Does the Prefrontal Cortex Play an Essential Role in Consciousness? Insights from Intracranial Electrical Stimulation of the Human Brain.

A central debate in philosophy and neuroscience pertains to whether PFC activity plays an essential role in the neural basis of consciousness. Neuroimaging and electrophysiology studies have revealed that the contents of conscious perceptual experience can be successfully decoded from PFC activity, but these findings might be confounded by postperceptual cognitive processes, such as thinking, reasoning, and decision-making, that are not necessary for consciousness. To clarify the involvement of the PFC in consciousness, we present a synthesis of research that has used intracranial electrical stimulation (iES) for the causal modulation of neural activity in the human PFC. This research provides compelling evidence that iES of only certain prefrontal regions (i.e., orbitofrontal cortex and anterior cingulate cortex) reliably perturbs conscious experience. Conversely, stimulation of anterolateral prefrontal sites, often considered crucial in higher-order and global workspace theories of consciousness, seldom elicits any reportable alterations in consciousness. Furthermore, the wide variety of iES-elicited effects in the PFC (e.g., emotions, thoughts, and olfactory and visual hallucinations) exhibits no clear relation to the immediate environment. Therefore, there is no evidence for the kinds of alterations in ongoing perceptual experience that would be predicted by higher-order or global workspace theories. Nevertheless, effects in the orbitofrontal and anterior cingulate cortices suggest a specific role for these PFC subregions in supporting emotional aspects of conscious experience. Overall, this evidence presents a challenge for higher-order and global workspace theories, which commonly point to the PFC as the basis for conscious perception based on correlative and possibly confounded information.

Mind-wandering as spontaneous thought: a dynamic framework.

Most research on mind-wandering has characterized it as a mental state with contents that are task unrelated or stimulus independent. However, the dynamics of mind-wandering - how mental states change over time - have remained largely neglected. Here, we introduce a dynamic framework for understanding mind-wandering and its relationship to the recruitment of large-scale brain networks. We propose that mind-wandering is best understood as a member of a family of spontaneous-thought phenomena that also includes creative thought and dreaming. This dynamic framework can shed new light on mental disorders that are marked by alterations in spontaneous thought, including depression, anxiety and attention deficit hyperactivity disorder.

Dynamics of neural recruitment surrounding the spontaneous arising of thoughts in experienced mindfulness practitioners.

Thoughts arise spontaneously in our minds with remarkable frequency, but tracking the brain systems associated with the early inception of a thought has proved challenging. Here we addressed this issue by taking advantage of the heightened introspective ability of experienced mindfulness practitioners to observe the onset of their spontaneously arising thoughts. We found subtle differences in timing among the many regions typically recruited by spontaneous thought. In some of these regions, fMRI signal peaked prior to the spontaneous arising of a thought - most notably in the medial temporal lobe and inferior parietal lobule. In contrast, activation in the medial prefrontal, temporopolar, mid-insular, lateral prefrontal, and dorsal anterior cingulate cortices peaked together with or immediately following the arising of spontaneous thought. We propose that brain regions that show antecedent recruitment may be preferentially involved in the initial inception of spontaneous thoughts, while those that show later recruitment may be preferentially involved in the subsequent elaboration and metacognitive processing of spontaneous thoughts. Our findings highlight the temporal dynamics of neural recruitment surrounding the emergence of spontaneous thoughts and may help account for some of spontaneous thought's peculiar qualities, including its wild diversity of content and its links to memory and attention.

The wandering brain: meta-analysis of functional neuroimaging studies of mind-wandering and related spontaneous thought processes.

The neural basis and cognitive functions of various spontaneous thought processes, particularly mind-wandering, are increasingly being investigated. Although strong links have been drawn between the occurrence of spontaneous thought processes and activation in brain regions comprising the default mode network (DMN), spontaneous thought also appears to recruit other, non-DMN regions just as consistently. Here we present the first quantitative meta-analysis of neuroimaging studies of spontaneous thought and mind-wandering in order to address the question of their neural correlates. Examining 24 functional neuroimaging studies of spontaneous thought processes, we conducted a meta-analysis using activation likelihood estimation (ALE). A number of key DMN areas showed consistent recruitment across studies, including medial prefrontal cortex, posterior cingulate cortex, medial temporal lobe, and bilateral inferior parietal lobule. Numerous non-DMN regions, however, were also consistently recruited, including rostrolateral prefrontal cortex, dorsal anterior cingulate cortex, insula, temporopolar cortex, secondary somatosensory cortex, and lingual gyrus. These meta-analytic results indicate that DMN activation alone is insufficient to adequately capture the neural basis of spontaneous thought; frontoparietal control network areas, and other non-DMN regions, appear to be equally central. We conclude that further progress in the cognitive and clinical neuroscience of spontaneous thought will therefore require a re-balancing of our view of the contributions of various regions and networks throughout the brain, and beyond the DMN.

