Josef Parvizi MD PhD

All Publications

• Direct cortical stimulation of human posteromedial cortex. Neurology Foster, B. L., Parvizi, J. 2017; 88 (7): 685-691

  Abstract

  The posteromedial cortex (PMC) is a collective term for an anatomically heterogeneous area of the brain constituting a core node of the human default mode network (DMN), which is engaged during internally focused subjective cognition such as autobiographical memory.We explored the effects of causal perturbations of PMC with direct electric brain stimulation (EBS) during presurgical epilepsy monitoring with intracranial EEG electrodes.Data were collected from 885 stimulations in 25 patients implanted with intracranial electrodes across the PMC. While EBS of regions immediately dorsal or ventral to the PMC reliably produced somatomotor or visual effects, respectively, we found no observable behavioral or subjectively reported effects when sites within the boundaries of PMC were electrically perturbed. In each patient, null effects of PMC stimulation were observed for sites in which intracranial recordings had clearly demonstrated electrophysiologic responses during autobiographical recall.Direct electric modulation of the human PMC produced null effects when standard functional mapping methods were used. More sophisticated stimulation paradigms (e.g., EBS during experimental cognitive tests) will be required for testing the causal contribution of PMC to human cognition and subjective experience. Nonetheless, our findings suggest that some extant theories of PMC and DMN contribution to human awareness and subjective conscious states require cautious re-examination.

  View details for DOI 10.1212/WNL.0000000000003607

  View details for PubMedID 28100728

  View details for PubMedCentralID PMC5317378

• Linking Electrical Stimulation of Human Primary Visual Cortex, Size of Affected Cortical Area, Neuronal Responses, and Subjective Experience NEURON Winawer, J., Parvizi, J. 2016; 92 (6): 1213-1219

  Abstract

  Electrical brain stimulation (EBS) complements neural measurements by probing the causal relationship between brain and perception, cognition, and action. Many fundamental questions about EBS remain unanswered, including the spatial extent of cortex responsive to stimulation, and the relationship between the circuitry engaged by EBS and the types of neural responses elicited by sensory stimulation. Here, we measured neural responses and the effects of EBS in primary visual cortex in four patients implanted with intracranial electrodes. Using stimulation, behavior, and retinotopic mapping, we show the relationship between the size of affected cortical area and the magnitude of electrical charge. Furthermore, we show that the spatial location of electrically induced visual sensations is matched to the receptive field of the cortical site measured with broadband field potentials, and less so with event related potentials. Together, these findings broaden our knowledge about the mechanism of EBS and the neuromodulation of the human brain.

  View details for DOI 10.1016/j.neuron.2016.11.008

  View details for Web of Science ID 000393117200011

  View details for PubMedID 27939584

  View details for PubMedCentralID PMC5182175

• Mapping human temporal and parietal neuronal population activity and functional coupling during mathematical cognition. Proceedings of the National Academy of Sciences of the United States of America Daitch, A. L., Foster, B. L., Schrouff, J., Rangarajan, V., Kasikçi, I., Gattas, S., Parvizi, J. 2016

  Abstract

  Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) have been shown to code for abstract quantity representations and for symbolic numerical representations, respectively. To explore the fast dynamics of activity within each region and the interaction between them, we used electrocorticography recordings from 16 neurosurgical subjects implanted with grids of electrodes over these two regions and tracked the activity within and between the regions as subjects performed three different numerical tasks. Although our results reconfirm the presence of math-selective hubs within the VTC and LPC, we report here a remarkable heterogeneity of neural responses within each region at both millimeter and millisecond scales. Moreover, we show that the heterogeneity of response profiles within each hub mirrors the distinct patterns of functional coupling between them. Our results support the existence of multiple bidirectional functional loops operating between discrete populations of neurons within the VTC and LPC during the visual processing of numerals and the performance of arithmetic functions. These findings reveal information about the dynamics of numerical processing in the brain and also provide insight into the fine-grained functional architecture and connectivity within the human brain.

  View details for PubMedID 27821758

  View details for PubMedCentralID PMC5135371

• 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

  Abstract

  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

  Abstract

  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

• A Brain Area for Visual Numerals JOURNAL OF NEUROSCIENCE Shum, J., Hermes, D., Foster, B. L., Dastjerdi, M., Rangarajan, V., Winawer, J., Miller, K. J., Parvizi, J. 2013; 33 (16): 6709-6715

  Abstract

  Is there a distinct area within the human visual system that has a preferential response to numerals, as there is for faces, words, or scenes? We addressed this question using intracranial electrophysiological recordings and observed a significantly higher response in the high-frequency broadband range (high γ, 65-150 Hz) to visually presented numerals, compared with morphologically similar (i.e., letters and false fonts) or semantically and phonologically similar stimuli (i.e., number words and non-number words). Anatomically, this preferential response was consistently localized in the inferior temporal gyrus and anterior to the temporo-occipital incisure. This region lies within or close to the fMRI signal-dropout zone produced by the nearby auditory canal and venous sinus artifacts, an observation that may account for negative findings in previous fMRI studies of preferential response to numerals. Because visual numerals are culturally dependent symbols that are only learned through education, our novel finding of anatomically localized preferential response to such symbols provides a new example of acquired category-specific responses in the human visual system.

  View details for DOI 10.1523/JNEUROSCI.4558-12.2013

  View details for Web of Science ID 000317723000002

  View details for PubMedID 23595729

• Numerical processing in the human parietal cortex during experimental and natural conditions. Nature communications Dastjerdi, M., Ozker, M., Foster, B. L., Rangarajan, V., Parvizi, J. 2013; 4: 2528-?

  Abstract

  Human cognition is traditionally studied in experimental conditions wherein confounding complexities of the natural environment are intentionally eliminated. Thus, it remains unknown how a brain region involved in a particular experimental condition is engaged in natural conditions. Here we use electrocorticography to address this uncertainty in three participants implanted with intracranial electrodes and identify activations of neuronal populations within the intraparietal sulcus region during an experimental arithmetic condition. In a subsequent analysis, we report that the same intraparietal sulcus neural populations are activated when participants, engaged in social conversations, refer to objects with numerical content. Our prototype approach provides a means for both exploring human brain dynamics as they unfold in complex social settings and reconstructing natural experiences from recorded brain signals.

  View details for DOI 10.1038/ncomms3528

  View details for PubMedID 24129341

  View details for PubMedCentralID PMC3826627

• 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

  Abstract

  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

  Abstract

  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

  Abstract

  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

• Detecting silent seizures by their sound Epilepsia Parvizi, J., Gururangan, K., Razavi, B., Chafe, C. 2018; 59 (4): 877-884

  Abstract

  The traditional approach to interpreting electroencephalograms (EEGs) requires physicians with formal training to visually assess the waveforms. This approach can be less practical in critical settings where a trained EEG specialist is not readily available to review the EEG and diagnose ongoing subclinical seizures, such as nonconvulsive status epilepticus.We have developed a novel method by which EEG data are converted to sound in real time by letting the underlying electrophysiological signal modulate a voice tone that is in the audible range. Here, we explored whether individuals without any prior EEG training could listen to 15-second sonified EEG and determine whether the EEG represents seizures or nonseizure conditions. We selected 84 EEG samples to represent seizures (n = 7), seizure-like activity (n = 25), or nonperiodic, nonrhythmic activity (normal or focal/generalized slowing, n = 52). EEGs from single channels in the left and right hemispheres were then converted to sound files. After a 4-minute training video, medical students (n = 34) and nurses (n = 30) were asked to designate each audio sample as "seizure" or "nonseizure." We then compared their performance with that of EEG-trained neurologists (n = 12) and medical students (n = 29) who also diagnosed the same EEGs on visual display.Nonexperts listening to single-channel sonified EEGs detected seizures with remarkable sensitivity (students, 98% ± 5%; nurses, 95% ± 14%) compared to experts or nonexperts reviewing the same EEGs on visual display (neurologists, 88% ± 11%; students, 76% ± 19%). If the EEGs contained seizures or seizure-like activity, nonexperts listening to sonified EEGs rated them as seizures with high specificity (students, 85% ± 9%; nurses, 82% ± 12%) compared to experts or nonexperts viewing the EEGs visually (neurologists, 90% ± 7%; students, 65% ± 20%).Our study confirms that individuals without EEG training can detect ongoing seizures or seizure-like rhythmic periodic patterns by listening to sonified EEG. Although sonification of EEG cannot replace the traditional approaches to EEG interpretation, it provides a meaningful triage tool for fast assessment of patients with suspected subclinical seizures.

  View details for DOI 10.1111/epi.14043

• Diagnostic utility of eight-channel EEG for detecting generalized seizures Clinical Neurophysiology Practice Gururangan, K., Razavi, B., Parvizi, J. 2018; 3

  View details for DOI 10.1016/j.cnp.2018.03.001

• Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity. Proceedings of the National Academy of Sciences of the United States of America Riès, S. K., Dhillon, R. K., Clarke, A., King-Stephens, D., Laxer, K. D., Weber, P. B., Kuperman, R. A., Auguste, K. I., Brunner, P., Schalk, G., Lin, J. J., Parvizi, J., Crone, N. E., Dronkers, N. F., Knight, R. T. 2017; 114 (23): E4530-E4538

  Abstract

  Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.

