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Study of sleep spindle properties in a G1D cohort

Gauri Anil Kathote

Pascual Laboratory

Department of Pediatrics

Weill Cornell Medicine

New York City, NY

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Team

Abe M. Chutorian, MD Professor of Pediatric Neurology and Chief of the Division of Pediatric Neurology

Juan M. Pascual, MD PhD

Mattia Bonzanni, Instructor of Neuroscience, Pediatrics Dept

Gauri Anil Kathote, Research Data Specialist II, Pediatrics Dept

Carlo Alberto Quaranta, MD, Visiting, Pediatrics Dept

Funding:

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Sleep oscillations as a proxy of thalamocortical circuit function in G1D

A. Impacted sleep macrostructure in G1D

B. Brain circuit oscillator

C. Vulnerable circuit in G1D

Normative – 7 years old

G1D – 7 years old

Schönauer M. et al. 2018

Glucose deficit, low GABA

Inhibitory neuron failure

Thalamocortical disinhibition

Aberrant synchrony

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Sleep spindle: A critical oscillation

11-16 Hz spindle (sigma) frequency

Thalamocortical sensory gating

Memory consolidation

Synaptic plasticity

Somatosensory development

Role of sleep spindles

A. EEG during sleep stages

B. Spindle structure and functions

C. Association with cognition

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Dysfunction of Thalamocortical loop physiology in G1D results in shorter sleep spindles

A. Demographic

B. Representative spindle traces

C. Spindle duration across the night (N=11)

D. Δ Spindle duration

Black: Normative children; Blue: Children with G1D

Statistics performed using a Bayesian model

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Triheptanoin does not improve sleep spindle duration

A. Anaplerotic action of triheptanoin

C. Effect of triheptanoin on sleep spindles

B. Chronic treatment study design

Glucose

Pyruvate

Suc-CoA

Succinate

OAA

Citrate

Ac-CoA

TCA

Triheptanoin

Heptanoate

Prop-CoA

Anaplerosis

Original diet

Original diet + Triheptanoin

6 months

Visit 1

(-) C7

Visit 2

(+) C7

Blue: Children with G1D; Green: Children with G1D after 6 months of Triheptanoin

Statistic performed using paired t-test and Pearson’s correlation

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Preliminary conclusion and long-term future direction

A. Preliminary conclusion in G1D cohort

Sleep spindle duration is decreased by 15% (median) in G1D

Triheptanoin does not improve spindle duration

Sustained attention and spindle duration are not associated

B. Sleep oscillations as a point of intervention

Sleep spindles are increased in patients with cognitive improvement after high‐dose diazepam
Spikes are reduced in patients with cognitive improvement

Pharmacological Intervention

Non-pharmacological Intervention

Auditory stimulation during sleep specifically evoked sleep oscillation response and boosted verbal memory consolidation