Dreaming and the default network: A review, synthesis, and counterintuitive research proposal.

This article argues that the default network, augmented by secondary visual and sensorimotor cortices, is the likely neural correlate of dreaming. This hypothesis is based on a synthesis of work on dream content, the findings on the contents and neural correlates of mind-wandering, and the results from EEG and neuroimaging studies of REM sleep. Relying on studies in the 1970s that serendipitously discovered episodes of dreaming during waking mind-wandering, this article presents the seemingly counterintuitive hypothesis that the neural correlates for dreaming could be further specified in the process of carrying out EEG/fMRI studies of mind-wandering and default network activity. This hypothesis could be tested by asking participants for experiential reports during moments of differentially high levels of default network activation, as indicated by mixed EEG/fMRI criteria. Evidence from earlier EEG/fMRI studies of mind-wandering and from laboratory studies of dreaming during the sleep-onset process is used to support the argument.

Electrocorticographic evidence of a common neurocognitive sequence for mentalizing about the self and others.

Neuroimaging studies of mentalizing (i.e., theory of mind) consistently implicate the default mode network (DMN). Nevertheless, the social cognitive functions of individual DMN regions remain unclear, perhaps due to limited spatiotemporal resolution in neuroimaging. Here we use electrocorticography (ECoG) to directly record neuronal population activity while 16 human participants judge the psychological traits of themselves and others. Self- and other-mentalizing recruit near-identical cortical sites in a common spatiotemporal sequence. Activations begin in the visual cortex, followed by temporoparietal DMN regions, then finally in medial prefrontal regions. Moreover, regions with later activations exhibit stronger functional specificity for mentalizing, stronger associations with behavioral responses, and stronger self/other differentiation. Specifically, other-mentalizing evokes slower and longer activations than self-mentalizing across successive DMN regions, implying lengthier processing at higher levels of representation. Our results suggest a common neurocognitive pathway for self- and other-mentalizing that follows a complex spatiotemporal gradient of functional specialization across DMN and beyond.

Intrinsic network architecture predicts the effects elicited by intracranial electrical stimulation of the human brain.

Intracranial electrical stimulation (iES) of the human brain has long been known to elicit a remarkable variety of perceptual, motor and cognitive effects, but the functional-anatomical basis of this heterogeneity remains poorly understood. We conducted a whole-brain mapping of iES-elicited effects, collecting first-person reports following iES at 1,537 cortical sites in 67 participants implanted with intracranial electrodes. We found that intrinsic network membership and the principal gradient of functional connectivity strongly predicted the type and frequency of iES-elicited effects in a given brain region. While iES in unimodal brain networks at the base of the cortical hierarchy elicited frequent and simple effects, effects became increasingly rare, heterogeneous and complex in heteromodal and transmodal networks higher in the hierarchy. Our study provides a comprehensive exploration of the relationship between the hierarchical organization of intrinsic functional networks and the causal modulation of human behaviour and experience with iES.

Intensity of affective experience is modulated by magnitude of intracranial electrical stimulation in human orbitofrontal, cingulate and insular cortices.

The subjective and behavioral effects of intracranial electrical stimulation (iES) have been studied for decades, but there is a knowledge gap regarding the relationship between the magnitude of electric current and the type, intensity and valence of evoked subjective experiences. We report on rare iES data from 18 neurosurgical patients with implanted intracranial electrodes in the orbitofrontal cortex (OFC), the insula (INS) and the anterior portion of cingulate cortex (ACC). ACC stimulation elicited somatic and visceral sensations, whereas OFC stimulation predominantly elicited olfactory and gustatory responses, and INS stimulation elicited a mix of effects involving somatic and visceral sensations, olfaction and gustation. Further, we found striking evidence that the magnitude of electric current delivered intracranially correlated positively with the perceived intensity of subjective experience and the evoked emotional state, a relationship observed across all three regions. Finally, we observed that the majority of reported experiences were negatively valenced and unpleasant, especially those elicited by ACC stimulation. The present study provides novel case studies from the human brain confirming that these structures contribute causally to the creation of affective states and demonstrates a direct relationship between the magnitude of electrical stimulation of these structures and the qualia of elicited subjective experience. Summary: This study provides critical knowledge about the effect of electrical charge magnitude on the intensity of human subjective experiences and emotional states. We shed light on the fundamental relationship between the electrical (physical) state of cortical tissue and the modality and intensity of human (subjective) experience. As electroceutical interventions are increasingly employed to treat neurological and psychiatric disorders, these findings highlight the importance of electrical stimulation magnitude for eliciting specific changes in human subjective experience.

Aging and the wandering brain: Age-related differences in the neural correlates of stimulus-independent thoughts.

