Figure 3.

Evidence for dose-dependent effects of activation of frontostriatal networks by high-frequency stimulation of the central lateral nucleus of the thalamus. A, Fiberoptic optogenetic activation of central lateral thalamic neurons shows frequency dependence (Liu et al., 2015). *p < 0.05, **p < 0.005, ***p < 0.001. B, Spatial characterization of evoked fMRI signals showing average coherence maps of brainwide activity during stimulation of excitatory central thalamus relay neurons at 100 Hz. Warm colors represent positive BOLD responses. Cool colors represent negative BOLD responses. MPFC, Medial prefrontal cortex; LPFC, lateral prefrontal cortex; SC, primary somatosensory cortex; Cg, cingulate cortex; Th, thalamus; MC, motor cortex. C, CT-DBS (Baker et al., 2016). Field shaping CT-DBS via cross-electrode stimulation markedly shifts power spectra of LFPs measured across various regions within the frontal cortex and dorsal striatum (data not shown) in the nonhuman primate. Average LFP power (left of vertical dashed line) and average Z score of LFP power (right side of vertical dashed line (for methods, see Baker et al., 2016) concatenated over a series of 10 trials before fsCT-DBS onset, indicated by dashed vertical line at Trial 0, and 15 trials during fsCT-DBS. LFP activity averaged >1305 separate recording sites within the frontal cortex and aggregated >1325 fsCT-DBS periods conducted in 144 experimental sessions. Stimulation amplitudes ranging from 0.75 to 2.5 mA, and stimulation frequencies of 150, 175, 200, and 225 Hz are included. D, Average Z score of the LFP power spectra shown in C but restricted to the delay period of Correct trials during fsCT-DBS ON periods, relative to the delay period activity of Correct trials recorded during fsCT-DBS OFF periods, including 95% CI. Dose-dependent effect of intensity over three sets of stimulation amplitudes, 0.75–1.25, 1.50–1.75, and 2.0–2.5 mA.