Application of electroencephalographic (EEG) biofeedback therapy in the rehabilitation of patients with chronic diseases.

Schizophrenia is one of the chronic mental disorders characterized by disturbances in thought, emotion, language, perception, and behavior. There is no cure for this disease, and most of the current treatments are palliative. In this study, we aimed to analyze the application of electroencephalographic (EEG) biofeedback therapy, an adjunctive treatment used for many psychiatric disorders, in the rehabilitation of schizophrenic patients. Schizophrenic patients were selected as the experimental subjects, and the initial diagnosis criteria were set accordingly. A primary and a secondary efficacy index was then developed for the evaluation of EEG biofeedback therapy rather than traditional drug treatment. Lastly, the effects of the two methods were compared. The findings indicate that traditional drugs could be used in the treatment of mild schizophrenia, but showed poor results for severe and moderate schizophrenia. EEG biofeedback therapy was effective for the treatment of various degrees of schizophrenia and improved patients' sleep quality and anxiety. These findings have significant practical implications for the rehabilitation of schizophrenic patients and patients with chronic diseases in general.

Cortical Microcircuit Mechanisms of Mismatch Negativity and Its Underlying Subcomponents.

In the neocortex, neuronal processing of sensory events is significantly influenced by context. For instance, responses in sensory cortices are suppressed to repetitive or redundant stimuli, a phenomenon termed "stimulus-specific adaptation" (SSA). However, in a context in which that same stimulus is novel, or deviates from expectations, neuronal responses are augmented. This augmentation is termed "deviance detection" (DD). This contextual modulation of neural responses is fundamental for how the brain efficiently processes the sensory world to guide immediate and future behaviors. Notably, context modulation is deficient in some neuropsychiatric disorders such as schizophrenia (SZ), as quantified by reduced "mismatch negativity" (MMN), an electroencephalography waveform reflecting a combination of SSA and DD in sensory cortex. Although the role of NMDA-receptor function and other neuromodulatory systems on MMN is established, the precise microcircuit mechanisms of MMN and its underlying components, SSA and DD, remain unknown. When coupled with animal models, the development of powerful precision neurotechnologies over the past decade carries significant promise for making new progress into understanding the neurobiology of MMN with previously unreachable spatial resolution. Currently, rodent models represent the best tool for mechanistic study due to the vast genetic tools available. While quantifying human-like MMN waveforms in rodents is not straightforward, the "oddball" paradigms used to study it in humans and its underlying subcomponents (SSA/DD) are highly translatable across species. Here we summarize efforts published so far, with a focus on cortically measured SSA and DD in animals to maintain relevance to the classically measured MMN, which has cortical origins. While mechanistic studies that measure and contrast both components are sparse, we synthesize a potential set of microcircuit mechanisms from the existing rodent, primate, and human literature. While MMN and its subcomponents likely reflect several mechanisms across multiple brain regions, understanding fundamental microcircuit mechanisms is an important step to understand MMN as a whole. We hypothesize that SSA reflects adaptations occurring at synapses along the sensory-thalamocortical pathways, while DD depends on both SSA inherited from afferent inputs and resulting disinhibition of non-adapted neurons arising from the distinct physiology and wiring properties of local interneuronal subpopulations and NMDA-receptor function.

Altered auditory feedback perception following an 8-week mindfulness meditation practice.

Our own ongoing motor actions are perceived through sensory feedback pathways, and are integrated with neural processes to modulate further actions. This sensory feedback mechanism is known to contribute to the rehabilitation of impaired motor functions. Recent evidence also suggests that mindfulness meditation improves our awareness to sensation; therefore, enhancement of awareness to sensory feedback through mindfulness meditation training may have potential clinical applications. This study investigated an effect of eight-week practice of mindfulness meditation on speech perception/production processes. Among the thirty healthy participants, half of them engaged in regular meditation practice of 10 min per day for eight weeks, and the other half were not given any instructions for their daily life. The change of speech performance in sentence reading under 200 ms delayed auditory feedback (DAF) condition were assessed compared to without delay condition. Also, event-related potential response to the short sound of /a/, were measured. The result showed that, after the eight-week practice, the meditation group showed significantly improved speech fluency in the DAF condition, when 16-min meditation was introduced before the experiments. Furthermore, significantly increased auditory evoked potentials were observed in the central-parietal region when the participants listened to the delayed auditory feedback sound of their own voice. These findings provide the first glimpses into the possible relationship between mindfulness meditation and auditory feedback. Different instructions for daily activity between the meditation and control groups should be considered in further studies.

