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Integrating animals into therapy is applied increasingly in patients in a minimally conscious state (MCS). This pilot study investigates the effect of animal presence on frontal brain activity in MCS patients compared to healthy subjects. O; 2; HB, HHb and tHb of two MCS patients and two healthy adults was measured in frontal cortex using functional near-infrared spectroscopy during three sessions with a live animal and three sessions with a mechanical toy animal present. Each session had five phases: (1) baseline, (2) watching animal, (3) passive contact, (4) active contact, (5) neutral. Data were descriptively analysed. All participants showed the largest hemodynamic response during direct contact with the live or toy animal compared to "baseline" and "watching." During active contact, three of the four participants showed a stronger response when stroking the live compared to the toy animal. All participants showed an inverted signal with higher HHb than O; 2; Hb concentrations while stroking the live or toy animal. Animal contact leads to a neurovascular reaction in both MCS patients and healthy subjects, indicating elevated neural activity in the frontal cortex. We conclude that while a toy animal can elicit attention processes, active contact to a living animal is combined with emotional processes.

In this paper, we investigate brain directed connectivity (BDC) networks for emotion recognition using electroencephalogram (EEG) source signals that were estimated from high-density sensor EEG signals, for the first time. Currently, a variety of features extracted from sensor EEG signals are used for emotion recognition. However, they cannot unambiguously describe the location of emotions associated with neural activities and information propagation or the interaction between brain regions. In addition, most current studies use low-density sensor EEG signals. Moreover, source signals estimated from high-density sensor EEG signal have not been employed for emotion recognition to date. We designed a BDC network-based framework using EEG source signals to investigate emotion recognition. The global cortex factor-based multivariate autoregressive (GCF-MVAR) method was utilized to extract emotion-related BDC features. Our study revealed that the combined BDC and DE features facilitated a recognition accuracy of up to 89.58 %, which is higher than the rate obtained from BDC features and DE features alone. The sensor features derived from high-density EEG signals also exhibited higher recognition accuracy compared to low-density EEG signals. These findings suggest that BDC features derived from EEG source signals can better characterize human emotional states and are meaningful for emotion recognition.

Minimally delayed (MD) saccades require inhibition of a prepotent response until a target is extinguished, and unlike the more extensively studied antisaccade task, do not require the additional cognitive component of vector inversion (i.e., 180° target spatial transposition). Here, participants completed separate blocks of MD and prepotent stimulus-driven saccades (i.e., respond at target onset) while cortical hemodynamics were measured via functional transcranial Doppler ultrasound. MD saccades produced longer and more variable reaction times (RT). In turn, MD and stimulus-driven saccade preparatory phase cortical hemodynamics increased and decreased, respectively, relative to baseline and the two conditions differed from one another throughout the preparatory phase. The longer RTs and increased cortical hemodynamics of MD saccades is taken to evince response complexity and the increased neural activity to accommodate response inhibition. To our knowledge, such findings provide the first work to examine the neural foundations of MD saccades.

The development of precise neural circuits is initially directed by genetic programming and subsequently refined by neural activity. In the mouse olfactory system, axons from various olfactory sensory neurons expressing the same olfactory receptor converge onto a few spatially invariant glomeruli, generating the olfactory glomerular map in the olfactory bulbs. Using the glomerular map formation as a model, this review summarizes the current understanding of mechanisms underlying topographic map development in the mouse olfactory system and highlights how neural activity instructs the map refinement process.

PURPOSE OF REVIEW: Adolescence is a developmental period often characterized by heightened risk taking and increased sensitivity to socially salient stimuli. In this report, we discuss how the developing brain serves as both a link between, and a susceptibility factor for, social contextual factors and risk taking in adolescence. RECENT FINDINGS: Neural activity in regions related to affective processing, cognitive control, and social cognition, which continue to develop across the adolescent years, shape the relationship between adolescents’ social environment and their risk taking. SUMMARY: Examining neural patterns of adolescent brain development enriches our understanding of how adolescents’ complex social environment modulates their risk-taking behavior, which may have implications for adolescents’ current and future substance use.

Across the perinatal period, the human brain undergoes a rapid yet highly programmed sequence of maturation. In this time, neural activity has a key role in establishing the brain’s early circuits and guiding essential processes including cell differentiation, neuronal and axonal growth, arborization and synaptogenesis. fMRI studies of young infants hold great potential to understand developmental changes in systems-wide activity and their relationship to regional growth and development. These studies have shown that the brain’s activity rapidly evolves across the perinatal period, as neurovascular coupling matures and resting state networks are established. The high variability of spatial and temporal properties in functional activity may be attributed to the sensitivity of neurovascular coupling to developing cellular structure and connectivity as well as fluctuations in cerebral physiology, behavioral state, and pathology. Longitudinal studies may precisely explore these relationships and provide mechanistic understanding of the relationship between physiology, behavior, injury, and functional activity.

The human brain is a complex organ with multiple competing imperatives. It must perceive and interpret the world, incorporate new information, and maintain its functional integrity over the lifespan. Neural activity is associated with all of these processes. Spontaneous BOLD signals have been invoked as representing neural activity associated with all of these processes. However, their exact role in these processes remains controversial. Here, we review learning machine theory, molecular mechanisms of synaptic plasticity and homeostasis, and recent experimental evidence to suggest that spontaneous BOLD activity may be more closely aligned with off-line plasticity and homeostatic processes than on-line fluctuations in cognitive content.

