Cortical high-frequency oscillations (≈ 110 Hz) in cats are state-dependent and enhanced by a subanesthetic dose of ketamine.

Ketamine is an NMDA receptor antagonist that has antidepressant and anesthetic properties. At subanesthetic doses, ketamine induces transient psychosis in humans, and is used to model psychosis in experimental animals. In rodents, subanesthetic doses of ketamine increase the power of high-frequency oscillations (HFO, > 100 Hz) in the electroencephalogram (EEG), a frequency band linked to cognitive functions. However, to date, the effects of ketamine in carnivores and primates have been poorly investigated. Here, we examined in the cat, cortical HFO during wakefulness, sleep, and after administering a sub-anesthetic dose of ketamine. Four cats were prepared with cortical electrodes for chronic polysomnographic recordings in head-restrained conditions. The cortical HFO power, connectivity, direction of the information flow using Granger Causality (GC) analysis, their relationships with respiratory activity, and the effect of auditory stimulation were analyzed. During wakefulness, but not during sleep, we found that HFO were coupled with the inspiratory phase of the respiration. After ketamine administration, HFO power was enhanced and remained associated with the inspiratory phase. GC analysis suggests that ketamine-enhanced HFO originate from the olfactory bulb (OB) and stream towards the prefrontal cortex (Pf). Accordingly, occluding the nostrils significantly reduced the power of the ketamine-enhanced HFO in both the OB and Pf. Finally, auditory stimulation did not affect HFO. In conclusion, the HFO are associated with respiration during wakefulness, but not during sleep. The enhancement of this rhythm by ketamine may disrupt cortical information processing, which could contribute to some of the neuropsychiatric effects associated with ketamine.

Auditory circuits: Watchmen of the sleeping brain.

A new study shows that glutamatergic neurons of the pontine central gray (PCG) play a key role in mediating rapid sound-induced awakenings from sleep by relaying short-latency auditory information to multiple arousal centers in the brain.

Awake prone positioning in an infant following living donor liver transplantation.

BACKGROUND: Prone position has been proven to improve ventilation and oxygenation in infants. Currently, there are few reports of early prone position ventilation after pediatric liver transplantation. Here, we present our experience with prone position in an infant following living donor liver transplantation, in an attempt to improve oxygenation. CASE PRESENTATION: An 8-month-old boy, 7.5 kg, experienced two failed extubations that presented with Type II respiratory failure due to dyspnea, potentially caused by consolidation and airway secretions. To prevent the third failure of extubation, prone position ventilation was implemented after the third extubation on the 11th postoperative day. Oxygenation increased after each prone position session with no signs of transplant liver ischemia or other adverse outcomes. Following two days of continuous prone position, airway secretions decreased, and the infant was discharged from the ICU. The third extubation procedure was successful. CONCLUSIONS: Prone position ventilation may be effective in this infant without adverse events, indicating that early prone position is not absolutely contraindicated after pediatric liver transplantation. Therefore, more reasonable prone position strategies should be sought in infants undergoing liver transplantation.

The temporal asymmetry of cortical dynamics as a signature of brain states.

The brain is a complex non-equilibrium system capable of expressing many different dynamics as well as the transitions between them. We hypothesized that the level of non-equilibrium can serve as a signature of a given brain state, which was quantified using the arrow of time (the level of irreversibility). Using this thermodynamic framework, the irreversibility of emergent cortical activity was quantified from local field potential recordings in male Lister-hooded rats at different anesthesia levels and during the sleep-wake cycle. This measure was carried out on five distinct brain states: slow-wave sleep, awake, deep anesthesia-slow waves, light anesthesia-slow waves, and microarousals. Low levels of irreversibility were associated with synchronous activity found both in deep anesthesia and slow-wave sleep states, suggesting that slow waves were the state closest to the thermodynamic equilibrium (maximum symmetry), thus requiring minimum energy. Higher levels of irreversibility were found when brain dynamics became more asynchronous, for example, in wakefulness. These changes were also reflected in the hierarchy of cortical dynamics across different cortical areas. The neural dynamics associated with different brain states were characterized by different degrees of irreversibility and hierarchy, also acting as markers of brain state transitions. This could open new routes to monitoring, controlling, and even changing brain states in health and disease.

Massive perturbation of sound representations by anesthesia in the auditory brainstem.

