LBCN Select Publications

Professor of Neurology (Adult Neurology) and, by courtesy, of Neurosurgery


  • Causal evidence for the processing of bodily self in the anterior precuneus. Neuron Lyu, D., Stieger, J. R., Xin, C., Ma, E., Lusk, Z., Aparicio, M. K., Werbaneth, K., Perry, C. M., Deisseroth, K., Buch, V., Parvizi, J. 2023


    To probe the causal importance of the human posteromedial cortex (PMC) in processing the sense of self, we studied a rare cohort of nine patients with electrodes implanted bilaterally in the precuneus, posterior cingulate, and retrosplenial regions with a combination of neuroimaging, intracranial recordings, and direct cortical stimulations. In all participants, the stimulation of specific sites within the anterior precuneus (aPCu) caused dissociative changes in physical and spatial domains. Using single-pulse electrical stimulations and neuroimaging, we present effective and resting-state connectivity of aPCu hot zone with the rest of the brain and show that they are located outside the boundaries of the default mode network (DMN) but connected reciprocally with it. We propose that the function of this subregion of the PMC is integral to a range of cognitive processes that require the self's physical point of reference, given its location within a spatial environment.

    View details for DOI 10.1016/j.neuron.2023.05.013

    View details for PubMedID 37295420

  • Multisite thalamic recordings to characterize seizure propagation in the human brain. Brain : a journal of neurology Wu, T. Q., Kaboodvand, N., McGinn, R. J., Veit, M., Davey, Z., Datta, A., Graber, K. D., Meador, K. J., Fisher, R., Buch, V., Parvizi, J. 2023


    Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important uncertainty is to what extent thalamic subregions other than the ANT could be recruited more prominently in the propagation of focal onset seizures. We designed the current study to simultaneously monitor the engagement of the ANT, mediodorsal (MD) and pulvinar (PUL) nuclei during seizures in patients who could be candidates for thalamic neuromodulation. We studied 11 patients with clinical manifestations of presumed temporal lobe epilepsy (TLE) undergoing invasive stereo-encephalography (sEEG) monitoring to confirm the source of their seizures. We extended cortical electrodes to reach the ANT, MD and PUL nuclei of the thalamus. More than one thalamic subdivision was simultaneously interrogated in nine patients. We recorded seizures with implanted electrodes across various regions of the brain and documented seizure onset zones (SOZ) in each recorded seizure. We visually identified the first thalamic subregion to be involved in seizure propagation. Additionally, in eight patients, we applied repeated single pulse electrical stimulation in each SOZ and recorded the time and prominence of evoked responses across the implanted thalamic regions. Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, highlighting the importance of invasive monitoring for accurate localization of SOZs. In all patients, seizures with the same propagation network and originating from the same SOZ involved the same thalamic subregion, with a stereotyped thalamic EEG signature. Qualitative visual reviews of ictal EEGs were largely consistent with the quantitative analysis of the corticothalamic evoked potentials, and both documented that thalamic nuclei other than ANT could have the earliest participation in seizure propagation. Specifically, pulvinar nuclei were involved earlier and more prominently than ANT in more than half of the patients. However, which specific thalamic subregion first demonstrated ictal activity could not be reliably predicted based on clinical semiology or lobar localization of SOZs. Our findings document the feasibility and safety of bilateral multisite sampling from the human thalamus. This may allow more personalized thalamic targets to be identified for neuromodulation. Future studies are needed to determine if a personalized thalamic neuromodulation leads to greater improvements in clinical outcome.

    View details for DOI 10.1093/brain/awad121

    View details for PubMedID 37137813

  • Causal mapping of human brain function. Nature reviews. Neuroscience Siddiqi, S. H., Kording, K. P., Parvizi, J., Fox, M. D. 2022


    Mapping human brain function is a long-standing goal of neuroscience that promises to inform the development of new treatments for brain disorders. Early maps of human brain function were based on locations of brain damage or brain stimulation that caused a functional change. Over time, this approach was largely replaced by technologies such as functional neuroimaging, which identify brain regions in which activity is correlated with behaviours or symptoms. Despite their advantages, these technologies reveal correlations, not causation. This creates challenges for interpreting the data generated from these tools and using them to develop treatments for brain disorders. A return to causal mapping of human brain function based on brain lesions and brain stimulation is underway. New approaches can combine these causal sources of information with modern neuroimaging and electrophysiology techniques to gain new insights into the functions of specific brain areas. In this Review, we provide a definition of causality for translational research, propose a continuum along which to assess the relative strength of causal information from human brain mapping studies and discuss recent advances in causal brain mapping and their relevance for developing treatments.

    View details for DOI 10.1038/s41583-022-00583-8

    View details for PubMedID 35444305

  • Intrinsic network architecture predicts the effects elicited by intracranial electrical stimulation of the human brain. Nature human behaviour Fox, K. C., Shi, L., Baek, S., Raccah, O., Foster, B. L., Saha, S., Margulies, D. S., Kucyi, A., Parvizi, J. 2020


    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

  • Cognitive refractory state caused by spontaneous epileptic high-frequency oscillations in the human brain. Science translational medicine Liu, S., Parvizi, J. 2019; 11 (514)


    Epileptic brain tissue is often considered physiologically dysfunctional, and the optimal treatment of many patients with uncontrollable seizures involves surgical removal of the epileptic tissue. However, it is unclear to what extent the epileptic tissue is capable of generating physiological responses to cognitive stimuli and how cognitive deficits ensuing surgical resections can be determined using state-of-the-art computational methods. To address these unknowns, we recruited six patients with nonlesional epilepsies and identified the epileptic focus in each patient with intracranial electrophysiological monitoring. We measured spontaneous epileptic activity in the form of high-frequency oscillations (HFOs), recorded stimulus-locked physiological responses in the form of physiological high-frequency broadband activity, and explored the interaction of the two as well as their behavioral correlates. Across all patients, we found abundant normal physiological responses to relevant cognitive stimuli in the epileptic sites. However, these physiological responses were more likely to be "seized" (delayed or missed) when spontaneous HFOs occurred about 850 to 1050 ms before, until about 150 to 250 ms after, the onset of relevant cognitive stimuli. Furthermore, spontaneous HFOs in medial temporal lobe affected the subjects' memory performance. Our findings suggest that nonlesional epileptic sites are capable of generating normal physiological responses and highlight a compelling mechanism for cognitive deficits in these patients. The results also offer clinicians a quantitative tool to differentiate pathological and physiological high-frequency activities in epileptic sites and to indirectly assess their possible cognitive reserve function and approximate the risk of resective surgery.

    View details for DOI 10.1126/scitranslmed.aax7830

    View details for PubMedID 31619544

  • Promises and limitations of human intracranial electroencephalography NATURE NEUROSCIENCE Parvizi, J., Kastner, S. 2018; 21 (4): 474–83


    Intracranial electroencephalography (iEEG), also known as electrocorticography when using subdural grid electrodes or stereotactic EEG when using depth electrodes, is blossoming in various fields of human neuroscience. In this article, we highlight the potentials of iEEG in exploring functions of the human brain while also considering its limitations. The iEEG signal provides anatomically precise information about the selective engagement of neuronal populations at the millimeter scale and the temporal dynamics of their engagement at the millisecond scale. If several nodes of a given network are monitored simultaneously with implanted electrodes, the iEEG signals can also reveal information about functional interactions within and across networks during different stages of neural computation. As such, human iEEG can complement other methods of neuroscience beyond simply replicating what is already known, or can be known, from noninvasive lines of research in humans or from invasive recordings in nonhuman mammalian brains.