In recent years, several studies have indicated that healthy older adults exhibit a reduction in task-unrelated thoughts compared to young adults. However, much less is known regarding age-related differences in time spent engaging in stimulus-independent thoughts or in their neural correlates in the absence of an ongoing task. In the current study, we collected functional magnetic resonance imaging (fMRI) data while 29 young (mean age = 22y) and 22 older (mean age = 70y) adults underwent experience sampling in the absence of an ongoing task (i.e., at "rest"). Although both age groups reported spending a similar amount of time engaged in stimulus-independent thoughts, older adults rated their thoughts as more present-oriented (rather than atemporal) and more novel. Moreover, controlling for these age-related differences in content, we found that experiencing stimulus-independent thoughts was associated with increased posterior cingulate and left angular gyrus activation across age groups compared to exhibiting an external focus of attention. When experiencing stimulus-independent thoughts, younger adults engaged medial and left lateral prefrontal cortex as well as left superior temporal gyrus to a greater degree than older adults. Taken together, our results suggest that, in the absence of an ongoing task, although young and older adults spend a similar amount of time engaging in stimulus-independent thoughts, the content and neural correlates of these thoughts differ with age.

Author Correction: The social and cultural roots of whale and dolphin brains.

In Table 1 of the Supplementary Information, the data presented in the column 'Corrected social repertoire' were incorrect. This error does not affect the analyses, statistics or conclusions of the study, which employed the correct values. The data have now been corrected in the Supplementary file.

Changes in subjective experience elicited by direct stimulation of the human orbitofrontal cortex.

OBJECTIVE: We applied direct cortical stimulation (DCS) to the orbitofrontal cortex (OFC) in neurosurgical patients implanted with intracranial electrodes to probe, with high anatomic precision, the causal link between the OFC and human subjective experience. METHODS: We administered 272 instances of DCS at 172 OFC sites in 22 patients with intractable focal epilepsy (from 2011 to 2017), none of whom had seizures originating from the OFC. RESULTS: Our observations revealed a rich variety of affective, olfactory, gustatory, and somatosensory changes in the subjective domain. Elicited experiences were largely neutral or negatively valenced (e.g., aversive smells and tastes, sadness, and anger). Evidence was found for preferential left lateralization of negatively valenced experiences and strong right lateralization of neutral effects. Moreover, most of the elicited effects were observed after stimulation of OFC tissue around the transverse orbital sulcus, and none were seen in the most anterior aspects of the OFC. CONCLUSIONS: Our study yielded 3 central findings: first, a dissociation between the "silent" anterior and nonsilent middle/posterior OFC where stimulation clearly elicits changes in subjective experience; second, evidence that the OFC might play a causal role in integrating affect and multimodal sensory experiences; and third, clear evidence for left lateralization of negatively valenced effects. Our findings provide important information for clinicians treating OFC injury or planning OFC resection and scientists seeking to understand the brain basis for the integration of sensation, cognition, and affect.

Intracranial Electrophysiology of the Human Default Network.

The human default network (DN) plays a critical role in internally directed cognition, behavior, and neuropsychiatric disease. Despite much progress with functional neuroimaging, persistent questions still linger concerning the electrophysiological underpinnings, fast temporal dynamics, and causal importance of the DN. Here, we review how direct intracranial recording and stimulation of the DN provides a unique combination of high spatiotemporal resolution and causal information that speaks directly to many of these outstanding questions. Our synthesis highlights the electrophysiological basis of activation, suppression, and connectivity of the DN, each key areas of debate in the literature. Integrating these unique electrophysiological data with extant neuroimaging findings will help lay the foundation for a mechanistic account of DN function in human behavior and cognition.

Affective neuroscience of self-generated thought.

Despite increasing scientific interest in self-generated thought-mental content largely independent of the immediate environment-there has yet to be any comprehensive synthesis of the subjective experience and neural correlates of affect in these forms of thinking. Here, we aim to develop an integrated affective neuroscience encompassing many forms of self-generated thought-normal and pathological, moderate and excessive, in waking and in sleep. In synthesizing existing literature on this topic, we reveal consistent findings pertaining to the prevalence, valence, and variability of emotion in self-generated thought, and highlight how these factors might interact with self-generated thought to influence general well-being. We integrate these psychological findings with recent neuroimaging research, bringing attention to the neural correlates of affect in self-generated thought. We show that affect in self-generated thought is prevalent, positively biased, highly variable (both within and across individuals), and consistently recruits many brain areas implicated in emotional processing, including the orbitofrontal cortex, amygdala, insula, and medial prefrontal cortex. Many factors modulate these typical psychological and neural patterns, however; the emerging affective neuroscience of self-generated thought must endeavor to link brain function and subjective experience in both everyday self-generated thought as well as its dysfunctions in mental illness.