Anesthesia modifies sensory representations in the thalamo-cortical circuit but is considered to have a milder impact on peripheral sensory processing. Here, tracking the same neurons across wakefulness and isoflurane or ketamine medetomidine anesthesia, we show that the amplitude and sign of single neuron responses to sounds are massively modified by anesthesia in the cochlear nucleus of the brainstem, the first relay of the auditory system. The reorganization of activity is so profound that decoding of sound representation under anesthesia is not possible based on awake activity. However, population-level parameters, such as average tuning strength and population decoding accuracy, are weakly affected by anesthesia, explaining why its effect has previously gone unnoticed when comparing independently sampled neurons. Together, our results indicate that the functional organization of the auditory brainstem largely depends on the network state and is ill-defined under anesthesia. This demonstrates a remarkable sensitivity of an early sensory stage to anesthesia, which is bound to disrupt downstream processing.

Comparison of the effectiveness of awake-prone positioning and high-flow nasal oxygen in patients with COVID-19-related acute respiratory failure between different waves.

OBJECTIVE: To compare the effectiveness of the awake-prone position on relevant clinical outcomes in patients with COVID-19-related acute respiratory failure requiring high-flow nasal oxygen between different waves in Argentina. METHODS: This multicenter, prospective cohort study included adult patients with COVID-19-related acute respiratory failure requiring high-flow nasal oxygen. The main exposure position was the awake-prone position (≥ 6 hours/day) compared to the non-prone position. The primary outcome was endotracheal intubation, and the secondary outcome was in-hospital mortality. The inverse probability weighting-propensity score was used to adjust the conditional probability of treatment assignment. We then adjusted for contextual variables that varied over time and compared the effectiveness between the first and second waves. RESULTS: A total of 728 patients were included: 360 during the first wave and 368 during the second wave, of whom 195 (54%) and 227 (62%) remained awake-prone for a median (p25 - 75) of 12 (10 - 16) and 14 (8 - 17) hours/day, respectively (Awake-Prone Position Group). The ORs (95%CIs) for endotracheal intubation in the Awake-Prone Position Group were 0.25 (0.13 - 0.46) and 0.19 (0.09 - 0.31) for the first and second waves, respectively (p = 0.41 for comparison between waves). The ORs for in-hospital mortality in the awake-prone position were 0.35 (0.17 - 0.65) and 0.22 (0.12 - 0.43), respectively (p = 0.44 for comparison between waves). CONCLUSION: The awake-prone position was associated with a reduction in the risk of endotracheal intubation and in-hospital mortality. These effects were independent of the context in which the intervention was applied, and no differences were observed between the different waves.

Parametric resonance brain model.

The paper introduces a parametric resonance model for characterizing some features of the brain's electrical activity. This activity is assumed to be a fundamental aspect of brain functionality underpinning functions from basic sensory processing to complex cognitive operations such as memory, reasoning, and emotion. A pivotal element of the proposed parametric model is neuron synchronization which is crucial for generating detectable brain waves. The analysis of the frequency content of brain waves, categorized as delta (0÷4 Hz), theta (4÷7 Hz), alpha (8÷12 Hz), beta (13÷30 Hz), and gamma (30÷100 Hz) reveals, notably, that the mean frequency of each of these brain wave classes is, in sequence, approximately the double of that of the previous one. Based on this observation, the proposed parametric resonance model suggests a cascade of amplification effects. Following the proposed model, in the transition from wakefulness to sleep, the brain wave bands are energized at double frequency by higher frequency neighboring bands; on the contrary, in the sleep to awake transition, brain waves are energized at a half frequency by their lower frequency neighbor waves. Finally, the trend of increasing amplitude values from higher to lower frequencies lends empirical support to the parametric resonant brain model validity.

Emerging Functions of Neuromodulation during Sleep.

Neuromodulators act on multiple timescales to affect neuronal activity and behavior. They function as synaptic fine-tuners and master coordinators of neuronal activity across distant brain regions and body organs. While much research on neuromodulation has focused on roles in promoting features of wakefulness and transitions between sleep and wake states, the precise dynamics and functions of neuromodulatory signaling during sleep have received less attention. This review discusses research presented at our minisymposium at the 2024 Society for Neuroscience meeting, highlighting how norepinephrine, dopamine, and acetylcholine orchestrate brain oscillatory activity, control sleep architecture and microarchitecture, regulate responsiveness to sensory stimuli, and facilitate memory consolidation. The potential of each neuromodulator to influence neuronal activity is shaped by the state of the synaptic milieu, which in turn is influenced by the organismal or systemic state. Investigating the effects of neuromodulator release across different sleep substates and synaptic environments offers unique opportunities to deepen our understanding of neuromodulation and explore the distinct computational opportunities that arise during sleep. Moreover, since alterations in neuromodulatory signaling and sleep are implicated in various neuropsychiatric disorders and because existing pharmacological treatments affect neuromodulatory signaling, gaining a deeper understanding of the less-studied aspects of neuromodulators during sleep is of high importance.

