Human memory is essential for everyday living, shows robust trajectories of improvement across childhood, and is known to be impaired in a number of neurodevelopmental disorders. There is substantial data in memory physiology in adults but a paucity of information on how this core human skill emerges in children. Further, noninvasive techniques 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. Electrocorticography (ECoG) in patients with surgically implanted subdural electrodes for treatment of intractable epilepsy is a powerful tool for examining the neural basis of human cognition. ECoG provides the spatial and temporal resolution needed to characterize the spatial and temporal dynamics of memory during childhood. This is the first project that will focus on assessing the neural basis of memory in children using ECoG. In the patient cohort, memory will be assessed with both ECoG and functional magnetic resonance imaging (fMRI). This will generate a multimodal data set to study basic questions regarding the development of memory but can also address fundamental unresolved questions on the neural signals recorded with fMRI. Additional fMRI data collected from a large sample of healthy children will help us determine the age differences in activation and connectivity between the medial temporal lobe (MTL) and the prefrontal cortex (PFC), key regions in the memory network. The ECoG data from pediatric epilepsy patients will be used to contextualize those developmental findings with remarkably high spatial and temporal precision that is not available with noninvasive methods commonly used with children. Our central hypothesis is that increased communication between MTL and PFC underlies memory capacity across healthy development. Guided by strong preliminary data, this hypothesis will be tested by pursuing:
Specific Aim 1) Identify regional activation supporting memory in children using ECoG and fMRI;
and Specific Aim 2) Identify inter-regional interactions supporting memory in children using ECoG and fMRI. Reliable ECoG measures for pre-surgical mapping of memory networks in children with intractable focal epilepsy undergoing resective surgery will ultimately be used to predict memory deficits following surgical resection. To that end, the investigators will determine whether the extent of surgical disruption of memory- related sites identified by ECoG activity predicts post-operative memory outcome (Specific Aim 3). Thus, findings from this project will provide crucial information for the future development of tools for pre-surgical mapping of memory networks in children with focal epilepsy. Such clinical applications will influence diagnostic and therapeutic surgical approaches, and ultimately improve quality of life in patients with medically refractory focal epilepsy.

Public Health Relevance

The proposed project is relevant to public health because the population being investigated consist of children with intractable focal epilepsy undergoing resective surgery. Investigating the neural basis of memory in this population in conjunction with fMRI in this cohort and in healthy controls will ultimately generate useful tools to minimize a decline in memory function following brain surgery. Thus, the proposed research is relevant to NIH's mission to develop fundamental knowledge and reduces the burdens of human disability.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Developmental Brain Disorders Study Section (DBD)
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Buhring, Bettina D
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Wayne State University
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United States
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