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Principal Investigator: Noa Ofen
Organization: UNIVERSITY OF TEXAS DALLAS
Fiscal Year: 2024
Award: $605,545
Funding agency: National Institute of Mental Health
PROJECT SUMMARY/ABSTRACT
The human ability to retrieve information from past experiences is essential for everyday living, shows robust
improvement across childhood, and is impaired in many psychiatric and neurological disorders.
Yet we know little about the neurophysiological mechanisms subserving this core cognitive ability in the
developing brain. Memory retrieval relies on precisely timed dynamic interactions between key brain regions,
but noninvasive techniques, commonly used to probe the neural basis of human memory development, are
unable to measure both the spatial and temporal properties of memory at high resolution. Intracranial EEG
(iEEG) in patients with surgically implanted electrodes for treatment of drug-resistant epilepsy provides the
resolution needed to characterize the spatial and temporal dynamics of memory and is thus a powerful tool for
examining the neural basis of human memory. During the prior funding period, the investigators established
pediatric iEEG as an invaluable tool for elucidating the neurophysiological basis of memory formation in the
developing brain. In this project, they will investigate memory retrieval and test the contributions of two
complementary processes to successful retrieval: the enactment of strategic control mediated by the prefrontal
cortex (PFC) and the representation of mnemonic content in the MTL and visual cortices. Guided by strong
preliminary data, the central hypothesis is that the robust improvement in memory ability between childhood
and adulthood is largely supported by the enactment of strategic control mediated by the PFC. In contrast, the
contribution of the reinstatement of mnemonic content in the MTL and visual cortices to successful retrieval is
largely stable across development and is a core component contributing to children’s memory. These
hypotheses will be tested with iEEG data collected from 50 pediatric epilepsy patients and fMRI data collected
longitudinally from 100 typically developing children, adolescents, and young adults by pursuing these specific
aims: Aim 1) Identify strategic control-dependent retrieval mechanisms mediated by PFC and Aim 2) Identify
content representation-dependent retrieval mechanisms in MTL and visual cortices. To establish the
translational relevance of the mechanisms identified with iEEG and fMRI, the investigators will link measure of
retrieval obtained with iEEG or fMRI to individual differences in standardized memory scores (Aim 3). This will
pave the way to utilizing these measures in the design of interventions to alleviate memory deficits in children.
Moreover, findings from this project will provide crucial insights for the feasibility of mapping of memory
networks in children with focal epilepsy which can influence diagnostic and therapeutic surgical approaches,
and ultimately improve quality of life in patients with drug-resistant focal epilepsy. At the completion of this
project, the investigators will have identified how mechanisms in the developing brain that coordinate memory
and bear broad translational relevance for the treatment of memory deficits prominent in many psychiatric and
neurological disorders.
Terms: <0-11 years old><12-20 years old><21+ years old><Address><Adolescence><Adolescent and Young Adult><Adult><Adult Human><Age><Behavior><Brain><Brain Nervous System><Brain region><Child><Child Youth><Childhood><Children (0-21)><Children's Hospital><Clinical><Complex><Coupling><Cues><Data><Data Bases><Data Set><Databases><Development><Diagnostic><Drug resistance><EEG><Electroencephalogram><Electroencephalography><Encephalon><Epilepsy><Epileptic Seizures><Epileptics><Evaluation><Failure><Focal Epilepsy><Focal Seizure Disorder><Frequencies><Functional MRI><Functional Magnetic Resonance Imaging><Funding><Goals><Human><Impairment><Implanted Electrodes><Individual><Individual Differences><Intractable Epilepsy><Investigators><Link><Localization-Related Epilepsy><Maps><Measures><Mediating><Memory><Memory Deficit><Memory impairment><Mental disorders><Mental health disorders><Methods><Michigan><Modern Man><Nervous System Diseases><Nervous System Disorder><Neurologic><Neurologic Disorders><Neurological><Neurological Disorders><Neuropsychologies><Neuropsychology><Operative Procedures><Operative Surgical Procedures><Partial Epilepsies><Partial Seizure Disorder><Participant><Patient Selection><Patients><Pediatric Hospitals><Pediatric cohort><Performance><Personal Satisfaction><Phase><Prefrontal Cortex><Process><Productivity><Property><Psychiatric Disease><Psychiatric Disorder><Public Health><QOL><Quality of life><Refractory epilepsy><Research Personnel><Researchers><Resolution><Retrieval><Sampling><Seizure Disorder><Standardization><Surgical><Surgical Interventions><Surgical Procedure><Techniques><Testing><Therapeutic><Visual><Visual Cortex><adolescence (12-20)><adulthood><age associated><age correlated><age dependent><age linked><age related><age specific><ages><child patients><childhood epilepsy><cognitive ability><data base><design><designing><developmental><drug resistant><drug-resistant epilepsy><early adversity><early childhood adversity><early life adversity><effective intervention><epilepsia><epileptogenic><experience><fMRI><fMRI/EEG><functional magnetic resonance imaging/electroencephalography><improved><insight><intervention design><kids><medial temporal area><medial temporal lobe><memory dysfunction><memory retrieval><mental illness><mesial temporal area><mesial temporal lobe><neural><neurological disease><neurophysiological><neurophysiology><neuropsychologic><novel><pediatric><pediatric epilepsy><pediatric patients><programs><psychiatric illness><psychological disorder><recruit><resistance to Drug><resistant to Drug><resolutions><spatiotemporal><surgery><therapy design><tool><treatment design><visual cortical><well-being><wellbeing><youngster>