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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 937 records · Page 52Linked to original sources

Virtual cortical resection reveals push-pull network control mechanism preceding seizure evolution

For approximately 20 million people with drug-resistant epilepsy, recurring, spontaneous seizures have a devastating impact on daily life. The efficacy of surgical treatment for controlling seizures is hindered by a poor understanding of how some seizures spread to and synchronize surrounding tissue while others remain focal. To pinpoint network regions that regulate seizure evolution, we present a novel method to assess changes in synchronizability in response to virtually lesioning cortical areas in a validated computational network model. In human patients implanted with electrocorticographic sensors, we apply our virtual cortical resection technique to time-varying functional networks and identify control regions that synchronize or desynchronize cortical areas using an antagonistic push-pull control scheme to raise or lower synchronizability. Our results suggest that synchronizability before seizures predicts seizure evolution: in focal seizures, the strongest controllers are located outside seizure-generating areas. These methods,while applied here to epilepsy, are generalizable to other brain networks, and have wide applicability in isolating and mapping functional drivers of brain dynamics in health and disease.

Neuroscience

Analysis of behavioral variables across domains and strains in zebrafish: Role of brain monoamines

Important neurochemical variations between strains or linages which correlate with behavioral differences have been identified in different species. Here, we report neurochemical and behavioral differences in four common zebrafish wild-type phenotypes (blue shortfin, longfin stripped, leopard and albino). Leopad zebrafish have been shown to display increased scototaxis in relation to the other strains, while both albino and leopard zebrafish show increased geotaxis. Moreover, leopard displayed increased nocifensive behavior, while albino zebrafish showed increased neophobia in the novel object task. Longfin zebrafish showed decreased turn frequency in both the novel tank and light/dark tests, and habituated faster in the novel tank, as well as displaying increased 5-HT levels. Leopard zebrafish showed decreased brain 5-HT levels and increased 5-HT turnover than other strains, and albino had increased brain DA levels. Finally, specific behavioral endpoints co-varied in terms of the behavioral and neurochemical differences between strains, identifying cross-test domains which included response to novelty, exploration-avoidance, general arousal, and activity.

Neuroscience

α4-containing GABAA receptors on dopamine D2 receptor-expressing neurons mediate instrumental responding for conditioned reinforcers, and its potentiation by cocaine

AbstractExtrasynaptic GABAA receptors (GABAARs) composed of 4, {beta} and {delta} subunits mediate GABAergic tonic inhibition and are pertinent molecular targets in the modulation of behavioural responses to drugs of abuse, including ethanol and cocaine. These GABAARs are highly expressed within the nucleus accumbens (NAc) where they influence the excitability of the medium spiny neurons (MSNs). Here we explore their role in modulating behavioural responses to reward-conditioned cues and the behaviour-potentiating effects of cocaine. 4-subunit constitutive knockout mice (4-/-) showed higher rates of instrumental responding for reward-paired stimuli in a test of conditioned reinforcement (CRf). A similar effect was seen following viral knockdown of GABAAR 4 subunits within the NAc. Local infusion of the {delta}-GABAAR-preferring agonist, THIP, into the NAc had no effect on responding when given alone, but reduced cocaine potentiation of responding for conditioned reinforcers in wildtype but not 4-/- mice. Finally, specific deletion of 4-subunits from dopamine D2-, but not D1-receptor-expressing neurons, mimicked the phenotype of the constitutive knockout, potentiating CRf responding and blocking intra-accumbal THIP attenuation of cocaine-potentiated CRf responding. These data demonstrate that 4-GABAAR mediated inhibition of dopamine D2 receptor-expressing neurons reduces instrumental-responding for a conditioned reinforcer, and its potentiation by cocaine, and emphasise the potential importance of GABAergic signalling within the NAc in mediating cocaines effects.