Event-related potentials in the odd-ball paradigm and behavioral scales for the assessment of children and adolescents with disorders of consciousness: A proof of concept study.

OBJECTIVE: Quantification of signatures of conscious processing in children with disorders of consciousness (DoC) using odd-ball paradigms in multiple modalities. METHOD: We review the diagnostic approaches available in the field, from clinical scales to neuroimaging methods, and concentrate upon measures derived from electroencephalographic event related potentials. RESULTS: Evoked potentials were recorded in five procedures, encompassing visual, auditory and tactile modalities, from ten pediatric DoC patients-six in a minimally conscious state (MCS), three in unresponsive wakefulness syndrome (UWS) and one who emerged from MCS (eMCS)-and the control group of 10 healthy children. In almost all the eMCS and MCS patients, higher amplitude of P300 was observed and the effect was statistically significant in at least one out of the five performed procedures. Additionally, signs of conscious information processing were detected in one UWS patient. CONCLUSION: The presented results provide a proof of concept for the possibility of applying ERP-derived electrophysiological measures as an aid in the assessment of children and adolescents in DoC.

Acute effects of meditation training on the waking and sleeping brain: Is it all about homeostasis?

Our recent finding of a meditation-related increase in low-frequency NREM sleep EEG oscillatory activities peaking in the theta-alpha range (4-12 Hz) was not predicted. From a consolidated body of research on sleep homeostasis, we would expect a change peaking in slow wave activity (1-4 Hz) following an intense meditation session. Here we compared these changes in sleep with the post-meditation changes in waking rest scalp power to further characterize their functional significance. High-density EEG recordings were acquired from 27 long-term meditators (LTM) on three separate days at baseline and following two 8-hr sessions of either mindfulness or compassion-and-loving-kindness meditation. Thirty-one meditation-naïve participants (MNP) were recorded at the same time points. As a common effect of meditation practice, we found increases in low and fast waking EEG oscillations for LTM only, peaking at eight and 15 Hz respectively, over prefrontal, and left centro-parietal electrodes. Paralleling our previous findings in sleep, there was no significant difference between meditation styles in LTM as well as no difference between matched sessions in MNP. Meditation-related changes in wakefulness and NREM sleep were correlated across space and frequency. A significant correlation was found in the EEG low frequencies (<12 Hz). Since the peak of coupling was observed in the theta-alpha oscillatory range, sleep homeostatic response to meditation practice is not sufficient to explain our findings. Another likely phenomenon into play is a reverberation of meditation-related processes during subsequent sleep. Future studies should ascertain the interplay between these processes in promoting the beneficial effects of meditation practice.

Defining and quantifying users' mental imagery-based BCI skills: a first step.

OBJECTIVE: While promising for many applications, electroencephalography (EEG)-based brain-computer interfaces (BCIs) are still scarcely used outside laboratories, due to a poor reliability. It is thus necessary to study and fix this reliability issue. Doing so requires the use of appropriate reliability metrics to quantify both the classification algorithm and the BCI user's performances. So far, classification accuracy (CA) is the typical metric used for both aspects. However, we argue in this paper that CA is a poor metric to study BCI users' skills. Here, we propose a definition and new metrics to quantify such BCI skills for mental imagery (MI) BCIs, independently of any classification algorithm. APPROACH: We first show in this paper that CA is notably unspecific, discrete, training data and classifier dependent, and as such may not always reflect successful self-modulation of EEG patterns by the user. We then propose a definition of MI-BCI skills that reflects how well the user can self-modulate EEG patterns, and thus how well he could control an MI-BCI. Finally, we propose new performance metrics, classDis, restDist and classStab that specifically measure how distinct and stable the EEG patterns produced by the user are, independently of any classifier. MAIN RESULTS: By re-analyzing EEG data sets with such new metrics, we indeed confirmed that CA may hide some increase in MI-BCI skills or hide the user inability to self-modulate a given EEG pattern. On the other hand, our new metrics could reveal such skill improvements as well as identify when a mental task performed by a user was no different than rest EEG. SIGNIFICANCE: Our results showed that when studying MI-BCI users' skills, CA should be used with care, and complemented with metrics such as the new ones proposed. Our results also stressed the need to redefine BCI user training by considering the different BCI subskills and their measures. To promote the complementary use of our new metrics, we provide the Matlab code to compute them for free and open-source.

