bioRxiv Subject Collection: Neuroscience's Journal
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Saturday, December 16th, 2023
| Time |
Event |
| 12:17a |
Learning regular cross-trial shifts of the target location in serial search involves awareness: an eye-tracking study
People can learn, and utilize, not only static but also dynamic (cross-trial) regularities in the positioning of target items in parallel, pop-out visual search. However, while static target-location learning also works in serial search, acquiring dynamic regularities seems prevented by the demands imposed by item-by-item scanning. Also, questions have been raised regarding a role of explicit awareness for utilizing (at least) dynamic regularities to optimize performance. The present study re-investigated whether dynamic regularities may be learned in serial search when regular shifts of the target location occur frequently, and whether such learning would correlate with awareness of the dynamic rule. To this end, we adopted the same regularity used by Yu et al. (2023) to demonstrate dynamic learning in parallel search: a cross-trial shift of the target location in, e.g., clockwise direction within a circular array in 80% of the trials, which was compared to irregular shifts in the opposite (e.g., counterclockwise; 10%) or some other, random direction (10%). The results showed that two-thirds of participants learned the dynamic regularity, with their performance gains correlating with awareness: the more accurately they estimated how likely the target shifted in the frequent direction, the greater their gains. Importantly, part of the gains accrued already early during search: a large proportion of the very first and short-latency eye movements was directed to the predicted location, whether or not the target appeared there. We discuss whether this rule-driven behavior is causally mediated by conscious control. (248 words). | | 3:45a |
Contributions of tactile information to the sense of agency and its metacognitive representations
We compared the contribution of tactile information to other sources of information in our representations of agency. Participants (N = 40) reached with their right hand toward a ridged plate with a specific orientation and saw online feedback that could match or differ from their action in one of three ways: the physical plate's orientation, the action's timing, or the hand's position in space. Absolute subjective ratings revealed that an increased mismatch in tactile information led to a diminished sense of agency, similar to what has been reported for spatial and temporal mismatches. Further, estimations of metacognitive efficiency revealed similar M-ratios in the identification of tactile violation predictions as compared to temporal violations (but lower than spatial). These findings emphasize the importance of tactile information in shaping our experience of acting voluntarily, and show how this important component can be experimentally probed. | | 3:45a |
miR-519a-3p, found to regulate cellular prion protein during Alzheimer's disease pathogenesis, as a biomarker of asymptomatic stages
MiRNAs induce post-transcriptional gene silencing by binding to the 3'-UTR of complementary messenger RNAs and causing either degradation or inhibition of translation. The clinical relevance of miRNAs as biomarkers is growing due to their stability and detection in biofluids. In this sense, diagnosis at asymptomatic stages of Alzheimer's disease (AD) remains a challenge since it can only be made at autopsy according to Braak NFT staging. Achieving the objective of detecting AD at early stages would allow possible therapies to be addressed before the onset of cognitive impairment. Many studies have determined that the expression pattern of some miRNAs is deregulated in AD patients, but to date, none has been correlated with downregulated expression of cellular prion protein (PrPC) during disease progression. That is why, by means of cross studies of miRNAs up-regulated in AD with in silico identification of potential miRNAs-binding to 3'UTR of human PRNP gene, we selected miR-519a-3p for our study. Other family members of miR-519 have been shown to bind to the 3'UTR region of PRNP in vitro and presumably degrade PRNP mRNA. In addition, up-regulation of some of them has been reported in various tissues from AD patients, including cerebrospinal fluid, plasma, and blood serum. In fact, miR-519d-3p is marked as a bridge regulator between mild cognitive impairment and severe AD. However, none of the studies address the prodromal stages of the disease or the expression profile of miR-519 in other neurodegenerative diseases that also may present dementia. Therefore, in this study we analyzed miR-519a-3p expression in cerebral samples of AD at different stages of evolution as well as other neurodegenerative diseases such as other tauopathies and synucleinopathies. Our results show the specific and early up-regulation of miR-519a-3p starting from Braak stage I of AD, suggesting its potential use as a biomarker of preclinical stages of the disease. | | 8:31p |
Neuronal Avalanches in Naturalistic Speech and Music Listening