    View details for PubMedID 29507407

  • Intracranial Electrophysiology of the Human Default Network TRENDS IN COGNITIVE SCIENCES Fox, K. R., Foster, B. L., Kucyi, A., Daitch, A. L., Parvizi, J. 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

  • Intrinsic and Task-Dependent Coupling of Neuronal Population Activity in Human Parietal Cortex NEURON Foster, B. L., Rangarajan, V., Shirer, W. R., Parvizi, J. 2015; 86 (2): 578-590


    Human neuroimaging studies have suggested that subregions of the medial and lateral parietal cortex form key nodes of a larger brain network supporting episodic memory retrieval. To explore the electrophysiological correlates of functional connectivity between these subregions, we recorded simultaneously from medial and lateral parietal cortex using intracranial electrodes in three human subjects. We observed electrophysiological co-activation of retrosplenial/posterior cingulate cortex (RSC/PCC) and angular gyrus (AG) in the high-frequency broadband (HFB, or high-gamma) range, for conditions that required episodic retrieval. During resting and sleeping states, slow fluctuations (<1 Hz) of HFB activity were highly correlated between these task-co-activated neuronal populations. Furthermore, intrinsic electrophysiological connectivity patterns matched those obtained with resting-state fMRI from the same subjects. Our findings quantify the spatiotemporal dynamics of parietal cortex during episodic memory retrieval and provide clear neurophysiological correlates of intrinsic and task-dependent functional connectivity in the human brain.

    View details for DOI 10.1016/j.neuron.2015.03.018

    View details for Web of Science ID 000353410000023

    View details for PubMedID 25863718

    View details for PubMedCentralID PMC4409557

  • The will to persevere induced by electrical stimulation of the human cingulate gyrus. Neuron Parvizi, J., Rangarajan, V., Shirer, W. R., Desai, N., Greicius, M. D. 2013; 80 (6): 1359-1367


    Anterior cingulate cortex (ACC) is known to be involved in functions such as emotion, pain, and cognitive control. While studies in humans and nonhuman mammals have advanced our understanding of ACC function, the subjective correlates of ACC activity have remained largely unexplored. In the current study, we show that electrical charge delivery in the anterior midcingulate cortex (aMCC) elicits autonomic changes and the expectation of an imminent challenge coupled with a determined attitude to overcome it. Seed-based, resting-state connectivity analysis revealed that the site of stimulation in both patients was at the core of a large-scale distributed network linking aMCC to the frontoinsular and frontopolar as well as some subcortical regions. This report provides compelling, first-person accounts of electrical stimulation of this brain network and suggests its possible involvement in psychopathological conditions that are characterized by a reduced capacity to endure psychological or physical distress.

    View details for DOI 10.1016/j.neuron.2013.10.057

    View details for PubMedID 24316296

    View details for PubMedCentralID PMC3877748

  • Electrical Stimulation of Human Fusiform Face-Selective Regions Distorts Face Perception JOURNAL OF NEUROSCIENCE Parvizi, J., Jacques, C., Foster, B. L., Withoft, N., Rangarajan, V., Weiner, K. S., Grill-Spector, K. 2012; 32 (43): 14915-14920


    Face-selective neural responses in the human fusiform gyrus have been widely examined. However, their causal role in human face perception is largely unknown. Here, we used a multimodal approach of electrocorticography (ECoG), high-resolution functional magnetic resonance imaging (fMRI), and electrical brain stimulation (EBS) to directly investigate the causal role of face-selective neural responses of the fusiform gyrus (FG) in face perception in a patient implanted with subdural electrodes in the right inferior temporal lobe. High-resolution fMRI identified two distinct FG face-selective regions [mFus-faces and pFus-faces (mid and posterior fusiform, respectively)]. ECoG revealed a striking anatomical and functional correspondence with fMRI data where a pair of face-selective electrodes, positioned 1 cm apart, overlapped mFus-faces and pFus-faces, respectively. Moreover, electrical charge delivered to this pair of electrodes induced a profound face-specific perceptual distortion during viewing of real faces. Specifically, the subject reported a "metamorphosed" appearance of faces of people in the room. Several controls illustrate the specificity of the effect to the perception of faces. EBS of mFus-faces and pFus-faces neither produced a significant deficit in naming pictures of famous faces on the computer, nor did it affect the appearance of nonface objects. Further, the appearance of faces remained unaffected during both sham stimulation and stimulation of a pair of nearby electrodes that were not face-selective. Overall, our findings reveal a striking convergence of fMRI, ECoG, and EBS, which together offer a rare causal link between functional subsets of the human FG network and face perception.

    View details for DOI 10.1523/JNEUROSCI.2609-12.2012

    View details for Web of Science ID 000310523900008

    View details for PubMedID 23100414

    View details for PubMedCentralID PMC3517886

  • Neural populations in human posteromedial cortex display opposing responses during memory and numerical processing PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Foster, B. L., Dastjerdi, M., Parvizi, J. 2012; 109 (38): 15514-15519


    Our understanding of the human default mode network derives primarily from neuroimaging data but its electrophysiological correlates remain largely unexplored. To address this limitation, we recorded intracranially from the human posteromedial cortex (PMC), a core structure of the default mode network, during various conditions of internally directed (e.g., autobiographical memory) as opposed to externally directed focus (e.g., arithmetic calculation). We observed late-onset (>400 ms) increases in broad high γ-power (70-180 Hz) within PMC subregions during memory retrieval. High γ-power was significantly reduced or absent when subjects retrieved self-referential semantic memories or responded to self-judgment statements, respectively. Conversely, a significant deactivation of high γ-power was observed during arithmetic calculation, the duration of which correlated with reaction time at the signal-trial level. Strikingly, at each recording site, the magnitude of activation during episodic autobiographical memory retrieval predicted the degree of suppression during arithmetic calculation. These findings provide important anatomical and temporal details-at the neural population level-of PMC engagement during autobiographical memory retrieval and address how the same populations are actively suppressed during tasks, such as numerical processing, which require externally directed attention.

    View details for DOI 10.1073/pnas.1206580109

    View details for Web of Science ID 000309211000087

    View details for PubMedID 22949666

    View details for PubMedCentralID PMC3458396

  • Corticocentric myopia: old bias in new cognitive sciences TRENDS IN COGNITIVE SCIENCES Parvizi, J. 2009; 13 (8): 354-359


    Traditionally, the cerebral cortex is seen to have the most important role in 'higher' functions of the brain, such as cognition and behavioral regulation, whereas subcortical structures are considered to have subservient or no roles in these functions. This article highlights the conceptual bias at the root of this corticocentric view of the human brain, and emphasizes its negative implications in current practices in the cognitive neurosciences. The aim of this article is to suggest that the 'corticocentric' view of the human brain is also a myopic view because it does not let us see that the 'higher' functions of the brain might in fact depend on the integrity of its 'lower' structures.