Representing space in past and future As an organism moves through space, its brain has to remember its most recent location and anticipate its future position, not just its current place in the world. Earlier studies reported so-called retrospective and prospective place coding in rats while they were running along linear tracks. However, it would be advantageous to study an animal that rapidly moves through three-dimensional space with high precision. Dotson and Yartsev recorded from flying bats to investigate whether place cell activity in hippocampus area CA1 represents local (current) or nonlocal positions. They discovered that the hippocampus not only encodes the bat's present location but also signals its positions in the past and future. Science , abg1278, this issue p. 242

Attending toward fearful faces and other threatening stimuli increase the chance of survival. The dot-probe task is a commonly used measure of spatial attention. Event-related potentials (ERPs) have been found to be a reliable measure of attentional bias. The dot-probe literature suggests that posterior contralateral N170 amplitudes are more enhanced by fearful faces compared to ipsilateral amplitudes. However, ERP methods remove non-phase locked frequencies, which provides additional information about neural activity. Specifically, theta oscillations (5–7 Hz) have been linked to attentional processing. The purpose of this study was to examine the relationship between posterior contralateral theta oscillations and N170 amplitudes in the dot-probe task. A modified dot-probe task was used with fear and neutral facial expressions and EEG data was recorded from 33 electrodes. The ERP and time-frequency data were extracted from the P7 and P8 electrodes (left and right occipitotemporal regions). This study found enhanced N170 amplitude and theta oscillations in the electrodes posterior contralateral to the fearful face. Contralateral N170 amplitudes and theta oscillations were related such that greater N170 amplitudes were associated with greater theta oscillations. The results indicated that increased contralateral N170 and theta oscillations are related to each other and underlie attentional bias to fearful faces.

In general, the mechanisms that maintain the activity of neural systems after a triggering stimulus has been removed are not well understood. Different mechanisms involving at the cellular and network levels have been proposed. In this work, based on analysis of a computational model of a spiking neural network, it is proposed that the spike that occurs after a neuron is inhibited (the rebound spike) can be used to sustain the activity in a recurrent inhibitory neural circuit after the stimulation has been removed. It is shown that, in order to sustain the activity, the neurons participating in the recurrent circuit should fire at low frequencies. It is also shown that the occurrence of a rebound spike depends on a combination of factors including synaptic weights, synaptic conductances and the neuron state. We point out that the model developed here is minimalist and does not aim at empirical accuracy. Its purpose is to raise and discuss theoretical issues that could contribute to the understanding of neural mechanisms underlying self-sustained neural activity.

The neurobiology of addiction has been an intense topic of investigation for more than 50 years. Over this time, technological innovation in methods for studying brain function rapidly progressed, leading to increasingly sophisticated experimental approaches. To understand how specific brain regions, cell types, and circuits are affected by drugs of abuse and drive behaviors characteristic of addiction, it is necessary both to observe and manipulate neural activity in addiction-related behavioral paradigms. In pursuit of this goal, there have been several key technological advancements in in vivo imaging and neural circuit modulation in recent years, which have shed light on the cellular and circuit mechanisms of addiction. Here we discuss some of these key technologies, including circuit modulation with optogenetics, in vivo imaging with miniaturized single-photon microscopy (miniscope) and fiber photometry, and how the application of these technologies has garnered novel insights into the neurobiology of addiction.

CREB (cAMP response element-binding) transcription factors are conserved markers of memory formation in the brain and peripheral circuits. We provide immunohistochemical evidence of CREB phosphorylation in the dwarf cuttlefish, Sepia bandensis, following the inaccessible prey (IP) memory experiment. During the IP experiment, cuttlefish are shown prey enclosed in a transparent tube, and tentacle strikes against the tube decrease over time as the cuttlefish learns the prey is inaccessible. The cues driving IP learning are unclear but may include sensory inputs from arms touching the tube. The neural activity marker, anti-phospho-CREB (anti-pCREB) was used to determine whether IP training stimulated cuttlefish arm sensory neurons. pCREB immunoreactivity occurred along the oral surface of the arms, including the suckers and epithelial folds surrounding the suckers. pCREB increased in the epithelial folds and suckers of trained cuttlefish. We found differential pCREB immunoreactivity along the distal-proximal axis of trained arms, with pCREB concentrated distally. Unequal CREB phosphorylation occurred among the 4 trained arm pairs, with arm pairs 1 and 2 containing more pCREB. The resulting patterns of pCREB in trained arms suggest that the arms obtain cues that may be salient for learning and memory of the IP experiment.

Objective Although cognitive models of obsessive-compulsive disorder (OCD) fall into two categories: cognitive deficit models and dysfunctional belief models, these approaches have their own ways and have hardly been reconciled. Therefore, this study aimed to investigate the potential relationships between cognitive deficit (using the Wisconsin Card Sorting Task, WCST) and dysfunctional belief (measured by scales of dysfunctional beliefs) mediated by neural activity in OCD patients. Methods Thirty OCD patients and 30 healthy participants performed the WCST condition and a baseline MATCH condition during the 3T-functional magnetic resonance imaging (fMRI) acquisition. Results Engagement of additional frontoparietal networks with poorer performance of WCST was found during the fMRI scan in OCD patients. Selected regions of interest from activated regions have positive relationships with dysfunctional beliefs and with the unacceptable thoughts symptom dimension in the OCD group. Conclusion Findings suggest that alteration in frontoparietal networks related to cognitive deficits can be associated with dysfunctional beliefs while performing conventional neurocognitive tasks and this association with dysfunctional beliefs may be pronounced in the unacceptable thoughts domain-dominant OCD patients.

Attentional lapses occur commonly and are associated with mind wandering, where focus is turned to thoughts unrelated to ongoing tasks and environmental demands, or mind blanking, where the stream of consciousness itself comes to a halt. To understand the neural mechanisms underlying attentional lapses, we studied the behaviour, subjective experience and neural activity of healthy participants performing a task. Random interruptions prompted participants to indicate their mental states as task-focused, mind-wandering or mind-blanking. Using high-density electroencephalography, we report here that spatially and temporally localized slow waves, a pattern of neural activity characteristic of the transition toward sleep, accompany behavioural markers of lapses and preceded reports of mind wandering and mind blanking. The location of slow waves could distinguish between sluggish and impulsive behaviours, and between mind wandering and mind blanking. Our results suggest attentional lapses share a common physiological origin: the emergence of local sleep-like activity within the awake brain., Attentional lapses occur in many forms such as mind-wandering or mindblanking. Here the authors show different types of attentional lapse are accompanied by slow waves, neural activity that is characteristic of transitions into sleep.

