Understanding how pupil-linked arousal couples with cortical state is crucial for uncovering the neural mechanisms underlying brain state-dependent cognitive and sensory processing. Pupil size fluctuations reflect rapid changes of the pupil-linked arousal system, indexing brain states as well as the activity of neuromodulatory systems, including the locus ceruleus–norepinephrine (LC–NE) system. We investigated the relationship among phasic pupil dilation, cortical state, and neuromodulation by combining optogenetic LC stimulation with electroencephalogram (EEG) recordings and pupillometry in awake mice of both sexes. A comparison between EEG signals during spontaneous phasic pupil dilation and those during phasic pupil dilation evoked by LC stimulation revealed distinct cortical states. Using machine learning techniques, we trained a convolutional neural network classifier to distinguish between types of pupil dilation based on the power dynamics of individual EEG frequency bands. The results confirmed that all EEG bands, but most significantly gamma, differ markedly between spontaneous phasic arousal and LC stimulation-evoked arousal. Moreover, pharmacological manipulations to either block α- or β-adrenergic receptors or agonize α-2–adrenergic receptors were employed to explore how adrenergic receptors could influence the coupling between phasic pupil dilation and cortical state. With each manipulation uniquely modulating EEG power and pupil size, our results highlight the differentiated role of adrenergic receptors in moderating the coupling between pupil-linked arousal and cortical state. This study provides new insights into the complex relationship between pupil-linked arousal and cortical arousal state, underscoring the significant role of the LC–NE system in influencing these arousal states.

Everyday auditory scenes contain overlapping sound objects, requiring attention to isolate relevant objects from irrelevant background objects. This study examined how selective attention shapes neural representations of complex sound scenes in the auditory cortex (AC). Using functional magnetic resonance imaging, we recorded brain activity from participants (12 males, 8 females) as they attended to a designated object in scenes comprising three overlapping sounds. Scenes were constructed in two manners: one where each object belonged to a different category (speech, animal, instrument) and another where all objects were from the same category. Attending to speech enhanced activations in lateral AC subfields, while attention to animal and instrument sounds preferentially modulated medial AC subfields, supporting models where attention modulates feature-selective neural gain in AC. Remarkably, however, spatial pattern analysis revealed that the attended object dominated the AC activation patterns of the entire scene in a manner depending on both object type and scene composition: When scene objects belonged to different categories, attention effects were dominated by category-level processing. In contrast, when all scene objects shared the same category, dominance shifted to exemplar-level processing in fields processing acoustic features. Thus, attention seems to dynamically prioritize the features offering maximal contrast within a given context, emphasizing object-specific patterns in feature-similar scenes and category-level patterns in feature-diverse scenes. Our results support models where top-down signals not only modulate gain but also affect scene decomposition and analysis—influencing stream segregation and gating of higher-level processing in a contextual manner, adapting to specific auditory environments.

Traumatic brain injury (TBI) triggers a cascade of secondary pathologies—such as neuroinflammation and glial activation—contributing to progressive neuronal loss and hindering functional recovery. While therapeutic hypothermia has shown neuroprotective potential, its clinical application is limited by systemic complications. Recent discoveries have identified hypothalamic Q neurons, whose activation induces a reversible, hibernation-like hypothermic state, termed Q neuron-induced hypothermic/hypometabolic states (QIH), without the need for external cooling. However, whether QIH can mitigate brain injury remains unknown. In this study, we examined the therapeutic effects of QIH following acute brain injury in male mice. Using a dorsal striatal stab injury model, we found that QIH-treated mice displayed significantly improved motor performance and grip strength compared with controls. Histological analyses revealed enhanced neuronal survival in the perilesional striatum, accompanied by markedly reduced astrocytic gliosis and microglial accumulation at the injury site. To investigate the mechanisms underlying these improvements, we employed a medial prefrontal cortex injury model and observed that QIH robustly suppressed astrocytic and microglial activation, as indicated by reduced GFAP and Iba1 expression. Additionally, QIH decreased the number of CD16/32- and CD68-positive microglia and downregulated iNOS expression, suggesting that QIH dampens both oxidative and phagocytic inflammatory responses. Morphometric analysis further revealed a shift toward ramified and rod-shaped microglia, phenotypes associated with neuroprotection. Our findings demonstrate that QIH ameliorates early neuroinflammation, preserves neuronal integrity, and promotes functional recovery following brain injury. These results highlight QIH as a novel and physiologically grounded neuroprotective strategy that may overcome the limitations of conventional hypothermia-based interventions.

Epileptic seizures involve a cortical excitation–inhibition imbalance driven by dysfunctional interneurons that contribute to gamma oscillation generation. While impaired gamma oscillations are commonly reported in epilepsy, the dynamics of broadband and narrowband gamma as well as beta oscillations remain underexplored. These oscillations may serve as noninvasive electrophysiological markers associated with altered cortical dynamics, potentially reflecting underlying excitation–inhibition imbalance in epilepsy. Here, we recorded high-density electroencephalography and magnetoencephalography data to investigate visual stimuli-elicited cortical oscillations in 48 neurotypical (20 females) and 49 children (26 females) with epilepsy. We found that epilepsy is characterized by reduced amplitude and prolonged latency of evoked cortical response compared with controls after visual stimulation, with alterations in N1 peaks and M100, M150, and M250 components (p < 0.05). Additionally, source imaging revealed disrupted oscillatory features in epilepsy patients, including suppressed power, reduced amplitude, and increased latency in evoked and induced beta and gamma oscillations from the visual cortex (p < 0.05). These alterations were consistent across diverse epilepsy subtypes, including focal, generalized, and nonlesional epilepsy cases. Utilizing these differences, we developed a novel classification model that differentiates individuals with epilepsy from controls with high accuracy, offering potential clinical utility in epilepsy diagnosis. Our results suggest disrupted beta and gamma oscillations may be associated with impaired inhibitory mechanisms and altered cortical dynamics, potentially indicative of an excitation–inhibition imbalance. Our findings highlight the potential of noninvasive electrophysiological biomarkers to capture cortical dynamics possibly influenced by excitation–inhibition imbalance in epilepsy, supporting their use in early diagnosis and disease monitoring.

