Behavioral Relevance Research Articles

Abstracts from The 39th Annual Symposium of the National Neurotrauma Society, including the AANS/CNS Joint Section on Neurotrauma and Critical Care

Abstracts from The 39^th Annual Symposium of the National Neurotrauma Society, including the AANS/CNS Joint Section on Neurotrauma and Critical Care

Flexible adjustment of anticipations in human outcome processing

To sense whether thoughts refer to current reality or not, a capacity called orbitofrontal reality filtering, depends on an orbitofrontal signal when anticipated outcomes fail to occur. Here, we explored the flexibility and precision of outcome processing in a deterministic reversal learning task. Healthy subjects decided which one of two colored squares hid a target stimulus. Brain activity was measured with high-density electroencephalography. Stimuli resembling, but not identical with, the target stimuli were initially processed like different stimuli from 210 to 250 ms, irrespective of behavioral relevance. From 250 ms on, they were processed according to behavioral relevance: If they required a subsequent switch, they were processed like different stimuli; if they had been declared potential targets, they were treated like true targets. Stimuli requiring a behavioral switch induced strong theta activity in orbitofrontal, ventromedial, and medial temporal regions. The study indicates flexible adaptation of anticipations but precise processing of outcomes, mainly determined by behavioral relevance.

Neural Processing of Naturalistic Echolocation Signals in Bats.

Echolocation behavior, a navigation strategy based on acoustic signals, allows scientists to explore neural processing of behaviorally relevant stimuli. For the purpose of orientation, bats broadcast echolocation calls and extract spatial information from the echoes. Because bats control call emission and thus the availability of spatial information, the behavioral relevance of these signals is undiscussable. While most neurophysiological studies, conducted in the past, used synthesized acoustic stimuli that mimic portions of the echolocation signals, recent progress has been made to understand how naturalistic echolocation signals are encoded in the bat brain. Here, we review how does stimulus history affect neural processing, how spatial information from multiple objects and how echolocation signals embedded in a naturalistic, noisy environment are processed in the bat brain. We end our review by discussing the huge potential that state-of-the-art recording techniques provide to gain a more complete picture on the neuroethology of echolocation behavior.

Mapping of Structure-Function Age-Related Connectivity Changes on Cognition Using Multimodal MRI

The relationship between age-related changes in brain structural connectivity (SC) and functional connectivity (FC) with cognition is not well understood. Furthermore, it is not clear whether cognition is represented via a similar spatial pattern of FC and SC or instead is mapped by distinct sets of distributed connectivity patterns. To this end, we used a longitudinal, within-subject, multimodal approach aiming to combine brain data from diffusion-weighted MRI (DW-MRI), and functional MRI (fMRI) with behavioral evaluation, to better understand how changes in FC and SC correlate with changes in cognition in a sample of older adults. FC and SC measures were derived from the multimodal scans acquired at two time points. Change in FC and SC was correlated with 13 behavioral measures of cognitive function using Partial Least Squares Correlation (PLSC). Two of the measures indicate an age-related change in cognition and the rest indicate baseline cognitive performance. FC and SC—cognition correlations were expressed across several cognitive measures, and numerous structural and functional cortical connections, mainly cingulo-opercular, dorsolateral prefrontal, somatosensory and motor, and temporo-parieto-occipital, contributed both positively and negatively to the brain-behavior relationship. Whole-brain FC and SC captured distinct and independent connections related to the cognitive measures. Overall, we examined age-related function-structure associations of the brain in a comprehensive and integrated manner, using a multimodal approach. We pointed out the behavioral relevance of age-related changes in FC and SC. Taken together, our results highlight that the heterogeneity in distributed FC and SC connectivity patterns provide unique information about the variable nature of healthy cognitive aging.

Dissociable multi-scale patterns of development in personalized brain networks

The brain is organized into networks at multiple resolutions, or scales, yet studies of functional network development typically focus on a single scale. Here, we derive personalized functional networks across 29 scales in a large sample of youths (n = 693, ages 8–23 years) to identify multi-scale patterns of network re-organization related to neurocognitive development. We found that developmental shifts in inter-network coupling reflect and strengthen a functional hierarchy of cortical organization. Furthermore, we observed that scale-dependent effects were present in lower-order, unimodal networks, but not higher-order, transmodal networks. Finally, we found that network maturation had clear behavioral relevance: the development of coupling in unimodal and transmodal networks are dissociably related to the emergence of executive function. These results suggest that the development of functional brain networks align with and refine a hierarchy linked to cognition.