The neural processes serving the orienting of attention toward goal-relevant stimuli are generally examined with informative cues that direct visual attention to a spatial location. However, cues predicting the temporal emergence of an object are also known to be effective in attentional orienting but are implemented less often. Differences in the neural oscillatory dynamics supporting these divergent types of attentional orienting have only rarely been examined. In this study, we utilized magnetoencephalography and an adapted Posner cueing task to investigate the spectral specificity of neural oscillations underlying these different types of attentional orienting (i.e., spatial vs. temporal). We found a spectral dissociation of attentional cueing, such that alpha (10–16 Hz) oscillations were central to spatial orienting and theta (3–6 Hz) oscillations were critical to temporal orienting. Specifically, we observed robust decreases in alpha power during spatial orienting in key attention areas (i.e., lateral occipital, posterior cingulate, and hippocampus), along with strong theta increases during temporal orienting in the primary visual cortex. These results suggest that the oscillatory dynamics supporting attentional orienting are spectrally and anatomically specific, such that spatial orienting is served by stronger alpha oscillations in attention regions, whereas temporal orienting is associated with stronger theta responses in visual sensory regions.

Newly learned information undergoes a process of awake reactivation shortly after the learning offset and we recently demonstrated that this effect can be observed as early as area V1. However, reactivating all experiences can be wasteful and unnecessary, especially for familiar stimuli. Therefore, here we tested whether awake reactivation occurs differentially for new and familiar stimuli. Subjects completed a brief visual task on a stimulus that was either novel or highly familiar due to extensive prior training on it. Replicating our previous results, we found that awake reactivation occurred in V1 for the novel stimulus. On the other hand, brief exposure to the familiar stimulus led to ‘awake suppression’ such that neural activity patterns immediately after exposure to the familiar stimulus diverged from the patterns associated with that stimulus. Further, awake reactivation was observed selectively in V1, whereas awake suppression had similar strength across areas V1–V3. These results are consistent with the presence of a competition between local awake reactivation and top-down awake suppression, with suppression becoming dominant for familiar stimuli., Bang & Rahnev tested whether awake reactivation occurs differentially for new and familiar stimuli, given that reactivating all experiences can be wasteful. They expose participants to brief visual tasks in which the stimulus was either novel or familiar. They observed that whilst novel stimuli were associated with reactivation of cortical area V1, familiar stimuli led to ‘awake suppression’ in which neural activity diverged from patterns previously associated with that stimulus. The results support the existence of competition between local awake reactivation and top-down awake suppression, with suppression being dominant for familiar stimuli.

Hippocampal sharp wave-ripples (SWR) are thought to mediate brain-wide reactivation of memory traces in service of memory consolidation. However, rather than the faithful replay of neural activity observed during a specific experience, reactivation in both the hippocampus and downstream regions is more variable. We suggest that variable reactivation is a unifying feature of recurrent brain circuits. In the hippocampus, self-organized activation during offline states is constrained by existing attractor manifolds, or maps, and may be biased toward particular mapped locations by salient experience, which results in the appearance of experience-specific replay. Similarly, the impact of SWR-associated reactivation on downstream regions is not a simple transfer of hippocampal representational content. Rather, the response of downstream regions depends on a transformation function, defined by both the feedforward and local circuit architecture, as well as the ‘listening state’ of the downstream region. We hypothesize that SWRs act as a multiplexed signal, the mnemonic specificity of which is largely determined by this transformation function, and discuss the implications of this framing for theories of systems consolidation.

Precise tongue control is necessary for drinking, eating and vocalizing(1–3). However, because tongue movements are fast and difficult to resolve, neural control of lingual kinematics remains poorly understood. Here we combine kilohertz-frame-rate imaging and a deep-learning-based neural network to resolve 3D tongue kinematics in mice drinking from a water spout. Successful licks required corrective submovements that—similar to online corrections during primate reaches(4–11)—occurred after the tongue missed unseen, distant or displaced targets. Photoinhibition of anterolateral motor cortex impaired corrections, which resulted in hypometric licks that missed the spout. Neural activity in anterolateral motor cortex reflected upcoming, ongoing and past corrective submovements, as well as errors in predicted spout contact. Although less than a tenth of a second in duration, a single mouse lick exhibits the hallmarks of online motor control associated with a primate reach, including cortex-dependent corrections after misses.

Movement‐related decreases in firing rate have been observed in basal ganglia output neurons. They may transmit motor signals to the thalamus, but the effect of these firing rate decreases on downstream neurons in the motor thalamus is not known. One possibility is that they lead to thalamic post‐inhibitory rebound spikes. However, it has also been argued that the physiological conditions permitting rebound spiking are pathological, and primarily present in Parkinson’s disease. As in Parkinson’s disease neural activity becomes pathologically correlated, we investigated the impact of correlations in basal ganglia output on the transmission of motor signals using a Hodgkin‐Huxley model of thalamocortical neurons. We found that such correlations disrupt the transmission of motor signals via rebound spikes by decreasing the signal‐to‐noise ratio and increasing the trial‐to‐trial variability. We further examined the role of sensory responses in basal ganglia output neurons and the effect of cortical excitation of motor thalamus in modulating rebound spiking. Interestingly, both could either promote or suppress the generation of rebound spikes depending on their timing relative to the motor signal. Finally, we determined parameter regimes, such as levels of excitation, under which rebound spiking is feasible in the model, and confirmed that the conditions for rebound spiking are primarily given in pathological regimes. However, we also identified specific conditions in the model that would allow rebound spiking to occur in healthy animals in a small subset of thalamic neurons. Overall, our model provides novel insights into differences between normal and pathological transmission of motor signals.