    View details for DOI 10.1016/j.tics.2009.04.008

    View details for Web of Science ID 000269411800008

    View details for PubMedID 19595625

  • Naturalistic acute pain states decoded from neural and facial dynamics. bioRxiv : the preprint server for biology Huang, Y., Gopal, J., Kakusa, B., Li, A. H., Huang, W., Wang, J. B., Persad, A., Ramayya, A., Parvizi, J., Buch, V. P., Keller, C. 2024


    Pain is a complex experience that remains largely unexplored in naturalistic contexts, hindering our understanding of its neurobehavioral representation in ecologically valid settings. To address this, we employed a multimodal, data-driven approach integrating intracranial electroencephalography, pain self-reports, and facial expression quantification to characterize the neural and behavioral correlates of naturalistic acute pain in twelve epilepsy patients undergoing continuous monitoring with neural and audiovisual recordings. High self-reported pain states were associated with elevated blood pressure, increased pain medication use, and distinct facial muscle activations. Using machine learning, we successfully decoded individual participants' high versus low self-reported pain states from distributed neural activity patterns (mean AUC = 0.70), involving mesolimbic regions, striatum, and temporoparietal cortex. High self-reported pain states exhibited increased low-frequency activity in temporoparietal areas and decreased high-frequency activity in mesolimbic regions (hippocampus, cingulate, and orbitofrontal cortex) compared to low pain states. This neural pain representation remained stable for hours and was modulated by pain onset and relief. Objective facial expression changes also classified self-reported pain states, with results concordant with electrophysiological predictions. Importantly, we identified transient periods of momentary pain as a distinct naturalistic acute pain measure, which could be reliably differentiated from affect-neutral periods using intracranial and facial features, albeit with neural and facial patterns distinct from self-reported pain. These findings reveal reliable neurobehavioral markers of naturalistic acute pain across contexts and timescales, underscoring the potential for developing personalized pain interventions in real-world settings.

    View details for DOI 10.1101/2024.05.10.593652

    View details for PubMedID 38766098

    View details for PubMedCentralID PMC11100805

  • The Cost of After-Hour Electroencephalography. Neurology. Clinical practice Ney, J. P., Nuwer, M. R., Hirsch, L. J., Burdelle, M., Trice, K., Parvizi, J. 2024; 14 (2): e200264


    Background and Objectives: High costs associated with after-hour electroencephalography (EEG) constitute a barrier for financially constrained hospitals to provide this neurodiagnostic procedure outside regular working hours. Our study aims to deepen our understanding of the cost elements involved in delivering EEG services during after-hours.Methods: We accessed publicly available data sets and created a cost model depending on 3 most commonly seen staffing scenarios: (1) technologist on-site, (2) technologist on-call from home, and (3) a hybrid of the two.Results: Cost of EEG depends on the volume of testing and the staffing plan. Within the various cost elements, labor cost of EEG technologists is the predominant expenditure, which varies across geographic regions and urban areas.Discussion: We provide a model to explain why access to EEGs during after-hours has a substantial expense. This model provides a cost calculator tool (made available as part of this publication in eAppendix 1, to estimate the cost of EEG platform based on site-specific staffing scenarios and annual volume.

    View details for DOI 10.1212/CPJ.0000000000200264

    View details for PubMedID 38585440

  • Spatiotemporal dynamics of successive activations across the human brain during simple arithmetic processing. The Journal of neuroscience : the official journal of the Society for Neuroscience Pinheiro-Chagas, P., Sava-Segal, C., Akkol, S., Daitch, A., Parvizi, J. 2024


    Previous neuroimaging studies have offered unique insights about the spatial organization of activations and deactivations across the brain, however these were not powered to explore the exact timing of events at the subsecond scale combined with precise anatomical source information at the level of individual brains. As a result, we know little about the order of engagement across different brain regions during a given cognitive task. Using experimental arithmetic tasks as a prototype for human-unique symbolic processing, we recorded directly across 10,076 brain sites in 85 human subjects (52% female) using intracranial electroencephalography (iEEG). Our data revealed a remarkably distributed change of activity in almost half of the sampled sites. Notably, an orderly successive activation of a set of brain regions - anatomically consistent across subjects- was observed in individual brains. Furthermore, the temporal order of activations across these sites was replicable across subjects and trials. Moreover, the degree of functional connectivity between the sites decreased as a function of temporal distance between regions, suggesting that information is partially leaked or transformed along the processing chain. Furthermore, in each activated region, distinct neuronal populations with opposite activity patterns during target and control conditions were juxtaposed in an anatomically orderly manner. Our study complements the prior imaging studies by providing hitherto unknown information about the timing of events in the brain during arithmetic processing. Such findings can be a basis for developing mechanistic computational models of human-specific cognitive symbolic systems.Significance statement Our study elucidates the spatiotemporal dynamics and anatomical specificity of brain activations across >10,000 sites during arithmetic tasks, as captured by intracranial EEG. We discovered an orderly, successive activation of brain regions, consistent across individuals, and a decrease in functional connectivity as a function of temporal distance between regions. Our findings provide unprecedented insights into the sequence of cognitive processing and regional interactions, offering a novel perspective for enhancing computational models of cognitive symbolic systems.

    View details for DOI 10.1523/JNEUROSCI.2118-22.2024

    View details for PubMedID 38485257

  • Intracranial recordings of the human orbitofrontal cortical activity during self-referential episodic and valenced self-judgments. The Journal of neuroscience : the official journal of the Society for Neuroscience Iravani, B., Kaboodvand, N., Stieger, J. R., Liang, E. Y., Lusk, Z., Fransson, P., Deutsch, G. K., Gotlib, I. H., Parvizi, J. 2024


    We recorded directly from the orbital (oPFC) and ventromedial (vmPFC) subregions of the orbitofrontal cortex (OFC) in 22 (9 female, 13 male) epilepsy patients undergoing intracranial electroencephalography (iEEG) monitoring during an experimental task in which the participants judged the accuracy of self-referential autobiographical statements as well as valenced self-judgments. We found significantly increased high-frequency activity (HFA) in about 13% of oPFC sites (10/18 subjects) and 16% of vmPFC sites (4/12 subjects) during both of these self-referential thought processes, with the HFA power being modulated by the content of self-referential stimuli. The location of these activated sites corresponded with the location of fMRI-identified limbic network. Furthermore, the onset of HFA in the vmPFC was significantly earlier than in the oPFC in all patients with simultaneous recordings in both regions. In 11 patients with available depression scores from comprehensive neuropsychological assessments, we documented diminished HFA activity in the OFC during positive self-judgment trials among individuals with higher depression scores; responses during negative self-judgment trials were not related to the patients' depression scores. Our findings provide new temporal and anatomical information about the mode of engagement in two important subregions of the OFC during autobiographical memory and self-judgment conditions. Our findings from the OFC support the hypothesis that diminished brain activity during positive self-evaluations, rather than heightened activity during negative self-evaluations, plays a key role in the pathophysiology of depression.Significance Statement In direct recordings from the human brain, we observed significant responses characterized by high-frequency activity, aka high gamma, in distinct populations of the orbital (oPFC) and ventromedial (vmPFC) regions of the orbitofrontal cortex (OFC) - corresponding to the location of the resting state limbic network and to a lesser extent default mode network - when human subjects were engaged in self-referential episodic memory retrieval and self-trait judgments. Notably, simultaneous recordings across the two OFC regions in the same individuals revealed earlier activations in vmPFC than oPFC, indicating that the two subregions are involved in different stages of self-referential thought processes. Lastly, in individuals with high depressive symptoms, the OFC responses were significantly reduced during positive self-judgments but not heightened during negative self-evaluations.

