Stimulating at the right time to recover network states in a model of the cortico-basal ganglia-thalamic circuit
Fig 5
Stimulation of the cortex phase locked to activity sensed in the STN can induce network-wide patterns of activity that resembles those corresponding to spectral fingerprints of spontaneous activity associated with changes in connection strength.
(A) Data simulated from the four network states PS-Up (purple), PS-Down (green), HD-Up (blue), and HD-Down (red) (see main text and Fig 2) was used to compute spectral fingerprints of spontaneous burst activity which were then compared against those constructed from the outcomes of phase locked stimulation. Only data during which stimulation was delivered (i.e., within a high amplitude STN beta burst event) was analysed. We used two different spectral fingerprints to compare network states with stimulated epochs: (B) the concatenated power spectra of each of the 6 populations in the CBGT circuit. Data were normalized to unit variance prior to concatenation such that comparisons were focused on the shape of spectra rather than large differences in amplitude. (C) Matrices of the pairwise phase synchronization (magnitude of the PLV) were estimated using the Hilbert transformed signals (see Fig 3A) for both β1 and β2 frequencies. (D, E, and F) Stimulation was applied across 12 phases in the fitted model and data were compared (using pooled R2) to each network state using: the concatenated spectra (D); the matrix of PLV magnitudes (E); and the two features combined (F). These results show that spectral fingerprints from stimulation outcomes resembles that from different network states (i.e., a change in synaptic connectivity) depending upon the phase at which stimulation was delivered. (G, H, I) The above was repeated but when varying the connection strength of the PS pathway. Results are plot as a heatmap color-coded to indicate the best fitting state at each phase (x-axis; angle of stimulation relative to STN activity) and connection strength (y-axis; percentage of fitted synaptic strength, dashed line indicates 100%- i.e., the model fit to the 6-OHDA lesion data and plot in D, E, and F). (J, K, and L) Same as G, H, and I, but for modulations of HD pathway strength.