Childhood adversity is a potent predictor of mental health problems across the lifespan, and cross-species literature implicates stress-sensitive corticolimbic circuits in adversity-related psychopathology. Structure-function coupling (SFC) is a multimodal marker that is sensitive to developmental plasticity. While emerging evidence suggests cortical SFC is sensitive to adversity exposure during early childhood, it is unknown how SFC in stress-sensitive corticolimbic circuits links adversity exposure with mental health across development. We examined associations between adversity exposure, transdiagnostic symptomatology, and both amygdala-cortical and hippocampal-cortical SFC across development in a large youth sample (N = 607, 39% F). Results revealed that adversity exposure moderated the association between age and amygdala-vmPFC SFC (partial R2 = 0.015, p = .007), such that age was positively associated with amygdala-vmPFC SFC in youth with higher, but not lower, levels of adversity exposure. Further, amygdala-vmPFC SFC moderated the association between adversity exposure and internalizing symptoms (partial R2 = 0.015, p = .012), such that the adversity-symptoms association was reduced in youth with stronger, but not weaker, amygdala-vmPFC SFC. Separately, higher adversity exposure was associated with weaker hippocampal-limbic SFC (partial R2 = 0.019, p = .037), which moderated the association between adversity and internalizing symptoms (partial R2 = 0.005, p = .010) such that the adversity-symptoms association was reduced in youth with weaker, but not stronger, hippocampal-limbic SFC. These findings highlight that neurodevelopment of amygdala-vmPFC and hippocampal-limbic circuits may adapt in distinct ways to support mental health following adversity, with implications for risk and resilience against internalizing psychopathology.Significance Statement Delineating how childhood adversity alters neurodevelopment is critical to understanding the origins of adversity-related risk for mental health disorders. Here, we leverage a multimodal marker of the correspondence between brain structure and function to test how corticolimbic circuits are associated with adversity exposure during development. Results reveal that the structure-function coupling of amygdala-vmPFC and hippocampal-limbic circuits is linked with adversity exposure and differentially moderates the association between adversity exposure and internalizing psychopathology. These findings suggest key roles for neural stress regulation and memory circuits in adapting to support optimal functioning following adversity exposure, and highlight the concordance of neural structure and function as an important indicator of individual-level risk and resilience.

Anhedonia reflects a transdiagnostic deficit in a range of processes that impact reward and motivation. While human neuroimaging has mainly focused on striatal-related alterations in anhedonia, animal models suggest hippocampal [HPC] novelty processing regulates mesolimbic dopamine activity, implicating mesolimbic-HPC alterations in anhedonia. Childhood trauma, which disproportionately impacts HPC structure and function, may exacerbate this vulnerability. The present study of 37 males and 55 females examined whether HPC alterations interact with childhood trauma to predict anhedonia in humans. Using fMRI in a sample enriched for anhedonia, we assessed three HPC-related processes: resting-state connectivity with mesolimbic targets in the ventral tegmental area [VTA] and nucleus accumbens [NAc], task-based HPC novelty response, and task-based HPC modulation of VTA activation reflecting novelty-evoked facilitation of target detection. Significant interactions emerged for anticipatory anhedonia: reduced HPC-NAc connectivity, reduced novelty response, and weaker HPC→VTA modulation were each associated with greater anticipatory anhedonia among individuals with high childhood trauma. Moreover, LASSO regression confirmed these interactions as unique predictors. These findings suggest that early life adversity interacts with alterations in HPC-mesolimbic signaling to contribute to individual differences in anhedonia, highlighting the HPC as a potential target of motivation-related deficits in striatum.Significance Statement The ability to process rewarding stimuli and initiate goal-directed behavior is critical for human functioning. While human neuroimaging has highlighted the role of striatal function in these processes, animal evidence suggests that hippocampal modulation of mesolimbic dopamine signaling is critical for motivated behavior. The present study translates this framework to humans, demonstrating that hippocampal-mesolimbic functional integrity interacts with childhood trauma to predict individual differences in anticipatory anhedonia (i.e., impairments in one's ability to anticipate and pursue rewards). These findings implicate the hippocampus as a potential upstream contributor to motivational deficits and highlight early life stress as a key context in which mesolimbic circuit dysfunction becomes behaviorally relevant.

