Periodic Reporting for period 2 - SleepEpisMemory (Sleep and episodic memory consolidation: ‘No-report’ paradigms, brain mechanisms, and dementia)
Reporting period: 2022-04-01 to 2023-09-30
Episodic memory, the memory of past experiences at particular places and times, is a key element of the human mind, but it remains unclear how such memory is stabilized for the long-term, and how sleep may aid this process. Understanding how sleep supports memory, and how this process may be improved, are of great importance for basic research, for treating clinical conditions such as Alzheimer’s disease, and for society at large. In this project, our overall objective was to test the hypothesis that a nocturnal “dialogue” during sleep, involving interactions between the hippocampus (key for forming new memories) and cortex (key for long-term memory), promotes memory consolidation in humans. We wanted to improve the methods used to study episodic memory, test the role of hippocampal-cortical dialogue (HCD) during sleep in mediating human memory consolidation, and understand if problems with this process are associated with impaired memory in memory and dementia.
In our work so far, we went beyond the latest sleep and memory research in several ways:
(Aim 1) we developed a new method to study episodic memory and its consolidation during sleep, which is more ecological and natural than most laboratory tests and doesn’t require verbal reports from participants. The method is based on a combination of repeated viewing of special movie episodes, and eye tracking. We are finding that specific gaze patterns can quantify episodic memory without the need for report. By using dedicated animations and a novel analysis pipeline, we can now study for the first time episodic memory without report. Preliminary results have been presented at international conferences and are now being prepared for publication that will ensure further dissemination.
(Aim 2) We tested the role of hippocampal-cortical dialogue (HCD) during sleep in mediating human memory consolidation. By working with patients with intracranial electrodes volunteering for research, we were able to first characterize how the sleeping brain, busy with internal process of memory consolidation, responds differently to external events such as sounds. This study was published free-access (and made it to the cover) in the July 2022 issue of the journal Nature Neuroscience.
Next, focusing on sleep and memory, we were able to enhance brain synchrony and human memory by deep brain stimulation during sleep. Intracranial stimulation during sleep using electric pulses in the prefrontal cortex, precisely timed with slow-wave activities in the medial temporal lobe around the hippocampus, enhanced coupling of neuronal oscillations across regions of the human brain and improved memory performance. This breakthrough discovery has been presented in leading international scientific conferences and is published free-access (and also made it to the cover) in the June 2023 issue of the journal Nature Neuroscience.
(Aim 3) We are studying to what extent disrupted HCD and pathological epileptic activity during sleep impair memory consolidation in dementia and aging. Our ongoing work is already revealing abnormal sleep in individuals with amnestic mild cognitive impairment (aMCI) compared to healthy elderly individuals. Moreover, we have developed novel tools to detect pathological electrical events occurring in brain activity during sleep non-invasively. These results have been presented at international conferences and are now being prepared for publication that will ensure further dissemination.
(Aim 1) we developed a new method to study episodic memory and its consolidation during sleep, which is more ecological and natural than most laboratory tests and doesn’t require verbal reports from participants. The method is based on a combination of repeated viewing of special movie episodes, and eye tracking. We are finding that specific gaze patterns can quantify episodic memory without the need for report. By using dedicated animations and a novel analysis pipeline, we can now study for the first time episodic memory without report. Preliminary results have been presented at international conferences and are now being prepared for publication that will ensure further dissemination.
(Aim 2) We tested the role of hippocampal-cortical dialogue (HCD) during sleep in mediating human memory consolidation. By working with patients with intracranial electrodes volunteering for research, we were able to first characterize how the sleeping brain, busy with internal process of memory consolidation, responds differently to external events such as sounds. This study was published free-access (and made it to the cover) in the July 2022 issue of the journal Nature Neuroscience.
Next, focusing on sleep and memory, we were able to enhance brain synchrony and human memory by deep brain stimulation during sleep. Intracranial stimulation during sleep using electric pulses in the prefrontal cortex, precisely timed with slow-wave activities in the medial temporal lobe around the hippocampus, enhanced coupling of neuronal oscillations across regions of the human brain and improved memory performance. This breakthrough discovery has been presented in leading international scientific conferences and is published free-access (and also made it to the cover) in the June 2023 issue of the journal Nature Neuroscience.
(Aim 3) We are studying to what extent disrupted HCD and pathological epileptic activity during sleep impair memory consolidation in dementia and aging. Our ongoing work is already revealing abnormal sleep in individuals with amnestic mild cognitive impairment (aMCI) compared to healthy elderly individuals. Moreover, we have developed novel tools to detect pathological electrical events occurring in brain activity during sleep non-invasively. These results have been presented at international conferences and are now being prepared for publication that will ensure further dissemination.
(Aim 1) Our ongoing study focusing on studying episodic memory without verbal reports is yielding major novel results that we believe will make a strong impact on cognitive research. We believe it has the potential to enable research on episodic memory in populations where it was not possible yet, such as in infants, patients with aphasia, or even animal models. Once published, we will make our tools widely available for the scientific community.
(Aim 2) Our work on sleep in epilepsy patients has far-reaching implications for the fundamental investigation of sleep and memory, paving the way for fresh avenues in future clinical interventions. The new techniques and tools developed here such as closed-loop intracranial stimulation and analysis of human sleep activities at a resolution of individual neurons are useful for other disciplines in neuroscience and cognitive research. From a perspective rooted in basic science, our findings furnish direct proof in humans, lending support to the prevailing model of memory consolidation at the systems level, which is dependent on sleep. They indicate that precise coordination between hippocampal ripples, thalamocortical sleep spindles, and neocortical slow waves may facilitate intricate communication between the human hippocampus and neocortex while asleep. On the clinical front, these findings emphasize the potential to enhance memory consolidation during the sleep period. In the future, through similar closed-loop deep brain stimulation, we may offer assistance to individuals afflicted with memory disorders. Future research can delve into the potential of this approach as a novel therapeutic modality for memory disorders and dementia.
(Aim 3) Our ongoing study of sleep abnormalities in mild cognitive impairment will contribute to our basic understanding of sleep and memory in aging and dementia, and help improve early diagnosis and prognosis in the early stages of Alzheimer’s disease.
(Aim 2) Our work on sleep in epilepsy patients has far-reaching implications for the fundamental investigation of sleep and memory, paving the way for fresh avenues in future clinical interventions. The new techniques and tools developed here such as closed-loop intracranial stimulation and analysis of human sleep activities at a resolution of individual neurons are useful for other disciplines in neuroscience and cognitive research. From a perspective rooted in basic science, our findings furnish direct proof in humans, lending support to the prevailing model of memory consolidation at the systems level, which is dependent on sleep. They indicate that precise coordination between hippocampal ripples, thalamocortical sleep spindles, and neocortical slow waves may facilitate intricate communication between the human hippocampus and neocortex while asleep. On the clinical front, these findings emphasize the potential to enhance memory consolidation during the sleep period. In the future, through similar closed-loop deep brain stimulation, we may offer assistance to individuals afflicted with memory disorders. Future research can delve into the potential of this approach as a novel therapeutic modality for memory disorders and dementia.
(Aim 3) Our ongoing study of sleep abnormalities in mild cognitive impairment will contribute to our basic understanding of sleep and memory in aging and dementia, and help improve early diagnosis and prognosis in the early stages of Alzheimer’s disease.