Neuronal avalanches are cascade-like events ubiquitously observed across imaging modalities and scales. Aperiodic timing and topographic distribution of these events have been related to the systemic physiology of brain states. However, it is still unknown whether neuronal avalanches are correlates of cognition, or purely reflect physiological properties. In this work, we investigate this question by analyzing intracranial recordings of epileptic participants during rest and passive listening of naturalistic speech and music stimuli. During speech or music listening, but not rest, participants' brains "tick" together, as the timing of neuronal avalanches is stimulus-driven and hence correlated across participants. Auditory regions are strongly participating in coordinated neuronal avalanches, but also associative regions, indicating both the specificity and distributivity of cognitive processing. The subnetworks where such processing takes place during speech and music largely overlap, especially in auditory regions, but also diverge in associative cortical sites. Finally, differential pathways of avalanche propagation across auditory and non-auditory regions differentiate brain network dynamics during speech, music and rest. Overall, these results highlight the potential of neuronal avalanches as a neural index of cognition. | | 8:31p |
Aberrant Connectivity Across the Lifespan in a Mouse Model of Alzheimer's disease and Rescue by mGlur5 Modulator Treatment
Amyloid accumulation in Alzheimer's disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD (AppNL-G-F/hMapt), monitoring brain connectivity by means of resting-state fMRI. While the 4-month-old AD mice are indistinguishable from wild-type controls (WT), decreased connectivity in the default-mode network is significant for the AD mice relative to WT mice by 6 months of age and is pronounced by 9 months of age. In a second cohort of 20-month-old mice with persistent functional connectivity deficits for AD relative to WT, we assess the impact of two-months of oral treatment with a silent allosteric modulator of mGluR5 (BMS-984923) known to rescue synaptic density. Functional connectivity deficits in the aged AD mice are reversed by the mGluR5-directed treatment. The longitudinal application of fMRI has enabled us to define the preclinical time trajectory of AD-related changes in functional connectivity, and to demonstrate a translatable metric for monitoring disease emergence, progression, and response to synapse-rescuing treatment. | | 8:31p |
Frequency-dependent phase entrainment of cortical cell types during tACS: Converging modeling evidence
Background: Transcranial alternating current stimulation (tACS) enables non-invasive modulation of brain activity, holding promise for clinical and research applications. Yet, it remains unclear how the stimulation frequency affects various neuron types. Objective: To quantify the frequency-dependent behavior of key neocortical cell types. Methods: We used both detailed (anatomical multicompartments) and simplified (three compartments) single-cell modeling approaches based on the Hodgkin-Huxley formalism to study neocortical excitatory and inhibitory cells under various-amplitude tACS frequencies within the 5-50 Hz range at rest and during basal 10 Hz activity. Results: L5 pyramidal cells (PC) exhibited the highest polarizability at DC, ranging from 0.21 to 0.25 mm and decaying exponentially with frequency. Inhibitory neurons displayed membrane resonance in the 5-15 Hz range with lower polarizability, although bipolar cells had higher polarizability. Layer 5 PC demonstrated the highest entrainment close to 10 Hz, which decayed with frequency. In contrast, inhibitory neurons entrainment increased with frequency, reaching level akin to PC. Results from simplified models could replicate the phase preferences, while amplitudes tend to follow opposite trends in PC. Conclusion: tACS-induced membrane polarization is frequency-dependent, revealing observable resonance behavior. This finding motivates further experimental studies of cell-specific frequency-dependent membrane responses to weak electric stimuli. Whilst optimal phase entrainment of sustained activity is achieved in PC when tACS frequency matches the activity, inhibitory neurons tend to be entrained at higher frequencies. Consequently, this presents the potential for precise, cell-specific targeting. | | 9:45p |
Locus Coeruleus Norepinephrine Neurons Facilitate Orbitofrontal Cortex Remapping and Behavioral Flexibility
To guide behavior, brain regions such as the orbitofrontal cortex (OFC) retain complex information about current tasks and expected outcomes in cellular representations referred to as cognitive maps. When actions produce undesirable results, OFC cognitive maps must update to promote behavioral change. Here, we show that this remapping is driven by the locus coeruleus (LC), a small brainstem nucleus that contains most of the brain's norepinephrine (NE)-releasing neurons. In a task that tests behavioral flexibility in rodents, LC-NE activity correlated with task acuity and altered depending on trial outcome. Silencing LC neurons caused perseverative behavior and impeded cognitive remapping in OFC, while enhancing LC activity disrupted the ability of new maps to stabilize. These findings reveal a novel role for bidirectional LC-NE signaling in regulation of OFC cognitive map stability and promotion of flexible behavior that differs from the traditional function of this circuit as a global arousal signal. |
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