    View details for DOI 10.1523/JNEUROSCI.1634-23.2024

    View details for PubMedID 38316564

  • Evolution of SEEG Strategy: Stanford Experience. Neurosurgery clinics of North America Buch, V. P., Parvizi, J. 2024; 35 (1): 83-85


    Overall stereoelectroencephalography (SEEG) has a favorable risk profile, patient tolerability, and superior investigative capability of individualized 3-dimensional seizure onset activity over subdural electrodes. Further, our recent surgical approach to safely enable multinuclear thalamic propagation mapping can only be performed with SEEG. For these reasons, SEEG has become the gold standard of phase II monitoring at our institution, and believe the ability to develop precision network-centric approaches to therapy will be critical to enhance our ability to care for medically refractory, and importantly, even complex multifocal, generalized, or surgically refractory epilepsy patients.

    View details for DOI 10.1016/

    View details for PubMedID 38000844

  • Subjective states induced by intracranial electrical stimulation matches the cytoarchitectonic organization of the human insula. Brain stimulation Duong, A., Quabs, J., Kucyi, A., Lusk, Z., Buch, V., Caspers, S., Parvizi, J. 2023


    Functions of the human insula have been explored extensively with neuroimaging methods and intracranial electrical stimulation studies that have highlighted a functional segregation across its subregions. A recently developed cytoarchitectonic map of the human insula has also segregated this brain region into various areas. Our knowledge of the functional organization of this brain region at the level of these fine-parceled microstructural areas remains only partially understood. We address this gap of knowledge by applying a multimodal approach linking direct electrical stimulation and task-evoked intracranial EEG recordings with microstructural subdivisions of the human insular cortex. In 17 neurosurgical patients with 142 implanted electrodes, stimulation of 40 % of the sites induced a reportable change in the conscious experience of the subjects in visceral/autonomic, anxiety, taste/olfactory, pain/temperature as well as somatosensory domains. These subjective responses showed a topographical allocation to microstructural areas defined by probabilistic cytoarchitectonic parcellation maps of the human insula. We found the pain and thermal responses to be located in areas lg2/ld2, while non-painful/non-thermal somatosensory responses corresponded to area ld3 and visceroceptive responses to area Id6. Lastly, the stimulation of area Id7 in the dorsal anterior insula, failed to induce reportable changes to subjective experience even though intracranial EEG recordings from this region captured significant time-locked high-frequency activity (HFA. Our results provide a multimodal map of functional subdivisions within the human insular cortex at the individual brain basis and characterize their anatomical association with fine-grained cytoarchitectonic parcellations of this brain structure.

    View details for DOI 10.1016/j.brs.2023.11.001

    View details for PubMedID 37949296

  • Gaining Clarity on the Claritɣ Algorithm. Neurocritical care Parvizi, J., Gururangan, K., Knickerbocker, D., Kamousi, B., Woo, R. 2023

    View details for DOI 10.1007/s12028-023-01797-z

    View details for PubMedID 37523108

  • Direct intracranial recordings in the human angular gyrus during arithmetic processing. Brain structure & function Pinheiro-Chagas, P., Chen, F., Sabetfakhri, N., Perry, C., Parvizi, J. 2022


    The role of angular gyrus (AG) in arithmetic processing remains a subject of debate. In the present study, we recorded from the AG, supramarginal gyrus (SMG), intraparietal sulcus (IPS), and superior parietal lobule (SPL) across 467 sites in 30 subjects performing addition or multiplication with digits or number words. We measured the power of high-frequency-broadband (HFB) signal, a surrogate marker for regional cortical engagement, and used single-subject anatomical boundaries to define the location of each recording site. Our recordings revealed the lowest proportion of sites with activation or deactivation within the AG compared to other subregions of the inferior parietal cortex during arithmetic processing. The few activated AG sites were mostly located at the border zones between AG and IPS, or AG and SMG. Additionally, we found that AG sites were more deactivated in trials with fast compared to slow response times. The increase or decrease of HFB within specific AG sites was the same when arithmetic trials were presented with number words versus digits and during multiplication as well as addition trials. Based on our findings, we conclude that the prior neuroimaging findings of so-called activations in the AG during arithmetic processing could have been due to group-based analyses that might have blurred the individual anatomical boundaries of AG or the subtractive nature of the neuroimaging methods in which lesser deactivations compared to the control condition have been interpreted as "activations". Our findings offer a new perspective with electrophysiological data about the engagement of AG during arithmetic processing.

    View details for DOI 10.1007/s00429-022-02540-8

    View details for PubMedID 35907987

  • Complex negative emotions induced by electrical stimulation of the human hypothalamus. Brain stimulation Parvizi, J., Veit, M. J., Barbosa, D. A., Kucyi, A., Perry, C., Parker, J. J., Shivacharan, R. S., Chen, F., Yih, J., Gross, J. J., Fisher, R., McNab, J. A., Falco-Walter, J., Halpern, C. H. 2022


    Stimulation of the ventromedial hypothalamic region in animals has been reported to cause attack behavior labeled as sham-rage without offering information about the internal affective state of the animal being stimulated.To examine the causal effect of electrical stimulation near the ventromedial region of the human hypothalamus on the human subjective experience and map the electrophysiological connectivity of the hypothalamus with other brain regions.We examined a patient (Subject S20_150) with intracranial electrodes implanted across 170 brain regions, including the hypothalamus. We combined direct electrical stimulation with tractography, cortico-cortical evoked potentials (CCEP), and functional connectivity using resting state intracranial electroencephalography (EEG).Recordings in the hypothalamus did not reveal any epileptic abnormalities. Electrical stimulations near the ventromedial hypothalamus induced profound shame, sadness, and fear but not rage or anger. When repeated single-pulse stimulations were delivered to the hypothalamus, significant responses were evoked in the amygdala, hippocampus, ventromedial-prefrontal and orbitofrontal cortices, anterior cingulate, as well as ventral-anterior and dorsal-posterior insula. The time to first peak of these evoked responses varied and earliest propagations correlated best with the measures of resting-state EEG connectivity and tractography.This patient's case offers details about the affective state induced by the stimulation of the human hypothalamus and provides causal evidence relevant to current theories of emotion and the importance of subcortical structures in processing emotions. The complexity of affective state induced by the stimulation of the hypothalamus and the profile of hypothalamic electrophysiological connectivity suggest that the hypothalamus ought to be seen as a causally important functional unit, within a broader human telencephalon, for our human subjective experience.

    View details for DOI 10.1016/j.brs.2022.04.008

    View details for PubMedID 35413481

  • Electrocorticographic evidence of a common neurocognitive sequence for mentalizing about the self and others. Nature communications Tan, K. M., Daitch, A. L., Pinheiro-Chagas, P., Fox, K. C., Parvizi, J., Lieberman, M. D. 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

  • Temporal order of signal propagation within and across intrinsic brain networks. Proceedings of the National Academy of Sciences of the United States of America Veit, M. J., Kucyi, A., Hu, W., Zhang, C., Zhao, B., Guo, Z., Yang, B., Sava-Segal, C., Perry, C., Zhang, J., Zhang, K., Parvizi, J. 2021; 118 (48)


    We studied the temporal dynamics of activity within and across functional MRI (fMRI)-derived nodes of intrinsic resting-state networks of the human brain using intracranial electroencephalography (iEEG) and repeated single-pulse electrical stimulation (SPES) in neurosurgical subjects implanted with intracranial electrodes. We stimulated and recorded from 2,133 and 2,372 sites, respectively, in 29 subjects. We found that N1 and N2 segments of the evoked responses are associated with intra- and internetwork communications, respectively. In a separate cognitive experiment, evoked electrophysiological responses to visual target stimuli occurred with less temporal separation across pairs of electrodes that were located within the same fMRI-defined resting-state networks compared with those located across different resting-state networks. Our results suggest intranetwork prior to internetwork information processing at the subsecond timescale.

