Enhancement Of Neural Activity Research Articles

Recurrent neural networks that learn multi-step visual routines with reinforcement learning.

Many cognitive problems can be decomposed into series of subproblems that are solved sequentially by the brain. When subproblems are solved, relevant intermediate results need to be stored by neurons and propagated to the next subproblem, until the overarching goal has been completed. We will here consider visual tasks, which can be decomposed into sequences of elemental visual operations. Experimental evidence suggests that intermediate results of the elemental operations are stored in working memory as an enhancement of neural activity in the visual cortex. The focus of enhanced activity is then available for subsequent operations to act upon. The main question at stake is how the elemental operations and their sequencing can emerge in neural networks that are trained with only rewards, in a reinforcement learning setting. We here propose a new recurrent neural network architecture that can learn composite visual tasks that require the application of successive elemental operations. Specifically, we selected three tasks for which electrophysiological recordings of monkeys' visual cortex are available. To train the networks, we used RELEARNN, a biologically plausible four-factor Hebbian learning rule, which is local both in time and space. We report that networks learn elemental operations, such as contour grouping and visual search, and execute sequences of operations, solely based on the characteristics of the visual stimuli and the reward structure of a task. After training was completed, the activity of the units of the neural network elicited by behaviorally relevant image items was stronger than that elicited by irrelevant ones, just as has been observed in the visual cortex of monkeys solving the same tasks. Relevant information that needed to be exchanged between subroutines was maintained as a focus of enhanced activity and passed on to the subsequent subroutines. Our results demonstrate how a biologically plausible learning rule can train a recurrent neural network on multistep visual tasks.

Postsynaptic neuronal activity promotes regeneration of retinal axons

The wiring of visual circuits requires that retinal neurons functionally connect to specific brain targets, a process that involves activity-dependent signaling between retinal axons and their postsynaptic targets. Vision loss in various ophthalmological and neurological diseases is caused by damage to the connections from the eye to the brain. How postsynaptic brain targets influence retinal ganglion cell (RGC) axon regeneration and functional reconnection with the brain targets remains poorly understood. Here, we established a paradigm in which the enhancement of neural activity in the distal optic pathway, where the postsynaptic visual target neurons reside, promotes RGC axon regeneration and target reinnervation and leads to the rescue of optomotor function. Furthermore, selective activation of retinorecipient neuron subsets is sufficient to promote RGC axon regeneration. Our findings reveal a key role for postsynaptic neuronal activity in the repair of neural circuits and highlight the potential to restore damaged sensory inputs via proper brain stimulation.

Trial-by-trial fluctuations in amygdala activity track motivational enhancement of desirable sensory evidence during perceptual decision-making.

People are biased toward seeing outcomes that they are motivated to see. For example, wanting their favored team to prevail biases sports fans to perceive an ambiguous foul in a manner that is favorable to the team they support. Here, we test the hypothesis that such motivational biases in perceptual decision-making are associated with amygdala activity. We used monetary incentives to experimentally manipulate participants to want to see one percept over another while they performed a categorization task involving ambiguous images. Participants were more likely to categorize an image as the category we motivated them to see, suggesting that wanting to see a particular percept biased their perceptual decisions. Heightened amygdala activity was associated with motivation consistent categorizations and tracked trial-by-trial enhancement of neural activity in sensory cortices encoding the desirable category. Analyses using a drift diffusion model further suggest that trial-by-trial amygdala activity was specifically associated with biases in the accumulation of sensory evidence. In contrast, frontoparietal regions commonly associated with biases in perceptual decision-making were not associated with motivational bias. Altogether, our results suggest that wanting to see an outcome biases perceptual decisions via distinct mechanisms and may depend on dynamic fluctuations in amygdala activity.

Short-Term Audiovisual Spatial Training Enhances Electrophysiological Correlates of Auditory Selective Spatial Attention.

Audiovisual cross-modal training has been proposed as a tool to improve human spatial hearing. Here, we investigated training-induced modulations of event-related potential (ERP) components that have been associated with processes of auditory selective spatial attention when a speaker of interest has to be localized in a multiple speaker (“cocktail-party”) scenario. Forty-five healthy participants were tested, including younger (19–29 years; n = 21) and older (66–76 years; n = 24) age groups. Three conditions of short-term training (duration 15 min) were compared, requiring localization of non-speech targets under “cocktail-party” conditions with either (1) synchronous presentation of co-localized auditory-target and visual stimuli (audiovisual-congruency training) or (2) immediate visual feedback on correct or incorrect localization responses (visual-feedback training), or (3) presentation of spatially incongruent auditory-target and visual stimuli presented at random positions with synchronous onset (control condition). Prior to and after training, participants were tested in an auditory spatial attention task (15 min), requiring localization of a predefined spoken word out of three distractor words, which were presented with synchronous stimulus onset from different positions. Peaks of ERP components were analyzed with a specific focus on the N2, which is known to be a correlate of auditory selective spatial attention. N2 amplitudes were significantly larger after audiovisual-congruency training compared with the remaining training conditions for younger, but not older, participants. Also, at the time of the N2, distributed source analysis revealed an enhancement of neural activity induced by audiovisual-congruency training in dorsolateral prefrontal cortex (Brodmann area 9) for the younger group. These findings suggest that cross-modal processes induced by audiovisual-congruency training under “cocktail-party” conditions at a short time scale resulted in an enhancement of correlates of auditory selective spatial attention.

