Figure 7.

Electrical-induced state changes to promote consciousness in animals and humans by means of thalamic stimulation. Consciousness depends on large-scale thalamocortical and corticocortical interactions. Many studies support non-specific thalamic nuclei (intralaminar nuclei) as critical structures. (A-B) Thalamic electrical stimulation in central thalamus arouses monkeys (adapted from the study by Bastos et al.¹¹⁵). (A) The histological images, using an acetylcholinerase staining, show the thalamic stimulation leads in the central thalamus. (B) The effects of thalamic electrical stimulation on cortical state in monkeys are shown by an example of the behavioural wake-up score as a function of thalamic current (left) and the mean firing rates with respect to electrical stimulation onset and offset across all cortical areas (right).¹¹⁵(C-D) Central–lateral thalamic stimulation arouses macaques from stable anaesthesia (adapted from the study by Redinbaugh et al.⁴²). (C) Stimulation sites (n = 90) in one subject collapsed along the anteroposterior axis are shown in the image. Circles represent the middle contact in the stimulation array, diameter scales with induced arousal. (D) An example of the behavioural and neural recordings during 50-Hz stimulation is shown in the left panel. The population mean arousal score pre, during (stim) and post stimulations is represented in the right panel. Using linear mixed effect models over all stimulations (n = 261) pre significantly differed from during the stimulation (F = 119.28, * = P < 0.001) and during stimulation significantly differed from post (F = 124.64, * = P < 0.001). Other abbreviations: MD, mediodorsal thalamic nuclei; LD, laterodorsal thalamic nuclei; LP, lateral posterior thalamic nuclei; VPL, ventral posterolateral thalamic nuclei; EMG, electromyography; FEF, right frontal eye field area; LIP, lateral intraparietal area; S, superficial layers; M, medium layers; D, deep layers. (E–F) The electrical stimulation of different intralaminar nuclei has been demonstrated to restore consciousness in patients with disorders of consciousness. (E) Example of deep brain stimulation (DBS) for treatment of a patient with the unresponsive wakefulness syndrome. The stimulating electrode was implanted for stimulation of the CM-PF. Computerized tomography (upper) and radiography (lower) show the trajectory and location of DBS electrode (adapted from the study by Yamamoto et al.²⁰³). (F) Bilateral DBS of the central thalamus modulates behavioural responsiveness in a patient who remained in minimally conscious state for 6 years following traumatic brain injury before the intervention. Comparison of pre-surgical baselines of achieving the maximal obtained behavioural score with this same metric with DBS on and DBS off periods during the cross-over phase (adapted from the study by Schiff et al.¹⁹⁵). Evaluated using two-tailed Pearson chi-square tests, where * = P < 0.001, Significant differences can be found between DBS-on and DBS-off for CRS-R arousal scores as well as limb control and oral feeding, all of which are better with DBS on.