bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generators of the frequency-following response in the subthalamic nucleus: implications for non-invasive deep brain stimulation
Authors: Hnazaee Mansoureh Fahimi , Zhao Haifeng , Hao Shenglin , Moorkens Aline , Lambert Christian , Zhan Shikun , Li Dianyou , Sun Bomin , Litvak Vladimir , Cao Chunyan 
Published: May 2024

AbstractWhile Deep Brain Stimulation (DBS) is effective treatment for several movement disorders, non-invasive stimulation modes have major clinical relevance. We report on a novel method holding potential for non-invasive subthalamic nucleus (STN) stimulation. We used an auditory frequency-following response task (FFR), a popular tool for studying the auditory brainstem as the neural response in the cortical and midbrain generator, as it precisely reflects the ongoing dynamics of a speech or non-speech sound. We recorded EEG and DBS electrodes from 5 patients, in 4 from the STN, and one from the anterior thalamus and a number of cortical and subcortical areas located in the hippocampus and frontal regions, during an FFR at a frequency higher than the upper limit of phase-locking in the cortex (333Hz). Our results revealed a neural response local to the STN, but not other structures. This finding is novel. Auditory perception in the basal ganglia is rather unexplored, and the STN generator of the FFR has likely gone unseen due to the limitations of our tools and research focus. The potential clinical implications are far-reaching. Future research should investigate whether auditory stimuli at common electrical stimulation frequencies and waveforms of electrical DBS stimulation can induce clinical improvement.
Endogenous opioid system modulates proximal and distal threat signals in the human brain
Authors: Seppälä Kerttu , Putkinen Vesa , Harju Harri , Rebelos Eleni , Hirvonen Jussi , Helin Semi , Rajander Johan , Karlsson Henry K. , Saunavaara Jani , Hyönä Jukka , Nummenmaa Lauri 
Published: May 2024

AbstractBACKGROUNDFear promotes rapid detection of threats and appropriate fight-or-flight responses. The endogenous opioid system modulates responses to pain and psychological stressors. Opioid agonists also have also anxiolytic effects. Fear and anxiety constitute major psychological stressors for humans, yet the contribution of the opioid system to acute human fear remains poorly characterized.METHODSWe induced intense unconditioned fear in the subjects by gradually exposing them to a living constrictor snake (threat trials) versus an indoor plant (safety trials). Brain haemodynamic responses were recorded from 33 subjects during functional magnetic resonance imaging (fMRI). In addition, 15 subjects underwent brain positron emission tomography (PET) imaging using [11C]carfentanil, a high affinity agonist radioligand for μ-opioid receptors (MORs). PET studies under threat or safety exposure were performed on separate days. Pupillary arousal responses to snake and plant exposure were recorded in 36 subjects. Subjective fear ratings were measured throughout the experiments.RESULTSSelf-reports and pupillometric responses confirmed significant experience of fear and autonomic activation during the threat trials. fMRI data revealed that proximity with the snake robustly engaged brainstem defense circuits as well as thalamus, dorsal attention network, and motor and premotor cortices. These effects were diminished during repeated exposures. PET data revealed that [11C]carfentanil binding to MORs was significantly higher during the fear versus safety condition, and the acute haemodynamic responses to threat were dependent on baseline MOR binding in the cingulate gyrus and thalamus. Finally, baseline MOR tone predicted dampening of the haemodynamic threat responses during the experiment.CONCLUSIONSPreparatory response during acute fear episodes involves a strong motor component in addition to the brainstem responses. These haemodynamic changes are coupled with a deactivation of the opioidergic circuit, highlighting the role of MORs in modulating the human fear response.
A survival-critical role forDrosophilagiant interneurons during predation
Authors: Chai Cynthia M. , Morrow Carmen M. , Parikh Dhyey D. , von Reyn Catherine R. , Leonardo Anthony , Card Gwyneth M. 
Published: May 2024

ABSTRACTLarge axon-diameter descending neurons are metabolically costly but transmit information rapidly from sensory neurons in the brain to motor neurons in the nerve cord. They have thus endured as a common feature of escape circuits in many animal species where speed is paramount. Though often considered isolated command neurons triggering fast-reaction-time, all-or-none escape responses, giant neurons are just one of multiple parallel pathways enabling selection between behavioral alternatives. Such degeneracy among escape circuits makes it unclear if and how giant neurons benefit prey fitness. Here we competedDrosophila melanogasterflies with genetically-silenced Giant Fibers (GFs) against flies with functional GFs in an arena with wild-caught damselfly predators and find that GF silencing decreases prey survival. Kinematic analysis of damselfly attack trajectories shows that decreased prey survival fitness results from GF-silenced flies failing to escape during predator attack speeds and approach distances that would normally elicit successful escapes. When challenged with a virtual looming predator, fly GFs promote survival by enforcing selection of a short-duration takeoff sequence as opposed to reducing reaction time. Our findings support a role for the GFs in promoting prey survival by influencing action selection as a means to enhance escape performance during realistically complex predation scenarios.
Voluntary adolescent alcohol exposure does not robustly increase adulthood consumption of alcohol in multiple mouse and rat models
Authors: Sicher Avery R. , Liss Andrea , Vozella Valentina , Marsland Paige , Seemiller Laurel R. , Springer Matthew , Starnes William D. , Griffith Keith R. , Smith Grace C. , Astefanous Amy , Deak Terrence , Roberto Marisa , Varodayan Florence P. , Crowley Nicole A. 
Published: May 2024

ABSTRACTAdolescence is a period of increased risk taking, including increased alcohol and drug use. Multiple clinical studies report a positive relationship between adolescent alcohol consumption and risk of developing an alcohol use disorder (AUD) in adulthood. However, few preclinical studies have attempted to tease apart the biological contributions of adolescent alcohol exposure, independent of other social, environmental, and stress factors, and studies that have been conducted show mixed results. Here we use several adolescent voluntary consumption of alcohol models, conducted across four labs in three institutes and with two rodent species, to investigate the ramifications of adolescent alcohol consumption on adulthood alcohol consumption in controlled, pre-clinical environments. We consistently demonstrate a lack of robust increases in adulthood alcohol consumption. This work highlights that risks seen in both human datasets and other murine drinking models may be due to unique social and environmental factors – some of which may be unique to humans.HIGHLIGHTSAdolescent drinking-in-the-dark (DID) binge drinking does not increase adulthood consumption in a DID model or a two bottle choice model in male and female SST-Cre:Ai9 miceAdolescent pair-housed intermittent access consumption of alcohol does not increase adulthood consumption in an identical adulthood model in male and female C57BL/6J miceAdolescent intermittent access to alcohol does not increase adulthood consumption in male and female Wistar or Fischer 344 ratsThese complementary datasets across murine models, labs and institutions highlight the need to consider human social factors as well as biological factors
Connectivity at fine scale: mapping structural connective fields by tractography of short association fibresin vivo
Authors: Attar Fakhereh Movahedian , Kirilina Evgeniya , Edwards Luke J. , Haenelt Daniel , Pine Kerrin J. , Trampel Robert , Chaimow Denis , Weiskopf Nikolaus 
Published: May 2024