Recurrent laryngeal nerve monitoring by flexible laryngoscopy during thyroid radiofrequency ablation in the awake patient.

Objective: Although radiofrequency ablation (RFA) is a safe and effective non-surgical treatment for benign thyroid nodules, injury to the recurrent laryngeal nerve (RLN), is a potential and feared complication. Intermittent voice checks have been proposed to monitor vocal cord (VC) function during RFA, but such assessment is highly subjective and effort-dependent. Methods: We are here reporting the methodological use of flexible laryngoscopy (FL) for VC monitoring during bilateral thyroid RFA treatment. The patient, a 35-year-old woman, was referred to the Endocrinology Unit for subclinical hyperthyroidism due to bilateral autonomously functioning thyroid nodules. Results: At the end of the treatment of the first nodule, the FL performed by an otorhinolaryngologist specialist allowed evaluating VC function and ruling out possible paralysis before proceeding with the contralateral RFA treatment. The patient was awake during the entire procedure and well tolerated the laryngoscopic examination. The TSH serum evaluations performed one month and 9 months after the procedure assessed an euthyroid state (TSH 3.2 mIU/L and 2.8 mIU/L, respectively). Conclusion: During bilateral thyroid RFA the use of FL for VC monitoring treatment resulted in a safe, easy-to-perform, and effective strategy to minimize and anticipate RLN injury risk in the awake patient. The prevention of RLN damage is advisable in the case of single RFA treatment, while it should be strongly recommended when RFA is performed on bilateral nodules.

An integrate-and-fire mathematical model of sleep-wake neuronal networks in the developing mammal.

Sleep behavior is present in nearly all animals, and is a vital part of growth, development, and overall health. Infant mammals cycle randomly between short bouts of sleep and wake, and the lengths of these bouts both follow an exponential distribution. As mammals mature into adulthood, the mean sleep and wake bout lengths increase, and we also observe a change in the distribution of wake bout lengths from exponential to power law. Focusing on three regions of the brainstem that are involved in sleep-wake regulation, we develop a novel integrate-and-fire neuronal network model to expand upon previous mathematical models of sleep-wake regulation in mammals, focusing on rats. This model allows fine control over neuronal connectivity while simultaneously increasing the size and complexity of the modeled system to make it more representative of reality. We establish a relationship between neuronal network structure and function that could explain the different sleep-wake behaviors observed in rats as they progress through development. We explore the relationship between three different neuronal populations as well as the overall network behavior of the system. We find that increasing synaptic connectivity strength between the wake-promoting region and the wake-active region accounts for the observed changes in mammalian sleep-wake patterns. This dynamic neuronal connectivity is a possible mechanism that accurately accounts for sleep-wake pattern changes observed during mammalian development.

Optimizing the safety and efficacy of the awake venovenous extracorporeal membrane oxygenation in patients with COVID-19-related ARDS.

BACKGROUND: Maintaining the patient awake and not intubated during the venovenous extracorporeal membrane oxygenation (VV ECMO) reduces the risk of ventilation-induced lung injury in patients with ARDS. Currently, there is a lack of data on outcomes and complications associated with the awake ECMO approach. OBJECTIVES: To evaluate outcomes and the occurrence of complications of awake ECMO approach guided by local safety protocol comprising ultrasound-guided cannulation, argatroban-based anticoagulation, respiratory support, and routine sedation targeted to reduce respiratory effort and keeping nurse-to-patient ratio of 1:1. DESIGN: A single-center retrospective case series analysis. METHODS: Consecutive patients with COVID-19-related acute respiratory distress syndrome (ARDS) (CARDS) treated by full awake VV ECMO approach from April 2019 to December 2023 were eligible. RESULTS: Our center treated 10 patients (mean age 54.7 ± 11.6 years) with CARDS with an awake ECMO approach. The reasons for awake ECMO included the presence of barotrauma in six patients, a team consensus to prefer awake ECMO instead of mechanical ventilation in three patients, and the patient's refusal to be intubated in one case. Before ECMO, patients were severely hypoxemic, with a mean value of Horowitz index of 48.9 ± 9.1 mmHg and a mean respiratory rate of 28.8 ± 7.3 breaths per minute on high-flow nasal cannula or noninvasive ventilation support. The mean duration of awake VV ECMO was 558.0 ± 173.6 h. Seven patients (70%) were successfully disconnected from ECMO and fully recovered. Intubation from respiratory causes was needed in three patients (30%), all of whom died eventually. In total, three episodes of delirium, two episodes of significant bleeding, one pneumothorax requiring chest tube insertion, and one oxygenator acute exchange occurred throughout the 5580 h of awake ECMO. No complications related to cannula displacement or malposition occurred. CONCLUSION: The awake ECMO strategy guided by safety protocol appears to be a safe approach in conscious, severely hypoxemic, non-intubated patients with COVID-19-related ARDS.