Neuroscience

A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging

Imaging is used to map activity across populations of neurons. Microscopes with cellular resolution have small (< 1 millimeter) fields of view and cannot simultaneously image activity distributed across multiple brain areas. Typical large field of view microscopes do not resolve single cells, especially in the axial dimension. We developed a 2-photon random access mesoscope (2p-RAM) that allows high-resolution imaging anywhere within a volume spanning multiple brain areas (O 5 mm x 1 mm cylinder). 2p-RAM resolution is near diffraction limited (lateral, 0.66 m, axial 4.09 m at the center; excitation wavelength = 970 nm; numerical aperture = 0.6) over a large range of excitation wavelengths. A fast threedimensional scanning system allows efficient sampling of neural activity in arbitrary regions of interest across the entire imaging volume. We illustrate the use of the 2p-RAM by imaging neural activity in multiple, non-contiguous brain areas in transgenic mice expressing protein calcium sensors.

Neuroscience

fMRI evidence of equivalent neural suppression by repetition and prior knowledge

Stimulus repetition speeds behavioral responding (behavioral priming) and is accompanied by suppressed neural responses (repetition suppression; RS) that have been observed up to three days after initial exposure. While some proposals have suggested the two phenomena are linked, behavioral priming has been observed many years after initial exposure, whereas RS is widely considered a transitory phenomenon. This raises the question: what is the true upper limit of RS persistence? To answer this question, we scanned healthy, English-native adults with fMRI as they viewed novel (Asian) proverbs, recently repeated (Asian) proverbs, and previously known (English) proverbs that were matched on various dimensions. We then estimated RS by comparing repeated or previously known proverbs against novel ones. Multivariate analyses linked previously known and repeated proverbs with statistically indistinguishable RS in a broad visual-linguistic network. In each suppressed region, prior knowledge and repetition also induced a common shift in functional connectivity, further underscoring the similarity of the RS phenomenon induced by these conditions. By contrast, activated regions readily distinguished prior knowledge and repetition conditions in a manner consistent with engagement of semantic and episodic memory systems, respectively. Our results illustrate that regardless of whether RS is understood in terms of its magnitude, spatial extent or functional connectivity profile, typical RS effects can be elicited even under conditions where recently triggered biological processes or episodic memory are unlikely to play a prominent role. These results provide important new evidence that RS (of the kind observed after an interval of at least several minutes) reflects the facilitation of perceptual and comprehension processes by any type of information retrieved from long-term memory.

Neuroscience

Detailed dendritic excitatory/inhibitory balance through heterosynaptic spike-timing-dependent plasticity

Balance between excitatory and inhibitory inputs is a key feature of cortical dynamics. Such balance is arguably preserved in dendritic branches, yet its underlying mechanism and functional roles remain unknown. Here, by considering computational models of heterosynaptic spike-timing-dependent plasticity (STDP), we show that the detailed excitatory/inhibitory balance on dendritic branch is robustly achieved through heterosynaptic interaction between excitatory and inhibitory synapses. The model well reproduces experimental results on heterosynaptic STDP, and provides analytical insights. Furthermore, heterosynaptic STDP explains how maturation of inhibitory neurons modulates selectivity of excitatory neurons in critical period plasticity of binocular matching. Our results propose heterosynaptic STDP as a critical factor in synaptic organization and resultant dendritic computation.\n\nSignificance statementRecent experimental studies have revealed that relative spike timings among neighboring Glutamatergic and GABAergic synapses on a dendritic branch significantly influences changes in synaptic efficiency of these synapses. This heterosynaptic form of spike-timing-dependent plasticity (STDP) is potentially important for shaping the synaptic organization and computation of neurons, but its functional role remains elusive. Here, through computational modeling, we show that heterosynaptic plasticity causes the detailed balance between excitatory and inhibitory inputs on the dendrite, at the parameter regime where previous experimental results are well reproduced. Our result reveals a potential principle of GABA-driven neural circuit formation.

