PaperPlayer biorxiv neuroscience

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551722v1?rss=1 Authors: Tunca, M. B., Rezaki, A., Nizamoglu, H., Urgen, B. A. Abstract: Perceptual load theory argues that attention is a limited resource and stimuli cannot be processed if there is insufficient perceptual capacity available. Although attention is known to modulate biological motion processing, whether this modulation differs among different perceptual loads remains unknown. To answer this question, three experiments are conducted in which biological motion is utilized as a task-irrelevant distractor. The first experiment showed that biological motion is processed differently than non-biological motion across different perceptual load conditions. The second experiment investigated the effect of attention on biological motion processing, revealing that higher eccentricities enhance biological motion processing but only when the perceptual load is low. The last experiment investigated the same question but with cortically magnified stimuli. It found that when the stimuli are cortically magnified, the enhancement effect of eccentricity is present regardless of the perceptual load. Overall, the results suggest that perceptual load modulates the processing of task-irrelevant biological motion and interacts with other factors (such as eccentricity) that modulate this processing. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551706v1?rss=1 Authors: Perez, C. I., Luis-Islas, J., Lopez, A., Diaz, X., Molina, O., Arroyo, B., Moreno, M. G., Lievana, E. G., Fonseca, E., Castaneda-Hernandez, G., Gutierrez, R. Abstract: Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target GLP-1 receptors have recently come to the market. Here we describe the effects of tesofensine, a novel anti-obesity drug that acts as a triple monoamine neurotransmitter reuptake inhibitor. We investigated its effects on weight loss and underlying neuronal mechanisms in mice and rats using various techniques. These include behavioral tasks, DeepLabCut videotaped analysis, electrophysiological ensemble recordings, optogenetic activation, and chemogenetic silencing of GABAergic neurons in the Lateral Hypothalamus (LH). We found that tesofensine induced greater weight loss in obese than lean rats, which was associated with changes in LH ensemble activity. In Vgat-ChR2 and Vgat-IRES-cre transgenic mice, we found for the first time that tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior, and chemogenetically silencing them enhanced tesofensine's food-suppressing effects. Unlike phentermine, a dopaminergic appetite suppressant, tesofensine causes few, if any, head-weaving stereotypy at therapeutic doses. Most importantly, we found that tesofensine prolonged the weight loss induced by 5-HTP, a serotonin precursor, and blocked the body weight rebound that often occurs after weight loss. Behavioral studies on rats with the tastant sucrose indicated that tesofensine's appetite suppressant effects are independent of taste aversion and do not directly affect the perception of sweetness or palatability of sucrose. In summary, our data provide new insights into the effects of tesofensine on weight loss and the underlying neuronal mechanisms, suggesting that tesofensine may be an effective treatment for obesity and that it may be a valuable adjunct to other appetite suppressants to prevent body weight rebound. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551576v1?rss=1 Authors: Kashyap, S., Oliveira, I. A. F., Uludag, K. Abstract: Cerebral blood flow (CBF) is a critical physiological parameter of brain health, and it can be non-invasively measured with arterial spin labelling (ASL) MRI. In this study, we evaluated and optimized whole-brain, high-resolution ASL as an alternative to the low-resolution ASL employed in the routine assessment of CBF in both healthy participants and patients. Two high-resolution protocols (i.e., pCASL and FAIR-Q2TIPS (PASL) with 2 mm isotropic voxels) were compared to a default clinical pCASL protocol (3.4x3.4x4 mm3), all of whom had an acquisition time of {approx} 5 min. We assessed the impact of high-resolution acquisition on reducing partial voluming and improving sensitivity to the perfusion signal, and evaluated the effectiveness of z-deblurring on the ASL data. We compared the quality of whole-brain ASL acquired using three available head coils with differing numbers of receive channels (i.e., 20, 32, and 64 ch). In conclusion, this study demonstrates the feasibility of high-spatial resolution whole-brain ASL within the clinical scanning duration, offering higher spatial fidelity and resolving power than those obtained with current standard clinical ASL protocols. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551583v1?rss=1 Authors: Guedj, C., Tyrand, R., Badier, E., Planchamp, L., Stringer, M., Zimmermann, M. O., Ferat, V., Ha-Vinh Leuchter, R., Grouiller, F. Abstract: Attention is a crucial cognitive function that enables us to selectively focus on relevant information from the surrounding world to achieve our goals. When this sustained ability to direct attention is impaired, individuals face significant challenges in everyday life. This is the case for children with Attention Deficit Hyperactivity Disorder (ADHD), a complex neurodevelopmental disorder characterized by impulsive and inattentive behavior. While psychostimulant medications are currently the most effective treatment for ADHD, they often come with unwanted side effects, and sustaining the benefits can be difficult for many children. Therefore, it is imperative to explore non-pharmacological treatments that offer longer-lasting outcomes. Here, we proposed a groundbreaking protocol that combines electroencephalography-based neurofeedback (EEG-NFB) with virtual reality (VR) as an innovative approach to treating attention deficits. By integrating a virtual classroom environment, we aimed to enhance the transferability of attentional control skills while simultaneously increasing motivation and interest among children. The present study demonstrated the feasibility of this approach through an initial assessment involving a small group of healthy children, showcasing its potential for future evaluation in children diagnosed with ADHD. Encouragingly, the preliminary findings indicated high engagement rates and positive feedback from the children participating in the study. Additionally, the pre- and post-protocol assessments using EEG and fMRI recordings appeared to converge towards an improvement in attentional function. Although further validation is required to establish the efficacy of the proposed protocol, it represents a significant advancement in the field of neurofeedback therapy for ADHD. The integration of EEG-NFB and VR presents a novel avenue for enhancing attentional control and addressing behavioral challenges in children with ADHD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551607v1?rss=1 Authors: Jiang, S., Chen, L., Qu, W.-M., Huang, Z.-L., Chen, C.-R. Abstract: General anesthetics benefit patients undergoing surgeries without consciousness, but the undesired stress response associated with general anesthesia (GA) causes delayed recovery and even increased morbidity in the clinic. Here, a core hypothalamic ensemble, corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVHCRH neurons) is discovered, which regulates the anesthetic effects and post-anesthesia stress response of sevoflurane GA. Chemogenetic activation of these neurons delay the induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition exert the opposite effects. Moreover, optogenetic stimulation of PVHCRH neurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVHCRH neurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These findings identify a common neural substrate integrating the anesthetic effect and post-anesthesia stress response of sevoflurane GA. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551631v1?rss=1 Authors: Hahn, A., Reed, M. B., Vraka, C., Godbersen, G. M., Klug, S., Komorowski, A., Falb, P., Nics, L., Traub-Weidinger, T., Hacker, M., Lanzenberger, R. Abstract: Positron emission tomography (PET) provides precise molecular information on physiological processes, but its low temporal resolution is a major obstacle. Consequently, we characterized the metabolic response of the human brain to working memory performance using an optimized functional PET framework at a temporal resolution of 3 seconds. Consistent with simulated kinetic modeling, we observed a constant increase in the [18F]FDG signal during task execution, followed by a rapid return to baseline after stimulation ceased. The simultaneous acquisition of BOLD fMRI revealed that the temporal coupling between hemodynamic and metabolic signals in the primary motor cortex was related to individual behavioral performance during working memory. Furthermore, task-induced BOLD deactivations in the posteromedial default mode network were accompanied by distinct temporal patterns in glucose metabolism, which depended on the task-positive network metabolic demands. In sum, the proposed approach enables the advancement from parallel to truly synchronized investigation of metabolic and hemodynamic responses during cognitive processing. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551859v1?rss=1 Authors: Di Antonio, G., Raglio, S., Mattia, M. Abstract: A general mathematical description of the way the brain encodes ordinal knowledge of sequences is still lacking. Coherently with the well-established idea of mixed selectivity in high-dimensional state spaces, we conjectured the existence of a linear solution for serial learning tasks. In this theoretical framework, the neural representation of the items in a sequence are read out as ordered projections along a suited "geometric" mental line learned via classical conditioning (delta rule learning). We show that the derived model explains all the behavioral effects observed in humans and other animal species performing the transitive inference task in presence of noisy sensory information and stochastic neural activity. This result is generalized to the case of recurrent neural networks performing motor decision, where the same geometric mental line is learned showing a tight correlation with the motor plan of the responses. Network activity is then eventually modulated according to the symbolic distance of presented item pairs, as observed in associative cortices of nonhuman primates. Serial ordering is thus predicted to emerge as a linear mapping between sensory input and behavioral output, highlighting a possible pivotal role of motor-related associative cortices in the transitive inference task. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.552059v1?rss=1 Authors: Christie, J. M., Yang, Z., Zhang, K., Gaffield, M. A., Gross, G. G., Arnold, D. B. Abstract: Climbing fibers supervise cerebellar learning by providing signals to Purkinje cells (PCs) that instruct adaptive changes to mistakenly performed movements. Yet, climbing fibers are regularly active, even during well performed movements, suggesting that a mechanism dynamically regulates the ability of climbing fibers to induce corrective plasticity in response to motor errors. We found that molecular layer interneurons (MLIs), whose inhibition of PCs powerfully opposes climbing-fiber-mediated excitation, serve this function. Optogenetically suppressing the activity of floccular MLIs in mice during the vestibulo-ocular reflex (VOR) induces a learned increase in gain despite the absence of performance errors. Suppressing MLIs when the VOR is mistakenly underperformed reveled that their inhibitory output is necessary to orchestrate gain-increase learning by conditionally permitting climbing fibers to instruct plasticity induction during ipsiversive head turns. Ablation of an MLI circuit for PC disinhibition prevents gain-increase learning during VOR performance errors which was rescued by re-imposing PC disinhibition through MLI activity suppression. Our findings point to a decisive role for MLIs in gating climbing-fiber-mediated learning through their context-dependent inhibition of PCs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551865v1?rss=1 Authors: Turpin, T., Uluc, I., Lankinen, K., Mamashli, F., Ahveninen, J. Abstract: Working memory (WM) reflects the transient maintenance of information in the absence of external input, which can be attained via multiple senses separately or simultaneously. Pertaining to WM, the prevailing literature suggests the dominance of vision over other sensory systems. However, this imbalance may be attributed to challenges of finding stimuli that are represented in comparable ways across modalities. Here, we addressed this methodological problem by using a balanced multisensory "retro-cue" WM design. The to-be-memorized stimuli consisted of combinations of auditory (ripple sounds) and visuospatial (Gabor patches) patterns, which have been shown to undergo similar transformations during WM encoding and retrieval. Using a staircase procedure, the auditory ripple velocities and spatial frequencies of Gabor patches were adjusted relative to each participant's just noticeable differences (JND) separately in each modality, before the main task. The task was to audiovisually compare the probes to the memorized items. In randomly ordered trials, the probe either fully matched or differed from the memory item auditorily, visually, or audiovisually. The participants correctly rejected a significantly larger number of auditory non-match probes than visual non-match probes. Our findings suggest that, in the case of inter-sensory competition during feature maintenance, auditory attributes of multisensory WM items can be retrieved more precisely than their visual counterparts when complexity of the content and task demands are bimodally equated. