Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit
Fig 2
Modulating the strength of inputs to the subthalamic nucleus (STN) from both hyperdirect (HD) and pallidosubthalamic (PS) pathways leaves distinct spectral features in the oscillatory activity and synchronization of cortex (M2) and STN.
Two discrete network states were defined for each pathway: a Down-regulated state fixed at 10% connectivity, as well as an Up-regulated state set at the connection strength eliciting ~200% increase in STN beta power. The fitted model (i.e., the 6-OHDA lesioned state, represented at 100% connectivity) is given in black. (A) Schematic of PS-Up (purple, 145% connection strength) and PS-Down (green, 30% connection strength). (B) Schematic of HD-Down (red, 30% connection strength) and HD-Up (blue, 350% connection strength). (C) Legend to the network states placed on a hypothetical scale from a dopamine intact state associated with a reduction in motor symptoms (far left), to the fitted model (with parameters constrained by data from 6-OHDA rat model of Parkinsonism; middle), to states indicating further progression of the pathology and worsening of motor symptoms (far right). (D) PS network states leave distinct spectral features in the power spectra of STN, with modulation occurring between lower (β1) and upper beta (β2) bands. (E) Similar responses can be seen in the M2 power spectra; as well as in (F) the functional connectivity between STN and M2 in terms of the magnitude squared coherence. (G, H, and I) Same as (D, E, and F) but for the HD defined states. Grey lines show the intermediate spectra generated between Up and Down states.