Electrical Stimulation of the Thalamus Modulates Cortico-Cortical Signaling

Nestor D Tomycz, Robert M Friedlander
2010 Neurosurgery  
Consciousness is the capacity to experience one's environment and internal states. The minimal mechanisms sufficient to produce this experience, the neural correlates of consciousness (NCC), are thought to involve thalamocortical and intracortical interactions, but the key operations and circuit paths are unclear. We simultaneously recorded neural activity in central thalamus and across layers of frontoparietal cortex in awake, sleeping and anesthetized macaques. Spiking activity was
more » ... vity was selectively reduced in deep cortical layers and thalamus during unconsciousness, as were intracolumnar and interareal interactions at alpha and gamma frequencies. Gammafrequency stimulation, when focused on the central lateral thalamus of anesthetized macaques, counteracted these neural changes and restored consciousness. These findings suggest that the NCC involve both corticocortical feedforward and feedback pathways coordinated with intracolumnar and thalamocortical loops. Summary: Stimulation of central lateral thalamus counters anesthesia to restore wake cortical dynamics and consciousness. Main Text: Information processing during wakefulness involves feedforward pathways carrying sensory information from superficial layers to superficial/middle layers of higherorder cortical areas, and feedback pathways carrying priorities and predictions from deep layers to superficial or deep layers of lower-order cortical areas (1, 2). Information processing is altered during sleep, anesthesia and disorders of consciousness, though All rights reserved. No reuse allowed without permission. Across 261 stimulation blocks, thalamic stimulation significantly increased arousal relative to pre-(F = 119.28, N = 261, p < 1.0x10 -10 ) and post-conditions (F= 124.64, N = 261, p = 1.0x10 -10 ) even accounting for differences in dose and anesthetic (Fig. 1, A and B; Fig. S1, A-C). Behavioral changes (Fig. 1A) were time-locked to stimulation: monkeys opened eyes with wake-like occasional blinks, performed full reaches/withdrawals with forelimbs (ipsi-or contralateral), made facial/body movements, showed increased reactivity (palpebral reflex, toe-pinch withdrawal) and altered vital signs (respiration rate, heartrate). Reconstruction of electrode tracks placed effective stimulations (arousal score ³ 3) near CL center (Fig. 1, C-F). Euclidian proximity of the stimulation array to CL significantly predicted changes in arousal (Fig. S1, G-I; T = -3.39, N = 225, p = 0.00082); when systematically varying array depth, proximity to CL center showed a significant quadratic relationship with arousal (T = -2.92, N = 225, p = 0.00393; Fig. 1F; Fig. S1, D-F). Effective stimulation sites remained so on separate recording days and with different anesthetics (Fig. 1G). Importantly, stimulation effectiveness depended on frequency (Fig. 1, G and H). At effective sites, only 50 Hz stimulations reliably increased arousal (T = 3.91, N = 44, p = 0.00035). These results show that CL stimulation can rouse animals from stable, anesthetized states. This allowed us to zero-in on NCCs, here identified as activity differences between wakefulness and anesthesia which are selectively restored by effective (arousal score ³ 3, N = 55, M = 4.70, SD = 1.70) relative to ineffective (arousal score < 3, N = 171, M = .77, SD = 0.74) 50 Hz stimulations. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/776591 doi: bioRxiv preprint We recorded 845 neurons across three brain areas (FEF, LIP, CL) during four states (wake, sleep, isoflurane, propofol; Fig. 2 ). Wake and anesthesia data derived from separate sessions, whereas the same neurons yielded sleep and wake data. Thalamic neurons showed state-dependent spike rate and bursting activity (Fig. 2, C and D) . CL neurons recorded during anesthesia (T= -4.67, N = 282, p = 3.0*10 -5 ) and NREM sleep (F = 16.40, N = 83, p = 0.001) had significantly lower spike rate than during wakefulness. Isoflurane and propofol effects were not significantly different (Fig. S2D ). Relative to wakefulness, CL neurons also increased bursting during anesthesia (T = 2.27, N = 172, p = 0.024) and sleep (F = 7.11, N = 121, p = 0.0095). We localized cortical neurons to superficial, middle or deep layers using current source density (CSD) responses to sounds in the passive oddball paradigm (Fig. 2, A and B ). Only deep neurons showed state-dependent activity (Fig. 2, E-H) . Firing rates during sleep were significantly lower than wakefulness; the state by layer interaction was significant in both FEF (F = 15.17, N = 101 , p = 0.008) and LIP (F = 7.70, N = 98, p = 0.031). Similarly, firing rates during anesthesia were lower than wake; state by layer interactions in FEF (T = 3.05, N = 281, p = 0.013) and LIP (T = 3.79, N = 282, p = 0.001) were significant. Only deep neurons increased bursting during anesthesia, evidenced by significant state by layer interaction (Fig. 2E; T = 2.12, N = 285, p = 0.035). Isoflurane and propofol yielded similar results (Fig. S2, A-C). Effective 50 Hz thalamic stimulation countered anesthesia effects in deep cortical layers of LIP (Fig 2, I-K); the four-way interaction of stimulation epoch, effectiveness, layer and area was significant (F = 5.19, N = 167, p = 0.023). Overall, states with higher consciousness level (stimulation-induced All rights reserved. No reuse allowed without permission. experimental findings and a global neuronal workspace framework. J. Physiol, Paris. 98, 374-84 (2004). 21. M. S. Livingstone, D.H. Hubel, Effects of sleep and arousal on the processing of visual information in the cat. Nature. 291, 554-61 (1981). 22. L. L. Glenn, M. Steriade, Discharge rate and excitability of cortically projecting intralaminar thalamic neurons during waking and sleep states.
doi:10.1227/01.neu.0000390619.11574.d2 pmid:21107173 fatcat:lq6pk7jcmbeppjrt6qxwvbslaa