  View details for DOI 10.1073/pnas.1620669114

  View details for PubMedID 28533406

• Theta Oscillations Rapidly Convey Odor-Specific Content in Human Piriform Cortex NEURON Jiang, H., Schuele, S., Rosenow, J., Zelano, C., Parvizi, J., Tao, J. X., Wu, S., Gottfried, J. A. 2017; 94 (1): 207-?

  Abstract

  Olfactory oscillations are pervasive throughout vertebrate and invertebrate nervous systems. Such observations have long implied that rhythmic activity patterns play a fundamental role in odor coding. Using intracranial EEG recordings from rare patients with medically resistant epilepsy, we find that theta oscillations are a distinct electrophysiological signature of olfactory processing in the human brain. Across seven patients, odor stimulation enhanced theta power in human piriform cortex, with robust effects at the level of single trials. Importantly, classification analysis revealed that piriform oscillatory activity conveys olfactory-specific information that can be decoded within 110-518 ms of a sniff, and maximally within the theta frequency band. This temporal window was also associated with increased theta-specific phase coupling between piriform cortex and hippocampus. Together these findings suggest that human piriform cortex has access to olfactory content in the time-frequency domain and can utilize these signals to rapidly differentiate odor stimuli.

  View details for DOI 10.1016/j.neuron.2017.03.021

  View details for Web of Science ID 000398262000020

  View details for PubMedID 28384472

• Mirroring in the Human Brain: Deciphering the Spatial-Temporal Patterns of the Human Mirror Neuron System. Cerebral cortex Perry, A., Stiso, J., Chang, E. F., Lin, J. J., Parvizi, J., Knight, R. T. 2017

  Abstract

  Embodied theories of cognition emphasize the central role of sensorimotor transformations in the representation of others' actions. Support for these theories is derived from the discovery of the mirror neuron system (MNS) in primates, from noninvasive techniques in humans, and from a limited number of intracranial studies. To understand the neural dynamics of the human MNS, more studies with precise spatial and temporal resolutions are essential. We used electrocorticography to define activation patterns in sensorimotor, parietal and/or frontal neuronal populations, during a viewing and grasping task. Our results show robust high gamma activation for both conditions in classic MNS sites. Furthermore, we provide novel evidence for 2 different populations of neurons: sites that were only active for viewing and grasping ("pure mirroring") and sites that were also active between viewing and grasping, and perhaps serve a more general attentional role. Lastly, a subgroup of parietal electrodes showed earlier peaks than all other regions. These results highlight the complexity of spatial-temporal patterns within the MNS and provide a critical link between single-unit research in monkeys and noninvasive techniques in human.

  View details for DOI 10.1093/cercor/bhx013

  View details for PubMedID 28137724

• Electrophysiological Responses in the Ventral Temporal Cortex During Reading of Numerals and Calculation CEREBRAL CORTEX Hermes, D., Rangarajan, V., Foster, B. L., King, J., Kasikci, I., Miller, K. J., Parvizi, J. 2017; 27 (1): 567-575

  Abstract

  Recent evidence suggests that specific neuronal populations in the ventral temporal cortex show larger electrophysiological responses to visual numerals compared with morphologically similar stimuli. This study investigates how these responses change from simple reading of numerals to the active use of numerals in an arithmetic context. We recorded high-frequency broadband (HFB) signals, a reliable measure for local neuronal population activity, while 10 epilepsy patients implanted with subdural electrodes performed separate numeral reading and calculation tasks. We found that calculation increased activity in the posterior inferior temporal gyrus (ITG) with a factor of approximately 1.5 over the first 500 ms of calculation, whereas no such increase was noted for reading numerals without calculation or reading and judging memory statements. In a second experiment conducted in 2 of the same subjects, we show that HFB responses increase in a systematic manner when the single numerals were presented successively in a calculation context: The HFB response in the ITG, to the second and third numerals (i.e., b and c in a + b = c), was approximately 1.5 times larger than the responses to the first numeral (a). These results provide electrophysiological evidence for modulation of local neuronal population responses to visual stimuli based on increasing task demands.

  View details for DOI 10.1093/cercor/bhv250

  View details for Web of Science ID 000397064800046

• Direct brain recordings reveal hippocampal rhythm underpinnings of language processing PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Piai, V., Anderson, K. L., Lin, J. J., Dewar, C., Parvizi, J., Dronkers, N. F., Knight, R. T. 2016; 113 (40): 11366-11371

  Abstract

  Language is classically thought to be supported by perisylvian cortical regions. Here we provide intracranial evidence linking the hippocampal complex to linguistic processing. We used direct recordings from the hippocampal structures to investigate whether theta oscillations, pivotal in memory function, track the amount of contextual linguistic information provided in sentences. Twelve participants heard sentences that were either constrained ("She locked the door with the") or unconstrained ("She walked in here with the") before presentation of the final word ("key"), shown as a picture that participants had to name. Hippocampal theta power increased for constrained relative to unconstrained contexts during sentence processing, preceding picture presentation. Our study implicates hippocampal theta oscillations in a language task using natural language associations that do not require memorization. These findings reveal that the hippocampal complex contributes to language in an active fashion, relating incoming words to stored semantic knowledge, a necessary process in the generation of sentence meaning.

  View details for DOI 10.1073/pnas.1603312113

  View details for Web of Science ID 000384528900084

  View details for PubMedID 27647880

  View details for PubMedCentralID PMC5056038

• Utility of electroencephalography: Experience from a U.S. tertiary care medical center. Clinical neurophysiology Gururangan, K., Razavi, B., Parvizi, J. 2016; 127 (10): 3335-3340

  Abstract

  To investigate the utility of electroencephalography (EEG) for evaluation of patients with altered mental status (AMS).We retrospectively reviewed 200 continuous EEGs (cEEGs) obtained in ICU and non-ICU wards and 100 spot EEGs (sEEGs) obtained from the emergency department (ED) of a large tertiary medical center. Main outcomes were access time (from study request to hookup), and diagnostic yield (percentage of studies revealing significant abnormality).Access time, mean±SD (maximum), was 3.5±3.2 (20.8) hours in ICU, 4.8±5.0 (25.6) hours in non-ICU, and 2.7±3.6 (23.9) hours in ED. Access time was not significantly different for stat requests or EEGs with seizure activity. While the primary indication for EEG monitoring was to evaluate for seizures as the cause of AMS, only 8% of cEEGs and 1% of sEEGs revealed seizures. Epileptiform discharges were detected in 45% of ICU, 24% of non-ICU, and 9% of ED cases, while 2% of ICU, 15% of non-ICU, and 45% of ED cases were normal.Access to EEG is hampered by significant delays, and in emergency settings, the conventional EEG system detects seizures only in a minority of cases.Our findings underscore the inefficiencies of current EEG infrastructure for accessing diagnostically important information, as well as the need for more prospective data describing the relationship between EEG access time and EEG findings, clinical outcomes, and cost considerations.

  View details for DOI 10.1016/j.clinph.2016.08.013

  View details for PubMedID 27611442

• Differential Processing of Consonance and Dissonance within the Human Superior Temporal Gyrus FRONTIERS IN HUMAN NEUROSCIENCE Foo, F., King-Stephens, D., Weber, P., Laxer, K., Parvizi, J., Knight, R. T. 2016; 10

  Abstract

  The auditory cortex is well-known to be critical for music perception, including the perception of consonance and dissonance. Studies on the neural correlates of consonance and dissonance perception have largely employed non-invasive electrophysiological and functional imaging techniques in humans as well as neurophysiological recordings in animals, but the fine-grained spatiotemporal dynamics within the human auditory cortex remain unknown. We recorded electrocorticographic (ECoG) signals directly from the lateral surface of either the left or right temporal lobe of eight patients undergoing neurosurgical treatment as they passively listened to highly consonant and highly dissonant musical chords. We assessed ECoG activity in the high gamma (γhigh, 70-150 Hz) frequency range within the superior temporal gyrus (STG) and observed two types of cortical sites of interest in both hemispheres: one type showed no significant difference in γhigh activity between consonant and dissonant chords, and another type showed increased γhigh responses to dissonant chords between 75 and 200 ms post-stimulus onset. Furthermore, a subset of these sites exhibited additional sensitivity towards different types of dissonant chords, and a positive correlation between changes in γhigh power and the degree of stimulus roughness was observed in both hemispheres. We also observed a distinct spatial organization of cortical sites in the right STG, with dissonant-sensitive sites located anterior to non-sensitive sites. In sum, these findings demonstrate differential processing of consonance and dissonance in bilateral STG with the right hemisphere exhibiting robust and spatially organized sensitivity toward dissonance.