Estimating How Sounds Modulate Orientation Representation in the Primary Visual Cortex Using Shallow Neural Networks.

Audiovisual perception results from the interaction between visual and auditory processing. Hence, presenting auditory and visual inputs simultaneously usually improves the accuracy of the unimodal percepts, but can also lead to audiovisual illusions. Cross-talks between visual and auditory inputs during sensory processing were recently shown to occur as early as in the primary visual cortex (V1). In a previous study, we demonstrated that sounds improve the representation of the orientation of visual stimuli in the naïve mouse V1 by promoting the recruitment of neurons better tuned to the orientation and direction of the visual stimulus. However, we did not test if this type of modulation was still present when the auditory and visual stimuli were both behaviorally relevant. To determine the effect of sounds on active visual processing, we performed calcium imaging in V1 while mice were performing an audiovisual task. We then compared the representations of the task stimuli orientations in the unimodal visual and audiovisual context using shallow neural networks (SNNs). SNNs were chosen because of the biological plausibility of their computational structure and the possibility of identifying post hoc the biological neurons having the strongest influence on the classification decision. We first showed that SNNs can categorize the activity of V1 neurons evoked by drifting gratings of 12 different orientations. Then, we demonstrated using the connection weight approach that SNN training assigns the largest computational weight to the V1 neurons having the best orientation and direction selectivity. Finally, we showed that it is possible to use SNNs to determine how V1 neurons represent the orientations of stimuli that do not belong to the set of orientations used for SNN training. Once the SNN approach was established, we replicated the previous finding that sounds improve orientation representation in the V1 of naïve mice. Then, we showed that, in mice performing an audiovisual detection task, task tones improve the representation of the visual cues associated with the reward while deteriorating the representation of non-rewarded cues. Altogether, our results suggest that the direction of sound modulation in V1 depends on the behavioral relevance of the visual cue.

Sound disrupts sleep-associated brain oscillations in rodents in a meaning-dependent manner

Sleep is essential but places animals at risk. Filtering acoustic information according to its relevance, a process generally known as sensory gating, is crucial during sleep to ensure a balance between rest and danger detection. The mechanisms of this sensory gating and its specificity are not understood. Here, we tested the effect that sounds of different meaning have on sleep-associated ongoing oscillations. We recorded EEG and EMG from mice during REM and NREM sleep while presenting sounds with or without behavioural relevance. We found that sound presentation per se, in the form of a neutral sound, elicited a weak or no change in the power of sleep-state-dependent EEG during REM and NREM sleep. In contrast, the presentation of a sound previously conditioned in an aversive task, elicited a clear and fast decrease in the EEG power during both sleep phases, suggesting a transition to lighter sleep without awakening. The observed changes generally weakened over training days and were not present in animals that failed to learn. Interestingly, the effect could be generalized to unfamiliar neutral sounds if presented following conditioned training, an effect that depended on sleep phase and sound type. The data demonstrate that sounds are differentially gated during sleep depending on their meaning and that this process is reflected in disruption of sleep-associated brain oscillations without behavioural arousal.

Brain Activation During Active Balancing and Its Behavioral Relevance in Younger and Older Adults: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

Age-related deterioration of balance control is widely regarded as an important phenomenon influencing quality of life and longevity, such that a more comprehensive understanding of the neural mechanisms underlying this process is warranted. Specifically, previous studies have reported that older adults typically show higher neural activity during balancing as compared to younger counterparts, but the implications of this finding on balance performance remain largely unclear. Using functional near-infrared spectroscopy (fNIRS), differences in the cortical control of balance between healthy younger (n = 27) and older (n = 35) adults were explored. More specifically, the association between cortical functional activity and balance performance across and within age groups was investigated. To this end, we measured hemodynamic responses (i.e., changes in oxygenated and deoxygenated hemoglobin) while participants balanced on an unstable device. As criterion variables for brain-behavior-correlations, we also assessed postural sway while standing on a free-swinging platform and while balancing on wobble boards with different levels of difficulty. We found that older compared to younger participants had higher activity in prefrontal and lower activity in postcentral regions. Subsequent robust regression analyses revealed that lower prefrontal brain activity was related to improved balance performance across age groups, indicating that higher activity of the prefrontal cortex during balancing reflects neural inefficiency. We also present evidence supporting that age serves as a moderator in the relationship between brain activity and balance, i.e., cortical hemodynamics generally appears to be a more important predictor of balance performance in the older than in the younger. Strikingly, we found that age differences in balance performance are mediated by balancing-induced activation of the superior frontal gyrus, thus suggesting that differential activation of this region reflects a mechanism involved in the aging process of the neural control of balance. Our study suggests that differences in functional brain activity between age groups are not a mere by-product of aging, but instead of direct behavioral relevance for balance performance. Potential implications of these findings in terms of early detection of fall-prone individuals and intervention strategies targeting balance and healthy aging are discussed.