Enhancing the safety and effectiveness of extracorporeal membrane oxygenation (ECMO) therapy in awake, spontaneously breathing patients with the most severe form of COVID-19-related acute respiratory distress syndrome (ARDS)Why Was the Study Done? Extracorporeal membrane oxygenation (ECMO) represents a life-saving therapeutic approach that ensures appropriate gas exchange in patients with the most severe form of respiratory failure ­ acute respiratory distress syndrome (ARDS). Typically, patients are connected to ECMO when already deeply sedated and mechanically ventilated. The awake ECMO approach (keeping the patient awake, not intubated, and breathing spontaneously during ECMO support) minimizes the risks associated with mechanical ventilation and provides several relevant physiological benefits. However, the awake ECMO approach is also associated with several significant risks, including delirium, bleeding, and cannula displacement. Published papers have reported relatively frequent complications and method failures. What Did the Researchers Do? To address safety concerns regarding the awake ECMO approach, we present a single-center retrospective analysis of ten COVID-19-related ARDS patients treated with the awake ECMO approach, guided by the local safety protocol. What Did the Researchers Find? The awake ECMO approach yielded success (i.e., the patient was not intubated for respiratory causes, was successfully disconnected from ECMO, and fully recovered in seven patients (70.0%), outperforming previously published efficacy ranges. Three patients were intubated due to the progression of respiratory failure and eventually died. The incidence of adverse events during the 5,580 hours of awake ECMO was considered low. No cannula displacement or malposition occurred despite routine active physiotherapy, including walking during ECMO treatment in three patients. What Do the Findings Mean? The general applicability of the study is limited by the low number of patients and the retrospective monocentric design. However, the presented data illustrate real-life clinical scenarios and could aid clinicians in managing severely hypoxemic but still conscious and cooperative patients.

Functional MRI of imprinting memory in awake newborn domestic chicks.

Filial imprinting, a crucial ethological paradigm, provides insights into the neurobiology of early learning and its long-term impact on behaviour. To date, invasive techniques like autoradiography or lesions have been used to study it, limiting the exploration of whole brain networks. Recent advances in fMRI for avian brains now open new windows to explore bird's brain functions at the network level. We developed an fMRI technique for awake, newly hatched chicks, capturing BOLD signal changes during imprinting experiments. While early memory acquisition phases are understood, long-term storage and retrieval remain unclear. Our findings identified potential long-term storage of imprinting memories across a neural network, including the hippocampal formation, the medial striatum, the arcopallium, and the prefrontal-like nidopallium caudolaterale. This paradigm opens up new avenues for exploring the broader landscape of learning and memory in neonatal vertebrates, enhancing our understanding of behaviour and brain networks.

Brain Tissue Oxygen Dynamics Under Localised Hypoxia in the Awake State and the Physical Neuroprotective Effects of General Anaesthesia.

Brain health directly depends on maintaining a level of tissue oxygen that is high enough to avoid global hypoxia and local brain ischaemia. It is well documented that general anaesthesia has an anti-hypoxic neuroprotective effect. Previous studies of this effect primarily assessed the biochemical actions of anaesthetics. Physical actions were not well studied because the quantification of oxygen dynamics has only recently been described. Based on known oxygen, blood, and neuronal measurements, under various anaesthesia protocols and in the awake state, we mathematically analysed physical anaesthesia effects on oxygen distribution for localised hypoxia. From this, we built a universal equation of oxygen dynamics which can be applied to both animal and human subjects in awake and anaesthetised states, under normoxia, hyperoxia, and hypoxia. Using this equation, we determined that a proper anaesthesia protocol can protect up to 167 mm3 of local hypoxic cortical brain tissue via oxygen diffusion from healthy neighbouring areas.