The power-law exponents of observed size and lifetime distributions of near-critical neural avalanches are calculated from neural field theory using diagrammatic methods. This brings neural avalanches within the ambit of neural field theory, which has also previously explained near-critical 1/f spectra and many other observed features of neural activity. This strengthens the case for near-criticality of the brain and opens the way for these other phenomena to be interrelated with avalanches and their dynamics.

Electrical signals from the peripheral nervous system have the potential to provide the necessary motor, sensory or autonomic information for implementing closed-loop control of neuroprosthetic or neuromodulatory systems. However, developing methods to recover information encoded in these signals is a significant challenge. Our goal was to test the feasibility of measuring physiologically generated nerve action potentials that can be classified as sensory or motor signals. A tetrapolar recording nerve cuff electrode was used to measure vagal nerve (VN) activity in a rodent model of upper airway obstruction. The effect of upper airway occlusions on VN activity related to respiration (RnP) was calculated and compared for 4 different cases: (1) intact VN, (2) VN transection only proximal to recording electrode, (3) VN transection only distal to the recording electrode, and (4) transection of VN proximal and distal to electrode. We employed a Support Vector Machine (SVM) model with Gaussian Kernel to learn a model capable of classifying efferent and afferent waveforms obtained from the tetrapolar electrode. In vivo results showed that the RnP values decreased significantly during obstruction by 91.7% ± 3.1%, and 78.2% ± 3.4% for cases of intact VN or proximal transection, respectively. In contrast, there were no significant changes for cases of VN transection at the distal end or both ends of the electrode. The SVM model yielded an 85.8% accuracy in distinguishing motor and sensory signals. The feasibility of measuring low-noise directionally-sensitive neural activity using a tetrapolar nerve cuff electrode along with the use of an SVM classifier was shown. Future experimental work in chronic implant studies is needed to support clinical translatability.

Affective future thinking allows us to prepare for future outcomes, but we know little about neural representation of emotional future simulations. We used a multi-voxel pattern analysis to determine whether patterns of neural activity can reliably distinguish between positive and negative future simulations. Neural patterning in the anterior cingulate and ventromedial prefrontal cortices distinguished positive from negative future simulations, indicating that these regions code for the emotional valence of future events. These results support prior findings that anterior medial regions contain representations of emotions across various stimuli, and contribute to identifying potential rewarding outcomes of future events. More broadly, these results demonstrate that the phenomenological features of future thinking can be decoded using neural activity.

Taste coding theories in the central nervous system have largely been based on those derived from peripheral structures. Two of these, the labeled line and across unit pattern theories, have both been applied to taste-related structures in the brain, with disappointing results. Recent work has underscored the influence of sensory modalities other than taste in every brain region in the gustatory pathway. In addition, neurons appear to track taste-related behavior, suggesting that the taste system is essentially sensorimotor, rather than exclusively sensory. Thus, when food enters the mouth, neural activity in taste-related structures across the brain is coordinated by its multimodal sensory and taste-driven motor components. This widespread alignment of activity can be thought of as a sensory acquisition ‘state’ that can be influenced by metabolic and attentional variables while maintaining the core purpose of the system, that is, to identify and consume food.

The readiness potential (RP), a slow buildup of electrical potential recorded at the scalp using electroencephalography, has been associated with neural activity involved in movement preparation. It became famous thanks to Benjamin Libet (Brain 1983;106:623-642), who used the time difference between the RP and self-reported time of conscious intention to move to argue that we lack free will. The RP's informativeness about self-generated action and derivatively about free will has prompted continued research on this neural phenomenon. Here, we argue that recent advances in our understanding of the RP, including computational modeling of the phenomenon, call for a reassessment of its relevance for understanding volition and the philosophical problem of free will.

There is growing concern about a potential decline in empathy among medical students over time. Despite the importance of empathy toward patients in medicine, it remains unclear the nature of the changes in empathy among medical students. Thus, we systematically investigated affective and cognitive empathy for patients among medical students using neuroscientific approach. Nineteen medical students who completed their fifth-year medical curriculum and 23 age- and sex-matched nonmedical students participated in a functional magnetic resonance imaging study. Inside a brain scanner, all participants read empathy-eliciting scenarios while adopting either the patient or doctor perspective. Brain activation and self-reported ratings during the experience of empathy were obtained. Behavioral results indicated that all participants reported greater emotional negativity and empathic concern in association with the patient perspective condition than with the doctor perspective condition. Functional brain imaging results indicated that neural activity in the posterior superior temporal region implicated in goal-relevant attention reorienting was overall increased under the patient perspective than the doctor perspective condition. Relative to nonmedical students, medical students showed decreased activity in the temporoparietal region implicated in mentalizing under the patient perspective versus doctor perspective condition. Notably, this same region showed increased activity under the doctor versus patient condition in medical students relative to nonmedical students. This study is among the first to investigate the neural mechanisms of empathy among medical students and the current findings point to the cognitive empathy system as the locus of the primary brain differences associated with empathy toward patients.

Autism spectrum disorders (ASD) are a group of neurological disorders which affect approximately 1% of children around the world. Social dysfunction is one of the two core syndromes of ASD, and still lacks effective treatment. Transcranial magnetic stimulation (TMS) is a noninvasive and safe procedure that uses magnetic fields to modulate neural activity. Whether it were effective in modulating social function remains unclear. By using 3-chamber test, ultrasonic vocalization recording and Western-blotting, we demonstrated that FMR1 (fragile X mental retardation protein) mutant mice, a model of ASD, exhibited obvious defects in social preference and ultrasonic communication. In addition, we detected increase of p-Akt (S473) and p-GSK-3β (S9), and decrease of p-PSD-95 (T19) in the anterior cingulate cortex (ACC) of FMR1−/− mice. Treating FMR1−/− mice with 1 Hz repetitive TMS (rTMS) exerted a long lasting effect in improving both the ultrasonic communication and social preference, as well as restoring the levels of Akt/GSK-3β activity and spine density in the FMR1−/−ACC. Our data, for the first time, demonstrated a beneficial effect of low frequency rTMS (LF-rTMS) on the social function of FMR1−/− mice and an involvement of Akt/GSK-3β signaling in this process, indicating LF-rTMS as a potential therapeutic strategy for ASD patients.