Impact on daily mobility and risk of falling in bilateral vestibulopathy

ObjectiveTo study the behavioral relevance of postural and ocular-motor deficits on daily activity and risk of falling in patients with bilateral vestibular hypofunction (BVH).MethodsThirty patients with BVH and 30 age- and gender-matched healthy controls participated in a continuous 2-week assessment of daily activities and mobility using a body-worn inertial sensor and a 6-month prospective fall risk assessment. At inclusion, patients and controls further underwent a multi-modal clinical, score- and instrument-based assessment of general health and balance status. We analyzed the relationship between clinical, lab-, and sensor-based measures and their validity to identify those patients at a risk of general, frequent, and severe falling.ResultsPatients exhibited impairments in daily activity in particular in terms of reduced ambulatory activity (p = 0.009). 43% of patients experienced falls (13% in controls, p = 0.008) and 70% of these patients reported recurrent falling (0% in controls, p = 0.001) during prospective assessment. Severe fall-related injuries that would require medical attention neither occurred in patients nor in controls. Classificatory models based on multi-modal clinical, lab-, and sensor-based measures of balance and mobility identified patients who fell with an accuracy of 93% and patients who recurrently fell with an accuracy of 89%.ConclusionBVH is linked to particular impairments of patients’ daily activities which in turn are related to patients’ fall risk. Hence, off-laboratory measures of daily mobility may supplement standard clinical assessment in BVH to more adequately capture the burden of disease and to reliably identify those patients at a specific risk of falling.

Pain and the Triple Network Model.

Acute pain is a physiological response that causes an unpleasant sensory and emotional experience in the presence of actual or potential tissue injury. Anatomically and symptomatically, chronic pathological pain can be divided into three distinct but interconnected pathways, a lateral “painfulness” pathway, a medial “suffering” pathway and a descending pain inhibitory circuit. Pain (fullness) can exist without suffering and suffering can exist without pain (fullness). The triple network model is offering a generic unifying framework that may be used to understand a variety of neuropsychiatric illnesses. It claims that brain disorders are caused by aberrant interactions within and between three cardinal brain networks: the self-representational default mode network, the behavioral relevance encoding salience network and the goal oriented central executive network. A painful stimulus usually leads to a negative cognitive, emotional, and autonomic response, phenomenologically expressed as pain related suffering, processed by the medial pathway. This anatomically overlaps with the salience network, which encodes behavioral relevance of the painful stimuli and the central sympathetic control network. When pain lasts longer than the healing time and becomes chronic, the pain- associated somatosensory cortex activity may become functionally connected to the self-representational default mode network, i.e., it becomes an intrinsic part of the self-percept. This is most likely an evolutionary adaptation to save energy, by separating pain from sympathetic energy-consuming action. By interacting with the frontoparietal central executive network, this can eventually lead to functional impairment. In conclusion, the three well-known pain pathways can be combined into the triple network model explaining the whole range of pain related co-morbidities. This paves the path for the creation of new customized and personalized treatment methods.

Dopamine transporter silencing in the rat: systems-level alterations in striato-cerebellar and prefrontal-midbrain circuits