Although TREK1 channels are widely expressed in several thalamic nuclei, the role of this K2P family member in modulating thalamic cell excitability and physiological thalamocortical oscillatory activity is not well studied. Here we explored the contribution of TREK1 channels to membrane properties of two important building blocks of the thalamocortical (TC) system, namely, GABAergic neurons of reticular thalamic nucleus (RTN) and TC neurons in different sensory thalamic nuclei including the ventrobasal complex (VB; somatosensory system) and the medial geniculate nucleus (MGN; auditory system), using male TREK1 knock-out (TREK1−/−) mice. Furthermore, we show that the loss of TREK1 channels has distinct effects on neuronal function in different thalamic nuclei. Compared with controls, TREK1−/− mice exhibit decreased excitability in RTN neurons, while VB neurons maintain similar excitability levels. Additionally, the absence of TREK1 channels alters the action potential (AP) characteristics in VB TC neurons and affects GABAergic inhibitory tone in RTN neurons. In TREK1−/− mice, the excitability of cortical pyramidal cells is increased. It is tempting to assume that this combination of changes contributes to a high number of sharp, spindle-like oscillations observed in sleep local field potential (LFP) recordings of these mice. In addition, TREK1−/− mice show a lower amount of delta (1–4 Hz) oscillations during slow-wave sleep and a time-of-day-dependent alteration in the amount of sleep and wakefulness. They also show disturbed auditory signal processing and altered excitability in the auditory thalamus. These findings underline the relevance of TREK1 channels’ broad contribution to the thalamus and thalamocortical system.

Finding what you are looking for is a ubiquitous task in everyday life that relies on a two-way comparison between what is currently viewed and internal search goals held in memory. Despite a wealth of studies tracking visual verification among external contents of perception, complementary verification processes among internal contents of memory remain elusive. Building on a recently established gaze marker of internal visual focusing in working memory, we uncover the internal inspection process associated with confirming or dismissing potential search targets. We show how male and female human participants “look back” into working memory when faced with external stimuli that are perceived as potential targets and link such internal inspection to the time needed for visual verification. A direct comparison between visual verification among the contents of working memory or perception further revealed how verification in both domains engages frontal theta activity in scalp electroencephalography but also how mnemonic verification is slower to deploy than perceptual verification. This establishes internal verification as an integral component of visual search and provides new ways to look into this underexplored component of human search behavior.

The brain has somewhat separate cognitive resources for the left and right sides of our visual field. Despite this lateralization, we have a smooth and unified perception of our environment. This raises the question of how the cerebral hemispheres are coordinated to transfer information between them. We recorded neural activity in the lateral prefrontal cortex, bilaterally, as two male nonhuman primates covertly tracked a target that moved from one visual hemifield (i.e., from one hemisphere) to the other. Beta (15–30 Hz) power, gamma (30–80 Hz) power, and spiking information reflected sensory processing of the target. In contrast, alpha (10–15 Hz) power, theta (4–10 Hz) power, and spiking information seemed to reflect an active handoff of attention as target information was transferred between hemispheres. Specifically, alpha power and spiking information ramped up in anticipation of the hemifield cross. Theta power peaked after the cross, signaling its completion. Our results support an active handoff of information between hemispheres. This “handshaking” operation may be critical for minimizing information loss, much like how mobile towers handshake when transferring calls between them.

Amblyopia (lazy eye) is a developmental disorder of the visual cortex that causes deficits in visual acuity and shape perception. The loss of visual acuity is thought to originate from weakened cortical responses to stimuli. Here, we provide evidence for a similar mechanism to explain distortions in shape perception. We introduce a computational model that simulates perceptual distortions of grating patterns drawn by humans with amblyopia (Barrett et al., 2003). The model simulates a large variety of distortions by performing a weighted sum of rectified sinusoidal gratings (average, 3.3 gratings ∼6 times larger than foveal receptive fields in the primary visual cortex) with different dark/light duty cycles. The simulations accurately reproduce self-reported perceptions of amblyopic patients and decrease drawing-percept differences when ideal percepts (stimuli) are replaced with simulated percepts (9.03 ± 12.37%; p = 0.0002; Wilcoxon test comparing normalized Laplacian pyramid distances; Laparra et al., 2016). The simulations also reveal an increase in the number of stimulus orientations contributing to visual percepts in amblyopia and a strong correlation between contrast sensitivity deficits and both magnitude of perceived visual distortions (r = 0.96; p = 0.0007) and predicted spread of cortical activation (r = 0.82; p = 0.02). The results also demonstrate a compensatory shift in the spatial frequency distribution of cortical filters in amblyopia, which closely resembles the spatial frequency shift caused by contrast reduction in thalamocortical inputs of male cats. Taken together, our results indicate that amblyopia compensates weakened cortical responses by increasing the spread of cortical activation to include neurons with mismatched stimulus preferences that cause perceptual distortions.