    View details for DOI 10.1073/pnas.2105031118

    View details for PubMedID 34819365

  • Overlapping Neuronal Population Responses in the Human Parietal Cortex during Visuospatial Attention and Arithmetic Processing JOURNAL OF COGNITIVE NEUROSCIENCE Liu, N., Pinheiro-Chagas, P., Sava-Segal, C., Kastner, S., Chen, Q., Parvizi, J. 2021; 33 (12): 2548-2558
  • Altered sense of self during seizures in the posteromedial cortex. Proceedings of the National Academy of Sciences of the United States of America Parvizi, J., Braga, R. M., Kucyi, A., Veit, M. J., Pinheiro-Chagas, P., Perry, C., Sava-Segal, C., Zeineh, M., van Staalduinen, E. K., Henderson, J. M., Markert, M. 2021; 118 (29)


    The posteromedial cortex (PMC) is known to be a core node of the default mode network. Given its anatomical location and blood supply pattern, the effects of targeted disruption of this part of the brain are largely unknown. Here, we report a rare case of a patient (S19_137) with confirmed seizures originating within the PMC. Intracranial recordings confirmed the onset of seizures in the right dorsal posterior cingulate cortex, adjacent to the marginal sulcus, likely corresponding to Brodmann area 31. Upon the onset of seizures, the patient reported a reproducible sense of self-dissociation-a condition he described as a distorted awareness of the position of his body in space and feeling as if he had temporarily become an outside observer to his own thoughts, his "me" having become a separate entity that was listening to different parts of his brain speak to each other. Importantly, 50-Hz electrical stimulation of the seizure zone and a homotopical region within the contralateral PMC induced a subjectively similar state, reproducibly. We supplement our clinical findings with the definition of the patient's network anatomy at sites of interest using cortico-cortical-evoked potentials, experimental and resting-state electrophysiological connectivity, and individual-level functional imaging. This rare case of patient S19_137 highlights the potential causal importance of the PMC for integrating self-referential information and provides clues for future mechanistic studies of self-dissociation in neuropsychiatric populations.

    View details for DOI 10.1073/pnas.2100522118

    View details for PubMedID 34272280

  • Hippocampal ripples and their coordinated dialogue with the default mode network during recent and remote recollection. Neuron Norman, Y., Raccah, O., Liu, S., Parvizi, J., Malach, R. 2021


    Hippocampal ripples are prominent synchronization events generated by hippocampal neuronal assemblies. To date, ripples have been primarily associated with navigational memory in rodents and short-term episodic recollections in humans. Here, we uncover different profiles of ripple activity in the human hippocampus during the retrieval of recent and remote autobiographical events and semantic facts. We found that the ripple rate increased significantly before reported recall compared to control conditions. Patterns of ripple activity across multiple hippocampal sites demonstrated remarkable specificity for memory type. Intriguingly, these ripple patterns revealed a semantization dimension, in which patterns associated with autobiographical contents become similar to those of semantic memory as a function of memory age. Finally, widely distributed sites across the neocortex exhibited ripple-coupled activations during recollection, with the strongest activation found within the default mode network. Our results thus reveal a key role for hippocampal ripples in orchestrating hippocampal-cortical communication across large-scale networks involved in conscious recollection.

    View details for DOI 10.1016/j.neuron.2021.06.020

    View details for PubMedID 34297916

  • Intracranial electroencephalography reveals selective responses to cognitive stimuli in the periventricular heterotopias. The Journal of neuroscience : the official journal of the Society for Neuroscience Akkol, S., Kucyi, A., Hu, W., Zhao, B., Zhang, C., Sava-Segal, C., Liu, S., Razavi, B., Zhang, J., Zhang, K., Parvizi, J. 2021


    Our recent work suggests that non-lesional epileptic brain tissue is capable of generating normal neurophysiological responses during cognitive tasks, which are then seized by ongoing pathological epileptic activity. Here, we aim to extend the scope of our work to epileptic periventricular heterotopias (PVH) and examine if the PVH tissue also exhibits normal neurophysiological responses and network-level integration with other non-lesional cortical regions. As part of routine clinical assessment, three adult patients with PVH underwent implantation of intracranial electrodes and participated in experimental cognitive tasks. We obtained simultaneous recordings from PVH and remote cortical sites during rest as well as controlled experimental conditions. In all three subjects (2 female), cognitive experimental conditions evoked significant electrophysiological responses in discrete locations within the PVH tissue that were correlated with responses seen in non-epileptic cortical sites. Moreover, the responsive PVH sites exhibited correlated electrophysiological activity with responsive, non-lesional cortical sites during rest conditions. Taken together, our work clearly demonstrates that the PVH tissue may be functionally organized and it may be functionally integrated within cognitively engaged cortical networks despite its anatomical displacement during neurodevelopment.SIGNIFICANCE STATEMENT:Periventricular heterotopias (PVH) are developmentally abnormal brain tissues that frequently cause epileptic seizures. In a rare opportunity to obtain direct electrophysiological recordings from PVH, we were able to show that, contrary to common assumptions, PVH functional activity is similar to healthy cortical sites during a well-established cognitive task and exhibits clear resting state connectivity with the responsive cortical regions.

    View details for DOI 10.1523/JNEUROSCI.2785-20.2021

    View details for PubMedID 33727335

  • Fidelity of first-person reports following intracranial neuromodulation of the human brain: An empirical assessment of sham stimulation in neurosurgical patients. Brain stimulation Fox, K. C., Parvizi, J. 2020


    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

  • Monitoring the Burden of Seizures and Highly Epileptiform Patterns in Critical Care with a Novel Machine Learning Method. Neurocritical care Kamousi, B., Karunakaran, S., Gururangan, K., Markert, M., Decker, B., Khankhanian, P., Mainardi, L., Quinn, J., Woo, R., Parvizi, J. 2020


    INTRODUCTION: Current electroencephalography (EEG) practice relies on interpretation by expert neurologists, which introduces diagnostic and therapeutic delays that can impact patients' clinical outcomes. As EEG practice expands, these experts are becoming increasingly limited resources. A highly sensitive and specific automated seizure detection system would streamline practice and expedite appropriate management for patients with possible nonconvulsive seizures. We aimed to test the performance of a recently FDA-cleared machine learning method (Claritgamma, Ceribell Inc.) that measures the burden of seizure activity in real time and generates bedside alerts for possible status epilepticus (SE).METHODS: We retrospectively identified adult patients (n=353) who underwent evaluation of possible seizures with Rapid Response EEG system (Rapid-EEG, Ceribell Inc.). Automated detection of seizure activity and seizure burden throughout a recording (calculated as the percentage of ten-second epochs with seizure activity in any 5-min EEG segment) was performed with Claritgamma, and various thresholds of seizure burden were tested (≥10% indicating≥30s of seizure activity in the last 5min,≥50% indicating≥2.5min of seizure activity, and≥90% indicating≥4.5min of seizure activity and triggering a SE alert). The sensitivity and specificity of Claritgamma's real-time seizure burden measurements and SE alerts were compared to the majority consensus of at least two expert neurologists.RESULTS: Majority consensus of neurologists labeled the 353 EEGs as normal or slow activity (n=249), highly epileptiform patterns (HEP, n=87), or seizures [n=17, nine longer than 5 min (e.g., SE), and eight shorter than 5 min]. The algorithm generated a SE alert (≥90% seizure burden) with 100% sensitivity and 93% specificity. The sensitivity and specificity of various thresholds for seizure burden during EEG recordings for detecting patients with seizures were 100% and 82% for≥50% seizure burden and 88% and 60% for≥10% seizure burden. Of the 179 EEG recordings in which the algorithm detected no seizures, seizures were identified by the expert reviewers in only two cases, indicating a negative predictive value of 99%.DISCUSSION: Claritgamma detected SE events with high sensitivity and specificity, and it demonstrated a high negative predictive value for distinguishing nonepileptiform activity from seizure and highly epileptiform activity.CONCLUSIONS: Ruling out seizures accurately in a large proportion of cases can help prevent unnecessary or aggressive over-treatment in critical care settings, where empiric treatment with antiseizure medications is currently prevalent. Claritgamma's high sensitivity for SE and high negative predictive value for cases without epileptiform activity make it a useful tool for triaging treatment and the need for urgent neurological consultation.