The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and oxygen. This supply is coordinated by the action of neurons, glial and vascular cells, known collectively as the neurovascular unit, which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular coupling. In many neurodegenerative diseases, changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier, cerebral blood flow and clearance of waste from the brain. In order to study disease mechanisms, we need improved physiologically-relevant human models of the neurovascular unit. Advances towards modeling the cellular complexity of the neurovascular unit in vitro have been made using stem-cell derived organoids and more recently, vascularized organoids, enabling intricate studies of non-cell autonomous processes. Engineering and design innovations in microfluidic devices and tissue engineering are progressing our ability to interrogate the cerebrovasculature. These advanced models are being used to gain a better understanding of neurodegenerative disease processes and potential therapeutics. Continued innovation is required to build more physiologically-relevant models of the neurovascular unit encompassing both the cellular complexity and designed features to interrogate neurovascular unit functionality.

Human and non-human animal behavior is highly malleable and adapts successfully to internal and external demands. Such behavioral success stands in striking contrast to the apparent instability in neural activity (i.e., variability) from which it arises. Here, we summon the considerable evidence across scales, species, and imaging modalities that neural variability represents a key, undervalued dimension for understanding brain-behavior relationships at inter- and intra-individual levels. We believe that only by incorporating a specific focus on variability will the neural foundation of behavior be comprehensively understood.

Short-term memory is associated with persistent neural activity that is maintained by positive feedback between neurons. To explore the neural circuit motifs that produce memory-related persistent activity, we measured coupling between functionally characterized motor cortex neurons in mice performing a memory-guided response task. Targeted two-photon photostimulation of small (

The use of scene context is a powerful way by which biological organisms guide and facilitate visual search. Although many studies have shown enhancements of target-related electroencephalographic activity (EEG) with synthetic cues, there have been fewer studies demonstrating such enhancements during search with scene context and objects in real world scenes. Here, observers covertly searched for a target in images of real scenes while we used EEG to measure the steady state visual evoked response to objects flickering at different frequencies. The target appeared in its typical contextual location or out of context while we controlled for low-level properties of the image including target saliency against the background and retinal eccentricity. A pattern classifier using EEG activity at the relevant modulated frequencies showed target detection accuracy increased when the target was in a contextually appropriate location. A control condition for which observers searched the same images for a different target orthogonal to the contextual manipulation, resulted in no effects of scene context on classifier performance, confirming that image properties cannot explain the contextual modulations of neural activity. Pattern classifier decisions for individual images was also related to the aggregated observer behavioral decisions for individual images. Together, these findings demonstrate target-related neural responses are modulated by scene context during visual search with real world scenes and can be related to behavioral search decisions.Significance StatementContextual relationships among objects are fundamental for humans to find objects in real world scenes. Although there is a larger literature understanding the brain mechanisms when a target appears at a location indicated by a synthetic cue such as an arrow or box, less is known about how the scene context modulates target-related neural activity. Here we show how neural activity predictive of the presence of a searched object in cluttered real scenes increases when the target object appears at a contextual location and diminishes when it appears at a place that is out of context. The results increase our understanding of how the brain processes real scenes and how context modulates object processing.

The existence of neural correlates of spatial attention is not limited to the reactive stage of stimulus processing: neural activities subtending spatial attention are deployed well ahead of stimulus onset. ERP evidence supporting this proactive (top-down) attentional control is based on trial-by-trial S1-S2 paradigms, where the onset of a directional cue (S1) indicates on which side attention must be directed to respond to an upcoming target stimulus (S2). Crucially, S1 onset trigger both attention and motor preparation, therefore, these paradigms are not ideal to demonstrate the effect of attention at preparatory stage of processing. To isolate top-down anticipatory attention, the present study used a sustained attention paradigm based on a steady cue that indicates the attended side constantly throughout an entire block of trials, without any onset of an attentional cue. The main result consists in the description of the attention effect on the visual negativity (vN) component, a growing neural activity starting before stimulus presentation in extrastriate visual areas. The vN was consistently lateralized in the hemisphere contralateral to the attended side, regardless of the hand to be used. At the opposite, the lateralized motor activity emerged long after, confirming that the hand-selection process followed the spatial attention orientation process. The present study confirms the anticipatory nature of the vN component and corroborate its role in terms of preparatory visuospatial attention.

The long-range temporal correlation (LRTC) in resting-state intrinsic brain activity is known to be associated with temporal behavioral patterns, including decision making based on internal criteria such as self-knowledge. However, the association between the neuronal LRTC and the subjective sense of identity remains to be explored; in other words, whether our subjective sense of consistent self across time relates to the temporal consistency of neural activity. The present study examined the relationship between the LRTC of resting-state scalp electroencephalography (EEG) and a subjective sense of identity measured by the Erikson Psychosocial Stage Inventory (EPSI). Consistent with our prediction based on previous studies of neuronal-behavioral relationships, the frontocentral alpha LRTC correlated negatively with identity confusion. Moreover, from the descriptive analyses, centroparietal beta LRTC showed negative correlations with identity confusion, and frontal theta LRTC showed positive relationships with identity synthesis. These results suggest that more temporal consistency (reversely, less random noise) in intrinsic brain activity is associated with less confused and better-synthesized identity. Our data provide further evidence that the LRTC of intrinsic brain activity might serve as a noise suppression mechanism at the psychological level.

