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Imagine how flicking through your photo album and seeing a picture of a beach sunset brings back fond memories of a tasty cocktail you had that night. Computational models suggest that upon receiving a partial memory cue (‘beach’), neurons in the hippocampus coordinate reinstatement of associated memories (‘cocktail’) in cortical target sites. Here, using human single neuron recordings, we show that hippocampal firing rates are elevated from ~ 500–1500 ms after cue onset during successful associative retrieval. Concurrently, the retrieved target object can be decoded from population spike patterns in adjacent entorhinal cortex (EC), with hippocampal firing preceding EC spikes and predicting the fidelity of EC object reinstatement. Prior to orchestrating reinstatement, a separate population of hippocampal neurons distinguishes different scene cues (buildings vs. landscapes). These results elucidate the hippocampal-entorhinal circuit dynamics for memory recall and reconcile disparate views on the role of the hippocampus in scene processing vs. associative memory. The hippocampus is involved both in episodic memory recall and scene processing. Here, the authors show that hippocampal neurons first process scene cues before coordinating memory-guided pattern completion in adjacent entorhinal cortex.

Concept neurons in the medial temporal lobe respond to semantic features of presented stimuli. Analyzing 61 concept neurons recorded from twelve patients who underwent surgery to treat epilepsy, we show that firing patterns of concept neurons encode relations between concepts during a picture comparison task. Thirty-three of these responded to non-preferred stimuli with a delayed but well-defined onset whenever the task required a comparison to a response-eliciting concept, but not otherwise. Supporting recent theories of working memory, concept neurons increased firing whenever attention was directed towards this concept and could be reactivated after complete activity silence. Population cross-correlations of pairs of concept neurons exhibited order-dependent asymmetric peaks specifically when their response-eliciting concepts were to be compared. Our data are consistent with synaptic mechanisms that support reinstatement of concepts and their relations after activity silence, flexibly induced through task-specific sequential activation. This way arbitrary contents of experience could become interconnected in both working and long-term memory. It is unclear how distinct concepts are processed in the brain. Here, the authors recorded from concept cells in human subjects with epilepsy and found that a subset of concept cells responded to non-preferred concepts if those non-preferred concepts required comparison to a preferred concept.

Epileptic seizures are characterized by abnormal and excessive neural activity, where cortical network dynamics seem to become unstable. However, most of the time, during seizure-free periods, cortex of epilepsy patients shows perfectly stable dynamics. This raises the question of how recurring instability can arise in the light of this stable default state. In this work, we examine two potential scenarios of seizure generation: (i) epileptic cortical areas might generally operate closer to instability, which would make epilepsy patients generally more susceptible to seizures, or (ii) epileptic cortical areas might drift systematically towards instability before seizure onset. We analyzed single-unit spike recordings from both the epileptogenic (focal) and the nonfocal cortical hemispheres of 20 epilepsy patients. We quantified the distance to instability in the framework of criticality, using a novel estimator, which enables an unbiased inference from a small set of recorded neurons. Surprisingly, we found no evidence for either scenario: Neither did focal areas generally operate closer to instability, nor were seizures preceded by a drift towards instability. In fact, our results from both pre-seizure and seizure-free intervals suggest that despite epilepsy, human cortex operates in the stable, slightly subcritical regime, just like cortex of other healthy mammalians.

Mind wandering (MW) and mindfulness have both been reported to be vital moderators of psychological wellbeing. Here, we aim to examine how closely associated these phenomena are and evaluate the psychometrics of measures often used to quantify them. We investigated two samples, one consisting of German-speaking unpaid participants (GUP, n = 313) and one of English-speaking paid participants (EPP, n = 228) recruited through MTurk.com. In an online experiment, we collected data using the Mindful Attention Awareness Scale (MAAS) and the sustained attention to response task (SART) during which self-reports of MW and meta-awareness of MW were recorded using experience sampling (ES) probes. Internal consistency of the MAAS was high (Cronbachs α of 0.96 in EPP and 0.88 in GUP). Split-half reliability for SART measures and self-reported MW was overall good with the exception of SART measures focusing on Nogo trials, and those restricted to SART trials preceding ES in a 10 s time window. We found a moderate negative association between trait mindfulness and MW as measured with ES probes in GUP, but not in EPP. Our results suggest that MW and mindfulness are on opposite sides of a spectrum of how attention is focused on the present moment and the task at hand.

Objectives The objective of this preliminary study was to explore long-term changes in neurobehavioral parameters, brain morphology and electroencephalography of sepsis patients who received intensive care compared to non-septic intensive care unit (ICU) patients. Methods Two-centre follow-up study 6–24 months after discharge from hospital using published norms and existing databases of healthy controls for comparison. Patients included 25 septic and 19 non-septic ICU survivors who were recruited from two ICUs of a university and community hospital. Measurements used include brain morphology, standard electroencephalography, cognition and psychiatric health and health-related quality of life. Results Sepsis survivors showed cognitive deficits in verbal learning and memory and had a significant reduction of left hippocampal volume compared to healthy controls. Moreover, sepsis and to some extent non-septic ICU patients had more low-frequency activity in the EEG indicating unspecific brain dysfunction. No differences were found in health-related quality of life, psychological functioning or depressive symptoms, and depression could be ruled out as a confounding factor. Conclusions This study demonstrates permanent cognitive impairment in several domains in both septic and non-septic ICU survivors and unspecific brain dysfunction. In the sepsis group, left-sided hippocampal atrophy was found compared to healthy controls. Further study is needed to clarify what contribution sepsis and other factors at the ICU make to these outcomes. Specific neuroprotective therapies are warranted to prevent persisting brain changes in ICU patients.