Neuroscience

Dopaminergic neurons modulate locomotion in Caenorhabditis elegans

Adaptation in the sensory-mechanical loop during locomotion is a powerful mechanism that allows organisms to survive in different conditions and environments. Motile animals need to alter motion patterns in different environments. For example, crocodiles and other animals can walk on solid ground but switch to swimming in water beds. The nematode Caenorhabditis elegans also shows adaptability by employing thrashing behaviour in low viscosity media and crawling in high viscosity media. The mechanism that enables this adaptability is an active area of research. It has been attributed previously to neuro-modulation by dopamine and serotonin.\n\nThe aim of this study is to physiologically investigate the neuronal mechanisms of modulation of locomotion by dopamine. The results suggest that the mechanosensory properties of the dopaminergic neurons PDE are not limited to touch sensation, but to surrounding environment resistance as well. The significance of such characterization is improving our understanding of dopamine gait switching which gets impaired in Parkinsons disease.

Neuroscience

Distinct combinations of variant ionotropic glutamate receptors mediate thermosensation and hygrosensation in Drosophila

Ionotropic Receptors (IRs) are a large subfamily of variant ionotropic glutamate receptors present across Protostomia. While these receptors are most extensively studied for their roles in chemosensory detection in insects, recent work has implicated two family members, IR21a and IR25a, in thermosensation in Drosophila. Here we characterize one of the most deeply conserved receptors, IR93a, and show that it is co-expressed and functions with IR21a and IR25a to mediate physiological and behavioral responses to cool temperatures. IR93a is also co-expressed with IR25a and a distinct receptor, IR40a, in a discrete population of sensory neurons in the sacculus, a multi-chambered pocket within the antenna. We demonstrate that this combination of receptors is important for neuronal responses to dry air and behavioral discrimination of humidity differences. Our results identify IR93a as a common component of molecularly and cellularly distinct IR pathways underlying thermosensation and hygrosensation in insects.

Neuroscience

Dnmts mediate neural processing after odor learning in the honeybee

DNA methyltransferases (Dnmts)-epigenetic writers catalyzing the transfer of methyl-groups to cytosine-regulate stimulus-specific olfactory long-term memory (LTM) formation and extinction in honeybees. The physiological relevance of their function in neural networks, however, remains unknown. Here, we investigated how Dnmts impact neuroplasticity in the bees primary olfactory center, the antennal lobe (AL) an equivalent of the olfactory bulb of vertebrates. The AL is crucial for odor discrimination, an indispensable process in stimulus-specific LTM. Using pharmacological inhibition, we show that Dnmts promote fast odor pattern separation in trained bees. We show Dnmt activity during memory formation increases both the number of responding glomeruli and the response magnitude to a novel odor. These data suggest that Dnmts are necessary for a form of homoeostatic network control which might involve inhibitory interneurons in the AL network and demonstrate that Dnmts influence neural network properties during memory formation in vivo.

Neuroscience

Anticorrelation between default and dorsal attention networks varies across default subsystems and cognitive states

Anticorrelation between the default network (DN) and dorsal attention network (DAN) is thought to be an intrinsic aspect of functional brain organization reflecting competing functions. However, the stability of anticorrelations across distinct DN subsystems, different contexts, and time, remains unexplored. Here we examine DN-DAN functional connectivity across six different cognitive states. We show that:(i) the DAN is anticorrelated with the DN core subsystem, but not with the two DN subsystems involved in mentalizing and mnemonic functions, respectively; (ii) DN-DAN interactions vary significantly across cognitive states; (iii) DN-DAN connectivity fluctuates across time between periods of anticorrelation and periods of positive correlation; and (iv) coupling between the frontoparietal control network (FPCN) and DAN predicts variation in the strength of DN-DAN anticorrelation across time. These findings reveal substantial variability in DN-DAN interactions, suggesting that these networks are not strictly competitive, and that the FPCN may act to modulate their anticorrelation strength.