The insula contributes to behavioral control and is disrupted by substance abuse, yet we know little about the neural signals underlying these functions or how they are disrupted after chronic drug self-administration. Here, male and female rats self-administered either cocaine (experimental group) or sucrose (control) for 12 consecutive days. After a 1 month withdrawal period, we recorded from insula while rats performed a previously learned reward-guided decision-making task. Cocaine-exposed rats were more sensitive to value manipulations and were faster to respond. These behavioral changes were accompanied by elevated counts of neurons in the insula that increased firing to reward. These neurons also fired more strongly at the start of long-delay trials, when a more immediate reward would be expected, and fired less strongly in anticipation of the actual delivery of delayed rewards. Although reward-related firing to immediate reward was enhanced after cocaine self-administration, reward-predicting cue and context signals were attenuated. In addition to revealing novel firing patterns unique to insula, our data suggest changes in such neural activity likely contribute to impaired decision making observed after drug use.SIGNIFICANCE STATEMENTThe insula plays a clear role in drug addiction and drug-induced impairments of decision making, yet there is little understanding of its underlying neural signals. We found that chronic cocaine self-administration reduces cue and context encoding in insula while enhancing signals related to immediate reward. These changes in neural activity likely contribute to impaired decision making and impulsivity observed after drug use.

Early adverse experiences are believed to have a profound effect on inhibitory control and the underlying neural regions. In the current study, behavioral and event-related potential (ERP) data were collected during a go/no-go task from adolescents who were involved with the child welfare system due to child maltreatment (n = 129) and low-income, nonmaltreated adolescents (n = 102). The nonmaltreated adolescents were more accurate than the maltreated adolescents on the go/no-go task, particularly on the no-go trials. Paralleling the results with typically developing populations, the nonmaltreated adolescents displayed a more pronounced amplitude of the N2 during the no-go trials than during the go trials. However, the maltreated adolescents demonstrated a more pronounced amplitude of the N2 during the go trials than during the no-go trials. Furthermore, while the groups did not differ during the go trials, the nonmaltreated adolescents displayed a more negative amplitude of the N2 than the maltreated adolescents during no-go trials. In contrast, there was not a significant group difference in amplitude of the P3. Taken together, these results provide evidence that the early adverse experiences encountered by maltreated populations impact inhibitory control and the underlying neural activity in early adolescence.

Synchronized activity the hallmark of neural networks. Early sharp waves (eSPW) form one type of synchronized activity – these are synchronized network discharges of neuronal ensembles seen in the developing hippocampus. Despite the fact that eSPW may play a central role in coordinating neural activity and forming hippocampal functions, little is known of changes in eSPW during early postnatal development. Our experiments on neonatal rat pups using multichannel extracellular electrodes showed that during the first two weeks of postnatal life, along with reductions in the duration of eSPW, there were increases in their frequency and amplitude. We also found an increase in extracellular recorded activity of neurons in the pyramidal layer of the hippocampus. These data lead to the suggestion that the dynamics of changes in eSPW and overall network hippocampal activity are associated with the development of the hippocampal neural network and bottom-up neuromodulator projections.

Modern recording techniques now permit brain-wide sensorimotor circuits to be observed at single-neuron resolution in small animals. Extracting theoretical understanding from these recordings requires principles that organize findings and guide future experiments. Here we review theoretical principles that shed light onto brain-wide sensorimotor processing. We begin with an analogy that conceptualizes principles as streetlamps that illuminate the empirical terrain, and we illustrate the analogy by showing how two familiar principles apply in new ways to brain-wide phenomena. We then focus the bulk of the review on describing three more principles that have wide utility for mapping brain-wide neural activity, making testable predictions from highly parameterized mechanistic models, and investigating the computational determinants of neuronal response patterns across the brain.

A fundamental scientific goal in auditory neuroscience is identifying what mechanisms allow the brain to transform an unlabeled mixture of auditory stimuli into distinct perceptual representations. This transformation is accomplished by a complex interaction of multiple neurocomputational processes, including Gestalt grouping mechanisms, categorization, attention, and perceptual decision-making. Despite a great deal of scientific energy devoted to understanding these principles of hearing, we still do not understand either how auditory perception arises from neural activity or the causal relationship between neural activity and auditory perception. Here, we review the contributions of cortical and subcortical regions to auditory perceptual decisions with an emphasis on those studies that simultaneously measure behavior and neural activity. We also put forth challenges to the field that must be faced if we are to further our understanding of the relationship between neural activity and auditory perception.

Reactivation refers to the phenomenon wherein patterns of neural activity expressed during perceptual experience are re-expressed at a later time, a putative neural marker of memory. Reactivation of perceptual content has been observed across many cortical areas and correlates with objective and subjective expressions of memory in humans. However, because reactivation emphasizes similarities between perceptual and memory-based representations, it obscures differences in how perceptual events and memories are represented. Here, we highlight recent evidence of systematic differences in how (and where) perceptual events and memories are represented in the brain. We argue that neural representations of memories are best thought of as spatially transformed versions of perceptual representations. We consider why spatial transformations occur and identify critical questions for future research.

The compact nervous system of the nematode Caenorhabditis elegans makes it a powerful playground to study how neural dynamics constrained by neuroanatomy generate neural function and behavior. The ability to record neural activity from the whole brain simultaneously in this worm has opened several research avenues and is providing insights into brain-wide neural coding of locomotion, sleep, and other behaviors. We review these findings and the development of new methods, including new microscopes, new genetic tools, and new modeling approaches. We conclude with a discussion of the role of theory in interpreting or driving new experiments in C. elegans and potential paths forward.