Foreground-Background Segmentation Revealed during Natural Image Viewing.

One of the major challenges in visual neuroscience is represented by foreground-background segmentation. Data from nonhuman primates show that segmentation leads to two distinct, but associated processes: the enhancement of neural activity during figure processing (i.e., foreground enhancement) and the suppression of background-related activity (i.e., background suppression). To study foreground-background segmentation in ecological conditions, we introduce a novel method based on parametric modulation of low-level image properties followed by application of simple computational image-processing models. By correlating the outcome of this procedure with human fMRI activity, measured during passive viewing of 334 natural images, we produced easily interpretable “correlation images” from visual populations. Results show evidence of foreground enhancement in all tested regions, from V1 to lateral occipital complex (LOC), while background suppression occurs in V4 and LOC only. Correlation images derived from V4 and LOC revealed a preserved spatial resolution of foreground textures, indicating a richer representation of the salient part of natural images, rather than a simplistic model of object shape. Our results indicate that scene segmentation occurs during natural viewing, even when individuals are not required to perform any particular task.

Reduction of implicit cognitive bias with cathodal tDCS to the left prefrontal cortex.

Implicit associations can interfere with cognitive operations and behavioral decisions without direct intention. Enhancement of neural activity with anodal transcranial direct current stimulation (tDCS) was proposed to reduce implicit associations by means of improved cognitive control. However, a targeted reduction of distractive implicit associations by inhibitory cathodal tDCS, recently shown in spatial-numerical associations, provides an interesting alternative approach to support goal-directed behavior with transcranial brain stimulation. To test this rationale with a sham-controlled cross-over design, a standardized Implicit Association Test (IAT) was performed by 24 healthy participants parallel to 1 mA cathodal or sham tDCS to the left prefrontal cortex. In this double-classification task, insect versus flower pictures and negative versus positive words are mapped together onto two shared response keys with crossed response assignments in separate blocks. Responses were faster when insect + negative and flower + positive stimuli required the same answer (IAT effect). Most critically, the IAT effect was reduced during cathodal tDCS as compared to sham stimulation. Thus, results are consistent with the proposed stimulation rationale, with previous observations, and complementary to previous studies using different tDCS configurations.

The Synergistic Enhancing-Memory Effect of Donepezil and S 38093 (a Histamine H3 Antagonist) Is Mediated by Increased Neural Activity in the Septo-hippocampal Circuitry in Middle-Aged Mice.

Donepezil, an acetylcholinesterase inhibitor, induces only moderate symptomatic effects on memory in Alzheimer’s disease patients. An alternative strategy for treatment of cognitive symptoms could be to act simultaneously on both histaminergic and cholinergic pathways, to create a synergistic effect. To that aim, 14 month old C57/Bl6 mice were administered per oesophagy during nine consecutive days with Donepezil (at 0.1 and 0.3 mg/kg) and S 38093 (at 0.1, 0.3, and 1.0 mg/kg), a H3 histaminergic antagonist developed by Servier, alone or in combination and tested for memory in a contextual memory task that modelized the age-induced memory dysfunction. The present study shows that the combination of Donepezil and S 38093 induced a dose-dependent synergistic memory-enhancing effect in middle-aged mice with a statistically higher size of effect never obtained with compounds alone and without any pharmacokinetic interaction between both compounds. We demonstrated that the memory-enhancing effect of the S 38093 and Donepezil combination is mediated by its action on the septo-hippocampal circuitry, since it canceled out the reduction of CREB phosphorylation (pCREB) observed in these brain areas in vehicle-treated middle-aged animals. Overall, the effects of drug combinations on pCREB in the hippocampus indicate that the synergistic promnesiant effects of the combination on memory performance in middle-aged mice stem primarily from an enhancement of neural activity in the septo-hippocampal system.

Neural activity promotes long-distance, target-specific regeneration of adult retinal axons.

Axons in the mammalian central nervous system (CNS) fail to regenerate after injury. Here we show that if retinal ganglion cell (RGC) activity is increased by visual stimulation or using chemogenetics, their axons regenerate. We also show that if enhancement of neural activity is combined with elevation of the cell growth-promoting pathway involving mammalian target of rapamycin (mTOR), RGC axons regenerate the long distances necessary to re-innervate the brain. Analysis of genetically-labeled RGCs revealed this regrowth can be target specific: RGC axons navigated back to their correct visual targets and avoided targets incorrect for their function. Moreover, these regenerated connections were successful in partially rescuing a subset of visual behaviors. Our findings indicate that combining neural activity with activation of mTOR can serve as powerful tool for enhancing axon regeneration and they highlight the remarkable capacity of CNS neurons to re-establish accurate circuit connections in the adult brain.