    View details for DOI 10.1007/s12028-020-01120-0

    View details for PubMedID 33025543

  • Deep posteromedial cortical rhythm in dissociation. Nature Vesuna, S., Kauvar, I. V., Richman, E., Gore, F., Oskotsky, T., Sava-Segal, C., Luo, L., Malenka, R. C., Henderson, J. M., Nuyujukian, P., Parvizi, J., Deisseroth, K. 2020


    Advanced imaging methods now allow cell-type-specific recording of neural activity across the mammalian brain, potentially enabling the exploration of how brain-wide dynamical patterns give rise to complex behavioural states1-12. Dissociation is an altered behavioural state in which the integrity of experience is disrupted, resulting in reproducible cognitive phenomena including the dissociation of stimulus detection from stimulus-related affective responses. Dissociation can occur as a result of trauma, epilepsy or dissociative drug use13,14, but despite its substantial basic and clinical importance, the underlying neurophysiology of this state is unknown. Here we establish such a dissociation-like state in mice, induced by precisely-dosed administration of ketamine or phencyclidine. Large-scale imaging of neural activity revealed that these dissociative agents elicited a 1-3-Hz rhythm in layer5 neurons of the retrosplenial cortex. Electrophysiological recording with four simultaneously deployed high-density probes revealed rhythmic coupling of the retrosplenial cortex with anatomically connected components of thalamus circuitry, but uncoupling from most other brain regions was observed-including a notable inverse correlation with frontally projecting thalamic nuclei. In testing for causal significance, we found thatrhythmic optogenetic activation of retrosplenial cortex layer5 neurons recapitulated dissociation-like behavioural effects. Local retrosplenial hyperpolarization-activated cyclic-nucleotide-gated potassium channel 1 (HCN1) pacemakers were required for systemic ketamine to induce this rhythm and to elicit dissociation-like behavioural effects. In a patient with focal epilepsy, simultaneous intracranial stereoencephalography recordings from across the brain revealed a similarly localized rhythm in the homologous deep posteromedial cortex that was temporally correlated with pre-seizure self-reported dissociation, and local brief electrical stimulation of this region elicited dissociative experiences. These results identify themolecular, cellular and physiological properties of a conserved deep posteromedial cortical rhythm that underlies states of dissociation.

    View details for DOI 10.1038/s41586-020-2731-9

    View details for PubMedID 32939091

  • Pupillary dynamics link spontaneous and task-evoked activations recorded directly from human insula. The Journal of neuroscience : the official journal of the Society for Neuroscience Kucyi, A., Parvizi, J. 2020


    Spontaneous activations within neuronal populations can emerge similarly to "task-evoked" activations elicited during cognitive performance or sensory stimulation. We hypothesized that spontaneous activations within a given brain region have comparable functional and physiological properties to task-evoked activations. Using human intracranial electroencephalography with concurrent pupillometry in 3 subjects (2 males, 1 female), we localized neuronal populations in the dorsal anterior insular cortex that showed task-evoked activations correlating positively with the magnitude of pupil dilation during a continuous performance task. The pupillary response peaks lagged behind insular activations by several hundreds of milliseconds. We then detected spontaneous activations, within the same neuronal populations of insular cortex, that emerged intermittently during a wakeful "resting state" and that had comparable electrophysiological properties (magnitude, duration, and spectral signature) to task-evoked activations. Critically, similar to task-evoked activations, spontaneous activations systematically preceded phasic pupil dilations with a strikingly similar temporal profile. Our findings suggest similar neurophysiological profiles between spontaneous and task evoked activations in the human insula and support a clear link between these activations and autonomic functions measured by dynamics of pupillary dilation.Significance StatementMost of our knowledge about activations in the human brain is derived from studies of responses to external events and experimental conditions (i.e., "task-evoked" activations). We obtained direct neural recordings from electrodes implanted in human subjects and showed that activations emerge spontaneously and have strong similarities to task-evoked activations (e.g. magnitude, temporal profile) within the same populations of neurons. Within the dorsal anterior insula, a brain region implicated in salience processing and alertness, activations that are either spontaneous or task-evoked are coupled with brief dilations of the pupil. Our findings underscore how spontaneous brain activity-a major current focus of human neuroimaging studies aimed at developing biomarkers of disease- is relevant to ongoing physiological and possibly self-generated mental processes.

    View details for DOI 10.1523/JNEUROSCI.0435-20.2020

    View details for PubMedID 32631937

  • Fast temporal dynamics and causal relevance of face processing in the human temporal cortex. Nature communications Schrouff, J., Raccah, O., Baek, S., Rangarajan, V., Salehi, S., Mourao-Miranda, J., Helili, Z., Daitch, A. L., Parvizi, J. 2020; 11 (1): 656


    We measured the fast temporal dynamics of face processing simultaneously across the human temporal cortex (TC) using intracranial recordings in eight participants. We found sites with selective responses to faces clustered in the ventral TC, which responded increasingly strongly to marine animal, bird, mammal, and human faces. Both face-selective and face-active but non-selective sites showed a posterior to anterior gradient in response time and selectivity. A sparse model focusing on information from the human face-selective sites performed as well as, or better than, anatomically distributed models when discriminating faces from non-faces stimuli. Additionally, we identified the posterior fusiform site (pFUS) as causally the most relevant node for inducing distortion of conscious face processing by direct electrical stimulation. These findings support anatomically discrete but temporally distributed response profiles in the human brain and provide a new common ground for unifying the seemingly contradictory modular and distributed modes of face processing.

    View details for DOI 10.1038/s41467-020-14432-8

    View details for PubMedID 32005819

  • Electrophysiological dynamics of antagonistic brain networks reflect attentional fluctuations. Nature communications Kucyi, A., Daitch, A., Raccah, O., Zhao, B., Zhang, C., Esterman, M., Zeineh, M., Halpern, C. H., Zhang, K., Zhang, J., Parvizi, J. 2020; 11 (1): 325


    Neuroimaging evidence suggests that the default mode network (DMN) exhibits antagonistic activity with dorsal attention (DAN) and salience (SN) networks. Here we use human intracranial electroencephalography to investigate the behavioral relevance of fine-grained dynamics within and between these networks. The three networks show dissociable profiles of task-evoked electrophysiological activity, best captured in the high-frequency broadband (HFB; 70-170Hz) range. On the order of hundreds of milliseconds, HFB responses peak fastest in the DAN, at intermediate speed in the SN, and slowest in the DMN. Lapses of attention (behavioral errors) are marked by distinguishable patterns of both pre- and post-stimulus HFB activity within each network. Moreover, the magnitude of temporally lagged, negative HFB coupling between the DAN and DMN (but not SN and DMN) is associated with greater sustained attention performance and is reduced during wakeful rest. These findings underscore the behavioral relevance of temporally delayed coordination between antagonistic brain networks.