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551950v1?rss=1 Authors: Goupell, M. J., Stecker, G. C., Williams, B. T., Bilokon, A., Tollin, D. J. Abstract: The interaural time difference (ITD) is a primary horizontal-plane sound localization cue computed in the auditory brainstem. ITDs are accessible in the temporal fine structure of pure tones with a frequency of no higher than about 1400 Hz. Explaining how listeners' ITD sensitivity transitions from very best sensitivity near 700 Hz to impossible to detect within 1 octave currently lacks a clear physiological explanation. Here, it was hypothesized that the rapid decline in ITD sensitivity is dictated not to a central neural limitation but by initial peripheral sound encoding, specifically, the low-frequency edge of the cochlear excitation pattern produced by a pure tone. To test this hypothesis, ITD sensitivity was measured in 16 normal-hearing listeners as a joint function of frequency (900-1500 Hz) and level (10-50 dB sensation level). Performance decreased with increasing frequency and decreasing sound level. The slope of performance decline was 90 dB/octave, consistent with the low-frequency slope of the cochlear excitation pattern. Consequently, fine-structure ITD sensitivity near 1400 Hz may be conveyed primarily by "off-frequency" activation of neurons tuned to lower frequencies near 700 Hz. Physiologically, this could be realized by a single narrow channel near 700 Hz that conveys fine-structure ITDs. Such a model is a major simplification and departure from the classic formulation of the binaural display, which consists of a matrix of neurons tuned to a wide range of relevant frequencies and ITDs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551937v1?rss=1 Authors: Luciani, M., Garsia, C., Beretta, S., Petiti, L., Peano, C., Merelli, I., Cifola, I., Miccio, A., Meneghini, V., Gritti, A. Abstract: Human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NSCs) are a promising source for cell therapy approaches to treat neurodegenerative and demyelinating disorders. Despite ongoing efforts to characterize hiPSC-derived cells in vitro and in vivo, we lack comprehensive genome- and transcriptome-wide studies addressing hiPSC-NSC identity and safety, which are critical for establishing accepted criteria for prospective clinical applications. Here, we evaluated the transcriptional and epigenetic signatures of hiPSCs and differentiated hiPSC-NSC progeny, finding that the hiPSC-to-NSC transition results in a complete loss of pluripotency and the acquisition of a radial glia-associated transcriptional signature. Importantly, hiPSC-NSCs share with somatic human fetal NSCs (hfNSCs) the main transcriptional and epigenetic patterns associated with NSC-specific biology. In vivo, long-term observation (up to 10 months) of mice intracerebrally transplanted as neonates with hiPSC-NSCs showed robust engraftment and widespread distribution of human cells in the host brain parenchyma. Engrafted hiPSC-NSCs displayed multilineage potential and preferentially generated glial cells. No hyperproliferation, tumor formation, or expression of pluripotency markers was observed. Finally, we identified a novel role of the Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) in the regulation of astroglial commitment of hiPSC-NSCs. Overall, these comprehensive in vitro and in vivo analyses provide transcriptional and epigenetic reference datasets to define the maturation stage of NSCs derived from different hiPSC sources, and to clarify the safety profile of hiPSC-NSCs, supporting their continuing development as an alternative to somatic hfNSCs in treating neurodegenerative and demyelinating disorders. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551861v1?rss=1 Authors: Kerstein, P. C., Santana Agreda, Y., Curran, B. M., Ma, L., Wright, K. M. Abstract: Within the neuronal classes of the retina, amacrine cells (ACs) exhibit the greatest neuronal diversity in morphology and function. We show that the selective expression of the transcription factor Gbx2 is required for cell fate specification and dendritic stratification of an individual AC subtype in the mouse retina. We identify Robo1 and Robo2 as downstream effectors that when deleted, phenocopy the dendritic misprojections seen in Gbx2 mutants. Slit1 and Slit2, the ligands of Robo receptors, are localized to the OFF layers of the inner plexiform layer where we observe the dendritic misprojections in both Gbx2 and Robo1/2 mutants. We show that Robo receptors also are required for the proper dendritic stratification of additional AC subtypes, such as Vglut3+ ACs. These results show both that Gbx2 functions as a terminal selector in a single AC subtype and identify Slit-Robo signaling as a developmental mechanism for ON-OFF pathway segregation in the retina. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551886v1?rss=1 Authors: Vo, V. A., Jain, S., Beckage, N., Chien, H.