The Enhanced-Deep-Super-Resolution (EDSR) model is a state-of-art convolutional neural network suitable for improving image spatial resolution. It was previously trained with general-purpose pictures and then, in this work, tested on biomedical Magnetic Resonance (MR) images, comparing the network outcomes with traditional up-sampling techniques. We explored possible changes in the model response when different MR sequences were analyzed. T1w and T2w MR brain images of 70 human healthy subjects (F:M 40:30) from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) repository were down-sampled and then up-sampled using EDSR model and BiCubic (BC) interpolation. Several reference metrics were used to quantitatively assess the performance of up-sampling operations (RMSE, pSNR, SSIM and HFEN). Two-dimensional and three-dimensional reconstructions were evaluated. Different brain tissues were analyzed individually. The EDSR model was superior to BC interpolation on the selected metrics, both for two- and th...

Intracerebral hemorrhage (ICH), the most common subtype of hemorrhagic stroke, leads to cognitive impairment and imposes significant psychological burdens on patients. Hippocampal neurogenesis has been shown to play an essential role in cognitive function. Our previous study has shown that tetrahydrofolate (THF) promotes the proliferation of neural stem cells (NSCs). However, the effect of THF on cognition after ICH and the underlying mechanisms remain unclear. Here, we demonstrated that administration of THF could restore cognition after ICH. Using Nestin-GFP mice, we further revealed that THF enhanced the proliferation of hippocampal NSCs and neurogenesis after ICH. Mechanistically, we found that THF could prevent ICH-induced elevated level of PTEN and decreased expressions of phosphorylated AKT and mTOR. Furthermore, conditional deletion of PTEN in NSCs of hippocampus attenuated the inhibitory effect of ICH on the proliferation of NSCs and abnormal neurogenesis. Taken together, these results provide mol...

Current theories of decision making propose that decisions arise through competition between choice options. Computational models of the decision process estimate how quickly information about choice options is integrated and how much information is needed to trigger a choice. Experiments using this approach typically report data from well-trained participants. As such, we do not know how the decision process evolves as a decision-making task is learned for the first time. To address this gap, we used a behavioral design separating learning the value of choice options from learning to make choices. We trained male rats to respond to single visual stimuli with different reward values. Then, we trained them to make choices between pairs of stimuli. Initially, the rats responded more slowly when presented with choices. However, as they gained experience in making choices, this slowing reduced. Response slowing on choice trials persisted throughout the testing period. We found that it was specifically associat...

What factors are associated with career outcomes among biomedical PhDs? Much of the research to-date has focused on drivers of interest in (and intention to pursue) various careers, especially during graduate school, but fewer studies have investigated participants’ ultimate career outcomes. Even less is known about what factors matter most for groups historically underrepresented in the US STEM workforce, such as women, some racial and ethnic groups, and persons with disabilities (National Center for Science and Engineering Statistics (NCSES), 2021a). This study reports a new analysis of data from 781 PhD neuroscientists that were obtained from a retrospective survey (Ullrich et al. (2021)) to investigate the factors that influence the career sector in which neuroscience PhDs are employed, and whether there were group differences according to social identity. We find evidence of academia as a “default path” for incoming PhD students, but interest in different careers increases gradually over time. Those w...

Retinal prosthetics are one of the leading therapeutic strategies to restore lost vision in patients with Retinitis Pigmentosa and age-related macular degeneration. Much work has described patterns of spiking in retinal ganglion cells (RGCs) in response to electrical stimulation, but less work has examined the underlying retinal circuitry that is activated by electrical stimulation to drive these responses. Surprisingly, little is known about the role of inhibition in generating electrical responses, or how inhibition might be altered during degeneration. Using whole-cell voltage clamp recordings during subretinal electrical stimulation in rd10 and wt retina, we found electrically evoked synaptic inputs differed between ON and OFF RGC populations, with ON cells receiving mostly excitation and OFF cells receiving mostly inhibition and very little excitation. We found that inhibition of OFF bipolar cells limits excitation in OFF RGCs, and a majority of both pre and post synaptic inhibition in the OFF pathway...