A central question in motor neuroscience is how the brain represents the state of the limbs to guide volitional movements. While the primate motor cortex is known to encode movement kinematics, such as velocity and direction, whether it also maintains a direct and explicit representation of hand position in 3D space remains debated. To address this, we recorded the activity of single neurons in the primary motor cortex (M1) and dorsal premotor cortex (PMd) of two male rhesus macaques performing a naturalistic, self-paced 3D reach-and-grasp task. We found significant populations of neurons in both M1 (36.2%) and PMd (21.3%) that are robustly tuned to the instantaneous 3D position of the hand. In these neurons, the tuning for hand position-characterized by localized, elongated fields-coexists with tunings for other kinematic variables, reflecting the principle of mixed selectivity. Critically, the spatial organization of these representations differs between the two areas: M1 fields are systematically oriented along cardinal axes and exhibit multi-scale spatial clustering, whereas PMd fields are more randomly organized. Furthermore, a small subset of these hand position-tuned cells is sufficient to decode the hand's 3D trajectory with high fidelity. Our findings demonstrate that an explicit and functionally organized representation of 3D hand position is a fundamental component of primate motor cortex, complementing dynamic motor signals to support high-fidelity motor control.Significance Statement To guide skilled actions, the brain must track the hand's location. While the motor cortex is known for controlling movement commands, we reveal it also creates an explicit, highly organized 3D map of hand position. This neural representation is systematically structured, differing between primary and premotor areas. This discovery reshapes our understanding of motor control, showing the brain merges spatial information ("where") with motor commands ("how") of the hand in the same areas. These insights are crucial for creating more effective brain-computer interfaces for individuals with paralysis.

Emotion and mood regulation critically depends on interactions between the anterior cingulate cortex (ACC) and the amygdala. However, the detailed architecture of ACC projections to their major targets, the basal (BA) and accessory (AcBA) basal nuclei of the amygdala, remains unclear. To address this issue, a combined retrograde and anterograde tracing with viral vectors were performed in macaques of either sex to map the projection patterns from the pregenual (pgACC), subgenual (sgACC), and dorsal (dACC) subareas. Data revealed that ACC neurons projecting to the BA arose predominantly from the superficial layers (II/III) of all subareas and the deep layers (V/VI) of the sgACC, whereas ACC neurons projecting to the AcBA originated mainly in the deep layers of the sgACC and dACC. The present study defines the topographic and layer-specific organization of ACC-amygdala connectivity in primates and subserves to provide an anatomical basis for future causal and translational approaches, such as targeted interventions against ACC-related mood disorders.Significance Statement Emotion and mood regulation critically depends on interactions between the anterior cingulate cortex (ACC) and the amygdala, and their dysfunctions have been implicated in mood disorders such as depression. However, the detailed organization of primate ACC-amygdala circuitry remains to be fully understood. Notably, the existence of projections from the pregenual ACC (pgACC) to the basal nucleus of the amygdala (BA) has been controversial. Using viral vector-based neural tracings in macaques, we have identified a distinct pgACC-BA pathway and shown that this pathway arises predominantly from the superficial layers of the cortex. Such unexpected laminar origin, atypical for cortico-subcortical projections, reveals a previously unrecognized circuit architecture and challenges prevailing models of cortico-amygdala linkage involved in mood disorders.