Silencing of dopamine transporter (DAT), a main controlling factor of dopaminergic signaling, results in biochemical and behavioral features characteristic for neuropsychiatric diseases with presumed hyperdopaminergia including schizophrenia, attention deficit hyperactivity disorder (ADHD), bipolar disorder, and obsessive-compulsive disorder (OCD). Investigation of DAT silencing thus provides a transdiagnostic approach towards a systems-level understanding of common underlying pathways. Using a high-field multimodal imaging approach and a highly sensitive cryogenic coil, we integrated structural, functional and metabolic investigations in tandem with behavioral assessments on a newly developed preclinical rat model, comparing DAT homozygous knockout (DAT-KO, N = 14), heterozygous knockout (N = 8) and wild-type male rats (N = 14). We identified spatially distributed structural and functional brain alterations encompassing motor, limbic and associative loops that demonstrated strong behavioral relevance and were highly consistent across imaging modalities. DAT-KO rats manifested pronounced volume loss in the dorsal striatum, negatively correlating with cerebellar volume increase. These alterations were associated with hyperlocomotion, repetitive behavior and loss of efficient functional small-world organization. Further, prefrontal and midbrain regions manifested opposite changes in functional connectivity and local network topology. These prefrontal disturbances were corroborated by elevated myo-inositol levels and increased volume. To conclude, our imaging genetics approach provides multimodal evidence for prefrontal-midbrain decoupling and striato-cerebellar neuroplastic compensation as two key features of constitutive DAT blockade, proposing them as transdiagnostic mechanisms of hyperdopaminergia. Thus, our study connects developmental DAT blockade to systems-level brain changes, underlying impaired action inhibition control and resulting in motor hyperactivity and compulsive-like features relevant for ADHD, schizophrenia and OCD.

Sound evoked fos-like immunoreactivity in the big brown bat.

Most bat species have highly developed audio-vocal systems, which allow them to adjust the features of echolocation calls that are optimized for different sonar tasks, such as detecting, localizing, discriminating and tracking targets. Furthermore, bats can also produce a wide array of social calls to communicate with conspecifics. The acoustic properties of some social calls differ only subtly from echolocation calls, yet bats have the ability to distinguish them and reliably produce appropriate behavioral responses. Little is known about the underlying neural processes that enable the correct classification of bat social communication sounds. One approach to this question is to identify the brain regions that are involved in the processing of sounds that carry behavioral relevance. Here, we present preliminary data on neuronal activation, as measured by c-fos expression, in big brown bats (Eptesicus fuscus) exposed to either social calls, echolocation calls or kept in silence. We focused our investigation on five relevant brain areas; three within the canonical auditory pathway (auditory cortex, inferior colliculus and medial geniculate body) and two that are involved in the processing of emotive stimulus content (amygdala and nucleus accumbens). In this manuscript we report c-fos staining of the areas of interest after exposure to conspecific calls. We discuss future work designed to overcome experimental limitations and explore whether c-fos staining reveals anatomical segregation of neurons activated by echolocation and social call categories.

The Effects of Monophasic Anodal Transcranial Pulsed Current Stimulation on Corticospinal Excitability and Motor Performance in Healthy Young Adults: A Randomized Double-Blinded Sham-Controlled Study.

Introduction: Transcranial pulsed current stimulation (tPCS) could be used to deliver electrical pulses at different frequencies to entrain the cortical neurons of the brain. Frequency dependence of these pulses in the induction of changes in corticospinal excitability (CSE) has not been reported. Objective: We aimed to assess the effect of anodal tPCS (a-tPCS) at theta (4 Hz), and gamma (75 Hz) frequencies on CSE as assessed by the peak-to-peak amplitude of transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) and motor performance. Method: In a randomized, double-blinded, sham-controlled, crossover design study, 17 healthy participants attended 3 experimental sessions and received either a-tPCS at 4 and 75 Hz, or sham a-tPCS with 1.5 mA for 15 min. The amplitude of TMS-induced resting MEPs and time for completion of the grooved pegboard test were recorded at baseline, immediately after, and 30 min after a-tPCS. Results: Both a-tPCS at 75 and 4 Hz showed significantly increased CSE compared with sham. The a-tPCS at 75 Hz induced significantly higher CSE changes compared with 4 Hz. There was a significant increase in intracortical facilitation and a significant reduction in short-interval intracortical inhibition with both 4 and 75 Hz stimulations. However, the inhibition and facilitation did not correlate with CSE. Motor performance was unaffected by the interventions. Conclusion: The high CSE changes in M1 in a-tPCS at 75 Hz provide an initial understanding of the frequency-specific effect of a-tPCS. More research is needed to establish this concept and to assess its behavioral relevance. Impact statement Transcranial pulsed current stimulation (tPCS) is a novel brain stimulation technique that can modulate neural oscillation via the pulsatile current induced by the stimulation. Using anodal tPCS, we demonstrate the neuromodulatory effect induced by the stimulation at theta and gamma frequencies. Our findings recommend anodal tPCS as a potential therapeutic tool for treating many neurological conditions with altered theta and gamma neural oscillatory activity.

