How Neural Activity is Organized During Sleep

Post by Lani Cupo

What's the science?

During sleep, the hippocampus is relied upon to consolidate experiences into long-term memories by synchronizing subcortical and cortical activity through different patterns of neuronal firing. By examining patterns of brain activity during sleep, researchers can investigate how communication occurs between distant regions, coordinating wide-spread activity. This week in PNAS, Skelin and colleagues probe the synchronization of activity between the hippocampus, subcortical structures, and cortex during sleep in human participants, examining the role of the hippocampus in memory consolidation.

How did they do it?

In order to assess brain activity during sleep, data from electrodes implanted into the brains of twelve participants with epilepsy for the purpose of seizure evaluation was obtained. While the participants slept, the electrodes recorded local brain activity (intracranial electroencephalography, iEEG), in the hippocampus, and its target regions, including the amygdala, temporal lobe, and frontal cortex. Two precise patterns of activity were identified within the overnight recordings. These included hippocampal sharp-wave ripples (SWRs), which are characterized by large, fast waves of activity (80-150 Hz), and high frequency activity (HFA; 70-200 Hz) in the target regions. HFA was previously shown to reflect the spiking activity in the electrode vicinity.

First, the researchers paired time series from each electrode in the hippocampus that contained at least 100 SWRs overnight with target sites acquired outside of the hippocampus. Each target site was identified as HFA+ if the HFA level was modulated during SWR or HFA- if it was not. This allowed the researchers to assess whether SWRs positively or negatively modulated HFA in target regions. Second, the researchers expected that SWRs would interact with slow-wave activity (SWA) or sleep spindles in target regions to modulate HFA, a hypothesis that they investigated by calculating synchrony between hippocampal SWRs and regional SWA, before correlating synchrony with the strength of HFA modulation. Finally, the researchers predicted that correlations between HFA amplitude across targets would indicate that modules of brain regions were functionally connected.

What did they find?

The authors first found that the most common modulations that occur simultaneously with SWRs are positive-modulations ipsilateral (in the same hemisphere) to the hippocampal activity in the temporal and amygdala regions of interest. This implies that SWRs in the hippocampus may play a role in stimulating neuronal activity predominantly in the amygdala and temporal lobe, especially in the same hemisphere of the brain.

The researchers also found that there was a consistent relationship between hippocampal SWRs phase-locking to SWA or sleep spindles in subcortical and cortical structures and HFA modulation in the same structures. These findings imply that SWA/spindles may play an important role in the SWRs modulation of HFA, and are involved in consolidating new memories. Interestingly, SWR-SWA coupling is present bilaterally (in both hemispheres), while the SWR-spindle coupling is present only in the brain hemisphere ipsilateral to SWR origin.

Regarding their final hypothesis, the findings suggest that slow waves are synchronized across brain regions that are anatomically distinct, providing a possible mechanism for the functional association of distributed memory traces.

What's the impact?

This study found an interaction between hippocampal SWRs and subcortical/cortical slow waves plays a role in modulating HFA of specific regions—especially the amygdala and temporal lobe. Simply, the activity of hippocampal neurons during sleep acts in concert with distant populations of neurons to coordinate the consolidation of memories. The uncommon opportunity to study this human population with implanted electrodes lends deeper insight into how distributed memory traces are formed during sleep.

Skelin et al. Coupling between slow-waves and sharp-wave ripples organizes distributed neural activity during sleep in humans. PNAS (2021). Access the original scientific publication here.