Temporal coordination of neuronal activity underlies human memory and learning

Memory-related disorders, such as Alzheimer’s disease and dementia, are devastating and often irreparable given our limited knowledge of how to effectively treat them. Animal studies have made significant advances in identifying neural correlates of memory, but in order to develop better interventions for memory loss, we need a deeper understanding of the neural basis of memory in the human brain. The main focus of my research is examining large-scale electrophysiological correlates of memory and learning in humans. In my studies, I recorded local field potential (LFP) data directly from the brains of neurosurgical patients performing memory tasks. First, in Chapter 2, I investigated the prevalence of sharp-wave ripples—synchronous high-frequency bursts of LFP activity—in the human hippocampus and cortex. I found that spectral characteristics of detected ripples closely matched those of other previously described high-frequency patterns in the human brain, thus raising important considerations for the detection and definition of ripple-like activity in humans. For my second study, in Chapter 3, I examined the impact of scopolamine, a cholinergic blocker, in the human hippocampal area during episodic memory. I found that the memory impairment caused by scopolamine was coupled to disruptions of both the amplitude and phase alignment of theta oscillations (2-10 Hz) during encoding. These findings suggest that cholinergic circuits support memory by coordinating the temporal dynamics of theta oscillations. Finally, in Chapter 4, I explored how brain oscillations in the medial temporal lobe (MTL) support learning. I found that subjects’ accuracy in a spatial memory task improved significantly within and across sessions, and that these short- and long-term learning effects were predicted by greater theta synchrony. My research translates important memory- and learning-related signals from animal studies, and extends those findings by revealing spectral patterns that are specifically relevant to humans. Together, my studies point to a key electrophysiological phenomenon underlying memory and learning in humans: the synchrony of neuronal activity in the brain. In particular, my results suggest that the temporal coordination of neuronal activity offered by brain oscillations, especially those in the theta frequency band, is vital for successful memory and learning. These findings expand our mechanistic understanding of the neurophysiology of human memory and learning, and suggest that improving the temporal coordination of neuronal activity in the MTL may provide a novel route to treating memory- and learning-related disorders

A consensus statement on detection of hippocampal sharp wave ripples and differentiation from other fast oscillations

Article suggests that common standards for recording, detection, and reporting for intracranial recordings in humans that suggest their role in episodic and semantic memory does not exist. Authors of the article outline the methodological challenges involved in detecting ripple events and offer practical recommendations to improve separation from other high-frequency oscillations, and argue that shared experimental, detection, and reporting standards will provide a solid foundation for future translational discovery

Acetylcholine modulates the temporal dynamics of human theta oscillations during memory

The cholinergic system is essential for memory. While degradation of cholinergic pathways characterizes memory-related disorders such as Alzheimer’s disease, the neurophysiological mechanisms linking the cholinergic system to human memory remain unknown. Here, combining intracranial brain recordings with pharmacological manipulation, we describe the neurophysiological effects of a cholinergic blocker, scopolamine, in the human hippocampal formation during episodic memory. We found that the memory impairment caused by scopolamine was coupled to disruptions of both the amplitude and phase alignment of theta oscillations (2–10 Hz) during encoding. Across individuals, the severity of theta phase disruption correlated with the magnitude of memory impairment. Further, cholinergic blockade disrupted connectivity within the hippocampal formation. Our results indicate that cholinergic circuits support human episodic memory by coordinating the timing of theta oscillations across the hippocampal formation. These findings expand our mechanistic understanding of the neurophysiology of human memory and offer insights into potential treatments for memory-related disorders