Cortical Slow Oscillations Drive Spikes That Can Disrupt Spindles
Abstract number :
1.095
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2022
Submission ID :
2204178
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:23 AM
Authors :
Anirudh Wodeyar, PhD – Boston University, Massachusetts General Hospital; Dhinakaran Chinappen, M. Eng, MBA – Massachusetts General Hospital, Boston University; Bryan Baxter, PhD – Harvard Medical School, Massachusetts General Hospital; Dimitrios Mylonas, PhD – Harvard Medical School, Massachusetts General Hospital; Dara Manoach, PhD – Harvard Medical School, Massachusetts General Hospital; Uri Eden, PhD – Boston University; Mark Kramer, PhD – Boston University; Catherine Chu, MD – Massachusetts General Hospital, Harvard Medical School
Rationale: Cognitive dysfunction is a common feature of epilepsy, extending to epileptic encephalopathy as the most severe form. Several epileptic encephalopathies share the feature of interictal epileptiform discharges (IEDs) that are potentiated during non-rapid eye movement (NREM) sleep. Sleep spindles are a prominent oscillation during NREM sleep that supports sleep-dependent memory processes. Prior work has proposed conflicting impacts of IEDs on spindles; IEDs have both been reported to precede and trigger spindles or to hijack the circuitry and thereby disrupt spindles. To reconcile these observations, we hypothesized that cortical slow oscillations drive both IEDs and spindles, and that cortical IEDs that propagate to the thalamus could disrupt spindles and contribute to intellectual impairment in epilepsy.
Methods: We analyzed simultaneous intracranial thalamic and cortical LFPs and scalp EEG in 11 human patients with epilepsy (n=7 with intellectual disability, n=4 with normal cognitive function). From each subject we selected bipolar cortical electrodes in the seizure onset zone, bipolar thalamic contacts in the centromedian nucleus (n=9) and anterior nucleus (n=2), and a bipolar scalp EEG derivation between central and parietal regions for spindles and spikes, and a far-field referenced central EEG channel for slow oscillations. We detected IEDs, spindles, and slow oscillations in each channel using established approaches. We applied cross-correlation histograms and Poisson generalized linear models to study the relationships between IED, spindles and slow waves between these brain structures during NREM sleep.
Results: We identified four key results: (1) Cortical IEDs drive thalamic IEDs in patients with intellectual disability but not those without (Figure 1). (2) Thalamic spindles co-occur with cortical and scalp spindles in both patients with and without intellectual disability. (3) IED rate and spindle rate are anti-correlated (Figure 2A) and this anti-correlation is partly driven by IEDs (Figure 2B). (4) Cortical slow oscillations precede thalamic IEDs and thalamic spindles at different lags, where IEDs precede, and may interfere with, spindle generation (Figure 2C).
Conclusions: Unique simultaneous voltage recordings from human scalp, cortex, and thalamus allow us to characterize the relationships between IEDs, spindles, and slow waves across brain structures. We find that slow oscillations during NREM sleep drive both IEDs and spindles, where IEDs can propagate to the thalamus and interfere with spindle generation in patients with intellectual disability. These data provide a direct mechanism through which IEDs can contribute to cognitive dysfunction in epilepsy.
Funding: NINDS: R01NS115868 and R01NS110669
Translational Research