Schizophrenia is associated with prefrontal cortex dysfunction, including neural disinhibition (reduced GABAergic inhibition) and hypoactivation ('hypofrontality'), alongside impaired reversal learning. However, evidence implicating prefrontal regions, including the rodent medial PFC (mPFC), in reversal learning is mixed. mPFC involvement may scale with demand for mPFC-dependent attention and cognitive control to overcome prepotent responses and to learn that reward contingencies can reverse, which is highest during early reversals. We therefore hypothesized that (1) the mPFC is required for early reversal learning but less important when reversal proficiency is high during late reversals. Furthermore, mPFC disinhibition may impair cognitive performance by causing circuit-level disruption outside the mPFC. Therefore, we hypothesized that (2) even when the mPFC is not required, mPFC disinhibition may impair reversal performance. To test hypotheses (1) and (2), we first examined the effect of mPFC functional inhibition and disinhibition, by microinfusion of the GABA-A receptor agonist muscimol and antagonist picrotoxin, on early reversals (reversals 1-3) versus late reversals (reversal 5 onwards) on a 2-lever discrimination task in adult male rats. mPFC functional inhibition by muscimol impaired only early reversals, increasing perseveration and impairing lose-shift behavior at reversal 2. In contrast, mPFC disinhibition by picrotoxin impaired late reversals, reducing lose-shift and win-stay behavior. Using chemogenetic mPFC disinhibition (hM4Di-mediated inhibition of GABAergic neurons), we further tested hypothesis (2). Similar to mPFC picrotoxin, chemogenetic mPFC disinhibition impaired late reversals, primarily disrupting win-stay behavior. Our findings suggest that reduced and disinhibited mPFC activity impair distinct aspects of reversal learning.Significance statement Schizophrenia is associated with reduced activation ("hypofrontality") and neural disinhibition (reduced GABAergic inhibition) within the prefrontal cortex (PFC). However, it is not clear if and how these distinct aspects of prefrontal dysfunction contribute to impaired reversal learning, a key feature of the cognitive inflexibility characterizing schizophrenia. Here, we combined bi-directional manipulations of prefrontal GABAergic inhibition with testing of reversal learning in rats. Increasing prefrontal functional inhibition (i.e., reducing prefrontal activation) selectively impaired early reversals, enhancing perseveration and reducing lose-shift behavior, whereas prefrontal disinhibition disrupted late reversals, impairing both lose-shift and win-stay behavior. Our findings suggest that reduced activation and disinhibition of PFC disrupt distinct aspects of reversal learning, by distinct mechanisms.

Animals must continually evaluate the relative value of social and nonsocial rewards to guide adaptive behavior. While both food and social stimuli engage overlapping reward networks, how these reward types are represented within specific nodes of the circuit remains unresolved. The basolateral amygdala (BLA), a region critical for valence and motivational processing, has been implicated in encoding both shared and distinct representations of social and food stimuli. Using in vivo calcium imaging in freely behaving male and female mice performing a two-choice social-sucrose operant task, we examined how individual BLA neurons encode these two different rewards within the same behavioral framework. We found that largely non-overlapping populations of BLA neurons respond to social and sucrose rewards, revealing distinct representational subspaces for each reward type. Under baseline conditions both sexes robustly encoded social and sucrose rewards, but water deprivation revealed a pronounced sex difference, shifting representations toward sucrose reward in females. Populations of sucrose reward responsive neurons in the BLA were selectively sensitive to reward omission. Specifically, sucrose-excited neurons were more strongly modulated by the absence of expected reward than sucrose-inhibited neurons, suggesting a key role for these neurons in signaling reward prediction violations. Together, these findings demonstrate that the BLA encodes social and sucrose rewards through distinct, state-dependent, and functionally heterogeneous neuronal populations, highlighting region-specific strategies for representing reward identity and internal motivational context.Significance Statement The brain's capacity to weigh different types of rewards, like sucrose versus social interaction, is fundamental to survival yet remains poorly understood. By imaging neuronal activity in the basolateral amygdala (BLA) as mice freely choose between social and sucrose rewards, we found that largely distinct populations of BLA neurons encode each reward type. Internal state selectively altered the recruitment of reward-responsive BLA neurons in a sex-dependent manner. We further show that individual BLA neurons are differentially sensitive to the omission of expected rewards based on baseline responses. Together, these findings highlight the functional diversity through which the brain assigns value across reward modalities and dynamically adapts to changing motivational states.

To investigate how altered neural signal processing influences fMRI-BOLD responses in the hippocampus, we performed simultaneous in vivo electrophysiology and BOLD-fMRI in male Wistar rats during electrical stimulation of the perforant pathway. By defining input activity via applied pulses and measuring output activity through population spikes, we were able to identify qualitative and quantitative changes in signal processing once the relationship between input and output changed. An initial series of three low-intensity stimulations (LIS) induced clear, consistent BOLD responses. However, following a high-intensity stimulation (HIS) that triggered brief neuronal after-discharges, subsequent series of three identical LIS resulted in significantly attenuated BOLD responses. Electrophysiological data revealed that while total neuronal activity remained stable across all LIS, only the initial LIS induced long-lasting changes in signal processing (persisting beyond 1 minute) and transiently increased gamma band activity. By contrast, after HIS, these changes were reversed and could no longer be re-induced, coinciding with the absence of further increases in gamma band activity. Pharmacological experiments using MK801 and isoflurane further demonstrated that the mechanisms underlying long-lasting changes in signal processing also enhance LIS-induced BOLD responses. These findings suggest that positive fMRI-BOLD responses reflect functionally relevant changes in neural network properties-such as long-lasting modifications in signal processing-rather than simple increases in total neuronal output.Significance Statement An increase in BOLD fMRI signal in a specific brain region is generally interpreted as reflecting increased neuronal activity, with larger increases taken to indicate higher levels of activity. Here, we show that identical inputs can elicit stronger BOLD responses when they also induce long-lasting changes in local network properties, even when the overall activity of principal neurons remains similar. This suggests that the BOLD response is better understood as an indicator of functionally relevant changes in local network processing rather than a purely quantitative measure of neuronal activity.