-Y. S., Obinwa, C., Huth, A. G. Abstract: Deep learning advances have revolutionized computational modeling approaches in neuroscience. However, their black-box nature makes it challenging to use deep learning models to discover new insights about brain function. Focusing on human language processing, we propose a new framework to improve the quality and interpretability of the inferences we make from deep learning-based models. First, we add interpretable components to a deep language model and use it to build a predictive encoding model. Then, we use the model's predictive abilities to simulate brain responses to controlled stimuli from published experiments. We find that our model, based on a multi-timescale recurrent neural network, captures many previously reported temporal context effects in human cortex. Its failure to capture other effects also highlights important gaps in current language models. Finally, we use this new framework to generate model-based evidence that supports the proposal that different linguistic features are represented at different timescales across cortex. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551829v1?rss=1 Authors: Berto, M., Reisinger, P., Ricciardi, E., Weisz, N., Bottari, D. Abstract: The processing of stationary sounds relies on both local features and compact representations. As local information is compressed into summary statistics, abstract representations emerge. Whether the brain is endowed with distinct neural architectures overseeing such computations is unknown. In this magnetoencephalography (MEG) study, we employed a validated protocol to localize cortical correlates of local and summary representations, exposing participants to triplets of synthetic sound textures systematically varying for either local details or summary statistics. Sounds also varied for their sound duration, specifically short (40ms) or long (478ms). Results revealed clear distinct activation patterns for local features and summary statistics changes. Such activations diverged in magnitude, spatiotemporal distribution, and hemispheric lateralization. For short sounds, a change in local features, compared to summary statistics, predominantly activated the right hemisphere. Conversely, for long sounds, a change in summary statistics elicited higher activation than a change in local features in both hemispheres. Specifically, while the right auditory cortex was responding more to changes in local features or summary statistics depending on sound duration (short or long, respectively), the left frontal lobe was selectively engaged in processing a change in summary statistics at a long sound duration. These findings provide insights into the neural mechanisms underlying the computation of local and summary acoustic information and highlight the involvement of distinct cortical pathways and hemispheric lateralization in auditory processing at different temporal resolutions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551983v1?rss=1 Authors: Schnupp, J. W., Buchholz, S., Buck, A. N., Budig, H. K., Khurana, L., Rosskothen-Kuhl, N. Abstract: Cochlear implants (CIs) have restored enough of a sense of hearing to around one million severely hearing impaired patients to enable speech understanding in quiet. However, several aspects of hearing with CIs remain very poor. This includes a severely limited ability of CI patients to make use of interaural time difference (ITD) cues for spatial hearing and noise reduction. A major cause for this poor ITD sensitivity could be that current clinical devices fail to deliver ITD information in a manner that is accessible to the auditory pathway. CI processors measure the envelopes of incoming sounds and then stimulate the auditory nerve with electrical pulse trains which are amplitude modulated to reflect incoming sound envelopes. The timing of the pulses generated by the devices is largely or entirely independent of the incoming sounds. Consequently, bilateral CIs (biCIs) provide veridical envelope (ENV) ITDs but largely or entirely replace the "fine structure" ITDs that naturally occur in sounds with completely arbitrary electrical pulse timing (PT) ITDs. To assess the extent to which this matters, we devised experiments that measured the sensitivity of deafened rats to precisely and independently controlled PT and ENV ITDs for a variety of different CI pulse rates and envelope shapes. We observed that PT ITDs completely dominate ITD perception, while the sensitivity to ENV ITDs was almost negligible in comparison. This strongly suggests that the confusing yet powerful PT ITDs that contemporary clinical devices deliver to biCI patients may be a major cause of poor binaural hearing outcomes with biCIs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC