Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience.

N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic, known to rapidly induce short-lasting alterations in conscious experience, characterized by a profound and immersive sense of physical transcendence alongside rich and vivid auditory distortions and visual imagery. Multimodal neuroimaging data paired with dynamic analysis techniques offer a valuable approach for identifying unique signatures of brain activity - and linked autonomic physiology - naturally unfolding during the altered state of consciousness induced by DMT. We leveraged simultaneous fMRI and EKG data acquired in 14 healthy volunteers prior to, during, and after intravenous administration of DMT, and, separately, placebo. fMRI data was preprocessed to derive individual dynamic activity matrices, reflecting the similarity of brain activity in time, and community detection algorithms were applied on these matrices to identify brain activity substates; EKG data was used to derive continuous heart rate. We identified a brain substate occurring immediately after DMT injection, characterized by increased superior temporal lobe activity, and hippocampal and medial parietal deactivations under DMT. Results revealed that hippocampus and medial parietal cortex hypoactivity correlated with scores of meaningfulness of the experience. During this first post-injection substate, increased heart rate under DMT correlated negatively with the meaningfulness of the experience and positively with hippocampus/medial parietal deactivation. These results suggest a chain of influence linking sympathetic regulation to hippocampal and medial parietal deactivations under DMT, which combined, may contribute to positive mental health outcomes related to self-referential processing following psychedelic administration.

Involuntary refreshing of mental representations.

Laboratory tasks have revealed that mental representations (e.g., mental imagery) can enter consciousness in a manner that is involuntary, reliable, and insuppressible. These effects illuminate the capacities of involuntary processes as well as the function of voluntary, conscious processing. The Reflexive Imagery Task was developed a decade ago to investigate these involuntary effects systematically. Can refreshing yield such involuntary effects? Refreshing is the reactivating in mind of a mental representation that was activated moments ago. It is associated with mental rehearsal and executive function. We investigated whether a mental representation (subvocalization of an object name) can arise in consciousness involuntarily after a delayed interval, when the relevant stimulus is no longer present, and in response to a cue. In Experiment 1, participants were instructed not to refresh a previously presented (6 s before) stimulus in response to a cue. Involuntary refreshing occurred on a substantive proportion (0.56) of the trials. Experiment 2 replicated and extended this finding (proportion of the trials = 0.53) with a refreshing task that was more challenging than that of Experiment 1. Our findings suggest that mental representations arising from processes such as refreshing can occur involuntarily. We discuss the theoretical implications of this conclusion.

The Generation of Involuntary Mental Imagery in an Ecologically-Valid Task.

Laboratory tasks (e.g., the flanker task) reveal that incidental stimuli (e.g., distractors) can reliably trigger involuntary conscious imagery. Can such involuntary effects, involving competing representations, arise during dual-task conditions? Another concern about these laboratory tasks is whether such effects arise in highly ecologically-valid conditions. For example, do these effects arise from tasks involving dynamic stimuli (e.g., simulations of semi-automated driving experiences)? The data from our experiment suggest that the answer to our two questions is yes. Subjects were presented with video footage of the kinds of events that one would observe if one were seated in the driver's seat of a semi-automated vehicle. Before being presented with this video footage, subjects had been trained to respond to street signs according to laboratory techniques that cause stimulus-elicited involuntary imagery. After training, in the Respond condition, subjects responded to the signs; in the Suppress condition, subjects were instructed to not respond to the signs in the video footage. Subjects in the Suppress condition reported involuntary imagery on a substantive proportion of the trials. Such involuntary effects arose even under dual-task conditions (while performing the n-back task or psychomotor vigilance task). The present laboratory task has implications for semi-automated driving, because the safe interaction between driver and vehicle requires that the communicative signals from vehicle to driver be effective at activating the appropriate cognitions and behavioral inclinations. In addition, our data from the dual-task conditions provide constraints for theoretical models of cognitive resources.

Closed-Loop Neurofeedback of α Synchrony during Goal-Directed Attention.