SummaryThe extraordinary number of short association fibres (SAF) connecting neighbouring cortical areas is a prominent feature of the large gyrified human brain. The contribution of SAF to the human connectome is largely unknown because of methodological challenges in mapping them. We present a method to characterise cortico–cortical connectivity mediated by SAF in topologically organised cortical areas. We introduce the ‘structural connective fields’ (sCF) metric which specifically quantifies neuronal signal propagation and integration mediated by SAF. This new metric complements functional connective field metrics integrating across contributions from short- and long-range white matter and intracortical fibres. Applying the method in the human early visual processing stream, we show that SAF preserve cortical functional topology. Retinotopic maps of V2 and V3 could be predicted from retinotopy in V1 and SAF connectivity. The sCF sizes increased along the cortical hierarchy and were smaller than their functional counterparts, in line with the latter being additionally broadened by long-range and intracortical connections.In vivosCF mapping provides insights into short-range cortico– cortical connectivity in humans comparable to tract tracing studies in animal research and is an essential step towards creating a complete human connectome.HighlightsNon-invasive mapping of Short Association Fibre (SAF) connectivity via diffusion-weighted MRI-based probabilistic tractography accurately predicted cortical functional neuroanatomy.The novel structural Connective Fields (sCF) concept provides a quantitative measure of cortico-cortical integration facilitated by SAF, complementing the existing functional Connective Field (CF) concept.Sub-millimeter resolution diffusion-weighted MRI enables tractography and connective field modeling of SAF, unlocking applications previously restricted to invasive tract tracing in animal studies.
Unveiling the crucial role of betaine: Modulation of GABA homeostasis via SLC6A1 transporter (GAT1)
Authors: Bhatt Manan , Lazzarin Erika , Alberto-Silva Ana Sofia , Domingo Guido , Zerlotti Rocco , Gradisch Ralph , Bazzone Andre , Sitte Harald H. , Stockner Thomas , Bossi Elena 
Published: May 2024

AbstractBetaine is an endogenous osmolyte that exhibits therapeutic potential by mitigating various neurological disorders. However, the underlying cellular and molecular mechanisms responsible for its neuroprotective effects remain puzzling.In this study, we describe a possible mechanism behind the positive impact of betaine in preserving neurons from excitotoxicity. Using electrophysiology, mass spectroscopy, radiolabelled cellular assay, and molecular dynamics simulation we demonstrate that betaine at mM concentration acts as a slow substrate of GAT1 (slc6a1), the predominant GABA transporter in the central nervous system. Intriguingly, when betaine is present at low concentration (0.01-3 mM) with GABA (at concentration <K0.5), it blocks the GABA reuptake. This GAT1 modulation occurs through the temporal inhibition of the transporter, i.e., the prolonged occupancy by betaine impedes the rapid transition of the transporter to the inward conformation. The temporal inhibition results in a crucial regulatory mechanism contributing to the maintenance of GABA homeostasis, preserving neurons from excitotoxicity.
Excitatory and inhibitory synapses form a tight subcellular balance along dendrites that decorrelates over development
Authors: Horton Sally , Mastrolia Vincenzo , Jackson Rachel , Kemlo Sarah , Pereira Machado Pedro M. , Carbajal Maria Alejandra , Hindges Robert , Fleck Roland A. , Aguiar Paulo , Neves Guilherme , Burrone Juan 
Published: May 2024

SummaryA balance between excitation and inhibition is crucial for neurotypical brain function. Indeed, disruptions in this relationship are frequently associated with the pathophysiology of neurodevelopmental disorders. Nevertheless, how this balance is established during the dynamic period of neurodevelopment remains unexplored. Using multiple techniques, includingin uteroelectroporation, electron microscopy and electrophysiology, we reveal a tight correlation in the distribution of excitatory and inhibitory synapses along dendrites of developing CA1 hippocampal neurons. This balance was present within short dendritic stretches (<20µm), and surprisingly, was most pronounced during early development, sharply declining with maturity. The tight matching between excitation and inhibition was unexpected, as inhibitory synapses lacked an active zone when formed and exhibited compromised evoked release. We propose that inhibitory synapses form as a stabilising scaffold, to counterbalance growing excitation levels. This relationship diminishes over time, suggesting a critical role for a subcellular balance in early neuronal function and circuit formation.
Feeling Senseless Sensations: A Crossmodal study of mismatching tactile and virtual visual experience
Authors: Lehser Caroline , Hillyard Steven A. , Strauss Daniel J. 
Published: May 2024