The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by cardiovascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anterior-to-posterior gradient of vulnerability to aging that may be altered by effects of cardiovascular health. In 174 healthy adults across the adult lifespan (mean age=53.56 ± 18.90, range=20-94 years old, 58.62% women), pulse pressure (calculated as participant's systolic minus diastolic blood pressure) was assessed to determine cardiovascular risk. A deterministic tractography approach via diffusion weighted imaging was utilized to extract fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General lin...

Norepinephrine (NE), a neuromodulator released by locus coeruleus (LC) neurons throughout cortex, influences arousal and learning through extra-synaptic vesicle exocytosis. While NE within cortical regions has been viewed as a homogenous field, recent studies have demonstrated heterogeneous axonal dynamics and advances in GPCR-based fluorescent sensors permit direct observation of the local dynamics of NE at cellular scale. To investigate how the spatiotemporal dynamics of NE release in the prefrontal cortex (PFC) affect neuronal firing, we employed in vivo two-photon imaging of layer 2/3 of PFC in order to observe fine-scale neuronal calcium and NE dynamics concurrently. In this proof of principle study, we found that local and global NE fields can decouple from one another, providing a substrate for local NE spatiotemporal activity patterns. Optic flow analysis revealed putative release and reuptake events which can occur at the same location, albeit at different times, indicating the potential to create...

Mismatch negativity (MMN) is commonly recognized as a neural signal of prediction error evoked by deviants from the expected patterns of sensory input. Studies show that MMN diminishes when sequence patterns become more predictable over a longer timescale. This implies that MMN is comprised of multiple subcomponents, each responding to different levels of temporal regularities. To probe the hypothesized subcomponents in MMN, we record human electroencephalography during an auditory local-global oddball paradigm where the tone-to-tone transition probability (local regularity) and the overall sequence probability (global regularity) are manipulated to control temporal predictabilities at two hierarchical levels. We find that the size of MMN is correlated with both probabilities and the spatiotemporal structure of MMN can be decomposed into two distinct subcomponents. Both subcomponents appear as negative waveforms, with one peaking early in the central-frontal area and the other late in a more frontal area. ...

Historically, the orbitofrontal cortex (OFC) has been implicated in a variety of behaviors ranging from reversal learning and inhibitory control to more complex representations of reward value and task space. While modern interpretations of the OFC's function have focused on a role in outcome evaluation, these cognitive processes often require an organism to inhibit a maladaptive response or strategy. Single unit recordings from the OFC in rats performing a stop-change task show that the OFC responds strongly to STOP trials. To investigate the role that the OFC plays in stop-change performance we expressed halorhodopsin (eNpHR3.0) in excitatory neurons in the OFC and tested rats on the stop-change task. Previous work suggests that the OFC differentiates between STOP trials based on trial sequence (i.e., gS trials: STOP trials preceded by a GO versus sS trials: STOP trials preceded by a STOP). We found that yellow light activation of the eNpHR3.0 expressing neurons significantly decreased accuracy only on S...

Mismatch negativity (MMN) is commonly recognized as a neural signal of prediction error evoked by deviants from the expected patterns of sensory input. Studies show that MMN diminishes when sequence patterns become more predictable over a longer timescale. This implies that MMN is composed of multiple subcomponents, each responding to different levels of temporal regularities. To probe the hypothesized subcomponents in MMN, we record human electroencephalography during an auditory local–global oddball paradigm where the tone-to-tone transition probability (local regularity) and the overall sequence probability (global regularity) are manipulated to control temporal predictabilities at two hierarchical levels. We find that the size of MMN is correlated with both probabilities and the spatiotemporal structure of MMN can be decomposed into two distinct subcomponents. Both subcomponents appear as negative waveforms, with one peaking early in the central-frontal area and the other late in a more frontal area. W...