α Oscillations in sensory cortex, under frontal control, desynchronize during attentive preparation. Here, in a selective attention study with simultaneous EEG in humans of either sex, we first demonstrate that diminished anticipatory α synchrony between the mid-frontal region of the dorsal attention network and ventral visual sensory cortex [frontal-sensory synchrony (FSS)] significantly correlates with greater task performance. Then, in a double-blind, randomized controlled study in healthy adults, we implement closed-loop neurofeedback (NF) of the anticipatory α FSS signal over 10 d of training. We refer to this closed-loop experimental approach of rapid NF integrated within a cognitive task as cognitive NF (cNF). We show that cNF results in significant trial-by-trial modulation of the anticipatory α FSS measure during training, concomitant plasticity of stimulus-evoked α/θ responses, as well as transfer of benefits to response time (RT) improvements on a standard test of sustained attention. In a third study, we implement cNF training in children with attention deficit hyperactivity disorder (ADHD), replicating trial-by-trial modulation of the anticipatory α FSS signal as well as significant improvement of sustained attention RTs. These first findings demonstrate the basic mechanisms and translational utility of rapid cognitive-task-integrated NF.SIGNIFICANCE STATEMENT When humans prepare to attend to incoming sensory information, neural oscillations in the α band (8-14 Hz) undergo desynchronization under the control of prefrontal cortex. Here, in an attention study with electroencephalography, we first show that frontal-sensory synchrony (FSS) of α oscillations during attentive preparation significantly correlates with task performance. Then, in a randomized controlled study in healthy adults, we show that neurofeedback (NF) training of this α FSS signal within the attention task is feasible. We show that this rapid cognitive NF (cNF) approach engenders plasticity of stimulus-evoked neural responses, and improves performance on a standard test of sustained attention. In a final study, we implement cNF in children with attention deficit hyperactivity disorder (ADHD), replicating the improvement of sustained attention found in adults.

Reconfiguration of Electroencephalography Microstate Networks after Breath-Focused, Digital Meditation Training.

Sustained attention and working memory were improved in young adults after they engaged in a recently developed, closed-loop, digital meditation practice. Whether this type of meditation also has a sustained effect on dominant resting-state networks is currently unknown. In this study, we examined the resting brain states before and after a period of breath-focused, digital meditation training versus placebo using an electroencephalography (EEG) microstate approach. We found topographical changes in postmeditation rest, compared with baseline rest, selectively for participants who were actively involved in the meditation training and not in participants who engaged with an active, expectancy-match, placebo control paradigm. Our results suggest a reorganization of brain network connectivity after 6 weeks of intensive meditation training in brain areas, mainly including the right insula, the superior temporal gyrus, the superior parietal lobule, and the superior frontal gyrus bilaterally. These findings provide an opening for the development of a novel noninvasive treatment of neuropathological states by low-cost, breath-focused, digital meditation practice, which can be monitored by the EEG microstate approach.

Focus on the Breath: Brain Decoding Reveals Internal States of Attention During Meditation.

Meditation practices are often used to cultivate interoception or internally-oriented attention to bodily sensations, which may improve health via cognitive and emotional regulation of bodily signals. However, it remains unclear how meditation impacts internal attention (IA) states due to lack of measurement tools that can objectively assess mental states during meditation practice itself, and produce time estimates of internal focus at individual or group levels. To address these measurement gaps, we tested the feasibility of applying multi-voxel pattern analysis (MVPA) to single-subject fMRI data to: (1) learn and recognize internal attentional states relevant for meditation during a directed IA task; and (2) decode or estimate the presence of those IA states during an independent meditation session. Within a mixed sample of experienced meditators and novice controls (N = 16), we first used MVPA to develop single-subject brain classifiers for five modes of attention during an IA task in which subjects were specifically instructed to engage in one of five states [i.e., meditation-related states: breath attention, mind wandering (MW), and self-referential processing, and control states: attention to feet and sounds]. Using standard cross-validation procedures, MVPA classifiers were trained in five of six IA blocks for each subject, and predictive accuracy was tested on the independent sixth block (iterated until all volumes were tested, N = 2,160). Across participants, all five IA states were significantly recognized well above chance (>41% vs. 20% chance). At the individual level, IA states were recognized in most participants (87.5%), suggesting that recognition of IA neural patterns may be generalizable for most participants, particularly experienced meditators. Next, for those who showed accurate IA neural patterns, the originally trained classifiers were applied to a separate meditation run (10-min) to make an inference about the percentage time engaged in each IA state (breath attention, MW, or self-referential processing). Preliminary group-level analyses demonstrated that during meditation practice, participants spent more time attending to breath compared to MW or self-referential processing. This paradigm established the feasibility of using MVPA classifiers to objectively assess mental states during meditation at the participant level, which holds promise for improved measurement of internal attention states cultivated by meditation.

