Fig. 3

Proposal of the mechanisms of lateral hypothalamic deep brain stimulation to modulate sleep and wakefulness, according to the flip-flop switch model of Saper and colleagues. The figure illustrates the functional interaction among LHA neurons, wake-active (W-A) centers, and sleep-active (S-A) centers in healthy (top panel) and parkinsonian (bottom panel) states. Arrows indicate excitatory input, while T-shape lines represent inhibitory input. The thickness of arrows and lines reflects the relative strength of input. Circle sizes denote the relative activities of each group of neurons where LHA sends excitatory input to W-A neurons. In the healthy state, robust homeostatic and circadian pressures maintain optimal wakefulness through the high activity of W-A neurons. In the parkinsonian state, dopamine depletion alters these pressures, leading to reduced W-A neurons activity and increased S-A neurons activity, which in turn causes increased sleepiness. In both conditions, LHA-DBS modulates these neural balances: low-frequency stimulation (LFS) activates the LHA to promote wakefulness, while high-frequency stimulation (HFS) inhibits LHA activity to promote sleep, leading to differential behavioral effects depending on the health state.