Evaluación de parámetros de banda ancha en la determinación de dominancia cerebral durante la hipnosis / Evaluation of wide band parameters in the determination of cerebral dominance during hypnosis

Se realizó un estudio cuasiexperimental de 21 estudiantes que cursaban la carrera de medicina, los cuales se encontraban en estado de hipnosis, atendidos en el Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba, desde septiembre del 2014 hasta junio del 2015, con vistas a identificar las medidas espectrales de banda ancha sensibles en la determinación de la dominancia cerebral durante dicho estado. Entre las variables analizadas figuraron: nivel de profundidad hipnótica, medidas espectrales de banda ancha y derivación. Se utilizó el estadígrafo false discovery rate como prueba de hipótesis para validar la información estadística y el análisis de varianza multivariado Manova. Los resultados revelaron que el poder relativo theta resultó ser la medida espectral con modificaciones más significativas y mostró un predominio discreto de la energía en el hemisferio izquierdo. Se concluyó que este hallazgo tuvo lugar como consecuencia de las tareas indicadas durante la hipnosis

A quasi-experiment of 21 students that were studying the medicine career, who were in hypnosis state, assisted in Dr Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, was carried out from September, 2014 to June, 2015, aimed at identifying the wide band spectral measures sensitive in the determination of cerebral dominance during this state. Among the analyzed variables we can mention: level of hypnotic depth and spectral measures of wide band and derivation. The false discovery rate stadigraph was used as hypothesis test to validate the statistical information and the Manova multivaried analysis of variance. The results revealed that theta relative power was the spectral measure with more significant modifications and showed a discreet prevalence of energy in the left hemisphere. It was concluded that this finding took place as a consequence of the given tasks during hypnosis

Effects of a brief mindfulness-meditation intervention on neural measures of response inhibition in cigarette smokers.

Research suggests that mindfulness-practices may aid smoking cessation. Yet, the neural mechanisms underlying the effects of mindfulness-practices on smoking are unclear. Response inhibition is a main deficit in addiction, is associated with relapse, and could therefore be a candidate target for mindfulness-based practices. The current study hence investigated the effects of a brief mindfulness-practice on response inhibition in smokers using behavioral and electroencephalography (EEG) measures. Fifty participants (33 females, mean age 20 years old) underwent a protocol of cigarette exposure to induce craving (cue-exposure) and were then randomly assigned to a group receiving mindfulness-instructions or control-instructions (for 15 minutes approximately). Immediately after this, they performed a smoking Go/NoGo task, while their brain activity was recorded. At the behavioral level, no group differences were observed. However, EEG analyses revealed a decrease in P3 amplitude during NoGo vs. Go trials in the mindfulness versus control group. The lower P3 amplitude might indicate less-effortful response inhibition after the mindfulness-practice, and suggest that enhanced response inhibition underlies observed positive effects of mindfulness on smoking behavior.

Mismatch Negativity and P3a in Adolescents and Young Adults with Autism Spectrum Disorders: Behavioral Correlates and Clinical Implications.

In a sample of 37 adolescents and young adults with autism spectrum disorder (ASD) and 35 typically-developing controls (TDC), we investigated sensory symptoms by clinical measures, and Mismatch Negativity and P3a component at Fz with the frequency and duration oddball paradigms of event-related potentials. Results showed that compared to TDC, ASD participants reported more sensory symptoms, and presented a shorter P3a peak latency in the duration paradigm, which was correlated with more social awareness deficits. In the frequency paradigm, P3a parameters were correlated with sensation avoiding and attention characteristics of ASD. Our findings suggest that sensory abnormality in ASD may extend into adolescence and young adulthood. P3a latency might be a potential neurophysiological marker for ASD.

Disgust but not Health Anxiety Graphic Warning Labels Reduce Motivated Attention in Smokers: A Study of P300 and Late Positive Potential Responses.

Background: Graphic health warning labels (GHWLs) on tobacco products attempt to leverage avoidance-promoting emotions, such as anxiety and disgust, to encourage cessation. Prior studies have relied on self-report or attentional metrics that may not accurately illuminate GHWLs' ability to motivate change. This report evaluates the impact of disgust- and anxiety-based GHWLs on electroencephalograph (EEG) measures of motivated attention among two groups of smokers-those that report higher versus lower cigarette dependence. We hypothesized that both anxiety and disgust GHWLs would reduce appetitive attention, as indexed by lowered P300 (P3) and late positive potential (LPP) activations. Methods: Sixty-one smokers provided demographic and smoking history before completing an oddball paradigm consisting of three counterbalanced stimuli blocks. Each block (100 trials) contained a neutral, GHWL-anxiety, or GHWL-disgust frequent image and a smoking cue as the oddball image (20%). Oddball trials for each block were averaged, P3 and LPP were identified at midline electrode positions (Fz, Cz, and Pz), and mean amplitude was analyzed. Results: Separate mixed-model ANOVAs of P3 and LPP reactivity revealed disgust-focused GHWLs reduced motivated attentional processing. Conversely, the anxiety-focused GHWL appeared to increase the salience of the smoking cue (Fz only). Less-dependent smokers showed lower P3 reactivity than those with higher dependence at Fz, but greater P3 reactivity at Cz and Pz. Conclusion: These results extend prior work in demonstrating that disgust, but not anxiety-based GHWLs, may reduce EEG-assessed motivated attention to smoking cues. Disgust may thus represent a more fruitful target for public health cessation efforts. Implications: Most GHWL evaluations have focused on fear (or anxiety) elicitation rather than disgust, an emotion that may have a unique link to smoking, having evolved specifically to facilitate the avoidance of contaminants via oral incorporation. Analyses of P300 and LPP responses to GHWLs suggest that disgust-focused images interfere with the EEG-indexed attentional processing of smoking cues and do so better than health anxiety-focused messages. However, interaction effects at different electrode sites indicated that GHWLs have complex effects in more versus less-dependent smokers and that an understanding of how smoking cues and anti-smoking imagery become associated over time is needed to identify relevant targets for public health efforts.

Risk of depression enhances auditory Pitch discrimination in the brain as indexed by the mismatch negativity.

OBJECTIVE: Depression is a state of aversion to activity and low mood that affects behaviour, thoughts, feelings and sense of well-being. Moreover, the individual depression trait is associated with altered auditory cortex activation and appraisal of the affective content of sounds. METHODS: Mismatch negativity responses (MMNs) to acoustic feature changes (pitch, timbre, location, intensity, slide and rhythm) inserted in a musical sequence played in major or minor mode were recorded using magnetoencephalography (MEG) in 88 subclinical participants with depression risk. RESULTS: We found correlations between MMNs to slide and pitch and the level of depression risk reported by participants, indicating that higher MMNs correspond to higher risk of depression. Furthermore we found significantly higher MMN amplitudes to mistuned pitches within a major context compared to MMNs to pitch changes in a minor context. CONCLUSIONS: The brains of individuals with depression risk are more responsive to mistuned and fast pitch stimulus changes, even at a pre-attentive level. SIGNIFICANCE: Considering the altered appraisal of affective contents of sounds in depression and the relevance of spectral pitch features for those contents in music and speech, we propose that individuals with subclinical depression risk are more tuned to tracking sudden pitch changes.

Physiological and psychological responses of humans to the index of greenness of an interior space.

The objective of this study was to identify the optimal index of greenness in terms of psychophysiological responses and subjective preference. We recruited 103 adult (51 male, 52 female) participants, who were examined individually in an interior space (lab) setting at Konkuk University, Seoul, South Korea. Participants observed plants in the space for 3min per experimental index of greenness (5%, 20%, 50%, and 80%). During this period, heart rate variability (HRV) and electroencephalographic (EEG) physiological responses were measured, and the participant's preference for index of greenness and subjective index of greenness was determined via surveys. HRV values were normal, and not significantly different, except that male participants showed higher mean variability between cardiac NN intervals and greater autonomic activity than female participants (P<0.05). EEG data were not significantly different, except that female participants had a significantly higher mean amplitude at the left occipital (O1) electrode than male participants (P<0.01). Subjectively, participants preferred the 50% index of greenness the most, though they consistently reported the subjective index of greenness to be ∼15% higher than the actual level. We conclude that given a limited interior space, even a small amount of greenery may exert a relaxing effect on people.

Predicting Mental Imagery-Based BCI Performance from Personality, Cognitive Profile and Neurophysiological Patterns.

Mental-Imagery based Brain-Computer Interfaces (MI-BCIs) allow their users to send commands to a computer using their brain-activity alone (typically measured by ElectroEncephaloGraphy-EEG), which is processed while they perform specific mental tasks. While very promising, MI-BCIs remain barely used outside laboratories because of the difficulty encountered by users to control them. Indeed, although some users obtain good control performances after training, a substantial proportion remains unable to reliably control an MI-BCI. This huge variability in user-performance led the community to look for predictors of MI-BCI control ability. However, these predictors were only explored for motor-imagery based BCIs, and mostly for a single training session per subject. In this study, 18 participants were instructed to learn to control an EEG-based MI-BCI by performing 3 MI-tasks, 2 of which were non-motor tasks, across 6 training sessions, on 6 different days. Relationships between the participants' BCI control performances and their personality, cognitive profile and neurophysiological markers were explored. While no relevant relationships with neurophysiological markers were found, strong correlations between MI-BCI performances and mental-rotation scores (reflecting spatial abilities) were revealed. Also, a predictive model of MI-BCI performance based on psychometric questionnaire scores was proposed. A leave-one-subject-out cross validation process revealed the stability and reliability of this model: it enabled to predict participants' performance with a mean error of less than 3 points. This study determined how users' profiles impact their MI-BCI control ability and thus clears the way for designing novel MI-BCI training protocols, adapted to the profile of each user.

Detection of stress/anxiety state from EEG features during video watching.

This paper studies the effect of stress/anxiety states on EEG signals during video sessions. The levels of arousal and valence that are induced to each subject while watching each video are self rated. These levels are mapped in stress and relaxed states and subjects that fufill criteria of adequate anxiety/stress scale were chosen leading to a subset of 18 subjects. Then, temporal, spectral and non linear EEG features are evaluated for being able to represent accurately states under investigation. Feature selection schemes choose the most significant of them in order to provide increased discrimination ability between relaxed and anxiety/stress states.

Spirituality aspects in patients with epilepsy.

PURPOSE: Do epilepsy and spirituality interact? This study aimed to determine whether an easy-to-administer scale, such as the spirituality self-rating scale (SSRS), could detect increased religiousness in people with epilepsy and verify how epilepsy influences spirituality. METHODS: A total of 196 consecutive patients with epilepsy (epilepsy group, EG) with a mean age and standard deviation of 46.5 ± 14.8 years and 66 subjects with no history of neurological or other chronic disorders (control group, CG) were assessed by the SSRS and neurologically. RESULTS: The SSRS scores of the EG and CG did not differ significantly (22.8 ± 5.1 and 22.0 ± 5.7, respectively). Patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) had significantly higher SSRS scores than those with other epileptic syndromes and, than in individuals of the CG. Multiple regression showed that the factors significantly associated with greater spirituality (greater SSRS score) for the EG, were lower education level, abnormal background EEG activity, and MTLE-HS. Other relationships with the clinical features of epilepsy and with the presence of psychiatric co-morbidity were not found. CONCLUSION: The present findings do not confirm a specific role of epilepsy in spirituality or of "epileptic hyperreligiosity," but suggest that spirituality in people with epilepsy is influenced by education level, and may also stem from epilepsy-related factors such as abnormal background EEG activity and the presence of MTLE-HS.

Natural stimuli from three coherent modalities enhance behavioral responses and electrophysiological cortical activity in humans.

Cues that involve a number of sensory modalities are processed in the brain in an interactive multimodal manner rather than independently for each modality. We studied multimodal integration in a natural, yet fully controlled scene, implemented as an interactive game in an auditory-haptic-visual virtual environment. In this imitation of a natural scene, the targets of perception were ecologically valid uni-, bi- and tri-modal manifestations of a simple event-a ball hitting a wall. Subjects were engaged in the game while their behavioral and early cortical electrophysiological responses were measured. Behavioral results confirmed that tri-modal cues were detected faster and more accurately than bi-modal cues, which, likewise, showed advantages over unimodal responses. Event-Related Potentials (ERPs) were recorded, and the first 200 ms following stimulus onset was analyzed to reveal the latencies of cortical multimodal interactions as estimated by sLORETA. These electrophysiological findings indicated bi-modal as well as tri-modal interactions beginning very early (~30 ms), uniquely for each multimodal combination. The results suggest that early cortical multimodal integration accelerates cortical activity and, in turn, enhances performance measures. This acceleration registers on the scalp as sub-additive cortical activation.

Pre-attentive modulation of brain responses to tones in coloured-hearing synesthetes.

BACKGROUND: Coloured-hearing (CH) synesthesia is a perceptual phenomenon in which an acoustic stimulus (the inducer) initiates a concurrent colour perception (the concurrent). Individuals with CH synesthesia "see" colours when hearing tones, words, or music; this specific phenomenon suggesting a close relationship between auditory and visual representations. To date, it is still unknown whether the perception of colours is associated with a modulation of brain functions in the inducing brain area, namely in the auditory-related cortex and associated brain areas. In addition, there is an on-going debate as to whether attention to the inducer is necessarily required for eliciting a visual concurrent, or whether the latter can emerge in a pre-attentive fashion. RESULTS: By using the EEG technique in the context of a pre-attentive mismatch negativity (MMN) paradigm, we show that the binding of tones and colours in CH synesthetes is associated with increased MMN amplitudes in response to deviant tones supposed to induce novel concurrent colour perceptions. Most notably, the increased MMN amplitudes we revealed in the CH synesthetes were associated with stronger intracerebral current densities originating from the auditory cortex, parietal cortex, and ventral visual areas. CONCLUSIONS: The automatic binding of tones and colours in CH synesthetes is accompanied by an early pre-attentive process recruiting the auditory cortex, inferior and superior parietal lobules, as well as ventral occipital areas.

Selective neuronal entrainment to the beat and meter embedded in a musical rhythm.

Fundamental to the experience of music, beat and meter perception refers to the perception of periodicities while listening to music occurring within the frequency range of musical tempo. Here, we explored the spontaneous building of beat and meter hypothesized to emerge from the selective entrainment of neuronal populations at beat and meter frequencies. The electroencephalogram (EEG) was recorded while human participants listened to rhythms consisting of short sounds alternating with silences to induce a spontaneous perception of beat and meter. We found that the rhythmic stimuli elicited multiple steady state-evoked potentials (SS-EPs) observed in the EEG spectrum at frequencies corresponding to the rhythmic pattern envelope. Most importantly, the amplitude of the SS-EPs obtained at beat and meter frequencies were selectively enhanced even though the acoustic energy was not necessarily predominant at these frequencies. Furthermore, accelerating the tempo of the rhythmic stimuli so as to move away from the range of frequencies at which beats are usually perceived impaired the selective enhancement of SS-EPs at these frequencies. The observation that beat- and meter-related SS-EPs are selectively enhanced at frequencies compatible with beat and meter perception indicates that these responses do not merely reflect the physical structure of the sound envelope but, instead, reflect the spontaneous emergence of an internal representation of beat, possibly through a mechanism of selective neuronal entrainment within a resonance frequency range. Taken together, these results suggest that musical rhythms constitute a unique context to gain insight on general mechanisms of entrainment, from the neuronal level to individual level.

Benefits of multi-domain feature of mismatch negativity extracted by non-negative tensor factorization from EEG collected by low-density array.

Through exploiting temporal, spectral, time-frequency representations, and spatial properties of mismatch negativity (MMN) simultaneously, this study extracts a multi-domain feature of MMN mainly using non-negative tensor factorization. In our experiment, the peak amplitude of MMN between children with reading disability and children with attention deficit was not significantly different, whereas the new feature of MMN significantly discriminated the two groups of children. This is because the feature was derived from multi-domain information with significant reduction of the heterogeneous effect of datasets.

Humans can learn new information during sleep.

During sleep, humans can strengthen previously acquired memories, but whether they can acquire entirely new information remains unknown. The nonverbal nature of the olfactory sniff response, in which pleasant odors drive stronger sniffs and unpleasant odors drive weaker sniffs, allowed us to test learning in humans during sleep. Using partial-reinforcement trace conditioning, we paired pleasant and unpleasant odors with different tones during sleep and then measured the sniff response to tones alone during the same nights' sleep and during ensuing wake. We found that sleeping subjects learned novel associations between tones and odors such that they then sniffed in response to tones alone. Moreover, these newly learned tone-induced sniffs differed according to the odor pleasantness that was previously associated with the tone during sleep. This acquired behavior persisted throughout the night and into ensuing wake, without later awareness of the learning process. Thus, humans learned new information during sleep.