Neuroscience

Age-Related Delay in Visual and Auditory Evoked Responses is Mediated by White- and Gray-matter Differences

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white- and gray-matter in a large (N=617, 18-88yrs), population-derived cohort (www.cam-can.org) to investigate the relationship between age-related structural differences and VEF and AEF delay across two different tasks. Using a novel technique, we show that VEFs exhibit a constant delay, whereas AEPs exhibit delay that accumulates over time. Visual delay is mediated by white-matter microstructure in the optic radiation, presumably reflecting increased transmission time, whereas auditory delay is mediated by gray-matter differences in auditory cortex, presumably reflecting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy.

Neuroscience

Task demands affect spatial reference frame weighting during tactile localization in sighted and congenitally blind adults

Task demands modulate tactile localization in sighted humans, presumably through weight adjustments in the spatial integration of anatomical, skin-based, and external, posture-based information. In contrast, previous studies have suggested that congenitally blind humans, by default, refrain from automatic spatial integration and localize touch using only skin-based information. Here, sighted and congenitally blind participants localized tactile targets on the palm or back of one hand, while ignoring simultaneous tactile distractors at congruent or incongruent locations on the other hand. We probed the interplay of anatomical and external location codes for spatial congruency effects by varying hand posture: the palms either both faced down, or one faced down and one up. In the latter posture, externally congruent target and distractor locations were anatomically incongruent and vice versa. Target locations had to be reported either anatomically (\"palm\" or \"back\" of the hand), or externally (\"up\" or \"down\" in space). Under anatomical instructions, performance was better for anatomically congruent than incongruent target-distractor pairs. In contrast, under external instructions, performance was better for externally congruent than incongruent pairs. These modulations were evident in sighted and blind individuals. Notably, distractor effects were overall far smaller in blind than in sighted participants, despite comparable target-distractor identification performance. Thus, the absence of developmental vision seems to be associated with an increased ability to focus tactile attention towards a non-spatially defined target. Nevertheless, that blind individuals exhibited effects of hand posture and task instructions in their congruency effects suggests that, like the sighted,, they automatically integrate anatomical and external information during tactile localization. Moreover, spatial integration in tactile processing is, thus, flexibly adapted by top-down information - here, task instruction - even in the absence of developmental vision.

Neuroscience

The human thalamus is an integrative hub for functional brain networks

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that the human thalamus displays network properties capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate heteromodal information and maintain the modular structure of cortical functional networks.

Neuroscience

Functional connectivity in neuromuscular system underlying bimanual muscle synergies

Neural synchrony has been suggested as mechanism for integrating distributed sensorimotor systems involved in coordinated movement. To test the role of corticomuscular and intermuscular coherence in the formation of bimanual muscle synergies, we experimentally manipulated the degree of coordination between hand muscles by varying the sensitivity of the visual feedback to differences in bilateral force. In 16 healthy participants, cortical activity was measured using 64-channel electroencephalography (EEG) and muscle activity of the flexor pollicis brevis muscle of both hands using 8x8-channel high-density electromyography (HDsEMG). Using the uncontrolled manifold framework, coordination between bilateral forces was quantified by the synergy index RV in the time and frequency domain. Functional connectivity was assed using corticomuscular coherence between muscle activity and cortical source activity and intermuscular coherence between bilateral EMG activity. As expected, bimanual synergies were stronger in the high coordination condition. RV was higher in the high coordination condition in frequencies between 0 and 0.5 Hz, and above 2 Hz. For the 0.5-2 Hz frequency band this pattern was inverted. Corticomuscular coherence in the beta band (16-30 Hz) was maximal in the contralateral motor cortex and was reduced in the high coordination condition. In contrast, intermuscular coherence was observed at 5-12 Hz and increased with bimanual coordination. Within-subject comparisons revealed a negative correlation between RV and corticomuscular coherence and a positive correlation between RV and intermuscular coherence. Our findings suggest two distinct neural pathways: (1) Corticomuscular coherence reflects direct corticospinal projections involved in controlling individual muscles; (2) intermuscular coherence reflects diverging pathways involved in the coordination of multiple muscles.