  View details for DOI 10.3389/fnhum.2016.00154

  View details for Web of Science ID 000373770500001

  View details for PubMedID 27148011

  View details for PubMedCentralID PMC4829599

• Frontal and motor cortex contributions to response inhibition: evidence from electrocorticography JOURNAL OF NEUROPHYSIOLOGY Fonken, Y. M., Rieger, J. W., Tzvi, E., Crone, N. E., Chang, E., Parvizi, J., Knight, R. T., Kraemer, U. M. 2016; 115 (4): 2224-2236

  Abstract

  Changes in the environment require rapid modification or inhibition of ongoing behavior. We used the stop-signal paradigm and intracranial recordings to investigate response preparation, inhibition, and monitoring of task-relevant information. Electrocorticographic data were recorded in eight patients with electrodes covering frontal, temporal, and parietal cortex, and time-frequency analysis was used to examine power differences in the beta (13-30 Hz) and high-gamma bands (60-180 Hz). Over motor cortex, beta power decreased, and high-gamma power increased during motor preparation for both go trials (Go) and unsuccessful stops (US). For successful stops (SS), beta increased, and high-gamma was reduced, indexing the cancellation of the prepared response. In the middle frontal gyrus (MFG), stop signals elicited a transient high-gamma increase. The MFG response occurred before the estimated stop-signal reaction time but did not distinguish between SS and US trials, likely signaling attention to the salient stop stimulus. A postresponse high-gamma increase in MFG was stronger for US compared with SS and absent in Go, supporting a role in behavior monitoring. These results provide evidence for differential contributions of frontal subregions to response inhibition, including motor preparation and inhibitory control in motor cortex and cognitive control and action evaluation in lateral prefrontal cortex.

  View details for DOI 10.1152/jn.00708.2015

  View details for Web of Science ID 000376056900029

  View details for PubMedID 26864760

  View details for PubMedCentralID PMC4869511

• Functional asymmetry between the left and right human fusiform gyrus explored through electrical brain stimulation. Neuropsychologia Rangarajan, V., Parvizi, J. 2016; 83: 29-36

  Abstract

  The ventral temporal cortex (VTC) contains several areas with selective responses to words, numbers, faces, and objects as demonstrated by numerous human and primate imaging and electrophysiological studies. Our recent work using electrocorticography (ECoG) confirmed the presence of face-selective neuronal populations in the human fusiform gyrus (FG) in patients implanted with intracranial electrodes in either the left or right hemisphere. Electrical brain stimulation (EBS) disrupted the conscious perception of faces only when it was delivered in the right, but not left, FG. In contrast to our previous findings, here we report both negative and positive EBS effects in right and left FG, respectively. The presence of right hemisphere language dominance in the first, and strong left-handedness and poor language processing performance in the second case, provide indirect clues about the functional architecture of the human VTC in relation to hemispheric asymmetries in language processing and handedness.

  View details for DOI 10.1016/j.neuropsychologia.2015.08.003

  View details for PubMedID 26277460

• Decoding intracranial EEG data with multiple kernel learning method. Journal of neuroscience methods Schrouff, J., Mourão-Miranda, J., Phillips, C., Parvizi, J. 2016; 261: 19-28

  Abstract

  Machine learning models have been successfully applied to neuroimaging data to make predictions about behavioral and cognitive states of interest. While these multivariate methods have greatly advanced the field of neuroimaging, their application to electrophysiological data has been less common especially in the analysis of human intracranial electroencephalography (iEEG, also known as electrocorticography or ECoG) data, which contains a rich spectrum of signals recorded from a relatively high number of recording sites.In the present work, we introduce a novel approach to determine the contribution of different bandwidths of EEG signal in different recording sites across different experimental conditions using the Multiple Kernel Learning (MKL) method.To validate and compare the usefulness of our approach, we applied this method to an ECoG dataset that was previously analysed and published with univariate methods.Our findings proved the usefulness of the MKL method in detecting changes in the power of various frequency bands during a given task and selecting automatically the most contributory signal in the most contributory site(s) of recording.With a single computation, the contribution of each frequency band in each recording site in the estimated multivariate model can be highlighted, which then allows formulation of hypotheses that can be tested a posteriori with univariate methods if needed.

  View details for DOI 10.1016/j.jneumeth.2015.11.028

  View details for PubMedID 26692030

  View details for PubMedCentralID PMC4758824

• Electrophysiological Responses in the Ventral Temporal Cortex During Reading of Numerals and Calculation. Cerebral cortex Hermes, D., Rangarajan, V., Foster, B. L., King, J., Kasikci, I., Miller, K. J., Parvizi, J. 2015

  Abstract

  Recent evidence suggests that specific neuronal populations in the ventral temporal cortex show larger electrophysiological responses to visual numerals compared with morphologically similar stimuli. This study investigates how these responses change from simple reading of numerals to the active use of numerals in an arithmetic context. We recorded high-frequency broadband (HFB) signals, a reliable measure for local neuronal population activity, while 10 epilepsy patients implanted with subdural electrodes performed separate numeral reading and calculation tasks. We found that calculation increased activity in the posterior inferior temporal gyrus (ITG) with a factor of approximately 1.5 over the first 500 ms of calculation, whereas no such increase was noted for reading numerals without calculation or reading and judging memory statements. In a second experiment conducted in 2 of the same subjects, we show that HFB responses increase in a systematic manner when the single numerals were presented successively in a calculation context: The HFB response in the ITG, to the second and third numerals (i.e., b and c in a + b = c), was approximately 1.5 times larger than the responses to the first numeral (a). These results provide electrophysiological evidence for modulation of local neuronal population responses to visual stimuli based on increasing task demands.

  View details for PubMedID 26503267

• Electrical Stimulation of the Left and Right Human Fusiform Gyrus Causes Different Effects in Conscious Face Perception JOURNAL OF NEUROSCIENCE Rangarajan, V., Hermes, D., Foster, B. L., Weiner, K. S., Jacques, C., Grill-Spector, K., Parvizi, J. 2014; 34 (38): 12828-12836

  Abstract

  Neuroimaging and electrophysiological studies across species have confirmed bilateral face-selective responses in the ventral temporal cortex (VTC) and prosopagnosia is reported in patients with lesions in the VTC including the fusiform gyrus (FG). As imaging and electrophysiological studies provide correlative evidence, and brain lesions often comprise both white and gray matter structures beyond the FG, we designed the current study to explore the link between face-related electrophysiological responses in the FG and the causal effects of electrical stimulation of the left or right FG in face perception. We used a combination of electrocorticography (ECoG) and electrical brain stimulation (EBS) in 10 human subjects implanted with intracranial electrodes in either the left (5 participants, 30 FG sites) or right (5 participants, 26 FG sites) hemispheres. We identified FG sites with face-selective ECoG responses, and recorded perceptual reports during EBS of these sites. In line with existing literature, face-selective ECoG responses were present in both left and right FG sites. However, when the same sites were stimulated, we observed a striking difference between hemispheres. Only EBS of the right FG caused changes in the conscious perception of faces, whereas EBS of strongly face-selective regions in the left FG produced non-face-related visual changes, such as phosphenes. This study examines the relationship between correlative versus causal nature of ECoG and EBS, respectively, and provides important insight into the differential roles of the right versus left FG in conscious face perception.

  View details for DOI 10.1523/JNEUROSCI.0527-14.2014

  View details for Web of Science ID 000341767800019

  View details for PubMedCentralID PMC4166163

• Dynamic changes in phase-amplitude coupling facilitate spatial attention control in fronto-parietal cortex. PLoS biology Szczepanski, S. M., Crone, N. E., Kuperman, R. A., Auguste, K. I., Parvizi, J., Knight, R. T. 2014; 12 (8)

  Abstract

  Attention is a core cognitive mechanism that allows the brain to allocate limited resources depending on current task demands. A number of frontal and posterior parietal cortical areas, referred to collectively as the fronto-parietal attentional control network, are engaged during attentional allocation in both humans and non-human primates. Numerous studies have examined this network in the human brain using various neuroimaging and scalp electrophysiological techniques. However, little is known about how these frontal and parietal areas interact dynamically to produce behavior on a fine temporal (sub-second) and spatial (sub-centimeter) scale. We addressed how human fronto-parietal regions control visuospatial attention on a fine spatiotemporal scale by recording electrocorticography (ECoG) signals measured directly from subdural electrode arrays that were implanted in patients undergoing intracranial monitoring for localization of epileptic foci. Subjects (n = 8) performed a spatial-cuing task, in which they allocated visuospatial attention to either the right or left visual field and detected the appearance of a target. We found increases in high gamma (HG) power (70-250 Hz) time-locked to trial onset that remained elevated throughout the attentional allocation period over frontal, parietal, and visual areas. These HG power increases were modulated by the phase of the ongoing delta/theta (2-5 Hz) oscillation during attentional allocation. Critically, we found that the strength of this delta/theta phase-HG amplitude coupling predicted reaction times to detected targets on a trial-by-trial basis. These results highlight the role of delta/theta phase-HG amplitude coupling as a mechanism for sub-second facilitation and coordination within human fronto-parietal cortex that is guided by momentary attentional demands.

  View details for DOI 10.1371/journal.pbio.1001936

  View details for PubMedID 25157678

  View details for PubMedCentralID PMC4144794

• Decoding memory processing from electro-corticography in human posteromedial cortex 4th International Workshop on Pattern Recognition in Neuroimaging (PRNI) Schrouff, J., Foster, B., Rangarajan, V., Phillips, C., Mourao-Miranda, J., Parvizi, J. IEEE. 2014

  View details for Web of Science ID 000345837700039

• Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging NATURE MEDICINE Mezer, A., Yeatman, J. D., Stikov, N., Kay, K. N., Cho, N., Dougherty, R. F., Perry, M. L., Parvizi, J., Hua, L. H., Butts-Pauly, K., Wandell, B. A. 2013; 19 (12): 1667-1672

  Abstract

  Here, we describe a quantitative neuroimaging method to estimate the macromolecular tissue volume (MTV), a fundamental measure of brain anatomy. By making measurements over a range of field strengths and scan parameters, we tested the key assumptions and the robustness of the method. The measurements confirm that a consistent quantitative estimate of MTV can be obtained across a range of scanners. MTV estimates are sufficiently precise to enable a comparison between data obtained from an individual subject with control population data. We describe two applications. First, we show that MTV estimates can be combined with T1 and diffusion measurements to augment our understanding of the tissue properties. Second, we show that MTV provides a sensitive measure of disease status in individual patients with multiple sclerosis. The MTV maps are obtained using short clinically appropriate scans that can reveal how tissue changes influence behavior and cognition.

  View details for DOI 10.1038/nm.3390

  View details for Web of Science ID 000328181400038

  View details for PubMedID 24185694

  View details for PubMedCentralID PMC3855886

• Proceedings of the Fourth International Workshop on Advances in Electrocorticography EPILEPSY & BEHAVIOR Ritaccio, A., Brunner, P., Crone, N. E., Gunduz, A., Hirsch, L. J., Kanwisher, N., Litt, B., Miller, K., Moran, D., Parvizi, J., Ramsey, N., Richner, T. J., Tandon, N., Williams, J., Schalk, G. 2013; 29 (2): 259-268

  Abstract

  The Fourth International Workshop on Advances in Electrocorticography (ECoG) convened in New Orleans, LA, on October 11-12, 2012. The proceedings of the workshop serves as an accurate record of the most contemporary clinical and experimental work on brain surface recording and represents the insights of a unique multidisciplinary ensemble of expert clinicians and scientists. Presentations covered a broad range of topics, including innovations in passive functional mapping, increased understanding of pathologic high-frequency oscillations, evolving sensor technologies, a human trial of ECoG-driven brain-machine interface, as well as fresh insights into brain electrical stimulation.

  View details for DOI 10.1016/j.yebeh.2013.08.012

  View details for Web of Science ID 000325422500001

  View details for PubMedID 24034899

• Human hippocampal increases in low-frequency power during associative prediction violations. Neuropsychologia Chen, J., Dastjerdi, M., Foster, B. L., LaRocque, K. F., Rauschecker, A. M., Parvizi, J., Wagner, A. D. 2013; 51 (12): 2344-2351

  Abstract

  Environmental cues often trigger memories of past events (associative retrieval), and these memories are a form of prediction about imminent experience. Learning is driven by the detection of prediction violations, when the past and present diverge. Using intracranial electroencephalography (iEEG), we show that associative prediction violations elicit increased low-frequency power (in the slow-theta range) in human hippocampus, that this low-frequency power increase is modulated by whether conditions allow predictions to be generated, that the increase rapidly onsets after the moment of violation, and that changes in low-frequency power are not present in adjacent perirhinal cortex. These data suggest that associative mismatch is computed within hippocampus when cues trigger predictions that are violated by imminent experience.

  View details for DOI 10.1016/j.neuropsychologia.2013.03.019

  View details for PubMedID 23571081

• Asynchronous Broadband Signals Are the Principal Source of the BOLD Response in Human Visual Cortex CURRENT BIOLOGY Winawer, J., Kay, K. N., Foster, B. L., Rauschecker, A. M., Parvizi, J., Wandell, B. A. 2013; 23 (13): 1145-1153

  Abstract

  Activity in the living human brain can be studied using multiple methods, spanning a wide range of spatial and temporal resolutions. We investigated the relationship between electric field potentials measured with electrocorticography (ECoG) and the blood oxygen level-dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI). We set out to explain the full set of measurements by modeling the underlying neural circuits.ECoG responses in visual cortex can be separated into two visually driven components. One component is a specific temporal response that follows each stimulus contrast reversal ("stimulus locked"); the other component is an increase in the response variance ("asynchronous"). For electrodes in visual cortex (V1, V2, V3), the two measures respond to stimuli in the same region of visual space, but they have different spatial summation properties. The stimulus-locked ECoG component sums contrast approximately linearly across space; spatial summation in the asynchronous ECoG component is subadditive. Spatial summation measured using BOLD closely matches the asynchronous component. We created a neural simulation that accurately captures the main features of the ECoG time series; in the simulation, the stimulus-locked and asynchronous components arise from different neural circuits.These observations suggest that the two ECoG components arise from different neural sources within the same cortical region. The spatial summation measurements and simulations suggest that the BOLD response arises primarily from neural sources that generate the asynchronous broadband ECoG component.

  View details for DOI 10.1016/j.cub.2013.05.001

  View details for Web of Science ID 000321605600015

  View details for PubMedID 23770184

  View details for PubMedCentralID PMC3710543

• Human Retrosplenial Cortex Displays Transient Theta Phase Locking with Medial Temporal Cortex Prior to Activation during Autobiographical Memory Retrieval. journal of neuroscience Foster, B. L., Kaveh, A., Dastjerdi, M., Miller, K. J., Parvizi, J. 2013; 33 (25): 10439-10446

  Abstract

  The involvement of retrosplenial cortex (RSC) in human autobiographical memory retrieval has been confirmed by functional brain imaging studies, and is supported by anatomical evidence of strong connectivity between the RSC and memory structures within the medial temporal lobe (MTL). However, electrophysiological investigations of the RSC and its interaction with the MTL have mostly remained limited to the rodent brain. Recently, we reported a selective increase of high-frequency broadband (HFB; 70-180 Hz) power within the human RSC during autobiographical retrieval, and a predominance of 3-5 Hz theta band oscillations within the RSC during the resting state. In the current study, we aimed to explore the temporal dynamics of theta band interaction between human RSC and MTL during autobiographical retrieval. Toward this aim, we obtained simultaneous recordings from the RSC and MTL in human subjects undergoing invasive electrophysiological monitoring, and quantified the strength of RSC-MTL theta band phase locking. We observed significant phase locking in the 3-4 Hz theta range between the RSC and the MTL during autobiographical retrieval. This theta band phase coupling was transient and peaked at a consistent latency before the peak of RSC HFB power across subjects. Control analyses confirmed that theta phase coupling between the RSC and MTL was not seen for other conditions studied, other sites of recording, or other frequency ranges of interest (1-20 Hz). Our findings provide the first evidence of theta band interaction between the human RSC and MTL during conditions of autobiographical retrieval.

  View details for DOI 10.1523/JNEUROSCI.0513-13.2013

  View details for PubMedID 23785155

• Hand posture classification using electrocorticography signals in the gamma band over human sensorimotor brain areas. Journal of neural engineering Chestek, C. A., Gilja, V., Blabe, C. H., Foster, B. L., Shenoy, K. V., Parvizi, J., Henderson, J. M. 2013; 10 (2): 026002-?

  Abstract

  Brain-machine interface systems translate recorded neural signals into command signals for assistive technology. In individuals with upper limb amputation or cervical spinal cord injury, the restoration of a useful hand grasp could significantly improve daily function. We sought to determine if electrocorticographic (ECoG) signals contain sufficient information to select among multiple hand postures for a prosthetic hand, orthotic, or functional electrical stimulation system.We recorded ECoG signals from subdural macro- and microelectrodes implanted in motor areas of three participants who were undergoing inpatient monitoring for diagnosis and treatment of intractable epilepsy. Participants performed five distinct isometric hand postures, as well as four distinct finger movements. Several control experiments were attempted in order to remove sensory information from the classification results. Online experiments were performed with two participants.Classification rates were 68%, 84% and 81% for correct identification of 5 isometric hand postures offline. Using 3 potential controls for removing sensory signals, error rates were approximately doubled on average (2.1×). A similar increase in errors (2.6×) was noted when the participant was asked to make simultaneous wrist movements along with the hand postures. In online experiments, fist versus rest was successfully classified on 97% of trials; the classification output drove a prosthetic hand. Online classification performance for a larger number of hand postures remained above chance, but substantially below offline performance. In addition, the long integration windows used would preclude the use of decoded signals for control of a BCI system.These results suggest that ECoG is a plausible source of command signals for prosthetic grasp selection. Overall, avenues remain for improvement through better electrode designs and placement, better participant training, and characterization of non-stationarities such that ECoG could be a viable signal source for grasp control for amputees or individuals with paralysis.

  View details for DOI 10.1088/1741-2560/10/2/026002

  View details for PubMedID 23369953

• Hand posture classification using electrocorticography signals in the gamma band over human sensorimotor brain areas JOURNAL OF NEURAL ENGINEERING Chestek, C. A., Gilja, V., Blabe, C. H., Foster, B. L., Shenoy, K. V., Parvizi, J., Henderson, J. M. 2013; 10 (2)

  Abstract

  Brain-machine interface systems translate recorded neural signals into command signals for assistive technology. In individuals with upper limb amputation or cervical spinal cord injury, the restoration of a useful hand grasp could significantly improve daily function. We sought to determine if electrocorticographic (ECoG) signals contain sufficient information to select among multiple hand postures for a prosthetic hand, orthotic, or functional electrical stimulation system.We recorded ECoG signals from subdural macro- and microelectrodes implanted in motor areas of three participants who were undergoing inpatient monitoring for diagnosis and treatment of intractable epilepsy. Participants performed five distinct isometric hand postures, as well as four distinct finger movements. Several control experiments were attempted in order to remove sensory information from the classification results. Online experiments were performed with two participants.Classification rates were 68%, 84% and 81% for correct identification of 5 isometric hand postures offline. Using 3 potential controls for removing sensory signals, error rates were approximately doubled on average (2.1×). A similar increase in errors (2.6×) was noted when the participant was asked to make simultaneous wrist movements along with the hand postures. In online experiments, fist versus rest was successfully classified on 97% of trials; the classification output drove a prosthetic hand. Online classification performance for a larger number of hand postures remained above chance, but substantially below offline performance. In addition, the long integration windows used would preclude the use of decoded signals for control of a BCI system.These results suggest that ECoG is a plausible source of command signals for prosthetic grasp selection. Overall, avenues remain for improvement through better electrode designs and placement, better participant training, and characterization of non-stationarities such that ECoG could be a viable signal source for grasp control for amputees or individuals with paralysis.

  View details for DOI 10.1088/1741-2560/10/2/026002

  View details for Web of Science ID 000316728700003

  View details for PubMedID 23369953

  View details for PubMedCentralID PMC3670711

• Proceedings of the Third International Workshop on Advances in Electrocorticography EPILEPSY & BEHAVIOR Ritaccio, A., Beauchamp, M., Bosman, C., Brunner, P., Chang, E., Crone, N., Gunduz, A., Gupta, D., Knight, R., Leuthardt, E., Litt, B., Moran, D., Ojemann, J., Parvizi, J., Ramsey, N., Rieger, J., Viventi, J., Voytek, B., Williams, J., Schalk, G. 2012; 25 (4): 605-613

  Abstract

  The Third International Workshop on Advances in Electrocorticography (ECoG) was convened in Washington, DC, on November 10-11, 2011. As in prior meetings, a true multidisciplinary fusion of clinicians, scientists, and engineers from many disciplines gathered to summarize contemporary experiences in brain surface recordings. The proceedings of this meeting serve as evidence of a very robust and transformative field but will yet again require revision to incorporate the advances that the following year will surely bring.

  View details for DOI 10.1016/j.yebeh.2012.09.016

  View details for Web of Science ID 000311784200024

  View details for PubMedCentralID PMC4041796

• Position sensitivity in the visual word form area PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rauschecker, A. M., Bowen, R. F., Parvizi, J., Wandell, B. A. 2012; 109 (24): E1568-E1577

  Abstract

  Seeing words involves the activity of neural circuitry within a small region in human ventral temporal cortex known as the visual word form area (VWFA). It is widely asserted that VWFA responses, which are essential for skilled reading, do not depend on the visual field position of the writing (position invariant). Such position invariance supports the hypothesis that the VWFA analyzes word forms at an abstract level, far removed from specific stimulus features. Using functional MRI pattern-classification techniques, we show that position information is encoded in the spatial pattern of VWFA responses. A right-hemisphere homolog (rVWFA) shows similarly position-sensitive responses. Furthermore, electrophysiological recordings in the human brain show position-sensitive VWFA response latencies. These findings show that position-sensitive information is present in the neural circuitry that conveys visual word form information to language areas. The presence of position sensitivity in the VWFA has implications for how word forms might be learned and stored within the reading circuitry.

  View details for DOI 10.1073/pnas.1121304109

  View details for Web of Science ID 000305511300011

  View details for PubMedID 22570498

  View details for PubMedCentralID PMC3386120

• Resting oscillations and cross-frequency coupling in the human posteromedial cortex NEUROIMAGE Foster, B. L., Parvizi, J. 2012; 60 (1): 384-391

  Abstract

  Using rare intracranial recordings from the posterior interhemispheric region of the human brain, we explored the oscillatory properties of the posteromedial cortex (PMC) during rest. The PMC is a core structure of the default mode network, which is known for its higher activity during the resting state. We found that resting PMC spectral power peaked in the theta band range (4-7 Hz) and was clearly distinguishable from adjacent cortical sites in the occipital lobe displaying peaks in the alpha band range (8-12 Hz). Additionally, the phase of PMC theta oscillations modulated the amplitude of ongoing high gamma (70-180 Hz) activity during the resting state. The magnitude of this cross-frequency modulation was shown to fluctuate at time scales comparable to those observed in functional neuroimaging studies of intrinsic functional connectivity networks (~0.1 Hz). The difference of canonical oscillations in the PMC compared to its adjacent cortical sites conforms to functional specialization across anatomical boundaries. Such differences may reflect separate oscillatory preferences between networks that are functionally connected.

  View details for DOI 10.1016/j.neuroimage.2011.12.019

  View details for Web of Science ID 000301218700039

  View details for PubMedID 22227048

  View details for PubMedCentralID PMC3596417

• Functional MRI of sleep spindles and K-complexes CLINICAL NEUROPHYSIOLOGY Caporro, M., Haneef, Z., Yeh, H. J., Lenartowicz, A., Buttinelli, C., Parvizi, J., Stern, J. M. 2012; 123 (2): 303-309

  Abstract

  Sleep spindles and K-complexes are EEG hallmarks of non-REM sleep. However, the brain regions generating these discharges and the functional connections of their generators to other regions are not fully known. We investigated the neuroanatomical correlates of spindles and K-complexes using simultaneous EEG and fMRI.EEGs recorded during EEG-fMRI studies of 7 individuals were used for fMRI analysis. Higher-level group analyses were performed, and images were thresholded at Z ≥ 2.3.fMRI of 106 spindles and 60 K-complexes was analyzed. Spindles corresponded to increased signal in thalami and posterior cingulate, and right precuneus, putamen, paracentral cortex, and temporal lobe. K-complexes corresponded to increased signal in thalami, superior temporal lobes, paracentral gyri, and medial regions of the occipital, parietal and frontal lobes. Neither corresponded to regions of decreased signal.fMRI of both spindles and K-complexes depicts signal subjacent to the vertex, which likely indicates each discharges' source. The thalamic signal is consistent with thalamic involvement in sleep homeostasis. The limbic region's signal is consistent with roles in memory consolidation. Unlike the spindle, the K-complex corresponds to extensive signal in primary sensory cortices.Identification of these active regions contributes to the understanding of sleep networks and the physiology of awareness and memory during sleep.

  View details for DOI 10.1016/j.clinph.2011.06.018

  View details for Web of Science ID 000299118600017

  View details for PubMedID 21775199

  View details for PubMedCentralID PMC3208090

• Disinhibition: More than a misnomer SOCIAL NEUROSCIENCE Parvizi, J. 2012; 7 (3): 311-316

  Abstract

  Despite great progress in the science of social cognition, the old Victorian notion of disinhibition is entrenched in our current thinking. According to this notion, the frontal lobes serve to inhibit the subcortical structures, and with the release of such inhibition, innate behaviors are released. This paper makes a case that the notion of disinhibition is more than a problem of semantics and is rooted in an erroneous, social Darwinistic view of brain organization as a hierarchical and dichotomous order between cortical and subcortical structures, which has no anchorage in the hardwiring of the brain neuroanatomy that suggests a mutually reciprocal relationship between these structures.