AbstractTo create highly immersive experiences in virtual reality (VR) it is important to not only include the visual sense but also to involve multimodal sensory input. To achieve optimal results, the temporal and spatial synchronization of these multimodal inputs is critical. It is therefore necessary to find methods to objectively evaluate the synchronization of VR experiences with a continuous tracking of the user. In this study a passive touch experience was incorporated in a visual–tactile VR setup using VR glasses and tactile sensations in mid–air. Inconsistencies of multimodal perception were intentionally integrated into a discrimination task. The participants’ electroencephalogram (EEG) was recorded to obtain neural correlates of visual-tactile mismatch situations. The results showed significant differences in the event-related potentials (ERP) between match and mismatch situations. A biphasic ERP configuration consisting of a positivity at 120 ms and a later negativity at 370 ms was observed following a visual–tactile mismatch. This late negativity could be related to the N400 that is associated with semantic incongruency. These results provide a promising approach towards the objective evaluation of visual–tactile synchronization in virtual experiences.
Heart-brain coupling and its relevance for individual trait characteristics
Authors: Karjalainen Suvi , Kujala Jan , Aro Tuija , Parviainen Tiina 
Published: May 2024

AbstractA bulk of recent neurophysiological research has focused on how bodily functions are intertwined with neural activity, but the dynamic heart-brain coupling and its relevance for individual trait characteristics remains largely unexamined. Thus, our aim was to investigate how ongoing oscillatory brain activity is modulated by the natural fluctuations in heart rate variability (HRV). We further explored whether heart-brain coupling is associated with individual trait characteristics. Magnetoencephalography (MEG) together with electrocardiography (ECG) were used to record neural activity and HRV during rest. Self-reported trait characteristics were examined using Behavioral Inhibition and Activation Systems Scale (BIS/BAS) and attunement to internal bodily sensations using Body Vigilance Scale (BVS). Statistically significant increases were observed for low HRV vs. high HRV state in alpha and beta power (p< 0.05) indicating that oscillatory brain activity is modulated by fluctuations in HRV. Moreover, we demonstrated that heart-brain coupling was associated with self-reported behavioral approach and avoidance tendencies. The results of the moderator analysis further indicated that the relationship between heart-brain coupling and trait characteristics is at least partly moderated by the attunement to internal bodily sensations. Our findings bring insights to the intricate interplay between cardiac and neural signaling and its relationship with individual trait characteristics.HighlightsOscillatory brain activity is modulated by the natural fluctuations in HRVAlpha and beta power increase during states of lower parasympathetic activityHeart-brain coupling is linked with self-reported individual trait characteristicsThis association is influenced by the attunement to the internal bodily milieu
The retina’s neurovascular unit: Müller glial sheaths and neuronal contacts
Authors: Grimes William N. , Berson David M. , Sabnis Adit , Hoon Mrinalini , Sinha Raunak , Tian Hua , Diamond Jeffrey S. 
Published: May 2024

SummaryThe neurovascular unit (NVU), comprising vascular, glial and neural elements, supports the energetic demands of neural computation, but this aspect of the retina’s trilaminar vessel network is poorly understood. Only the innermost vessel layer – the superficial vascular plexus (SVP) – is ensheathed by astrocytes, like brain capillaries, whereas glial ensheathment in other layers derives from radial Müller glia. Using serial electron microscopy reconstructions from mouse and primate retina, we find that Müller processes cover capillaries in a tessellating pattern, mirroring the tiled astrocytic endfeet wrapping brain capillaries. However, gaps in the Müller sheath, found mainly in the intermediate vascular plexus (IVP), permit different neuron types to contact pericytes and the endothelial cells directly. Pericyte somata are a favored target, often at spine-like structures with a reduced or absent vascular basement lamina. Focal application of adenosine triphosphate (ATP) to the vitreal surface evoked Ca2+signals in Müller sheaths in all three vascular layers. Pharmacological experiments confirmed that Müller sheaths express purinergic receptors that, when activated, trigger intracellular Ca2+signals that are amplified by IP3-controlled intracellular Ca2+stores. When rod photoreceptors die in a mouse model of retinitis pigmentosa (rd10), Müller sheaths dissociate from the deep vascular plexus (DVP) but are largely unchanged within the IVP or SVP. Thus, Müller glia interact with retinal vessels in a laminar, compartmentalized manner: glial sheathes are virtually complete in the SVP but fenestrated in the IVP, permitting direct neural-to-vascular contacts. In the DVP, the glial sheath is only modestly fenestrated and is vulnerable to photoreceptor degeneration.
A function of Spalt proteins in heterochromatin organization and maintenance of genomic DNA integrity
Authors: Ostalé Cristina M. , Azpiazu Natalia , Peropadre Ana , Martín Mercedes , Ruiz-Losada Mireya , López-Varea Ana , Viales Rebecca R. , Girardot Charles , Furlong Eileen E.M. , de Celis Jose F. 
Published: May 2024

