Native speakers excel at parsing continuous speech into smaller elements and entraining their neural activities to the linguistic hierarchy at different levels (e.g., syllables, phrases and sentences) to achieve speech comprehension. However, how a nonnative brain tracks hierarchical linguistic structures in second language (L2) speech comprehension and whether it relates to top-down attention and language proficiency remains elusive. Here, we applied a frequency-tagging paradigm in human adults and investigated the neural tracking responses to hierarchically organized linguistic structures (i.e., the syllabic rate of 4 Hz, the phrasal rate of 2 Hz and the sentential rate of 1 Hz) in both first language (L1) and L2 listeners when they attended to a speech stream or ignored it. We revealed disrupted neural responses to higher-order linguistic structures (i.e., phrases and sentences) for L2 listeners in which the phrasal-level tracking was functionally related to an L2 subject’s language proficiency. We also...

Interoception, the representation of the body’s internal state, serves as a foundation for emotion, motivation, and wellbeing. Yet despite its centrality in human experience, the neural mechanisms of interoceptive attention are poorly understood. The Interoceptive/Exteroceptive Attention Task (IEAT) is a novel neuroimaging paradigm that compares behavioral tracking of the respiratory cycle (Active Interoception) to tracking of a visual stimulus (Active Exteroception). Twenty-two healthy participants completed the IEAT during two separate scanning sessions (N = 44) as part of a randomized control trial of Mindful Awareness in Body-oriented Therapy (MABT). Compared to Active Exteroception, Active Interoception deactivated somatomotor and prefrontal regions. Greater self-reported interoceptive sensibility (MAIA scale) predicted sparing from deactivation within the anterior cingulate cortex (ACC) and left-lateralized language regions. The right insula—typically described as a primary interoceptive cortex—was o...

During the embryonic period, neuronal communication starts before the establishment of the synapses with alternative forms of neuronal excitability, called here Embryonic Neural Excitability (ENE). ENE has been shown to modulate the unfolding of development transcriptional programs, but the global consequences for developing organisms are not all understood. Here we monitored calcium transients in the telencephalon of zebrafish embryos as a proxy for ENE to assess the efficacy of transient pharmacological treatments to either increase or decrease ENE. Increasing or decreasing ENE at the end of the embryonic period promoted an increase or a decrease in the numbers of dopamine (DA) neurons, respectively. This plasticity of dopaminergic specification occurs in the subpallium of zebrafish larvæ at 6 dpf, within a relatively stable population of vMAT2-positive cells. Non-dopaminergic vMAT2-positive cells hence constitute an unanticipated biological marker for a reserve pool of DA neurons that can be recruited b...

Chronic nicotine results in dependence with withdrawal symptoms upon discontinuation of use, through desensitization of nicotinic acetylcholine receptors and altered cholinergic neurotransmission. Nicotine withdrawal is associated with increased whole-brain functional connectivity and decreased network modularity, however, the role of cholinergic neurons in those changes is unknown. To identify the contribution of nicotinic receptors and cholinergic regions to changes in the functional network, we analyzed the contribution of the main cholinergic regions to brain-wide activation of the immediate early-gene FOS during withdrawal in male mice and correlated these changes with the expression of nicotinic receptor mRNA throughout the brain. We show that the main functional connectivity modules included the main long-range cholinergic regions, which were highly synchronized with the rest of the brain. However, despite this hyperconnectivity they were organized into two anticorrelated networks that were separate...

Sepsis-associated encephalopathy (SAE) is a frequent severe complication of sepsis and the systemic inflammatory response syndrome, associated with high mortality and long-term neurological consequences in surviving patients. One of the main clinical signs of SAE are discontinuous sleep periods that are fragmented by frequent awakenings. Even though this brain state fragmentation strongly impacts the functionality of the nervous- and other systems, its underlying network mechanisms are still poorly understood. In this work, we therefore aim to characterize the properties and dynamics of brain oscillatory states in response to SAE in an acute rat model of sepsis induced by high dose LPS (10 mg/kg). To focus on intrinsically generated brain state dynamics, we used a urethane model that spares oscillatory activity in REM- and NREM-like sleep states. Intraperitoneal LPS injection led to a robust instability of both oscillatory states resulting in several folds more state transitions. We identified opposing shi...