The importance of including both sexes in preclinical sleep studies and analyses.

A significant effort in biomedical sciences has been made to examine relationships between sex and the mechanisms underlying various disease states and behaviors, including sleep. Here, we investigated biological sex differences in sleep using male and female C57BL/6J mice (n = 267). Physiological parameters were recorded for 48-h using non-invasive piezoelectric cages to determine total sleep, non-rapid eye movement (NREM) sleep, rapid eye movement (REM)-like sleep, and wakefulness (WAKE). We fit hierarchical generalized linear mixed models with nonlinear time effects and found substantial sex differences in sleep. Female mice slept less overall, with less NREM sleep compared to males. Females also exhibited more REM-like sleep and WAKE and had shorter NREM sleep bout lengths. We also conducted a simulation exercise where we simulated a hypothetical treatment that altered the sleep of female mice, but not male mice. In models that included an appropriate sex by treatment interaction, a female-specific treatment response was accurately estimated when sample sizes were equal but was not detected when sample sizes were unequal, and females were underrepresented. Failure to include both sexes in experimental designs or appropriately account for sex during analysis could lead to inaccurate translational recommendations in pre-clinical sleep studies.

Awake surgery with mapping-based resection to treat focal epilepsy in eloquent brain areas.

OBJECTIVES: Resective surgery is a potential therapeutic option for select patients with intractable focal epilepsy. However, the presence of ictal onset zones within or surrounding highly functional brain areas presents a surgical challenge, leading to poor seizure and functional outcomes. This report describes our experiences with awake mapping-tailored resection of epileptogenic areas involving eloquent cortices and evaluates their feasibility, tolerance, limitations, and significance. METHODS: The study included patients who underwent surgery for drug-resistant focal epilepsy at our center under awake conditions. The surgical approach aimed to achieve maximum resection of preoperatively defined epileptogenic zones, considering the boundaries defined by surrounding functional areas. We collected data on preoperative evaluations, intraoperative tests and seizures, postoperative status epilepticus, and neurological functional outcomes. RESULTS: We included 22 patients, 10 of whom had non-lesional epilepsy. Language, motor function, and sensory function were at risk in 19, 9, and 4 patients, respectively. Resection was performed as planned in 14 (63.6%) patients, while modifications were necessary in 8 (36.4%) patients due to functional constraints. The mean follow-up duration was 29.8 months. Sixteen (72.7%) patients achieved Engel class Ia outcomes, indicating seizure freedom, while none of the patients experienced clinically significant permanent postoperative neurological deficits. SIGNIFICANCE: Resective surgery with intraoperative brain mapping under awake conditions was a valid treatment option for achieving a cure in cases of drug-resistant focal epilepsy, even in situations in which the condition is considered inoperable due to the risk of significant postoperative neurological deficits.

Impact of awake extracorporeal membrane oxygenation on patients mortality with cardiogenic shock: a systematic review and trial sequential meta-analysis based on observational studies.

OBJECTIVES: The use of awake extracorporeal membrane oxygenation (ECMO, without intubation or sedation under ECMO support in patients with cardiogenic shock is growing rapidly because emerging clinical investigations indicates it may reduce morbidity associated with sedation and intubation. We systematically reviewed the efficacy of awake ECMO and provided evidence for clinical practitioners and researchers. DESIGN: Systematic review and trial sequential meta-analysis based on observational studies. DATA SOURCES: Data was retrieved from seven databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database and Cochrane Library) up to 1 March 2024. ELIGIBILITY CRITERIA: We included observational studies that compared the differences in clinical outcomes between awake ECMO and non-awake ECMO in patients with cardiogenic shock. DATA EXTRACTION AND SYNTHESIS: Two reviewers rigorously conducted literature retrieval, screening and data extraction. The RevMan software was used for data synthesis. RESULTS: Five retrospective observational studies involving 1044 patients with cardiogenic shock were included. Compared with non-awake ECMO, awake ECMO was associated with a lower mortality rate of patients with cardiogenic shock (OR=0.28; 95% CI, (0.15, 0.49); p<0.0001; I2=50%). Trial sequential analysis indicated that the sample mortality outcome reached the required information size. No significant differences were observed between the two groups on secondary outcomes such as the occurrence of ventilator-associated pneumonia, weaning from ECMO, tracheostomy, haemorrhage, thrombosis, limb ischaemia and nosocomial infection. CONCLUSIONS: Implementing awake ECMO may result in better clinical outcomes in patients with cardiogenic shock. Because of the limited sample sizes and potential bias of the current studies, more rigorously designed large-scale trials are urgently needed to verify the above findings. PROSPERO REGISTRATION NUMBER: CRD42023407607.