Closed-loop digital meditation for neurocognitive and behavioral development in adolescents with childhood neglect.

Adverse childhood experiences are linked to poor attentive behaviors during adolescence, as well as increased risk for mental health disorders in adults. However, no study has yet tested targeted interventions to optimize neurocognitive processes in this population. Here, we investigated closed-loop digital interventions in a double-blind randomized controlled study in adolescents with childhood neglect, and evaluated the outcomes using multimodal assessments of neuroimaging, cognitive, behavioral, and academic evaluations. In the primary neuroimaging results, we demonstrate that a closed-loop digital meditation intervention can strengthen functional connectivity of the dorsal anterior cingulate cortex (dACC) in the cingulo-opercular network, which is critically developing during the adolescent period. Second, this intervention enhanced sustained attention and interference-resolution abilities, and also reduced behavioral hyperactivity at a 1-year follow-up. Superior academic performance was additionally observed in adolescents who underwent the digital meditation intervention. Finally, changes in dACC functional connectivity significantly correlated with improvements in sustained attention, hyperactivity, and academic performance. This first study demonstrates that closed-loop digital meditation practice can facilitate development of important aspects of neurocognition and real-life behaviors in adolescents with early childhood neglect.

Involuntary attentional shifts as a function of set and processing fluency.

In laboratory tasks, involuntary cognitions of various kinds (e.g., mental imagery) have been elicited by external stimuli. These effects reveal, among other things, the capacities of involuntary processes. In most cases, these cognitions do not require, for their generation, executive functions such as a shift in selective attention. In Experiment 1, subjects were presented with a clock of 12 words in the stead of numbers and were instructed to focus on the center of the screen and to not count the number of letters of a word at a certain location. Involuntary counting of the critical word occurred on 39% of the trials. This effect requires an involuntary shift of attention. Experiment 2, involving Chinese ideographs, concerned the effect of stimulus fidelity and processing fluency. Native English speakers and a separate group of subjects who could read Chinese ideographs were presented with an array similar to that of Experiment 1 and instructed to not read any of the words. Some words were easy to read (e.g., regular Chinese words and English words), and some words were more difficult to read (e.g., Chinese "loan" words and English pseudowords). For the subjects who could read Chinese ideographs, more involuntary reading occurred for regular ideographs than for loan words. For the Native English speakers, comparable effects were found with the English stimuli. Together, these studies reveal that attentional phenomena of this kind can be influenced involuntarily and systematically through external control.

Involuntary mental rotation and visuospatial imagery from external control.

The Reflexive Imagery Task (RIT) was developed to investigate the entry into consciousness of involuntary imagery. Subjects are presented with objects and instructed to not think of the names of the objects. Involuntary subvocalizations arise on many trials. RIT effects reveal the capacities of involuntary processing. These cognitions do not require symbol manipulation. Can mental rotation and visuospatial imagery, too, arise in this involuntary manner? In the mental rotation task, subjects were first taught to mentally rotate two-dimensional objects. Subjects were then instructed to not mentally rotate objects. In the chess task, subjects were taught how to move in their minds objects in specified ways, much as one could imagine how chess pieces move on a chessboard. Subjects were then instructed to not have such visuospatial imagery. For both tasks, involuntary imagery occurred on a substantial proportion of trials, revealing that symbol manipulation can be influenced involuntarily through external control.

Closed-loop digital meditation improves sustained attention in young adults.

Attention is a fundamental cognitive process that is critical for essentially all aspects of higher-order cognition and real-world activities. Younger generations have deeply embraced information technology and multitasking in their personal lives, school and the workplace, creating myriad challenges to their attention. While improving sustained attention in healthy young adults would be beneficial, enhancing this ability has proven notoriously difficult in this age group. Here we show that 6 weeks of engagement with a meditation-inspired, closed-loop software program (MediTrain) delivered on mobile devices led to gains in both sustained attention and working memory in healthy young adults. These improvements were associated with positive changes in key neural signatures of attentional control (frontal theta inter-trial coherence and parietal P3b latency), as measured by electroencephalography. Our findings suggest the utility of delivering aspects of the ancient practice of focused-attention meditation in a modern, technology-based approach and its benefits on enhancing sustained attention.

Involuntary symbol manipulation (Pig Latin) from external control: Implications for thought suppression.

