The specific contents of human consciousness rely on the activity of specialized neurons in cerebral cortex. We hypothesized that the conscious experience of a specific visual motion axis is reflected in response amplitudes of direction-selective clusters in the human motion complex. Using submillimeter fMRI at ultrahigh field (7 T) we identified fine-grained clusters that were tuned to either...
Significance Standard antidepressant treatments require weeks to show effectiveness. A single subanesthetic dose of ketamine rapidly attenuates many clinical signs and symptoms of depression; however, ketamine treatment also has many adverse effects, including dissociation and potential for abuse, which are mediated by NMDA glutamate receptor (NMDAR) inhibition. Previous work has revealed that...
Significance Loneliness (i.e., feeling alone) and social isolation (i.e., being alone) are among the most robust known risk factors for poor health and accelerated mortality. Yet mitigating these social risk factors is challenging, as few interventions have been effective for both reducing loneliness and increasing social contact. Mindfulness interventions, which train skills in monitoring...
Psychedelics exert unique effects on human consciousness. The thalamic filter model suggests that core effects of psychedelics may result from gating deficits, based on a disintegration of information processing within cortico-striato-thalamo-cortical (CSTC) feedback loops. To test this hypothesis, we characterized changes in directed (effective) connectivity between selected CTSC regions after...
Archaeological studies have found evidence of ritual consumption of psychoactive plants among native cultures in South America. However, the evidence is fragmentary, preventing researchers from piecing together a coherent picture of hallucinogen use in ancient South America. Melanie Miller et al. (pp. 11207–11212) analyzed the chemical makeup of artifacts in a 1,000-year-old ritual bundle...
Significance A metabolite of ketamine, (2 R ,6 R )-hydroxynorketamine [(2 R ,6 R )-HNK], produces rapid and sustained antidepressant effects in animal models but without the side effects of ketamine. Notably, (2 R ,6 R )-HNK does not block the NMDA receptor, the primary target of ketamine. Here, we demonstrate that the antidepressant effects of (2 R ,6 R )-HNK require activity dependent release...
Significance People often feel defensive when reminded of their unhealthy behavior. We propose that self-transcendence, encouraged by focusing on others’ well-being, can lessen subsequent focus on threatened aspects of the self and increase receptivity. We show that activating self-transcendent mindsets, either by reflecting on self-transcendent values or making positive wishes for others,...
Subjective feelings are a central feature of human life. We defined the organization and determinants of a feeling space involving 100 core feelings that ranged from cognitive and affective processes to somatic sensations and common illnesses. The feeling space was determined by a combination of basic dimension rating, similarity mapping, bodily sensation mapping, and neuroimaging...
Regions of transmodal cortex, in particular the default mode network (DMN), have historically been argued to serve functions unrelated to task performance, in part because of associations with naturally occurring periods of off-task thought. In contrast, contemporary views of the DMN suggest it plays an integrative role in cognition that emerges from its location at the top of a cortical...
Recent reports have begun to elucidate mechanisms by which learning and experience produce white matter changes in the brain. We previously reported changes in white matter surrounding the anterior cingulate cortex in humans after 2-4 weeks of meditation training. We further found that low-frequency optogenetic stimulation of the anterior cingulate in mice increased time spent in the light in a...
Low-dose ketamine, an open-channel N-methyl d-aspartate receptor (NMDAR) antagonist, mediates rapid antidepressant effects in humans that are mimicked in preclinical rodent models. Disinhibition of pyramidal cells via decreased output of fast-spiking GABAergic interneurons has been proposed as a key mechanism that triggers the antidepressant response. Unfortunately, to date, disinhibition has...
The visual system has the remarkable ability to integrate fragmentary visual input into a perceptually organized collection of surfaces and objects, a process we refer to as perceptual integration. Despite a long tradition of perception research, it is not known whether access to consciousness is required to complete perceptual integration. To investigate this question, we manipulated access to...
Meditation training induces changes at both the behavioral and neural levels. A month of meditation training can reduce self-reported anxiety and other dimensions of negative affect. It also can change white matter as measured by diffusion tensor imaging and increase resting-state midline frontal theta activity. The current study tests the hypothesis that imposing rhythms in the mouse anterior...
Emotional states of consciousness, or what are typically called emotional feelings, are traditionally viewed as being innately programmed in subcortical areas of the brain, and are often treated as different from cognitive states of consciousness, such as those related to the perception of external stimuli. We argue that conscious experiences, regardless of their content, arise from one system...
We often engage in two concurrent but unrelated activities, such as driving on a quiet road while listening to the radio. When we do so, does our brain split into functionally distinct entities? To address this question, we imaged brain activity with fMRI in experienced drivers engaged in a driving simulator while listening either to global positioning system instructions (integrated task) or...
Among the opioid receptors, the κ-opioid receptor (κOR) has been gaining considerable attention as a potential therapeutic target for the treatment of complex CNS disorders including depression, visceral pain, and cocaine addiction. With an interest in discovering novel ligands targeting κOR, we searched natural products for unusual scaffolds and identified collybolide (Colly), a nonnitrogenous...
Serotonin transporter (SERT) is responsible for reuptake and recycling of 5-hydroxytryptamine (5-HT; serotonin) after its exocytotic release during neurotransmission. Mutations in human SERT are associated with psychiatric disorders and autism. Some of these mutations affect the regulation of SERT activity by cGMP-dependent phosphorylation. Here we provide direct evidence that this...
Social ties are crucial for physical and mental health. However, psychiatric patients frequently encounter social rejection. Moreover, an increased reactivity to social exclusion influences the development, progression, and treatment of various psychiatric disorders. Nevertheless, the neuromodulatory substrates of rejection experiences are largely unknown. The preferential serotonin (5-HT)...
How, why, and when consciousness evolved remain hotly debated topics. Addressing these issues requires considering the distribution of consciousness across the animal phylogenetic tree. Here we propose that at least one invertebrate clade, the insects, has a capacity for the most basic aspect of consciousness: subjective experience. In vertebrates the capacity for subjective experience is...
Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in...
Significance Measuring the degree of causal influences among multiple elements of a system is a fundamental problem in physics and biology. We propose a unified framework for quantifying any combination of causal relationships between elements in a hierarchical manner based on information geometry. Our measure of integration, called geometrical integrated information, quantifies the strength of...
Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely...
The default mode network (DMN) and semantic network (SN) are two of the most extensively studied systems, and both are increasingly used as clinical biomarkers in neurological studies. There are strong theoretical reasons to assume a relationship between the networks, as well as anatomical evidence that they might rely on overlapping cortical regions, such as the anterior temporal lobe (ATL) or...
According to recent evidence, stimulus-tuned neurons in the cerebral cortex exhibit reduced variability in firing rate across trials, after the onset of a stimulus. However, in order for a reduction in variability to be directly relevant to perception and behavior, it must be realized within trial--the pattern of activity must be relatively stable. Stability is characteristic of decision states...
Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging,...