Caffeine Intake Alters Recovery Sleep after Sleep Deprivation.

BACKGROUND: Caffeine is a well-known psychostimulant reputed to alleviate the deleterious effects of sleep deprivation. Nevertheless, caffeine can alter sleep duration and quality, particularly during recovery sleep. We evaluated the effects of acute caffeine intake on the duration and quality of recovery sleep following total sleep deprivation (TSD), taking into account daily caffeine consumption. METHODS: Forty-one participants performed a double-blind, crossover TSD protocol (38 h of continuous wakefulness) with acute caffeine or placebo. Caffeine (2.5 mg/kg) or placebo was administered twice during continuous wakefulness (last treatment 6.5 h before bedtime for the recovery night). Polysomnographic measurements were recorded using a connected headband. RESULTS: TSD was associated with a rebound in total sleep time (TST) on the recovery night (+110.2 ± 23.2 min, p < 0.001). Caffeine intake decreased this recovery TST (-30.2 ± 8.2 min p = 0.02) and the N3 sleep stage duration (-35.6 ± 23.2 min, p < 0.01). Caffeine intake altered recovery sleep continuity (increased number of long awakenings), stability (higher stage transition frequency), and organization (less time spent in complete sleep cycle) and decreased the delta power spectral density during NREM sleep. On the recovery night, habitual daily caffeine consumption was negatively correlated with TST in caffeine and placebo conditions and positively correlated with wake after sleep onset (WASO) duration and with the frequency of long (>2 min) awakenings in the caffeine condition only. CONCLUSIONS: Acute caffeine intake during TSD affects nighttime recovery sleep, with an interaction with daily consumption. These results may influence advice on caffeine intake for night-shift workers. (NCT03859882).

Measuring the dynamic balance of integration and segregation underlying consciousness, anesthesia, and sleep in humans.

Consciousness requires a dynamic balance of integration and segregation in brain networks. We report an fMRI-based metric, the integration-segregation difference (ISD), which captures two key network properties: network efficiency (integration) and clustering (segregation). With this metric, we quantify brain state transitions from conscious wakefulness to unresponsiveness induced by the anesthetic propofol. The observed changes in ISD suggest a profound shift towards the segregation of brain networks during anesthesia. A common unimodal-transmodal sequence of disintegration and reintegration occurs in brain networks during, respectively, loss and return of responsiveness. Machine learning models using integration and segregation data accurately identify awake vs. unresponsive states and their transitions. Metastability (dynamic recurrence of non-equilibrium transient states) is more effectively explained by integration, while complexity (diversity of neural activity) is more closely linked with segregation. A parallel analysis of sleep states produces similar findings. Our results demonstrate that the ISD reliably indexes states of consciousness.

Single-neuron representations of odours in the human brain.

Olfaction is a fundamental sensory modality that guides animal and human behaviour1,2. However, the underlying neural processes of human olfaction are still poorly understood at the fundamental-that is, the single-neuron-level. Here we report recordings of single-neuron activity in the piriform cortex and medial temporal lobe in awake humans performing an odour rating and identification task. We identified odour-modulated neurons within the piriform cortex, amygdala, entorhinal cortex and hippocampus. In each of these regions, neuronal firing accurately encodes odour identity. Notably, repeated odour presentations reduce response firing rates, demonstrating central repetition suppression and habituation. Different medial temporal lobe regions have distinct roles in odour processing, with amygdala neurons encoding subjective odour valence, and hippocampal neurons predicting behavioural odour identification performance. Whereas piriform neurons preferably encode chemical odour identity, hippocampal activity reflects subjective odour perception. Critically, we identify that piriform cortex neurons reliably encode odour-related images, supporting a multimodal role of the human piriform cortex. We also observe marked cross-modal coding of both odours and images, especially in the amygdala and piriform cortex. Moreover, we identify neurons that respond to semantically coherent odour and image information, demonstrating conceptual coding schemes in olfaction. Our results bridge the long-standing gap between animal models and non-invasive human studies and advance our understanding of odour processing in the human brain by identifying neuronal odour-coding principles, regional functional differences and cross-modal integration.