Selective disruption of sleep slow-waves increases motor cortical excitability in major depressive disorder

Major depressive disorder (MDD) may involve dysregulation of excitatory/inhibitory balance. Because sleep slow-waves facilitate homeostatic downscaling of excitatory synaptic strength, this study examined whether slow-wave disruption (SWD) could alter motor cortical excitability in individuals with and without MDD.

Thirty-seven adults (13 healthy controls [HC]; 24 with MDD) completed two overnight laboratory sessions (baseline and SWD, order counterbalanced). Slow-waves were reduced using auditory stimulation. Motor cortical excitability was assessed the following morning using transcranial magnetic stimulation (TMS)-generated single- and paired-pulse motor evoked potentials (MEPs).

SWD increased MEPs during both single-pulse and paired-pulse TMS in individuals with MDD, whereas HC showed a pattern of decreased MEPs. At baseline, both groups exhibited reliable intracortical facilitation (ICF) and inhibition (ICI). Following SWD, facilitation patterns were preserved in both groups, while inhibitory effects were weakened in the HC but preserved in the MDD group. Relative values of ICF and ICI were unchanged following SWD in both groups.

SWD increased motor cortical excitability in individuals with MDD, consistent with disruption of sleep-dependent synaptic downscaling. Because relative ICF and ICI remained unchanged despite shifts in raw MEP amplitude, these findings suggest that the heightened excitability may be driven by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated mechanisms.

Slow-wave modulation may represent a non-pharmacologic approach to increasing motor cortical excitability and normalizing excitatory/inhibitory balance in MDD.