2012 — 2016 |
Parvizi, Josef |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Memory, Attention, and Default Mode Processes in Human Posteromedial Cortex
DESCRIPTION (provided by applicant): Human mind is hallmarked by a continuous interplay between processing information from the physical environment and processing spontaneously generated information from long-term memory in the form of current concerns, future plans, wishes and recollections. This proposal aims to explore how this interplay is made possible by specific brain structures. For this purpose, we propose to study the function of the human posteromedial cortex (PMC) and determine its interaction with lateral parietal cortex (LPC) and medial temporal lobe (MTL) structures known to subserve attention and memory. The PMC is an important part of the brain structures that demonstrate reduced activity during the performance of externally directed attention tasks, while demonstrating higher activity during resting states when subjects are not engaged in any external interactions and when their minds wander. To date, the neurophysiological correlates of PMC function in the human brain, including its anatomical and temporal specificity, remain unexplored. We will address this gap of knowledge by directly monitoring and reversibly altering the activity of the PMC during cognitive tasks of attention and memory in conscious human subjects who are implanted with intracranial electrodes, as part of routine presurgical epilepsy evaluation. The proposed work will be the first to combine direct electrocorticography (ECoG) and electrical brain stimulation (EBS) in the human PMC. The neurophysiological activity of each PMC subregion will be directly recorded with high temporal resolution and individual subject anatomical precision, and will be altered to test the effect of 'transient lesions' in each subregion of the PMC during attention and memory conditions. Our overarching framework is that two PMC subregions, namely the posterior cingulated cortex (PCC) and the retrosplenial cortex (RSC), have non-overlapping roles and selective interactions with the networks of attention and memory, respectively. The resulting progress promises to shed light on the deficits associated with PMC dysfunction, in patients with attention deficit disorders, autism, epilepsy, and dementia.
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2014 — 2018 |
Parvizi, Josef |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Intracranial Electrophysiology and Electrical Stimulation of the Human Default Mode Network
Our brains are highly active when we are up and about doing things, such as, cooking, eating, dancing, or when we are sitting quietly solving mathematical equations, or thinking about our past memories and future dreams. Only recently, scientists learned that a set of brain structures, known as the default mode network (DMN), show reduced activity during the performance of many tasks but increased activity when we are at rest or remembering what happened in the past. This is the opposite of what scientists have seen in many other areas of the brain. To date, almost the entire literature about the DMN function is based on neuroimaging methods (e.g. fMRI) that follow the changes of blood flow in the brain, and thus have limited temporal resolution. With support from the National Science Foundation, Drs. Parvizi and Wagner of Stanford University will combine functional imaging (fMRI), direct electrophysiological recordings from the surface of the human cerebral cortex (ECoG), and electrical brain stimulation (EBS) to measure the activity of DMN structures during rest, attention, and recall conditions and determine their interactions with brain areas involved in attention and memory functions. This study will provide unprecedented information about the modes of our brain function when we switch from rest to solving difficult tasks and vice versa.
Pathological changes in the DMN are known to hallmark the onset of disorders such as Alzheimer's disease and attention-deficit disorder and autism all of which represent a pervasive public health issue. This project will lead to knowledge about the working of DMN and may one day contribute to development of intervention and treatment methods. Findings from this research will have significant societal impact. This collaborative research will also offer unique training opportunities for students and fellows to learn the multimodal approach with fMRI, ECoG, and EBS.
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2016 — 2020 |
Parvizi, Josef |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Numbers in the Human Brain
? DESCRIPTION (provided by applicant): Human civilizations are hallmarked by communicating magnitude, time, and space in the form of numeral symbols. Humans learn to speak a certain language and read its symbols depending on the culture they live in. All brains are known to have specialized group of neuronal populations in the visual system that, through education and culture, are pruned to recognize these visual symbols, and be able to feed them to specific networks of the brain where they are processed. The existence of neuronal populations in the brain's visual system to respond selectively to numerals is a fascinating example of how nurture affects our nature, i.e., how cultural experience and education change the brain's biological function. Yet, relatively little is known about the way these specialized populations of neurons operate in the visual system and with the networks of language and numerosity. The proposed work will be the first multimodal approach to combine direct recordings from the surface of the human brain (electrocorticography, ECoG) as well as causing reversible functional perturbations by electrical brain stimulation (EBS). The proposed work aims to provide a comprehensive map of the location and functional properties and connectivity of the specialized areas of the ventral temporal cortex (VTC) for numerals (i.e., visual numeral area (VNA). Lastly, we propose to study how the neuronal population activities change in the VTC when human subjects learn to associate foreign symbols with their categorical and semantic identities. We are hopeful and confident that our novel multimodal approach will provide unprecedented spatiotemporal information to clarify the outstanding questions about the functional contributions of VTC subregions to how numbers are processed in the human brain.
