eNeuro最新文献

Inner speech refers to the silent production of language in one's mind. As a purely mental action without obvious physical manifestations, inner speech has been notoriously difficult to quantify. To address this issue, the present study repurposed the phenomenon of speaking-induced suppression, wherein overt speech has been consistently shown to elicit reduced auditory evoked potentials compared with externally generated speech, as well as changes in oscillatory activity in gamma and theta frequency bands. Given the functional similarities between inner and overt speech, we used an established experimental protocol to investigate whether similar metrics could be used to distinguish the content of inner speech. Healthy participants (n = 129) produced an inner syllable at a precisely specified time. An audible syllable was concurrently presented which either matched or mismatched the content of the inner syllable. The results revealed that Match and Mismatch conditions could be differentiated on the basis of their evoked oscillations in the gamma, theta, and alpha bands. Notably, there was a gamma-band oscillation in the vicinity of the P2 that differed between the Match and Mismatch conditions, suggesting that "late" gamma-band activity may index consciously perceived expectancy violations, or cognitive prediction errors. Regarding the auditory evoked potentials, the N1 component was suppressed in the Match condition while the P2 component was suppressed in the Mismatch condition, replicating previous findings. This study provides support for the existence of "inner speaking-induced suppression", and demonstrates that inner syllables can be differentiated based on their influence on the electroencephalographic activity elicited by simultaneously-presented audible syllables.

High-frequency stimulation (HFS)-induced long-term potentiation (LTP) is generally regarded as a homosynaptic Hebbian-type LTP, where synaptic changes are thought to occur at the synapses that project from the stimulation site and terminate onto the neurons at the recording site. In this study, we first investigated HFS-induced LTP on urethane-anesthetized rats and found that cortical HFS enhances neural responses at the recording site through the strengthening of local connectivity with nearby neurons at the stimulation site rather than through synaptic strengthening at the recording site. This enhanced local connectivity at the stimulation site leads to increased output propagation, resulting in signal potentiation at the recording site. Additionally, we discovered that HFS can also nonspecifically strengthen distant afferent synapses at the HFS site, thereby expanding its impact beyond local neural connections. This form of plasticity exhibits a neo-Hebbian characteristic as it exclusively manifests in the presence of cholecystokinin release, induced by HFS. The cortical HFS-induced local LTP was further supported by a behavioral task, providing additional evidence. Our results unveil a previously overlooked mechanism underlying cortical plasticity: synaptic plasticity is more likely to occur around the soma site of strongly activated cortical neurons rather than solely at their projection terminals.

A common impairment in aging is age-related hearing loss (presbycusis), which manifests as impaired spectrotemporal processing. Presbycusis can be caused by a dysfunction of the peripheral and central auditory system, and these dysfunctions might differ between the sexes. To date, the circuit mechanisms in the central nervous system responsible for age-related auditory dysfunction remain mostly unknown. In the auditory cortex (ACtx), aging is accompanied by alteration in normal inhibitory (GABA) neurotransmission and changes in excitatory (NMDA and AMPA) synapses, but which circuits are affected has been unclear. Here we investigated how auditory cortical microcircuits change with age and if sex-dependent differences existed. We performed laser-scanning photostimulation (LSPS) combined with whole-cell patch-clamp recordings from layer (L) 2/3 cells in the primary auditory cortex (A1) in young adult (2-3 months) and aged (older than 18 months) male and female CBA/CaJ mice which have normal peripheral hearing. We found that L2/3 cells in aged male animals display functional hypoconnectivity of inhibitory circuits originating from L2/3 and L4. Compared with cells from young adult mice, cells from aged male mice have weaker excitatory connections from L2/3. We also observed an increased diversity of excitatory and inhibitory inputs. These results suggest a sex-specific reduction and diversification in excitatory and inhibitory intralaminar cortical circuits in aged mice compared with young adult animals. We speculate that these unbalanced changes in cortical circuits contribute to the functional manifestations of age-related hearing loss in both males and females.

The use of supervised machine learning to approximate poses in video recordings allows for rapid and efficient analysis of complex behavioral profiles. Currently, there are limited protocols for automated analysis of operant self-administration behavior. We provide a methodology to (1) obtain videos of training sessions via Raspberry Pi microcomputers or GoPro cameras, (2) obtain pose estimation data using the supervised machine learning software packages DeepLabCut (DLC) and Simple Behavioral Analysis (SimBA) with a local high-performance computer cluster, (3) compare standard Med-PC lever response versus quadrant time data generated from pose estimation regions of interest, and (4) generate predictive behavioral classifiers. Overall, we demonstrate proof of concept to use pose estimation outputs from DLC to both generate quadrant time results and obtain behavioral classifiers from SimBA during operant training phases.

Observing lip movements of a speaker facilitates speech understanding, especially in challenging listening situations. Converging evidence from neuroscientific studies shows stronger neural responses to audiovisual stimuli compared with audio-only stimuli. However, the interindividual variability of this contribution of lip movement information and its consequences on behavior are unknown. We analyzed source-localized magnetoencephalographic responses from 29 normal-hearing participants (12 females) listening to audiovisual speech, both with and without the speaker wearing a surgical face mask, and in the presence or absence of a distractor speaker. Using temporal response functions to quantify neural speech tracking, we show that neural responses to lip movements are, in general, enhanced when speech is challenging. After controlling for speech acoustics, we show that lip movements contribute to enhanced neural speech tracking, particularly when a distractor speaker is present. However, the extent of this visual contribution to neural speech tracking varied greatly among participants. Probing the behavioral relevance, we demonstrate that individuals who show a higher contribution of lip movements in terms of neural speech tracking show a stronger drop in comprehension and an increase in perceived difficulty when the mouth is occluded by a surgical face mask. In contrast, no effect was found when the mouth was not occluded. We provide novel insights on how the contribution of lip movements in terms of neural speech tracking varies among individuals and its behavioral relevance, revealing negative consequences when visual speech is absent. Our results also offer potential implications for objective assessments of audiovisual speech perception.