Experiments that take advantage of head fixed behavioral tasks have been a staple of systems neuroscience research for half a century. More recently, rodents came to the forefront of these efforts, primarily due to the rich experimental possibilities afforded by modern genetic tools. There is however a considerable barrier to entering this field, requiring expertise in engineering, hardware- and software development, and significant time- and financial commitment. Here, we present a comprehensive, open-source hardware and software solution to implement a Head-fixed Environment for Rodent Behaviors (HERBs). Our solution provides access to three frequently used experimental frameworks (two-alternative forced choice, go-nogo, or passive sensory stimulus presentation) in a single package. The required hardware can be built at a relatively low cost compared to commercially available solutions, from off-the-shelf components. Our graphical user interface (GUI) based software provides great experimental flexibilit...

Opioid drugs are widely used as analgesics but cause respiratory depression, a potentially lethal side-effect with overdose, by acting on µ-opioid receptors (MORs) expressed in brainstem regions involved in the control of breathing. Although many brainstem regions have been shown to regulate opioid-induced respiratory depression, the types of neurons involved have not been identified. Somatostatin is a major neuropeptide found in brainstem circuits regulating breathing, but it is unknown whether somatostatin-expressing circuits regulate respiratory depression by opioids. We examined the co-expression of Sst (gene encoding somatostatin) and Oprm1 (gene encoding MORs) mRNAs in brainstem regions involved in respiratory depression. Interestingly, Oprm1 mRNA expression was found in the majority (> 50%) of Sst -expressing cells in the preBötzinger Complex, the nucleus tractus solitarius, the nucleus ambiguus, and the Kölliker-Fuse nucleus. We then compared respiratory responses to fentanyl between wild-type and ...

The impact of alcohol abuse on Alzheimer’s disease (AD) is poorly understood. Here, we show that the onset of neurocognitive impairment in a mouse model of AD is hastened by repeated alcohol intoxication through exposure to alcohol vapor, and we provide a comprehensive gene expression dataset of the prefrontal cortex by the single-nucleus RNA sequencing of 113,242 cells. We observed a broad dysregulation of gene expression that involves neuronal excitability, neurodegeneration, and inflammation, including interferon genes. Several genes previously associated with AD in humans by genome-wide association studies were differentially regulated in specific neuronal populations. Gene expression patterns of AD mice with a history of alcohol intoxication were more similar to gene expression signatures of older AD mice with more advanced disease and cognitive impairment than those of younger AD mice with prodromic disease, suggesting that alcohol promotes transcriptional changes consistent with AD progression. Our ...

Saccade planning and execution can be affected by a multitude of factors present in a target selection task. Recent studies have shown that the similarity between a target and nearby distractors affects the curvature of saccade trajectories, due to target-distractor competition. To further understand the nature of this competition, we varied the distance between and the similarity of complex target and distractor objects in a delayed match-to-sample task to examine their effects on human saccade trajectories and better understand the underlying neural circuitry. For trials with short saccadic reaction times (SRTs) when target-distractor competition is still active, the distractor is attractive and saccade trajectories are deviated towards the distractor. We found a robust effect of distance consistent with saccade vector averaging, whereas the effect of similarity suggested the existence of an object-based suppressive surround. At longer SRTs there was sufficient time for competition between the objects to...

Nicotine is an addictive drug whose popularity has recently increased, particularly among adolescents, because of the availability of electronic nicotine devices (i.e., “vaping”) and nicotine e-liquids containing additives with rich chemosensory properties. Some efforts to understand the role of these additives in nicotine reward suggest that they increase nicotine reward and reinforcement, but the sensory contributions of additives, especially in their vapor forms, are largely untested. Here, to better understand how a fruit-flavored (i.e., strawberry) additive influences nicotine reward and aversion, we used a conditioned place preference (CPP) procedure in which nicotine and a strawberry additive were delivered as a vapor to male and female adolescent mice. We found that nicotine vapor alone can lead to a dose-dependent CPP when using a biased design. The strawberry additive did not produce CPP on its own, and we did not observe an effect of the strawberry additive on nicotine vapor-induced reward. Neve...