Reiterated Concerns and Further Challenges for Mindfulness and Meditation Research: A Reply to Davidson and Dahl.

In response to our article, Davidson and Dahl offer commentary and advice regarding additional topics crucial to a comprehensive prescriptive agenda for future research on mindfulness and meditation. Their commentary raises further challenges and provides an important complement to our article. More consideration of these issues is especially welcome because limited space precluded us from addressing all relevant topics. While we agree with many of Davidson and Dahl's suggestions, the present reply (a) highlights reasons why the concerns we expressed are still especially germane to mindfulness and meditation research (even though those concerns may not be entirely unique) and (b) gives more context to other issues posed by them. We discuss special characteristics of individuals who participate in mindfulness and meditation research and focus on the vulnerability of this field inherent in its relative youthfulness compared to other more mature scientific disciplines. Moreover, our reply highlights the serious consequences of adverse experiences suffered by a significant subset of individuals during mindfulness and other contemplative practices. We also scrutinize common contemporary applications of mindfulness and meditation to illness, and some caveats are introduced regarding mobile technologies for guidance of contemplative practices.

Mind the Hype: A Critical Evaluation and Prescriptive Agenda for Research on Mindfulness and Meditation.

During the past two decades, mindfulness meditation has gone from being a fringe topic of scientific investigation to being an occasional replacement for psychotherapy, tool of corporate well-being, widely implemented educational practice, and "key to building more resilient soldiers." Yet the mindfulness movement and empirical evidence supporting it have not gone without criticism. Misinformation and poor methodology associated with past studies of mindfulness may lead public consumers to be harmed, misled, and disappointed. Addressing such concerns, the present article discusses the difficulties of defining mindfulness, delineates the proper scope of research into mindfulness practices, and explicates crucial methodological issues for interpreting results from investigations of mindfulness. For doing so, the authors draw on their diverse areas of expertise to review the present state of mindfulness research, comprehensively summarizing what we do and do not know, while providing a prescriptive agenda for contemplative science, with a particular focus on assessment, mindfulness training, possible adverse effects, and intersection with brain imaging. Our goals are to inform interested scientists, the news media, and the public, to minimize harm, curb poor research practices, and staunch the flow of misinformation about the benefits, costs, and future prospects of mindfulness meditation.

The social and cultural roots of whale and dolphin brains.

Encephalization, or brain expansion, underpins humans' sophisticated social cognition, including language, joint attention, shared goals, teaching, consensus decision-making and empathy. These abilities promote and stabilize cooperative social interactions, and have allowed us to create a 'cognitive' or 'cultural' niche and colonize almost every terrestrial ecosystem. Cetaceans (whales and dolphins) also have exceptionally large and anatomically sophisticated brains. Here, by evaluating a comprehensive database of brain size, social structures and cultural behaviours across cetacean species, we ask whether cetacean brains are similarly associated with a marine cultural niche. We show that cetacean encephalization is predicted by both social structure and by a quadratic relationship with group size. Moreover, brain size predicts the breadth of social and cultural behaviours, as well as ecological factors (diversity of prey types and to a lesser extent latitudinal range). The apparent coevolution of brains, social structure and behavioural richness of marine mammals provides a unique and striking parallel to the large brains and hyper-sociality of humans and other primates. Our results suggest that cetacean social cognition might similarly have arisen to provide the capacity to learn and use a diverse set of behavioural strategies in response to the challenges of social living.

The neurobiology of self-generated thought from cells to systems: Integrating evidence from lesion studies, human intracranial electrophysiology, neurochemistry, and neuroendocrinology.

Investigation of the neural basis of self-generated thought is moving beyond a simple identification with default network activation toward a more comprehensive view recognizing the role of the frontoparietal control network and other areas. A major task ahead is to unravel the functional roles and temporal dynamics of the widely distributed brain regions recruited during self-generated thought. We argue that various other neuroscientific methods - including lesion studies, human intracranial electrophysiology, and manipulation of neurochemistry - have much to contribute to this project. These diverse data have yet to be synthesized with the growing understanding of self-generated thought gained from neuroimaging, however. Here, we highlight several areas of ongoing inquiry and illustrate how evidence from other methodologies corroborates, complements, and clarifies findings from functional neuroimaging. Each methodology has particular strengths: functional neuroimaging reveals much about the variety of brain areas and networks reliably recruited. Lesion studies point to regions critical to generating and consciously experiencing self-generated thought. Human intracranial electrophysiology illuminates how and where in the brain thought is generated and where this activity subsequently spreads. Finally, measurement and manipulation of neurotransmitter and hormone levels can clarify what kind of neurochemical milieu drives or facilitates self-generated cognition. Integrating evidence from multiple complementary modalities will be a critical step on the way to improving our understanding of the neurobiology of functional and dysfunctional forms of self-generated thought.