ABSTRACTThe phylogenetically conserved Spalt proteins regulate gene expression and participate in a variety of cell fate choices during multicellular development, generally acting as transcriptional repressors in different gene regulatory networks. Paradoxically, besides their roles as DNA sequence-specific transcription factors, Spalt proteins show a consistent localization to heterochromatic regions. They can act through interactions with the Nucleosome remodeling and deacetylase complex (NuRD) to promote closing of open chromatin domains, but their activities as epigenetic regulators also rely on interactions with DNA Methyltransferases or with the Lysine-specific histone demethylase LSD1, suggesting that they can participate in multiple regulatory mechanisms. Here we describe several major consequences of loss ofspaltfunction inDrosophilacells, including changes in chromatin accessibility affecting mostly pericentromeric heterochromatin, the generation of DNA damage, alterations in the localization of chromosomes within the nucleus in polyploid cells of the salivary glands and miss-expression of transposable elements. We suggest that most of these effects are related to roles of Spalt proteins in the regulation of heterochromatin formation. We propose thatDrosophilaSpalt proteins have two complementary functions, acting as sequence-specific transcriptional repressors on specific target genes and regulating more global gene silencing through the generation or maintenance of heterochromatic domains.
Lateral Prefrontal Theta Oscillations Causally Drive a Computational Mechanism Underlying Conflict Expectation and Adaptation
Authors: Martínez-Molina María Paz , Valdebenito-Oyarzo Gabriela , Soto-Icaza Patricia , Zamorano Francisco , Figueroa-Vargas Alejandra , Carvajal-Paredes Patricio , Stecher Ximena , Salinas César , Valero-Cabré Antonie , Polania Rafael , Billeke Pablo 
Published: May 2024

AbstractAdapting our behavior to environmental demands relies on our capacity to perceive and manage potential conflicts within our surroundings. While evidence implicates the involvement of the lateral prefrontal cortex and theta oscillations in detecting conflict stimuli, their roles in conflict expectation remain elusive. Consequently, the exact computations and neural mechanisms underlying these cognitive processes still need to be determined. To address this gap, we employed an integrative approach involving cognitive computational modeling, fMRI, TMS, and EEG. Our results revealed a computational process underlying conflict expectation, which correlated with activity in the superior frontal gyrus (SFG). Furthermore, rhythmic TMS in the theta range applied over the SFG, but not over the inferior frontal junction, induced endogenous theta activity, enhancing computations associated with conflict expectation. These findings provide compelling evidence for the causal involvement of SFG theta activity in learning and allocating cognitive resources to address forthcoming conflict stimuli.Significant StatementAlterations in the processing of expectations of conflict events have been associated with several neuropsychiatric disorders that significantly affect the quality of life for many individuals. This article describes a cognitive computation underlying the conflict expectation and its causal neural mechanism involving theta brain activity in the superior frontal gyrus (SFG). Thus, unraveling this mechanism holds promise for developing interventions to address cognitive alterations related to anticipation of conflict events in neuropsychiatric disorders, improving overall cognitive function and quality of life.