Characterization and modulation of neural signals that support human memory
Creators: Mohan, Uma Rani
Publisher: name: Columbia University
Year: 2021
Subjects: subject: Biomedical engineering
subject: Neurosciences
subject: FOS: Clinical medicine
subject: Memory--Research
subject: Brain--Research
subject: Cerebral cortex
subject: Brain mapping
subject: Brain stimulation

description: Memory is critical to our everyday lives, allowing us to attach meaning to our experiences of the world. However, a number of neurocognitive disorders can result in the loss of this fundamental function. The development of effective treatments for loss of episodic memory depends on a detailed understanding of the neural signals that support memory and a thorough characterization of how brain stimulation may be targeted to modulate memory-related patterns of brain activity. In this dissertation, I approach these questions with a series of three studies to examine the effects of direct electrical brain stimulation, the role of large-scale patterns of brain activity in memory, and how stimulation can be used to modulate these signals. In my first study, I characterize changes in neuronal activity across the brain that resulted from delivering stimulation at a range of frequencies, amplitudes, and locations. To do this, I developed an analysis framework and applied it to a large-scale dataset of direct human brain recordings from electrodes implanted in neurosurgical epilepsy patients while intracranial stimulation was delivered. With these analyses, I found that stimulation most often had an inhibitory effect; however, high-frequency stimulation delivered near white-matter tracts was most likely to excite neuronal activity. In my second study, I investigated the functional role of brain oscillations that moved across the cortex during memory tasks. I found that traveling waves of low-frequency oscillations that moved anteriorly across the cortex most often supported successful memory encoding. Additionally, the timing, or phase, of brain oscillations propagating across specific areas of the cortex predicted efficient memory retrieval. In my last study, having determined that the direction of traveling waves is important for memory processes, I then investigated how different types of stimulation changed the direction of traveling waves of low-frequency oscillations. By analyzing intracranial recordings during a stimulation mapping procedure, I found that stimulation at high frequencies oriented in line with the direction of wave propagation was most effective in changing the propagation direction of traveling waves. Additionally, I tested how changes traveling wave direction from stimulation affected patients’ memory performance during an episodic memory task. For patients where stimulation changed the propagation direction of their waves from anterior to posterior directions, stimulation also impaired their memory, and when stimulation had the opposite effect on direction, it enhanced their memory. This provides the first preliminary causal evidence that stimulation can be targeted to modulate specific features of large-scale patterns of brain oscillations— the direction of traveling waves— and, in turn, affect memory performance. Broadly, this body of work shows that direct electrical stimulation of the brain applied with specific parameters holds the potential to modulate neural activity related to memory. This work expands our current understanding of the functional role of brain oscillations by showing that specific features of traveling waves across the cortex are key signals linked to human behavior. These findings provide both a basic understanding of how neural oscillations support human behavior as well as a foundation for designing stimulation protocols to precisely target desired changes in neural activity with the potential to improve diagnostic and therapeutic applications.