  View details for DOI 10.1080/17470919.2011.614004

  View details for Web of Science ID 000303567300008

• Proceedings of the Second International Workshop on Advances in Electrocorticography EPILEPSY & BEHAVIOR Ritaccio, A., Boatman-Reich, D., Brunner, P., Cervenka, M. C., Cole, A. J., Crone, N., Duckrow, R., Korzeniewska, A., Litt, B., Miller, K. J., Moran, D. W., Parvizi, J., Viventi, J., Williams, J., Schalk, G. 2011; 22 (4): 641-650

  Abstract

  The Second International Workshop on Advances in Electrocorticography (ECoG) was convened in San Diego, CA, USA, on November 11-12, 2010. Between this meeting and the inaugural 2009 event, a much clearer picture has been emerging of cortical ECoG physiology and its relationship to local field potentials and single-cell recordings. Innovations in material engineering are advancing the goal of a stable long-term recording interface. Continued evolution of ECoG-driven brain-computer interface technology is determining innovation in neuroprosthetics. Improvements in instrumentation and statistical methodologies continue to elucidate ECoG correlates of normal human function as well as the ictal state. This proceedings document summarizes the current status of this rapidly evolving field.

  View details for DOI 10.1016/j.yebeh.2011.09.028

  View details for Web of Science ID 000298067600003

  View details for PubMedID 22036287

• Problem of signal contamination in interhemispheric dual-sided subdural electrodes EPILEPSIA Nune, G., Winawer, J., Rauschecker, A. M., Dastjerdi, M., Foster, B. L., Wandell, B., Parvizi, J. 2011; 52 (11): E176-E180

  Abstract

  Dual-sided subdural electrodes are used in the localization and lateralization of seizure-onset zones when the area of interest is within the interhemispheric fissure. We designed the current study to test the validity of the assumption that each side of the dual-sided electrodes records from the hemisphere it faces. We recorded with dual-sided strip and grid electrodes implanted in the occipital interhemispheric space in two patients with nonoccipital epilepsy during two visual stimulation tasks in which subjects were presented with visual stimuli in the ipsilateral or contralateral visual hemifields. Our findings show substantial contamination of recordings from the opposite hemisphere. Although, as expected, electrodes recording through the falx record faintly from the contralateral cortical surface, they unexpectedly pick up strong signals from the cortex behind them. Therefore, we conclude that these electrodes should not be used for lateralization of the origin of epileptic activity or evoked responses.

  View details for DOI 10.1111/j.1528-1167.2011.03284.x

  View details for Web of Science ID 000297049700004

  View details for PubMedID 21973215

  View details for PubMedCentralID PMC3644859

• Gelastic epilepsy and hypothalamic hamartomas: neuroanatomical analysis of brain lesions in 100 patients BRAIN Parvizi, J., Le, S., Foster, B. L., Bourgeois, B., Riviello, J. J., Prenger, E., Saper, C., Kerrigan, J. F. 2011; 134: 2960-2968

  Abstract

  Hypothalamic hamartomas present with isolated fits of ictal laughter (gelastic epilepsy) or a combination of gelastic and other types of seizures. Many of these patients also suffer from cognitive decline, neuropsychiatric comorbidities and precocious puberty. Although there is a large body of anecdotal evidence about hypothalamic hamartomas and gelastic seizures, many questions still remain to be answered. For instance, which specific hypothalamic regions are most affected by the location of hamartomas causing laughing versus other types of seizures? Does the neuroanatomical localization of the lesions differ in cases with only gelastic seizures or a combination of gelastic and other types of seizures? Does the location of the lesions correlate with the presence of precocious puberty, and does the type of lesion influence the severity or the type of seizures? In a retrospective review of clinical and structural neuroimaging data from 100 cases of gelastic epilepsy and hypothalamic hamartoma, we aimed to address these questions by analysing the clinical presentation and the neuroanatomical features of the hypothalamic lesions in these patients. Our findings suggest that in all 100 cases, lesions were centred at the level of the mammillary bodies in the posterior hypothalamus. Compared with the patients with pure gelastic seizures (n = 32), those with gelastic and other types of seizures (n = 68) had significantly longer duration of epilepsy (P < 0.001), whereas age of seizure onset, the volume of lesions and the proximity to the mammillary bodies were not different between the two groups. In contrast, patients with cognitive or developmental impairment and those with precocious puberty had significantly larger lesions involving the anterior and posterior hypothalamus.

  View details for DOI 10.1093/brain/awr235

  View details for Web of Science ID 000295681400015

  View details for PubMedID 21975589

• Illusions of Visual Motion Elicited by Electrical Stimulation of Human MT Complex PLOS ONE Rauschecker, A. M., Dastjerdi, M., Weiner, K. S., Witthoft, N., Chen, J., Selimbeyoglu, A., Parvizi, J. 2011; 6 (7)

  Abstract

  Human cortical area MT(+) (hMT(+)) is known to respond to visual motion stimuli, but its causal role in the conscious experience of motion remains largely unexplored. Studies in non-human primates demonstrate that altering activity in area MT can influence motion perception judgments, but animal studies are inherently limited in assessing subjective conscious experience. In the current study, we use functional magnetic resonance imaging (fMRI), intracranial electrocorticography (ECoG), and electrical brain stimulation (EBS) in three patients implanted with intracranial electrodes to address the role of area hMT(+) in conscious visual motion perception. We show that in conscious human subjects, reproducible illusory motion can be elicited by electrical stimulation of hMT(+). These visual motion percepts only occurred when the site of stimulation overlapped directly with the region of the brain that had increased fMRI and electrophysiological activity during moving compared to static visual stimuli in the same individual subjects. Electrical stimulation in neighboring regions failed to produce illusory motion. Our study provides evidence for the sufficient causal link between the hMT(+) network and the human conscious experience of visual motion. It also suggests a clear spatial relationship between fMRI signal and ECoG activity in the human brain.

  View details for DOI 10.1371/journal.pone.0021798

  View details for Web of Science ID 000292781500016

  View details for PubMedID 21765915

  View details for PubMedCentralID PMC3135604

• Functional imaging of sleep vertex sharp transients CLINICAL NEUROPHYSIOLOGY Stern, J. M., Caporro, M., Haneef, Z., Yeh, H. J., Buttinelli, C., Lenartowicz, A., Mumford, J. A., Parvizi, J., Poldrack, R. A. 2011; 122 (7): 1382-1386

  Abstract

  The vertex sharp transient (VST) is an electroencephalographic (EEG) discharge that is an early marker of non-REM sleep. It has been recognized since the beginning of sleep physiology research, but its source and function remain mostly unexplained. We investigated VST generation using functional MRI (fMRI).Simultaneous EEG and fMRI were recorded from seven individuals in drowsiness and light sleep. VST occurrences on EEG were modeled with fMRI using an impulse function convolved with a hemodynamic response function to identify cerebral regions correlating to the VSTs. A resulting statistical image was thresholded at Z>2.3.Two hundred VSTs were identified. Significantly increased signal was present bilaterally in medial central, lateral precentral, posterior superior temporal, and medial occipital cortex. No regions of decreased signal were present.The regions are consistent with electrophysiologic evidence from animal models and functional imaging of human sleep, but the results are specific to VSTs. The regions principally encompass the primary sensorimotor cortical regions for vision, hearing, and touch.The results depict a network comprising the presumed VST generator and its associated regions. The associated regions functional similarity for primary sensation suggests a role for VSTs in sensory experience during sleep.

  View details for DOI 10.1016/j.clinph.2010.12.049

  View details for Web of Science ID 000291102300017

  View details for PubMedID 21310653

  View details for PubMedCentralID PMC3105179

• Automatisms: Bridging clinical neurology with criminal law EPILEPSY & BEHAVIOR Rolnick, J., Parvizi, J. 2011; 20 (3): 423-427

  Abstract

  The law, like neurology, grapples with the relationship between disease states and behavior. Sometimes, the two disciplines share the same terminology, such as automatism. In law, the "automatism defense" is a claim that action was involuntary or performed while unconscious. Someone charged with a serious crime can acknowledge committing the act and yet may go free if, relying on the expert testimony of clinicians, the court determines that the act of crime was committed in a state of automatism. In this review, we explore the relationship between the use of automatism in the legal and clinical literature. We close by addressing several issues raised by the automatism defense: semantic ambiguity surrounding the term automatism, the presence or absence of consciousness during automatisms, and the methodological obstacles that have hindered the study of cognition during automatisms.

  View details for DOI 10.1016/j.yebeh.2010.09.033

  View details for Web of Science ID 000288976100001

  View details for PubMedID 21145287

• Differential electrophysiological response during rest, self-referential, and non-self-referential tasks in human posteromedial cortex PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Dastjerdi, M., Foster, B. L., Nasrullah, S., Rauschecker, A. M., Dougherty, R. F., Townsend, J. D., Chang, C., Greicius, M. D., Menon, V., Kennedy, D. P., Parvizi, J. 2011; 108 (7): 3023-3028

  Abstract

  The electrophysiological basis for higher brain activity during rest and internally directed cognition within the human default mode network (DMN) remains largely unknown. Here we use intracranial recordings in the human posteromedial cortex (PMC), a core node within the DMN, during conditions of cued rest, autobiographical judgments, and arithmetic processing. We found a heterogeneous profile of PMC responses in functional, spatial, and temporal domains. Although the majority of PMC sites showed increased broad gamma band activity (30-180 Hz) during rest, some PMC sites, proximal to the retrosplenial cortex, responded selectively to autobiographical stimuli. However, no site responded to both conditions, even though they were located within the boundaries of the DMN identified with resting-state functional imaging and similarly deactivated during arithmetic processing. These findings, which provide electrophysiological evidence for heterogeneity within the core of the DMN, will have important implications for neuroimaging studies of the DMN.

