EIT-features and eGFR, and the classification scheme shows sensitivity and specificity of 76.2% and 74.6% respectively considering stages 1 and 2 CKD versus stages 3, 4 and 5 CKD. These results suggest the feasibility of EIT to be used as a portable, self-administrated and home-based approach for CKD early diagnostic screening and longitudinal monitoring.Clinical Relevance-The results presented here demonstrates a cost-effective, home-based and self-administrative screening process on chronic kidney disease patients, thereby enhancing the quality and area of possible application of telemedicine. By achieving this, the process presented here can relieve the burden of public health system.

Standalone electrical impedance tomography predicts spirometry indicators and enables regional lung assessment.

Electrical impedance tomography (EIT) is a bio-medical imaging modality that has several clinical applications namely for human lungs. Yet, its relationship with gold standard lung diagnostic tools including spirometry is not available. In this study, simultaneous EIT and spirometry measurements were collected for 14 healthy subjects who performed forced breathing paradigms of different efforts simulating a wide range of spirometry indicators. It is demonstrated that EIT can predict standard spirometry indicators over a wide dynamic range, with a potential sensitivity and specificity of 98% and 100%, respectively, in detecting obstructive patterns. It is also shown that EIT can provide a regional mapping of the spirometry indicator which are shown to be consistent with their corresponding global indicators. Overall, EIT can predict spirometry indicators and can assess regional lung health through parametric mapping. Clinical Relevance- This study shows that EIT can infer standard spirometry indicators and potentially assess regional lung health. Therefore, EIT can be used for screening, diagnosis, and monitoring of obstructive and resistive lung diseases.

Bio-conductivity characteristics of chronic kidney disease stages examined by portable frequency-difference electrical impedance tomography.

Chronic kidney disease (CKD) is an escalating global health concern, and non-invasive means for early CKD detection is eagerly awaited. Here, we explore the potential of using home-based frequency-difference electrical impedance tomography (fdEIT) to evaluate CKD based on bio-conductivity characteristics. We first verified the feasibility of using portable EIT capturing bio-conductivity in fresh pig kidneys ex vivo. We further performed bio-conductivity measurement in vivo paired with standard eGFR measurements on CKD patients by EIT and traditional blood test, respectively. Our results showed a significant correlation between renal bio-conductivity changes captured by fdEIT and standard eGFR scores. These results hold promise to be developed into a non-invasive and portable device for early CKD detection and longitudinal CKD treatment monitoring in clinical, community and home-based settings. Clinical Relevance - A novel non-invasive bio-conductivity approach was developed for CKD classification. The renal assessment with portable EIT device demonstrated the potential to ameliorate the detection and classification of CKD into a portable, accessible, self-administrable home-based process.

Unmixing multi-spectral electrical impedance tomography (EIT) predicts clinical-standard controlled attenuation parameter (CAP) for nonalcoholic fatty liver disease classification: a feasibility study.

Here, we tested the feasibility of predicting CAP with multi-spectral EIT. Conductivity and CAP were acquired from nonalcoholic fatty liver disease patients using a portable EIT system and vibration-controlled transient elastography (VCTE). We then used frequency-difference conductivity and waist-over-height as prediction features to estimate CAP and found an adj. R2 of 0.92. We further developed a novel prediction method by incorporating EIT spectral unmixing reconstruction and demonstrated an improvement in CAP estimation. Last, we optimized the EIT acquisition process by minimizing the total variance of the CAP estimator. Clinical Relevance: EIT can estimate clinical-standard liver disease classification. This portable EIT system is potentially cost-effective and self-administrable with short acquisition time (3 mins), while VCTE are costly and usually requires a trained personnel to operate with longer acquisition time (5-10 mins).

Affordable, portable and self-administrable electrical impedance tomography enables global and regional lung function assessment.

Accessibility of diagnostic screening and treatment monitoring devices for respiratory diseases is critical in promoting healthcare and reducing sudden complications and mortality. Spirometry is the standard for diagnosing and monitoring several lung diseases. However, it lacks regional assessment capabilities necessary for detecting subtle regional changes in certain diseases. It also requires challenging breathing maneuvers difficult for elderlies, children, and diseased patients. Here, we actualized an affordable, portable, and self-administrable electrical impedance tomography (EIT) system for home-based lung function assessment and telemedicine. Through simultaneous EIT-spirometry trials on healthy subjects, we demonstrated that our device can predict spirometry indicators over a wide range and can provide regional mapping of these indicators. We further developed a close-to-effortless breathing paradigm and tested it by longitudinally monitoring a COVID-19 discharged subject and two healthy controls with results suggesting the paradigm can detect initial deterioration followed by recovery. Overall, the EIT system can be widely applicable for lung function screening and monitoring both at homes and clinics.