Neuroscience

The Human Octopus: controlling supernumerary hands with the help of virtual reality

We investigated the \"human octopus\" phenomenon where subjects controlled virtual supernumerary hands through hand tracking technology and virtualreality. Four experiments were developed to study how subjects (n=10) operate with different number and behaviour of supernumerary hands. The behaviours involved inserting movement delays to the virtual hands and adjustingtheir movement scale or position. It was found that having more hands to operate with does not necessarily mean higher success rate while performinga certain task. However, supernumerary hands could bemade more effective by adjusting the associated movement scales of the extra hands. The subjective feeling and ownership of the hands diminished when a delay was inserted for the virtual hands or when their position was altered.

Neuroscience

Predicting future learning from baseline network architecture

Human behavior and cognition result from a complex pattern of interactions between brain regions. The flexible reconfiguration of these patterns enables behavioral adaptation, such as the acquisition of a new motor skill. Yet, the degree to which these reconfigurations depend on the brains baseline sensorimotor integration is far from understood. Here, we asked whether spontaneous fluctuations in sensorimotor networks at baseline were predictive of individual differences in future learning. We analyzed functional MRI data from 19 participants prior to six weeks of training on a new motor skill. We found that visual-motor connectivity was inversely related to learning rate: sensorimotor autonomy at baseline corresponded to faster learning in the future. Using three additional scans, we found that visual-motor connectivity at baseline is a relatively stable individual trait. These results suggest that individual differences in motor skill learning can be predicted from sensorimotor autonomy at baseline prior to task execution.\n\nHighlightsO_LISensorimotor autonomy at rest predicts faster motor learning in the future.\nC_LIO_LIConnection between calcarine and superior precentral sulci form strongest predictor.\nC_LIO_LISensorimotor autonomy is a relatively stable individual trait.\nC_LI

Neuroscience

Can pornography be addictive? An fMRI study of men seeking treatment for problematic pornography use.

Pornography consumption is highly prevalent, particularly among young adult males. For some individuals, problematic pornography use (PPU) is a reason for seeking treatment. Despite the pervasiveness of pornography, PPU appears under-investigated, including with respect to the underlying neural mechanisms.\n\nUsing functional magnetic resonance imaging (fMRI), we examined ventral striatal responses to erotic and monetary stimuli, disentangling cue-related wanting from reward-related liking among 28 heterosexual males seeking treatment for PPU and 24 heterosexual males without PPU. Subjects engaged in an incentive delay task in the scanner, in which they received erotic or monetary rewards preceded by predictive cues. BOLD responses to erotic and monetary cues were analyzed and examined with respect to self-reported data on sexual activity collected over the 2 preceding months.\n\nMen with and without PPU differed in their striatal responses to cues predicting erotic pictures, but not in their responses to erotic pictures. PPU subjects when compared to control subjects showed increased activation of ventral striatum specifically for cues predicting erotic pictures but not for cues predicting monetary gains. Relative sensitivity to cues predicting erotic pictures versus monetary gains was significantly related to the increased behavioral motivation to view erotic images (suggestive of higher wanting), severity of PPU, amount of pornography use per week and number of weekly masturbations.\n\nOur findings suggest that, similar to what is observed in substance and gambling addictions, the neural and behavioral mechanisms associated with the anticipatory processing of cues specifically predicting erotic rewards relate importantly to clinically relevant features of PPU. These findings suggest that PPU may represent a behavioral addiction and that interventions helpful in targeting behavioral and substance addictions warrant consideration for adaptation and use in helping men with PPU.

Neuroscience

Decoding of generic mental representations from functional MRI data using word embeddings

Several different groups have demonstrated the feasibility of building forward models of functional MRI data in response to concrete stimuli such as pictures or video, and of using these models to decode or reconstruct stimuli shown while acquiring test fMRI data. In this paper, we introduce an approach for building forward models of conceptual stimuli, concrete or abstract, and for using these models to carry out decoding of semantic information from new imaging data. We show that this approach generalizes to topics not seen in training, and provides a straightforward path to decoding from more complex stimuli such as sentences or paragraphs.

Neuroscience