The locus coeruleus (LC) is the primary source of norepinephrine in the brain and has been implicated in the processes of attention, arousal, and perceptual decision making. Although prior work has linked transient LC activation to both sensory stimulus processing and motor processing, the precise contribution of LC to the distinct sensory and motor components of perceptual decisions remains unclear. Here, we recorded the spiking activity of single LC neurons in rhesus macaques (1 male, 1 female) while they performed a visual two-alternative forced-choice change detection task with a saccadic report, designed to cleanly dissociate sensory and motor contributions to LC activity. We found that the large majority of recorded neurons showed robust increases in response tightly locked to the choice saccade, while only a small fraction showed significant responses to the visual stimuli. Saccade-aligned LC responses did not vary with behavioral outcome, perceptual difficulty, reaction time, or session-wide fluctuations in perceptual sensitivity and criterion, indicating that LC motor-related signals were dissociated from perceptual performance. Together, these results demonstrated the existence of a subpopulation of LC neurons whose activity was tightly coupled to oculomotor output across both voluntary and involuntary eye movements during perceptual decision making, but were independent of perceptual decision accuracy. Our findings support a role for LC in facilitating motor preparation and execution in response to behaviorally significant sensory events.Significance Statement The locus coeruleus has been implicated as a main source of changes in the state of the brain through its brain-wide neuromodulatory inputs. We recorded from this deep brain structure during a task that helped separately assess how it contributes to sensory signals and eye movements to report a decision. We found that the locus coeruleus has activity consistent with a role in facilitating motor preparation relevant to perceptual decisions.

Brain networks coordinate distributed neuronal assemblies to support cognition. Spike-timing-dependent plasticity (STDP) and neuronal oscillations are key substractes for state-gated learning rules that shape network coupling and cognitive operations; nonetheless, how STDP mechanisms interact with neuronal oscillations is largely unexplored in humans. Corticocortical paired associative stimulation (ccPAS) provides a noninvasive system-level model of associative timing rules by pairing dual-site transcranial magnetic stimulation (TMS) across axonally connected regions with an interstimulus interval matched to pathway conduction. Here we (1) synthesize ccPAS applications and barriers to brain-state-coupled implementation in cognitive networks; (2) provide an actionable roadmap for real-time state estimation, targeting, and dual-site parameter selection; and (3) demonstrate a novel implementation of theta phase-locked frontoparietal (FP) ccPAS with concurrent EEG in adult human participants. We tested whether ccPAS delivered at the positive phase of ongoing theta (POS) induces distinct changes in evoked EEG activity and FP connectivity compared with phase-uncoupled ccPAS (RAND) and phase-locked single-site prefrontal (PREF) controls. At the evoked level, POS produced a frontocentral polarity reversal of the canonical N45 component and a right parietotemporal negativity relative to both controls. At the network level, POS induced frequency-specific reconfigurations in postintervention connectivity beyond either control ingredient alone. Together, these changes in evoked activity and rapid network reconfiguration provide the first empirical evidence consistent with phase-gated STDP in humans-whereby oscillatory phase gates cortical excitability and modulates STDP efficacy-emerging as short-term network-level expression. Future work will assess long-term plasticity by tracking connectivity at later time points and testing for concomitant behavioral effects.

