Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation

Bastos, André M.; Donoghue, Jacob A.; Brincat, Scott L.; Mahnke, Meredith; Yanar, Jorge; Correa, Josefina; Waite, Ayan S.; Lundqvist, Mikael; Roy, Jefferson E.; Brown, Emery N.; Miller, Earl K.

doi:10.1101/2020.07.07.190132

Cited by 6 publications

(12 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, we used this DBS method to increase consciousness in anesthetized macaques in a frequency-dependent manner that was CL-selective and maximally effective at 50Hz (Redinbaugh et al, 2020). This result contrasts with another recent study achieving similar arousing effects using more traditional methodology, but at a much higher stimulation frequency (150Hz) and current (1.0-2.0mA vs our 200 μ A) (Bastos et al, 2021). These discrepancies could imply a fundamental difference in mechanism between the DBS methods.…”

Section: Discussioncontrasting

confidence: 99%

“…(1.0-2.0mA vs our 200μA) (Bastos et al, 2021). These discrepancies could imply a fundamental difference in mechanism between the DBS methods.…”

Section: Discussionmentioning

confidence: 61%

“…Intralaminar thalamic DBS can be an effective tool to increase consciousness in minimally conscious state patients (Schiff et al, 2007) and anesthetized primates (Redinbaugh et al, 2020; Bastos et al, 2021). Of the intralaminar nuclei, the central lateral nucleus (CL) appears the most promising target, with anatomical connectivity well-suited to modulate consciousness.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Thalamic deep brain stimulation as a paradigm to reduce consciousness: implications for cortico-striatal dynamics, absence epilepsy and consciousness studies

Redinbaugh

Afrasiabi

Phillips

et al. 2021

Preprint

View full text Add to dashboard Cite

Anesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but nonspecific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in corticostriatothalamic (CST) systems, thereby influencing consciousness and related processes. We used multimicroelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes reminiscent of absence epilepsy, here termed absence-like activity (ALA), with decreased behavior and vacant staring coinciding with low-frequency oscillations. DBS modulated ALA likelihood in a frequency-specific manner. ALA events corresponded to decreases in measures of neural complexity (entropy) and integration (Phi*), an index of consciousness, and substantial changes to communication in CST circuits. During ALA, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamoparietal and corticostriatal pathways. Decreased consciousness and neural integration corresponded to shifts in corticostriatal network configurations that dissociated parietal and subcortical structures. Overall, the features of ALA and implicated networks were similar to those of absence epilepsy. As this same multimicroelectrode DBS method, but at different stimulation frequencies, can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of absence epilepsy and other consciousness disorders.

show abstract

Section: Discussioncontrasting

confidence: 99%

“…(1.0-2.0mA vs our 200μA) (Bastos et al, 2021). These discrepancies could imply a fundamental difference in mechanism between the DBS methods.…”

Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thalamic deep brain stimulation as a paradigm to reduce consciousness: implications for cortico-striatal dynamics, absence epilepsy and consciousness studies

Redinbaugh

Afrasiabi

Phillips

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Specifically, the historical dichotomy between the cortex as the substrate of contents of consciousness and the thalamus and brainstem as substrates of arousal has oversimplified the various and diverse roles of subcortical systems [96]. As a first step, efforts should be directed toward a detailed mapping of how key subcortical structures (e.g., thalamus, brainstem nuclei, and basal ganglia) interact with specific cortical layers by using high-field structural and functional neuroimaging and complementary animal models [97,98]. A relevant example of how current oversimplified views of the subcortical-cortical interplay can be refined into region-and lamina-specific accounts is provided by Redinbaugh et al [97], who used thalamic stimulation in the anesthetized macaque to reveal that consciousness-relevant thalamic influence differs between deep and superficial cortical layers.…”

Section: Linking Micro-and Macroscalesmentioning

confidence: 99%

Mechanisms Underlying Disorders of Consciousness: Bridging Gaps to Move Toward an Integrated Translational Science

et al. 2021

Self Cite

View full text Add to dashboard Cite

Aim In order to successfully detect, classify, prognosticate, and develop targeted therapies for patients with disorders of consciousness (DOC), it is crucial to improve our mechanistic understanding of how severe brain injuries result in these disorders. Methods To address this need, the Curing Coma Campaign convened a Mechanisms Sub-Group of the Coma Science Work Group (CSWG), aiming to identify the most pressing knowledge gaps and the most promising approaches to bridge them. Results We identified a key conceptual gap in the need to differentiate the neural mechanisms of consciousness per se, from those underpinning connectedness to the environment and behavioral responsiveness. Further, we characterised three fundamental gaps in DOC research: (1) a lack of mechanistic integration between structural brain damage and abnormal brain function in DOC; (2) a lack of translational bridges between micro- and macro-scale neural phenomena; and (3) an incomplete exploration of possible synergies between data-driven and theory-driven approaches. Conclusion In this white paper, we discuss research priorities that would enable us to begin to close these knowledge gaps. We propose that a fundamental step towards this goal will be to combine translational, multi-scale, and multimodal data, with new biomarkers, theory-driven approaches, and computational models, to produce an integrated account of neural mechanisms in DOC. Importantly, we envision that reciprocal interaction between domains will establish a “virtuous cycle,” leading towards a critical vantage point of integrated knowledge that will enable the advancement of the scientific understanding of DOC and consequently, an improvement of clinical practice.

show abstract

“…10). We anticipate more detailed pairwise relationships between units can be identified in future studies without these confounds [68][69][70] or using further analytical techniques accounting for the specific effects of anesthesia [71][72][73] .…”

Section: Timing and Interactions Among Single Unitsmentioning

confidence: 99%

Large-scale neural recordings with single-cell resolution in human cortex using high-density Neuropixels probes

Kfir

Khanna

et al. 2021

Preprint

View full text Add to dashboard Cite

Recent advances in multi-electrode array technology have made it possible to monitor large neuronal ensembles at high resolution. In humans, however, current approaches either restrict recordings to only a few neurons per penetrating electrode or combine the signals of thousands of neurons in local field potential (LFP) recordings. Here, we describe a set of techniques which enable simultaneous recording from over 200 well-isolated cortical single units in human participants during intraoperative neurosurgical procedures using Neuropixels silicon probes. We characterized a diversity of extracellular waveforms with eight separable single unit classes, with differing firing rates, positions along the length of the linear electrode array, spatial spread of the waveform, and modulation by LFP events such as inter-ictal discharges and burst suppression. While some additional challenges remain in creating a turn-key system capable of recording, Neuropixels technology could pave the way to studying human-specific cognitive processes and their dysfunction at unprecedented spatiotemporal resolution.

show abstract

Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation

Cited by 6 publications

References 55 publications

Thalamic deep brain stimulation as a paradigm to reduce consciousness: implications for cortico-striatal dynamics, absence epilepsy and consciousness studies

Thalamic deep brain stimulation as a paradigm to reduce consciousness: implications for cortico-striatal dynamics, absence epilepsy and consciousness studies

Mechanisms Underlying Disorders of Consciousness: Bridging Gaps to Move Toward an Integrated Translational Science

Large-scale neural recordings with single-cell resolution in human cortex using high-density Neuropixels probes

Contact Info

Product

Resources

About