In ironic processing, one is more likely to think about something (e.g., white bears) when instructed to not think about that thing. Entry into consciousness of such content may be automatic, reflecting the 'encapsulated' nature of the generation of conscious contents. Based on this research, the Reflexive Imagery Task (RIT) reveals that, following the activation of action sets, conscious contents can arise involuntarily and systematically in response to external stimuli. In the most basic version of this paradigm, participants are presented with visual objects and instructed to not think of the names of the objects, which is challenging. Here, we addressed one criticism of the RIT-that the effect arises only for automatic processes (e.g., forms of cued-memory retrieval) and not for more complex processes (e.g., symbol manipulation). Participants were first trained to perform a word-manipulation task similar to the game of Pig Latin (e.g., "CAR" becomes "AR-CAY"). Such a task involves complex symbol manipulations that are associated with processes in frontal cortex. After training, participants were instructed to not transform stimulus words in this way. The RIT effect still arose under these conditions. This striking finding is relevant to theories of cognitive control, psychopathology, and conscious/unconscious processing.

Age-Related Changes in 1/f Neural Electrophysiological Noise.

Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15-53 years) and scalp EEG data from healthy younger (20-30 years) and older (60-70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <-1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. Significance statement: Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise-induced deficits in neural communication.

Closed-loop cognition: the next frontier arrives.

A new study trains attention by implementing a closed-loop neurofeedback approach that monitors attention status in the whole brain using real-time fMRI. Offline analyses underscore information carried by the frontoparietal attention network as most relevant for the training-driven behavioral improvements.

Age-equivalent top-down modulation during cross-modal selective attention.

Selective attention involves top-down modulation of sensory cortical areas, such that responses to relevant information are enhanced whereas responses to irrelevant information are suppressed. Suppression of irrelevant information, unlike enhancement of relevant information, has been shown to be deficient in aging. Although these attentional mechanisms have been well characterized within the visual modality, little is known about these mechanisms when attention is selectively allocated across sensory modalities. The present EEG study addressed this issue by testing younger and older participants in three different tasks: Participants attended to the visual modality and ignored the auditory modality, attended to the auditory modality and ignored the visual modality, or passively perceived information presented through either modality. We found overall modulation of visual and auditory processing during cross-modal selective attention in both age groups. Top-down modulation of visual processing was observed as a trend toward enhancement of visual information in the setting of auditory distraction, but no significant suppression of visual distraction when auditory information was relevant. Top-down modulation of auditory processing, on the other hand, was observed as suppression of auditory distraction when visual stimuli were relevant, but no significant enhancement of auditory information in the setting of visual distraction. In addition, greater visual enhancement was associated with better recognition of relevant visual information, and greater auditory distractor suppression was associated with a better ability to ignore auditory distraction. There were no age differences in these effects, suggesting that when relevant and irrelevant information are presented through different sensory modalities, selective attention remains intact in older age.

Subjective aspects of working memory performance: memoranda-related imagery.

Although it is well accepted that working memory (WM) is intimately related to consciousness, little research has illuminated the liaison between the two phenomena. To investigate this under-explored nexus, we used an imagery monitoring task to investigate the subjective aspects of WM performance. Specifically, in two experiments, we examined the effects on consciousness of (a) holding in mind information having a low versus high memory load, and (b) holding memoranda in mind during the presentation of distractors (e.g., visual stimuli associated with a response incompatible with that of the memoranda). Higher rates of rehearsal (conscious imagery) occurred in the high load and distractor conditions than in comparable control conditions. Examination of the temporal properties of the rehearsal-based imagery revealed that, across subjects, imagery events occurred evenly throughout the delay. We hope that future variants of this new imagery monitoring task will reveal additional insights about WM, consciousness, and action control.

Preserved discrimination performance and neural processing during crossmodal attention in aging.

In a recent study in younger adults (19-29 year olds) we showed evidence that distributed audiovisual attention resulted in improved discrimination performance for audiovisual stimuli compared to focused visual attention. Here, we extend our findings to healthy older adults (60-90 year olds), showing that performance benefits of distributed audiovisual attention in this population match those of younger adults. Specifically, improved performance was revealed in faster response times for semantically congruent audiovisual stimuli during distributed relative to focused visual attention, without any differences in accuracy. For semantically incongruent stimuli, discrimination accuracy was significantly improved during distributed relative to focused attention. Furthermore, event-related neural processing showed intact crossmodal integration in higher performing older adults similar to younger adults. Thus, there was insufficient evidence to support an age-related deficit in crossmodal attention.