    View details for DOI 10.1038/s41467-019-14166-2

    View details for PubMedID 31949140

  • Evaluating the Clinical Impact of Rapid Response Electroencephalography: The DECIDE Multicenter Prospective Observational Clinical Study. Critical care medicine Vespa, P. M., Olson, D. M., John, S. n., Hobbs, K. S., Gururangan, K. n., Nie, K. n., Desai, M. J., Markert, M. n., Parvizi, J. n., Bleck, T. P., Hirsch, L. J., Westover, M. B. 2020


    To measure the diagnostic accuracy, timeliness, and ease of use of Ceribell rapid response electroencephalography. We assessed physicians' diagnostic assessments and treatment plans before and after rapid response electroencephalography assessment. Primary outcomes were changes in physicians' diagnostic and therapeutic decision making and their confidence in these decisions based on the use of the rapid response electroencephalography system. Secondary outcomes were time to electroencephalography, setup time, ease of use, and quality of electroencephalography data.Prospective multicenter nonrandomized observational study.ICUs in five academic hospitals in the United States.Patients with encephalopathy suspected of having nonconvulsive seizures and physicians evaluating these patients.Physician bedside assessment of sonified electroencephalography (30 s from each hemisphere) and visual electroencephalography (60 s) using rapid response electroencephalography.Physicians (29 fellows or residents, eight attending neurologists) evaluated 181 ICU patients; complete clinical and electroencephalography data were available in 164 patients (average 58.6 ± 18.7 yr old, 45% females). Relying on rapid response electroencephalography information at the bedside improved the sensitivity (95% CI) of physicians' seizure diagnosis from 77.8% (40.0%, 97.2%) to 100% (66.4%, 100%) and the specificity (95% CI) of their diagnosis from 63.9% (55.8%, 71.4%) to 89% (83.0%, 93.5%). Physicians' confidence in their own diagnosis and treatment plan were also improved. Time to electroencephalography (median [interquartile range]) was 5 minutes (4-10 min) with rapid response electroencephalography while the conventional electroencephalography was delayed by several hours (median [interquartile range] delay = 239 minutes [134-471 min] [p < 0.0001 using Wilcoxon signed rank test]). The device was rated as easy to use (mean ± SD: 4.7 ± 0.6 [1 = difficult, 5 = easy]) and was without serious adverse effects.Rapid response electroencephalography enabled timely and more accurate assessment of patients in the critical care setting. The use of rapid response electroencephalography may be clinically beneficial in the assessment of patients with high suspicion for nonconvulsive seizures and status epilepticus.

    View details for DOI 10.1097/CCM.0000000000004428

    View details for PubMedID 32618687

  • Midline and Parasagittal Seizures are Rare in Adult Patients. Neurocritical care Gururangan, K., Parvizi, J. 2019


    BACKGROUND: For decades, half of the electrodes used in traditional electroencephalography (EEG) have been dedicated to midline and parasagittal coverage. Recently, newer EEG devices have used fewer electrodes without direct coverage over the midline or parasagittal regions. However, no systematic study to date has explored the prevalence of midline parasagittal seizures, and as such the risk of missing such seizures with only ten electrodes remains unknown.METHODS: We reviewed retrospective EEG data from a cohort of 300 patients at Stanford University Medical Center and determined the frequency of seizures localized to the midline parasagittal regions. We then compiled previously reported EEG cohorts that reported the prevalence of midline parasagittal seizures to validate our findings.RESULTS: In our cohort, only two EEGs (0.66%) were identified with a midline or parasagittal seizure focus. In a subsequent study, we compiled literature evidence from 169510 EEGs and found that the prevalence of midline or parasagittal epileptic spikes/seizures was similarly less than 1%.CONCLUSIONS: Our study serves as the first to systematically explore the scope of EEG abnormalities captured exclusively by midline or parasagittal electrodes and document their very low prevalence.

    View details for DOI 10.1007/s12028-019-00804-6

    View details for PubMedID 31414373

  • Brain Mechanisms of Arithmetic: A Crucial Role for Ventral Temporal Cortex Pinheiro-Chagas, P., Daitch, A., Parvizi, J., Dehaene, S. SAGE PUBLICATIONS LTD. 2019: 170–71
  • Intensity of affective experience is modulated by magnitude of intracranial electrical stimulation in human orbitofrontal, cingulate and insular cortices SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE Yih, J., Beam, D. E., Fox, K. R., Parvizi, J. 2019; 14 (4): 339–51
  • Temporal Dynamics and Response Modulation across the Human Visual System in a Spatial Attention Task An ECoG Study JOURNAL OF NEUROSCIENCE Martin, A. B., Yang, X., Saalmann, Y. B., Wang, L., Shestyuk, A., Lin, J. J., Parvizi, J., Knight, R. T., Kastner, S. 2019; 39 (2): 333-352
  • Electrical stimulation of the human claustrum. Epilepsy & behavior : E&B Bickel, S. n., Parvizi, J. n. 2019


    To probe the causal importance of the claustrum in human subjective experience, we delivered electrical pulses either unilaterally or bilaterally within the core of this structure in five neurosurgical patients implanted with intracranial electrodes. Patients reported subjective experiences in various sensory domains and exhibited reflexive movements after real but not sham stimulations. However, none of the stimulations evoked loss of consciousness or lack of subjective awareness even with strong bilateral stimulations. Our study is the first to probe the effects of electrical perturbation of human claustrum through electrodes implanted within the claustrum itself and provide novel causal information about the human claustrum.

    View details for DOI 10.1016/j.yebeh.2019.03.051

    View details for PubMedID 31196825

  • A systematic study of stereotypy in epileptic seizures versus psychogenic seizure-like events EPILEPSY & BEHAVIOR Vogrig, A., Hsiang, J., Ng, J., Rolnick, J., Cheng, J., Parvizi, J. 2019; 90: 172-177
  • A systematic study of stereotypy in epileptic seizures versus psychogenic seizure-like events. Epilepsy & behavior : E&B Vogrig, A., Hsiang, J. C., Ng, J., Rolnick, J., Cheng, J., Parvizi, J. 2018; 90: 172–77


    OBJECTIVE: The objective of this study was to quantify the features of stereotypy in epileptic seizures and compare it with that of stereotypy in psychogenic nonepileptic seizure-like events (PNES) confirmed by video-electroencephalography (VEEG) monitoring.METHODS: Video-electroencephalography monitoring records of 20 patients with temporal lobe seizures (TLS) and 20 with PNES were retrospectively reviewed (n = 138 seizures, 48 TLS and 90 PNES). We analyzed the semiology of 59 behaviors of interest for their presence, duration, sequence, and continuity using quantified measures that were entered into statistical analysis.RESULTS: We identified discontinuity as the parameter that was clearly distinct between PNES and epileptic TLS events: there were significantly more frequent pauses of behavior (i.e., "on-off" pattern) in PNES compared with TLS (P = 0.012). The frequency of pauses during an event was diagnostic of PNES events. For instance, the presence of 2 "pauses" during an episode determines a 69% probability of the seizure being nonepileptic. Moreover, PNES events had significantly greater duration (143 s) than TLS events (68 s) (excluding outliers, P = 0.002) and greater duration variability from one event to another in the same subject (P = 0.005).SIGNIFICANCE: Our work provides the first quantified measure of behavioral semiology during epileptic and nonepileptic seizures and offers novel behavioral measures to differentiate them from each other.