  View details for DOI 10.1073/pnas.1017098108

  View details for Web of Science ID 000287377000073

  View details for PubMedID 21282630

  View details for PubMedCentralID PMC3041085

• Disinhibition: More than a misnomer. Social neuroscience Parvizi, J. 2011

  Abstract

  Despite great progress in the science of social cognition, the old Victorian notion of disinhibition is entrenched in our current thinking. According to this notion, the frontal lobes serve to inhibit the subcortical structures, and with the release of such inhibition, innate behaviors are released. This paper makes a case that the notion of disinhibition is more than a problem of semantics and is rooted in an erroneous, social Darwinistic view of brain organization as a hierarchical and dichotomous order between cortical and subcortical structures, which has no anchorage in the hardwiring of the brain neuroanatomy that suggests a mutually reciprocal relationship between these structures.

  View details for DOI 10.1080/17470919.2011.614004

  View details for PubMedID 21943028

• Shifts in gamma phase-amplitude coupling frequency from theta to alpha over posterior cortex during visual tasks FRONTIERS IN HUMAN NEUROSCIENCE Voytek, B., Canolty, R. T., Shestyuk, A., Crone, N. E., Parvizi, J., Knight, R. T. 2010; 4

  Abstract

  The phase of ongoing theta (4-8 Hz) and alpha (8-12 Hz) electrophysiological oscillations is coupled to high gamma (80-150 Hz) amplitude, which suggests that low-frequency oscillations modulate local cortical activity. While this phase-amplitude coupling (PAC) has been demonstrated in a variety of tasks and cortical regions, it has not been shown whether task demands differentially affect the regional distribution of the preferred low-frequency coupling to high gamma. To address this issue we investigated multiple-rhythm theta/alpha to high gamma PAC in two subjects with implanted subdural electrocorticographic grids. We show that high gamma amplitude couples to the theta and alpha troughs and demonstrate that, during visual tasks, alpha/high gamma coupling preferentially increases in visual cortical regions. These results suggest that low-frequency phase to high-frequency amplitude coupling is modulated by behavioral task and may reflect a mechanism for selection between communicating neuronal networks.

  View details for DOI 10.3389/fnhum.2010.00191

  View details for Web of Science ID 000289309000001

  View details for PubMedID 21060716

  View details for PubMedCentralID PMC2972699

• Electrical stimulation of the human brain: perceptual and behavioral phenomena reported in the old and new literature FRONTIERS IN HUMAN NEUROSCIENCE Selimbeyoglu, A., Parvizi, J. 2010; 4

  Abstract

  In this review, we summarize the subjective experiential phenomena and behavioral changes that are caused by electrical stimulation of the cerebral cortex or subcortical nuclei in awake and conscious human subjects. Our comprehensive review contains a detailed summary of the data obtained from electrical brain stimulation (EBS) in humans in the last 100 years. Findings from the EBS studies may provide an additional layer of information about the neural correlates of cognition and behavior in healthy human subjects, or the neuroanatomy of illusions and hallucinations in patients with psychosis and the brain symptomatogenic zones in patients with epilepsy. We discuss some fundamental concepts, issues, and remaining questions that have defined the field of EBS, and review the current state of knowledge about the mechanism of action of EBS suggesting that the modulation of activity within a localized, but distributed, neuroanatomical network might explain the perceptual and behavioral phenomena that are reported during focal electrical stimulation of the human brain.

  View details for DOI 10.3389/fnhum.2010.00046

  View details for Web of Science ID 000282826500001

  View details for PubMedID 20577584

  View details for PubMedCentralID PMC2889679

• Thalantic projections to the posteromedial cortex in the macaque JOURNAL OF COMPARATIVE NEUROLOGY Buckwalter, J. A., Parvizi, J., Morecraft, R. J., Van Hoesen, G. W. 2008; 507 (5): 1709-1733

  Abstract

  The medial parietal, posterior cingulate, and retrosplenial cortices collectively constitute a region of cortex referred to as the posteromedial cortices (PMC). In an effort to shed light on the neuroanatomical organization of the PMC, we undertook a study to identify and analyze the thalamocortical connections of these cortices. Retrograde tracer injections were placed in the posterior cingulate (PCC), retrosplenial (RSC), medial parietal cortices (MPC), and posterior cingulate sulcus (PCS), and the labeling patterns within the thalamus were analyzed. Three afferent projection patterns were observed to the PMC from the thalamus: a PCC/RSC pattern that involved the anterior thalamic nuclei, an MPC pattern that involved the lateral posterior and pulvinar nuclei, and a PCS pattern that involved the ventral thalamic nuclei. Additionally, a shared pattern of projections from the anterior intralaminar nuclei (AILN) and posterior thalamic nuclei (PTN) to all cortical regions of the PMC was observed. Our findings suggest that distinct regions within the PMC are supplied by distinctive patterns of thalamic input, but also share common projections from intralaminar and posterior thalamic sources. In addition, we relate our findings to functional abnormalities in aging and dementia, and address a domain-like pattern of thalamocortical labeling of the PMC that is drawn selectively and collectively from multiple thalamic nuclei.

  View details for DOI 10.1002/cne.21647

  View details for Web of Science ID 000253964900005

  View details for PubMedID 18253938

• Neural connections of the posteromedial cortex in the macaque PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Parvizi, J., Van Hoesen, G. W., Buckwalter, J., Damasio, A. 2006; 103 (5): 1563-1568

  Abstract

  The posterior cingulate and the medial parietal cortices constitute an ensemble known as the posteromedial cortex (PMC), which consists of Brodmann areas 23, 29, 30, 31, and 7m. To understand the neural relationship of the PMC with the rest of the brain, we injected its component areas with four different anterograde and retrograde tracers in the cynomolgus monkey and found that all PMC areas are interconnected with each other and with the anterior cingulate, the mid-dorsolateral prefrontal, the lateral parietal cortices, and area TPO, as well as the thalamus, where projections from some of the PMC areas traverse in an uninterrupted bar-like manner, the dorsum of this structure from the posteriormost nuclei to its rostralmost tip. All PMC regions also receive projections from the claustrum and the basal forebrain and project to the caudate, the basis pontis, and the zona incerta. Moreover, the posterior cingulate areas are interconnected with the parahippocampal regions, whereas the medial parietal cortex projects only sparsely to the presubiculum. Although local interconnections and shared remote connections of all PMC components suggest a functional relationship among them, the distinct connections of each area with different neural structures suggests that distinct functional modules may be operating within the PMC. Our study provides a large-scale map of the PMC connections with the rest of the brain, which may serve as a useful tool for future studies of this cortical region and may contribute to elucidating its intriguing pattern of activity seen in recent functional imaging studies.

  View details for DOI 10.1073/pnas.0507729103

  View details for Web of Science ID 000235094300073

  View details for PubMedID 16432221

• Differential distribution of calbindin D28K and parvalbumin among functionally distinctive sets of structures in the macaque brainstem JOURNAL OF COMPARATIVE NEUROLOGY Parvizi, J., DAMASIO, A. R. 2003; 462 (2): 153-167

  Abstract

  In a study of brainstem in the cynomolgus monkey, we found that the distribution of calbindin D28K (CB) and parvalbumin (PV) is nonoverlapping among functionally distinct sets of brainstem structures. Nuclei involved in representation and regulation of the organism's internal state contain CB, whereas those involved in the representation of the external environment and the representation or execution of externally directed actions contain only PV. Moreover, our findings indicate that different nuclei known as components of the ascending reticular activating system (ARAS) contain either CB or PV or both, suggesting that this system in primates operates with both CB and PV. In line with previously reported findings, we also found that unmyelinated pathways contain only CB, whereas myelinated pathways contain PV. Distribution of CB and PV in the macaque brainstem follows a pattern comparable to, but in some instances significantly different than, the pattern previously reported in the rat. We argue that the nonoverlapping distribution of CB and PV among different structures of the brainstem might reflect underlying differences in the physiological, anatomic, and perhaps phylogenetic properties of these structures. Considering our recent findings of selective vulnerability of brainstem structures to Alzheimer's disease, the present data suggest that the majority of macaque brainstem nuclei that contain CB are vulnerable to neurofibrillary tangles in humans. By contrast, only few nuclei that contain PV exhibit pathologic changes. Some of these nuclei are affected with a high number of neuritic plaques without ever developing neurofibrillary tangles.