Comparison of hearing thresholds obtained using pure-tone behavioral audiometry, the Cantonese Hearing in Noise Test (CHINT) and cortical evoked response audiometry.

CONCLUSION: Speech thresholds measured using Cantonese Hearing in Noise Test (CHINT) and cortical evoked response audiometry (CERA) thresholds were highly correlated with pure-tone behavioral results. Both tests are considered to provide good estimates of hearing thresholds and can be employed to confirm the degree of hearing loss in Cantonese-speaking communities. OBJECTIVES: This study aimed to evaluate how well a speech threshold obtained using a newly developed speech assessment tool (the CHINT) and CERA thresholds relate to pure-tone behavioral results and how the results compared in terms of their ability to predict hearing thresholds. SUBJECTS AND METHODS: Thirty adults with normal hearing to profound sensorineural hearing loss were tested. Speech thresholds were measured using the CHINT in four conditions: quiet, noise from the front, noise from the right, and noise from the left. CERA thresholds were measured at 0.5, 1, 2, and 4 kHz in both ears. RESULTS: Most participants had speech thresholds in quiet within+/-10 dB of pure-tone averages, and had CERA thresholds within+/-15 dB of pure-tone thresholds. Speech and CERA thresholds were highly correlated (p<0.01) with pure-tone behavioral thresholds.

Structures of eukaryotic ribosomal stalk proteins and its complex with trichosanthin, and their implications in recruiting ribosome-inactivating proteins to the ribosomes.

Ribosome-inactivating proteins (RIP) are RNA N-glycosidases that inactivate ribosomes by specifically depurinating a conserved adenine residue at the α-sarcin/ricin loop of 28S rRNA. Recent studies have pointed to the involvement of the C-terminal domain of the eukaryotic stalk proteins in facilitating the toxic action of RIPs. This review highlights how structural studies of eukaryotic stalk proteins provide insights into the recruitment of RIPs to the ribosomes. Since the C-terminal domain of eukaryotic stalk proteins is involved in specific recognition of elongation factors and some eukaryote-specific RIPs (e.g., trichosanthin and ricin), we postulate that these RIPs may have evolved to hijack the translation-factor-recruiting function of ribosomal stalk in reaching their target site of rRNA.

Occupational hearing loss: screening with distortion-product otoacoustic emissions.

Hearing assessment of applicants for occupational hearing loss compensation can be a time-consuming process. An accurate screening procedure that is sensitive to occupational hearing loss may have application in many situations. The present study developed distortion-product otoacoustic emission (DPOAE) screening criteria to identify subjects likely to meet the Hong Kong requirements for occupational hearing loss compensation, namely a bilateral sensorineural loss > or = 40 dB HL (average of 1000, 2000 and 3000 Hz). The screening criteria of 1500 and/or 2000 Hz, with a signal-to-noise ratio of > 0 or 3 dB, yielded high sensitivity and specificity. DPOAE measures therefore have the potential to accurately indicate possible occupational hearing loss. However, DPOAEs should be used as a screening tool only, as conventional puretone audiometry remains the more comprehensive measure of hearing sensitivity.

Accuracy of cortical evoked response audiometry in the identification of non-organic hearing loss.

Cortical evoked response audiometry (CERA) has been used to identify the presence of a non-organic component in cases where compensation for hearing disability is claimed. This study aims at verifying the magnitude of discrepancy between thresholds estimated by CERA and by pure-tone audiometry (PTA). Results from 204 claimants (408 ears) with reliable PTA and CERA records showed mean discrepancy values between PTA and CERAT of less than 5 dB at high frequencies. Over 83.2% of claimants had a CERAT and PTA threshold discrepancy within 10 dB. Results suggested that while CERA threshold measurement could not accurately predict PTA in all cases, it could still be used as an objective guideline to rule out the presence of a non-organic component in hearing disability compensation claimants.