    View details for PubMedID 30580068

  • Brain Mechanisms of Arithmetic: A Crucial Role for Ventral Temporal Cortex JOURNAL OF COGNITIVE NEUROSCIENCE Pinheiro-Chagas, P., Daitch, A., Parvizi, J., Dehaene, S. 2018; 30 (12): 1757–72


    Elementary arithmetic requires a complex interplay between several brain regions. The classical view, arising from fMRI, is that the intraparietal sulcus (IPS) and the superior parietal lobe (SPL) are the main hubs for arithmetic calculations. However, recent studies using intracranial electroencephalography have discovered a specific site, within the posterior inferior temporal cortex (pITG), that activates during visual perception of numerals, with widespread adjacent responses when numerals are used in calculation. Here, we reexamined the contribution of the IPS, SPL, and pITG to arithmetic by recording intracranial electroencephalography signals while participants solved addition problems. Behavioral results showed a classical problem size effect: RTs increased with the size of the operands. We then examined how high-frequency broadband (HFB) activity is modulated by problem size. As expected from previous fMRI findings, we showed that the total HFB activity in IPS and SPL sites increased with problem size. More surprisingly, pITG sites showed an initial burst of HFB activity that decreased as the operands got larger, yet with a constant integral over the whole trial, thus making these signals invisible to slow fMRI. Although parietal sites appear to have a more sustained function in arithmetic computations, the pITG may have a role of early identification of the problem difficulty, beyond merely digit recognition. Our results ask for a reevaluation of the current models of numerical cognition and reveal that the ventral temporal cortex contains regions specifically engaged in mathematical processing.

    View details for PubMedID 30063177

  • Direct Cortical Recordings Suggest Temporal Order of Task-Evoked Responses in Human Dorsal Attention and Default Networks JOURNAL OF NEUROSCIENCE Raccah, O., Daitch, A. L., Kucyi, A., Parvizi, J. 2018; 38 (48): 10305-10313
  • Temporal dynamics and response modulation across the human visual system in a spatial attention task: an ECoG study. The Journal of neuroscience : the official journal of the Society for Neuroscience Martin, A. B., Yang, X., Saalmann, Y. B., Wang, L., Shestyuk, A., Lin, J. J., Parvizi, J., Knight, R. T., Kastner, S. 2018


    The selection of behaviorally relevant information from cluttered visual scenes (often referred to as 'attention') is mediated by a cortical large-scale network consisting of areas in occipital, temporal, parietal, and frontal cortex that is organized into a functional hierarchy of feedforward and feedback pathways. In the human brain, little is known about the temporal dynamics of attentional processing from studies at the mesoscopic level of electrocorticography (ECoG), that combines millisecond temporal resolution with precise anatomical localization of recording sites. We analyzed high frequency broadband responses (HFB) responses from 626 electrodes implanted in 8 epilepsy patients, who performed a spatial attention task. Electrode locations were reconstructed using a probabilistic atlas of the human visual system. HFB responses showed high spatial selectivity and tuning, constituting ECoG response fields (RFs), within and outside the topographic visual system. In accordance with monkey physiology studies, both RF widths and onset latencies increased systematically across the visual processing hierarchy. We utilized the spatial specificity of HFB responses to quantitatively study spatial attention effects and their temporal dynamics to probe a hierarchical top-down model suggesting that feedback signals back propagate the visual processing hierarchy. Consistent with such a model, the strengths of attentional modulation were found to be greater and modulation latencies to be shorter in posterior parietal cortex, middle temporal cortex and ventral extrastriate cortex as compared to early visual cortex. However, inconsistent with such a model, attention effects were weaker and more delayed in anterior parietal and frontal cortex.SIGNIFICANCE STATEMENTIn the human brain, visual attention has been predominantly studied using methods with high spatial, but poor temporal resolution such as fMRI, or high temporal, but poor spatial resolution such as EEG/MEG. Here, we investigate temporal dynamics and attention effects across the human visual system at a mesoscopic level that combines precise spatial and temporal measurements by using electrocorticography in epilepsy patients performing a classical spatial attention task. Electrode locations were reconstructed using a probabilistic atlas of the human visual system, thereby relating them to topography and processing hierarchy. We demonstrate regional differences in temporal dynamics across the attention network. Our findings do not fully support a top-down model that promotes influences on visual cortex by reversing the processing hierarchy.

    View details for PubMedID 30459219

  • Changes in subjective experience elicited by direct stimulation of the human orbitofrontal cortex NEUROLOGY Fox, K. R., Yih, J., Raccah, O., Pendekanti, S. L., Limbach, L. E., Maydan, D. D., Parvizi, J. 2018; 91 (16): E1519-1527
  • Direct Cortical Recordings Suggest Temporal Order of Task Evoked Responses in Human Dorsal Attention and Default Networks. The Journal of neuroscience : the official journal of the Society for Neuroscience Raccah, O., Daitch, A. L., Kucyi, A., Parvizi, J. 2018


    The past decade has seen a large number of neuroimaging studies focused on the anti-correlated functional relationship between the default mode network (DMN) and the dorsal attention network (DAN). Due principally to the low-temporal resolution of functional neuroimaging modalities, the fast-neuronal dynamics across these networks remains poorly understood. Here we report novel human intracranial electrophysiology data from six neurosurgical patients (four males) with simultaneous coverage of well-characterized nodes of the DMN and DAN. Subjects performed an arithmetic processing task, shown previously to evoke reliable deactivations (below baseline) in the DMN and activations in the DAN. In this cohort, we show that DMN deactivations lag DAN activations by over 200 milliseconds. Our findings suggest a clear temporal order of processing across the two networks during the current task and place the DMN further than the DAN in a plausible information-processing hierarchy.Significance Statement: The human brain contains an intrinsic and strictly organized network architecture. Our understanding of the interplay across association networks has relied primarily on the slow fluctuations of the hemodynamic response, and as such it has lacked critical evidence regarding the temporal dynamics of activity across these networks. The current study presents evidence from high spatiotemporal methods showing that well-studied areas of the default mode network (DMN) display delayed task-induced activity relative to divergent responses in dorsal attention network (DAN) nodes. This finding provides direct and critical evidence regarding the temporal chronology of neuronal events across opposing brain networks.

    View details for PubMedID 30315126

  • Rapid Bedside Evaluation of Seizures in the ICU by Listening to the Sound of Brainwaves: A Prospective Observational Clinical Trial of Ceribell's Brain Stethoscope Function NEUROCRITICAL CARE Hobbs, K., Krishnamohan, P., Legault, C., Goodman, S., Parvizi, J., Gururangan, K., Mlynash, M. 2018; 29 (2): 302–12
  • Changes in subjective experience elicited by direct stimulation of the human orbitofrontal cortex. Neurology Fox, K. C., Yih, J., Raccah, O., Pendekanti, S. L., Limbach, L. E., Maydan, D. D., Parvizi, J. 2018


    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

  • Neuronal Population Responses in the Human Ventral Temporal and Lateral Parietal Cortex during Arithmetic Processing with Digits and Number Words JOURNAL OF COGNITIVE NEUROSCIENCE Baek, S., Daitch, A. L., Pinheiro-Chagas, P., Parvizi, J. 2018; 30 (9): 1315-1322