  View details for DOI 10.1002/cne.10711

  View details for Web of Science ID 000183600700003

  View details for PubMedID 12794740

• Neuroanatomical correlates of brainstem coma BRAIN Parvizi, J., DAMASIO, A. R. 2003; 126: 1524-1536

  Abstract

  The brainstem tegmentum, including the reticular formation, contains distinct nuclei, each of which has a set of chemical, physiological and anatomical features. Damage to the brainstem tegmentum is known to cause coma, the most radical disturbance of consciousness. However, it has remained unclear which nuclei within the tegmentum are crucial for the maintenance of consciousness in humans. Accordingly, we initiated a retrospective study of MRIs obtained from 47 patients with brainstem stroke. The lesion boundaries were charted on patient MRIs and transferred onto a corresponding series of 4.7 T MRIs obtained from a control brainstem specimen that later was cut on a freezing microtome and analysed histologically. In addition, medical charts and available post-mortem materials were used to obtain relevant clinical and anatomical data to verify the MRI readings in each case. We found that in the 38 patients who did not have coma, brainstem damage either was located outside the tegmentum (n = 29) or produced a very small and unilateral compromise of the tegmentum (n = 9). In contrast, in patients who had coma (n = 9), the lesions in the tegmentum were mostly bilateral (n = 7) and were located either in the pons alone (n = 4) or in the upper pons and the midbrain (n = 5). The maximum overlap territory of the lesions coincided with the location of the rostral raphe complex, locus coeruleus, laterodorsal tegmental nucleus, nucleus pontis oralis, parabrachial nucleus and the white matter in between these nuclei. We also found that four coma subjects developed hyperthermia and died in the absence of any infections. In these cases, the maximum lesion overlap was centred in the core of pontine tegmentum. Our findings suggest that lesions confined to the upper pons can cause coma in humans even in the absence of damage to the midbrain. The findings also point to the brainstem nuclei whose lesions are likely to be associated with loss of consciousness and fatal hyperthermia in humans.

  View details for DOI 10.1093/brain/awg166

  View details for Web of Science ID 000184206700003

  View details for PubMedID 12805123

• Pathological laughter and crying - A link to cerebellum BRAIN Parvizi, J., Anderson, S. W., Martin, C. O., Damasio, H., DAMASIO, A. R. 2001; 124: 1708-1719

  Abstract

  Patients with pathological laughter and crying (PLC) are subject to relatively uncontrollable episodes of laughter, crying or both. The episodes occur either without an apparent triggering stimulus or following a stimulus that would not have led the subject to laugh or cry prior to the onset of the condition. PLC is a disorder of emotional expression rather than a primary disturbance of feelings, and is thus distinct from mood disorders in which laughter and crying are associated with feelings of happiness or sadness. The traditional and currently accepted view is that PLC is due to the damage of pathways that arise in the motor areas of the cerebral cortex and descend to the brainstem to inhibit a putative centre for laughter and crying. In that view, the lesions 'disinhibit' or 'release' the laughter and crying centre. The neuroanatomical findings in a recently studied patient with PLC, along with new knowledge on the neurobiology of emotion and feeling, gave us an opportunity to revisit the traditional view and propose an alternative. Here we suggest that the critical PLC lesions occur in the cerebro-ponto-cerebellar pathways and that, as a consequence, the cerebellar structures that automatically adjust the execution of laughter or crying to the cognitive and situational context of a potential stimulus, operate on the basis of incomplete information about that context, resulting in inadequate and even chaotic behaviour.

  View details for Web of Science ID 000171312800004

  View details for PubMedID 11522574

• Consciousness and the brainstem COGNITION Parvizi, J., Damasio, A. 2001; 79 (1-2): 135-159

  Abstract

  In the first part of this article we summarize a theoretical framework and a set of hypotheses aimed at accounting for consciousness in neurobiological terms. The basic form of consciousness, core consciousness is placed in the context of life regulation; it is seen as yet another level of biological processing aimed at ensuring the homeostatic balance of a living organism; and the representation of the current organism state within somato-sensing structures is seen as critical to its development. Core consciousness is conceived as the imaged relationship of the interaction between an object and the changed organism state it causes. In the second part of the article we discuss the functional neuroanatomy of nuclei in the brainstem reticular formation because they constitute the basic set of somato-sensing structures necessary for core consciousness and its core self to emerge. The close relationship between the mechanisms underlying cortical activation and the bioregulatory mechanisms outlined here is entirely compatible with the classical idea that the reticular formation modulates the electrophysiological activity of the cerebral cortex. However, in the perspective presented here, that modulation is placed in the setting of the organism's homeostatic regulation.

  View details for Web of Science ID 000167587700005

  View details for PubMedID 11164026

• The selective vulnerability of brainstem nuclei to Alzheimer's disease ANNALS OF NEUROLOGY Parvizi, J., Van Hoesen, G. W., Damasio, A. 2001; 49 (1): 53-66

  Abstract

  In a study of thioflavin S-stained serial sections from the entire brainstem, we found that the inferior and superior colliculi and the autonomic, monoaminergic, cholinergic, and classical reticular nuclei were affected with varying degrees of severity and frequencies in 32 patients with Alzheimer's disease, whereas no changes were seen in the brainstems of 26 control subjects. The majority of the affected nuclei in patients with Alzheimer's disease exhibit either neurofibrillary tangles or senile plaques, and only a few display both. However, when sections were immunostained with the antibodies 10D5 and AT8 or ALZ50, both beta-amyloid and hyperphosphorylated epitopes of tau protein were found to be present in various concentrations in all the affected nuclei. Our findings suggest that each brainstem nucleus has a distinct vulnerability to Alzheimer's disease-related pathological changes. Given that each nucleus has idiosyncratic neuroanatomical connections and prevailing neurochemical characteristics, the heterogeneous collection of brainstem nuclei can be considered a suitable anatomical ground for further investigation of selective vulnerability in Alzheimer's disease. The finding of severe pathological changes in some brainstem nuclei also raises the possibility that the dysfunction of these nuclei may contribute to the cognitive defects and increased rates of morbidity and mortality in patients with Alzheimer's disease.

  View details for Web of Science ID 000166968000008

  View details for PubMedID 11198297

• Subcortical and cortical brain activity during the feeling of self-generated emotions NATURE NEUROSCIENCE DAMASIO, A. R., Grabowski, T. J., Bechara, A., Damasio, H., Ponto, L. L., Parvizi, J., Hichwa, R. D. 2000; 3 (10): 1049-1056

  Abstract

  In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.

  View details for Web of Science ID 000167177500024

  View details for PubMedID 11017179

• Selective pathological changes of the periaqueductal gray matter in Alzheimer's disease ANNALS OF NEUROLOGY Parvizi, J., Van Hoesen, G. W., Damasio, A. 2000; 48 (3): 344-353

  Abstract

  The periaqueductal gray matter (PAG) is a major neuroanatomical component of the brainstem and has pivotal roles in autonomic functions, behavior, and cognition, most notably in the processing of emotions and feelings. In a study of 32 brains obtained from patients with Alzheimer's disease (AD), thioflavin S-stained sections from the PAG contained major pathological changes in 81% of cases. These changes were absent in all 26 control brains (13 from normal subjects and 13 from non-AD patients). In the AD cases, both sides of the PAG were affected symmetrically; in 72%, there were only senile plaques, but there were both senile plaques and neurofibrillary tangles in 9%. Using immunohistochemical methods with 10D5, ALZ-50, and AT8 antibodies, we also established the presence of beta-amyloid peptide and abnormally phosphorylated tau protein in the PAG. Furthermore, we found that the type and density of pathological changes were expressed differently in different PAG regions and correlated with gender and the duration of dementia. These findings constitute a first step in documenting the selective changes of PAG in AD. The compartmentalized pattern of AD changes in PAG also reveals for the first time the columnar organization of PAG in human subjects.

  View details for Web of Science ID 000089024600009

  View details for PubMedID 10976641

• Orbitofrontal cortex pathology in Alzheimer's disease CEREBRAL CORTEX Van Hoesen, G. W., Parvizi, J., Chu, C. C. 2000; 10 (3): 243-251

  Abstract

  The orbitofrontal cortex has been examined in Alzheimer's disease (AD) from the viewpoint of neurofibrillary tangle (NFT) pathology, its laminar distribution and topography. NFT pathology in the orbitofrontal cortex is extensive in AD. In cases with extensive cortical pathology, NFTs extend from the pole of the frontal lobe to the orbitoinsular junction. In lesser affected cases, the anterior granular part of the orbital cortex is less invested by NFTs. Layers III and V contain the greatest density of NFTs and these are most dense in the dysgranular areas, posterior to the transverse orbital sulcus. Posterior and medial orbitofrontal areas, forming area 13 and the posterior tip of the paraolfactory gyrus, are the most severely damaged, as are the smaller agranular fields that surround the olfactory tract and cortex. The widespread orbitofrontal damage in AD affecting projection neurons suggests that this pathology may contribute heavily to the many non-memory-related behavior changes observed in this disorder.

  View details for Web of Science ID 000085865600004

  View details for PubMedID 10731219