Dr. Fox holds a PhD in cognitive neuroscience and is currently pursuing an MD at Stanford's School of Medicine. His doctoral research focused on the brain basis of meditation and mindfulness and on meta-analytic integration of functional and structural neuroimaging data. He currently works in Stanford’s Department of Neurology and Neurological Sciences, using intracranial electrical stimulation of the human brain to conduct research on cognition and emotion in patients with severe epilepsy. His original research has appeared in high-impact peer-reviewed publications, including Neurology, Nature Human Behaviour, and Nature Ecology & Evolution, as well as theoretical and review articles in Nature Reviews Neuroscience and Trends in Cognitive Sciences. His research has garnered widespread attention, including coverage in The Guardian, Scientific American, and the BBC.
Electrocorticographic evidence of a common neurocognitive sequence for mentalizing about the self and others.
2022; 13 (1): 1919
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.
View details for DOI 10.1038/s41467-022-29510-2
View details for PubMedID 35395826
Does the Prefrontal Cortex Play an Essential Role in Consciousness? Insights from Intracranial Electrical Stimulation of the Human Brain.
The Journal of neuroscience : the official journal of the Society for Neuroscience
2021; 41 (10): 2076–87
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.
View details for DOI 10.1523/JNEUROSCI.1141-20.2020
View details for PubMedID 33692142
Fidelity of first-person reports following intracranial neuromodulation of the human brain: An empirical assessment of sham stimulation in neurosurgical patients.
BACKGROUND: Brain stimulation, both invasive and non-invasive, is increasingly being used to modulate mood and other aspects of subjective experience in various neuropsychiatric conditions. Because this enterprise is deeply dependent on first-person reports provided by patients, sham stimulation is routinely employed to control for demand characteristics and placebo effects. However, a general empirical assessment of the fidelity of this control is missing.OBJECTIVE: To provide an empirical exploration of the fidelity of first-person reports following intracranial electrical stimulation (iES) in neurosurgical patients.METHODS: We assessed Type I (false positive) error rate following 159 sham stimulations administered to 44 adult epilepsy patients implanted with intracranial electrodes and undergoing iES as part of routine clinical procedures at the Stanford Medical Center.RESULTS: The majority of our patients (75%) never committed a single Type I error, and 93% of our sham stimulations (n = 148) yielded true negative reports. False positives were restricted to only 11 patients, and no patient committed more than a single Type I error, even after multiple sham stimulations.CONCLUSION: Neurosurgical patients are highly resilient to Type I errors following sham intracranial brain stimulation. Our findings support the validity of prior research exploring first-person experiences elicited by electrical stimulation of the human brain. More broadly, our data are relevant to emerging efforts to use brain stimulation to modulate mood and other aspects of human subjective experience.
View details for DOI 10.1016/j.brs.2020.10.015
View details for PubMedID 33130019
Intrinsic network architecture predicts the effects elicited by intracranial electrical stimulation of the human brain.
Nature human behaviour
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.
View details for DOI 10.1038/s41562-020-0910-1
View details for PubMedID 32632334
Intensity of affective experience is modulated by magnitude of intracranial electrical stimulation in human orbitofrontal, cingulate and insular cortices
SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
2019; 14 (4): 339–51
View details for DOI 10.1093/scan/nsz015
View details for Web of Science ID 000470060000001
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.
View details for PubMedID 30232252
Affective neuroscience of self-generated thought.
Annals of the New York Academy of Sciences
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.
View details for PubMedID 29754412
Intracranial Electrophysiology of the Human Default Network
TRENDS IN COGNITIVE SCIENCES
2018; 22 (4): 307–24
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.
View details for PubMedID 29525387
View details for PubMedCentralID PMC5957519
The social and cultural roots of whale and dolphin brains
NATURE ECOLOGY & EVOLUTION
2017; 1 (11): 1699–1705
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.
View details for PubMedID 29038481
Letter to the Editor: Miscommunicating Mindfulness
PERSPECTIVES ON PSYCHOLOGICAL SCIENCE
View details for DOI 10.1177/1745691620924057
View details for Web of Science ID 000556264600001
View details for PubMedID 32750262
Mind-wandering as creative thinking: neural, psychological, and theoretical considerations
CURRENT OPINION IN BEHAVIORAL SCIENCES
2019; 27: 123–30
View details for DOI 10.1016/j.cobeha.2018.10.009
View details for Web of Science ID 000470659000021
Aging and the wandering brain: Age-related differences in the neural correlates of stimulus-independent thoughts.
2019; 14 (10): e0223981
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.
View details for DOI 10.1371/journal.pone.0223981
View details for PubMedID 31613920
Mind-Wandering as a Scientific Concept: Cutting through the Definitional Haze
TRENDS IN COGNITIVE SCIENCES
2018; 22 (11): 957–59
View details for PubMedID 30220476
Reiterated Concerns and Further Challenges for Mindfulness and Meditation Research: A Reply to Davidson and Dahl
PERSPECTIVES ON PSYCHOLOGICAL SCIENCE
2018; 13 (1): 66–69
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.
View details for PubMedID 29016240
View details for PubMedCentralID PMC5817993
Mind the Hype: A Critical Evaluation and Prescriptive Agenda for Research on Mindfulness and Meditation
PERSPECTIVES ON PSYCHOLOGICAL SCIENCE
2018; 13 (1): 36–61
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.
View details for PubMedID 29016274
View details for PubMedCentralID PMC5758421