Attention distributed across sensory modalities enhances perceptual performance.

This study investigated the interaction between top-down attentional control and multisensory processing in humans. Using semantically congruent and incongruent audiovisual stimulus streams, we found target detection to be consistently improved in the setting of distributed audiovisual attention versus focused visual attention. This performance benefit was manifested as faster reaction times for congruent audiovisual stimuli and as accuracy improvements for incongruent stimuli, resulting in a resolution of stimulus interference. Electrophysiological recordings revealed that these behavioral enhancements were associated with reduced neural processing of both auditory and visual components of the audiovisual stimuli under distributed versus focused visual attention. These neural changes were observed at early processing latencies, within 100-300 ms poststimulus onset, and localized to auditory, visual, and polysensory temporal cortices. These results highlight a novel neural mechanism for top-down driven performance benefits via enhanced efficacy of sensory neural processing during distributed audiovisual attention relative to focused visual attention.

Diminished top-down control underlies a visual imagery deficit in normal aging.

Mental imagery is involved in a wide variety of cognitive abilities, including reasoning, spatial navigation, and memory. Cognitive aging is associated with impairments in these abilities, suggesting that diminished fidelity of mental images in older adults may be related to diverse cognitive deficits. However, an age-related deficit in mental imagery and its role in memory impairment is still a matter of debate. Previous human fMRI studies demonstrated that visual imagery activates representations in category-selective visual cortex via top-down control mechanisms. Here, we use fMRI to show that normal aging is associated with diminished selectivity of visual cortex activation during visual imagery, with a corresponding reduction in the selectivity of functional connections between prefrontal cortex and visual cortices. Moreover, a relationship between reduced imagery selectivity and visual memory in older adults was established. These results reveal that aging disrupts neural networks that subserve mental imagery and offers evidence of this as a factor in age-related memory decline.

Neural mechanisms underlying the impact of visual distraction on retrieval of long-term memory.

Filtering information on the basis of what is relevant to accomplish our goals is a critical process supporting optimal cognitive performance. However, it is not known whether exposure to irrelevant environmental stimuli impairs our ability to accurately retrieve long-term memories. We hypothesized that visual processing of irrelevant visual information would interfere with mental visualization engaged during recall of the details of a prior experience, despite goals to direct full attention to the retrieval task. In the current study, we compared performance on a cued-recall test of previously studied visual items when participants' eyes were closed to performance when their eyes were open and irrelevant visual stimuli were presented. A behavioral experiment revealed that recollection of episodic details was diminished in the presence of the irrelevant information. A functional magnetic resonance imaging experiment using the same paradigm replicated the behavioral results and found that diminished recollection was associated with the disruption of functional connectivity in a network involving the left inferior frontal gyrus, hippocampus and visual association cortex. Network connectivity supported recollection of contextual details based on visual imagery when eyes were closed, but declined in the presence of irrelevant visual information. We conclude that bottom-up influences from irrelevant visual information interfere with top-down selection of episodic details mediated by a capacity-limited frontal control region, resulting in impaired recollection.

Functional connectivity during working memory maintenance.

Neurophysiological experiments with monkeys have demonstrated that working memory (WM) is associated with persistent neural activity in multiple brain regions, such as the prefrontal cortex (PFC), the parietal cortex, and posterior unimodal association areas. WM maintenance is believed to require the coordination of these brain regions, which do not function in isolation but, rather, interact to maintain visual percepts that are no longer present in the environment. However, single-unit physiology studies and traditional univariate analyses of functional brain imaging data cannot evaluate interactions between distant brain regions, and so evidence of regional integration during WM maintenance is largely indirect. In this study, we utilized a recently developed multivariate analysis method that allows us to explore functional connectivity between brain regions during the distinct stages of a delayed face recognition task. To characterize the neural network mediating the on-line maintenance of faces, the fusiform face area (FFA) was defined as a seed and was then used to generate whole-brain correlation maps. A random effects analysis of the correlation data revealed a network of brain regions exhibiting significant correlations with the FFA seed during the WM delay period. This maintenance network included the dorsolateral and ventrolateral PFC, the premotor cortex, the intraparietal sulcus, the caudate nucleus, the thalamus, the hippocampus, and occipitotemporal regions. These findings support the notion that the coordinated functional interaction between nodes of a widely distributed network underlies the active maintenance of a perceptual representation.