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2018 — 2021 |
Parvizi, Josef |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Project 1: Cortical Dynamics of Top-Down Control in Visual Active Sensing @ Columbia University Health Sciences
Visual perception is limited by two fundamental rhythms, a 7-10 Hz theta/alpha rhythm that describes fluctuations in psychophysical performance and a 3-5 Hz rhythm related to saccadic eye movements. The structure of a task may impose or entrain an additional rhythm, such as when a target stimulus follows a cue at a fixed interval. The goal of this project is to identify in humans the neural correlates of these rhythms and determine their relationship to intrinsic rhythms of spontaneous activity. Neural activity is measured using electrocorticography (ECoG) in patients undergoing surgery for epilepsy. In Expt. 1, localizers are conducted to identify electrodes that respond to saccadic eye movements, foveal stimuli, and/or show spatially selective responses to peripheral stimuli. Functional magnetic resonance imaging is used to identify the large-scale brain network associated with each electrode. In Expt. 2 subjects are cued to detect a target under conditions of temporal uncertainty. In the one-location condition, the target only appears at the cued location. In the two- location condition, the target appears equi-probably at one of two locations. Consistent with previous studies indicating a fixed sampling rhythm, performance should fluctuate in the 1-location condition at twice the frequency as the fluctuations in each location of the 2-location condition. We then identify the neural correlate(s) of this rhythm in electrodes identified by the localizer. These correlates may be associated with local field potentials, modulations of band-limited power, or phase-amplitude relationships that couple low frequencies to high frequencies. In addition, we determine whether these correlates can be identified in intrinsic activity measured at rest. Expt. 3 compares the 1-location and 2-location conditions when the interval between the cue and target is fixed, corresponding to a task-imposed rhythm and temporal certainty. The question is whether the neural correlates of the task-imposed rhythm are independent of the intrinsic rhythms measured in Expt. 2. Finally, Expt. 4 compares the neural rhythms that are generated when subjects process foveal stimuli during a sequence of saccades as compared to the same foveal stimuli when fixation is maintained. We test the hypothesis that saccades produce a phase reset that aligns the maximal excitability phase of internal rhythms with incoming sensory signals. This hypothesis predicts that high gamma sensory evoked responses and behavioral performance should be facilitated by saccades. We also determine the relationship between the neural correlates of the saccadic rhythm, the 7-10 Hz sampling rhythm, and spontaneous rhythms measured at rest. We will interact closely with Project 2, which uses 2 of these tasks in monkey intracortical recordings, and with Projects 3 and 4 that study parallel auditory tasks in humans and monkeys, respectively. Along with Project 3, we will supply data to dynamical network modeling studies (Project 5), and use their findings to refine and/or modify our paradigms as work progresses. Integration of findings across these studies will build more robust models of brain mechanisms operating in Active Sensing.
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0.954 |
2021 |
Parvizi, Josef |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Experimental Study of Goal-Directed Behavior and Memory During Temporal Lobe Epileptic Activity
PROJECT SUMMARY A broad and overarching goal of clinical neurosciences is to develop a mechanistic account of neural processes within a specific anatomical functional network that explains a specific clinical phenotype. There is a fundamental gap in understanding how seizures and epileptic pathological activity (i.e., not only seizures but also epileptic activity such as high frequency oscillations) affect a patient?s cognition. A core part of human cognition is the ability to remember. While the mechanisms of memory functions and their relationship with medial temporal lobe structures have been investigated in detail, and there is a wealth of information on memory dysfunction in temporal lobe epilepsy, it is yet to be known how memory functions are affected during epileptic discharges and seizures. It also remains unknown whether focal temporal lobe seizures are able to impair goal-oriented task performance. In clinical practice, we classify seizures based on whether the patient remembers the events or not, and yet we have no mechanistic understanding of what happens to the patient?s memory during seizures and how seizures impact memory for preceding and subsequent experiences. Likewise, we know little about the nature of cognitive deficits during postictal state. The goal of the proposed project is to overcome methodological limitations and test goal-directed behavior and memory in patients with MTL epilepsy. The objective here is to characterize the relationship between epileptic activities and goal-oriented task performance and memory processing. The central hypothesis of the project is that epileptic activities in the MTL will not only affect memory processing at the time of their occurrence but will also have retrograde effects by disturbing the consolidation of memory items presented before the occurrence of epileptic pathological activity and they will also have an anterograde lasting effect on encoding, consolidation and retrieval of memory items after they have disappeared. This conceptual framework is based on recent published preliminary data. The conceptual framework combined with our novel approach present an innovative platform to address the existing gap of knowledge. The proposed research is significant because it will serve as a systematic investigation to provide clear evidence about the nature of memory impairments caused by epileptic activity in the MTL. This will guide future work to design interventions in order to reduce the deleterious effects of pathological epileptic activity using novel neuromodulation methods. Our long-term ambition is that in patients implanted with chronic neuromodulation devices we use our evidence to design novel means by which we not only control seizures but more importantly reverse the cognitive deficits or even enhance the reserve functions of the epileptic tissue by silencing ongoing pathological epileptic discharges that we confirm to be toxic to human cognition.
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