Learning from punishment allows animals to suppress actions that produce adverse consequences while maintaining other rewarded behaviors. However, the brain mechanisms of this learning are poorly understood. Here, we combined instrumental behavioural analysis, whole-brain Fos mapping, spatial transcriptomics, computational network analysis, and chemogenetic inhibition in male and female mice. A within-subjects yoking procedure showed that suppression depended on the instrumental response-punisher contingency rather than matched shock exposure or embedded Pavlovian stimulus-shock relations. Whole-brain Fos network analysis showed marked reorganization of brain-wide Fos correlation structure after punishment learning. Punishment preserved modular, small-world organization characteristic of brain networks while reallocating regional community membership and increasing the centrality of the basolateral amygdala, zona incerta, and midbrain tegmentum. Spatial transcriptomics within these regions identified punishment-associated transcriptional programs in basolateral amygdala glutamatergic neurons, zona incerta GABAergic neurons, and multiple ventral midbrain GABAergic and dopaminergic populations. In silico deletion predicted that the basolateral amygdala, zona incerta, and rostral linear nucleus jointly support punishment learning. Consistent with this, multisite chemogenetic inhibition of these regions impaired punishment learning. Single-region inhibition revealed dissociable contributions of basolateral amygdala and zona incerta to within-session and between-session retention of punishment learning. Together, these findings show that punishment learning is supported by a brain network that enables animals to selectively suppress actions that produce adverse consequences.Significance statement Punishment learning is essential for adaptive behaviour because it allows animals to stop actions that produce harm while maintaining other rewarded actions. We show that this form of learning is not explained by shock exposure, Pavlovian fear, or activation of a single brain region. Instead, punishment learning reorganises brain-wide activity networks, recruits spatially structured transcriptional programs in specific neuronal populations, and depends on the function of the basolateral amygdala, zona incerta, and rostral linear nucleus of the raphe. These findings provide a multiscale account of how the brain learns from adverse consequences.

Subjective arousal, or feelings of activation and alertness, can dynamically modulate affect, behavior, and cognition. Momentary changes in subjective arousal have typically been assessed with self-report in humans, which may alter those very feelings. Although researchers have traditionally used pupil size as a physiological index of arousal, links between pupil dynamics and momentary changes in subjective arousal remain unclear. Here, we combined continuous pupillometry with repeated self-report probes of changing arousal as individuals engaged in a modified Monetary Incentive Delay task. Across Virtual Reality (N = 28; 12 females, 16 males) and Functional Magnetic Resonance Imaging (N = 27; 15 females, 12 males) studies, tonic and phasic pupil measures jointly predicted subsequent self-reported arousal beyond stated incentive value and at a temporal lag of approximately 1.5-3.5 seconds. Neural activity associated with pupil dynamics further predicted pupil size, self-reported arousal, and behavioral motivation in held-out data. Together, these convergent findings establish pupil size as a temporally-precise marker of momentary fluctuations in self-reported arousal.Significance Statement Subjective feelings of arousal can critically shape people's subsequent thoughts and behavior, yet tracking its continuous fluctuations remains challenging. Here, we investigated the association of pupil size with momentary changes in self-reported arousal. Across virtual reality and FMRI studies, we demonstrate that pupil size robustly predicts subsequent self-reported arousal with a specific lag of 1.5-3.5 seconds. We further dissociate these dynamics into separable tonic and phasic pupil components that reflect changes in arousal over different timescales. Crucially, neural activity driving these pupil dynamics also predicted self-reported arousal. These findings establish pupil size as a temporally precise index of momentary changes in self-reported arousal, linking physiological changes to affective experience.

Over tens of thousands of years of coevolution with humans, dogs have developed exceptional communicative abilities through both inherited adaptations and individual learning. Using diffusion MRI tractography in 108 dogs (50 males and 58 females), we disentangled how long-term selection and short-term training shape the neural architecture of communication. Comparing modern breeds to premodern dogs revealed that selective breeding for close interaction with humans has rewired communication-related networks, increasing hemispheric asymmetry and altering temporal and associative connectivity involved in vocal and lexical processing. In contrast, training induced localized plasticity: trained and released service dogs differed in sensorimotor and associative pathways supporting cue interpretation and response execution. Connectivity strength further predicted trainability, with higher behavioral scores linked to stronger cortical but weaker medial geniculate connections. Notably, trained dogs showed enhanced coupling between vocal premotor and secondary auditory regions associated with receptive vocabulary. Thus, the dog brain's communicative capacity reflects selection and experience acting across evolutionary and individual timescales.Significance Statement Dogs provide a unique model for understanding how human influence shapes brain communication systems across evolutionary and individual timescales. Here, we show that artificial selection and training leave dissociable signatures in the dog brain. Selective breeding for human-oriented roles is associated with broad changes in hemispheric asymmetry and communication-related connectivity, especially within temporal and associative networks. In contrast, intensive service-dog training is linked to more localized reconfiguration of sensorimotor and auditory-premotor pathways involved in interpreting cues and executing responses. Connectivity strength also predicts trainability across dogs. These findings suggest that canine communicative abilities emerge from the combined effects of inherited selection pressures and lifetime learning, revealing how experience and evolution jointly shape neural networks supporting interspecies communication.