Resolution of diaschisis contributes to early recovery from post-stroke aphasia

Diaschisis is a phenomenon observed in stroke that is defined as neuronal dysfunction in regions spared by the infarction but connected to the lesion site.We combined lesion network mapping and task-based functional MRI in 71 patients with post-stroke aphasia to investigate, whether diaschisis and its resolution contribute to early loss and recovery of language functions. Language activation acquired in the acute, subacute and chronic phase was analyzed in compartments with high and low normative resting-state functional connectivity to the lesion site on an individual basis.Regions with high compared to regions with low lesion connectivity showed a steeper increase in language reactivation from the acute to the subacute phase. This finding is compatible with the assumption of resolution of diaschisis. Additionally, language performance in the subacute phase and improvement from the subacute to the chronic phase significantly correlated with the diaschisis effect and its resolution, respectively, suggesting a behavioral relevance of this effect.We therefore assume that undamaged but functionally connected regions become dysfunctional due to missing input from the lesion contributing to the aphasic deficit. Since these regions are structurally intact, dysfunction resolves over time contributing to the rapid early behavioral improvement observed in aphasic stroke patients. Our results demonstrate that diaschisis and its resolution might be a relevant mechanism of early loss and recovery of language function in acute stroke patients.

Electrophysiological foundations of the human default-mode network revealed by intracranial-EEG recordings during resting-state and cognition

Investigations using noninvasive functional magnetic resonance imaging (fMRI) have provided significant insights into the unique functional organization and profound importance of the human default mode network (DMN), yet these methods are limited in their ability to resolve network dynamics across multiple timescales. Electrophysiological techniques are critical to address these challenges, yet few studies have explored the neurophysiological underpinnings of the DMN. Here we investigate the electrophysiological organization of the DMN in a common large-scale network framework consistent with prior fMRI studies. We used intracranial EEG (iEEG) recordings, and evaluated intra- and cross-network interactions during resting-state and its modulation during a cognitive task involving episodic memory formation. Our analysis revealed significantly greater intra-DMN phase iEEG synchronization in the slow-wave (< 4 Hz), while DMN interactions with other brain networks was higher in the beta (12–30 Hz) and gamma (30–80 Hz) bands. Crucially, slow-wave intra-DMN synchronization was observed in the task-free resting-state and during both verbal memory encoding and recall. Compared to resting-state, slow-wave intra-DMN phase synchronization was significantly higher during both memory encoding and recall. Slow-wave intra-DMN phase synchronization increased during successful memory retrieval, highlighting its behavioral relevance. Finally, analysis of nonlinear dynamic causal interactions revealed that the DMN is a causal outflow network during both memory encoding and recall. Our findings identify frequency specific neurophysiological signatures of the DMN which allow it to maintain stability and flexibility, intrinsically and during task-based cognition, provide novel insights into the electrophysiological foundations of the human DMN, and elucidate network mechanisms by which it supports cognition.

Insular dichotomy in the implicit detection of emotions in human faces.

The functional roles of the insula diverge between its posterior portion (PI), mainly connected with somato-sensory and motor areas, and its anterior section (AI) connected with the frontal, limbic, and cingulate regions. We report intracranial recordings of local field evoked potentials from PI, AI, and the visual fusiform gyrus to a full array of emotional faces including pain while the individuals' attention was diverted from emotions. The fusiform gyrus and PI responded equally to all types of faces, including neutrals. Conversely, the AI responded only to emotional faces, maximally to pain and fear, while remaining insensitive to neutrals. The two insular sectors reacted with almost identical latency suggesting their parallel initial activation via distinct functional routes. The consistent responses to all emotions, together with the absence of response to neutral faces, suggest that early responses in the AI reflect the immediate arousal value and behavioral relevance of emotional stimuli, which may be subserved by "fast track" routes conveying coarse-spatial-frequency information via the superior colliculus and dorsal pulvinar. Such responses precede the conscious detection of the stimulus' precise signification and valence, which need network interaction and information exchange with other brain areas, for which the AI is an essentialhub.

