Noninvasive modulation of prefrontal contributions to the organization of episodic memories

Prefrontal cortex has been implicated in the formation of long-term episodic memories, although its contributions have not been fully specified. The primary goal of this project is to evaluate the utility of noninvasive brain stimulation for selective modulation of specific prefrontal processes that contribute to episodic memory. Our approach is based on the notion that hippocampal-dependent relational binding builds episodic memories by linking the various sights, sounds, thoughts, and other content that occur with unique context and timing during events. We hypothesize that specific prefrontal cortical regions contribute critically to this binding process by selecting and organizing the various episode components into a coherent structure for binding by hippocampus. We propose to temporarily modulate the function of these regions in healthy adults using transcranial magnetic stimulation. The effects of this modulation on memory will be assessed using sophisticated cognitive neuroscience paradigms to identify behavioral and neural correlates of prefrontal selection/organization processes that contribute to episodic memory as distinct from other concurrent prefrontal processes that contribute to episodic memory. These paradigms blend manipulations of active versus passive learning with sensitive behavioral and eye-movement tracking measures to provide high specificity to distinct prefrontal processes during episodic memory formation. This will allow thorough evaluation of the ability to modulate specific prefrontal processes contributing to memory formation using transcranial magnetic stimulation. Functional neuroimaging will be used to assess mechanisms for effects of noninvasive stimulation on memory. Validation of noninvasive brain stimulation for the selective modulation of specific prefrontal contributions to episodic memory would open the door for strong causal tests of prefrontal contributions to memory and other cognitive functions and could motivate new stimulation-based interventions for neuropsychiatric and neurological disorders of prefrontal cortex.