Thalamic strokes that severely impair arousal extend into the brainstem

Hindman, Joseph; Bowren, Mark; Bruss, Joel; Wright, Bryon E.; Geerling, Joel C.; Boes, Aaron D.

doi:10.1002/ana.25377

Cited by 39 publications

(27 citation statements)

References 23 publications

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“…The function of PB input to these thalamic nuclei is unknown, but we speculate that they convey painful and/or other (pruritic, thermal, gustatory, other viscerosensory) stimuli that increase the gain of somatomotor activation (via broad excitatory output to the striatum) and of cortical–limbic networks subserving arousal and attention (via broad excitatory output to prefrontal cortex). Consistent with the latter possibility, a minority of ischemic strokes in the thalamus impair arousal, and this finding correlates with a posterior location, centered in or near the human CM and PF (Hindman et al, 2018). Further, rodent experiments demonstrated an arousal‐promoting role for both PVT and CM/PF (Gent, Bandarabadi, Herrera, & Adamantidis, 2018; Ren et al, 2018).…”

Section: Discussionmentioning

confidence: 68%

Efferent projections of Vglut2, Foxp2, and Pdyn parabrachial neurons in mice

Huang

Grady

Peltekian

et al. 2020

J of Comparative Neurology

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The parabrachial nucleus (PB) is a complex structure located at the junction of the midbrain and hindbrain. Its neurons have diverse genetic profiles and influence a variety of homeostatic functions. While its cytoarchitecture and overall efferent projections are known, we lack comprehensive information on the projection patterns of specific neuronal subtypes in the PB. In this study, we compared the projection patterns of glutamatergic neurons here with a subpopulation expressing the transcription factor Foxp2 and a further subpopulation expressing the neuropeptide Pdyn. To do this, we injected an AAV into the PB region to deliver a Cre-dependent anterograde tracer (synaptophysin-mCherry) in three different strains of Cre-driver mice. We then analyzed 147 neuroanatomical regions for labeled boutons in every brain (n = 11). Overall, glutamatergic neurons in the PB region project to a wide variety of sites in the cerebral cortex, basal forebrain, bed nucleus of the stria terminalis,

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Section: Discussionmentioning

confidence: 68%

Efferent projections of Vglut2, Foxp2, and Pdyn parabrachial neurons in mice

Huang

Grady

Peltekian

et al. 2020

J of Comparative Neurology

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“…In summary, arousal pathways are traditionally partitioned into two quasi-independent streams: a dorsal stream extending into the thalamus and a ventral stream extending into the hypothalamus and basal forebrain 11 . The relative importance of these two pathways remains a hotly debated issue 10,59,60 . We propose neuromodulation is a promising avenue for restoring wakefulness after brain injury.…”

Section: Discussionmentioning

confidence: 99%

Activating an anterior nucleus gigantocellularis subpopulation triggers emergence from pharmacologically-induced coma in rodents

et al. 2019

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Multiple areas within the reticular activating system (RAS) can hasten awakening from sleep or light planes of anesthesia. However, stimulation in individual sites has shown limited recovery from deep global suppression of brain activity, such as coma. Here we identify a subset of RAS neurons within the anterior portion of nucleus gigantocellularis (aNGC) capable of producing a high degree of awakening represented by a broad high frequency cortical reactivation associated with organized movements and behavioral reactivity to the environment from two different models of deep pharmacologically-induced coma (PIC): isoflurane (1.25%–1.5%) and induced hypoglycemic coma. Activating aNGC neurons triggered awakening by recruiting cholinergic, noradrenergic, and glutamatergic arousal pathways. In summary, we identify an evolutionarily conserved population of RAS neurons, which broadly restore cerebral cortical activation and motor behavior in rodents through the coordinated activation of multiple arousal-promoting circuits.

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“…Next, we used lesion network mapping to test for associations between lesion connectivity and LOC. We focused on connectivity between lesion locations and the dorsal brainstem given the established role of this region in supporting human consciousness (Fischer et al, 2016;Fuller, Sherman, Pedersen, Saper, & Lu, 2011;Hindman et al, 2018;Parvizi & Damasio, 2003). We hypothesized that cortical lesions producing LOC could be defined by their functional connectivity to a recently described coma-specific area of the brainstem tegmentum (Fischer et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Cortical lesions causing loss of consciousness are anticorrelated with the dorsal brainstem

Snider

Hsu

Darby

et al. 2020

Human Brain Mapping

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Brain lesions can provide unique insight into the neuroanatomical substrate of human consciousness. For example, brainstem lesions causing coma map to a specific region of the tegmentum. Whether specific lesion locations outside the brainstem are associated with loss of consciousness (LOC) remains unclear. Here, we investigate the topography of cortical lesions causing prolonged LOC (N = 16), transient LOC (N = 91), or no LOC (N = 64). Using standard voxel lesion symptom mapping, no focus of brain damage was associated with LOC. Next, we computed the network of brain regions functionally connected to each lesion location using a large normative connectome dataset (N = 1,000). This technique, termed lesion network mapping, can test whether lesions causing LOC map to a connected brain circuit rather than one brain region. Connectivity between cortical lesion locations and an a priori coma‐specific region of brainstem tegmentum was an independent predictor of LOC (B = 1.2, p = .004). Connectivity to the dorsal brainstem was the only predictor of LOC in a whole‐brain voxel‐wise analysis. This relationship was driven by anticorrelation (negative correlation) between lesion locations and the dorsal brainstem. The map of regions anticorrelated to the dorsal brainstem thus defines a distributed brain circuit that, when damaged, is most likely to cause LOC. This circuit showed a slight posterior predominance and had peaks in the bilateral claustrum. Our results suggest that cortical lesions causing LOC map to a connected brain circuit, linking cortical lesions that disrupt consciousness to brainstem sites that maintain arousal.

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Thalamic strokes that severely impair arousal extend into the brainstem

Cited by 39 publications

References 23 publications

Efferent projections of Vglut2, Foxp2, and Pdyn parabrachial neurons in mice

Efferent projections of Vglut2, Foxp2, and Pdyn parabrachial neurons in mice

Activating an anterior nucleus gigantocellularis subpopulation triggers emergence from pharmacologically-induced coma in rodents

Cortical lesions causing loss of consciousness are anticorrelated with the dorsal brainstem

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