Cortical neural dynamics organizes over multiple anatomical and temporal scales. The mechanistic origin of the temporal organization and its contribution to cognition remain unknown. Here we demonstrate the cause of this organization by studying a specific temporal signature (autocorrelogram time constant and latency) of neural activity. In monkey frontal areas, recorded during flexible cognitive decisions, temporal signatures display highly specific area-dependent ranges, as well as anatomical and cell-type distributions. Moreover, temporal signatures are functionally adapted to behaviorally relevant timescales. Fine-grained biophysical network models, constrained to account for temporal signatures, reveal that after-hyperpolarization potassium and inhibitory GABA-B conductances critically determine areas’ specificity. They mechanistically account for temporal signatures by organizing activity into metastable states, with inhibition controlling state stability and transitions. As predicted by models, state durations non-linearly scale with temporal signatures in monkey, matching behavioral timescales. Thus, local inhibitory-controlled metastability constitutes the dynamical core specifying the temporal organization of cognitive functions in frontal areas.

Mature behaviors emerge from neural circuits sculpted by genetic programs and spontaneous and evoked neural activity. However, how neural activity is refined to drive maturation of learned behavior remains poorly understood. Here, we explore how transient hormonal signaling coordinates a neural activity state transition and maturation of associative learning. We identify spontaneous, asynchronous activity in a Drosophila learning and memory brain region, the mushroom body. This activity declines significantly over the first week of adulthood. Moreover, this activity is generated cell-autonomously via Cacophony voltage-gated calcium channels in a single cell-type, α’/β’ Kenyon cells. Juvenile hormone, a crucial developmental regulator, acts transiently in α’/β’ Kenyon cells during a young adult sensitive period to downregulate spontaneous activity and enable subsequent enhanced learning. Hormone signaling in young animals therefore controls a neural activity state transition and is required for improved associative learning, providing insight into the maturation of circuits and behavior.

Semantic processing impairments are present in a proportion of individuals with autism spectrum disorder (ASD). Despite the numerous imaging studies investigating this language domain in ASD, there is a lack of consensus regarding the brain structures showing abnormal pattern of activity. This meta-analysis aimed to identify neural activation patterns present during semantic processing in ASD. Findings reveal activation of areas associated with semantic processing and executive functions in ASD. However, the activation was less concise in comparison to controls and there was less activation in the right hemisphere and in areas associated with executive functions. This provides strong support for impaired semantic processing in ASD that is consistently associated with abnormal patterns of neural activity in the semantic network.

Neural activity exhibits complex dynamics related to various brain functions, internal states and behaviors. Understanding how neural dynamics explain specific measured behaviors requires dissociating behaviorally relevant and irrelevant dynamics, which is not achieved with current neural dynamic models as they are learned without considering behavior. We develop preferential subspace identification (PSID), which is an algorithm that models neural activity while dissociating and prioritizing its behaviorally relevant dynamics. Modeling data in two monkeys performing three-dimensional reach and grasp tasks, PSID revealed that the behaviorally relevant dynamics are significantly lower-dimensional than otherwise implied. Moreover, PSID discovered distinct rotational dynamics that were more predictive of behavior. Furthermore, PSID more accurately learned behaviorally relevant dynamics for each joint and recording channel. Finally, modeling data in two monkeys performing saccades demonstrated the generalization of PSID across behaviors, brain regions and neural signal types. PSID provides a general new tool to reveal behaviorally relevant neural dynamics that can otherwise go unnoticed.

Rumination, repetitively thinking about the causes, consequences, and one's negative affect, has been considered as an important factor of depression. The intrusion of ruminative thoughts is not easily controlled, and it may be useful to visualize one's neural activity related to rumination and to use that information to facilitate one's self‐control. Real‐time fMRI neurofeedback (rtfMRI‐nf) enables one to see and regulate the fMRI signal from their own brain. This proof‐of concept study utilized connectivity‐based rtfMRI‐nf (cnf) to normalize brain functional connectivity (FC) associated with rumination. Healthy participants were instructed to brake or decrease FC between the precuneus and the right temporoparietal junction (rTPJ), associated with high levels of rumination, while engaging in a self‐referential task. The cnf group (n = 14) showed a linear decrease in the precuneus‐rTPJ FC across neurofeedback training (trend [112] = −0.180, 95% confidence interval [CI] −0.330 to −0.031, while the sham group (n = 14) showed a linear increase in the target FC (trend [112] = 0.151, 95% CI 0.017 to 0.299). Although the cnf group showed a greater reduction in state‐rumination compared to the sham group after neurofeedback training (p, Regions of interest (ROI) for the connectivity‐based rtfMRI‐nf and the neurofeedback algorithm. (a) ROIs for the connectivity‐based rtfMRI‐nf. (b) Neurofeedback algorithm and display. Red circles and arrows indicate the precuneus ROI and BOLD activities, and blue circles and arrows indicate the right temporoparietal junction (rTPJ) ROI and BOLD activities. The sidebars on the screen were updated every 2‐s with positive feedback (+1: light blue color) or no feedback (0: blank color).

Transcranial alternating current stimulation (tACS) was introduced about a decade ago as a non-invasive brain stimulation method to modulate neural oscillations in a relatively safe manner in humans. However, the possibility to induce genuine neural entrainment with low current intensities has been questioned. In a recent study, Johnson and colleagues provide direct evidence for the efficacy of low-intensity tACS to induce neural entrainment in awake monkeys. These findings have important translational implications for human non-invasive neuromodulation research. ISSN:1935-861X ISSN:1876-4754

OBJECTIVE Report pilot findings of neurobehavioral gains and network changes observed in persons with disordered consciousness (DoC) who received repetitive transcranial magnetic stimulation (rTMS) or amantadine (AMA), and then rTMS+AMA. PARTICIPANTS Four persons with DoC 1 to 15 years after traumatic brain injury (TBI). DESIGN Alternate treatment-order, within-subject, baseline-controlled trial. MAIN MEASURES For group and individual neurobehavioral analyses, predetermined thresholds, based on mixed linear-effects models and conditional minimally detectable change, were used to define meaningful neurobehavioral change for the Disorders of Consciousness Scale-25 (DOCS) total and Auditory-Language measures. Resting-state functional connectivity (rsFC) of the default mode and 6 other networks was examined. RESULTS Meaningful gains in DOCS total measures were observed for 75% of treatment segments and auditory-language gains were observed after rTMS, which doubled when rTMS preceded rTMS+AMA. Neurobehavioral changes were reflected in rsFC for language, salience, and sensorimotor networks. Between networks interactions were modulated, globally, after all treatments. CONCLUSIONS For persons with DoC 1 to 15 years after TBI, meaningful neurobehavioral gains were observed after provision of rTMS, AMA, and rTMS+AMA. Sequencing and combining of treatments to modulate broad-scale neural activity, via differing mechanisms, merits investigation in a future study powered to determine efficacy of this approach to enabling neurobehavioral recovery.