Sensory-Related Neural Activity Regulates the Structure of Vascular Networks in the Cerebral Cortex

Neurovascular interactions are essential for proper brain function. While the effect of neural activity on cerebral blood flow has been extensively studied, whether or not neural activity influences vascular patterning remains elusive. Here, we demonstrate that neural activity promotes the formation of vascular networks in the early postnatal mouse barrel cortex. Using a combination of genetics, imaging, and computational tools to allow simultaneous analysis of neuronal and vascular components, we found that vascular density and branching were decreased in the barrel cortex when sensory input was reduced by either a complete deafferentation, a genetic impairment of neurotransmitter release at thalamocortical synapses, or a selective reduction of sensory-related neural activity by whisker plucking. In contrast, enhancement of neural activity by whisker stimulation led to an increase in vascular density and branching. The finding that neural activity is necessary and sufficient to trigger alterations of vascular networks reveals an important feature of neurovascular interactions.

Hypothalamic Sirt1 in aging

Hypothalamic Sirt1 in aging

Functional Magnetic Resonance Imaging Analysis of Food-Related Brain Activity in Patients with Lipodystrophy Undergoing Leptin Replacement Therapy

Lipodystrophy is a disease characterized by a paucity of adipose tissue and low circulating concentrations of adipocyte-derived leptin. Leptin-replacement therapy improves eating and metabolic disorders in patients with lipodystrophy. The aim of the study was to clarify the pathogenic mechanism of eating disorders in lipodystrophic patients and the action mechanism of leptin on appetite regulation. We investigated food-related neural activity using functional magnetic resonance imaging in lipodystrophic patients with or without leptin replacement therapy and in healthy controls. We also measured the subjective feelings of appetite. Although there was little difference in the enhancement of neural activity by food stimuli between patients and controls under fasting, postprandial suppression of neural activity was insufficient in many regions of interest including amygdala, insula, nucleus accumbens, caudate, putamen, and globus pallidus in patients when compared with controls. Leptin treatment effectively suppressed postprandial neural activity in many of these regions of interest, whereas it showed little effect under fasting in patients. Consistent with these results, postprandial formation of satiety feeling was insufficient in patients when compared with controls, which was effectively reinforced by leptin treatment. This study demonstrated the insufficiency of postprandial suppression of food-related neural activity and formation of satiety feeling in lipodystrophic patients, which was effectively restored by leptin. The findings in this study emphasize the important pathological role of leptin in eating disorders in lipodystrophy and provide a clue to understanding the action mechanism of leptin in human, which may lead to development of novel strategies for prevention and treatment of obesity.

Neural Repetition Effects in the Medial Temporal Lobe Complex are Modulated by Previous Encoding Experience

It remains an intriguing question why the medial temporal lobe (MTL) can display either attenuation or enhancement of neural activity following repetition of previously studied items. To isolate the role of encoding experience itself, we assessed neural repetition effects in the absence of any ongoing task demand or intentional orientation to retrieve. Experiment 1 showed that the hippocampus and surrounding MTL regions displayed neural repetition suppression (RS) upon repetition of past items that were merely attended during an earlier study phase but this was not the case following re-occurrence of items that had been encoded into working memory (WM). In this latter case a trend toward neural repetition enhancement (RE) was observed, though this was highly variable across individuals. Interestingly, participants with a higher degree of neural RE in the MTL complex displayed higher memory sensitivity in a later, surprise recognition test. Experiment 2 showed that massive exposure at encoding effected a change in the neural architecture supporting incidental repetition effects, with regions of the posterior parietal and ventral-frontal cortex in addition to the hippocampus displaying neural RE, while no neural RS was observed. The nature of encoding experience therefore modulates the expression of neural repetition effects in the MTL and the neocortex in the absence of memory goals.

Interoceptive awareness enhances neural activity during empathy

Empathy is a multicomponent function that includes sensorimotor, affective, and cognitive components. Although especially the affective component may implicate interoception and interoceptive awareness, the impact of interoception on empathy has never been evaluated behaviorally or neurophysiologically. Here, we tested how a preceding period of interoceptive awareness impacts and modulates neural activity during subsequent empathy. We used functional magnetic resonance imaging (fMRI) and measured the sequential interaction between interoception and empathy using fMRI in 18 healthy subjects. We found that the preceding interoceptive awareness period significantly enhanced neural activity during empathy in bilateral anterior insula and various cortical midline regions. The enhancement of neural activity during empathy in both interoceptive and empathy networks by preceding interoceptive awareness suggests a close relationship between interoception and empathy; thereby, interoception seems to be implicated to yielding empathy.