Recording extracellulary from neurons in the brains of animals in vivo is among the most established experimental techniques in neuroscience, and has recently become feasible in humans. Many interesting scientific questions can be addressed only when extracellular recordings last several hours, and when individual neurons are tracked throughout the entire recording. Such questions regard, for example, neuronal mechanisms of learning and memory consolidation, and the generation of epileptic seizures. Several difficulties have so far limited the use of extracellular multi-hour recordings in neuroscience: Datasets become huge, and data are necessarily noisy in clinical recording environments. No methods for spike sorting of such recordings have been available. Spike sorting refers to the process of identifying the contributions of several neurons to the signal recorded in one electrode. To overcome these difficulties, we developed Combinato: a complete data-analysis framework for spike sorting in noisy recordings lasting twelve hours or more. Our framework includes software for artifact rejection, automatic spike sorting, manual optimization, and efficient visualization of results. Our completely automatic framework excels at two tasks: It outperforms existing methods when tested on simulated and real data, and it enables researchers to analyze multi-hour recordings. We evaluated our methods on both short and multi-hour simulated datasets. To evaluate the performance of our methods in an actual neuroscientific experiment, we used data from from neurosurgical patients, recorded in order to identify visually responsive neurons in the medial temporal lobe. These neurons responded to the semantic content, rather than to visual features, of a given stimulus. To test our methods with multi-hour recordings, we made use of neurons in the human medial temporal lobe that respond selectively to the same stimulus in the evening and next morning.

Our brains create new memories by capturing the ‘who/what’, ‘where’ and ‘when’ of everyday experiences. On a neuronal level, mechanisms facilitating a successful transfer into episodic memory are still unclear. We investigated this by measuring single neuron activity in the human medial temporal lobe during encoding of item-location associations. While previous research has found predictive effects in population activity in human MTL structures, we could attribute such effects to two specialized sub-groups of neurons: concept cells in the hippocampus, amygdala and entorhinal cortex (EC), and a second group of parahippocampal location-selective neurons. In both item- and location-selective populations, firing rates were significantly higher during successfully encoded trials. These findings are in line with theories of hippocampal indexing, since selective index neurons may act as pointers to neocortical representations. Overall, activation of distinct populations of neurons could directly support the connection of the ‘what’ and ‘where’ of episodic memory. Whether specialized neuronal firing in the human MTL predicts successful memory encoding remains unknown. Here, the authors find this to be the case for two distinct populations of single neurons responding to items and locations, respectively.

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

Sensory experience elicits complex activity patterns throughout the neocortex. Projections from the neocortex converge onto the medial temporal lobe (MTL), in which distributed neocortical firing patterns are distilled into sparse representations. The precise nature of these neuronal representations is still unknown. Here, we show that population activity patterns in the MTL are governed by high levels of semantic abstraction. We recorded human single-unit activity in the MTL (4,917 units, 25 patients) while subjects viewed 100 images grouped into 10 semantic categories of 10 exemplars each. High levels of semantic abstraction were indicated by representational similarity analyses (RSAs) of patterns elicited by individual stimuli. Moreover, pattern classifiers trained to decode semantic categories generalised successfully to unseen exemplars, and classifiers trained to decode exemplar identity more often confused exemplars of the same versus different categories. Semantic abstraction and generalisation may thus be key to efficiently distill the essence of an experience into sparse representations in the human MTL. Although semantic abstraction is efficient and may facilitate generalisation of knowledge to novel situations, it comes at the cost of a loss of detail and may be central to the generation of false memories.

A central function of the human brain is to adapt to new situations based on past experience. Adaptation is reflected behaviorally by shorter reaction times to repeating or similar stimuli, and neurophysiologically by reduced neural activity in bulk-tissue measurements with fMRI or EEG. Several potential single-neuron mechanisms have been hypothesized to cause this reduction of activity at the macroscopic level. We here explore these mechanisms using an adaptation paradigm with visual stimuli bearing abstract semantic similarity. We recorded intracranial EEG (iEEG) simultaneously with spiking activity of single neurons in the medial temporal lobes of 25 neurosurgical patients. Recording from 4917 single neurons, we demonstrate that reduced event-related potentials in the macroscopic iEEG signal are associated with a sharpening of single-neuron tuning curves in the amygdala, but with an overall reduction of single-neuron activity in the hippocampus, entorhinal cortex, and parahippocampal cortex, consistent with fatiguing in these areas. Behavioural adaptation from semantic priming is accompanied by reduced neural activity in bulk-tissue measurements, but the underlying single neuron mechanisms remain unclear. Here, the authors leverage simultaneous intracranial EEG and single neuron spiking recordings in the human medial temporal lobe to unveil differential sharpening and fatiguing mechanisms across different temporal lobe areas.