Experience is thought to modify neural connections to adapt the network to be more optimal for the environment. Given the brain's complexity, multiple network changes could each move the system toward optimality. Standard approaches examine each connection independently; these studies have often shown considerable inter-individual variability and modest effects (Marek et al., 2022). Here, we take a different strategy, determining how a whole-brain connection pattern differs from the typical pattern, that is, how 'idiosyncratic' the pattern is. We examined how the idiosyncrasy of whole-brain connection patterns varies with frequency of the use of that part of cortex for attention-demanding tasks, focusing on central versus peripheral vision in healthy individuals (who use central vision more frequently for attention-demanding tasks). We found that the whole-brain pattern of functional connections to the cortical representations of central vision is idiosyncratic, whereas patterns of connections to representations of peripheral vision were very similar person-to-person in healthy vision controls (14 females, 9 males). In a second set of analyses, we examined the brains of people with central vision loss (11 females, 10 males) who use a portion of peripheral vision (the preferred retinal locus) more frequently for attention-demanding tasks in their daily lives. The cortical representation of the preferred retinal locus exhibits more idiosyncratic connections, compared to a control brain region or compared to the same brain region in matched healthy vision controls. These results are consistent with the hypothesis that increased attentive use of a brain area results in idiosyncratic patterns of whole-brain connections.Significance Statement We found that increased attentive use of a brain region results in more idiosyncratic patterns of connections of that region to the rest of the brain. Our findings support the view that the primary visual cortex retains the capacity for plasticity well beyond the critical period and that these adaptations are idiosyncratic to the individual's experiences. This approach suggests that tailoring personalized rehabilitation plans for individuals with retinal diseases may be more effective than a 'one size fits all' approach. More generally, it offers a promising framework for investigating brain plasticity in both typical and clinical populations, especially in the context of sensory loss and compensatory adaptation.

Extratelencephalic (ET) neurons in layers (L)5 and 6b of the auditory cortex (ACtx) provide major corticofugal outputs to subcortical structures and contribute to auditory learning and experience-dependent plasticity. Although both ET subtypes innervate overlapping downstream targets, they differ in morphology, intrinsic physiology, and molecular identity, suggesting distinct functional roles. However, their in vivo response properties remain incompletely characterized. Here, we used a projection-defined viral strategy to express GCaMP8s selectively in L5 and L6b ET neurons in the ACtx of male and female mice and recorded calcium activity during presentation of diverse acoustic stimuli. L5 ET neurons predominantly exhibited sound-evoked excitation, higher response sparseness, and greater trial-to-trial reliability than L6b ET neurons; these differences were most pronounced for pure tones and sinusoidally amplitude-modulated (sAM) noise. In contrast, L6b ET neurons frequently exhibited sound-evoked suppression, particularly for more complex stimuli (including sAM noise and spectrotemporal ripples). Unsupervised clustering identified separable temporal response motifs and tuning profiles. L5 ET neurons favored single-peaked frequency tuning and monotonically increasing intensity tuning, whereas L6b ET neurons exhibited complex frequency tuning, monotonically decreasing intensity tuning, and stronger pairwise functional coupling (noise correlations). Together, these results support complementary corticofugal processing streams, with L5 ET neurons conveying more selective acoustic feature representations and L6b ET neurons conveying more integrative corticofugal signals.Significance Statement The primary auditory cortex sends extensive descending projections to subcortical structures, shaping how sounds are processed. These projections arise from distinct extratelencephalic (ET) neurons in cortical layers 5 and 6b, yet how these populations encode sound has remained unclear. Using projection-specific two-photon imaging in awake mice, we show that layer 5 ET neurons convey sparse, reliable, and selective representations of acoustic features, whereas layer 6b ET neurons more often show sound-evoked suppression, complex tuning, lower reliability, and stronger coupling to one another. These findings reveal two complementary descending channels, one relaying precise feature information and the other broader, integrative signals, that together enrich cortical control over subcortical auditory processing.