Impact of interhemispheric inhibition on bimanual movement control in young and old

Interhemispheric interactions demonstrate a crucial role for directing bimanual movement control. In humans, a well-established paired-pulse transcranial magnetic stimulation paradigm enables to assess these interactions by means of interhemispheric inhibition (IHI). Previous studies have examined changes in IHI from the active to the resting primary motor cortex during unilateral muscle contractions; however, behavioral relevance of such changes is still inconclusive. In the present study, we evaluated two bimanual tasks, i.e., mirror activity and bimanual anti-phase tapping, to examine behavioral relevance of IHI for bimanual movement control within this behavioral framework. Two age groups (young and older) were evaluated as bimanual movement control demonstrates evident behavioral decline in older adults. Two types of IHI with differential underlying mechanisms were measured; IHI was tested at rest and during a motor task from the active to the resting primary motor cortex. Results demonstrate an association between behavior and short-latency IHI in the young group: larger short-latency IHI correlated with better bimanual movement control (i.e., less mirror activity and better bimanual anti-phase tapping). These results support the view that short-latency IHI represents a neurophysiological marker for the ability to suppress activity of the contralateral side, likely contributing to efficient bimanual movement control. This association was not observed in the older group, suggesting age-related functional changes of IHI. To determine underlying mechanisms of impaired bimanual movement control due to neurological disorders, it is crucial to have an in-depth understanding of age-related mechanisms to disentangle disorder-related mechanisms of impaired bimanual movement control from age-related ones.

Behavioral Prioritization Enhances Working Memory Precision and Neural Population Gain.

Humans allocate visual working memory (WM) resource according to behavioral relevance, resulting in more precise memories for more important items. Theoretically, items may be maintained by feature-tuned neural populations, where the relative gain of the populations encoding each item determines precision. To test this hypothesis, we compared the amplitudes of delay period activity in the different parts of retinotopic maps representing each of several WM items, predicting the amplitudes would track behavioral priority. Using fMRI, we scanned participants while they remembered the location of multiple items over a WM delay and then reported the location of one probed item using a memory-guided saccade. Importantly, items were not equally probable to be probed (0.6, 0.3, 0.1, 0.0), which was indicated with a precue. We analyzed fMRI activity in 10 visual field maps in occipital, parietal, and frontal cortex known to be important for visual WM. In early visual cortex, but not association cortex, the amplitude of BOLD activation within voxels corresponding to the retinotopic location of visual WM items increased with the priority of the item. Interestingly, these results were contrasted with a common finding that higher-level brain regions had greater delay period activity, demonstrating a dissociation between the absolute amount of activity in a brain area and the activity of different spatially selective populations within it. These results suggest that the distribution of WM resources according to priority sculpts the relative gains of neural populations that encode items, offering a neural mechanism for how prioritization impacts memory precision.

Deadlines and Cognitive Limitations

This paper studies the interplay between deadlines and cognitive limitations. We analyze an agent’s decision to complete a one-off task under a deadline. Postponing the task can be beneficial for the agent; missing the deadline, however, leads to a drop in the agent’s rewards. If the agent exhibits cognitive limitations, postponing increases the risk of becoming inattentive and failing to complete the task in time. Our framework provides a rich set of predictions on the behavioral implications of deadlines. We test these predictions in a field experiment at a dental clinic, in which we exogenously vary deadlines and rewards for arranging check-up appointments. The empirical results underline the behavioral relevance of cognitive limitations. Imposing relatively tight deadlines induces patients to act earlier and at a persistently higher frequency than without a deadline. Evidence from a follow-up experiment and complementary surveys supports the notion that deadlines may serve as a powerful instrument when individuals’ cognitive capacity is limited.

Emergence and function of cortical offset responses in sound termination detection.

Offset responses in auditory processing appear after a sound terminates. They arise in neuronal circuits within the peripheral auditory system, but their role in the central auditory system remains unknown. Here, we ask what the behavioral relevance of cortical offset responses is and what circuit mechanisms drive them. At the perceptual level, our results reveal that experimentally minimizing auditory cortical offset responses decreases the mouse performance to detect sound termination, assigning a behavioral role to offset responses. By combining in vivo electrophysiology in the auditory cortex and thalamus of awake mice, we also demonstrate that cortical offset responses are not only inherited from the periphery but also amplified and generated de novo. Finally, we show that offset responses code more than silence, including relevant changes in sound trajectories. Together, our results reveal the importance of cortical offset responses in encoding sound termination and detecting changes within temporally discontinuous sounds crucial for speech and vocalization.