Epilepsy study uncovers 'wake slow waves' link to brain balance and cognition

By Dr. Priyom Bose, Ph.D.Dec 4 2023Reviewed by Lily Ramsey, LLM

A recent Nature Communications study investigated the association between local wake slow waves (LoWS) and cognitive processing.

Study: Wake slow waves in focal human epilepsy impact network activity and cognition. Image Credit: SewCreamStudio/Shutterstock.com

Background

A fundamental component of sleep is slow waves of neuronal activity that offer homeostatic and restorative functions. Neurons undergo slow functions of membrane potential during non-rapid eye movement (NREM) sleep. These fluctuations alternate between a burst firing mode (up-state) and inhibition of activity (down-state).

The aforementioned fluctuations could be observed through the slow oscillations of the local field potential (LFP), referred to as slow wave activity (SWA). Previous studies have revealed the importance of SWA in sleep homeostasis, metabolic regulation, and clearance of metabolic waste.

After a wake period, the sleep pressure gets elevated, reflected by the increase in the amplitude, rates, and slope of sleep slow waves (SWs). In contrast, SWs decrease at night.

Synaptic normalization of sleep SWs favors an elevated neuronal firing during the up-state and neuronal silence during the down-state. It must be noted that under pathological circumstances (e.g., epilepsy), a distinct SWA occurs following different generative mechanisms.

Similar to cognitive processing and wakefulness, epileptic activity also leads to elevated synaptic connectivity and metabolic needs. After repetitive seizures, increased SWA was observed during sleep.

This event has been described as a compensatory mechanism that counteracts the enhanced local metabolic requirement. It is imperative to understand whether SW has a beneficial impact on epileptic activity. Not many studies have investigated if SWs appear during wakefulness.

About the study

The current study demonstrated the presence of high LoWS that recapitulate the core features of sleep SWs using intracranial macro- and micro-electrode recordings from the temporal lobe of people with pharmacoresistant epilepsy.

The association between sleep SWs and the down-state of neuronal spiking activity was also demonstrated.

A total of 25 patients, including 11 females, with medically refractory epilepsy were recruited in this study. The mean age of the patients was 38.5 years. Macroelectrode and microelectrode recordings of 17 and eight participants were analyzed. 

Each patient underwent intracranial EEG monitoring at the hospital for clinical purposes. Patients with high epileptic activity were excluded because it could affect the analysis of slow-wave activity.

The associative memory task was divided into encoding and retrieval phases. In the encoding phase, participants were asked to observe 27 pairs of images of a person, place, or object that remained for six seconds on the screen. This image was preceded by a two-second fixation cross and followed by a two-second blank screen.

The retrieval phase included a single cue image for three seconds, drawn from one of the nine images shown during encoding or an equal number of similar new event images that were not shown during encoding.

Participants were asked about the images they observed. There was no time limit set within which they had to respond. Reaction times (RTs) were recorded.

The current study hypothesized that LoWS should aid in homeostatic purposes by regularizing neuronal activity to prevent epileptic discharges and echoing the function of sleep SWs.

There are two key events that occur when LoWS serves a homeostatic function. Firstly, it responds to an elevated network excitability that precedes interictal epileptiform discharges (IEDs). Secondly, there is a reduction in abnormal activity linked with IEDs.

Study findings

This study observed the existence of SW during wakefulness, which is analogous to the unique features of sleep SW.

Here, a similar down-state of neuronal activity was observed. Importantly, these SWs were unrelated due to a sporadic elevation in delta power during lesions or within epileptogenic foci.

The changes in LoWS properties, i.e., amplitude and slop, prior to IEDs were documented, which recapitulated the alterations in sleep SW under high homeostatic sleep pressure.

Furthermore, this study revealed that if an IED is closer to the preceding LoWS there is a decrease in the associated network excitability. These findings strongly indicate that LoWS regulates key components of epilepsy homeostasis, analogous to sleep homeostasis regulated by sleep SWs.

A negative association between LoWS rate and IED rate indicated that IEDs occur more commonly in patients with fewer protective LoWS. However, these beneficial effects were also linked with adverse cognitive processing, i.e., decelerating RTs in an associative memory task.

This reduction in cognitive processing was consistent with the effect of SW on neuronal activity. LoWS was identified in healthy brain regions within the MNI dataset, an independent dataset obtained from the MNI Open iEEG Atlas.

Conclusions

The current study demonstrated micro-sleep modules during wakefulness in epilepsy. Prominent homeostatic features that revealed an increase in network excitability before IEDs were presented.

Besides the beneficial effect, a negative impact on cognitive processing was also observed. Further research is required to understand better the properties that differentiate post-IED waves from LoWS. Furthermore, the therapeutic potential of LoWS against epilepsy must be evaluated.