We recorded neural activity in male monkeys playing a variant of the game ‘chicken’ in which they made decisions to cooperate or not cooperate to obtain rewards of different sizes. Neurons in the middle superior temporal sulcus (mSTS)—previously implicated in social perception—signaled strategic information, including payoffs, intentions of the other player, reward outcomes and predictions about the other player. Moreover, a subpopulation of mSTS neurons selectively signaled cooperatively obtained rewards. Neurons in the anterior cingulate gyrus, previously implicated in vicarious reinforcement and empathy, carried less information about strategic variables, especially cooperative reward. Strategic signals were not reducible to perceptual information about the other player or motor contingencies. These findings suggest that the capacity to compute models of other agents has deep roots in the strategic social behavior of primates and that the anterior cingulate gyrus and the mSTS support these computations. Ong et al. analyzed behavior, gaze patterns and neuronal activity of monkeys playing the game ‘chicken’. Monkeys seemed to develop models of the behavior of the partner, and neurons in the mSTS and the ACCg signaled strategic information to guide their decisions.

Hearing is a crucial sense in underwater environments for communication, hunting, attracting mates, and detecting predators. However, the tools currently used to study hearing are limited, as they cannot controllably stimulate specific parts of the auditory system. To date, the contributions of hearing organs have been identified through lesion experiments that inactivate an organ, making it difficult to gauge the specific stimuli to which each organ is sensitive, or the ways in which inputs from multiple organs are combined during perception. Here, we introduce Bio-Opto-Acoustic (BOA) stimulation, using optical forces to generate localized vibrations in vivo, and demonstrate stimulation of the auditory system of zebrafish larvae with precise control. We use a rapidly oscillated optical trap to generate vibrations in individual otolith organs that are perceived as sound, while adjacent otoliths are either left unstimulated or similarly stimulated with a second optical laser trap. The resulting brain-wide neural activity is characterized using fluorescent calcium indicators, thus linking each otolith organ to its individual neuronal network in a way that would be impossible using traditional sound delivery methods. The results reveal integration and cooperation of the utricular and saccular otoliths, which were previously described as having separate biological functions, during hearing., Existing tools to study hearing are limited. Here the authors report Bio-OptoAcoustic (BOA) stimulation wherein they use optical forces to generate localised sound and activate the auditory system of zebrafish larvae.

The population of hippocampal neurons actively coding space continually changes across days as mice repeatedly perform tasks. Many hippocampal place cells become inactive while other previously silent neurons become active, challenging the idea that stable behaviors and memory representations are supported by stable patterns of neural activity. Active cell replacement may disambiguate unique episodes that contain overlapping memory cues, and could contribute to reorganization of memory representations. How active cell replacement affects the evolution of representations of different behaviors within a single task is unknown. We trained mice to perform a Delayed Non-Match to Place (DNMP) task over multiple weeks, and performed calcium imaging in area CA1 of the dorsal hippocampus using head-mounted miniature microscopes. Cells active on the central stem of the maze “split” their calcium activity according to the animal’s upcoming turn direction (left or right), the current task phase (study or test), or both task dimensions, even while spatial cues remained unchanged. We found that, among reliably active cells, different splitter neuron populations were replaced at unequal rates, resulting in an increasing number of cells modulated by turn direction and a decreasing number of cells with combined modulation by both turn direction and task phase. Despite continual reorganization, the ensemble code stably segregated these task dimensions. These results show that hippocampal memories can heterogeneously reorganize even while behavior is unchanging.

BACKGROUND: The medial prefrontal cortex (mPFC) is a brain region involved in the evaluation and selection of motivationally relevant outcomes. Neural activity in mPFC is altered following acute ethanol (EtOH) use and, in rodent models, doses as low as 0.75 g/kg yield cognitive deficits. Deficits in decision-making following acute EtOH are thought to be mediated, at least in part, by decreases in mPFC firing rates (FRs). However, the data leading to this conclusion have been generated exclusively in anesthetized rodents. The present study characterizes the effects of acute EtOH injections on mPFC neural activity in awake-behaving rodents. METHODS: Awake-behaving and anesthetized in vivo electrophysiological recordings were performed. We utilized three groups: the first received two saline injections, the second received a saline injection followed by 1.0 g/kg EtOH, the last received saline followed by 2 g/kg EtOH. One week later an anesthetized recording occurred where a saline injection was followed by an injection of 1.0 g/kg EtOH. RESULTS: The anesthetized condition showed robust decreases in neural activity and differences in up-down state dynamics. In the awake-behaving condition, FRs were grouped according to behavioral state: moving, not moving, and sleep. The differences in median FRs were found for each treatment and behavioral state combination. A FR decrease was only found in the 2.0 g/kg EtOH treatment during not moving states. However, robust decreases in FR variability were found across behavioral state in both the 1.0 g/kg and 2.0 g/kg EtOH treatment. Sleep was separately analyzed. EtOH modulated the up-down states during sleep producing decreases in FRs. CONCLUSIONS: In conclusion, the changes in neural activity following EtOH administration in anesthetized animals are not conserved in awake-behaving animals. The most prominent difference following EtOH was a decrease in FR variability suggesting that acute EtOH may be affecting decision-making via this mechanism.