For comprehensive anatomical analysis of a mouse brain, accurate and efficient registration of the experimental brain samples to a reference atlas is necessary. Here, we introduce Bell Jar, a semiautomated solution that can align and annotate tissue sections with anatomical structures from a reference atlas as well as detect fluorescent signals with cellular resolution (e.g., cell bodies or nuclei). Bell Jar utilizes Mattes mutual information-directed B-spline transformations to achieve precise alignments, even with damaged sample tissues. While user input remains a requirement for fine-tuning section matches, the platform streamlines the process, aiding rapid analyses in high-throughput neuroanatomy studies. As a standalone desktop application with a user-friendly interface, Bell Jar's performance, which surpasses traditional manual and existing automated methods, can improve the reproducibility and throughput of histological analyses.

Food intake is controlled by multiple converging signals: hormonal signals that provide information about energy homeostasis and hedonic and motivational aspects of food and food cues that can drive nonhomeostatic or "hedonic" feeding. The ventral pallidum (VP) is a brain region implicated in the hedonic and motivational impact of food and food cues, as well as consumption of rewards. Disinhibition of VP neurons has been shown to generate intense hyperphagia, or overconsumption. While VP GABA neurons have been implicated in cue-elicited reward-seeking and motivation, the role of these neurons in the hyperphagia resulting from VP activation remains unclear. Here, we used designer receptors exclusively activated by designer drugs to activate VP GABA neurons in nonrestricted male and female rats during chow and sucrose consumption. We found that activation of VP GABA neurons increases consumption of chow and sucrose in male rats, but not female rats. Together, these findings suggest that activation of VP GABA neurons can stimulate consumption of routine or highly palatable rewards selectively in male rats.

Chronic pain is a debilitative disease affecting one in five adults globally and is a major risk factor for anxiety ( Goldberg and McGee, 2011; Lurie, 2018). Given the current dearth of available treatments for both individuals living with chronic pain and mental illnesses, there is a critical need for research into the molecular mechanisms involved in order to discover novel treatment targets. Cellular homeostasis is crucial for normal bodily functions, and investigations of this process may provide better understanding of the mechanisms driving the development of chronic pain. Using the spared nerve injury (SNI) model of neuropathic pain, we found contrasting roles for BECLIN-1 in the development of pain hypersensitivity and anxiety-like behaviors in a sex-dependent manner. Remarkably, we found that male SNI mice with impaired BECLIN-1 function demonstrated heightened mechanical and thermal hypersensitivity compared with male wild-type SNI mice, while female SNI mice with impaired BECLIN-1 function demonstrated similar thresholds to the female wild-type SNI mice. We also found that disruptions of BECLIN-1 prevented SNI-induced increases in anxiety-like behaviors in male mice. Our data thus indicate that BECLIN-1 is differentially involved in the nociceptive and emotional components of chronic pain in male but not female mice.

The anterior hypothalamic area (AHA) is a key brain region for orchestrating defensive behaviors. Using in vivo calcium imaging in mice, we observed that AHA neuronal activity increases during footshock delivery and footshock-associated auditory cues. We found that following shock-induced increases in AHA activity, a decrease in activity coincides with the onset of grooming behavior. Next, we optogenetically activated the projections from the ventromedial hypothalamus (VMH) to the AHA and observed that photoactivation of the VMH→AHA pathway drives avoidance. Interestingly, repetitive grooming behavior occurs following cessation of stimulation. To identify changes in brain-wide activity patterns that occur due to optogenetic VMH→AHA stimulation, we combined optogenetic stimulation with positron emission tomography (PET)-based metabolic mapping. This approach revealed the amygdala as a downstream area activated by the stimulation of this pathway. Our findings show that the rise and fall of AHA neuronal activity triggers repetitive grooming behavior following learned fear and optogenetic stimulation. In addition, activation of the VMH→AHA pathway triggers changes in the activity patterns of downstream brain regions that are reported to be associated with displacement grooming.

Selectively stopping individual parts of planned or ongoing movements is an everyday motor skill. For example, while walking in public, you may stop yourself from waving at a stranger who you mistook for a friend while continuing to walk. Despite its ubiquity, our ability to selectively stop actions is limited. Canceling one action can delay the execution of other simultaneous actions. This stopping-interference effect on continuing actions during selective stopping may be attributed to a global inhibitory mechanism with widespread effects on the motor system. Previous studies have characterized a transient global reduction in corticomotor excitability by combining brain stimulation with electromyography (EMG). Here, we examined whether global motor inhibition during selective stopping can be measured peripherally and with high temporal resolution using EMG alone. Eighteen participants performed a bimanual anticipatory response inhibition task with their index fingers while maintaining a tonic contraction of the task-irrelevant abductor digiti minimi (ADM) muscles. A time series analysis of the ADM EMG signal revealed transient inhibition during failed stopping compared with go response trials 150 to 203 ms following the stop signal. The pattern was observed in both hands during bimanual stop-all trials as well as selective stop-left and stop-right trials of either hand. These results indicate that tonic muscle activity is sensitive to the effects of global motor suppression even when stopping fails. Therefore, EMG can provide a physiological marker of global motor inhibition to probe the time course and extent of stopping processes.